bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiating Latent Tuberculosis from Active Tuberculosis Through Activation Phenotypes and Chemokine Markers HLA-DR, CD38, MCP-1, and RANTES: A Systematic Review and Meta-Analysis
Authors: Kadi Chaimae , Ahmadi Narjisse , Houdou Anass , Badisy Imad El , Bouaddi Oumnia , Mennane Zakaria , Najimi Nouhaila , Benlamari Maryam , Boutayeb Saber , Khalis Mohamed , Mtili Noureddine EL , Seghrouchni Fouad
Published: January 2025

Background:

Latent TB infection (LTBI) affects one fourth of the global population. Currently, there is an absence of an optimal strategy for distinguishing between active tuberculosis (aTB) and LTBI. While some researchers have explored cytokines other than interferon-gamma (IFN-γ) as biomarkers, results have shown significant variability in their ability to differentiate between these conditions. This meta-analysis aims to evaluate the performance of activation phenotype and chemokine markers in distinguishing between aTB and LTBI.

Objectives:

To assess the diagnostic accuracy of specific biomarkers (HLA-DR+ IFNγ+, CD38+ IFNγ+, MCP-1, and RANTES) in differentiating aTB from LTBI.

Design:

This study was conducted in accordance with the PRISMA guidelines for systematic reviews and meta-analyses of diagnostic studies.

Data sources and methods:

We conducted a comprehensive search of PubMed, Scopus, Sciences Direct, and Web of Science for primary studies published in English up to 2023. Studies were included if they reported sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) for the biomarkers in question. We calculated pooled diagnostic sensitivity, specificity, DOR, and AUC, and used the summary receiver operating characteristic curve (SROC) to summarize the diagnostic performance of each biomarker.

Results:

Sixteen studies involving 1696 participants were included in the analysis. Among them, 925 individuals were diagnosed with aTB, while 771 were classified as having LTBI. The specificity, sensitivity, DOR, and AUC for CD38+ IFNγ+, HLA-DR+ IFNγ+, RANTES, and MCP-1 were (0.97 [95% CI: 0.72-1.00], 0.90 [95% CI: 0.75-0.96], 291.863, and 0.9432), (0.90 [95% CI: 0.70-0.97], 0.83 [95% CI: 0.63-0.94], 41.819, and 0.8598), (0.68 [95% CI: 0.55-0.79], 0.72 [95% CI: 0.56-0.84], 5.733, and 0.7979), and (0.63 [95% CI: 0.54-0.72], 0.63 [95% CI: 0.50-0.75], 2.892, and 0.7290) respectively.

Conclusion:

The findings indicate that CD38+ IFNγ+ and HLA-DR+ IFNγ+ demonstrated the highest diagnostic accuracy. Additional prospective research is necessary to identify the optimal combination of biomarkers to enhance diagnostic accuracy in clinical settings.

Registration:

This review has been registered on PROSPERO: (CRD42023472091). Available from: https://www.crd.york.ac.uk/prospero/#recordDetails
Co-development of a gamified physical education movement competence intervention with school stakeholders
Authors: Rice Jenna , Foweather Lawrence , Foulkes Jonathan , Magill Ceriann , Meester An De , Stodden David , Lenoir Matthieu , Davies Katie Fitton
Published: January 2025

Movement competence (MC) and emotional intelligence (EI) are positively associated and important for child development. Intervention research is needed to determine causal relationships between these outcomes. Gamification is a pedagogical model that may enhance MC and EI, but implementing interventions in schools is complex and requires multi-stakeholder involvement to ensure feasibility, acceptability and sustainability. However, methodological evidence to inform co-development work within physical education (PE) is lacking and further research is required. This study describes the process of co-developing a gamified PE intervention with school stakeholders to increase MC and EI among primary-aged children. A total of 91 children and four classroom teachers from three primary schools participated in a series of co-development workshops. Data from the workshops were thematically analysed and informed the development of three school-specific gamified PE curriculums. Findings from children included: (1) the social and foundational movement skills (FMS) to improve during the intervention; (2) the enjoyable components of PE, which included skill development and social interaction; (3) a desire to include more equipment in PE lessons; and (4) games, activities and gamification strategies to incorporate in the intervention. Findings from teachers included: (1) the barriers and facilitators to implementing a gamified model in PE; (2) the successful components of PE lessons; and (3) the overall development of the intervention. This methodology provides a framework for co-developing PE interventions within a school context. Results provide strategies to operationalise gamification. Future research should explore the feasibility and acceptability of the co-developed interventions to increase MC and EI.
Exploring the readiness to practice of underrepresented healthcare workers: A scoping review
Authors: Hussein Sara , Ishaky Liam , Nowrouzi-Kia Behdin , Laughton Sarah , Gohar Basem
Published: January 2025

Background:

Studies across the extant literature suggest that less-experienced healthcare workers are more likely to experience adverse outcomes such as burnout, sick leaves, or intend to leave the profession. Thus, one’s readiness to practice is an important element that requires more attention. While extensive research exists on the readiness of certain professions like nurses, a notable gap remains concerning other healthcare workers.

Purpose:

This study sought to explore studies examining readiness to practice among various underrepresented healthcare workers.

