Browse Articles

Identification of core biomarkers for tuberculosis progression through bioinformatics analysis and in vitro research

Machine learning model to predict the adherence of tuberculosis patients experiencing increased levels of liver enzymes in Indonesia

Indonesia is still the second-highest tuberculosis burden country in the world. The antituberculosis adverse drug reaction and adherence may influence the success of treatment. The objective of this study is to define the model for predicting the adherence in tuberculosis patients, based on the increased level of liver enzymes. The longitudinal study using adult tuberculosis patients treated with the first line of antituberculosis was conducted prospectively. The pregnant women and patients with complications such as gout, diabetes mellitus, liver disorder and HIV were excluded. We measured the total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and adherence over the 2nd, 4th, and 6th months of the treatment. We used the ORANGE Data mining as the machine learning to predict the adherence. We recruited 201 patients, whereas the male participants and less than 61 years old as the dominant participants. Around 33%, 35% and 35% tuberculosis patients experienced the increase level of bilirubine, ALT and AST, respectively. There were significant differences in ALT and AST between good and poor adherence groups, especially in the female patients. The Neural Network and Random Forests were the most suitable models to predict tuberculosis patients’ adherence with good Area Under The Curve (AUC).

Composite cardiac computed tomography angiography score for improved risk assessment in chronic coronary syndromes

Respiratory extracellular vesicle isolation optimization through proteomic profiling of equine samples and identification of candidates for cell-of-origin studies

Growing evidence supports the importance of extracellular vesicle (EV) as mediators of communication in pathological processes, including those underlying respiratory disease. However, establishing methods for isolating and characterizing EVs remains challenging, particularly for respiratory samples. This study set out to address this challenge by comparing different EV isolation methods and evaluating their impacts on EV yield, markers of purity, and proteomic signatures, utilizing equine/horse bronchoalveolar lavage samples. Horses can serve as effective translational animal models for respiratory studies due to similarities with human immune responses, shared environmental exposures, and naturally occurring respiratory diseases including asthma. Further, horses are long-lived large animals that allow for longitudinal sample collection, and provide large sample volume and cell yield, which are particularly useful since EV research is commonly limited by low sample yields. Here, EVs were isolated from horse bronchoalveolar lavage fluid (BALF) using four different methods (ultracentrifugation, microcentrifugation, and two sizes of size exclusion chromatography columns) and characterized by measuring particle counts, EV purity, total protein yield, and proteomic cargo, with a specific focus on vesicle surface marker expression potentially informing cell type of origin. We found that size exclusion chromatography yielded the highest particle counts, greatest EV purity markers and elevated vesicle surface marker expression. Overall proteomic profiles differed across isolation methods, with size exclusion chromatography clustering separately from centrifugation. Taken together, our results demonstrate that different isolation methods impact characteristics of EVs, notably that size exclusion chromatography, compared to centrifugation methods, resulted in higher EV purity and better characterized proteomic diversity, including information on EV cell-of-origin. This is the first study to characterize proteomic profiles of EVs following different isolation methods using equine BALF. The results of this study will pave the way for future studies using equine and human samples to characterize respiratory tract EVs.

Neonatal near miss and associated factors among neonates delivered at East Gojjam zone public health hospitals, Northwest Ethiopia

What sustain Chinese adult second language (L2) learners’ engagement in online classes? A sequential mix-methods study on the roles of L2 motivation and enjoyment

Recent research has integrated positive psychology with the Second Language Motivational Self System (L2MMS) to explore how enjoyment, L2 self-guides (including ideal L2 self and ought-to L2 self), and engagement interact among school-aged second-language (L2) learners. However, there is a significant gap in understanding these dynamics among adult learners, particularly those who primarily learn a second language online—a group that has been largely overlooked. To address this gap, our study examined the underlying mechanisms connecting these constructs. We employed a sequential mixed-methods approach with 367 adult L2 learners enrolled in online language courses at three universities in China. Quantitative data were analyzed using structural equation modeling (SEM) with Amos 24, revealing several key findings. Enjoyment was found to directly and positively predict engagement. However, contrary to existing literature, ideal L2 self did not directly predict either enjoyment or engagement. In contrast, ought-to L2 self directly and positively predicted both enjoyment and engagement, and it indirectly influenced engagement through enjoyment. Qualitative data, gathered through semi-structured interviews with five participants and analyzed using MAXQDA 2022, provided deeper insights into these statistical trends. This study concludes by discussing its implications and suggesting directions for future research.

