In this study, we have focused on studying the heterogenous degradation kinetics of regarding the decomposition of emergency contraceptive agent levonorgestrel (LNG), which is a second-generation synthetic progestogen that is the active component of the racemic mixture of norgestrel. The degradation processes of the active pharmaceutical ingredient (API) were compared with the ones obtained from model system containing the API along with the excipients that are found in a commercialized pharmaceutical formulation in a mass ratio of 1:1 (LNGMIX), in order to observe if the excipients have a stabilizing or destabilizing effect for the degradation of this progestogen. To achieve this, the following investigational methods were used: FTIR (Fourier transform infrared) spectroscopy and thermal analysis (TG/DTG/DSC analysis). For the kinetic analysis the data obtained from two main decomposition processes observed on the DTG curves were used and processed with a preliminary method, namely ASTM E698 and two isoconversional methods: Friedman and Flynn-Wall-Ozawa. The isoconversional study revealed that the decomposition mechanism of both LNG and LNGMIX are complex, and the excipients have a stabilizing effect over decomposition of API in tablet.

Since life on earth developed, parasitic microbes have thrived. Increases in host numbers, or the conquest of a new species, provides an opportunity for such a pathogen to enjoy, before host defense systems kick in, a similar upsurge in reproduction. Outbreaks ‒ caused by ‘endemic’ pathogens ‒ and epidemics ‒ caused by ‘novel’ pathogens ‒ have thus been creating chaos and destruction since prehistorical times. To study such (pre)historic epidemics, recent advances in the ancient DNA field, applied to both archeological and historical remains, have helped tremendously to elucidate the evolutionary trajectory of pathogens. These studies offered new and unexpected insights in the evolution of, for instance, smallpox virus, hepatitis B virus and the plague-causing bacterium Yersinia pestis. Furthermore, burial patterns and historical publications can help in tracking down ancient pathogens. Another source of information is our genome, where selective sweeps in immune-related genes relate to past pathogen attacks, while multiple viruses have left their genomes behind for us to study.

Antimicrobial resistance (AMR) is a worldwide healthcare problem. Multidrug resistant organisms (MDRO) have the ability to spread quickly owing to their resistance mechanisms. Although colonized individuals are crucial MDRO dispensers, colonizing microbes have the potential to turn pathogenic under certain conditions, leading to symptomatic infections in carriers. Carbapenemase producing Enterobacterales (CPE) are among the most important MDRO involved in infections and colonizations, associating with multiple resistance mechanisms and virulence factors, causing infections with severe outcomes. All research papers identified in the most comprehensive online databases which contained information related to the topic of this article were analyzed, and relevant data was extracted and included. The first information on CPE could be traced back to the mid-2000s, but pertinent data for many African countries was established in the past 5-8 years. Information is presented chronologically for each country. Although no clear conclusions could be drawn for some countries, it was observed that CPE colonizations are present in most African countries and carbapenem-resistance levels are rising. The most common CPE involved are Klebsiella pneumoniae and Escherichia coli, and the most prevalent carbapenemases are NDM-type and OXA-48-type enzymes. Prophylactic measures, such as screening, are required to combat this phenomenon.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with a distinct set of facial features, growth limitations, and limb anomalies. Its clinical spectrum is broad and presents significant challenges in pediatric diagnosis and management. The variable presentation of the disorder, due to cohesin complex mutations, requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients, alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, with an emphasis on innovations in genetic testing, including the detection of mosaicism and novel genetic variations. The aim is to synthesise case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment, and aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

The research deals with the particularities of the initiation in the sport of kin ball, of 94 students (54 boys and 40 girls), without a history of practicing the sport intensively, and the measure of the influence of some components of the motor capacity. Kin ball is a sport that appeared in Canada, in an academic setting and can become an alternative sport in the common university curricula in Romania. The research was carried out in 4 research groups in 2019 and 2022, two of boys and two of girls, similarly, before and after the declaration of the acute phase of the Covid-19 Pandemic, generating physical activity constraints. The originality of the research refers to the initiation, unprecedented in Romania, in the Kin ball sport, through 20 training sessions, carried out in 10-day stages and the evaluation of some motor skills on the subjects. During the experiment, the following components were tested pre- and post-intervention Kin-Ball: palmar muscle strength using the dynamometer, general resistance by running as long as possible for 2 min and general coordination function - body balance, by the Matorin test. The statistical calculation included the application of the Kolmogorov-Smirnov test, depending on which parametric or non-parametric statistical significance tests were applied and the estimation of the size of the intervention effect. The results highlighted particularities of initiation in Kin ball, but also significant differences (p<0.05) in all measurements performed in 2022. The tests in 2019 recorded both significant and statistically insignificant differences, also highlighted by the calculation of the d indicator of to Cohen. The lower initial level of all motor components measured in 2022 and their significant improvement represent aspects that can be understood as collateral effects of the lack of movement during the pandemic.

The purpose of this article is to investigate and analyze the practices of scientific management within the County Departments of Sports and Youth (CDYS) in Romania. Conducted through a comprehensive research endeavor spanning from January to June 2022, the study utilized a standardized questionnaire as its primary instrument for data collection, distributed among CDYS directors. A notable finding from the study indicates that a significant proportion of respondents (44.9%) perceive notable disparities in the normative-functional elements governing the National Sports System in Romania compared to international standards. Moreover, the majority (51%) consistently adhere to regulatory acts, while a substantial portion (69.4%) underscore the importance of strict adherence to internal regulations in strategy formulation. Furthermore, an overwhelming majority (88.9%) acknowledge the substantial influence of available resources on strategy development, with collaboration with authorities primarily occurring through direct communication channels. Respondents prioritize multiple objectives (44.9%), affirm the necessity of various competencies (53.1%), and identify a lack of human and financial resources (59.2%) as the most significant obstacle. Notable achievements highlighted in the study include the improvement of the county's sports performance (53.1%). Respondents also believe that setting clear and realistic objectives (38.8%) is pivotal to enhancing CDYS management, while considerations in formulating strategies emphasize trends in the sports domain (42.9%) and the specific needs of the local sports community (42.9%). Overall, this research contributes to the understanding and promotion of more efficient practices in managing sports and youth departments within Romania's counties.

Background: Since 2000, vaccine coverage in Sub-Saharan Africa (SSA) has surpassed multiple milestones. Its contribution to global health, especially in low-middle-income countries is one of the achievements in global governance of modern medicine, averting 2-3 million child deaths every year. However, in Nigeria, vaccine-preventable-diseases still account for one in eight child deaths before their fifth-year birthday and remains one of the ten countries where 4.3 million children under five are without complete immunization. The reasons for declining childhood vaccine demand are unclear. Therefore, the goal of this contribution is to shed light on the reasons to set a foundation for future interventions. Methods: Four focus group discussions were conducted. The primary targets were mothers of children 0 – 12 months old in Nigeria. A simplified quota sampling approach was used to select mothers in four geographical clusters of Nigeria’s Federal Capital Territory. At least six mothers from each cluster were randomly included, giving a total of 24 participants. An interview guide developed from the 5C psychological antecedence model was used (assessing confidence, complacency, calculation, constraints, collective responsibility); two additional variables were included that had proved meaningful in previous work (religion and masculinity). The data were analyzed using meta-aggregation approach such as framework synthesis, which summarized data in a stepwise fashion. Results: The sample was generally relatively positive towards vaccination. Still, mothers reported low trust in vaccine safety and the healthcare system (confidence). Yet, they had great interest in seeking additional information during antenatal visits (calculation), difficulties in prioritizing vaccination over other equally competing priorities (constraints) and were aware that vaccination translates into overall community health and wellbeing (collective responsibility). They had a bias towards God as ultimate giver of good health (religion) and reported that their husbands played a dominant role in vaccination decision-making (masculinity). Mothers perceived their children vulnerable to disease outbreaks, which motivated them to get them vaccinated (complacency). Conclusion: The 5C model and the added determinants provided a useful qualitative tool for understanding mothers’ vaccination decision-making in low resources settings.

In this article, management control has been studied from the perspective of intention towards sustainable development of companies. The main idea focuses on the analysis of relations between sustainable management control and the system of performance appraisal using as a reference the resource-based theory. These relations have been assessed both theoretically by reviewing literature in the field, and empirically based on data collected in a questionnaire from top management, as well as data from Annual Reports from the main segment of Bucharest Stock Exchange. The authors have shown that financial performance has a significant influence on management control, and the return on capital employed is one of the most recommended indicators. The sustainable nature attributed to management control is the result of institutional theory evolution, provisions of Directive 2014/95/EU and Guide of Global Management Accounting Principles (2015) using stewardship. Consequently, profits are not the main element any more in the assessment of financial „health” of a company. To ensure the sustainable success, sustainable balanced scorecard is one of real measures for managing financial and non-financial performance.

Autologous micrografting technology (AMT®) involves the use of autologous micrografts to stimulate/enhance the repair of damaged tissue. This study assessed the efficacy and safety of the AMT® procedure in patients with early stages of knee osteoarthritis. Briefly, the AMT® procedure involved extraction of auricular cartilage, disaggregation using the Rigeneracons® SRT in 4.0 mL of saline solution and injection of the disaggregated micrografts into the external femorotibial compartment area of the affected knee. Ten patients (4 men, 6 women; age range: 37─84 years) were included in the study. In all patients, there was a steady improvement in knee instability, pain, swelling, mechanical locking, stair climbing and squatting at 1- and 6-months post-procedure. Improvement in mobility was observed as early as 3 weeks post-procedure in 2 patients. Significant improvements were seen in mean scores of all five subscales of Knee Injury and Osteoarthritis Outcome Score (KOOS [KOOS symptoms, KOOS pain, KOOS ADL, KOOS sport and recreation, and KOOS quality-of-life]) between pre-procedure and 1- and 6-months post-procedure (all p≤0.05). Autologous auricular cartilage micrografts obtained by AMT® procedure (using Rigenera® technology) is an effective and safe protocol in the treatment of early-stage knee osteoarthritis. These encouraging findings need to be validated in a larger patient population.

