The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to that seen with BA.5.2.1 (up to day 6 post infection) but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686-694) in the viral genome (ORF1ab) responsible for production of non-structural protein 1 which resulted in the loss of three amino acids (aa 141-143).

The Golden Syrian hamster (Mesocricetus auratus) is now commonly used in preclinical research for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the assessment of vaccines, drugs and therapeutics. Here we show that hamsters inoculated via the intranasal route with the same infectious virus dose of prototypical SARS-CoV-2 administered in a different volume present with different clinical signs, weight loss and viral shedding, with a reduced volume resulting in reduced severity of disease similar to that obtained by a 500-fold reduction in challenge dose. The tissue burden of virus and the severity of pulmonary pathology were also significantly affected by different challenge inoculum volumes. These findings suggest that direct comparison between the severity of SARS-CoV-2 variants or studies assessing the efficacy of treatments determined by hamster studies cannot be made unless both the challenge dose and inoculation volume are matched when using the intranasal route. Additionally, analysis of sub-genomic and total genomic RNA PCR data demonstrated no link between sub-genomic and live viral titres and that sub-genomic analyses do not provide any information beyond that provided by more sensitive total genomic PCR.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

：Non-Euclidean data, such as social networks, and citation relationships between documents, has node information and structural information. Graph Convolutional Network(GCN) can automatically learn node features and association information between nodes. The core ideology of the graph convolutional network is to aggregate node information by using edge information, thereby generating a new node feature. In the process of updating node features, there are two core influencing factors. One is the number of neighboring nodes of the central node, the other is the contribution of the neighboring nodes to the central node. Due to the previous GCN methods not simultaneously considering the numbers and different contributions of neighboring nodes to the central node, we design the Adaptive Attention Mechanism(AAM). To further enhance the representational capability of the model, we utilize Multi-Head Graph Convolution(MHGC). Finally, we adopt cross-entropy(CE) loss function to describe the difference between the predicted results of node categories and the ground truth (GT). Combined with backpropagation, this ultimately achieves accurate node classification. Based on AAM, MHGC and CE, we contrive the novel Graph Adaptive Attention Network (GAAN). Experiments show that the classification accuracy has achieved outstanding performances on Cora, Citeseer and Pubmed datasets.

The existing segmentation-based scene text detection methods mostly need complicated post-processing, and the post-processing operation is separated from the training process, which greatly reduces the detection performance. The previous method, DBNet successfully simplified post-processing and integrated the post-processing into a segmentation network. However, the training process of the model took a long time for 1200 epochs and the sensitivity to texts of various scales was lacking, leading to some text instances being missed. Considering the above two problems, we design the text detection Network with Binarization of Hyperbolic Tangent(HTBNet). First of all, we propose Binarization of Hyperbolic Tangent (HTB), optimized along with which, the segmentation network can expedite the initial convergent speed by reducing the amount of epochs from 1200 to 600. Because features of different channels in the same scale feature map focus on the information of different regions in the image, to better represent the important features of all objects in the image, we devise the Multi-Scale Channel Attention(MSCA). Meanwhile considering that multi-scale objects in the image cannot be simultaneously detected, we propose a novel module named Fused Module with Channel and Spatial(FMCS), which can fuse the multi-scale feature maps from channel and spatial dimension. Finally we adopt cross entropy as the loss function, which measures the difference between predicted values and ground truths. The experimental results show that HTBNet compared with lightweight models has achieved competitive performance and speed on Total-Text(F-measure:86.0%, FPS:30) and MSRA-TD500 (F-measure:87.5%, FPS:30).

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in training programmes for medical and dental students. The major challenge is to create such resources that have quality content and are acceptable to students. We investigated the opinions of a sample of 551 students from 4 medical universities in Romania in order to identify the characteristics of the instructional videos that students prefer and we comparatively analysed these characteristics according to gender, age group, but also according to their general preferences for using Internet services. We used univariate (hypothesis testing) and multivariate (Two-Step Clustering) data analysis techniques and revealed three clusters of students, primarily determined by perceptions of the visual appearance of instructional videos. The structure of the clusters by gender and age group is relatively similar, but we recorded differences between them associated with students' expressed preferences for certain Internet services compared to others. Students who prefer instructional videos to contain images used only for aesthetic purposes, to fill in breaks, use Internet services mainly for communication, while students who prefer in videos the use of already drawn explanatory diagrams are slightly younger than the others and use Internet services mainly for information and communication.

Bamboo agroforestry is currently being promoted as a viable land use option to reduce dependence on natural forest for wood fuels in Ghana. To align the design and introduction of bamboo agroforestry in conformity with farmers’ needs, perceptions, skills and local cultural practices, information on its acceptability and adoption potential among farmers is necessary. It is therefore the objective of this study to (1) describe bamboo ethnobotany and (2) assess socioeconomic factors that affect the acceptability and adoption of bamboo and its integration into farming practices. Accordingly, information has been collected from 200 farmers in the dry semi-deciduous forest zone of Ghana. The study identified the socioeconomic risks and uncertainties as well as biophysical factors that are likely to influence the potential adoption of bamboo agroforestry in the study region. Gender, age, farmers’ known uses of bamboo, the practice of leaving trees on farmlands, farmers’ networking and access to extension services, land availability and ownership by farmers were identified as suitable predictor variables for the adoption of bamboo agroforestry. It is envisaged that bamboo agroforestry is a good bet in the DSFZ though there is the need to explore domestic energy (fuelwood) provision and substitution potential in order to have a broader picture of the technology.

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate, F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

1) Background- Coronary artery bypass grafting (CABG) is a common surgical intervention for patients with severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has been widely used to predict mortality risk in patients with end-stage liver disease, but its utility in predicting postoperative outcomes in cardiac surgery patients is less well-established. 2) Methods-This retrospective study aims to investigate the association between preoperative MELD score and post-operative complications, length of hospital stay, and mortality in patients under-going coronary artery bypass grafting. This is a single-center, retrospective cohort study conducted at a tertiary care academic medical center. The study includes all adult patients who underwent elective coronary artery bypass grafting between January 2011 and December 2020. Preoperative MELD scores were calculated for each patient, and postoperative outcomes including major ad-verse cardiac events, length of hospital stay, and 30-day mortality was assessed. To ensure a homogeneous study cohort, we excluded patients who underwent emergent cardiac procedures or had incomplete data necessary for the calculation of MELD scores and assessment of postoperative outcomes. Data was extracted from the electronic medical records, including patient de-mographics, comorbidities, preoperative laboratory values, operative details, and postoperative outcomes. The study protocol was approved by the Institutional Review Board, and the require-ment for informed consent was waived due to the retrospective nature of the study.3) Results- This study reveals a statistical association between the MELD score calculated at admission and the length of hospital stay, duration in the ICU, patient age, and the duration of aortic clamping and extracorporeal circulation. Specifically, there is an exponential increase in the MELD score corre-lating with the rise in these factors, both collectively and individually, highlighting a significant relationship between the duration of extracorporeal circulation and aortic clamping time. 4) Conclusion-Patients with a high MELD score had an increased risk of postoperative complications and mortality compared to those with a low MELD score. Careful preoperative patient selection and optimization of the patient's clinical condition may improve outcomes in patients with advanced liver disease undergoing cardiac surgery.

Intrusion Detection Systems (IDS) plays a part in modern cyber security, as a result of the increasing need for cyber security systems in the “real” world due to the increasing number of cyber attacks, more sophisticated systems are required in order to prevent these attacks - an IDS can provide this protection. Due to the sophistication of these systems, they must be properly understood, developed and analyzed - research papers can be used as a tool to improve IDS systems. This paper is composed of two main sections: a survey and a taxonomy, providing information, reviews and interpretations from relevant papers, a timeline of important papers, a discussion on the future of IDS and a classification on IDS and how to apply this.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

This study explores the complexities involved in the extraction and purification of catechins, prominent bioactive compounds found in plant extracts and tea. It addresses challenges arising from the intricate molecular structure of catechins and their inherent variability across botanical sources. Despite these obstacles, catechins present significant potential, particularly in healthcare. Their potent antioxidant properties have been extensively investigated and associated with numerous health benefits, positioning them as promising therapeutic agents for combating chronic diseases. Furthermore, catechins have diverse applications across various industries, including food and beverage, cosmetics, agriculture, and materials science. This abstract emphasizes the importance of continued research and innovation in catechin extraction and utilization, which hold promise for advancing human health and technological progress across multiple domains.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

BackgroundLiving donor liver transplantation offers comparable long-term results to cadaveric donor transplantation. This study analyzes the selection process of living liver donors at a Western transplant center that utilizes both donation forms. MethodsThis retrospective analysis examined potential living donors, collecting medical data and reasons for refusal, and divided patients by indication and urgency for transplantation. ResultsFrom January 2013 to December 2023, 594 potential living donors were assessed at Jena University Hospital. Of these, 124 living donor transplants were performed. During outpatient evaluation, 357 potential donors were excluded. Subsequently, 238 individuals underwent inpatient assessment, with 100 more being excluded. Main reasons for donor refusal included medical or psychological issues (n=160), disease progression in recipients (n=90), and recipient refusal or donor withdrawal (n=54). The evaluation process showed a trend towards considering more distant relatives and acquaintances as donor candidates with increasing severity of the recipient's disease.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

This study explores the dynamics of transparency and accountability in supplier relationship management (SRM) within the e-commerce sector. It investigates how e-commerce platforms and their suppliers navigate complexities to foster trust, enhance collaboration, and ensure ethical practices in global supply chains. The research employs a qualitative approach, utilizing semi-structured interviews with industry stakeholders to gather insights into current practices, challenges, and strategies in SRM. Findings highlight transparency as pivotal for sharing critical information such as sales forecasts, inventory levels, and pricing strategies, enabling suppliers to align operations with market demands effectively. However, achieving transparency faces hurdles including data privacy concerns and competitive sensitivities, necessitating robust data security measures and clear communication protocols. Accountability mechanisms, such as formal agreements and governance frameworks, emerge as essential for mitigating risks, resolving disputes, and ensuring compliance with ethical and regulatory standards across diverse contexts. Technological innovations like AI, blockchain, and big data analytics are transforming SRM by enhancing supply chain visibility, operational efficiency, and decision-making capabilities. Cultural factors and regulatory compliance also significantly influence SRM practices, shaping communication styles, relationship dynamics, and legal considerations. Emerging trends such as sustainable sourcing practices and collaborative partnerships are reshaping SRM, emphasizing sustainability and responsible business practices. This study contributes to the understanding of effective SRM strategies, offering insights and recommendations for stakeholders navigating the complexities of e-commerce supply chains.