Characterizing safety, toxicity, and breast cancer risk reduction using a long-term fulvestrant eluting implant

Abstract For individuals at high risk of developing breast cancer, interventions to mitigate this risk include surgical removal of their breasts and ovaries or five years treatment with the anti-estrogen tamoxifen or aromatase inhibitors. We hypothesized that a silicone based anti-estrogen-eluting implant placed within the breast would provide the risk reduction benefit of hormonal therapy, but without the adverse effects that limit compliance. To this end, we demonstrate that when placed adjacent to mammary tissue in the 7,12-dimethylbenz[a]anthracene-induced rat breast cancer model a fulvestrant-eluting implant delays breast cancer with minimal systemic exposure. Using adult female sheep, surgical placement of fulvestrant-eluting implants was safe and did not elicit significant breast tissue pathology when placed at the base of the udder for directed elution into the mammary tissue. At 30 days of elution, fulvestrant was found to penetrate mammary tissue forming a concentration gradient beyond 15 mm from the implant. Consistent with the small animal rat study, minimal systemic fulvestrant biodistribution was found. Together, these studies provide the proof of principle that a breast indwelling fulvestrant-eluting implant can reduce the risk of breast cancer and limit systemic exposure, while penetrating and distributing through breast tissue.

Physical demands and physiological response of soccer referees in high-level matches: A systematic review

Background The match physical demands placed on soccer referees are intrinsically connected to their capacity to make accurate judgments, becoming the second most studied theme in associate soccer refereeing. Objective This study aims to review the external and internal load performed by soccer referees in high-level competitions, to identify changes in these indicators over different periods as the competition progresses, and to analyze the standards for dividing speed zones and heart rate zones. Methods Web of Science, PubMed, Scopus, and EBSCOhost were thoroughly searched. Grey literature sources and Google Scholar were also consulted, with a focus on analysing and comparing the physical demands of soccer referees at different phases of high-level matches. Results A total of 14 manuscripts were included in this review. Studies revealed that the total distance (TD) covered by referees during a full match ranged from 9 to 12 km. High-intensity running (HIR) constituted 2.0–18.7% of TD, accounting for approximately 38% of total time (TT). Referees reached 80–100% of their maximal heart rate during matches. The standards for dividing speed zones and heart rate zones varied among the selected studies. Discussion This systematic review aimed to provide a comprehensive overview of referees’ physical demands (e.g., TD, HIR, and HR) to offer practitioners valuable biological data for training and competition preparation. The lack of uniform criteria for dividing speed and heart rate zones limits data collection, thereby affecting the reporting of distances covered at different exercise intensities.

Analysis of postmarketing neuropsychiatric adverse events of avapritinib based on the FDA adverse event reporting system

Healthcare resource utilization and costs in immunodeficient patients receiving subcutaneous Ig: Real-world evidence from France

Background Subcutaneous immunoglobulin (SCIg) replacement therapy is indicated for patients with hypogammaglobulinemia caused by primary (PID) and secondary immunodeficiencies (SID). Objective To compare healthcare resource utilization (HCRU) and related direct medical costs of patients in France treated with weekly conventional SCIg (cSCIg) vs monthly hyaluronidase-facilitated SCIg (fSCIg). Methods This retrospective study of Ig-naïve patients with PID or SID newly receiving a SCIg between 2016 and 2018, extracted from the French National Healthcare reimbursement database (SNDS), analyzed the SCIg-related HCRU and reimbursed costs generated from in-hospital (hospitalizations and SCIg doses) or at-home (nurse visits [NV] and pump provider visits [PPV], drug doses) SCIg administration. Results Overall, 2,012 patients (PID:534; SID:1,478) were analyzed. The follow-up duration varied between 7.5 and 8.7 months according to sub-groups. Compared with fSCIg-treated patients, monthly mean rates of NV and PPV were respectively 2.5 and 3.1 times higher in PID, and 1.6 and 3.1 times higher in SID cSCIg-treated patients. Monthly mean rates for SCIg administration-related hospitalizations were lower overall, while their costs were 1.6 and 1.8 times higher for cSCIg than fSCIg subgroups, in PIDs and SIDs respectively; these results are due to more frequent hospitalizations with fSCIg being mainly shorter, without stayover. Total HCRU costs from the French NHI’s perspective were estimated to be lower with fSCIg vs cSCIg, in PIDs and SIDs. Conclusion This study provides real-world evidence of SCIg administration in a large French population. Patients with PID or SID treated with fSCIg had fewer at-home HCRU and lower overall costs for in-hospital or at-home SCIg administration compared with cSCIg-treated patients.

