The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

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

AbstractPolyamines (PAs) including putrescine (PUT), spermidine (SPD) and spermine (SPM) are small, versatile molecules with two or more positively charged amino groups. Despite their importance for almost all forms of life, their specific roles in molecular and cellular biology remain partly unknown. The molecular structures of PAs suggest two presumable biological functions: (i) as potential buffer systems and (ii) as interactants with poly-negatively charged molecules like nucleic acids.The present report focuses on the question, whether the molecular structures of PAs are essential for such functions, or whether other simple molecules like small peptides with closely spaced positively charged side chains might be suitable as well. Consequently, we created titration curves for PUT, SPD, and SPM, as well as for oligolysines like tri-, tetra-, and penta-lysine. None of the molecules provided substantial buffering capacity at physiological intracellular pH values. Apparently, the most important mechanism for intracellular pH homeostasis in neurons is not a buffer system but is provided by the actions of the sodium-hydrogen and the bicarbonate-chloride antiporters.In a similar approach we investigated the interaction with DNA by following the extinction at 260 nm when titrating DNA with the above molecules. Again, PUT and tri-lysine were not able to interact with herring sperm DNA, while SPD and SPM were. Obviously, the presence of several positively charged groups on its own is not sufficient for the interaction with nucleic acids. Instead, the precise spacing of these groups is necessary for biological activity.

Background: The popularity of climbing via ferratas (VF) in the European Alps has increased a lot. We have analysed the pattern of injuries from accidents, which have occurred on VF, and First Aid (FA) knowledge from the persons on such alpine routes. The aim was to create specific FA courses for those who climb VF. Material and Methods: Incidences and FA knowledge of the alpinists were investigated by a questionnaire. Data included details of the individual’s alpine experience, accidents or any kind of medical emergency they have ever experienced. FA knowledge was evaluated by 18 multiple choice questions with 5 answers each. The questionnaire was based on those of previous studies but was slightly adopted for VF. For this data from rescue operations on VF were used. Finally every participant was asked to judge his FA knowledge by a Likert scale (1 to 5). Results: The collective consisted of 391 participants (28.4% women) with an average age of 41 years. A significant portion did no regular fitness training and in most cases the last FA training was years ago. Nobody had joined a specific FA course for climbers or mountaineers. The most common causes of emergencies were: weather conditions (19%), stumble (18.6%), falls (13.4%), and weariness and deficiency in concentration (13.4%). FA questions most often answered correctly were cardiac emergencies (49.6%), high altitude cerebral edema (HACE) (43.2%), snow blindness (40.9%), injuries of the head (37.1%) and hemorrhagic shock (35.3%). Those most often wrong were injuries of the back (1.0%), injuries of the thorax (2.8%), frostbite (9.0%), acute mountain sickness (AMS) (4.1%) and strategy of rescue (4.1%). VF climbers show significant less FA knowledge than mountaineers in the Western Alps and trekkers. Conclusions: Data support the need of a specific FA training for VF climbers. Their FA knowledge does not fit with the demands in the mountains while some other knowledge they have is negligible on VFs (e.g. HACE). This is in accordance with earlier studies in “classic” alpine mountaineering and in trekking.

The spillover of the terrorist activities of Boko Haram, a Nigerian jihadi group, into Cameroon’s northern region has resulted in security challenges and humanitarian activity opportunities for Christian churches. The insurgents have attacked and destroyed churches, abducted Christians, worsened Muslim-Christian relations, and caused a humanitarian crisis. Aggregately, these ensuing phenomena have adversely affected Christian churches in this region, triggering an aura of responses: coping strategies, humanitarian work among refugees, and inter-faith dialogue. These responses are predicated on Christianity’s potential as a resource for peace, compassion, and love. In this study we emphasize the role of Christian churches in dealing with the Boko Haram insurgency. It opens up with a contextualization of Boko Haram in Cameroon’s north. This is followed by an examination of the brutality meted out on Christians and church property. The final section is an examination of the spiritual, humanitarian and relief services provided by Christian churches. The paper argues that although Christian churches have suffered at the hands of Boko Haram insurgents, they have engaged in various beneficial responses underpinned by the Christian values of peace and love.

The life and work of Ignacio Ellacuría, S.J. is of radical vision, and revolutionary change. His dynamic life and works accompanied El Salvador and the Universidad Centroamericana through perhaps the most tumultuous years of the country’s history, yet there has been limited work done to examine his contributions. This paper shows how Ellacuría viewed the role of a Christian intellectual, and a Christian university within his philosophical and theological framework. I argue that Ignacio Ellacuría held, similarly to his soteriological views, that the intellectual must also be willing to sacrifice all for the sake of his/her work in a pattern of discipleship/martyrdom prefigured by his exemplars Christ and Socrates. It was this dedication to praxis and theory that western theology and philosophy had respectfully lost since their foundations which he sought to restore to a central role. In conclusion, the Christian intellectual and institution, according to Ellacuría, must use its voice and life in service of the people even to the point of martyrdom; he would argue, the implicit reason for Christian martyrdom and the crucifixion of Christ himself.

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

Background: Despite procedural advancements in the management of univentricular heart patients palliated with a Fontan-type circulation, their exercise capacity and quality of life remain limited. Postoperative exercise training programs offer potential benefits, yet practical implementation and adherence to guidelines are often inadequate. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Method: A systematic search was conducted on August 24, 2023, using PubMed, Scopus, Web of Science, and Cochrane Library. Studies were screened via Rayyan QCRI based on pre-set exclusion criteria, and their quality was assessed using the Cochrane RoB Tool 2 and the STROBE checklist. A meta-analysis employed a continuous random-effects model to assess the efficacy of cardiac rehabilitation interventions. Results: The study included twenty-six studies (7 RCTs, 19 cohorts) representing 22 individual cohorts. The key findings were that aerobic exercise, lower-extremity resistance training, and inspiratory muscle training significantly improved VO2, enhancing exercise capacity in Fontan patients. Conclusion: While the results are promising, it's crucial to remember that training programs varied widely. Exercise training shows promise for postoperative management, potentially improving exercise capacity, cardiac biomarkers, lung function, and lower limb strength. However, further research is not just a suggestion, but a necessity. It's necessary to refine protocols, assess long-term impacts, and investigate underlying mechanisms, especially for Fontan patients with severe clinical conditions. This emphasizes the importance and urgency of further research in this area.