This study explores the complexities of sport manager selection, investigating the impact of affirmative action, recruitment strategies, organizational culture, diversity initiatives in board selection, and career advancement insights from coaches' perspectives. To conduct this investigation, a purposive sampling technique was employed, selecting 65 prominent sports managers and coaches from Romania. Participants, aged between 35 to 58 years old, boasted an average of 10 to 20 years of sports experience and were chosen based on specific criteria, including academic qualifications. Data collection occurred over an extended period, spanning from fall 2022 to spring 2024, through semi-structured interviews with sport managers and coaches. The findings unveiled persistent challenges in effectively implementing affirmative action measures, as sport managers grapple with balancing the promotion of deserving candidates while maintaining continuity in board culture. Achieving meaningful diversity necessitates nuanced approaches that consider both candidate quality and cultural compatibility. Moreover, the study sheds light on coaches' perspectives when considering executive council positions, highlighting various pathways to career advancement. Recruitment practices prioritized informal methods, emphasizing board cohesion. Despite the recognized importance of diversity, challenges persist in selecting candidates solely based on demographic representation. The study provides valuable insights into promoting diversity and inclusivity within sports organizations' executive councils. Future research directions may include exploring longitudinal trends and delving into the qualitative experiences of underrepresented groups, with the aim of advancing understanding and promoting equity within sports organizations.

The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There is a limited number of antifungal medications available for treating IFIs and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, have become increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity: manogepix, rezafungin, ibrexafungerp, and olorofim against 100 isolates of Aspergillus section Terrei, containing amphotericin B (AmB) wildtypes/non-wildtypes and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against tested isolates, exhibiting a geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentrations (MIC) range respectively as follows: manogepix (0.048 mg/L, 0.032-0.5 mg/L), rezafungin (0.020 mg/L, 0.016-0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032-2 mg/L), and olorofim (0.008 mg/L, 0.008-0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus and cryptic species that were azole-resistant and AmB non-wildtype.

Solidago virgaurea L. (European goldenrod, Woundwort), Asteraceae, is a familiar medicinal plant in Europe and other parts of the world, widely used and among the most researched species from its genus. The aerial parts of European goldenrod have long been used for urinary tract conditions and as an anti-inflammatory agent in the traditional medicine of different peoples. Its main chemical constituents are flavonoids (mainly derived from quercetin and kaempferol), C6-C1 and C6-C3 compounds, terpenes (mostly from the essential oil), and a large number of saponin molecules (mainly virgaureasaponins and solidagosaponins). Published research on its potential activities is critically reviewed here: antioxidant, antiinflammatory, analgesic, spasmolitic, antihypertensive, diuretic, antibacterial, antifungal, antiparasite, cytotoxic and antitumor, antimutagenic, antiadipogenic, antidiabetic, cardioprotective, and antisenescence. The evidence concerning its potential benefits is mainly derived from non-clinical studies, some effects are rather modest, whereas others are more promising, but need more confirmation in both non-clinical models and clinical trials.

We assessed depression, anxiety, and stress in healthcare workers (HCWs) in 2023 and the evo-lution of depression in 2023 compared with 2022. In September-November 2023, 181 HCWs from the Infectious Diseases Hospital, Cluj-Napoca, Romania, completed the Depression, Anxiety, and Stress 21 Scale (DASS-21 R), the Patient Health Questionnaire-9 (PHQ-9), and the Hamilton Anxiety Rating Scale (HAM-A). The prevalence of moderate-to-severe levels was 13.81% for DASS-Depression, 18.79% for DASS-Anxiety, 16.02% for DASS-Stress, 19.89% for PHQ-9, and 12.16% for HAM-A. Moderate-to-severe PHQ-9 clinical depression was found in 19.89% of respondents, and moderate-to-severe HAM-A clinical anxiety in 12.16%. Moderate-to-severe PHQ-9 depres-sion was significantly lower in the 2023 study group (19.89%, N=181) compared with 2022 (30.60%, N=114) (p=0.036), also within the 2022-2023 follow-up study group (N=88) (p=0.026). We did not find significant statistical differences between those infected vs. non-infected, vaccinated vs. non-vaccinated, working with vs. non-working with SARS-CoV-2 infected patients. Males were significantly more stressed (p=0.018) and anxious (p=0.034), and physicians in training had the highest prevalence of moderate-to-severe depression (31.60%), followed by physicians (25.64%). In 2023, depression, anxiety, and stress symptoms decreased but remained within a concerning range. By addressing these psychological issues, we can prevent professional crises in the healthcare system.

Two novel dsRNA mycoviruses were found in different isolates of Diplodia fraxini, NW FVA 1581 and NW FVA 1706, which were isolated from a root, associated with stem collar necrosis of Fraxinus excelsior L. Both mycelia are infected by a novel fusagravirus, which was named Diplodia fraxini fusagravirus 1 (DfFV1), and isolate NW FVA 1706 is additionally infected by a novel partitivirus, which was denominated as Diplodia fraxini partitivirus 1 (DfPV1). The one-segmented, bicistronic genome of DfFV1 is composed of about 8,500 bp. Their ORFs are connected by a 1 slippery heptamer sequence and the 3’ terminal ORF is coding for the viral RdRp. The genome of DfPV1 is composed of three, monocistronic dsRNA segments ranging from 1,755 bp (dsRNA 1) over 1,588 bp (dsRNA 2) to 1,233 bp (dsRNA 3). Based on genome organization and phylogenetic positions, DfFV1 was assigned to the proposed family of “Fusagraviridae” and DfPV1 to the genus Gammapartitivirus within the family of Partitiviridae. Ultra-structural analysis showed that polysomal structures were stabilized in the single infection and none of these structures could be isolated in the double infection. It is assumed that DfFV1 has an opportunistic lifestyle, being either protected by ribosomes or by transcapsidation from particles of DfPV1.

This study aimed to investigate Romanian physicians' awareness, recommendation practices, and opinions regarding using Foods for Special Medical Purposes (FSMPs) products. A total of ten physicians were interviewed using a structured questionnaire, and their responses were analysed using thematic content analysis. The study found that physicians were aware of FSMPs and recommended them to their patients based on nutritional deficits, weight loss, or deglutition impairments. In addition, disease stage, treatment scheme, taste, affordability, and availability were identified as factors influencing the recommendation and use of FSMPs. While physicians generally did not consult clinical trials, clinical experience was deemed essential for recommending FSMPs to patients. Patients' feedback regarding the usage and sourcing of FSMPs was generally positive, with some expressing concerns about the availability of different flavours and the costs of purchasing the products. The study concludes that physicians play a vital role in recommending FSMPs to patients and ensuring they have the necessary nutritional support during treatment. However, more patient education materials and collaboration with nutritionists may be required to improve patient outcomes and reduce patient financial burden.

(1) Background: This study aimed to evaluate the implications of IL-31 in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Our data have shown higher serum levels of IL-31 in CSU patients compared to controls. A correlation between the serum level of IL-31 and other inflammatory markers, such as ERS, CRP, or serum eosinophils and total IgE was not identified. On the other hand, statistically significant differences were found in IL-31 serum values in UCS patients depending on the severity of the disease, its impact on the patients' quality of life, the severity of itching, and the response to H1 antihistamines. (4) Conclusions: In the present study, IL-31 did not change directly with non-specific inflammation, nor with eosinophilic inflammation or atopy. However, its expression was modified in CSU depending on major characteristics of the disease: severity, pruritus, and response to H1 antihistamines. The focus on the pathogenesis of CSU is of indisputable significance since any additional information in understanding the mechanisms of this disease can open doors to new therapeutic targets. This is particularly important considering that the available therapies are deficient, incomplete, and the remaining symptoms are uncontrolled in many cases.

Carcinoembriogenic antigen (CEA) is a routine marker for follow-up of colo-rectal cancers. We aimed to determine whether a CEA increase within the normal range can be linked to a recurrence risk. We included 78 consecutive patients with colo-rectal cancer, who underwent curative surgical treatment with or without chemo- or radiotherapy. As reference, we used the smallest value of the CEA during follow-up. A total of 34/78 patients (43.6%) had fluctuations of CEA of at least 1.1 ng/ml, with or without increases above 5 ng/ml. In 27/34 patients (79.4%) increases of CEA were explained either by recurrence (15/34 patients, 44.1%), adjuvant chemotherapy (7/34 patients, 20.6%) or benign pathology (5/34 patients, 14.7%). In 5 of 22 recurrences (23%) a CEA increase of at least 1.1 ng/ml, but below 5 ng/ml preceded the clinical relapse by a median of 8 months (range 3-22 months). The 4-year disease-free survival was 89% in patients with postoperative CEA <2.5 ng/ml, and 55% in patients with CEA >2.5 ng/ml. CEA increase by at least 1.1 ng/ml within the normal range, after curative treatment of colorectal cancer can be either an early sign of relapse or can be usually explained by other pathological processes.