Methods:

We conducted a scoping review to determine the available research related to clinical and nonclinical areas related to the readiness to practice of healthcare workers, excluding physicians and nurses. We examined three databases, MEDLINE, CINAHL, and PsycINFO, from 1 January 2000 to 31 December 2023. Our search focused on readiness to practice among various healthcare professions, whether clinically focused or broadly related to professionalism.

Results:

Our search identified 41 articles meeting the inclusion criteria from several professions, including but not limited to physiotherapists and occupational therapists, pharmacists, osteopaths/chiropractors, and social workers. Overall, studies differed in assessing readiness to practice with a broad range of identified clinical competencies that varied between professions and regions. Nonclinical skills, such as communication, conflict management, and cultural competence, were common barriers across professions.

Conclusion:

Despite the heterogeneity in job roles, work settings, and geographical reasons, there is evidence to suggest that new healthcare professionals may be clinically adept but may be lacking in other nonclinical skills that could affect their work and well-being. With early-career healthcare workers particularly vulnerable to adverse outcomes in the workplace, future research should standardize core competencies, including nonclinical skills and well-being-related activities, as a prevention method across various health groups.
Systemic sclerosis-associated severe gastric antral vascular ectasia treated with tocilizumab:A case report and review of the literature
Authors: Rodolfi Stefano , Denton Christopher P , Ong Voon H
Published: January 2025

Gastric antral vascular ectasia is a frequent and potentially severe complication of systemic sclerosis. Management is presently limited to supportive care, acid suppression and endoscopic treatment. Many cases of gastric antral vascular ectasia tend to be refractory or partially responsive to standard treatment and require multiple endoscopic procedures to control the recurrent bleeding. Immunosuppression is not part of the recommended management of gastric antral vascular ectasia: limited data exist on the role of cyclophosphamide or autologous stem cell transplant in severe cases, but no prospective data or randomised controlled trial supports its routine use. Here, we present a case of an adult male patient with diffuse cutaneous systemic sclerosis complicated by arthritis and severe gastric antral vascular ectasia. The latter required multiple endoscopic procedures and remained transfusion-dependent. Due to progressive skin disease and active arthritis refractory to conventional synthetic disease-modifying antirheumatic drugs, the patient was started on tocilizumab. While he showed an early response in terms of scores related to skin involvement and arthritis, response to gastric antral vascular ectasia was unexpected. As soon as the biologic therapy was started, the patient was no longer transfusion-dependent and haemoglobin levels started to rise. Subsequent endoscopic investigations confirmed resolution of gastric antral vascular ectasia. This case is illustrative of an unexpected response to tocilizumab, and this observation is supported by the biological rationale of interleukin-6 in vascular remodelling.
Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke
Authors: Patel Rakesh B. , Jha Abhishek B , Verma Abhishek K , Jain Aditi , Saini Saurabh , Muia Joshua , Gurung Prajwal , Perlman Stanley , Budnik Ivan , Chauhan Anil
Published: January 2025

Respiratory tract infections (RTIs) caused by bacteria or viruses are associated with stroke severity. Recent studies have revealed an imbalance in the von Willebrand factor (VWF)-ADAMTS13 axis in patients with RTIs, including COVID-19. We examined whether this imbalance contributes to RTI-mediated stroke severity. Wild-type (WT), Vwf −/−, or Adamts13−/− mice with respective littermate controls (Vwf +/+, or Adamts13+/+) were infected intranasally with sublethal doses of S. aureus (on days 0, 2, and 5) or mouse-adapted SARS-CoV-2 (on day 0) and subjected to transient (30 or 45 min) cerebral ischemia followed by reperfusion. In S. aureus-infected mice, infarct volumes were assessed on day 2 and functional outcomes on weeks 1 and 4 post-reperfusion. In SARS-CoV-2-infected mice, infarct volumes and functional outcomes (Bederson score) were assessed on day 1 post-reperfusion. We demonstrated that S. aureus or SARS-CoV-2 RTI was accompanied by an imbalance in the VWF-ADAMTS13 axis and an increase in plasma levels of IL-6, CXCL1, and MCP-1, which was associated with larger infarcts and worse functional outcomes (P<0.05 vs. mock-infection). S. aureus- or SARS-CoV-2-infected Vwf −/− mice exhibited reduced infarcts and improved functional outcomes, while infected Adamts13−/− mice displayed greater stroke severity (P<0.05 vs. control). In the models of RTI preceding stroke, VWF contributes to stroke severity, while ADAMTS13 is protective.
Open-source 3D printed manifolds for exposure studies using human airway epithelial cells
Authors: Singer Ryan , Milad Nadia , Ball Elizabeth , Nguyen Jenny P. , Cao Quynh , Selvaganapathy Ravi , Zhang Boyang , Dabaghi Mohammadhossein , Satia Imran , Hirota Jeremy A.
Published: January 2025

Rationale

In vitrostudies using air-liquid interface (ALI) cultures enable controlled investigation of human airway epithelial cell (HAEC) responses to clinically relevant exposures. Commercialin vitroexposure systems provide precise and reproducible dosage but require significant investment. Exposure science may benefit from a more accessible customizable open-source exposure system. We present 3D printed manifolds for applying a range of exposures uniformly across standard, commercially available 6- and 24-well plates with ALI culture inserts.