Carol Winkelmann, in her book ‘The Language of Battered Women’ describes not only the fact that domestic abuse is almost a daily occurrence in the lives of many women but that the language of religion and faith is often used by women in attempts to explain, understand and cope with such abuse . While religious belief and domestic violence may seem contradictory in terms of religious values of faith, virtue and love, research demonstrates that domestic violence in religious families and amidst religious congregations is prevalent. In fact, religious beliefs and practices are often embedded in cultural contexts and thus perpetuate patriarchal notions of dominance, power and submission. Abused Christian women, for example, are more likely to seek help from (male) ministers and others in positions of authority in their local church communities and are equally more likely to remain in or return to unsafe relationships, citing their religious beliefs to support their avoidance of ‘family break-ups’ because of abuse. What, then, is the response of ministers and church authorities to domestic abuse in their congregations? Despite recent calls for the training of pastors and other religious leaders in an understanding of domestic violence and in the recognition of appropriate, helpful responses, the language of some Christian churches can be seen to foster notions of submission so that women and pastors alike can appear confused concerning the experience of abuse. Religious congregations, while acting in love to help the poor and needy, for example, often fail to recognise domestic abuse amongst their own members and, indeed, such a topic can remain taboo in some church communities. Women, in turning to their pastors or other Christian leaders for help, can be silenced by the language of the religion itself, so that the role of wives and mothers may be seen to be submissive and the ‘keeper of the home’; to leave an abusive relationship may thus ‘break-up’ a home and imply failure of the woman to understand her role and fulfil her ‘maternal vocation’. On the other hand, religious beliefs offer victims of domestic violence both hope and comfort. Religious practices, such as prayer, liturgies and corporal (physical) works of mercy, can provide solace and practical assistance for women who suffer abuse. Domestic violence in religious congregations can be addressed within the context of the faith itself, with an emphasis on love and respect, helping women to understand their dignity with avenues of help so that the women can remove themselves and their children from abusive relationships, and the religious congregation and its leaders can call the partners to accountability. This paper seeks to outline a picture of domestic violence in religious congregations, specifically Christian church communities, by drawing on current research in the Western world. It then describes the language of some religious congregations that perpetuates domestic violence, with emphasis on contemporary studies in religious belief and domestic abuse. Finally, the paper makes some suggestions on how religious belief and practice can, in contrast to perpetuating abuse through norms, serve to assist women as victims of domestic violence, and how the connections between domestic violence and religious language or belief can be severed.

This article presents a new input device for spastic patients and others with similar symptoms. The sensor consists of a disc used to determine positions and can replace standard joysticks in medical devices such as electric-powered wheelchairs. Using a standard joystick while operating a powered wheelchair can result in dangerous situations when spastic movements occur and extremities cramp making them uncontrollable. To avoid this, a disc was developed that can be controlled with any body part. By shifting weight (x- and y-axis) the disc can tilt in any direction creating a proportional output signal and can also be pushed down in the center (z-axis) to open a menu on a screen for example. When spasms occur it is impossible for users to get stuck on the input device because the disc is flat and can be mounted within a control panel. Body parts coming into contact with the disc would merely slide across the disc without triggering unintentional actions. The sensor presented here is also adaptive and can be adjusted to fit a user’s strength and range of motion. This proposal aims to develop an input device that enables spastic patients to operate sensitive systems safely.

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

We aimed to provide a comprehensive assessment of exercise physiology of adult Fontan patients (FP) and factors limiting functional capacity (FC). A prospective single-centre study of 37 FP aged ≥16years and 19 healthy-controls (HC), who underwent CPET on cycle-ergometer in February-March 2022. Lung function was impaired in FP, mostly mild restrictive pattern (56.8%). Mean peakVO2 was 21±5.4ml/kg/min, 55% predicted. Morphologically left-single ventricle showed higher peakVO2%predicted (57.4±14.4% vs 43.4±8.1%, p=0.045). A lower peakVO2%predicted was observed in patients with an early flattened and/or descending O2 pulse at maximal exertion (52±14% vs 62±12.5, p=0.04 and 47.6±9% vs 60±14 respectively, p=0.018) and chronotropic insufficiency (53±12% vs 69.8±20%, p=0.008). Strong positive correlation was observed between %OUES and peakVO2%predicted (r=0.726, p>0.001). PeakVO2%predicted was progressively higher as the level of physical activity increased (low-level 49.5±14%, moderate-level 55±12%, intense-level 69±20%). FP showed lower inspiratory muscle strength compared to HC but it was no statistically associated with either peakVO2 or VE/VCO2 slope. In FP OUES is a useful submaximal parameter in those who fail to reach maximal exertion. Chronotropic insufficiency and early flattened or descending oxygen pulse slope were factors associated with low peakVO2. Regular intense physical activity improves FC. Although FP have inspiratory muscle weakness, its impact on FC is unclear.

This article presents the development of a Faith-Informed Advocacy Model that integrates faith-based principles and values into advocacy efforts within Christian social work. Drawing from the intersection of Christian ethics and social work principles, this model provides a framework for Christian social workers to engage in advocacy work that is grounded in their faith and guided by ethical principles. The article includes case studies that illustrate the application of the model in real-world scenarios.

Introduction: The Fontan procedure, a palliative surgery for univentricular heart physiology, of-ten reduces exercise capacity and quality of life. This study aimed to evaluate the impact of cardiac rehabilitation (CR) on improving outcomes in Fontan patients to inform evidence-based care. Methods: Fontan patients aged 8-30 participated in a structured CR program for at least three months. The program included weekly aerobic and resistance training sessions, with educational and nutritional guidance. Baseline and post-CR assessments included cardiac function, fitness, daily activity, and health-related quality of life (HRQOL). Results: The cohort included ten Fontan patients, of whom six had a right systemic ventricle. CR significantly improved cardiorespiratory fitness, as seen in VO2 max (from 27.92 ± 5.15 to 34.69 ± 1.14 mL/kg/min, p = 0.0089) and per cent predicted VO2 (from 0.67 ± 0.18 to 0.90 ± 0.02, p = 0.005). VCO2 increased by +8.68 ± 8.59 mL/kg/min, but did not reach statistical significance (p = 0.05). Most haemodynamic and ventila-tory parameters showed no significant improvement. All the SF-36 questionnaire domains showed significant HRQOL gains (p < 0.001). High adherence (85-93%), no adverse events, and reduced NT-proBNP levels supported the program's safety. Conclusion: This study's findings have im-portant implications for the care of Fontan patients. CR significantly improved exercise capacity and HRQOL in Fontan patients across various anatomies, particularly in the right systemic ven-tricle. Integrating physical conditioning into standard care could reduce long-term morbidity and mortality; however, further research is needed to refine the protocols and confirm sustained ben-efits.

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

Taiwan’s auditors have suffered from processing excessive audit data, including drawing audit evidence. This study advances sampling techniques by integrating machine learning with sampling. This machine learning integration helps avoid sampling bias, keep randomness and variability, and target the risker samples. We first apply a Naive Bayes classifier to classify data into some classes. Next, a user-based, item-based, or hybrid approach is employed to draw audit evidence. The representativeness index is the primary metric for measuring the representativeness of audit evidence. The user-based approach denotes the selection of samples between two percentiles in a class as audit evidence. It may be equivalent to a combination of monetary and variable sampling methods. The item-based approach represents the choice of risky samples as audit evidence. It may be identical to a combination of non-statistical and monetary sampling methods. Auditors can hybridize those user-based and item-based approaches to balance representativeness and riskiness in selecting audit evidence. Three experiments show that sampling using machine learning integration has the benefits of drawing unbiased samples, handling complex patterns, correlations, and unstructured data, and improving efficiency in sampling big data. However, the limitations are the classification accuracy output by machine learning algorithms and the range of prior probabilities.