This article aims to analyze the relationship between non-obstructive coronary artery disease (NOCAD) and atrial fibrillation (AF), exploring the underlying pathophysiological mechanisms and implications for clinical management. NOCAD and AF are prevalent cardiovascular conditions that often coexist, yet their interrelation is not well understood. NOCAD, characterized by the presence of atherosclerotic plaques without significant luminal stenosis, can lead to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. Atrial fibrillation, on the other hand, is the most common sustained cardiac arrhythmia, associated with an increased risk of stroke and heart failure, which may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Therefore, NOCAD and AF seems to be a complex Interplay with one begets another.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

This qualitative study explores the dynamics of Supplier Relationship Management (SRM) and its impact on innovation within the e-commerce sector. Through in-depth interviews and documentary analysis of three case study firms known for their innovative practices, the study examines how collaborative SRM practices influence innovation outcomes, organizational resilience, and competitive advantage in dynamic market environments. Key themes include the pivotal role of trust, transparency, and joint problem-solving in fostering effective SRM relationships, enabling knowledge sharing and co-development of innovative products and services. Innovation outcomes observed encompass product innovation, process improvements, and technological advancements facilitated by close collaboration between e-commerce firms and their suppliers. Challenges such as managing supplier diversity, navigating regulatory complexities, and mitigating geopolitical risks highlight the complexities and strategic imperatives of SRM implementation in global supply chains. The study also emphasizes the transformative role of digital technologies, including real-time data exchange, predictive analytics, and agile supply chain management, in enhancing SRM effectiveness and innovation capabilities. Strategic alignment with organizational goals and market strategies further enhances the impact of SRM, enabling firms to prioritize innovation initiatives, allocate resources effectively, and sustain growth amidst economic uncertainties. The findings contribute to theoretical understanding and practical insights into SRM strategies that promote innovation excellence and competitive positioning within e-commerce. The implications for practice underscore the importance of fostering collaborative supplier relationships, investing in digital transformation, and adopting proactive strategies to manage risks and regulatory compliance.

This study investigates the critical factors of trust, commitment, and adaptation within supplier relationship management (SRM) in the context of e-commerce. Through qualitative research methods, including semi-structured interviews and documentary analysis, the study explores how these factors influence relationship dynamics and organizational outcomes in digital business environments. Trust is examined as foundational to effective SRM, encompassing integrity, reliability, and shared values between buyers and suppliers. Commitment is analyzed in terms of long-term orientation, resource allocation, and relationship-specific investments aimed at mutual growth and sustainability. Adaptation emerges as essential for navigating the dynamic e-commerce landscape, encompassing proactive strategies, flexibility, and innovation to respond to market changes and technological advancements. The findings highlight the interplay and mutual reinforcement among trust, commitment, and adaptation, contributing synergistically to relationship resilience and organizational performance. However, challenges such as information asymmetry, cybersecurity risks, and organizational inertia are identified as barriers to effective SRM. Practical implications include strategies for enhancing trust, fostering commitment, and cultivating adaptive capabilities through continuous learning, collaborative innovation, and technology integration. By integrating these insights, businesses can strengthen supplier relationships, drive sustainable growth, and achieve competitive advantage in the digital economy.

This qualitative study explores the pivotal roles of trust and communication in supplier relationship management (SRM) within the e-commerce sector. Drawing on interviews and thematic analysis, the study examines how trust, comprising dimensions of competence, benevolence, integrity, and reliability, underpins collaborative partnerships and operational resilience between e-commerce platforms and suppliers. Effective communication strategies, including proactive engagement, transparent feedback mechanisms, and real-time updates via digital platforms, are identified as critical enablers for enhancing information exchange and fostering mutual understanding in SRM. Challenges such as cultural differences, technological complexities, and regulatory compliance requirements are also discussed, highlighting the need for strategic management and investment to mitigate risks and maintain trust in supplier engagements. Relational competencies such as empathy, active listening, conflict resolution, and trust-building skills are recognized as essential for navigating interpersonal dynamics and fostering collaborative relationships in e-commerce SRM. Strategically, integrating these findings into comprehensive SRM frameworks is emphasized to cultivate a positive organizational culture characterized by openness, ethical integrity, collaboration, and adaptability. This approach aims to enhance supplier relationships, drive innovation, and achieve sustainable growth in a competitive marketplace.

This qualitative study explores the intricacies of building sustainable supplier relationships in the e-commerce sector, focusing on best practices and strategic approaches. Through in-depth interviews with procurement managers, supply chain experts, and supplier representatives, the research identifies four critical themes: trust, technology integration, ethical practices, and performance measurement. Trust is found to be the foundation of effective supplier relationships, fostering open communication and collaboration, which are essential for addressing challenges and co-creating solutions. The integration of digital technologies such as supply chain management software, blockchain, and the Internet of Things significantly enhances transparency, decision-making, and operational efficiency, providing a competitive edge. Ethical practices, including adherence to fair labor standards and environmental sustainability, are increasingly crucial as consumer and regulatory expectations evolve, necessitating alignment between e-commerce companies and their suppliers. Performance measurement and continuous improvement are vital for maintaining quality and efficiency, with clear metrics and regular evaluations driving constructive feedback and optimization of supply chain processes. The study underscores the interdependence of these elements in fostering resilient and adaptable supplier relationships. The findings offer practical guidance for e-commerce businesses and suppliers, emphasizing the need for a holistic approach to supplier management that balances trust, technology, ethics, and performance. This approach not only enhances operational effectiveness but also ensures the long-term sustainability of supplier relationships in the dynamic e-commerce landscape. The research contributes to the theoretical understanding of supplier relationship management, providing a comprehensive framework for future studies and practical applications in the e-commerce industry.

Background: Virtual Reality (VR) is an emerging tool in the management of anxiety, one of the most disturbing symptoms of Alcohol Use Disorder (AUD), which often leads to relapse. Still, patients with Alcohol Use Disorder frequently have a history of Acute Symptomatic Seizures, and they are subsequently excluded from studies using VR because of the hypothesized fear of inducing photosensitive seizures. The first part of this narrative review explores the pathophysiological mechanisms of seizures associated with AUD, specifically acute symptomatic seizures. In contrast, the second part explores virtual reality’s safe use in seizure-prone individuals, highlighting that the current state-of-the-art is based on a biased per-ception and old epidemiological data from studies conducted on photosensitive seizures in the late 90s. VR exposure has yet to be reported as triggering seizures within known pharmacovigilance databases. Significance: The implications weigh heavily on VR research currently associated with this significant adverse event. Further studies are necessary to address the risk of seizures triggered by VR in patients predisposed to developing seizures, like alcohol use disorder patients with a history of acute symptomatic seizures. Such research is essential to ensure that the potential benefits of Virtual Reality as a tool for managing anxiety in individuals with alcohol use disorder and acute symptomatic seizures are not unduly restricted. Furthermore, AUD can also serve as an intervention model feasible to de-bias attitudes toward the current lack of evidence base concerning the significant adverse events of VR-induced seizures, therefore facilitating the clinical implementation of this unharnessed digital treatment interface.