Methods

A chamber-style exposure system and designed manifolds were evaluated for exposure uniformityviasimulations and deposition of nebulized FITC-labelled dextran. Chamber and manifolds were manufactured using 3D stereolithography printing. Cannabis concentrate vapour was generated from 3 different vaporizers and applied to well plates using the manifold system. Calu-3 cells and primary HAECs were cultured on Transwell™ inserts for exposure studies.

Results

The manifolds produced less variation in simulations and physical deposition of FITC-dextran aerosol across well plates compared to the chamber system. Distinct doses of cannabis concentrate vapour were delivered to well plates with minimal variation among wells. Whole tobacco smoke exposure using the manifold system induced functional changes in Calu-3 barrier function, cytokine production (IL-6 and IL-8), and cell membrane potential. Cannabis smoke led to reduced primary HAEC barrier function in a dose- and strain-dependent manner.

Conclusions

Our data demonstrate the feasibility and the validity of our open-source 3D printed manifolds for use in studying multiple exposures and position our designs as an accessible option in parallel with commercially available systems.

All article content is licensed under a Creative Commons Attribution (CC BY-NC 4.0) license (https://creativecommons.org/licenses/by-nc/4.0/).
External validation of the LENT and PROMISE prognostic scores for malignant pleural effusion
Authors: Mounsey Craig A , Kanellakis Nikolaos I , Addala Dinesh N , Mawhinney Jamie A , Freemantle Nick , Rahman Najib M
Published: January 2025

Background

Accurate survival estimation in malignant pleural effusion is essential to guide clinical management strategies and inform patient discussion. The LENT and PROMISE scores were developed to aid prognostication in malignant pleural effusion, however their uptake in practice has been limited. We aimed to conduct a detailed external validation of the LENT and PROMISE scores to develop recommendations regarding clinical utility, and to highlight factors limiting performance.

Methods

Medical records of patients diagnosed with malignant pleural effusion between 2015–2023 at Oxford University Hospitals were retrospectively reviewed to determine length of survival and the LENT and PROMISE scores at diagnosis. Performance of the scores in predicting overall survival and chance of survival at 3-, 6- and 12-months was assessed using measures of discrimination, calibration and overall model performance. Kaplan-Meier analysis and Cox models were utilised to further investigate individual score variables.

Results

773 patients with malignant pleural effusion were included. Both scores showed predictive ability for overall survival, however median survival estimates lacked precision. Score performance in predicting survival at 3-, 6- and 12-months was stronger, with C-indices around 0.8 for both at each time-point, and the models appearing well-calibrated. Limited stratification of tumour types and lack of consideration of sensitising mutations were demonstrated to be potential factors restricting performance.

Conclusions

Both scores have ability to prognosticate in malignant pleural effusion, and greater use in practice should be considered. However, areas to improve score performance were also highlighted, and these may aid future model development.
Biodegradation of azo dyes by Aspergillus flavus and its bioremediation potential using seed germination efficiency
Authors: Ghanaim Amira M. , Mahdy Omima M. El , Mohamed Heba I.
Published: January 2025

The worldwide textile industry extensively uses azo dyes, which pose serious health and environmental risks. Effective cleanup is necessary but challenging. Developing bioremediation methods for textile effluents will improve color removal efficiency. The recent attention to effectively utilizing microbes to convert toxic industrial azo dyes into non-hazardous compounds has garnered significant attention. In the present study, four fungal strains—Aspergillus flavus, Aspergillus terreus, Aspergillus niger, and Fusarium oxysporium—were employed to screen for the degradation and detoxification of azo dyes including congo red, crystal violet, bromophenol blue, and malachite green. After eight days, A. flavus had degraded azo dyes at the maximum proportion. The maximum decolorization (%) was achieved at 50 mg/L of dye concentration, 8 days of incubation, pH 6, 30 °C temperature, sucrose as a carbon source, NaNO3 as a nitrogen source, Ca+2 as minerals, and using static culture. The efficient production of laccases, lignin peroxidase, and manganese peroxidase enzymes by A. flavus proved that the enzyme played a crucial role in decolorizing the harmful azo dyes. The Fourier Transform Infrared spectrometer (FT-IR) data validated the decolorization and degradation process brought on by absorption and biodegradation. Compared to control plants, the results of the phytotoxicity assay showed that the degraded product was less harmful to maize and common bean plant's growth and germination rates. As a result, the findings indicate that A. flavus is a viable option for remediating azo dyes. This aids in the biodegradation of azo dyes found in wastewater.
Identify the underlying true model from other models for clinical practice using model performance measures
Authors: Li Yan
Published: January 2025

Objective

To assess whether the outcome generation true model could be identified from other candidate models for clinical practice with current conventional model performance measures considering various simulation scenarios and a CVD risk prediction as exemplar.

Study design and setting

Thousands of scenarios of true models were used to simulate clinical data, various candidate models and true models were trained on training datasets and then compared on testing datasets with 25 conventional use model performance measures. This consists of univariate simulation (179.2k simulated datasets and over 1.792 million models), multivariate simulation (728k simulated datasets and over 8.736 million models) and a CVD risk prediction case analysis.

Results

True models had overall C statistic and 95% range of 0.67 (0.51, 0.96) across all scenarios in univariate simulation, 0.81 (0.54, 0.98) in multivariate simulation, 0.85 (0.82, 0.88) in univariate case analysis and 0.85 (0.82, 0.88) in multivariate case analysis. Measures showed very clear differences between the true model and flip-coin model, little or none differences between the true model and candidate models with extra noises, relatively small differences between the true model and proxy models missing causal predictors.