Background:Fontan completion is the last stage of univentricular repair, which drains the inferior vena cava against gravity to a higher-pressure pulmonary arterial circulation. The passivity and anti-gravity nature of this circulation render a failing Fontan, not an uncommon encounter, twenty years ago, Rodefeld and colleagues, decided to explore the feasibility of vascular pumps to support the passive nature of Fontan circulation, and since then, trials are still ongoing, and we aimed through this review to wrap up the results of these trials. Methods:A literature review has been conducted, to identify any in vivo or in vitro trial of a Fontan assist device. Several outcome parameters determined whether the trial will be included or not in this review, including, the flow rate of a pump if applicable, the number of compressions per minute if a compression device has been used, the resultant flow rate, the inferior and superior vena cava pressures, associated with each setting of the respective device, and any evidence of hemolysis or clotting within the circuit. Results:A total of ten trials have been included, with 23 different settings. Three designs have been identified, out of which two fall within the pump design, namely the connecting chamber and the intravascular pump designs; only one trial explored the possible use of a compression device. The commonest design encountered in in-vivo trials was the intravascular pump (67%). No reports of significant hemolysis or thrombosis were found. An increasing flow rate beyond 5L/min was associated with a negative outcome in the connecting chamber design, increasing upstream pressure in the SVC, while intravascular pumps did not display this limitation. Conclusion:Univentricular heart patients are a relatively small population, with very extensive needs, despite twenty years of trials, no study has yet concluded the optimal design or settings for a Fontan assist device. In this review, we identified that the intravascular pump remains the most practical design, due to its easy mode of insertion, and that it is not faced with the limitation or risk of increasing upstream resistance. There is still a long way to conclude its use as other designs such as compression devices have not yet been fully studied.

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

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

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

Research on White Etching Cracks (WEC) apparent in multiple bearing applications has identified various drivers to cause them. Lubricants, Electricity combined with contact mechanics are proven to catalyze WEC significantly. However, none of them is solely causing WEC by its own, instead combinations discretize whether WEC appears or not. Hence, the WEC topic appears to be multidimensional, making WEC still unpredictable. The current paper is about a systematic study by the use of a DGBB test rig on how lubricant chemicals combined with electricity and by varying oil flow and pressure lead to WEC. It becomes evident, that even WEC critical conditions turn to be WEC free by simply increasing the oil flow and decrease the contact pressure.

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

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

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

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

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

The topical therapy with rifampicin (RF)-based formulations is beneficial to treat infections and to healing the wounds. Despite recent research highlighting the antibiotic's significant an-ti-inflammatory properties, limited topical wound healing products are currently available. Present study aimed to prove that the newly synthesized nanoparticles based on grafted alginate and poly(N-vinylcaprolactam (pNVCL) and poly-lactic-co-glycolic acid (PLGA) contributes to the healing process of a wound. The methods used were at first the synthesis of the copolymer of al-ginate and pNVCL via grafting from technique and radical polymerization followed by wa-ter-in-oil-in water (W/O/W) emulsification by using as oil phase PLGA dissolved in dichloromethane (DCM). The formed nanoparticles were than characterized. The loaded RF was determined to be 160 µg/mL for a 20 mg formulation and within a four-hour time frame approximately 10% of the total loaded amount was released. The inhibitory concentrations (IC50) were 192 µg/mL for the nanoparticle, 208 µg/mL for pure rifampicin, and 718 µg/mL for the rifampicin-loaded nanopar-ticles. Considering the double role Rifampicin was used for, the result was considered satisfactory in the way that these formulations could be used more with the wound irrigation post-surgery to avoid infections and to contribute to the healing.

Purpose: To analyze the genetic and molecular profile of liver nodules in the context of Fontan-associated liver disease (FALD) with the aim of identifying possible biomarkers for predictive outcome and personalized therapy. Methods: this retrospective monocentric study included 9 patients who developed FALD in the context of congestive cirrhosis:1 regenerative nodular hyperplasia, 2 hepatic adenomas (HA) and 4 hepatocellular carcinoma (HCC), 1 fibrolamellar carcinoma (FLC) and 1 intrahepatic cholangiocarcinoma (ICC). The lesions were analyzed by histology and immunohistochemistry (b-catenin, glypican 3, glutamine synthetase and SOX9). To study the molecular profile of neoplastic FALD, targeted NGS was performed on DNA and RNA from formalin-fixed paraffin embedded neoplastic liver tissue of 1 HA, 2 HCCs, 1 FLC and 1 ICC. Results: Molecular analysis showed 3 patients with copy number alteration involving FGFR3, and one patient with a hotspot mutation on CTNNB1 and NRAS genes. All 5 patients showed a tumor mutational burden ranging from low to intermediate. Variants of unknown significance in GNAS were present in 2 HCC and 1 ICC. The single FLC had a DNAJB1-PRKACA fusion. Conclusions: The molecular results seem to be consistent with a peculiar molecular profile of the malignant FALD which may be useful for new target therapies for HCC/ICC in FALD.

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

The open burning of sugarcane residue is commonly used as a low-cost and fast method during pre-harvest and post-harvest periods. However, this practice releases various pollutants, including dioxins. This study aims to predict polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, or dioxins) emissions using the Grey Model (GM (1,1)) and to map the annual flux spatial distribution at the provincial level from 2023 to 2028. Using the activity rate of dry crop residue from national agencies and literature, and following the guidelines set by the United Nations Environment Programme (UNEP), an annual emission inventory was developed at the provincial level. The distribution of emissions from 2016 to 2022 was then mapped. The average PCDD/Fs emission values exhibit significant variation among the provinces, averaging 309 pg TEQ/year. Spatially, in line sugarcane production, South Sumatra and East Jawa consistently show high emissions, often exceeding 400 pg/m². Emissions based on the UNEP emission factor tend to be higher compared to other factors, due to its generic nature and lack of regional specificity. The emission predictions using the Grey Model GM (1,1) indicate that North Sumatra is expected to experience a steady increase in PCDD/Fs emissions, whereas South Sumatra and Lampung are projected to see a slight decline. This forecast assumes there will be any changes in regional intervention strategies. Most regions in Jawa Island show a gradual increase in emissions, except for East Jawa, which is predicted to have a slight decline from 416 pg/year in 2023 to 397 pg/year in 2028. Additionally, regions like Gorontalo and parts of East Jawa are projected to remain "hotspots" with consistently high emissions, suggesting the need for targeted interventions. Future studies should consider developing monthly emissions profiles to account for local agricultural practices and seasonal conditions. The emission data generated in this study, which includes both spatial and temporal distributions, is valuable for air quality modeling studies. Utilizing this data can help assess the impact of current and future emissions on ambient air quality.

Background and Aims: Sustained virologic response (SVR) lead to the decrease of portal hypertension, the regression of fibrosis, the improvement of the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in HCV cirrhotic patients treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological and coagulation tests were collected at baseline, EOT and SVR12/24. Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVR. The MELD score decrease at EOT (13.48 ± 4.273; p =0.001), and SVR (9.88 ± 2.774; p = 0.000), compared to baseline (14.92 ± 4.707). Fibroscan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT) there was a trend towards improvement during treatment, changes that were statistically significant for the majority of patients. Factor II low at baseline (75.40 ± 7.506), increases at EOT (87.40 ± 9.587), and later at SVR (99.12 ± 11.695; p = 0.000). FVIII values increased at baseline (175.52 ± 16.414) decrease at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). FvW values decreased during treatment (146.84 ± 9.428 – baseline, 141.32 ± 9.690; p =0.000 – EOT, 126.68 ± 17.960 – SVR). In regards to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the “reset” of the coagulopathy might be due to the improving of the liver function due to viral eradication secondary to AAD therapy.

Sepsis is a life-threatening condition caused by the body's overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which ranks among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection was frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. These data indicate similarity and interdependences of both syndromes, but also significant differences which will be discussed in the present review.

Aging is associated with a decline in immune system functionality. So-called immunosenescence may impair successful vaccination of elderly people. Thus, improved vaccination strategies specifically adapted to an aged immune system are required. We characterized a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein (MVA-ST) in an aged-hamster model for COVID-19. Intramuscular MVA-ST immunization resulted in protection from disease and severe lung pathology. Importantly, protection correlated with potent activation of SARS-CoV-2 specific T-cells and neutralizing antibodies. Our results suggest that MVA vector vaccines merit further evaluation as clinical candidate vaccines in elderly people to overcome limitations of age-dependent immunosenescence.