The double burden of malnutrition (DBM) is escalating in low- and middle-income countries (LMICs), including in Rwanda, most notably in urbanizing areas. The 2019-2020 Rwanda Demographic Health Survey (DHS) revealed 33% of children under 5 are stunted while 42% of women in urban areas are overweight or obese. This coexistence has contributed to a surge in non-communicable diseases (NCDs), particularly in secondary cities. Using the World Health Organization’s (WHOs) “double-duty action” (DDA) concept, this study aims to identify and evaluate interventions with double-duty potential in Rwanda, focusing on the districts of Rusizi and Rubavu. Guided by Hawkes et al.’s conceptual framework for identifying DDA entry points, a desk review of national policies pinpointed 4 programs with DDA potential: early childhood development (ECD) centers, the school feeding program, farmer field schools (FFS), and the provision of nutrition-sensitive direct support. In-person interviews with key stakeholders assessed their implementation and a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis informed context-specific recommendations for their improvement. Recommendations include targeting beliefs surrounding nutrition, improving trainings for community educators, enhancing parent – particularly father – involvement, and close follow-up. These findings offer actionable strategies for governments and nutrition stakeholders and may benefit similar interventions in other rapidly urbanizing LMICs.

This study aims to establish whether the use of biomaterials, particularly polydimethylsiloxane (PDMS), for surgical reconstruction of the esophagus with templates, Montgomery salivary tube, after radical oncology surgery for malignant neoplasia is an optimal choice for patients’ safety and for optimal function preservation and organ rehabilitation. Methods: Structural analysis by Raman spectrometry and biomechanical properties with dynamic mechanical analysis are performed for fatigue strength and toughness, essential factors in durability of a prosthesis in the reconstruction practice of the esophagus. Nanocomposites with silicone elastomers and nanoparticles used in implantable devices and in the reconstruction surgery are facing risks of infection and fatigue strength when required to perform a mechanical effort for long periods of time. Results: This report takes into account the effect of silver (Ag) nanoparticles on the fatigue strength using polydimethylsiloxane (PDMS) matrix, representative for silicon elastomers used in implantable devices. PDMS with 5% (wt) Ag nanoparticles of 100-150 nm during mechanical fatigue testing at shear strength loses elasticity properties after 400 loading-unloading cycles and up to 15% shear strain. The fatigue strength, toughness, maximum shear strength are the key issues in designing Montgomery salivary tube with appropriate biomechanical behavior for each patient. Conclusions: Prosthesis design needs to indulge both clinical outcome as well as design methods and research in the field of biomaterials.

This research investigates entrepreneurial attitudes among 415 students in the academic sports domain. Utilizing a 15-item questionnaire, participants were categorized into four groups based on their sports background: individual and team sports with competitive history, amateur athletes, and non-practitioners. The questionnaire exhibited good internal consistency (Cronbach's alpha coefficient = 0.755). Statistical analysis using the Chi-Square Test of Homogeneity across criteria such as gender, competitive sports involvement, type of competitive sports, and engagement in amateur sports revealed significant differences in nine out of 60 comparisons. Furthermore, this study employs an explanatory approach to elucidate the distinctions among athletes, amateur, and non-athlete students in academic sports programs regarding assumption of responsibilities, proactive initiative, determination to establish their own businesses, perception of the comfort zone, and the perception of post-sports career adaptation. Additionally, a gender comparison is conducted concerning the perception of business risk, comfort and security in a stable workplace, and the applicability of sports-oriented approaches in business. These results provide valuable insights into how sports backgrounds shape entrepreneurial perspectives, thereby contributing to the development of customized entrepreneurial programs. Moreover, the study seeks to offer a nuanced comprehension of the diverse factors influencing the entrepreneurial attitudes and perceptions of students in sports academic programs.

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be latently activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8 and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways “PKA signaling”, “PTEN signaling” and “leukocyte extravasation”. Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of latently activated granulocytes upon IL8 stimulation, and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.

The aim of this review was to search in literature, data regarding the inflammasome, involvement in, oral pathologies (mainly periodontitis) and other diseases and the approaches to control the inflammasome-related pathogenic mechanisms. The review also investigated how phytochemicals and pharmaceutical substances could be used to inhibit the inflammasome activity. Inflammasomes are involved in inflammatory, autoimmune and autoinflammatory diseases. Pharmaceutical substances can control the inflammasome by three mechanisms: inhibiting of intracellular signaling pathways (Allopurinol and SS-31), blocking inflammasome components (VX-765, Emricasan and VX-740), and inhibiting cytokines mediated by the inflammasome (Canakinumab, Anakinra and Rilonacept). Phytochemical inhibit the inflammasome, by neutralization of reactive oxygen species. Biomaterials functionalized by the adsorption of therapeutic agents on different nanomaterials may represent a future research direction to facilitate multimodal and sequential treatment in oral pathologies.

The Emergency Department (ED) represents an important setting for addressing inappropriate antimicrobial prescribing practices, due to the time constraints and duration of microbiolo-gical diagnosis. The purpose of this study was to evaluate the etiology and antimicrobial resistance (AMR) pattern of the community-acquired pathogens, as well as the epidemiological characteristics of patients admitted through ED, in order to guide appropriate antibiotic therapy. (2) Methods: A retrospective observational study was performed on 657 patients, from whom clinical samples for microbiological diagnosis were collected, in the first 3 days after presentation in the ED. The identification of pathogens and the antibiogram with minimum inhibitory concentration determination were carried out according to the laboratory protocols. (3) Results: From the 767 biological samples analyzed, 903 microbial isolates were identified. E. coli was isolated most frequently (24.25%), followed by Klebsiella spp, S. aureus (SA) and non-fermentative Gram-negative bacilli. E. coli strains maintained their natural susceptibility to most antibiotics tested. In the case of Pseudomonas spp. and Acinetobacter spp., increased rates of AMR were identified. Also, 32.3% of SA strains were community-acquired MRSA. (4) Conclusions: The introduction of rapid microbiological diagnostic methods in emergency medicine is imperative in order to timely identify AMR strains and improve therapeutic protocols.

This study investigates the complex interplay between public sentiment, as captured through news titles and descriptions, and the stock prices of three major tech companies: Microsoft (MSFT), Tesla (TSLA), and Apple (AAPL). Leveraging advanced analytical methods including Pearson correlation, wavelet coherence, and regression analysis, this research probes the degree to which stock price fluctuations can be attributed to the polarity of media sentiment. The methodology combines statistical techniques to assess sentiment's predictive power on stock opening and closing prices, while wavelet coherence analysis unveils the temporal dynamics of these relationships. Results demonstrate a significant correlation between sentiment polarity and stock prices, with description polarity affecting Microsoft's opening prices, title polarity influencing Tesla's opening prices, and a positive impact of title polarity on Apple's closing prices. However, Tesla's stock showed no significant coherence, indicating a potential divergence in how sentiment affects stock behavior across companies. The study highlights the importance of sentiment analysis in forecasting stock market trends, revealing not only direct correlations but also lagged influences on stock prices. Despite its focus on large-cap tech firms, this research provides a foundational understanding of sentiment's financial implications, suggesting further investigation into smaller firms and other market sectors.

The objective of this study was to investigate the impact of athletes' respiratory muscle strength, as assessed through maximal inspiratory (MIP) and expiratory pressure (MEP), on aerobic endurance, as indicated by maximal oxygen consump-tion (Max VO2) kinetics. Respiratory muscle strength was assessed using a digital spirometer (Pony FX Cosmed, Italy), while maximal oxygen utilization capacity was measured using a breath-by-breath automatic portable gas analysis system (Cosmed K5, Italy). Statistical analysis was conducted utilizing SPSS 22.0. Based on the standardized regression coefficients (β), it was found that MEP (mean ± SD: 130.95 ± 42.82) and inspiratory diaphragmatic circumference values significantly influenced ventilatory equivalent (VE), oxygen consumption (VO2), and carbon dioxide pro-duction (VCO2). Conversely, the remaining predictor variables did not exhibit a sig-nificant effect on VE (mean ± SD: 134.80 ± 36.69), VO2 (mean ± SD: 3877.52 ± 868.47 ml), and VCO2 (mean ± SD: 4301.27 ± 1001.07 ml). In contrast, measurements of chest circumference (mean ± SD: 91.40 ± 10.72 cm), MEP, and diaphragmatic cir-cumference during inspiration (mean ± SD: 95.20 ± 10.21 cm) were found to signifi-cantly impact Max VO2 (mean ± SD: 58.52 ± 10.74 ml/kg/min), while the other pre-dictor variables did not demonstrate a significant effect on Max VO2. Conclusively, the study revealed that measured values of diaphragmatic circumference during inspiration and MEP exerted a notable influence on Max VO2, VE, VO2, and VCO2. Our findings underscore the importance of considering respiratory muscle strength in assessing and enhancing athletes' aerobic performance. These insights contribute to a deeper understanding of the interplay between respiratory function and exercise capacity, offering potential avenues for optimizing training regimens and perfor-mance outcomes in athletic contexts.

The strong competition in the automotive industry has required manufacturers to implement lean production, both with methods and techniques specific to Industry 4.0. At the same time, universities must provide graduates with specific skills for applying these new production methods and techniques. In this context, a Lean Learning Factory was developed in the Pitesti University Center, which allows students to learn, experiment, and research, in an environment similar to that of enterprises, the new Lean Manufacturing methods and techniques, and Industry 4.0. The research presented in this study had as its objective identifying the minimum number of repetitions necessary to train operators who serve two differently organized workstations, one classic, the other including digital techniques, but on which the same assembly operation is performed. Several indicators were considered in the analysis, such as the number of errors, the number of stops, the effective duration of the work cycle, and the percentage ratio between the standard duration of cyclical activities and the effective duration of the work cycle. The evolution of these indicators was mathematically modelled by regression functions, using the least squares method. The obtained results also highlight the usefulness of applying the DOJO method as a Lean manufacturing-specific learning technique and the efficiency of implementing digital techniques in work organization.