Conclusion

The study found the true model is not always identified as the “outperformed” model by current conventional measures for binary outcome, even though such true model is presented in the clinical data. New statistical approaches or measures should be established to identify the casual true model from proxy models, especially for those in proxy models with extra noises and/or missing causal predictors.
Assessing neonatal nurses: transitioning preterm infants to oral feeding - a multicenter cross-sectional study
Authors: Hendy Abdelaziz , Osman Yasmine M. , Alharbi Hanan F. , Alshammari Maha Suwailem Shuaib , Al-Jabri Mohammed Musaed Ahmed , Alzahrani Naif S. , Hendy Ahmed , Almarwani Abdulaziz Mofdy
Published: January 2025

Background

In Egypt, approximately 10% of preterm deliveries occur between 32 and fewer than 37 weeks, leading to high neonatal intensive care unit (NICU) admissions. Preterm infants often face oral feeding difficulties due to immature development, which can lead to extended hospital stays and increased health risks.

Aim

To assess neonatal nurses’ performance in terms of the transition to oral feeding in preterm infants, focusing on knowledge, practices, and attitudes.

Methods

A descriptive, quantitative, multicenter, cross-sectional study was conducted across 16 hospitals in five governorates in Egypt from November 2023 to March 2024 involving 553 neonatal nurses. The data were collected through a self-administered questionnaire assessing knowledge and attitudes and through an observed checklist for nurses’ practices. The study used statistical methods, including binary logistic regression, to analyze the data.

Results

The findings revealed significant knowledge gaps among nurses, particularly in terms of oro-motor function, suck-swallow-breathe patterns, and nonnutritive sucking. A total of 64.6% of the nurses had unsatisfactory knowledge, 58.6% had unsatisfactory practices, and 45% had a negative attitude toward the oral feeding transition. Key predictors of satisfactory practices included higher education levels, full-time employment, and positive attitudes.

Conclusion

This study highlights critical gaps in neonatal nurses’ knowledge and practices regarding the transition to oral feeding in preterm infants. Addressing these gaps through targeted educational interventions and ongoing support is essential for improving care quality and outcomes for infants. The findings revealed that a substantial proportion of nurses lacked adequate knowledge of critical areas, such as oro-motor function, the suck-swallow-breathe pattern, and nonnutritive sucking. These knowledge deficits could hinder the ability of nurses to provide optimal care during this crucial transition.
The role of hospital pharmacists in supporting the appropriate and safe use of CGT/ATMPs: a scoping review of current insights
Authors: Shi Junnan , Chen Xianwen , Hu Hao , Ung Carolina Oi Lam
Published: January 2025

Background

The role of hospital pharmacists in managing cell and gene therapy (CGT) and advanced therapy medicinal products (ATMPs) is gradually being recognized but the evidence about impact of their role has not been systematically reported.

Objective

This study was aimed to summarize the professional services provided by hospital pharmacists on managing CGT/ATMPs and the evidence about the effects on patient care, as well as to identify the perceptions about pharmacists assuming a role that supports the appropriate and safe use of CGT/ATMPs.

Methods

Literature from 4 electronic databases (PubMed, ScienceDirect, Web of Science, Scopus) were searched following PRISMA checklist to yield publications on the interventions provided by hospital pharmacists in the management of CGT/ATMPs dated since 1 January 2013 till 30 April 2023.

Results

Thirty-four publications were included in this review. Eight studies involving hospital pharmacists participating in interventions for 1,012 hematopoietic stem cell transplant (HSCT) patients from 8 hospitals in 5 countries were identified. Common pharmacist-led interventions centered on medicine administration, prescribing, and monitoring of medicines use, resulting in significant improvement in patient adherence, satisfaction and knowledge. Of 26 studies, the perspectives assuming their roles in CGT/ATMPs management were categorized when patients receiving ATMPs (n = 2), HSCT and cellular-based therapy (n = 12), gene therapy (n = 6), and the chimeric antigen receptor (CAR) T-cell therapy (n = 6), mainly covering procurement, influences on prescribing, preparation and delivery, administration, monitoring of medicines use, human resources, training and development. The anticipated impact was primarily intended to promote pharmacy practice, multidisciplinary collaboration and improve patient clinical outcomes.

Conclusion

Leveraging the role of hospital pharmacists in multidisciplinary healthcare teams to develop a coordinated approach that supports pharmacy practice will better meet the management of CGT/ATMPs. For hospital pharmacists to step up their role in the multidisciplinary healthcare team, advancing their skillset in terms of clinical practice standards and medication management is essential.
Late-life physical activity, midlife-to-late-life activity patterns, APOE ε4 genotype, and cognitive impairment among Chinese older adults: a population-based observational study
Authors: Zhao Xunying , Wu Xueyao , Ma Tianpei , Xiao Jinyu , Chen Xin , Tang Mingshuang , Zhang Li , Zhang Tao , Fan Mengyu , Liao Jiaqiang , Zhang Ben , Jiang Xia , Li Jiayuan
Published: January 2025

Background

Although physical activity (PA) has been linked to cognitive health, the nuanced relationships between different dimensions of PA and cognitive impairment remain inconclusive. This study investigated associations between late-life PA levels, midlife-to-late-life activity patterns, and cognitive impairment in Chinese older adults, considering potential moderation by apolipoprotein E (APOE) ε4 genotype.