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

Unmetamorphosed carbonaceous chondrites provide important information concerning the formation and evolution of organic matter, such as amino acids. However, terrestrial contamination remains a valid concern when investigating the organic inventory of meteorites that have fallen to Earth. Accordingly, JAXA’s Hayabusa2 and NASA’s OSIRIS-REx have been launched with the task of returning uncontaminated C-type asteroid material to Earth. The successful Hayabusa2 mission has a very limited sample size (5.4 g). Therefore, many conventional compound specific techniques will struggle to detect amino acids above detection limit with available sample amounts (~several mg to 10’s of mg) being much smaller than those typically used. Here a novel method utilizing ultrahigh performance liquid chromatography-Orbitrap-mass spectrometry is validated and applied to very small meteorite samples, thus providing an approach that can overcome the small sample size constraints of sample return missions. The method is highly sensitive, enabling the detection of amino acids in the carbonaceous chondrites Murchison (2.28 mg) and Orgueil (2.30 mg). Furthermore, quantitation was possible for many of the detected amino acids in Murchison and Orgueil. Using the data presented here, both the amino acid reservoirs of Murchison and Orgueil and the potential application of this method to sample return samples are discussed.

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

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

The endorsement from Christian circles in facilitating the rise of right-wing populism in Brazil, the United States, as well as the support and alliance of the Polish Catholic Church with the Law and Justice (PiS) government, is widely acknowledged. Embedded within the intricate fabric of multifaceted factors contributing to the surge of right-wing populism, the Culture War assumes a pivotal yet often underestimated role. Manifesting as a profound confrontation, the Culture War signifies an existential clash between contrasting perspectives concerning socio-cultural values grounded in religious scripture. Progressive endeavors strive to deconstruct longstanding norms, advocating for the ascendancy of post-materialistic ideals, while conservative domains portray an unwavering commitment to safeguarding national and religious socio-cultural values as sacrosanct. Both factions employ moral-ethical justifications in their respective pursuits, rendering the landscape of cultural discourse a nuanced tapestry of ideological contention. The influence of Christian doctrine on the conflict surrounding social justice, and the potential convergence between Christian doctrine and the positions of Populist right-wing movements on social justice issues, is underscored. By employing a singular case study focused on Portugal, owing to the nation's enduring relationship with Catholicism spanning from Monarchical times to the Republic and the Fascist Catholic regime, Portugal emerges as indisputably one of the most religious countries in the Western world, akin to Poland. Consequently, in theory, the support of the Portuguese Catholic Church for the nascent Populist right-wing and Christian-oriented party should be evident amidst the Culture War conflict, wherein conservative religious Christian values face existential challenge. However, the backing extended to CHEGA by both the Catholic Church and the Portuguese Episcopal Conference assumes an ambivalent and markedly diminished stance, diverging from the previously robust support observed in established center-right mainstream parties such as the PSD and CDS. Despite this reality and the absence of official support for CHEGA, numerous Christian politicians or activists have expressed endorsement or alignment with the right-wing party, departing from their former affiliations, primarily due to social justice concerns.

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

Aquatic environments are generally heterogeneous in space and time, and the marine organisms have their ways response to those environmental heterogeneities. Cutlassfish (Trichiurus spp.) once is one of the “Chinese Four Major Marine Fish Species” along the coast of northwest Pacific Ocean. There are some comments on the cutlassfish (T. spp.) name identification. In this study, three cutlassfish species, namely, the largehead hairtail (T. japonicas) in East China Sea (ECS), Chinese short-tailed hairtail (T. brevis), and South China Sea (SCS) cutlassfish (T. nanhaiensis), have been identified in the northwest Pacific Ocean. This work integrated 115 studies in cutlassfish population dynamics from 24 sites across 8 countries in the world. The biomass distribution of T. japonicas in the ECS and T. nanhaiensis in SCS, was found to be highly correlated with water temperature and salinity. Spatiotemporal heterogeneity of cutlassfish is found to correlate with both genetic and environmental characteristics in the northwest Pacific Ocean (e.g., density dependency, primary productivity and climate ocean oscillation). Closely related species coexisting in the same shelf region (e.g., T. japonicus and T. nanhaiensis in ESC) often differ in diet and microhabitat. The difference of skull phenology between T. nanhaiens and T. brevis is found to correlate with species separation and environmental heterogeneity. With the implications for the design of ecological research programs on cutlassfish, our study found that the effect of temporal changes outweighs (to some extent) the effect of spatial changes on cutlassfish in those shelf regions.

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

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

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

In Taiwan, mountainous areas account for approximately two-thirds of the total area. The steep terrain and concentrated rainfall during typhoons cause landslides, which pose a considerable threat to mountain settlements. Therefore, models for analyzing rainfall-induced landslide hazards are urgently required to ensure adequate land use in mountainous areas. In this study, focusing on Pingtung County in southern Taiwan, we developed a landslide hazard index (IRL) to land use. Using FORMOSA-2 and SPOT-5 satellite images, data were collected before and after four typhoons (one in 2009 and three in 2013). The ArcGIS random tree classifier was used for interpreting satellite images to explore surface changes and disasters, which were used to analyze slope disturbances. The product of the maximum 3-h rolling rainfall intensity and effective accumulated rainfall was used as a rainfall trigger index (IRT). Considering environmental and slope disturbance factors, an index of slope environmental strength potential (ISESP) was developed through logistic regression (LR). Landslide hazard to land use was estimated using IRT and ISESP. The average coefficient of agreement (Kappa) was approximately 0.71 (medium to high accuracy); the overall accuracy of slope environmental strength potential analysis was approximately 80.4%. At a constant ISESP, IRT increased with the increasing hazard potential of rainfall-induced landslides. Furthermore, IRT and ISESP were positively correlated with landslide occurrence. When large ISESP values occur (e.g., fragile environment and high land development intensity), small IRT values may induce landslides.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C&gt;T, not yet reported, and c.838C&gt;T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Objectives: The purposes of this study were to 1) analyze the disruption of intracardiac flow by flow components and kinetic energy (KE) parameters in single ventricle physiology patients and compare with controls; 2) investigate left ventricular diastolic dysfunction in terms of 4D flow parameters in repaired Fontan (rFontan) group; 3) compare intracardiac flow parameters in morphologic LV and RV rFontan patient groups. Methods: Twenty-five rFontan patients (age: 10±3, M/F: 15/10) and fourteen controls (age: 10±2, M/F: 8/6) were prospectively recruited. All underwent cine and 4D flow cardiovascular magnetic resonance (CMR) on 3.0T scanner. Cardiac function and inter-ventricular mechanical dyssynchrony were analyzed using cine images. From 4D flow CMR, ventricular flow components were assessed: direct flow, retained inflow, delayed ejection flow and residual volume. Global and regional blood flow KE parameters, normalized to end-diastolic volume (EDV) were analyzed for functional single ventricle (FSV). Left ventricular (LV) diastolic dysfunction was assessed on echocardiography guidelines. Results: In comparison of rFontan vs. controls, median FSV residual volume (28% vs. 23%, P= 0.034) were higher in rFontan; median FSV direct flow (32% vs. 40%, P=0.005) and delayed ejection flow (17% vs. 24%, P=0.024) were lower in rFontan. FSV KEiEDV parameters were all lower in rFontan (all P<0.05). No significant differences were observed for flow components and KE parameters between patients with and without inter-ventricular dyssynchrony. FSV direct flow (AUC=0.76, Sensitivity=86%, Specificity=70%) was an independent predictor of LV diastolic dysfunction. Residual volume and E-wave KEiEDV were significantly different between morphologic RV and morphologic LV patient group. Conclusions: The changed flow pattern and decreased KE may be hemodynamic disturbances and impaired ventricular filling in rFontan patients. Reduced direct flow is associated with LV diastolic dysfunction. Morphologic right ventricular subgroup is worse than morphologic left ventricular group in terms of the intracardiac hemodynamics.