The current disruptive innovation model has a limitation in incorporating customers’ demands while the customer can be a co-creator of value on performance, design, and price innovation. Thus, this research attempted to explore the disruptive innovation model which can include both the incumbent’s innovation trajectory and customer’s demand, and how incumbents behave to enable disruptive innovation in the smartphone market. Based on the Apple iPhone case study, this study verified that the current disruptive innovation model can incorporate customers’ demand by reflecting their demand in the direction of innovating the performance, design, or price of smartphones with the price-adjusted innovation trajectory. The secondary innovation trajectory which was found uniquely in this study is meaningful since it can be a creative solution for the innovator’s dilemma. Besides, Apple, as an incumbent, has behaved to innovate iPhone performance and design demands of customers creating significant papers and patents as outcomes of innovation activities. This study has practical implications for incumbents’ managers as well as customers to enable disruptive innovation in the smartphone market.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Few studies have examined the pros and cons of integrated TB and HIV service delivery in public healthcare facilities, and even fewer have proposed conceptual models for improved integration. This study intends to fill that vacuum by outlining the development of a facility-based paradigm for integrating TB, HIV and patients services. The design of the proposed model were in stages that involved the evaluation of existing TB-HIV integration model and synthesis of both quantitative and qualitative data from the study sites which were selected public healthcare facilities at both rural and peri-urban settings in Oliver Reginald (O.R) Tambo District Municipality in Eastern Cape, South Africa. Secondary data on 2009-2013 TB-HIV clinical outcomes were obtained from multiple sources for quantitative analysis. Qualitative data involved focus group discussions among patient and heath care staff, which was thematically analysed. The development of a possibly better model and validation of this model show that the district's health system was reinforced by the model's guiding principles, which placed a strong emphasis on inputs, processes, outcomes, and integration effects.The model is adaptable to different healthcare delivery systems but will require support from healthcare stakeholders and professionals to be successful.

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement, but for its use adapted to the peculiarities of the disease manifestation and of the patients. A “broad” comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation and platelet-rich plasma therapies. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation, in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using the latest algorithms for meta-analysis and meta-regression implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, HA-based products, currently under circumspection, are still clinically useful.

Indoor crop cultivation systems such as vertical farms or plant factories necessitate artificial lighting. Light spectral quality can affect plant growth and metabolism and, consequently, the amount of biomass produced and the value of the produce. Conflicting results on the effects of light spectrum in different plant species and cultivars make it critical to implement a singular lighting solution. In this study we explored the response of green and red leaf lettuce cultivars (’Aquino’, CVg, or ‘Barlach’, CVr, respectively) to long-term blue-enriched light application (WB). Plants were grown for 30 days in a growth chamber with optimal environmental condi-tions (temperature: 20°C, relative humidity: 60%, ambient CO2, Photon Flux Density (PFD) of 260 µmol m-2 s-1 over an 18-h photoperiod). At 15 days after sowing (DAS) white spectrum LEDs (WW) were compared to WB (λPeak = 423 nm) maintaining the same PFD of 260 µmol m-2 s-1. At 30 DAS, both lettuce cultivars resulted adapted to the blue light variant, though the adaptive re-sponse was specific to the variety. Rosette weight, light use efficiency and maximum operating efficiency of PSII photochemistry in the light, Fv/Fm’, were comparable between the two light treatments. Significant light quality effect was detected on stomatal density and conductance (20% and 17% increase under WB, respectively, in CVg) and, on the modified anthocyanin re-flectance index (mARI) (40% increase under WB, in CVr). Net photosynthesis response was gen-erally stronger in CVg compared to CVr; e.g. net photosynthetic rate, Pn, at 1000 µmol m-2 s-1 PPFD increased from WW to WB by 23% in CVg, compared to 18% in CVr. Results obtained suggest the occurrence of distinct physiological adaptive strategies in green and red pigmented lettuce cultivars to adapt to the higher proportion of blue light environment.

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.

The primary objective of this study is to determine the existence of a significant correlation between inflammation levels, as measured by inflammatory markers IL-6, IL-1β, and TNF-α, and the severity of depressive symptoms assessed using HAM-D assessment scale. This could provide additional evidence supporting the hypothesis that inflammation plays a notable role in the pathogenesis of depression. The data analysis supports the hypothesis that the biological mechanisms of inflammation contributes to the clinical manifestations of depression. Elevated levels of inflammatory markers, especially interleukins (IL6, IL1β), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) have been identified in patients with major depressive disorder compared to the findings in healthy controls. Materials and Methods: Inflammatory markers (IL-6, IL-1β, and TNF-α) were measured in a sample of 31 patients hospitalized at the Socola Institute of Psychiatry in Iasi, Romania, and compared to a control group with no psychiatric or inflammatory conditions. One of the main objectives is to determine if there is a significant correlation between inflammation levels, measured by inflammatory markers (IL-6, IL-1β, and TNF-α), and the severity of depressive symptoms assessed using HAM-D scores. Conclusions: The study results suggest a significant correlation between inflammation levels measured by inflammatory markers IL-1β and IL-6 and the severity of depressive symptoms evaluated by HAM-D scores in the study group. These findings support the hypothesis that inflammation may play an important role in the development or exacerbation of depressive symptoms. The relationship between inflammation and depression is also influenced by risk and protective factors that require further research.

There is a large potential for cost-effective solutions to reduce greenhouse gas emissions and to improve the sustainability of the transport sector that is yet unexploited, in particular in the urban context. Considering the cost-effectiveness and the potential for co-benefits, it is hard to understand why energy gains and mitigation action in the transport sector is still lagging behind the potential. Particularly interesting is the fact that there is substantial difference among countries with relatively similar economic performances, such as the OECD countries in the development of their transport CO2 emission over the past thirty years despite the fact that these countries had relatively similar access to efficient technologies and vehicles. This study aims to apply some well established political science theories on the particular example of climate change mitigation in the transport sector in order to identify some of the factors that could help explain the variations in success of policies and strategies in this sector. The analysis suggests that institutional arrangements that contribute to consensus building in the political process provide a high level of political and policy stability which is vital to long-term changes in energy end-use sectors that rely on long-term investments. However, there is no direct correlation between institutional structures, e.g. corporatism and success in reducing greenhouse gas emissions in the transport sector. Environmental objectives need to be built into the consensus-based policy structure before actual policy progress can be observed. This usually takes longer in consensus democracies than in politically more agile majoritarian policy environments, but the policy stability that builds on corporatist institutional structures is likely to experience changes over a longer-term, in this case to a shift towards low-carbon transport that endures.

Eco-labels are an instrument for enabling informed food choices and supporting a demand-sided change towards a more and urgently needed sustainable food system. Lately, novel eco-labels that depict a product’s environmental life-cycle assessment on a multi-level scale are being tested across Europe’s retailers. This study elicits consumers preferences and willingness to pay (WTP) for a multi-level eco-label. A Discrete Choice Experiment was conducted in Austria. Individual partworth utilities were estimated by means of Hierarchical Bayes. Results show higher WTP for a positive evaluated multi-level label, revealing consumers’ perceived benefits of colorful multi-level labels over binary black-and-white designs. Even a negative evaluated multi-level label showed higher WTP compared to no label, pointing towards limited effectiveness of eco-labels. Respondents’ preferences for eco-labels were independent from their subjective eco-label knowledge, health consciousness, and environmental concern. The attribute “protein source” was most important, and preferences for animal-based protein source (beef) was strongly correlated with consumers’ meat attachment, implying that a shift towards more sustainable protein sources is challenging and sustainability labels have only a small impact on the meat product choice of average consumers.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

A set of polymer composite bolted T-joints with novel configuration consisting of internal skeleton and external skin was fabricated using a prepreg-RTM co-curing molding process. Experiments were conducted to study their mechanical properties under bending load. A finite element model with a polymer resin area between the skin and skeleton was established and verified by the experimental results. Then, the damage propagation process and failure mechanism of the joint and the influence of three factors related to the layer characteristics of the skin and skeleton were investigated by the validated models. The results show that the bending stiffness and the yield limit load of the novel composite T-joint are 0.81 times and 1.65 times that of the 2A12 aluminum T-joint respectively, while at only 55.4% of its weight. The damage of the joint initiates within the resin area and leads to a degradation of the joint bending performances. The preferred stacking sequence of the skeleton is [0/+45/90/-45]ns when primarily subjected to bending loads. The decrease in bending performances is within 5% with the inclining angle of the skeleton less than 12 degrees. The more layers of 90° in the skin, the better bending performances of the joints, while the more layer of 0°, the poorer bending performances.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Land degradation is a serious impediment to improving rural livelihoods in Eastern Africa. This paper identifies major land degradation patterns and causes, and analyzes the determinants of sustainable land management (SLM) in three countries (Ethiopia, Malawi and Tanzania). The results show that land degradation hotspots cover about 51%, 41%, 23% and 23% of the terrestrial areas in Tanzania, Malawi and Ethiopia respectively. The analysis of nationally representative household surveys shows that the key drivers of SLM in these countries are biophysical, demographic, regional and socio-economic determinants. Secure land tenure, access to extension services and market access are some of the determinants incentivizing SLM adoption. The implications of this study are that policies and strategies that facilities secure land tenure and access to SLM information are likely to incentivize investments in SLM. Local institutions providing credit services, inputs such as seed and fertilizers, and extension services must also not be ignored in the development policies.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

With the evolution of toxic chemicals continuing to progress, developing methods for the destruction of chemical warfare agents (CWAs) has become an increasingly important research topic. Metal-organic frameworks (MOFs) are a class of porous crystalline solids that have sparked interest in this area. Due to their exceptional porosities and large surface areas, MOFs possess superior adsorption, reactivity, and catalytic abilities, making them structurally ideal candidates for the capture and decomposition of target species. Additionally, the tunable networks of MOFs allow their chemical functionalities to be customized for various applications and operating conditions, making them practicable in personal protective equipment and adjustable to dynamic environments. This paper reviews experimental and computational studies on CWA removal by MOFs, with a special emphasis on nerve agent (GB, GD, and VX) removal via hydrolysis and sulfur mustard (HD) removal via selective photooxidation. With extraordinary structural stability and reusability, zirconium-based MOFs are the most promising materials for hydrolytic and photooxidative degradation of CWAs and are thus the primary focus of this work. First-principles approximations of the intrinsic catalytic reaction mechanisms towards different agents in Zr-MOFs are summarized, and developments in the structure-property relationships governing Zr-MOF design rules for efficient degradation in the aqueous and solid phases are discussed. We also examine recent progress in tuning and functionalizing MOFs to promote practical CWA removal under realistic battlefield conditions.