Adapted and personalized motor activities prove to be effective for meeting the specific needs of children with SEN, tailoring to their unique limitations and abilities. Our focus was to craft and apply a structured program for psychomotor abilities development, targeting balance and motor-cognitive skills. The study aims to enhance the behavior and psychomotor manifestations of 28 students with SEN (aged 12-14) from two institutional centers in Romania. The "Sfântul Ștelian" Inclusive Education School Center of Costesti, Arges (CC-12 subjects), and the "Sfânta Filofteia" Inclusive Education School Center of Ștefănești (CS-16 subjects). Across a 36-week training regimen, participants engaged in sessions lasting 30 minutes, twice weekly. Evaluation of their psychomotor skills involved a battery of tests: assessing balance, both with eyes open and closed, brain processing speed, upper limb motor laterality. Initial and final data were gathered to assess their motor development and physical state. Instruments utilized included the Optojump Next optical system for movement analysis, Witty SEM intelligent semaphore, Sensamove balance miniboard. Statistical analysis compared the initial and final assessments using the Kolmogorov-Smirnov test and Wilcoxon Z test. Out of the total comparisons made between the initial and final assessments for the evaluation of the psychomotor component, statistically significant differences were found in only 37.5% of these comparisons.

Edible mushrooms have been recognized as highly nutritional food for a long time, due to their specific flavor, texture and also for therapeutic effects. This study proposes a new simple approach, based on FT-IR analysis, followed by statistical methods, in order to differentiate three wild mushrooms species from Romanian spontaneous flora, namely Armillaria mellea, Boletus edulis and Cantharellus cibarius. The preliminary data treatment consisted of data set reduction with principal component analysis (PCA), which provided scores for the next methods. Linear discriminant analysis (LDA) manage to 100% classify the three species and the cross validation step of the method returned 97.4% of correctly classified samples. Only one A. mellea sample overlapped on B. edulis group. When kNN was used in the same manner as LDA, the overall percent of correctly classified samples from the training step was 86.21%, while for holdout set the percent raised at 94.74%. The lowered values obtained for the training set was due to one C. cibarius sample, two B. edulis and five A. mellea, which were placed to other species. Anyway, for holdout sample set, only one sample from B. edulis was misclassified. The fuzzy c-means clustering (FCM) analysis successfully classified investigated mushroom samples according to their species, meaning that in every partition the predominant specie had the biggest DOMs, while samples belonging to other specie had lower DOMs.

Keywords: Trichoderma sp., biogenic selenium nanoparticles, capping biomolecules, bio-corona, agriculture, plant biostimulants, phytopathogens, physicochemical properties, bioactivity mechanism

Life Cycle Cost Analysis is a method used to assess long-term economic efficiency among equivalent competing processes or products. The purpose of the paper is to investigate the nature and level of costs for an organic orchard located in Southern Romania, using a complex approach covering the entire chain of production, through the life span. The research results, based on a dynamic analysis and an integrated evaluation of the orchard's performance, have been ranked on investment and operational costs, broken down on three categories (establishment and production, post-harvest and transport costs). The highest cost, representing 151726 euros/ha/20 years, about 52.72% of the total operational costs and 50.4% of the total farm costs/ha/20 years, was recorded in exploitation stage. The scenarios for the sensitivity analysis considered different levels of average yield (40, and, respectively 60 tons/ha) with different rate of sold production (85%, optimistic scenario; 70%, pessimistic scenario). The hotpoints identified at the production stage were use of agricultural machinery, several pesticides, the costs of seedlings, anti-hail net, plastic boxes and labor cost, while at the post-harvest stage, were those related to labor and energy consumption. The transport stage has had important costs with tractor operation and the track.

This study explores the potential of data science software solutions like Customer Relationship Management Software (CRM) for increasing the revenue generation of businesses. We focused on those businesses in Accommodation and Food Service sector across the European Union (EU). The investigation is contextualized within the rising trend of data-driven decision making, examining the potential correlation between data science application and business revenue. Employing a comprehensive evaluation of Eurostat datasets from 2014 to 2021, we used both univariate and multivariate analyses, we assessed e-commerce sales data across countries, focusing on the usage of big data and CRM tools. Big data utilization showed a clear, positive relationship with enhanced e-commerce sales. However, CRM tools exhibited a dualistic impact: while their use in marketing showed no significant effect on sales, their application in non-marketing functions had a negative correlation. These findings underscore the potential role of CRM and data science solutions in enhancing business performance in the EU's Accommodation and Food Service industry.

Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the regain of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it would be beneficial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, exhibiting a similar morphology to PTEC, expressing prototypical PTEC markers and performing albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycemia. Plant-based therapies are characterized by low bioavailability in ocular tissues. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR, were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Fundus of retinal arterioles, retina histopathology and lens transmission electron microscopy (TEM), were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fiber disorganization. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately edematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA formation and increased antioxidant capacity. Retinal edema and disorganization in lens fibers were still present.

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

This research delves into the epidemiology, clinical manifestations, and management of hyperprolactinemia, particularly focusing on prolactin-secreting pituitary adenomas, or prolactinomas, in Dolj County, a region historically underrepresented in medical literature. Hyperprolactinemia, a prevalent endocrine disorder, arises from excessive prolactin secretion by the pituitary gland's lactotrope cells and presents a diverse clinical picture. The most significant etiological contributors identified are prolactinomas, accounting for approximately 39% of all secretory pituitary tumors. In light of hyperprolactinemia's substantial morbidity and prevalence, this study underscores the necessity of comprehensive understanding of its regional epidemiology and clinical presentations. Our methodology incorporated collecting retrospective data across various medical facilities in Dolj, ensuing a meticulous analysis of clinical features, paraclinical investigation outcomes, and therapeutic responses among patients with prolactinomas. Emphasis was placed on discerning risk factors, demographic characteristics, and associated comorbidities to encapsulate the full spectrum of these tumors' impact within the community. Preliminary results suggest a nuanced incidence rate of prolactinomas within Dolj, with specific demographic and clinical trends potentially distinct from those reported in wider literature. These findings stress the critical role of localized studies in enhancing screening, diagnostic, and therapeutic protocols. Ultimately, this investigation offers critical insights into the epidemiology and symptomatology of prolactinomas in Dolj, significantly augmenting existing literature and informing regional medical practices.

Dermal penetration is considered to mainly occur via passive diffusion. Therefore, a high concentration gradient of dissolved active ingredient between formulation and skin is needed to achieve an effective dermal penetration. The concentration gradient between formulation and skin can be changed by changing the amount of dissolved active ingredient in the formulation. In case of poorly soluble active ingredients this can be achieved by using nanosized drug material instead of larger sized material. The smaller size and the resulting larger surface increase the kinetic solubility and thus increase the concentration gradient of dissolved active ingredient between formulation and skin, which then results in an increased dermal penetration. In this study we demonstrated that the concentration gradient between formulation and skin can also be influenced by the number of particles being present in the formulation and by the dose (volume of formulation) applied to the skin. Particles of undissolved active ingredient are known to act as a reservoir by releasing dissolved molecules in the liquid phase of the formulation. It could now be demonstrated that the particles - once the liquid in which they are dispersed evaporates - can connect to the skin via an aqueous meniscus. The aqueous meniscus contains dissolved active ingredient and therefore creates a small local spot with a locally high concentration gradient and improved dermal penetration. Therefore, the dermal penetration can be increased with formulations that contain high amounts of particles. This can be achieved by applying formulations with high numbers of particles and/or by applying larger volumes of particle containing formulations to the skin.

Enhancement of orthodontic tooth movement (OTM) through local administration of biofunctional molecules has become increasingly significant, particularly for adult patients seeking aesthetic and functional improvements. This comprehensive systematic review analyzes the efficacy of various biofunctional molecules in modulating OTM, focusing on the method of administration and its feasibility, especially considering the potential for topical application. A search across multiple databases yielded 36 original articles of experimental human and animal OTM models, which examined biofunctional molecules capable of interfering with the biochemical reactions that cause tooth movement during orthodontic therapy, accelerating the OTM rate through their influence on the bone metabolism (Calcitriol, Prostaglandins, Recombinant human Relaxin, RANKL and RANKL expression plasmid, growth factors, PTH, osteocalcin, vitamin C and E, biocompatible reduced graphene oxide, exogenous thyroxine, sclerostin protein, a specific EP4 agonist (ONO-AE1-329), carrageenan and herbal extracts). The results indicated a variable efficacy in accelerating OTM, with Calcitriol, Prostaglandins (PGE1 and PGE2), RANKL, growth factors and PTH, among others, showing promising outcomes. PGE1, PGE2 and Calcitriol experiments had statistically significant outcomes in both human and animal studies, and, while other molecules underwent only animal testing, they could be validated in the future for human use. Notably, only one of the animal studies explored topical administration, which also suggests a future research direction. This review concluded that while certain biofunctional molecules demonstrated potential for OTM enhancement, the evidence is not definitive. The development of suitable topical formulations for human use could offer a patient-friendly alternative to injections, emphasizing comfort and cost-effectiveness. Future research should focus on overcoming current methodological limitations and advancing translational research to confirm these biomolecules' efficacy and safety in clinical orthodontic practice.

We aim to map the ESG patterns of emerging-market companies from 2018 to 2021 in order to determine whether the COVID-19 pandemic exerted any influence on sustainable corporate behavior. Thus, the ESG performances were assessed by applying the Kohonen neural network for clustering purposes at three main levels: i) ESG overall, including country and sectoral perspectives; ii) ESG thematic; and iii) ESG four-folded (stakeholder, perspective, management level, and focus strategic views). Our results show that emerging-market companies focus their ESG efforts on social and governance issues rather than on environmental. However, environmental, and social behavior differ more acutely than governance behavior across clusters. The ESG pillars country-level and eleven market-based economic sectors analysis corroborate the geographic and sector dependence of ESG performance. The thematic-level analysis indicate that operational activities and community issues received more attention, which suggests that emerging-market companies address distinct ESG topics according to their particularities and competitiveness. Furthermore, our empirical findings provide evidence that the ESG behavior of companies has changed over the course of the COVID-19 pandemic. Thus, our findings are relevant to policymakers involved in regulating ESG disclosure practices, investors focused on enhancing their sustainable investment strategies, and firms engaged in improving their ESG involvement.