In the British setting, the deployment of the phrase ‘doing god’ has become increasingly common to refer to an emerging trend whereby religion has acquired an increasingly prominent role in political spaces and discourses. This was particularly prominent while David Cameron was Prime Minister and leader of the Conservative Party. While historically, religion has not had a prominent place in either the former Prime Minister David Cameron. Here, the findings from critical analyzing a series of Cameron’s public pronouncements about religion—and Christianity in particular—is set out to try and better understand his own adherence to Christianity (the personal) how this intersected with his politics and role as Prime Minister (the political), and more importantly how this shaped his views about Britain being a Christian country (the national). Contextualised within the embryonic scholarly literature relating to the phenomenon of ‘doing god’ in the contemporary British setting, this article concludes by considering alternative and analogous frames through which greater elucidation of the true motivations of his pronouncements might be understood.

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

Ankle sprains are the most frequently occurring musculoskeletal injuries among recreational athletes. Ankle support through bandages following the initial orthotic treatment might be beneficial for rehabilitation purposes. Since hardly any study has investigated the impact of bandages in the acute phase of ankle sprains, our study examined the immediate effects of wearing an ankle bandage on fine coordination, proprioception, and motor performance in subjects five weeks after an acute ankle injury. In total, 70 subjects with acute unilateral supination trauma were tested. All subjects completed several rating questionnaires and biomechanical investigations, including a fine coordination and proprioception test, single leg stances, the Y-Balance test and gait analysis. All biomechanical investigations were conducted for the subject's injured leg with and without a bandage (MalleoTrain® Bauerfeind AG) and the healthy leg. Subjects reported moderate to strong improvements in ankle stability and pain when wearing the bandage. Wearing the bandage significantly normalized subjects’ single leg stance performance, as well as the stance phase duration, and the vertical ground reaction forces during walking. However, the bandage did not have a clear effect on fine coordination and proprioception. Wearing a bandage in the acute phase of an ankle sprain may immediately improve motor performance, including standing and walking.

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

Background: At altitudes beyond 2500 m the risk of developing high altitude pulmonary edema (HAPE) grows with the increases in pulmonary arterial pressure. HAPE is characterized by severe pulmonary hypertension, though the incidence and relevance of individual risk factors are not yet predictable. However, the systolic pulmonary pressure (SPAP) and peak in tricuspid regurgitation velocity (TVR) are crucial factors when diagnosing pulmonary hypertension by echocardiography. Methods: The SPAP and TVR of 27 trekkers aged 20-65 years en route in the Solu Khumbu region of Nepal was assessed. Echocardiograph measurements were performed at Lukla (2,860 m), Gorak Shep (5170 m), and the summit of Kala Patthar (5,675 m). The altitude profile and the participant’s characteristics were also compiled for correlation with the measured data. Results: The results showed a highly significant increase of SPAP and TVR after ascending Kala Patthar. The study revealed a lower increase of SPAP and TVR in the group of older participants, although the initial respective measurements in Gorak Shep were significantly higher for this group. A similar finding occurred in those using Diamox® as prophylaxis. There was an inverse relationship between TVR and SPAP, the peripheral capillary oxygen saturation and heart rate. Conclusions: The echocardiograph results indicate that older people are a risk group for developing a HAPE. The prophylactic use of acetazolamid led to higher initial SPAP values in Gorak Shep, and a lower increase of SPAP as well as TRV after ascending Kala Patthar. Arterial oxygen saturation measurements can provide an indicator for the self-assessment for the risk of developing HAPE and provide a rule of thumb for the altitude profile but does not replace a HAPE diagnosis. The collected data variables concerning backpack weight, sex, workload (actual ascent speed), and pre-existing diseases were not statistically significant factors related to SPAP and TVR (p=<0.05).

Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T cell response, but far from all patients elicit a sufficient immunological response. This witnesses a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic healthy human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy showing E1-specific T cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors, and preferably in patient samples.

This study investigates the comparative performance of autoencoders and traditional machine learning (ML) algorithms in predicting tumor dynamics following Gamma Knife radiosurgery (GKRS) for brain metastases (BMs). The research retrospectively analyzed clinical data from 77 patients (median age: 64 years; 45 males, 32 females) treated at the “Prof. Dr. NicolaeOblu” Emergency Clinic Hospital-Iasi. The dataset comprised 12 variables, including socio-demographic, clinical, treatment, and radiosurgery-related factors. The primary outcome was tumor progression or regression within three months post-GKRS, with 71 cases of regression and 6 cases of progression observed. Traditional ML models—Logistic Regression, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Extra Trees, Random Forest, and XGBoost—were evaluated, achieving accuracy rates ranging from 0.91 (KNN) to 1.00 (Extra Trees). When incorporating features extracted by autoencoders, the performance of these models generally improved, especially with compression in the bottleneck layer. For instance, Logistic Regression's accuracy increased from 0.91 to 0.94, while SVM's accuracy improved significantly from 0.85 to 0.96. XGBoost consistently performed well across both traditional and hybrid setups, maintaining an accuracy of 0.94 with an AUC of 0.98. The findings suggest that hybrid approaches combining deep learning with traditional ML techniques can significantly enhance predictive accuracy and robustness, particularly in the context of GKRS for BMs. This improved performance has potential implications for more informed clinical decision-making in personalized medicine.

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

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

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

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphoma (PTCL), which is a diverse group of aggressive lymphomas with a bleak prognosis. Recent evidence has shown that HDACi are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to other treatments, and there are few available options. Several clinical trials have demonstrated that HDACi, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCL, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor actions by regulating gene expression through inhibiting histone deacetylases, which results in the halting of cell division, programmed cell death, and the transformation of cancerous T-cell, as indicated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACi presents a significant and beneficial treatment choice for PTCL. However, although HDACi showed potential effectiveness, they couldn’t cure most patients. Therefore, new combination with conventional drugs as well as new targeted agents are under investigation.

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

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

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

Context: The compartmental description, well-known from the description of infection diseases and epidemics, is applied to describe the temporal evolution of the baryonic matter in interstellar gas and stars. The introduction of gaseous and stellar fractions of the total baryonic matter as the basic dynamical variables is advantageous because it allows to apply the description to a variety of astrophysical systems. Aims: The competition of spontaneous star formation, stellar feedback and stellar evolution is theoretically investigated to understand the baryonic matter cycle including luminous baryonic matter in main-sequence stars and weakly luminous matter in white dwarfs, neutron stars and black holes (referred to as locked-in matter). Of particular interest is the understanding of the cosmic star formation history and the present-day gas fraction with compartmental models. Methods: For stationary rates of spontaneous star formation, continuous stellar feedback and stellar evolution exact analytical solutions of the time evolution of the fractions of gaseous, luminous stellar and locked-in stellar matter are derived. The accuracy of the analytical solutions is proven by the favorite comparison with the exact numerical solutions of the dynamical equations. Results: The observed cosmological star formation rate and the integrated stellar density as a function of redshift are reasonably well explained by the compartmental model without triggered star formation by the competition of spontaneous star formation and stellar evolution whereas the influence of stellar feedback is less important. The action of stellar evolution provides a significant redshift dependent reduction factor when calculating the integrated stellar density from the star formation rate. Without stellar evolution the observations cannot be reproduced very well. Then the fits to the observation allow us conclusions on the relative importance of spontaneous star formation, stellar evolution and feedback in the early universe after the recombination era until today. The gas, luminous star and locked-in stellar matter fractions indicate that the vast majority of the baryons in the present-day universe resides in the form of locked-in stellar matter in white dwarfs, neutron stars and black holes.