Methods

We analyzed baseline data from 6,899 participants (median age 68 years, 55.78% female) in the West China Health and Aging Cohort study, with 6,575 participants having APOE genotyping data. Late-life PA and midlife-to-late-life activity patterns were assessed using the Global Physical Activity Questionnaire and a standardized question, respectively. Cognitive function was evaluated using the Chinese version of Mini-Mental State Examination. Logistic regression models were used to examine associations.

Results

Compared to low PA level, moderate (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.55 ~ 0.99) and high PA levels (OR = 0.60, 95%CI = 0.48 ~ 0.75) were associated with lower risk of cognitive impairment. Engaging in work-, transport-, recreation-related, and moderate-intensity PA were each significantly associated with lower cognitive impairment risk. Maintaining activity levels from midlife to late life was associated with lower cognitive impairment risk compared to decreasing levels (OR = 0.75, 95%CI = 0.60 ~ 0.94). These associations were more pronounced in APOE ε4 non-carriers, with an interaction observed between APOE ε4 genotype and recreation-related PA (P-value = 0.04).

Conclusions

Our findings underscore the multifaceted benefits of PA in mitigating cognitive impairment risk among older Chinese adults. Public health strategies should focus on promoting overall late-life PA levels, especially moderate-intensity PA, and maintaining activity levels comparable to midlife, with potential for personalized interventions based on genetic risk profiles.
The antiosteoporotic effect of oxymatrine compared to testosterone in orchiectomized rats
Authors: Shaban Anwaar M. , Ali Eman A. , Tayel Sara G. , Rizk Sara Kamal , El Agamy Dalia F.
Published: January 2025

Background

Castration of adult male rats led to the development of osteoporosis. Oxidative stress and inflammatory factors have been identified as potential causative factors. Notably, oxymatrine (OMT) possesses potent anti-inflammatory and antioxidant activities. This study aims to elucidate the antiosteoporotic effects of OMT compared to testosterone in an orchiectomized (ORX) rat model of osteoporosis.

Methods

A total of 60 Wistar male rats were divided into the following groups: control (CTRL), surgery + no orchiectomy (SHAM), ORX, ORX + testosterone, and ORX + OMT. Urinary deoxypyridinoline (DPD), calcium (Ca), and phosphorus (P), as well as serum testosterone, parathormone (PTH), alkaline phosphatase (ALP), osteocalcin, N-telopeptide of type I collagen (NTX I), tartrate resistance acid phosphatase (TRAP), and total Ca and P levels were evaluated. Bone was assessed for malondialdehyde (MDA), reduced glutathione (GSH), interleukin 6 (IL-6), Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) expression, and receptor activator of nuclear factor κB ligand/ osteoprotegerin (RANKL/OPG) ratio. Bone dual-energy X-ray absorptiometry (DEXA) scan and histological and immunohistochemical studies were performed.

Results

Testosterone or OMT treatment ameliorated the reduced bone mineral density (BMD) and bone mineral content (BMC) in the DEXA scan and the changes in PTH and Ca levels. Compared to the ORX group, bone formation, and turnover markers were also significantly reversed in the treatment groups. Treatment with testosterone or OMT significantly reduced bone MDA, IL-6, Keap1, RANKL, and RANKL/OPG ratio, and significantly elevated bone GSH, Nrf2, and HO-1. Moreover, testosterone or OMT treatment has restored cortical bone thickness and osteocyte number and reduced bone levels of TNF-α in ORX rats. Consequently, treatment with either testosterone or OMT exhibited nearly equal therapeutic efficacy; however, neither of them could normalize the measured parameters.

Conclusion

OMT treatment showed equal efficacy compared to testosterone in ameliorating osteoporosis in ORX rats, possibly by improving some inflammatory and oxidative stress parameters.
ONC213: a novel strategy to resensitize resistant AML cells to venetoclax through induction of mitochondrial stress
Authors: Carter Jenna L. , Su Yongwei , Al-Antary Eman T. , Zhao Jianlei , Qiao Xinan , Wang Guan , Edwards Holly , Polin Lisa , Kushner Juiwanna , Dzinic Sijana H. , White Kathryn , Buck Steven A. , Hüttemann Maik , Allen Joshua E. , Prabhu Varun V. , Yang Jay , Taub Jeffrey W. , Ge Yubin
Published: January 2025

Background

Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and a salvage therapy for relapsed/refractory patients who have been treated with intensive chemotherapy. While this is an important treatment option, many patients fail to achieve complete remission and of those that do, majority relapse. Leukemia stem cells (LSCs) are believed to be responsible for AML relapse and can be targeted through oxidative phosphorylation reduction. We previously reported that ONC213 disrupts oxidative phosphorylation and decreases Mcl-1 protein, which play a key role in venetoclax resistance. Here we investigated the antileukemic activity and underlying molecular mechanism of the combination of ONC213 + venetoclax against AML cells.