The aim of the study was to gain deeper insights in the potential for polyclonal stimulation of PBMC from cows and pigs with banana lectin (BanLec) from Musa paradisiaca. BanLec induced a marked proliferative response in cow and pig PBMC. The response in pigs was even higher than to Concanavalin A. Molecular processes associated with respective responses were examined with differential proteome analyses. Discovery proteomic experiments was applied to BanLec stimulated PBMC and cellular and secretome responses were analyzed with label free LC-MS/MS. In PBMC, 3955 proteins were identified. After polyclonal stimulation with BanLec, 459 proteins showed significantly changed abundance in PBMC. In respective PBMC secretomes, 2867 proteins were identified with 231 differentially expressed candidates as reaction to BanLec stimulation. The transcription factor `E74 like ETS transcription factor 1 (ELF1)` was solely enriched in BanLec stimulated PBMC. BanLec induced secretion of several immune regulators, amongst them positive regulators of activated T cell proliferation and Jak-STAT signaling pathway. Top changed immune proteins were CD226, CD27, IFNG, IL18, IL2, CXCL10, LAT, ICOS, IL2RA, LAG3 and CD300C. BanLec stimulates PBMC of cows and pigs polyclonally and induces IL2 pathway and further proinflammatory cytokines. Proteomics data are available via ProteomeXchange with identifier PXD027505.

Popular geo-computer vision works make use of aerial imager with sizes ranging from 64 × 64 to 1024 × 1024 pixels without any overlap, although the learning process of deep learning models can be affected by the reduced semantic context or the lack of information near image boundaries. In this work, the impact of three image sizes (256 × 256, 512 × 512, and 1024 × 1024 pixels) and two image overlap levels (no overlap and 12.5% overlap) on the performance of road classification models was statistically evaluated. For this, two convolutional neural networks used in various tasks of geospatial object extraction were trained (using the same hyperparameters) on a large dataset (containing aerial image data covering 8650 km² of the Spanish territory that was labelled with binary road information) under twelve different scenarios, each scenario featuring a different combination of tile size and overlap. To assess their generalisation capacity, the performance of all resulting models was evaluated on a data from novel areas covering approximately 825 km². The performance metrics obtained were analysed using appropriate descriptive and inferential statistical techniques to evaluate the impact of the performance at distinct levels of the fixed factors (tile size, tile overlap, neural network architecture). Statistical tests were applied to study the main and interaction effects of the fixed factors on the performance. A significance level of 0.05 was applied to all the null hypothesis tests. The results were highly significant for the main effects (p-values lower than 0.001), while the two-way and three-way interaction effects among them had different levels of significance. The results indicate that the training of road classification models on images with a higher tile size (more semantic context) and tile overlap (additional border context and continuity) significantly impacts their performance. The best model was trained on a dataset featuring tiles with a size of 1024 × 1024 pixels and a 12.5% overlap and achieved a loss value of 0.0984, an F1 score of 0.8728, and an ROC-AUC score of 0.9766, together with an error rate of 3.5% on the test set.

The most important prognostic factors in curatively treated prostate cancer at the initial diagnosis are T and N stage, histological subtype, Gleason score, initial PSA, PSA density and percentage of core biopsy positivity. Newer, but non-standard prognostic factors are urine PCA3 and genetic markers of prostate cancer. A simple, but seemingly underestimated standard test is serum Calcium (Ca) level, which has been shown by a previous study group to be a good predictor of lethal prostate cancer, but there is scarce evidence regarding the prognostic value of calcium levels at diagnosis. We aimed to determine whether a Ca level in the upper part of normal values has a prognostic value in curatively treated prostate cancer. We have retrospectively included 84 consecutive patients with prostate cancer, who underwent curative radiotherapy (primary or adjuvant; external beam RT with or without brachytherapy). We have performed statistical analysis of available prognostic factors. Ca level at diagnosis was found to be a statistically significant predictor of disease-free survival.

Background: Besides anemia, iron deficiency may cause more subtle symptoms including those of the restless legs syndrome (RLS), the chronic fatigue syndrome (CFS) or sleeping disorders. Objective: The aim of this pre-planned secondary analysis was to compare the frequency and severity of symptoms associated with iron deficiency before and after (intravenous or oral) iron supplementation in iron deficient blood donors. Methods/Design: Prospective, randomized, controlled, single centre trial. (ClinicalTrials.gov: NCT01787526). Setting: Tertiary care center in Graz, Austria Participants: 138 female and 38 male whole blood and platelet apheresis donors aged ≥18 and ≤65 years with iron deficiency (ferritin ≤30ng/ml at the time of blood donation). Interventions: Intravenous iron (1 g ferric carboxymaltose, n=86) or oral iron supplementation (10 g iron fumarate, 100 capsules, n=90). Measurements: Clinical symptoms were evaluated by a survey before iron therapy (visit 0, V0) and after 8-12 weeks (visit 1, V1) including questions about symptoms of RLS, CFS, sleeping disorders, quality of life and symptoms like headaches, dyspnoea, dizziness, palpitations, pica and trophic changes of fingernails or hair. Results: We found a significant improvement in the severity of symptoms for RLS, fatigue and sleep quality (p<0.001). Furthermore, a significant decrease of headaches, dyspnoea, dizziness and palpitations was reported (p<0.05). There was no difference between the type of iron supplementation (intravenous versus oral) and clinical outcome data. Conclusion: Iron supplementation in iron deficient blood donors may be an effective strategy to improve symptoms related to iron deficiency and the wellbeing of blood donors.

NAD⁺ is known classically as a metabolite that participates in catabolic and anabolic pathways throughout the metabolism that is taught to students in introductory biochemistry courses. However, non-classical studies starting over a decade ago found that NAD⁺ is also involved in higher order functions, in part because of its involvement in the activation of SIRTs and the support of the mitochondrial unfolded protein response. Many studies since have suggested that NAD⁺ is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes, Further, healthy aging and longevity appear to be closely related to NAD⁺ and its related metabolites, including NAR and NMN. Together, these studies show that this system has value as a dietary supplement to improve general health overall, as well as mitigating specific disease conditions. Accordingly, many are now recommending the consumption of materials in this system as dietary supplements. Nicotinamide riboside (NAR) appears to have special value in this regard. It appears to be better tolerated than other molecules in this system, as well as better pharmacodynamics and greater potency. Unfortunately, NAR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Indeed, HPLC analyses of many commercial samples of NAR shows that they contain substantial amounts of material that are not, in fact, NAR. In some of these commercial preparations, NAR is a minority component. Therefore, more stable derivatives of NAR that are easily converted upon consumption into NAR are therefore desired. Recently work related to prebiotic chemistry provided the borate derivative of NAR. NARB is considerably more stable than NAR itself. However, immediately upon consumption, the borate dissociates from NARB, and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NAR left behind is expected to behave pharmacologically in ways identical to NAR itself. This review provides a comprehensive summary (through Q1 of 2023) of literature that makes the case for the consumption of NAR as a dietary supplement. It then summarizes the challenges of delivering quality NAR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NAR-borate in these processes.

The molecular study of fat cell development in the human body is essential for our understanding of obesity and related diseases. Mesenchymal stem/stromal cells (MSC) are the ideal source to study fat formation as they are the progenitors of adipocytes. In this work, we used human MSCs, received from surgery waste, and differentiate them into fat adipocytes. The combination of several layers of information coming from lipidomics, metabolomics and proteomics enabled comprehensive analysis of the biochemical pathways in adipogenesis. Simultaneous analysis of metabolites, lipids and proteins in cell culture is challenging due to the compound’s chemical difference so that most studies involve separate analysis with unimolecular strategies. In this study, we employed a multimolecular approach using a two–phase extraction to monitor the crosstalk between lipid metabolism and protein-based signaling in a single sample (~105 cells). We developed an innovative analytical workflow including standardization with in-house produced 13C-isotopically labeled compounds, hyphenated high-end mass spectrometry (high-resolution Orbitrap MS) and chromatography (HILIC, RP) for simultaneous untargeted screening and targeted quantification. Metabolite and lipid concentrations ranged over 3-4 orders of magnitude and were detected down to the low fmol (absolute on column) level. Biological validation and data interpretation of the multiomics workflow was performed based on proteomics network reconstruction, metabolic modelling (MetaboAnalyst 4.0) and pathway analysis (OmicsNet). Comparing MSCs and adipocytes, we observed significant regulation of different metabolites and lipids such as triglycerides, gangliosides and carnitine with 113 fully reprogrammed pathways. The observed changes are in accordance with literature findings dealing with adipogenic differentiation of MSC. These results are a proof of principle for the power of multimolecular extraction combined with orthogonal LC-MS assays and network construction. Considering the analytical and biological validation performed in this study, we conclude that the proposed multiomics workflow is ideally suited for comprehensive follow-up studies on adipogenesis and is fit for purpose for different applications.