Probiotics are becoming more and more popular in the growing of fin and shellfish because these species are consumed worldwide and because different techniques are employed to maximize the productivity and efficiency of fin and shellfish. Probiotic Bacillus is one of the many types of probiotics that are used, but it stands out due to its superior qualities. For instance, because of its ability to sporulate, it can survive in harsh environments, produce antimicrobial substances, and is safe to feed to fish. The different species of Bacillus used in the farming of fin and shell fish were discussed in this review, along with the benefits of using Bacillus spp. as a good substitute in sustainable aquaculture to improve feed utilization, immune system response, stress adaptation, resistance to infectious diseases, tissue preservation integrity, and water quality. Additionally, we discussed the possible risks to safety that Bacillus poses when raising these significant species. For the purpose of future research and development regarding Bacillus application in aquaculture, a summary of the findings of recent studies about the advantages of applying Bacillus to enhance fin and shellfish aquatic animal culture has been provided.

Adjunctive treatment of periodontitis lacks solutions allowing enough time for wound healing in the periodontal pockets by avoiding a fast re-colonization. Such a solution might be an antibiotic containing formulation with a controlled release over weeks. Here, a recently described minocycline containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development and degradation studies. Animal studies were done in two different (mouse-chamber, rat Porphyromonas gingivalis challenging) models, including effects on inflammation markers, bone loss and bone structure. Also, serum concentrations of minocycline after local application were determined by HPLC-MS/MS. The resistance status of bacterial clinical isolates against minocycline was investigated and the degradation of the formulation was characterized by laser scanning- and scanning electron microscopy. Animal studies clearly demonstrated the applicability of the new formulation in the investigated models. Inflammation markers decreased dosage dependent and reduced bone loss compared to non-treated group was observed. Thereby, the systemic burden of the antibiotic was neglectable. Minocycline is still effective against oral pathogens; resistance development was not seen. The biodegradable thread was first swollen and subsequently degraded over weeks. The results support the continued clinical development of this new formulation. A phase I clinical trial is planned to further evaluate its safety and efficacy.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

Reactions of Co(OAc)24H2O, N‚N'-bis(3-pyridylmethyl)oxalamide (L) and 4,4’-sulfonyldibenzoic acid (H2SDA) afforded four coordination polymers with the same mixed ligands, {[Co(L)(SDA)(H2O)2]·H2O·CH3OH}n, 1, {[Co(L)0.5(SDA)]·2H2O·0.5L}n, 2, {[Co(L)1.5(SDA)(H2O)]·H2O}n, 3, and {[Co2(L)1.5(SDA)2(H2O)2]·4H2O}n, 4, which have been structurally characterized by using single crystal X-ray crystallography. Complexes 1 – 4 are 2D layers, revealing the topologies of sql, 2,6L1, (4,4)Ia and 6L12, respectively, and demonstrating that the metal to ligand ratio, solvent system and reaction temperature are important in determining the structural diversity. Immersion of these complexes into various solvents show that the structural types govern the chemical stabilities of 1 – 4. Reversible structural transformation can be shown for complexes 1 and 2 upon solvent removal and adsorption, while those of 3 and 4 are irreversible.

In this paper, we report a comprehensive and consistent annotation of the locus encoding the horse T cell receptor b-chain (TRB), as inferred from the most recent genome assembly. The horse TRB locus spans approximately 1 Mb, making it the largest locus among the mammalian species stud-ied to date, with a significantly higher number of genes related to extensive duplicative events. In the region, 136 TRBV, belonging to 29 subgroups, 2 TRBD, 13 TRBJ and 2 TRBC genes, were iden-tified. The general genomic organization resembles that of other mammals, with a V-cluster of 135 TRBV genes, located upstream of two in-tandem aligned TRBD-J-C clusters, and an inverted TRBV gene at the 3’ end of the last TRBC gene. However, the horse b-chain repertoire would be affected by a high number of non-functional TRBV genes. Thus, we queried a transcriptomic da-taset derived from splenic tissue of a healthy adult horse, using each TRBJ gene as a probe to ana-lyse clonotypes encompassing the V(D)J junction. This analysis provided insights into the usage of the TRBV, TRBD and TRBJ genes and the variability of the juxtaposition region. Our results clearly demonstrated that the horse β-chain constitutes a complex level of variability broadly like that described in other mammalian species.

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

Background: Existing human cell immortalization methods made the cells obtain oncogenesis phenotype and/or caused the cells gain and/or lose chromosomes. Immortalized normal human T cells lines provide critical in vitro models for basic research and therapeutic products development.Methods: We utilized a CRISPR/Cas9 system to replace a single copy of the exon 2 of the cell cycle inhibitor gene CDKN2A (encoding p16 and p14 proteins) with a single copy of human telomerase reverse transcriptase (hTERT) to immortalize human primary CD8⁺ T cells (hCD8⁺T-TERT). By using Cas9 protein and low donor DNA copies/cell, we successfully immortalized hCD8⁺T cells with a single copy of hTERT transgene, which also avoided uncontrolled insertion of Cas9 gene and guide RNA vector.Results: Human primary CD8+ cells were immortalized and expanded more than 2.6 × 10⁷ times. Characterization of the cells revealed that the immortalized CD8⁺ T-TERT cells retained most of the cell surface markers and normal karyotype. The CD8⁺ T-TERT cells also retained the dependence of IL-2 and CD3/CD28 activator for survival and expansion.Conclusion: we established a stable immortalized CD8⁺ T cell line that had a phenotype consistent with T cells and will be a useful research model.

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

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

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

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

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

Dipole antennas, fundamental components in wireless communication systems, have garnered significant attention due to their versatility and efficiency across various applications. This literature review explores the performance analysis of dipole antennas, focusing on recent advancements and methodologies from 2019 to 2024. Employing a systematic approach, the review synthesizes findings from multiple databases, emphasizing peer-reviewed studies that delve into dipole antenna designs and applications. Through meticulous data extraction, key parameters influencing dipole antenna performance, such as material properties and operating frequency, are identified and analyzed. Results highlight the widespread utilization of dipole antennas in wireless communication systems, including indoor positioning, mobile communication, and antenna calibration, among others. Discussions underscore the evolution of dipole antennas in base station environments and their role in filtering applications. The review concludes by emphasizing the continued relevance and evolution of dipole antennas, showcasing their adaptability and potential across diverse wireless communication contexts.