Methods

Flow cytometry was used to determine drug-induced apoptosis. Protein level changes were determined by western blot. An AML cell line-derived xenograft mouse model was used to determine the effects of ONC213 + venetoclax on survival. A patient-derived xenograft (PDX) mouse model was used to determine drug effects on CD45+/CD34+/CD38-/CD123 + cells. Colony formation assays were used to assess drug effects on AML progenitor cells. Mcl-1 and Bax/Bak knockdown and Mcl-1 overexpression were used to confirm their role in the mechanism of action. The effect of ONC213 + venetoclax on mitochondrial respiration was determined using a Seahorse bioanalyzer.

Results

ONC213 + venetoclax synergistically kills AML cells, including those resistant to venetoclax alone as well as venetoclax + azacitidine. The combination significantly reduced colony formation capacity of primary AML progenitors compared to the control and either treatment alone. Further, the combination prolonged survival in an AML cell line-derived xenograft model and significantly decreased LSCs in an AML PDX model.

Conclusions

ONC213 can resensitize VEN + AZA-resistant AML cells to venetoclax therapy and target LSCs ex vivo and in vivo.
Interplay of swine acute diarrhoea syndrome coronavirus and the host intrinsic and innate immunity
Authors: Zhao Fei , Cong Xiao , Huang Xiaobo , Zheng Yi , Zhao Qin , Wen Yiping , Wu Rui , Du Senyan , Cao Sanjie , Cong Feng , Wang Yiping
Published: January 2025

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), a novel HKU2-related coronavirus of bat origin, is a newly emerged swine enteropathogenic coronavirus that causes severe diarrhoea in piglets. SADS-CoV has a broad cell tropism with the capability to infect a wide variety of cells from human and diverse animals, which implicates its ability to hold high risks of cross-species transmission. The intracellular antiviral immunity, comprised of the intrinsic and innate immunity, represents the first line of host defence against viral infection prior to the onset of adaptive immunity. To date, there are no vaccines and drugs approved to prevent or treat SADS-CoV infection. Understanding of the mutual relationship between SADS-CoV infection and host immunity is crucial for the development of novel vaccines and drugs against SADS-CoV. Here, we review recent advancements in our understanding of the interplay between SADS-CoV infection and the host intrinsic and innate immunity. The extensive and in-depth investigation on their interactive relationship will contribute to the identification of new targets for developing intervention strategies to control SADS-CoV infection.
Molecular characterization of swine acute diarrhea syndrome coronavirus detected in Vietnamese pigs
Authors: Le Nam Phuong , Le Bac Tran , Le Van Phan , Park Jung-Eun
Published: January 2025

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine coronavirus that was recently identified in southern China in 2017. At present, there is a lack of nationwide epidemiological investigations of the newly emerged SADS-CoV. Because Vietnam is geographically adjacent to southern China, many diseases have spread from China to Vietnam. To assess SADS-CoV transmission to Vietnam, we conducted a retrospective study to detect SADS-CoV in samples collected from pig farms in northern Vietnam. Among the 69 fecal samples tested, 5 were positive for SADS-CoV. The spike gene sequence showed high genetic homology with strains circulating in China. Our study is the first to show that SADS-CoV has spread from China to Vietnam and highlights the need for global epidemiological investigations of SADS-CoV.
Maladaptive changes in the homeostasis of AEA-TRPV1/CB1R induces pain-related hyperactivity of nociceptors after spinal cord injury
Authors: Hu JiaQi , Fan WenYong , Xu Yue , Li XiaoFei , Zhang HaoYang , Li Shun , Xue Lei
Published: January 2025

Background

Neuropathic pain resulting from spinal cord injury (SCI) is associated with persistent hyperactivity of primary nociceptors. Anandamide (AEA) has been reported to modulate neuronal excitability and synaptic transmission through activation of cannabinoid type-1 receptors (CB1Rs) and transient receptor potential vanilloid 1 (TRPV1). However, the role of AEA and these receptors in the hyperactivity of nociceptors after SCI remains unclear.

Results

In this study, we investigated the effects of AEA and its receptors on the hyperexcitability of mouse dorsal root ganglion (DRG) neurons after SCI. Using a whole-cell patch-clamp technique, we found that the timing of SCI-induced hyperexcitability in nociceptors paralleled an increase in the endocannabinoid AEA content. The expression of TRPV1 and CB1R was also upregulated at different time points after SCI. High-dose extracellular administration of AEA increased the excitability of naive DRG neurons, leading to the transition from a rapidly accommodating (RA) hypoexcitable state to a highly excitable non-accommodating (NA) state. These AEA-induced transitions were facilitated by increased TRPV1 transcription. Pharmacological and Ca2+ imaging experiments revealed that AEA induced hyperexcitability in nociceptors after SCI via the AEA-TRPV1-Ca2+ pathway, whereas activation of CB1Rs reduced SCI-induced hyperexcitability and maintained cytosolic Ca2+ concentration ([Ca2+]cyto) at low levels in the early stages of SCI. As the AEA and TRPV1 levels increased after SCI, adaptive neuroprotection transitioned to a maladaptive hyperactive state, leading to sustained pain.

Conclusions

Taken together, this study provides new insights into how endocannabinoids regulate nociceptor activity after SCI, offering potential targets for the treatment of neuropathic pain.
Effectiveness of digital health applications on the quality of life in patients with overweight or obesity: a systematic review
Authors: Mäder Melanie , Schönfelder Tonio , Heinrich Ria , Militzer-Horstmann Carsta , Timpel Patrick
Published: January 2025

Background

Globally, more than half of the adult population is overweight, including those who are obese, which increases the risk of premature death and reduces quality of life (QoL). Technologies such as digital health applications (DiHA) can potentially improve clinical outcomes (e.g., health status, illness duration, QoL) or patient-related factors (e.g., therapy monitoring, adherence, health literacy). To date, there is no systematic review addressing the effectiveness of DiHA on the QoL in patients with overweight or obesity.