The C-type lectin-like receptor 2 (CLEC-2) is expressed on platelets and mediates binding to podoplanin (PDPN) on various cell types. The binding to circulating tumor cells (CTCs) leads to platelet activation and promote metastatic spread. The increased level of soluble CLEC-2 (sCLEC-2), presumably, released from activated platelets was shown in patients with thromboinflammatory and malignant disease. However, the functional role of sCLEC-2 and the mechanism of sCLEC-2 release is not known. In this study, we focused on the effect of platelet activation on CLEC-2 expression and the sCLEC-2 plasma level in cancer patients. First, citrated blood from healthy volunteer donors (n=20) was used to measure the effect of platelet stimulation by classical agonists and PDPN on aggregation, CLEC-2 expression on platelets by flow cytometry, sCLEC-2 release to the plasma by ELISA and total CLEC-2 expression by Western blot analysis. Second, sCLEC-2 was determined in plasma samples from healthy donors (285) and patients with colorectal carcinoma (CRC; 194), melanoma (160), breast cancer (BC; 99) or glioblastoma (49). PDPN caused a significant increase of the aggregation response induced by classical agonists. ADP or PDPN stimulation of platelets caused a significant decrease of CLEC-2 on platelets and sCLEC-2 in the plasma, whereas, total CLEC-2 in platelet lysates remained the same. Thus, the increased plasma level of sCLEC-2 is not a suitable biomarker of platelet activation. In patients with CRC (median 0.9 ng/mL), melanoma (0.9 ng/mL) or BC (0.7 ng/mL) we found significantly lower sCLEC-2 levels (p&lt;0.0001), whereas, glioblastoma patients displayed higher levels (2.6 ng/mL; p=0.0233) compared to healthy controls (2.1 ng/mL). The low sCLEC-2 plasma level observed in most of the tumor entities of our study, presumably, results from the internalization of sCLEC-2 by activated platelets or binding of sCLEC-2 to CTC.

Background: The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study is to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen. Methods: changes in PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the trombogram graphic (thrombin variation over time); lagTime; Endogenous Thormbin Potential(ETP); peak; time to reach peak(ttpeak), startTail e velocity Index. Platelet aggregation was assessed by testing different agonists using turbidimetry method. Results: Four FCS patients and 4 matched healthy controls were included in the present study. Changes in PLC at Tw12 was 30% and 34% at T36w. Thrombin generation results show values in normal range (for patients and controls respectively lagTime:10,42±4,40 and 9,25±0,99; ttPeak:14,33± 4,01 and 13,10±0,67; startTail:32,13±3,54 and 29,46±1,69; velocityIndex:20,21±3,63 and 33,05±13,21; ETP 599,80±73,47 and 900,2±210,99; peak value 76,84±1,07 and 123,30±39,45) and no significant difference between cases and controls. Platelet aggregation test showed values in range with no significant difference with healthy controls Conclusions: Our study showed for the first time that no significant changes in the general haemostasis assessed by TG and in platelet function have been observed in FCS patients receiving volanesorsen.

Background and Objectives: Ultrasound (US) is a non-invasive tool for the in-vivo detection of peripheral nerve alterations. Materials and Methods: In this study we applied nerve US to assist the discrimination between the spectrum of Amyotrophic Lateral Sclerosis (ALS, n=11), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n=5) and genetically confirmed Charcot-Marie-Tooth disease (CMT, n=5). All participants and n=15 controls without neurological diseases underwent high-resolution US of the bilateral tibial nerve. Nerve cross-sectional area (CSA) and nerve microvascular blood flow were compared between the groups and related to cerebrospinal fluid (CSF) measures, clinical symptoms and nerve conduction studies. Analyses are part of a larger multimodal study on the comparison between US and 7 Tesla (T) magnetic resonance neurography (MRN). Results: Patients and controls were matched with respect to their demographical data. CMT had the longest disease duration, followed by CIDP and ALS. CSA was related to age, weight and disease duration. CSA was larger in CMT and CIDP compared to ALS and controls. Blood flow was greatest in CIDP, and higher than in CMT, ALS and controls. In ALS, greater CSA was correlated with greater CSF total protein and higher albumin quotient. US measures did not correlate with clinical scores or nerve conduction studies in any of the subgroups. Conclusion: Our results point towards the feasibility of CSA and blood flow to discriminate between ALS, CIDP and CMT, even in small sample sized groups. In ALS, larger CSA could indicate an inflammatory disease subtype characterized by reduced blood-nerve barrier integrity. Our upcoming analysis will focus on the additive value of 7T MRN in combination with US to disentangle the spectrum between more inflammatory or more degenerative disease variants along the disease groups.

Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity of conventional culture techniques, serologic tests, and PCR-based assays in patients on antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.

(1) Background: This study aimed to outline the antitumoral, antioxidant, and cytotoxic proprie-ties of various types of Perilla frutescens extracts obtained from the leaves of the species; (2) Methods: We determined total polyphenols, flavonoids and anthocyanins contents, as well as the in vitro antioxidant, antitumoral, and cytotoxic actions in 3 types of ethanolic extracts (E1, E2, E3) and in 3 types of ethanol: acetone extracts (A1, A2, A3) of Perilla frutescens according to standardized procedures; (3) Results: We found that Perilla frutescens ethanolic extracts had higher total phenol concentrations (p= 0.002). Flavonoids and anthocyanins concentrations were not statistically different between the two extracts. The iron chelating capacity, hydroxyl radical scavenging capacity, superoxide anion radical scavenging capacity, and lipoxygenase inhibition capacity showed a significant increase with higher concentrations of Perilla frutescens extracts, particularly the ethanolic extracts. Perillyl alcohol had greater cytotoxic capacity on MG-63 cell line and E1 extract showed similar significant cytotoxic effects on A431 cell line; (4) Conclusions: Both ethanolic and ethanol: acetone extracts from Perilla frutescens exhibited important antioxi-dant and antitumoral actions in vitro, which proportionally increased with concentration. The cytotoxic threshold determined in this study for various types of extracts could help determine the best dosage with the maximum antioxidant and antitumoral potential.

Canine distemper virus (CDV) is a serious contagious disease of canines, cats and sometimes ra-coons. The study included seven raccoons from Timisoara Zoo. The detection of CDV in all raccoons was accomplished using qRT-PCR, but several other exams were also conducted. Clinically, severe digestive disorders were observed, characterized by diarrhea and repeated hematemesis. Pseudomembranous gastroenteritis, congestion and pulmonary edema were found during the ne-cropsy of two racoons. Immunohistochemically, the brown color was highlighted in the examined sectionsand it was present in the cytoplasm of the cells from the germinal centers of the medullary area. Histopathological examination revealed lymphocyte depletion and intranuclear and intracy-toplasmic inclusions in the intestine. Based on the qRT-PCR assay, laboratory tests and lesions ob-served, it was established that the raccoons got infected with CDV, and two of them died as a result. The necropsy, histological lesions and immunohistochemical results are comparable between dogs and racoons. Through the results obtained, it was concluded that the interspecific infection is possible and the epidemiological risk of infection transmitted by racoons to domestic animals, such as dogs and cats, needs to be examined in the future.

The release of the active substance from the matrix modified-release tablets based on Kollidon®SR and chitosan depends on its solubility in the dissolution medium and on the composition of the matrix-forming polymers. The study is based on new oral matrix tablets based on Kollidon®SR and chitosan, formulated to optimize the low oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug, a class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method, and their combination at 1:1, 1:2, 1:3 chlorzoxazone/ excipients, 20%-40% (w/w) Kollidon®SR, 3-7% (w/w) chitosan and the auxiliary substances were formulated in constant concentrations. Pharmaco-technical characterization included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, Carr Index), and of pharmaco-chemical characteristics (mass and dose uniformity, thickness, diameter, mechanical strength, Friability, degree of softening, in vitro release profile) of the tablets. Based on the initial evaluation of the pharmaco-technical analysis, pharmaco-chemical characteristics, and in vitro release profile, only three matrix tablet formulations (F1b, F2b, and F3b) were further tested. They were evaluated through Fourier-transform infrared spectrometry, X-ray Diffraction, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified release oral formulations. In vitro kinetic study reveals a complex mechanism of release occurring in the first (0 - 2 hours) and second (2.0 hours – 36 hours) steps of drug release. Two factors have been calculated to assess the release profile of chlorzoxazone: f1 - the similarity factor and f2 - the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. In vitro dissolution tests revealed the F2b sample, data suggesting a faster drug release. The three formulations showed optimum pharmaco-technical properties and in vitro kinetic study, and they had tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone.

Introduction Cone Beam Computed Tomography (CBCT) scans should be digitally oriented using a reference plane before being evaluated for patient growth and treatment outcome. Current orientation planes are usually dependent on the Porion points. Using more reliable landmarks than the Porion, we introduce the Acta plane and investigate its reliability as an alternative reference plane for cases in which the Porion point is inaccessible. Methods To test its reliability, a dental student and an orthodontist located sixteen skeletal and dental landmarks in sixteen CBCT scans, before and after reorientation. Also, four measurements were calculated based on these landmarks’ coordinates. The reorientation of these CBCT scans with the Acta plane was done by another dental student. Intraclass Correlation Coefficient (ICC) was calculated before and after orientation, intra- and inter-examiner. The data were tested for significance through the Shapiro Wilk test with a threshold set at 0.05. Through the ICC variation of the points’ coordinates, this article also evaluated the reliability of this plane with the t-paired and exact-sign tests. Results: The identification of landmarks was more reliable in the reoriented CBCT images than in the original images, with a significant increase of 0.012 in the median of the ICC. Linear and angular measures showed no significant differences between groups. Conclusion This plane is a reliable alternative for the orientation of CBCT images. The design of the Acta plane might allow the use of a smaller field of view and, consequently, a reduction in the radiation dose.