Background: Pregnancy can be a period of increased psychological susceptibility for women living with HIV. This study aimed to determine the prevalence and factors associated with depression and psychological stress among women living with HIV during their perinatal period in Ibadan, Nigeria. Methods: This study was a facility-based cross-sectional survey conducted in three HIV treatment centers. The study population consisted of women living with HIV 18 years and above who were pregnant or had given birth within the last two years. Data obtained were analyzed using Statistical Package for Social Science version 25. Results: A total of 402 participants were eligible for this study. About 69.0% and 78.0% of the participants were depressed and had perceived stress respectively. Women who had positive partners (OR=0.60, 95% CI=0.20-1.30) were found to be significantly associated with perceived depression. Women who reported having a gestational age between 29-40 weeks (OR=0.054 95% CI = 0.006, 0.500) were found to be significantly associated with perceived stress. Factors associated with the co-occurrence of symptoms of depression and perceived stress were partner status, income level, family support, gestational age, and years on ART. Conclusions: Given the high prevalence of major depression, perceived stress, and the co-occurrence of depression and perceived stress among women living with HIV, mental health care should be incorporated into the routine maternal healthcare for all women, especially those living with HIV.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

In this work, we study the existence of strange star in the background of f(T,T) gravity in the Einstein spacetime geometry, where T is the torsion tensor and T is the trace of the energy-momentum tensor. The equations of motion are derived for anisotropic pressure within the spherically symmetric strange star. We explore the physical features like energy conditions, mass-radius relations, modified TOV equations, principal of causality, adiabatic index, redshift and stability analysis of our model. These features are realistic and appealing to further investigation of properties of compact objects in f(T,T) gravity as well as their observational signatures.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

A co-curing resin system consisting of 9368 epoxy resin for prepreg and 6808 epoxy resin for resin transfer molding (RTM) was developed. A corresponding preparation method of novel polymer composite bolted T-joint with internal skeleton and external skin was proposed based on prepreg-RTM co-curing process, and novel T-joints were fabricated. A series of conventional configuration T-joints based on RTM process and T-joints made of 2A12 aluminum alloy were prepared simultaneously. Bending performances were studied on these T-joints experimentally. The results indicate that 9368 epoxy resin and 6808 epoxy resin exhibit good compatibility in rheological and thermophysical properties. The novel T-joints prepared with prepreg-RTM co-curing process show no obvious fiber local winding or resin-rich regions inside, and the interface quality between internal skeleton and external skin is excellent. The main failure modes of the novel T-joint under bending load include separation of skin and skeleton and fracture along the thickness on the base panel; the skeleton carries the main bending load, but there is still load transfer between external skin and internal skeleton through their interface. The internal damages of the novel T-joint are highly consistent with surface damages observed visually, facilitating the detection and timely discovery of damages. The initial stiffness, damage initiation load, and ultimate load of the novel T-joint are 1.65 times, 5.89 times, and 3.45 times that of conventional T-joint, respectively. When considering the influence of density, the relative initial stiffness and relative ultimate load of the novel T-joint are 1.44 times and 2.07 times that of aluminum alloy T-joint, respectively.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

This qualitative study explores the role of Supplier Relationship Management (SRM) in optimizing inventory within the context of e-commerce. Through semi-structured interviews with e-commerce managers and supply chain experts, the study investigates the strategies, challenges, and outcomes associated with SRM practices. Key findings highlight the critical importance of strategic partnerships with suppliers, emphasizing trust, transparency, and goal alignment as foundational elements for effective SRM. Participants underscored the transformative impact of technological advancements, including advanced analytics and blockchain technology, in enhancing supply chain visibility, optimizing inventory levels, and improving operational agility. However, the study also identifies challenges in SRM implementation, such as cultural differences, regulatory compliance, and geographical distances, which require proactive management strategies. Innovation emerges as a key driver of competitive advantage in e-commerce, facilitated through collaborative R&D initiatives and co-innovation with suppliers. Strategic alignment with organizational goals is crucial for integrating SRM practices with broader business objectives, including operational efficiency and risk mitigation. Recommendations include adopting integrated SRM strategies that leverage technological innovations while maintaining a focus on relationship-building and sustainability. Enhanced supplier performance monitoring, proactive risk management, and the integration of sustainable practices are proposed to strengthen supplier relationships and enhance supply chain resilience. By addressing these insights, e-commerce firms can optimize inventory management, drive innovation, and achieve sustainable growth in the digital economy.

This study investigates the critical role of Supplier Relationship Management (SRM) in enhancing the e-commerce user experience. In an increasingly competitive digital marketplace, effective SRM practices are essential for optimizing supply chain operations and meeting customer expectations. The research employs a qualitative approach, combining semi-structured interviews with industry stakeholders, extensive literature review, and case studies to explore various dimensions of SRM. Key findings reveal that strategic supplier selection criteria, including quality, cost efficiency, reliability, innovation, and sustainability, are pivotal in ensuring a robust and adaptable supply chain. Effective communication practices, such as transparency, frequent updates, and digital tools, foster strong supplier relationships and enable timely issue resolution. Performance management strategies, centered on KPI monitoring and continuous improvement, support operational excellence and customer satisfaction. Risk management practices, including diversification, contingency planning, and advanced analytics, are crucial for mitigating disruptions and ensuring supply chain resilience, as highlighted by the challenges posed during the COVID-19 pandemic. Technological integration with blockchain, AI, IoT, data analytics, and automation enhances efficiency, transparency, and decision-making capabilities in SRM. Furthermore, the study underscores the evolving integration of sustainability and ethical sourcing into SRM strategies, reflecting broader corporate responsibility goals. Ultimately, this research contributes to understanding how effective SRM strategies drive competitive advantage in e-commerce by enhancing supply chain reliability, responsiveness, and customer-centricity. As e-commerce continues to evolve, adapting and innovating SRM practices will be vital for companies aiming to sustain growth and meet the dynamic demands of global markets.

This study explores the influence of cultural differences on Supplier Relationship Management (SRM) within global e-commerce, examining communication styles, trust-building, negotiation strategies, and strategic alignment across diverse cultural contexts. Through qualitative research including interviews with e-commerce professionals, the study identifies how cultural factors shape SRM practices and outcomes, highlighting the importance of cultural sensitivity and adaptive strategies in fostering effective supplier relationships. Findings underscore the significance of communication preferences, trust norms, and strategic orientations in navigating cultural complexities to enhance operational efficiency and mitigate risks in global markets. Practical implications suggest integrating cultural dimensions into SRM frameworks, prioritizing cultural competence development, and leveraging cultural diversity for innovation and collaboration. Future research directions include exploring digitalization's impact on cross-cultural SRM and longitudinal studies on evolving cultural dynamics in global business. By advancing understanding in this area, e-commerce firms can enhance resilience, maintain competitive advantage, and achieve sustainable growth in the global marketplace.

This qualitative research explores Supplier Relationship Management (SRM) practices within the e-commerce fashion industry, aiming to uncover key strategies and their impacts. Through semi-structured interviews with supply chain managers, procurement officers, and supplier representatives, critical themes emerged: communication, trust, risk management, sustainability, and digital technologies. Effective communication, characterized by transparency and regular updates, emerged as pivotal for aligning expectations and resolving issues promptly. Trust-building practices, including fair dealings and formal agreements, were essential in fostering long-term partnerships, reducing transaction costs, and enhancing collaboration. Robust risk management strategies, such as supplier diversification and contingency planning, were identified as crucial for mitigating disruptions and ensuring supply chain resilience. Sustainability was highlighted as a strategic imperative, driven by ethical sourcing and environmental standards, supported by technologies like blockchain for transparency. The transformative role of digital technologies—supply chain management software, blockchain, IoT, and data analytics—was evident in enhancing visibility and decision-making across global supply chains. Viewing suppliers as strategic partners, rather than mere vendors, promoted collaborative innovation and mutual growth. Despite challenges like cultural differences and regulatory complexities, opportunities exist to enhance SRM through integrated best practices. By prioritizing effective communication, trust-building, risk management, sustainability, and digital innovation, companies can strengthen supplier relationships, optimize supply chain performance, and achieve competitive advantage in the e-commerce fashion sector.

This qualitative study explores supplier collaboration in e-commerce product development, examining motivations, challenges, strategies, outcomes, and ethical considerations. Through in-depth interviews with stakeholders from diverse e-commerce sectors, the study identifies key themes shaping collaboration dynamics. Motivations include innovation, operational efficiency, and strategic partnerships, driving companies to integrate supplier expertise early in product development. Challenges such as global supply chain complexities, goal misalignment, and communication barriers underscore the need for robust governance and cultural sensitivity. Strategies for success include technology adoption, supplier development programs, and collaborative decision-making, enhancing supply chain visibility and mutual benefits. Effective collaboration yields improved product quality, cost efficiencies, and enhanced customer satisfaction, supporting competitive advantage. Ethical sourcing practices and sustainability initiatives are crucial for maintaining trust and regulatory compliance. Cultural and organizational factors, including leadership support and change management, significantly influence collaboration outcomes. The study concludes with implications for theory and practice, emphasizing the role of innovative strategies and continuous improvement in supplier relationships. Future research could explore digital transformation, sustainability trends, and technological impacts on supplier collaboration in e-commerce. Practical applications include optimizing supply chain strategies to navigate complexities and capitalize on market opportunities.