Influence of pyridinic nitrogen on tautomeric shifts and charge transport in single molecule keto enol equilibria

Realist evaluation of the AKU-SONAM mentorship program

Background & objectives The context, mechanism, and outcome (CMO) framework is meant to identify specific contextual factors (C) related to organizational and program structure that trigger certain mechanisms (M) involving the unique characteristics of a program, leading to specific outcomes (O). The purpose of this study was to explore the contextual underpinnings, operational processes, and resultant effects of the faculty mentorship program at AKU-SONAM. This exploration involved the context in terms of organizational culture, mechanisms examining processes such as communication between mentors and mentees, quality of relationships, the challenges encountered, and the program’s adaptability to cope up while, outcomes encompassed improvements in interpersonal relationships, career advancement, and skill development. Methods A qualitative exploratory study was conducted at AKU-SONAM, involving in-depth interviews (IDIs) with program leadership and administrators, as well as focus group discussions (FGDs) with mentors and mentees. A semi-structured interview guide, comprising open-ended, introductory, probing, and concluding questions, was developed, validated, and reviewed by experts to ensure its effectiveness and relevance. The process included transcription of interviews, verification through member checks, and thematic analysis where codes and categories were identified and themes, were developed guided by the CMO (Context-Mechanism-Outcome) configuration framework. Results Three IDIs were conducted with administrators and leadership while two FGD were conducted independently with mentors and mentees. Themes for context, mechanism, and outcome were identified. The theme “Navigating Mentorship Challenges in the Professional Landscape” described the Context with subthemes: “Existence of mentorship culture”, Origins and Evolution of Mentoring” “Mentor’s pool, Availability of resources and Mentorship to Seniors. ‘Synergies in Professional Development: From Interdepartmental Collaboration to Mentor-Mentee Connections’ was the theme for mechanisms with subthemes; ‘Fostering Interdepartmental Collaboration’ ‘Building Connections’, ‘sharing of thoughts’, Work Driven Model, Mentor mentee pairing and Selection of mentor. Theme: ‘Cultivating Excellence in the Orchard for Outcome’ emerged from ‘Exchange of Insights in the Orchard of Mentorship’ and ‘Skills Development” constituted the Outcome theme. Conclusions The mentorship program at AKU-SONAM facilitated mentors and mentees to establish connections and exchange ideas. While the mentor-mentee pairing process was clearly outlined, participants emphasized the need to address the challenges encountered by mentees. Although the outcomes were not explicitly clarified, the program contributed to the advancement of the professional development of mentees at AKU-SONAM.

Evaluating the effect of biochar rate and combination with fertilizer on the dynamics of soil nitrogen supply in tea plantation

Comparative readability of information on different treatment options for breast cancer, based on WeChat public accounts

Objective To evaluate and compare the readability of information on different treatment options for breast cancer from WeChat public accounts, propose targeted improvement strategies based on the evaluation of the results of the various treatment options, and provide a reference for producers of WeChat public accounts from which to write highly readable information regarding breast cancer treatment options. Methods With “breast cancer” as keywords in April 2021, searches were implemented on Sogou WeChat website (https://weixin.sogou.com/) and WeChat mobile app. The selected WPAs were aimed to provided breast cancer health information, and the four latest articles of each WPA were included in the evaluation. Two independent observers assessed the readability of the articles through the Suitability Assessment of Materials (SAM) tool, and compared the readability of information on different treatment options, i.e., surgical treatment, medical treatment, complementary and alternative medicine (CAM), and comprehensive treatment. Results A total of 136 articles on different types of breast cancer treatments from 37 WeChat public accounts were included in the present study. The median SAM score was 50 (IQR, 41–60). In terms of treatment options, the readability of articles in the CAM category scored higher in the content 75 (IQR, 63–81), learning stimulation and motivation 75 (IQR, 50–83) and cultural appropriateness 75 (IQR, 75–75) categories than in the medical and surgical treatment categories (P < 0.05). Additionally, the readability of articles in the CAM category scored higher in the cultural appropriateness 75 (IQR, 75–75) category than those for comprehensive and medical treatment (P < 0.05). Conclusions The overall readability of information on breast cancer treatment options in WeChat public accounts was in the lower portion of the “adequate” level. The readability of articles on medical treatment options is poor, especially on clinical trial articles, which could be improved in terms of content, graphics, learning stimulation, and motivation to make them more suitable for public reading.

Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts

Weight trajectories in aging humanized APOE mice with translational validity to human Alzheimer’s risk population: A retrospective analysis

Translational validity of mouse models of Alzheimer’s disease (AD) is variable. Because change in weight is a well-documented precursor of AD, we investigated whether diversity of human AD risk weight phenotypes was evident in a longitudinally characterized cohort of 1,196 female and male humanized APOE (hAPOE) mice, monitored up to 28 months of age which is equivalent to 81 human years. Autoregressive Hidden Markov Model (AHMM) incorporating age, sex, and APOE genotype was employed to identify emergent weight trajectories and phenotypes. In the hAPOE-AD mouse cohort, five distinct weight trajectories emerged: three trajectories were associated with a weight loss phenotype (36% of mice, n = 426), one with weight gain (13% of mice, n = 152), and one trajectory of no change in weight (34% of mice, n = 403). The AHMM model findings were validated with post-hoc survival analyses, revealing differences in survival rates across the five identified phenotypes. Further validation was performed using body composition and plasma β-amyloid data from mice within the identified gain, loss and stable weight trajectories. Weight gain trajectory was associated with elevated plasma β-amyloid levels, higher body fat composition, lower survival rates and a greater proportion of APOE4/4 carriers. In contrast, weight loss was associated with greater proportion of hAPOE3/4 carriers, better survival rates and was predominantly male. The association between weight change and AD risk observed in humans was mirrored in the hAPOE-AD mouse model. Weight trajectories of APOE3/3 mice were equally distributed across weight gain, loss and stability. Surprisingly, despite genetic uniformity, comparable housing, diet and handling, distinct weight trajectories and divergence points emerged for subpopulations. These data are consistent with the heterogeneity observed in the human population for change in body weight during aging and highlight the importance of longitudinal phenotypic characterization of mouse aging to advance the translational validity of preclinical AD mouse models.

Knockdown of zebrafish tmem242 enhances the production of ROS that signals to increase f9a expression resulting in DIC-like condition

Correction: The Video Manipulation Effect (VME): A quantification of the possible impact that the ordering of YouTube videos might have on opinions and voting preferences

A machine learning based algorithm accurately stages liver disease by quantification of arteries

Association of chronic kidney disease with acute clinical outcomes and hospitalization costs of cancer resection

Purpose Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been noted to face increased cancer incidence. Yet, the impact of concomitant renal dysfunction on acute outcomes following elective surgery for cancer remains to be elucidated. Methods All adult hospitalizations entailing elective resection for lung, esophageal, gastric, pancreatic, hepatic, or colon cancer were identified in the 2016–2020 National Inpatient Sample. Based on stage of renal dysfunction, CKD patients were sub-classified as CKD1-3, CKD4-5, or ESRD (others: Non-CKD). Multivariable regression models were developed to assess the association of comorbid CKD/ESRD with in-hospital mortality, perioperative complications, and resource utilization. Results Of ~515,145 patients, 32,195 (6.2%) had CKD (5.1% CKD1-3, 0.7% CKD4-5, 0.5% ESRD). The incidence of CKD among patients undergoing cancer resection increased from 5.3% in 2016 to 7.3% in 2020 (P<0.001). Following risk adjustment, CKD1-3 and CKD4-5 remained linked with similar likelihood of mortality and hospitalization costs, but greater need for blood transfusion (CKD1-3 AOR 1.21, CI 1.09–1.35; CKD4-5 AOR 1.73 CI 1.38–2.18). CKD4-5 was also associated with greater odds of infection (AOR 1.88, CI 1.34–2.62) and respiratory sequelae (AOR 1.36, CI 1.05–1.77). Further, ESRD was linked with greater odds of in-hospital mortality (AOR 2.74, CI 1.69–4.45), infection (AOR 2.31, CI 1.62–3.30) and respiratory complications (AOR 1.72, CI 1.31–2.26), as well as greater resource utilization, relative to Non-CKD. Conclusion Comorbid renal dysfunction was linked with inferior clinical and financial outcomes following elective cancer resection. Future work is needed to develop optimal management strategies and recovery pathways for this complex cohort.