The article continues the exposition of the results obtained in the research of an agricultural machine for processing soil, designed for research with applications including exploitation. The MCLS complex cultivator was designed for the research of the working processes of the instruments intended for soil processing. The MCLS cultivator is a modulated machine (it can work for three working widths: 1, 2, and 4 m, with tractors of different powers) that is designed to use a wide range of working bodies. The experimental data obtained with the structure with a working width of 1 m and the results of their processing within the framework of the theory of random vibrations are presented in this article. The experimental results are analysed as random vibrations of the supports of the active body. As a result, the main characteristics of random vibrations are exposed: the distribution function, the average value, the autocorrelation, and the frequency spectrum. These general results regarding random vibrations are used for several critical applications in the design, execution, and exploitation of some subassemblies and assemblies of agricultural machines of this type. The main applications are: estimating the probability of the occurrence of dangerous load peaks, counting and selecting the load peaks that produce fatigue accumulation in the material of the supports of the working bodies, identifying some design deficiencies or defects in the work regime, estimating the effects of vibrations on the quality of soil processing. All the outcomes are comprised of applications in MCLS research and exploitation. The applications pursue well-known objectives of modeling the working processes of agricultural machines: safety at work, increasing the quality of work, optimizing energy consumption, and increasing productivity, all in a broad context to obtain a compromise situation

The natural compounds of boron have many applications, including as dietary supplement. Communication is based on the discovery that diester chlorogenoborate complex can be detected and quantified from green coffee bean. The study reports that such diester molecule can also be synthesized in stable form by direct reaction of boric acid and chlorogenic acid, in a mixture of acetonitrile–water (1:1, v/v), left to evaporate over a period of 48 hours, at room temperature, resulting a spirocyclic form (diester complex). The diester complex, with its molecular structure and digestibility attributes has potential application as prebiotic in gut health, oral health and as micronutrient essential for microbiota to human and animals.

Waste biogenic materials from seafood exploitation are valuable resources of new compounds exploitation within the blue bioeconomy concept. Here, we describe the effectiveness of Raman technology implementation as an in-line tool for demineralization process control of crustaceans or gastropods. We produced transparent chitin polymer foils from three waste crustacean shells (C. sapidus, S. mantis and M. squinado) using a slow, green chemical approach employing acetic acid, and showed the progressive process of biogenic carbonate dissolution and increasing the Raman characteristic signal of chitin, in a time dependence manner. It turned that chitin foils obtaining is species-specific, and the demineralization bath of waste shell mixture can be effectively tracked by Raman spectroscopy, for solvent control and the recovery of the calcium acetate as valuable by-product. Comparatively, calcium acetate drug, a compound widely used in kidney failure diseases, or as additive in nutraceuticals and food industry, has been obtained here, following a green demineralization path of the sea snail Rapana venosa intact shell, assisted by Raman tech-nology, using 9% acetic acid (vinegar) solution for 14 days. To validate the final products identity and quality, The process of waste shells demineralization and the final products of the treatment were investigated using various Raman techniques and technologies, cross-validating the results with FT-IR, XRD and SEM-EDX techniques. NIR Raman spectroscopy revealed chitin bands in a time-dependent manner, while Resonance Raman spectroscopy showed the preservation of ca-rotenoids after two weeks of acetic acid treatment. A hand-held flexible TacticID Raman system with a 1064 nm excitation demonstrated its effectiveness as a rapid, in-line decision making tool during process control and revealed excellent reproducibility of the lab-based instrument signal, suitable for in situ evaluation of the demineralization status and solvent saturation control. The calcium acetate recovered from residual treatment solutions was assessed regarding its hydration status, purity, and suitability as recrystallized material for further use as pharmaceutical product or ingredient in complex formulations.

Vaccine hesitancy substantially impacts global vaccination rates. During the COVID-19 pandem-ic in Germany, vaccination uptake exhibited considerable regional disparities. To assess the fac-tors contributing to this variation, we examined the influence of sociodemographic variables on COVID-19, COVID-19 booster, and influenza vaccinations within a cohort of 37,078 participants from 13 German federal states in the digital health cohort study, DigiHero. Our findings re-vealed variations in vaccination rates based on sociodemographic factors. However, these fac-tors had limited explanatory power regarding regional differences in vaccine uptake. In contrast, we found substantial correlations between regional support of specific parties during last local elections and the vaccination uptake at Landkreis-level. In conclusion, sociodemographic factors alone did not suffice to explain the regional disparities in vaccine uptake. Political stances can play a major role, but the current investigation did not assess the individual political orienta-tion, but used only ecological approach.

Resveratrol (RSV), a naturally occurring phytoalexin, is the most important stilbenoid synthesized by plants, as a defense mechanism, in response to microbial aggression, toxins or ultraviolet radiation. RSV came to the attention of researchers both as a potential chemopreventive agent and a possible explanation for the low incidence of cardiovascular disease (CVD) in French people with a high-fat diet. RSV is mainly administered as a food supplement, its properties being evaluated in vitro or in vivo, on various experimental models. RSV modulates signaling pathways that limit the spread of tumor cells, protects nerve cells from damage, is useful in the prevention of diabetes, and generally acts as an anti-aging natural compound. It was highlighted that RSV could ameliorate the consequences of an unhealthy lifestyle caused by an exaggerated caloric intake. This paper reviews the evidence supporting the beneficial effect of RSV for various pathological conditions, e.g., neoplastic diseases, neurodegeneration, metabolic syndrome, diabetes, obesity, CVDs, immune diseases, bacterial, viral, and fungal infections. The study also focused on the chromatographic analysis of trans-RSV (tRSV) in Romanian wine samples, providing a comprehensive overview of tRSV content across different types of wine.

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

Aiming at the problems of inaccurate segmentation of long object and information loss of small object in real-time semantic segmentation algorithm, this paper proposes a lightweight multi-branch real-time semantic segmentation network based on BiseNetV2. The new auxiliary branch makes full use of spatial details and context information to cover the long object in the field of view. Meanwhile, in order to ensure the inference speed of the model, the asymmetric convolution is used in each stage of the auxiliary branch to design a structure with low computational complexity. In the multi-branch fusion stage, the alignment and fusion module is designed to provide guidance information for deep and shallow feature mapping, so as to make up for the problem of feature misalignment in the fusion of information at different scales, and thus reduce the loss of small target information. In order to further improve the model’s awareness of key information, a global context module is designed to capture the most important features in the input data. The proposed network uses NVIDIA GeForce RTX 3080 Laptop GPU experiment, on the road street view data set Cityscapes and CamVid average occurring simultaneously ratio reached 77.1% and 78.4% respectively, with running speed of 127 frames/s respectively and 112 frames/s. The experimental results show that the proposed algorithm can achieve real-time segmentation and improve the accuracy significantly, showing good semantic segmentation performance

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

In this paper we study a class of impulsive delayed neural networks with parameter uncertainties and reaction-diffusion terms. Using the properties of M-matrices and some inequality techniques, some sufficient conditions are derived to guarantee the global exponential stability of the given system. The results obtained are presented by simple algebraic inequalities, which are certainly more concise than previous methods. Finally, the validity and usefulness of our results are illustrated by arithmetic examples.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named as PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full-length of PyCaV is 10855 bp with the polyA tail, containing a single open reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical Iflavirus structure, including two rhv domains, a RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and a RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignements analysis suggedted PyCaV is new member in unassigned genus of family Iflaviridae. Further in-depth analysis of virus-infection-part showed that PyCaV is distributing in the whole longan lanternfly, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV were detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and locations.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

With the burgeoning growth of online retail, the issue of counterfeit products has become a significant threat to both consumer trust and brand integrity, posing challenges to sustainable market practices. Online retail platforms are promoted to redesign their channel structures and enhance brand traceability to tackle counterfeits using blockchain technology. To investigate the interactions between blockchain technology and the channel structures of online retail platforms, we design a game theory model incorporating a manufacturer with(out) blockchain participation selling products via an online retail platform that operates an agency channel and/or a reselling channel. We show that the critical trade-off of blockchain participation comprises the brand assurance effect of the blockchain, the channel competition intensification effect, and the blockchain adoption cost. The platform is capable of strategically designing the channel structure to encourage (while discouraging) blockchain participation by the manufacturer. Our analysis highlights the complementarity between blockchain participation and the channel structure. Furthermore, the effect of the consumer’s belief in the reselling channel, the commission fee in the agency channel, and the substitutability between channels are investigated in depth. The research provides valuable insights for online retail platforms and policymakers seeking to foster a sustainable and trustworthy e-commerce ecosystem.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

The studied solar pot is a recent invention, which gained a utility model protection in 2021 from the Hungarian Intellectual Property Office under patent number 5489. The device is made for environmentally friendly cooking or heating (by utilizing solar energy) of foods and liquids. Its structure is similar to a double pipe heat exchanger, it has an outer mantle and an inner cooking tank. The goals of the paper are proposing a new physically-based mathematical model describing the solar pot and carrying out computer experiments with it, assembling an experimental system of the pot connected with a solar collector and performing measurements on it. Based on the results, the solar pot can successfully be used for cooking or sterilizing foods or liquids during the studied time period, in Hungary.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

The continuous casting process of helical fiber reinforced metal matrix composites was proposed, and the experimental equipment was designed and manufactured. The relationship model be-tween the process parameters and the helical shape of the fibers in the metal matrix is analyzed by differential geometry. Helical carbon fiber reinforced lead matrix composites were prepared under different conditions. When the melting temperature and cooling intensity were increased, the helical radius of helical carbon fiber in lead matrix was increased. When the fiber rotation speed was increased, the helical radius was decreased, and the helical pitch was de-creased proportionally. The experimental results are consistent with the process model. Carbon fiber rein-forced aluminum composites were prepared. Scanning electron microscopy showed that the infiltration between the aluminum matrix and the carbon fiber was not complete. As the volume fraction of carbon fiber which was added in composites is too small, the mechanical properties of the composites have not been significantly improved.

This article presents an innovative approach to the design of a safe adaptive backstepping control system. Tailored specifically for underactuated marine robots, the system utilizes simple sensors for enhanced practicality and efficiency. Given their operation in diverse oceanic environments fraught with various sources of uncertainties, ensuring the system's safe and robust behavior holds paramount importance in the control literature. To address this concern, this paper introduces a control strategy designed to ensure robustness at both the kinematic and dynamic levels. By emphasizing the compensation for the system uncertainties, the design integrates a straightforward fuzzy system structure. To further ensure the system's safety, a funnel surface is defined, followed by the design of a suitable nonlinear sliding surface as a function of the funnel and tracking error. Specifically leveraging the Lyapunov function, the study formally establishes the Semi-globally Practically Finite-time Stability of the closed-loop system, validated through simulations conducted on underactuated marine robots.