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

This manuscript explores significant advancements and emerging challenges in CAR T cell therapies, focusing on the production methodologies and regulatory complexities. The discussion highlights ongoing challenges like the lack of in vivo persistence, lengthy production times, and elevated costs associated with current CAR T cell therapies. It analyzes innovative solutions such as genetic engineering techniques aimed at enhancing cellular efficacy and endurance, alongside cutting-edge manufacturing processes, including closed systems and development of allogeneic products. These advancements hold promise for reducing costs and improving production efficiency, potentially increasing patient access to these transformative therapies globally. Furthermore, the manuscript underscores the necessity for expanding ongoing research and enhancing regulatory frameworks to fully realize and implement these innovations in CAR T cell manufacturing and bring these innovations to fruition.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

We have introduced a sign operator of energy, analogous to the operator helicity, but in the direction of what we call energy vector. However, this energy vector needs a time vector. To give physical senses to the components of such a time vector, we try to explain the time dilation in special relativity and try to relate the components of the time vector to the tunneling times when an electron crosses a potential barrier.

Three different approaches show that, contrary to a longstanding conviction older than 160 years, the advance of Mercury perihelion can be achieved in Newtonian gravity with a very high precision by correctly analysing the situation without neglecting Mercury's mass. General relativity remains more precise than Newtonian physics, but Newtonian framework is more powerful than researchers and astronomers were thinking till now, at least for the case of Mercury. The Newtonian formula of the advance of planets' perihelion breaks down for the other planets. The predicted Newtonian result is indeed too large for Venus and Earth. Therefore, it is also shown that corrections due to gravitational and rotational time dilation, in an intermediate framework which analyzes gravity between Newton and Einstein, solve the problem. By adding such corrections, a result consistent with the one of general relativity is indeed obtained. Thus, the most important results of this paper are two: i) It is not correct that Newtonian theory cannot predict the anomalous rate of precession of the perihelion of planets' orbit. The real problem is instead that a pure Newtonian prediction is too large. ii) Perihelion's precession can be achieved with the same precision of general relativity by extending Newtonian gravity through the inclusion of gravitational and rotational time dilation effects. This second result is in agreement with a couple of recent and interesting papers of Hansen, Hartong and Obers. Differently from such papers, in the present work the importance of rotational time dilation is also highlighted. Finally, it is important to stress that a better understanding of gravitational effects in an intermediate framework between Newtonian theory and general relativity, which is one of the goals of this paper, could, in principle, be crucial for a subsequent better understanding of the famous Dark Matter and Dark Energy problems.

Three different approaches show that, contrary to a longstanding conviction older than 160 years, the advance of Mercury perihelion can be achieved in Newtonian gravity with a very high precision by correctly analysing the situation without neglecting Mercury's mass. General relativity remains more precise than Newtonian physics, but Newtonian framework is more powerful than researchers and astronomers were thinking till now, at least for the case of Mercury. The Newtonian formula of the advance of planets' perihelion breaks down for the other planets. The predicted Newtonian result is indeed too large for Venus and Earth. Therefore, it is also shown that corrections due to gravitational and rotational time dilation, in an intermediate framework which analyzes gravity between Newton and Einstein, solve the problem. By adding such corrections, a result consistent with the one of general relativity is indeed obtained. Thus, the most important results of this paper are two: i) It is not correct that Newtonian theory cannot predict the anomalous rate of precession of the perihelion of planets' orbit. The real problem is instead that a pure Newtonian prediction is too large. ii) Perihelion's precession can be achieved with the same precision of general relativity by extending Newtonian gravity through the inclusion of gravitational and rotational time dilation effects. This second result is in agreement with a couple of recent and interesting papers of Hansen, Hartong and Obers. Differently from such papers, in the present work the importance of rotational time dilation is also highlighted.

This study examines the bias in weighted least absolute deviation (WL1) estimation within the context of stationary first-order bifurcating autoregressive (BAR(1)) models, which are frequently employed to analyze binary tree-like data, including applications in cell lineage studies. Initial findings indicate that WL1 estimators can demonstrate substantial and problematic biases, especially when small to moderate sample sizes. The autoregressive parameter and the correlation between model errors influence the volume and direction of the bias. To address this issue, we propose two bootstrap-based bias-corrected estimators for the WL1 estimator. We conduct extensive simulations to assess the performance of these bias-corrected estimators. Our empirical findings demonstrate that these estimators effectively reduce the bias inherent in WL1 estimators, with their performance being particularly pronounced at the extremes of the autoregressive parameter range.

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

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

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

Persons high in the manipulative, misanthropic trait Machiavellianism make use of various forms of deception to attain their goals. A recent study demonstrated that different facets of Machiavellianism account for different kinds of deception (Blötner & Bergold, 2023; https://doi.org/10.1111/bjso.12559). Intelligence could be another predictor of deception production. This research examined the interactions between different facets of Machiavellianism and verbal reasoning to predict the production of empty, vague pseudo-information that is supposed to help achieve desired states or prevent undesired ones (co-called “bullshit”). In a sample of 525 participants, and consistent with the hypotheses, individuals with high scores in the goal-oriented facet of Machiavellianism produced “bullshit” more frequently to achieve certain goals if they also scored high in verbal reasoning. Thus, and opposing common assumptions, Machiavellianism is not sufficient to explain engagement in deceptive behavior as it only reflects the motivation to do so. Especially in the case of verbally expressed deception, verbal skills are also required to be successful.

Purpose: This study aimed to investigate useful preoperative clinical and hematologic variables in predicting malignancy in patients with the atypia of undetermined significance (AUS) nodules, and to suggest a machine learning-based prediction model. Methods: We enrolled 280 patients who underwent surgery for the AUS nodules at Wonju Severance Christian Hospital between 2018 and 2022. We evaluated preoperative hematologic indices, including Delta Neutrophil Index (DNI), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), as well as preoperatively identifiable clinical variables such as age and sex at diagnosis, history of radiation exposure, familial history of thyroid cancer, primary tumor size, and the 2016 Korean Thyroid Imaging Reporting and Data System (K-TIRADS) classification. Results: A total of 116 patients (41.4%) were finally diagnosed with various types of thyroid malignancy, excluding 32 patients (11.4%) with thyroid cancer incidentally identified. Age at diagnosis (p = 0.012), primary tumor size (p = 0.048), and the K-TIRADS classification (p = 0.003) were independent risk factors to predict the diagnosis of malignancy in patients with AUS nodules younger than 55 years, not in those aged of 55 years or older. Adding the NLR to these risk factors significantly improved the predictability for malignancy in the same patient group (p < 0.001). Conclusions: The inclusion of NLR in the ma-lignancy prediction model enhances the predictive accuracy for malignancy in younger patients with AUS nodules. This finding suggests that incorporating NLR into preoperative assessment could refine management strategies and improve decision-making for surgical interventions.

This article conceptualises the link between firms’ value chains and distribution networks and the requirements for double materiality assessments in contemporary reporting regulations worldwide. The new European Sustainability Reporting Standards (ESRS) and the standards for sustainability reporting issued by the International Sustainability Standards Board (ISSB), called IFRS S1 and IFRS S2, require companies to report their own direct (scope 1) and indirect (scope 2) greenhouse gas (GHG) emissions as well as GHG emissions in their value chains and distribution networks (both scope 3). However, GHG emissions comprise just one dimension of information that is relevant to understand when assessing, managing and reporting the footprints and impacts of a firm and are, therefore, only a fraction of the key performance indicators (KPIs) related to ESG that should be disclosed. Through a case study, this article demonstrates the connection between the due diligence analysis of firms’ value chains and distribution networks, the analysis of the competitive parameters of the business model, the identified impacts, risks and opportunities, and the double materiality perspective. The double materiality perspective prioritises actions based on probability and significance, creating a natural space to identify KPIs. The article concludes by applying the REGS model and illustrating how it can assist firms in identifying relevant KPIs based on double-materiality assessments.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlighting the clinical importance, underlying mechanisms, and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

We show that the respective oversights in the von Neumann's general theorem against all hidden variable theories and Bell's theorem against their local-realistic counterparts are homologous. Both theorems unjustifiably assume the additivity of expectation values within hidden variable theories to derive their respective conclusions. However, for non-commuting observables, the equivalence of a sum of expectation values and the expectation value of the sum of measurement results, although respected within quantum mechanics, need not hold for hidden variable theories, regardless of specific characteristics such as local realism they may respect. Once this oversight is ameliorated from Bell's argument and local realism is implemented correctly, the bounds on the CHSH correlator work out to be +/-2\/2 instead of +/-2, thereby mitigating the conclusion of Bell's theorem. Consequently, what is ruled out by the Bell-test experiments is not local realism but the additivity of expectation values.