This qualitative research explores the impact of Supplier Relationship Management (SRM) on e-commerce brand reputation, focusing on the strategic imperatives, operational challenges, and economic implications within digital supply chains. Trust emerges as a foundational element in effective SRM practices, facilitating consistent product quality, timely delivery, and consumer trust, thereby enhancing brand credibility and loyalty. Strategic alignment of SRM with organizational goals enables e-commerce brands to leverage supplier capabilities for mutual growth and innovation. Operational challenges such as technological constraints and logistical complexities underscore the importance of digital integration and proactive risk management strategies to optimize SRM effectiveness. Digital technologies, including AI and blockchain, play a transformative role in enhancing transparency, efficiency, and resilience in SRM strategies, enabling e-commerce firms to mitigate risks and capitalize on market opportunities. Emotional intelligence (EI) competencies among supply chain professionals facilitate effective communication, conflict resolution, and sustainable supplier relationships that bolster brand reputation resilience. Economically, effective SRM practices yield cost efficiencies, improved financial performance, and resilience against supply chain disruptions, supporting sustainable growth in competitive digital markets. This study contributes valuable insights for practitioners and scholars aiming to enhance SRM strategies, optimize supplier relationships, and strengthen brand reputation management in e-commerce. By prioritizing trust, strategic alignment, digital innovation, EI competencies, and proactive risk management, e-commerce brands can navigate complexities, capitalize on opportunities, and foster positive brand reputations in the evolving landscape of digital commerce.

This qualitative research explores Supplier Relationship Management (SRM) within the context of subscription-based e-commerce models. Through in-depth interviews and thematic analysis, the study investigates key elements such as trust, collaboration, technology integration, sustainability, risk management, cultural alignment, innovation, cost management, globalization, supplier selection, and performance measurement. Findings reveal that trust is foundational in fostering reliable interactions and open communication between e-commerce businesses and suppliers. Collaboration emerges as crucial for innovation and operational efficiency, facilitating co-development and shared risk management. Technology integration, including AI and blockchain, enhances supply chain visibility and decision-making capabilities. Sustainability considerations drive businesses to engage with suppliers adhering to environmental standards, enhancing brand reputation and consumer loyalty. Effective risk management strategies mitigate disruptions and ensure supply chain resilience. Cultural alignment fosters harmonious partnerships and mutual understanding across diverse global markets. Innovation through supplier collaboration drives product development and market responsiveness. Cost management practices optimize operational efficiency and strategic supplier relationships. Globalization necessitates adaptive strategies to manage diverse cultural and regulatory landscapes. Strategic supplier selection and continuous performance measurement drive ongoing improvement and alignment with business objectives. This study contributes empirical insights and practical implications for enhancing SRM in subscription-based e-commerce, informing strategies to navigate challenges and leverage opportunities in a competitive marketplace.

This qualitative study explores the pivotal role of Supplier Relationship Management (SRM) in enhancing resilience within e-commerce supply chains. In an era marked by rapid digital transformation and global interconnectedness, the resilience of supply chains has become a strategic imperative for organizations striving to maintain operational efficiency and meet customer expectations. Through semi-structured interviews with supply chain managers, procurement officers, and strategic sourcing specialists across diverse industries, this research investigates the strategies, challenges, and outcomes associated with SRM practices. Findings reveal that effective communication and collaboration are fundamental to successful SRM, fostering trust, transparency, and responsiveness in supplier relationships. Strategic risk management through proactive identification and mitigation strategies enables organizations to navigate uncertainties such as economic fluctuations and geopolitical tensions. SRM implementation yields significant organizational benefits, including improved supply chain efficiencies, enhanced product quality, and increased customer satisfaction. However, challenges such as technological complexities, cultural differences among global suppliers, and regulatory compliance issues underscore the need for adaptive strategies and digital investments. The integration of digital technologies such as AI and blockchain enhances SRM effectiveness by enabling real-time data exchange, predictive insights, and decision-making capabilities. Ultimately, SRM emerges as a cornerstone of sustainable growth and competitive advantage in e-commerce, empowering organizations to optimize supply chain performance and resilience amidst dynamic market conditions.

This qualitative study explores Supplier Relationship Management (SRM) in the context of digital transformation within e-commerce businesses, focusing on the implications of emerging digital technologies. Through semi-structured interviews and documentary analysis, the study examines how organizations leverage technologies like artificial intelligence (AI), blockchain, and Internet of Things (IoT) to enhance SRM practices. Findings reveal that digitalization enables improved operational efficiencies, real-time data analytics, and expanded supplier networks through platforms such as Amazon Business and Alibaba. Strategic shifts are noted towards collaborative supplier relationships, emphasizing joint innovation, technology co-investment, and shared risk management strategies. However, the implementation of digital SRM strategies presents challenges, including data privacy concerns, integration complexities, cybersecurity threats, and regulatory compliance issues. Organizations must navigate these challenges by developing robust governance frameworks and cybersecurity protocols to protect sensitive information and ensure regulatory adherence. Key performance indicators (KPIs) such as supplier performance, cost savings, innovation impact, risk management effectiveness, and sustainability integration are critical for evaluating the success of digital SRM initiatives. Strategically, businesses are advised to prioritize leadership commitment, cross-functional collaboration, and continuous learning to optimize digital SRM practices effectively. Future research should explore emerging trends in digital SRM, investigate technological impacts on supplier dynamics and organizational performance, and examine ethical considerations in digitalization. By integrating these insights into strategic decision-making, businesses can enhance supplier relationships, mitigate operational risks, and achieve sustainable growth in the global marketplace.

This qualitative research investigates the influence of Corporate Social Responsibility (CSR) on Supplier Relationship Management (SRM) within the e-commerce sector. Through semi-structured interviews and secondary data analysis, the study explores motivations, challenges, impacts, and strategic outcomes of integrating CSR practices into supplier relationships. Motivations for adopting CSR include ethical considerations, regulatory compliance, and meeting stakeholder expectations, reflecting a strategic alignment with corporate values and societal demands. Challenges such as resource constraints, regulatory complexities, and cultural differences highlight operational hurdles and strategic considerations e-commerce firms face in implementing CSR initiatives effectively. The study reveals that CSR enhances trust, collaboration, and risk mitigation within e-commerce supply chains through transparent communication, shared values, and ethical practices. Strategically, CSR contributes to enhanced brand equity, competitive advantage, and long-term value creation by differentiating firms in competitive markets and attracting socially conscious consumers and investors. However, economic trade-offs, stakeholder divergence, and operational complexities require firms to adopt adaptive strategies that balance short-term financial goals with long-term sustainability objectives. The findings suggest avenues for future research exploring longitudinal impacts of CSR on supplier relationships, cross-sectoral comparisons, and technological advancements in CSR-driven SRM practices. Practically, e-commerce firms should prioritize strategic alignment of CSR initiatives with core business objectives, engage stakeholders in CSR strategy development, and embrace continuous improvement to foster ethical conduct, stakeholder trust, and sustainable business practices.

Supplier diversity has emerged as a critical strategy for enhancing e-commerce operations by fostering inclusivity and innovation within supply chains. This qualitative research explores the role of supplier diversity in e-commerce, examining its impact on organizational strategies, competitive advantage, and stakeholder perceptions. Through semi-structured interviews with procurement managers, diversity officers, and supply chain executives from diverse e-commerce platforms, this study identifies key themes related to the benefits, challenges, and strategic implications of supplier diversity initiatives. Findings indicate that supplier diversity significantly enhances innovation and creativity within supply chains by integrating diverse perspectives and expertise. This diversity not only enriches product development and market responsiveness but also strengthens corporate reputation and brand equity, demonstrating organizational commitment to ethical business practices and community engagement. However, the study reveals persistent challenges, including financial barriers, systemic biases, and scalability issues, which hinder the effective implementation and scalability of supplier diversity programs. Effective supplier relationship management emerges as critical for maximizing the benefits of supplier diversity, fostering trust, collaboration, and long-term partnerships with diverse suppliers. Looking forward, the future of supplier diversity lies in digital transformation, globalization of supplier networks, and integration of sustainable sourcing practices to enhance transparency, efficiency, and resilience in supply chain operations. This study contributes to the growing literature on supplier diversity by providing empirical insights and practical implications for organizations aiming to leverage diversity as a strategic asset in e-commerce and global supply chain management.

This qualitative research explores Supplier Relationship Management (SRM) as a pivotal driver of sustainable practices in the e-commerce sector. Through in-depth interviews with industry experts, practitioners, and scholars, the study investigates how SRM strategies integrate sustainability criteria into procurement processes, mitigate environmental and ethical risks, and enhance operational efficiencies. Key findings highlight the strategic importance of collaborative relationships with suppliers, technological innovations such as blockchain and data analytics in promoting transparency and accountability, and the influence of consumer preferences for sustainable products on market dynamics. Despite challenges such as regulatory complexities and global supply chain dynamics, businesses are increasingly adopting sustainable SRM practices to strengthen brand reputation, achieve cost savings, and align with evolving sustainability standards. The study underscores the interconnected nature of sustainability within e-commerce operations and calls for continued research to advance technological solutions, refine regulatory frameworks, and foster industry-wide collaboration. By embracing sustainability as a strategic imperative, businesses can navigate complexities, drive innovation, and contribute to a more resilient and sustainable future for the e-commerce industry.