Several types of guided bone regeneration materials are available with various properties and clinical indications. Among them, dentin-derived matrix from extracted teeth is an excellent alternative to traditional graft materials, such as allografts and xenografts. Different clinical preparation protocols exist: block form versus powder form, demineralized versus non-demineralized form. Out of these methods, demineralization protocols for dentin-derived matrix from extracted teeth have been noted for a wide range of successful clinical outcomes. The purpose of this animal study was to find out the most effective method of demineralizing dentin-derived matrix to result in the highest regenerative ability in the bone graft material in rabbit calvaria. The study conducted a comparative histomorphometric analysis of four groups in distinguished matrix conditions: a control group without graft placement, a non-demineralized dentin-derived matrix graft placement group, a 15-minute demineralized dentin-derived matrix graft placement group, and a 30-minute demineralized dentin-derived matrix graft placement group. Regenerative processes were evaluated three times at 2, 4, and 8 weeks post-graft placement. These groups of rabbits were evaluated randomly in a blinded setting to prevent bias. Among the four groups compared, the group with a 15-minute demineralized dentin-derived matrix graft showed the most efficient bone regeneration in the histomorphometric analysis. Based on this animal study, it was apparent that a 15-minute demineralization of dentin-derived matrix is the preferred preparation protocol to maximize the regenerative potential in the matrix.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

Cocoa (Theobroma Cacao, L.) represents an important market that gained relevance and became an esteemed commodity thanks to cocoa powder, chocolate, and other related products. This work has analyzed 59 cocoa powder samples from the European market. Three distinct subgroups were identified: organic or conventional, alkalized or not alkalized, and raw or roasted processing. The impact of the technological process was evaluated on the pH, color, and compositional traits, as content of biogenic amines and salsolinol. The phenolic fraction was also investigated trough both common and emerging methods. Results depict that the influence of the agronomical practices (organic/conventional) did not affect significatively (p&lt;0.05) the composition of cocoa powders; similarly, the roasting process was not discriminative for the compounds traced. On the other hand, the alkalinization process greatly impacted on color, and pH, no matter of cocoa provenience, obtention, or other processes, also resulting reducing the phenolic fraction of treated samples. Principal components analysis confirmed that the alkali process acts on pH, color, and phenolic composition, but not on other bioactives molecules (BAs and salsolinol). All samples resulted safe while alkalized powders have a great reduction in beneficial biocompounds. A novel strategy could be to emphasize non-alkalized powders in the label, to meet the demand for more beneficial products.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Estimating the ocean’s subsurface thermohaline information from satellite measurements is essential for understanding ocean dynamics and El Niño phenomenon. This paper proposes an improved double-output Residual Neural Network (DO-ResNet) model to concurrently estimate the ocean subsurface temperature (OST) and ocean subsurface salinity (OSS) in the tropical Western Pacific using multi-source remote sensing data, including sea surface temperature (SST), sea surface salinity (SSS), sea surface height anomaly(SSHA), sea surface wind (SSW), and geographical information (including longitude (LON) and latitude (LAT)). In the model experiment, Argo data were used to train and validate the model, and the root mean square error (RMSE), normalized root mean square error (NRMSE) and coefficient of determination (R²) were employed to evaluate the model's performance. The results showed that the sea surface parameters selected in this study have a positive effect on the estimation process, and the average RMSE and R² values for estimating OST (OSS) by the proposed model are 0.34 °C (0.05 psu) and 0.91 (0.95), respectively. Under the data conditions considered in this study, DO-ResNet demonstrates superior performance relative to the extreme gradient boosting model, random forest model, and artificial neural network model. Additionally, this study evaluates the model’s accuracy by comparing its estimations of OST and OSS across different depths with Argo-derived data, demonstrating the model's ability to effectively capture the most spatial features, and by comparing NRMSE across different depths and seasons, the model displays strong seasonal adaptability. In conclusion, this research introduces a novel artificial intelligence technique for estimating OST and OSS in the tropical Western Pacific Ocean.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

Phased injection of natural gas into internal combustion marine engines is a promising solution for optimizing performance and reducing harmful emissions, particularly unburned methane, a potent greenhouse gas. This innovative practice distinguishes itself from continuous injection because it allows for more precise control of the combustion process with only a slight increase in system complexity. By synchronizing the injection of natural gas with the intake and exhaust valve opening and closing times while also considering the gas path in the manifolds, methane release into the atmosphere is significantly reduced, making a substantial contribution to efforts to address climate change. Moreover, phased injection improves the efficiency of marine engines, resulting in reduced overall fuel consumption, lower fuel costs, and increased ship autonomy. This technology has been tested on a single-cylinder, large-bore, four-stroke research engine designed for marine applications, operating in dual-fuel mode with diesel and natural gas. Performance was compared with that of the conventional continuous feeding method. Evaluation of the effect on equivalent CO2 emissions indicates a potential reduction of up to approximately 20%. This reduction effectively brings greenhouse gas emissions below those of the diesel baseline case, especially when injection control is combined with supercharging control to optimize the air-fuel ratio.

In numerical simulations, achieving high accuracy without significantly increasing computational costs is often challenging. To address this, this paper presents an improved finite volume weighted essentially non-oscillatory (WENO) scheme tailored for applicability in computational fluid dynamics (CFD) and implemented in the flow solver NUAA-Turbo for simulating turbomachinery flows using both RANS and RANS/LES coupling. Firstly, the new WENO scheme is validated against classic numerical test cases to assess its stability and reliability in handling discontinuities, the Double problem, and Raleigh-Taylor (RT) instability issues. Compared to the original format, this enhanced finite volume WENO scheme demonstrates superior stability near discontinuities and resolves flow features with the same grid resolution more effectively. Next, for engineering applications related to turbomachinery, such as compressor and turbine characteristics, computations are performed using RANS, and the results obtained using WENO-ZQ3 and WENO-JS3 are compared. Finally, the new fifth-order WENO scheme is applied to RANS/LES coupled simulations of turbine wakes and film cooling. The results show that the enhanced finite volume WENO scheme offers improved stability and accuracy in engineering applications, allowing for high-precision calculations with fewer grid points to capture more detailed flow physics, thereby reducing computational costs in aerodynamic applications.

To conduct high-precision and high-resolution numerical simulation of complex flow structures in turbomachinery, a high-order finite volume weighted essentially non-oscillatory (WENO) scheme for the large eddy simulation (LES) is improved and embedded into the three-dimensional viscous unsteady CFD solver NUAA-Turbo. Firstly, the spectral characteristics and unsteady convergence of the improved WENO scheme are studied. Compared with the classical WENO scheme, the improved WENO scheme has better dissipation and dispersion characteristics and faster convergence speed. Then, the coefficient CW of the Wall-Adapting Local Eddy-viscosity (WALE) model is calibrated by decaying homogeneous isotropic turbulence (DHIT) test case. Finally, the scheme is applied to conduct high-precision LES calculations of turbulent boundary layer flow, supersonic compression corner flow, and low-pressure turbine cascade separation flow. The numerical simulation results show that this WENO scheme has excellent shock wave capture ability and turbulence resolution and can capture more flow field details with less mesh size, greatly reducing the computational cost and laying a foundation for large-scale engineering application of LES.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

Intermetallic compounds are increasingly being expected to utilize in tribological environments, but to date the works are hindered by insufficient ductility at low and medium temperature. This paper presents a novel multiphase intermetallic alloy with the chemical composition of Mo-40Ni-13Si (at.%). Microstructure characterization reveals that a certain amount of ductile Mo phases formed during the solidification process of ternary Mo-Ni-Si alloy melt, which is undoubtedly beneficial to the ductility improvement of intermetallic alloy. Tribological properties of the designed alloy, including wear resistance, friction coefficient and metallic tribological compatibility, were evaluated under dry sliding wear test conditions at room temperature. Results suggested that the multiphase alloy possesses an excellent property for room-temperature wear applications, which is attributed to the unique microstructural features and thereby good combination in hardness and ductility. The corresponding wear mechanism is also reported by observing the worn surface, subsurface and wear debris of alloy, which to be found is soft abrasive wear.

With the integrated development of the Internet, wireless sensor technology, cloud computing, and mobile Internet, there has been a lot of attention given to research about and applications of the Internet of Things. A Wireless Sensor Network (WSN) is one of the important information technologies in the Internet of Things; it integrates multi-technology to detect and gather information in a network environment by mutual cooperation, using a variety of methods to process and analyze data, implement awareness, and perform tests. This paper mainly researches the localization algorithm of sensor nodes in a wireless sensor network. Firstly, a multi-granularity region partition is proposed to divide the location region. In the range-based method, the RSSI (Received Signal Strength indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized by the use of dividing region. Rach anchor node is regarded as the center of each region; the whole position region is divided into several regions and the sub-region of neighboring nodes is combined into triangles while the unknown node is locked in the ultimate area. Secondly, the multi-granularity regional division and Lagrange multiplier method are used to calculate the final coordinates. Because nodes are influenced by many factors in the practical application, two kinds of positioning methods are designed: the unknown node is in the positioning unit or not. When the unknown node is on the side of the positioning unit, we use the method of vector similarity. Moreover, we use the centroid algorithm to calculate the ultimate coordinates of unknown node. When the unknown node is not on the side of the positioning unit, we establish a Lagrange equation containing the constraint condition to calculate the first coordinates. Furthermore, we use the Taylor expansion formula to correct the coordinates of the unknown node. In addition, this localization method has been validated by establishing the real environment.