Objective

The objective was to investigate the impact of DiHA on QoL in overweight or obese patients.

Methods

A systematic literature search was conducted in MEDLINE via PubMed, Cochrane Library, and Embase via Ovid in 2023, supplemented by additional manual searches. The eligibility criteria included patients with overweight and/or obesity who used a digital intervention independently and without interaction with a healthcare professional. The outcome of interest was QoL. As potentially eligible trials had to demonstrate effectiveness, only randomized controlled trials (RCT) were included as the minimum evidence standard. The study screening (title-abstract, full-text) was conducted independently by two researchers using pre-specified eligibility criteria. CONSORT-EHEALTH checklist was used for data extraction of qualitative and quantitative data (study characteristics and study results) and the Cochrane Risk of Bias Tool (version 2) for quality assessment independently by two researchers.

Results

Seven RCT conducted in Europe and the United States were included in this systematic review with a total sample size of N = 946. Observation periods were heterogeneous and ranged from 3 to 24 months. The evaluated interventions consisted of websites or apps, all of which included nutrition and physical activity features, and functioned independently with minimal or no involvement of a healthcare professional. All studies showed a high risk of bias, no statistically significant improvement and no effects regarding QoL using different validated questionnaires.

Conclusions

This systematic review provides a comprehensive analysis of DiHA effectiveness on QoL in patients with overweight or obesity. Overall, there is heterogeneity regarding the operationalization of QoL and the examined interventions have no statistically significant impact on QoL. Comparable systematic reviews show that digital interventions have the potential to improve the QoL of these patients, but further RCT and high-quality studies are needed to assess the impact of DiHA on QoL.

Trial registration

PROSPERO CRD42023408994.
Characteristics of e-scooter and bicycle injuries at a university hospital in a large German city – a one-year analysis
Authors: Hartz Frederik , Zehnder Philipp , Resch Tobias , Römmermann Gregor , Hartmann Victoria , Schwarz Markus , Kirchhoff Chlodwig , Biberthaler Peter , Zyskowski Michael
Published: January 2025

Background

The increasing adoption of individual urban mobility in European cities is contributing to a rise in the number of bicycle and e-scooter users. Consequently, a corresponding increase in accidents, along with an additional burden on emergency departments, is anticipated, particularly in metropolitan areas. The objective of this prospective cross-sectional study was to gather detailed information regarding the patient demographics, accident mechanisms, and injury patterns of e-scooter riders in comparison to cyclists. Identifying any differences between these groups will provide a foundation for developing targeted prevention strategies and safety measures aimed at reducing the incidence of accidents and injuries.

Methods

All patients who presented to the emergency department of our level I university trauma center after an accident involving a traditional bicycle without electric assistance or an e-scooter in 2022 were recorded. Demographic data as well as information regarding the trauma mechanism, injury pattern, alcohol influence, treatment requirements and helmet use were analyzed and compared between the two groups.

Results

In 2022, a total of 626 patients were identified after a bicycle accident and 98 patients after an e-scooter accident. E-scooter riders were with a mean age of 31.0 years (standard deviation (SD) 10.7) significantly younger compared to bicycle riders at 43.2 years (SD 16.5; p < 0.001). More than half of the patients in both groups were male (e-scooter 69.4% versus bicycle 60.7%). E-scooter riders were more likely to be intoxicated (31.6% vs. 5.4%; p < 0.001), not wearing a helmet (93.9% vs. 78.4%; p < 0.001) and to have had accidents at nighttime (39.8% vs. 11.5%; p < 0.001). There was no significant difference between the distribution of minor (e-scooter 75.2% vs. bicycle 70.3%) and major (24.8% vs. 29.7%) injuries. In terms of body regions, e-scooter riders suffered from major injuries to the skull, facial cranium, cervical spine (43.8% e-scooter vs. 22.4% bicycle; p = 0.008) and less frequently to the trunk, thoracic and lumbar spine and pelvis (0.0% vs. 13.6%).

Conclusion

Compared to cyclists, injured e-scooter riders are younger, mostly do not wear a helmet and more often ride under the influence of alcohol. E-scooter accidents occur more frequently at night and the riders are more likely to suffer serious head injuries.
Availability, pricing, and affordability of antithrombotic medicines in Addis Ababa, Ethiopia: implications for health policy
Authors: Birhanu Selam , Tamiru Melaku Tileku , Kedir Hanan Muzeyin , Tadesse Tamrat Assefa
Published: January 2025

Background

Antithrombotic medications are essential for the management of abnormal clot formation. However, their availability, pricing, and affordability in Ethiopia, particularly in Addis Ababa, have not been comprehensively studied.