This study explores the strategic importance of leveraging supplier relationships for competitive advantage in the e-commerce industry. Strong supplier relationships are crucial for enhancing operational efficiencies, cost management, quality assurance, innovation, sustainability, and overall supply chain resilience. Through collaborative partnerships, e-commerce companies can streamline logistics, reduce costs, ensure consistent product quality, and foster innovation through joint development initiatives. Ethical sourcing and sustainable practices play a pivotal role in supplier relationship management (SRM), aligning with consumer expectations and enhancing brand reputation. Advanced technologies such as AI, blockchain, and IoT further transform SRM practices by improving transparency, efficiency, and decision-making capabilities across the supply chain. The study also discusses challenges in managing global supplier relationships, emphasizing the importance of effective communication, cultural sensitivity, and strategic risk management. By addressing these challenges and nurturing trust-based relationships with suppliers, e-commerce firms can navigate market complexities and achieve sustainable growth. This research provides insights for e-commerce companies seeking to optimize their supplier relationships and maintain competitive advantage in a dynamic market environment.

This qualitative study investigates the management of supplier risks in e-commerce through relationship management strategies, focusing on trust-building, communication practices, digital technology integration, risk assessment methodologies, challenges, innovation initiatives, and ethical considerations. The research aims to provide nuanced insights into how e-commerce companies navigate the complexities of global supply chains to mitigate operational, financial, and reputational risks associated with supplier relationships. Through semi-structured interviews with 20 key stakeholders in the e-commerce sector, data were collected and analyzed using thematic analysis. The findings underscored the foundational role of trust in establishing resilient supplier relationships, facilitated by transparent communication, consistent performance evaluation, and mutual respect for contractual obligations. Effective communication practices, supported by digital platforms and technologies such as AI, blockchain, IoT, and cloud computing, enhanced operational transparency and decision-making capabilities across supply chains. The study identified diverse approaches to risk assessment, from qualitative evaluations to quantitative models utilizing predictive analytics and scenario planning. However, participants highlighted challenges including geopolitical uncertainties, trade disruptions, regulatory changes, and cultural barriers, necessitating adaptive strategies and diversified sourcing options. Innovation initiatives such as joint product development and technology adoption were crucial in enhancing supply chain agility and competitive advantage. Ethical considerations emerged as a critical aspect, influencing supplier selection criteria, CSR initiatives, environmental sustainability practices, and labor standards compliance. Integrating ethical guidelines into supplier contracts reinforced corporate values and enhanced brand reputation. Overall, this study contributes practical implications for e-commerce practitioners seeking to enhance supply chain resilience, mitigate supplier risks, and sustain competitive advantage in a dynamic global marketplace.

This research investigates the pivotal role of Supplier Relationship Management (SRM) in enhancing e-commerce scalability. SRM practices are essential for optimizing supply chain operations and fostering strategic partnerships with suppliers, crucial in the dynamic and competitive e-commerce landscape. Through a comprehensive analysis of case studies, expert interviews, and secondary data, the study examines how leading e-commerce companies such as Amazon and Alibaba implement effective SRM strategies to achieve scalability. Key findings reveal that strategic supplier selection based on capabilities and alignment with business goals, coupled with continuous evaluation and development programs, ensures consistent supply chain performance and customer satisfaction. Technological advancements, including data analytics, artificial intelligence, and blockchain, play a transformative role in modern SRM by enhancing transparency, efficiency, and decision-making capabilities. These technologies enable real-time monitoring, automated processes, and risk mitigation strategies that bolster supply chain resilience and operational efficiency. Best practices in SRM, such as clear performance metrics, a culture of continuous improvement, and ethical sourcing policies, are critical for driving supplier accountability, innovation, and sustainability. Moreover, sustainability emerges as a growing priority in SRM, with businesses integrating environmental and social considerations into supplier management strategies to meet regulatory requirements and stakeholder expectations. Theoretical frameworks like the Resource-Based View and Transaction Cost Economics provide insights into the strategic implications of SRM, emphasizing its role in fostering competitive advantage and long-term business success. As e-commerce continues to evolve, businesses must adapt and innovate in their SRM approaches to navigate global supply chain complexities effectively. By prioritizing effective SRM practices, leveraging advanced technologies, and embracing sustainability, businesses can enhance their scalability, resilience, and competitiveness in the digital economy.

Effective management of supplier relationships is crucial for e-commerce companies to navigate complex supply chain dynamics and mitigate risks associated with supplier disputes. This qualitative study explores the strategies and challenges involved in resolving supplier disputes through relationship management in the context of e-commerce. Through semi-structured interviews with supply chain managers, procurement officers, and executives from diverse e-commerce firms, the study investigates key themes including communication strategies, trust-building initiatives, negotiation dynamics, technological integration, organizational culture, and global supply chain alignment. Findings reveal that clear and transparent communication plays a foundational role in preventing misunderstandings and fostering collaboration with suppliers. Trust-building initiatives, such as consistency in commitments and transparency in business dealings, are essential for cultivating resilient supplier relationships. Negotiation strategies emphasizing principled negotiation and collaborative problem-solving facilitate the resolution of disputes while preserving long-term partnerships. Technological integration through data analytics, automation, and digital platforms enhances operational efficiency and decision-making capabilities in managing supplier relationships. Organizational culture characterized by collaboration, innovation, and leadership commitment to strategic alignment with global supply chains promotes resilience and responsiveness to market dynamics. Challenges including power dynamics, operational constraints, and cultural differences underscore the importance of proactive risk management and cultural sensitivity in supplier relationship management. This study contributes actionable insights for practitioners to enhance supplier relationship management practices, navigate disputes effectively, and foster sustainable competitive advantage in e-commerce. By integrating these findings into strategic planning, e-commerce firms can strengthen supplier partnerships, optimize supply chain performance, and mitigate risks in a dynamic business environment.

This qualitative research explores the transformative role of Artificial Intelligence (AI) in Supplier Relationship Management (SRM) within the e-commerce sector. SRM is critical for e-commerce platforms to maintain efficient supply chains, optimize supplier interactions, and ensure competitive advantage in a dynamic marketplace. AI technologies offer advanced capabilities such as predictive analytics, machine learning algorithms, and natural language processing, which revolutionize traditional SRM practices by enhancing decision-making accuracy, mitigating supply chain risks, and fostering personalized supplier relationships. Through semi-structured interviews with 20 e-commerce professionals and industry experts, this study investigates AI's impact on supplier selection, operational efficiencies, and strategic supplier relationships. Findings highlight AI's ability to streamline supplier evaluation processes, improve demand forecasting accuracy, and optimize inventory management strategies. AI also facilitates personalized supplier engagement through sentiment analysis and real-time insights, promoting collaboration and trust. Ethical considerations, including algorithmic bias and data privacy, emerge as significant concerns in AI adoption for SRM. Addressing these challenges is crucial to maintaining stakeholder trust and ensuring responsible AI deployment. Furthermore, technological integration barriers and organizational readiness are identified as critical factors influencing successful AI implementation. Looking forward, the study underscores the potential of AI to drive innovation and competitiveness in e-commerce SRM, emphasizing the importance of ethical AI practices, technological infrastructure investments, and organizational preparedness for sustainable growth.

This qualitative research explores the integration of digital technologies to enhance supplier engagement in e-commerce, examining the transformative impact of AI, blockchain, and IoT on supplier relationship management (SRM). Through semi-structured interviews and documentary analysis with 15 industry experts, the study reveals that digital technologies enable organizations to optimize supply chain operations, improve transparency, and foster collaborative partnerships with suppliers. Strategic initiatives such as co-development projects and joint innovation efforts are pivotal in accelerating product development cycles and enhancing market competitiveness. Emotional intelligence (EI) emerges as critical in cultivating trust, empathy, and effective communication, underscoring the human dimension of supplier relationships amidst technological advancements. Challenges identified include technological complexity, data privacy concerns, and resistance to change, necessitating robust cybersecurity measures and proactive compliance strategies. Economically, organizations benefit from significant cost savings, improved efficiency, and enhanced profitability through digital transformation initiatives in SRM. By leveraging digital platforms and data-driven insights, organizations can optimize procurement processes, streamline operations, and mitigate risks to achieve sustainable growth and resilience.