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

The novel coronavirus named by WHO and Coronavirus Study Group (CSG) as SARS-COV-2 is the etiological agent of the newly emerged Coronavirus disease (COVID-19). COVID-19 has become a pandemic threat as the WHO declared it a public health emergency of international concern. Early and precise detection of the virus is important for effective diagnosis and treatment. Various testing kits and assays, including real-time reverse Transcriptase PCR, thermal screening guns, ELISA-based immunoassays, and Point-of-Care (POC), have been implemented or are being explored to detect the virus and/or characterise cellular and antibody responses to the infection. However, these approaches have inherent limitations such as non-specificity, high cost, characterize by long turnaround times for test results, and can be labour intensive. Aptamers, which are single-stranded oligonucleotides, generated artificially by SELEX (Evolution of Ligands by Exponential Enrichment) may offer the capacity to generate high affinity bioprobes for monitoring relevant SARS-COV 2 and COVID-19 biomarkers. This article discusses the prospects of implementing aptasensing technologies for rapid point-of-care detection of SARS-COV-2.

In this paper, we work with a diffusion-perturbed risk model comprising a surplus generating process and an investment return process. The investment return process is of standard Black-Scholes type, that is, it comprises a single risk-free asset that earns interest at a constant rate and a single risky asset whose price process is modelled by a geometric Brownian motion. Additionally, the company is allowed to purchase noncheap proportional reinsurance priced via the expected value principle. Using the Hamilton-Jacobi-Bellman approach, we derive a second-order Volterra integrodifferential equation which we transform into a linear Volterra integral equation of the second kind. We proceed to solve this integral equation numerically using the block-by-block method for the optimal reinsurance retention level that minimizes the ultimate ruin probability. The numerical results based on light- and heavy-tailed distributions show that proportional reinsurance and investments play a vital role in enhancing the survival of insurance companies. But the ruin probability exhibits sensitivity to the volatility of the stock price.

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

Three different approaches show that, contrary to a longstanding conviction older than 160 years, the advance of Mercury perihelion can be achieved in Newtonian gravity with a very high precision by correctly analysing the situation without neglecting Mercury’s mass. General relativity remains more precise than Newtonian physics, but Newtonian framework is more powerful than researchers and astronomers were thinking till now, at least for the case of Mercury. The Newtonian formula of the advance of planets' perihelion breaks down for the other planets. The predicted Newtonian result is indeed too strong for Venus and Earth. Therefore, it is also shown that corrections due to gravitational and rotational time dilation, in an intermediate framework which analyzes gravity between Newton and Einstein, solve the problem. By adding such corrections, a result consistent with the one of general relativity is indeed obtained. Thus, the most important results of this paper are two: i) It is not correct that Newtonian theory cannot predict the anomalous rate of precession of the perihelion of planets' orbit. The real problem is instead that a pure Newtonian prediction is too strong. ii) Perihelion's precession can be achieved with the same precision of general relativity by extending Newtonian gravity through the inclusion of gravitational and rotational time dilation effects. This second result is in agreement with a couple of recent and interesting papers of Hansen, Hartong and Obers. Differently from such papers, in the present work the importance of rotational time dilation is also highlighted.

The purpose of this paper is to assess the differential impacts of transformational and transactional leadership styles on employee performance during change initiatives within commercial banks in Sierra Leone. The research study utilised a cross-sectional survey design, and data was collected from 903 participants employed in the banking industry. The study used the structural equation model as the investigative instrument to examine the hypotheses. The findings reveal that transformational and transactional leadership styles demonstrate a strong bearing on employee performance, with the latter having a bigger influence. Organisational citizenship behaviour has a mediating effect between leadership styles and employee performance, while employee commitment does not act as a mediator between transformational leadership and employee performance, but it acts as a mediator between transactional leadership and employee performance. Commercial banks need to devise training programmes that will advance both leadership styles to arouse, energise, or inspire followers to display favourable behaviour and commitment to attain organisational. The paper makes an insightful contribution to the existing leadership literature by ascertaining the significance of leadership styles on performance and the role of commitment and organisational citizenship behaviour as mediators of the nexus between leadership styles and performance in the Sierra Leone banking industry.

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

Sierra Madre Mountain Range (SMMR) is the backbone of Luzon Islands that contains high concentration of highly important ecological resources distributed among the 68 protected areas therewith. The present study aimed to assess the tree species composition and diversity in a secondary forest within the SMMR. A 2.25-km transect with 10 900-m2 was established to record tree species with a diameter at breast height of at least 10 cm. The findings revealed 148 individuals of trees from 38 morphospecies, 28 genera, and 20 families. Importance values unveiled the Aurora endemic Macaranga stonei Whitmore as the most important species in terms of the relative values of its abundance, frequency, and dominance. The area was also found to be home for 33 natives, 12 endemics, five IUCN threatened species, and nine Philippine threatened trees. Furthermore, the study site was also found to have a considerably high diversity with Shannon Weiner Index value of 3.269 and a relatively even distribution of individuals among species supported by the Simpson’s Evenness index value of 0.9453. Significant correlational relationships were also found among species richness, Shannon Weinder index, and Simpson’s Evenness index with correlation coefficients ranging from 0.881 to .934 all significant at p < .001. Lastly, the study was able to produce a distribution map necessary in implementing targeted conservation strategies. These findings provided valuable implications for future research and implementation of targeted and participatory biodiversity conservation and protection strategies.

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

In 2004, first absolute gravity (AG) measurements were performed on the mountain tops of Mt. Zugspitze (2 sites) and Mt. Wank (1 site), and at the Wank foot (1 site). Wank (summit height 1780 m) and Zugspitze (2960 m) are about 20 km apart from each other and belong geologically to different parts of the Northern Limestone Alps. Bridging a time span of 15 years, the deduced gravity variations for Zugspitze are in the order of 0.30 μm/s² with a standard uncertainty of 0.04 μm/s². The Wank stations (foot and top) show no significant gravity variation. The vertical stability of Wank summit is also confirmed by results of continuous GNSS recordings. Because an Alpine mountain uplift of 1 or 2 mm/yr cannot explain the obtained gravity decline at Zugspitze, the dominating geophysical contributions are assumed to be due to the diminishing glaciers in the vicinity. The modelled gravity trend caused by glacier retreat between epochs 1999 and 2018 amounts to -0.012 μm/s²/yr at both Zugspitze AG sites. This explains more than half of the observed gravity decrease. Long-term variations on inter-annual and climate-relevant decadal scale will be investigated in the future using as a supplement superconducting gravimetry (installed in 2019) and GNSS equipment (since 2018).

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