Methods

A cross-sectional study was conducted in Addis Ababa, Ethiopia to assess the availability, pricing, and affordability of essential antithrombotic medicines. This study utilized the World Health Organization (WHO) and International Health Action Organization methodology. Five public hospital outpatient pharmacies, four private hospitals, ten private pharmacies, four Kenema pharmacies, and two Red Cross pharmacies in Addis Ababa, Ethiopia, were included in the study. All essential antithrombotic medicines in the 6th edition of Ethiopia’s Essential Medicines List were included in this study. Data were collected for originator brands and the lowest-priced generic medicines available at each medicine outlet.

Results

The availability of low-priced generic (LPG) antithrombotic medicines was 31%, with private hospitals having the highest availability (52%). Original-brand antithrombotic medicines were rarely available, averaging only 3%, with private pharmacies showing a slightly higher availability (10%). The median price of LPG antithrombotic medicines is higher in private settings. Original-brand (OB) antithrombotic medicines in private hospitals and pharmacies were unaffordable, costing between 256.14 and 3,418 days of wages.

Conclusion

The availability of most antithrombotic medicines was low across all sectors compared with the WHO target. Private hospitals showed relatively higher availability of LPG medicines than other pharmacy outlets included in the study. There is a significant disparity between the availability and affordability of LPG and OB medicines. To address these issues, the national drug procurement and distribution systems must be strengthened. Exploring local production and financial assistance programs, implementing effective stock management, regulating medicine prices, promoting high-quality generic medicines, and conducting further research to understand the national landscape are all essential.
A proposal of a fecal scoring system based on physicochemical analyses of suckling pig feces
Authors: Pons Ana Maria , González Blanca , Pujols Joan , Serratosa Jordi , Segalés Joaquim , Gómez Ernesto A. , Martínez Jorge
Published: January 2025

Background

Digestive disorders are one of the main health problems in suckling piglets. The correct visual identification of feces in suckling piglets is an important tool for the diagnosis of enteric diseases. The aim of the present observational study was to analyze different physicochemical parameters of the feces of suckling piglets aged 0 to 21 days: visual appearance (color and consistency), fecal dry matter (FDM) content and pH. A total of 482 fecal samples were collected and visually classified into six categories: meconium, colostrum stage feces and 4 further scores according to the degree of consistency: 0 = form; 1 = pasty; 2 = liquid; and 3 = watery feces. The percentage of FDM was estimated by two drying methods, oven and microwave, doing duplicates in each one to evaluate methods, and both were compared.

Results

The most frequent colors of each feces category were dark green or dark brown for meconium; orange for colostrum; formed feces were mostly ocher and for the rest of the feces, the colors varied predominantly cream and ocher. Regarding FDM, liquid and watery categories had no statistically significant differences between them; meconium and colostrum feces FDM were not statistically different from pasty feces. The correlation coefficient between the FDM values of the duplicate analyses of the samples by both methods (oven and microwave) was very high (> 0.988). Importantly, no differences were found while comparing the results between both methods (p = 0.078), and the correlation coefficient between all samples analyzed with both methods was very high (> 0.98). Meconium was the only one that differed significantly from the rest in terms of pH.

Conclusion

The physicochemical study of the feces of suckling piglets including color, FDM and pH allowed the establishment of an objective fecal score to characterize the stools in this age group.
Tracing the ties that bind: navigating the static and dynamic connectedness between NFTs and equity markets in ASEAN based on QVAR-approach
Authors: Naveed Muhammad , Ali Shoaib , Tiwari Aviral Kumar
Published: January 2025

Based on market integration theory, we investigate the static and dynamic connectedness between nonfungible tokens (NFTs) and the Association of Southeast Asian Nations (ASEAN) equity markets using the Quantile Vector Auto Regressive model. We also compute optimal weights and hedge ratios for our variable of interest to establish their diversification and hedging potential. Our analysis infers a moderate level of return transmission at the median quantile, where equity markets evolved as the net recipients of return spillover from the system, while NFTs emerge as key transmitters. In extreme market conditions, transmission between variables is amplified, but the increase is symmetrical across extreme quantiles, suggesting a similar impact. However, the interlinkage among assets is symmetric across conditional quantiles. The dynamic analysis demonstrates that the system integration amplifies during uncertain times (e.g., COVID-19 and the Russia–Ukraine conflict). Our portfolio analysis shows that NFTs provide diversification and hedging in all market conditions. However, the period of turmoil dampened the diversification potential, and hedging became expensive. Our study offers detailed and insightful information about the transmission mechanism and enables the participants of financial markets to diversify and hedge their portfolio.
ESG disagreement and corporate debt maturity: evidence from China
Authors: Jiang Kangqi , Zhang Jie , Zhou Mengling , Chen Zhongfei
Published: January 2025

This study explores the relationship between corporate environmental, social, and governance (ESG) disagreements and corporate debt maturity. By examining panel samples from Chinese non-financial listed companies covering 2007 to 2020, we find that ESG disagreements negatively influence corporate debt maturity. Even after conducting a series of robustness tests and addressing endogeneity concerns, the adverse effects of ESG disagreements persisted. A heterogeneity analysis shows that this negative impact is more significant for non-state-owned enterprises, small enterprises, enterprises with high capital intensity, enterprises with low analyst attention, and enterprises in high-tech industries. Through a mechanism analysis, we discovered that ESG disagreements can lead to information asymmetry and heightened default risk, subsequently affecting the maturity of corporate debt. Further analysis confirms that the negative impact of ESG on the debt structure inhibits long-term investment and exacerbates the mismatch between investment and financing terms.