Supplier Relationship Management (SRM) plays a pivotal role in enhancing delivery performance within the e-commerce sector, yet understanding its nuanced impacts remains crucial for optimizing operational efficiencies and customer satisfaction. This qualitative research explores the intricate dynamics of SRM in e-commerce, focusing on strategic alignment, technological integration, trust, collaboration, and risk management as key determinants of delivery reliability. Through in-depth interviews and thematic analysis, the study reveals that strategic alignment of supplier capabilities with firm objectives is fundamental for maintaining a responsive and synchronized supply chain. Technological integration, including AI-driven analytics and blockchain applications, emerges as critical for real-time monitoring and adaptive decision-making, thereby improving delivery accuracy and efficiency. Trust and collaboration are identified as essential pillars for building resilient supplier relationships, fostering transparent communication and joint problem-solving. Effective risk management practices, such as supplier diversification and contingency planning, mitigate disruptions and ensure consistent delivery performance. Despite these benefits, challenges such as technological adoption barriers, cultural differences, communication complexities, resource constraints, and supplier reliability issues persist, necessitating strategic interventions. Recommendations include investing in advanced SRM technologies, promoting cultural understanding, enhancing communication protocols, allocating adequate resources, and fostering collaborative initiatives with suppliers. These strategies aim to overcome challenges and optimize SRM practices, ultimately enhancing delivery performance and competitiveness in the e-commerce landscape.

This qualitative study explores collaborative supplier relationships within the context of e-commerce, aiming to uncover the dynamics, challenges, strategies, impacts, and future trends shaping these partnerships. Through thematic analysis of interviews with e-commerce platform managers, supplier representatives, and industry experts, the study identifies three primary types of relationships: transactional, relational, and strategic. Critical factors influencing these relationships include trust, effective communication, technological integration, and regulatory compliance. Challenges such as information asymmetry, cultural differences, logistical complexities, and competitive pressures are examined, alongside strategies for enhancing collaboration, including clear communication protocols, performance evaluations, and technological advancements. The findings highlight the significant impact of collaborative supplier relationships on business performance, including cost efficiencies, supply chain resilience, innovation capacity, customer satisfaction, and market competitiveness. Looking forward, trends in digital transformation, sustainability initiatives, global supply chain networks, resilience-building strategies, and industry collaboration are discussed as shaping the future landscape of e-commerce partnerships. Embracing these trends presents opportunities for organizations to innovate, adapt, and sustain growth in the competitive digital marketplace.

Supplier Relationship Management (SRM) tools play a crucial role in enhancing efficiency and competitiveness within e-commerce supply chains. This qualitative research explores the effectiveness of SRM tools in optimizing procurement processes, mitigating risks, and fostering collaborative partnerships with suppliers. The study employs semi-structured interviews with key stakeholders in diverse e-commerce sectors to gather insights into the implementation and outcomes of SRM tools. Findings reveal that technological advancements, including AI, blockchain, and data analytics, facilitate real-time communication, decision-making, and supply chain visibility, thereby enabling organizations to achieve cost savings and operational efficiencies. Enhanced supplier relationships through SRM tools contribute to collaborative innovation, faster product development cycles, and improved customer satisfaction. However, challenges such as technological complexity, regulatory compliance, and supplier resistance necessitate strategic management and investment in cybersecurity and compliance frameworks. The research underscores the importance of executive sponsorship, stakeholder engagement, and continuous improvement in driving successful SRM implementations.

This qualitative research explores Supplier Relationship Management (SRM) strategies within the context of e-commerce customization, aiming to understand how businesses effectively manage relationships with suppliers to meet personalized consumer demands. Through semi-structured interviews with industry professionals, key themes such as trust, communication, technological integration, strategic alignment, sustainability, and collaboration emerged as critical factors influencing SRM effectiveness. Trust was found to be foundational, fostering cooperation and commitment between e-commerce businesses and suppliers through transparent interactions. Effective communication and the integration of advanced technologies like AI and blockchain enhanced operational efficiency and innovation capabilities, enabling businesses to deliver tailored customer experiences. Strategic alignment between businesses and suppliers proved essential for shared success and mutual benefit, while sustainability practices increasingly shaped consumer preferences and brand reputation. Collaboration facilitated joint innovation and accelerated product customization, underscoring the importance of partnerships in achieving strategic goals. However, challenges including supply chain complexity, managing consumer expectations, and regulatory compliance highlighted the need for continuous improvement and adaptive strategies. Overall, this research contributes valuable insights for e-commerce businesses seeking to optimize SRM strategies, enhance supply chain efficiency, and navigate the complexities of customization in a competitive digital marketplace. By leveraging trust, communication, technology, strategic alignment, sustainability, and collaboration, businesses can effectively meet evolving consumer demands and achieve sustainable growth.

This qualitative research investigates the impact of Supplier Relationship Management (SRM) on e-commerce innovation adoption. Through semi-structured interviews and document analysis, the study explores how SRM practices influence organizational capabilities to innovate in the context of digital commerce. Key themes emerged, emphasizing the critical role of trust, communication, collaboration, strategic alignment, technology integration, organizational culture, leadership, and external factors in shaping e-commerce innovation. Trust was found to be foundational, fostering transparent communication and collaborative relationships that facilitate innovation. Effective communication channels and collaborative initiatives enabled organizations and suppliers to leverage combined expertise, driving the development of innovative e-commerce solutions. Strategic alignment ensured that both parties worked towards shared goals, supported by technology integration that enhanced operational efficiency and decision-making. Organizational culture and leadership were identified as crucial in creating environments conducive to continuous innovation. External factors such as market dynamics, regulatory requirements, and technological advancements influenced innovation strategies, highlighting the need for adaptive and responsive SRM practices. The findings underscore the interconnectedness of these factors within the SRM framework, offering insights into how organizations can enhance their innovation capabilities and competitiveness in the digital economy. By strategically managing SRM practices and integrating sustainable initiatives, organizations can navigate challenges, seize opportunities, and achieve sustained success in e-commerce innovation.

This qualitative study explores how businesses are adapting their Supplier Relationship Management (SRM) strategies to address the challenges and capitalize on the opportunities presented by evolving e-commerce trends. Through in-depth interviews with key industry stakeholders, the research investigates the integration of advanced technologies such as artificial intelligence (AI), blockchain, and the Internet of Things (IoT) into SRM practices. Findings reveal that these technologies enhance efficiency, transparency, and responsiveness within supply chains, enabling businesses to navigate complexities such as supply chain dynamics, fluctuating consumer demand, and regulatory compliance. The study identifies effective strategies employed by businesses, including enhancing communication channels with suppliers, diversifying supplier bases, and investing in technological advancements. These strategies enable businesses to mitigate risks, improve collaboration, and drive innovation, thereby maintaining competitive advantage in the digital marketplace. Collaborative practices such as joint product development, shared risk management, and co-investment in technology emerge as critical drivers of successful SRM. Ultimately, this research contributes to a deeper understanding of SRM in the context of e-commerce, offering insights into how businesses can optimize their supply chain operations amidst technological disruptions and market fluctuations. The findings underscore the importance of proactive adaptation and strategic alignment with suppliers to foster resilient and agile supply chains. As e-commerce continues to evolve, businesses must leverage these insights to refine their SRM strategies and sustain growth in an increasingly competitive environment.

This qualitative study explores the transformative role of Supplier Relationship Management (SRM) in the context of e-commerce, focusing on the integration of digital technologies and evolving supplier interactions. As digital advancements such as artificial intelligence, blockchain, data analytics, cloud computing, and the Internet of Things (IoT) reshape traditional SRM practices, e-commerce companies are experiencing significant improvements in efficiency, transparency, and collaboration. This research employs semi-structured interviews, document analysis, and case studies to examine the impact of these technologies on SRM, identify key collaborative practices, and assess risk management strategies. Findings indicate that digital integration enhances decision-making, streamlines operations, and fosters deeper, trust-based supplier relationships. AI facilitates predictive analytics and automates processes, while blockchain provides transparency and reduces fraud. Data analytics supports informed sourcing decisions and risk mitigation, and cloud platforms improve real-time collaboration. IoT enhances supply chain visibility, allowing for better inventory management. Despite these benefits, challenges such as high implementation costs, integration difficulties, data privacy concerns, and security risks remain significant barriers. Collaboration practices, including joint development, shared resources, and coordinated marketing, contribute to innovation and mutual growth, emphasizing the need for effective communication and trust. Risk management strategies, such as scenario planning and supplier diversification, are crucial for maintaining supply chain resilience. Strategic alignment between e-commerce companies and suppliers, including goal congruence and capability matching, is essential for seamless coordination and competitive advantage. The study underscores the importance of a holistic approach to SRM, integrating technology, collaboration, risk management, and strategic alignment to navigate the complexities of supplier relationships in the digital age. These insights provide a framework for e-commerce companies to optimize their SRM practices and achieve sustainable growth in a dynamic marketplace.

Since its conception with the smallpox vaccination, worldwide-used vaccines have thwarted multiple pandemics including the recent COVID-19 outbreak. Insightful studies uncovered complexities of different functional networks of CD4 T cells [T helper 1 (Th1); Th2, Th17] and CD8 T cells (T cytotoxic; Tc) as well as B cells (BIgM, BIgG, BIgA and BIgE) subsets during response to vaccination. Both T and B cell subsets forge central, peripheral and tissue-resident subsets during vaccination. It also became apparent that each vaccination formed the network of T regulatory subsets, namely CD4+CD25+Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+Foxp3− T regulatory 1 (Tr1) as well as many others, are shaping the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on presenting how pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work revealed that the Treg/Tr1 involvement evoked different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response by increasing a dose, changing the delivery route and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Ra chain) or anti-PD-1 (programmed cell death protein) monoclonal antibody (mAb) to decrease Tregs and boost the T/B cell immune response. All these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals as well as organ transplant patients.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

High temperatures (HT) and high hydrostatic pressures (HHP) are characteristic of deep-sea hydrothermal vents and other deep crustal settings. These environments host vast and diverse microbial populations, yet only a small fraction of those populations have been successfully cultured. This is due, in part, to the difficulty of sampling while maintaining these in situ conditions and also replicating those high-temperature and high-pressure conditions in the laboratory. In an effort to facilitate more HT-HHP cultivation, we present two HT-HHP batch culture incubation systems for cultivating deep-sea vent and subsurface (hyper)thermophilic microorganisms. One HT-HHP system can be used for batch cultivation up to 110 MPa and 121°C, and requires sample decompression during subsampling. The second HT-HHP system can be used to culture microorganisms up to 100 MPa and 160°C with variable-volume, pressure-retaining vessels that negate whole-sample decompression during subsampling. Here, we describe how to build cost effective heating systems for these two types of high-pressure vessels, as well as the protocols for HT-HHP microbial batch cultivation in both systems. Additionally, we demonstrate HHP transfer between the variable-volume vessels, which has utility in sampling and enrichment without decompression, laboratory isolation experiments, as well as HHP filtration.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Intensive application of synthetic pesticides was the routine practice of commercial agriculture during the Green Revolution to boost agricultural productivity to meet global food demand. Alongside this, the application of chemical pesticides caused adverse effects on the environment and its ecoreceptors including human health. Negative externalities arising from conventional farming instigated the call for sustainable development during the sixties to promote and balance the nexus between socially acceptable economic growth and environmental protection. Consequently, a blueprint of 17 Sustainable Development Goals (SDGs) and 169 targets including ecological stewardship and food security was drafted. Eight out of the 17 SDGs are directly linked to sustainable agriculture based on the direct impact of agriculture, judicious use of critical resources and conservation and the Principles of green chemistry. As a green chemical agent, biopesticides have been shown to have the potentials to substitute chemical pesticides with equal agricultural productivity. The adoption of bio-based pesticides via integrated pest management (IPM) has proven to be the most effective option to influence most dimensions of sustainable agriculture. Therefore, biopesticide-driven IPM if utilized with requisite education, skills and research would boost sustainable agriculture. This chapter reviews the prospects, importance, and limitations of biopesticides to sustainable agriculture and how sustainable agriculture is connected to sustainable development, Green Chemistry, and integrated pest management.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the key focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection in pre-clinical models and human trials. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses delivered by replication-deficient vector ChAdOx1. It focuses T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the beta-coronavirus family.

Global stress is widespread in todays post-pandemic world of political and economic uncertainty. Vibroacoustic technology is a vibrotactile intervention with multiple uses, and its impact on stress lacks interpretation. This research assessed if the vibroacoustic technology of a Vibroacoustic Sound Massage (VSM) can reduce psychological, physiological and cognitive stress. The Perceived Stress Scale (PSS-10), and electrocardiogram (ECG) and electroencephalogram (EEG) biosignals were used to quantify results. Participants were divided into Low Stress and High Stress groups. ECG results show VSM increased parasympathetic activity for all participants, with the Low Stress group more effected. EEG results indicate increased concentration (TBR), reduced arousal and increased relaxation (BAR), and non-significant effects on participant well-being (FAA), though variability in this metric was homogenised after VSM. Together, these results validate VSM as an effective support tool for stress management and further research is required.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

Abstract: Qatar and other Gulf States have a diverse range of marine vegetation that is adapted to the stressful environmental conditions of seawater. The industrial wastewater produced by oil and gas activities adds further detrimental conditions for marine aquatic photosynthetic organ-isms on the Qatari coastlines. Thus, these organisms experience severe stress from both seawater and industrial wastewater. This review discusses the biodiversity in seawater around Qatar, as well as remediation methods and metabolic pathways to reduce the negative impacts of heavy metals and petroleum hydrocarbons produced during these activities. These methods include phyto-stabilization phyto-accumulation, phyto-volatilization, and phyto-degradation. Phy-to-degradation in particular is discussed in detail, including metabolic pathways such as alkane and aromatic-compound degradation pathways. The role of microorganisms that are adjacent to or associated with these aquatic marine organisms is discussed, including rhizosphere biodeg-radation. In this type of biodegradation, exudates are released by plant roots and supply nutrients to microorganisms in the rhizosphere, which enhances their ability to degrade organic pollutants. Special attention is paid to mangrove forests and their roles in remediating shores polluted by industrial wastewater. Seagrasses (Halodule uninervis, Halophila ovalis, and Thalassia hemprichii) and seaweeds (Chlorophyta, Phaeophyta, and Rhodophyta) around the peninsula of Qatar are also discussed.

The planning of bicycle infrastructure across our cities remains is a complex task involving many key stakeholders including the community, who traditionally have had limited involvement in the planning process. This research develops an interactive bicycle prioritisation index tool which includes participatory spatial and textual citizen feedback. The research involves three components. Firstly, a survey of current cyclists in Sydney, their current level of participation, priorities in investment in cycling, and preferred locations for cycling infrastructure. Secondly, it documents the development of an interactive digital bicycle planning tool which is informed through citizen feedback. Thirdly, it evaluates the approach in conversation with potential end-users, including government, planning practitioners, and advocacy group members. The research proposes the combination of multiple passive and active data traces with end-user evaluation to legitimise the citizen co-design of bicycle investment prioritisation initiatives. A case study approach has been taken, focusing on the city of Sydney, Australia. The bicycle planning support system can be used by cities when engaging in cycle prioritisation initiatives, particularly with a focus on integrating citizen feedback and navigating new and complex data landscapes introduced through recent, passively collected big data sets.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

For quantitative determination of honokiol (HNK) and metformin hydrochloride (M-HCl) by HPLC from formulations and from dissolution studies, a QbD approach using three factors - three levels design was implemented to optimize the chromatographic conditions. To study the impact of each variable on the peak area of both compounds and retention time of last compound eluted, the 3D response surface plots were developed. HNK and M-HCl were separated on a Thermoscientific ODS Hypersyl TM (250 x 4.6 mm, 5 μm) column mantained at 30 C, using 0.02 M acetate buffer (pH = 3) / methanol (15 / 85, v / v) as mobile phase with a flow rate of 1 mL/min. The injected volume was 20 L, and the detection wavelengths were 256 nm for HNK and 236 nm for M-HCl. The validation of proposed method showed a linearity range of 4 – 1200 μg/mL for M-HCl (r2 = 0.9992) and 1 – 300 μg/mL for HNK (r2 = 0.9998), good precision (RSD &lt; 2% for both HNK and M-HCl, in intra- and inter-day studies) and accuracy (mean recovery = 100.09% in the range 99.80 – 100.43% for M-HCl and mean recovery = 100.12% in the range 99.70 – 100.38% for HNK). The environmentally friendly nature of the method was confirmed by the evaluation of the method’s greenness. The proposed method was applied for the determination of HNK and M-HCl from oral dosage forms and in dissolution studies.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Within this paper, electro-mechanical long-term tests on a thrust bearing are presented. The effects of an additional electrical load on the bearing raceways and the used lubricant are investigated. Chemical and rheological investigations are presented which show the changes in the lubricant. These investigations are compared with the electrical loads and the occurring raceway damage. In addition, a comparison is made with mechanical reference tests. This procedure makes it possible to classify the changes that occur due to the electrical load and to distinguish the effects from each other. The background to these investigations is the increased occurrence of parasitic currents in electric motors, which can lead to damage to machine elements. The phenomena that occur here are new challenges in the development of drive trains.

Rainfall, or more generally the precipitation process (flux), is a clear example of chaotic variables resulting from a highly nonlinear dynamical system, the atmosphere, represented by a set of physical equations such as the Navier-Stokes equations, energy balances and hydrological cycle among others. As a generalization of the Euclidean (ordinary) measurements, chaotic solutions of these equations are characterized by fractal dimensions, which are non-integer values that represent the complexity of variables like the precipitation. However, observed precipitation is measured as an aggregate variable over time, thus physical analysis of the observed fluxes is very limited. Therefore, this review aims to go through the different approaches used in the identification and analysis of the complexity of the observed precipitation, taking advantage of its geometry footprint. To address the review, it ranges from classical perspectives of fractal-based techniques to new perspectives at temporal and spatial scales as well as for classification of climatic features, including monofractal dimension, multifractal approaches, Hurst exponent, Shannon entropy and time scaling in intensity-duration-frequency curves.

Most recent university campuses follow the North American model, built on city limits or countryside, with large separate buildings in open green spaces. Studies suggest that prevalence and severity of mental health issues among university students are increasing over the past decade in most countries. University services were created to face this growing problem, however individual based interventions have limited effects on mental health and well-being of a large population. Our aim was to verify if and how the natural environment in Campuses is focused on programs to cope with the issue of mental health and well-being among students. Systematic review of literature was undertaken with search in Scopus and LILACS with the keywords “green areas” AND “well-being” AND “Campus”, following PRISMA guidelines. As a result, 32 articles were selected. Research on the topic is recent, mostly in the USA, Bulgaria, and China. Most studies used objective information on campuses’ greenness and/or university students’ perception. Mental health was usually measured by validated scores. Findings of all the studies indicated positive association between campus greenery and well-being of students. We conclude that there is a large potential for use of university campuses in programs and sites for students´ restoration and stress relief.