bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing of anti-malarial drugs for the treatment of tuberculosis: realistic strategy or fanciful dead end?
Authors: Hanscheid Thomas , del Portal Luyten Claire Ruiz , Hermans Sabine M. , Grobusch Martin P. 
Published: May 2024

Abstract
Background
Drug repurposing offers a strategic alternative to the development of novel compounds, leveraging the known safety and pharmacokinetic profiles of medications, such as linezolid and levofloxacin for tuberculosis (TB). Anti-malarial drugs, including quinolones and artemisinins, are already applied to other diseases and infections and could be promising for TB treatment.

Methods
This review included studies on the activity of anti-malarial drugs, specifically quinolones and artemisinins, against Mycobacterium tuberculosis complex (MTC), summarizing results from in vitro, in vivo (animal models) studies, and clinical trials. Studies on drugs not primarily developed for TB (doxycycline, sulfonamides) and any novel developed compounds were excluded. Analysis focused on in vitro activity (minimal inhibitory concentrations), synergistic effects, pre-clinical activity, and clinical trials.

Results
Nineteen studies, including one ongoing Phase 1 clinical trial, were analysed: primarily investigating quinolones like mefloquine and chloroquine, and, to a lesser extent, artemisinins. In vitro findings revealed high MIC values for anti-malarials versus standard TB drugs, suggesting a limited activity. Synergistic effects with anti-TB drugs were modest, with some synergy observed in combinations with isoniazid or pyrazinamide. In vivo animal studies showed limited activity of anti-malarials against MTC, except for one study of the combination of chloroquine with isoniazid.

Conclusions
The repurposing of anti-malarials for TB treatment is limited by high MIC values, poor synergy, and minimal in vivo effects. Concerns about potential toxicity at effective dosages and the risk of antimicrobial resistance, especially where TB and malaria overlap, further question their repurposing. These findings suggest that focusing on novel compounds might be both more beneficial and rewarding.
Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis
Authors: Wang Ying , Meng Zhaowei , Wei Sen , Li Xuebing , Su Zheng , Jiang Yong , Wu Heng , Pan Hongli , Wang Jing , Zhou Qinghua , Qiao Youlin , Fan Yaguang 
Published: May 2024

Abstract
Background
Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample.

Methods
We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin.

Results
In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers.

Conclusions
Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.
Engineered nanoparticles promote cardiac tropism of AAV vectors
Authors: Switala Lauren , Di Lin , Gao Huiyun , Asase Courteney , Klos Matthew , Rengasamy Palanivel , Fedyukina Daria , Maiseyeu Andrei 
Published: May 2024

AbstractCardiac muscle targeting is a notoriously difficult task. Although various nanoparticle (NP) and adeno-associated viral (AAV) strategies with heart tissue tropism have been developed, their performance remains suboptimal. Significant off-target accumulation of i.v.-delivered pharmacotherapies has thwarted development of disease-modifying cardiac treatments, such as gene transfer and gene editing, that may address both rare and highly prevalent cardiomyopathies and their complications. Here, we present an intriguing discovery: cargo-less, safe poly (lactic-co-glycolic acid) particles that drastically improve heart delivery of AAVs and NPs. Our lead formulation is referred to as ePL (enhancer polymer). We show that ePL increases selectivity of AAVs and virus-like NPs (VLNPs) to the heart and de-targets them from the liver. Serotypes known to have high (AAVrh.74) and low (AAV1) heart tissue tropisms were tested with and without ePL. We demonstrate up to an order of magnitude increase in heart-to-liver accumulation ratios in ePL-injected mice. We also show that ePL exhibits AAV/NP-independent mechanisms of action, increasing glucose uptake in the heart, increasing cardiac protein glycosylation, reducing AAV neutralizing antibodies, and delaying blood clearance of AAV/NPs. Current approaches utilizing AAVs or NPs are fraught with challenges related to the low transduction of cardiomyocytes and life-threatening immune responses; our study introduces an exciting possibility to direct these modalities to the heart at reduced i.v. doses and, thus, has an unprecedented impact on drug delivery and gene therapy. Based on our current data, the ePL system is potentially compatible with any therapeutic modality, opening a possibility of cardiac targeting with numerous pharmacological approaches.
Graphical Abstract
Physiologic oxygen responses to smoking opioids: an observational study using continuous pulse oximetry at overdose prevention services in British Columbia, Canada
Authors: Moe Jessica , Buxton Jane A. , Wang Yueqiao Elle , Chavez Tamara , Feldman-Kiss Damian , Marr Charotte , Purssell Roy A. , Otterstatter Michael 
Published: May 2024

Abstract
Background
In British Columbia, Canada, smoking is the most common modality of drug use among people who die of opioid toxicity. We aimed to assess oxygen saturation (SpO2) while people smoked opioids during a pilot study that introduced continuous pulse oximetry at overdose prevention services (OPS) sites.

Methods
This was an observational cohort study, using a participatory design. We implemented our monitoring protocol from March to August 2021 at four OPS. We included adults (≥ 18 years) presenting to smoke opioids. A sensor taped to participants’ fingers transmitted real-time SpO2 readings to a remote monitor viewed by OPS staff. Peer researchers collected baseline data and observed the timing of participants’ inhalations. We analyzed SpO2 on a per-event basis. In mixed-effects logistic regression models, drop in minimum SpO2 ≤ 90% in the current minute was our main outcome variable. Inhalation in that same minute was our main predictor. We also examined inhalation in the previous minute, cumulative inhalations, inhalation rate, demographics, co-morbidities, and substance use variables.

Results
We recorded 599 smoking events; 72.8% (436/599) had analyzable SpO2 data. Participants’ mean age was 38.6 years (SD 11.3 years) and 73.1% were male. SpO2 was highly variable within and between individuals. Drop in SpO2 ≤ 90% was not significantly associated with inhalation in that same minute (OR: 1.2 [0.8–1.78], p = 0.261) or inhalation rate (OR 0.47 [0.20–1.10], p = 0.082). There was an association of SpO2 drop with six cumulative inhalations (OR 3.38 [1.04–11.03], p = 0.043); this was not maintained ≥ 7 inhalations. Demographics, co-morbidities, and drug use variables were non-contributory.

Conclusions
Continuous pulse oximetry SpO2 monitoring is a safe adjunct to monitoring people who smoke opioids at OPS. Our data reflect challenges of real-world monitoring, indicating that greater supports are needed for frontline responders at OPS. Inconsistent association between inhalations and SpO2 suggests that complex factors (e.g., inhalation depth/duration, opioid tolerance, drug use setting) contribute to hypoxemia and overdose risk while people smoke opioids.
Surgical management of right hepatectomy after coronary artery bypass grafting using the right gastroepiploic artery: a case report and literature review
Authors: Kawaguchi Nao , Kizawa Shun , Daimon Masahiro , Minami Hiroki , Ueda Yasuhiko , Tomioka Atsushi , Komeda Koji , Asakuma Mitsuhiro , Tomiyama Hideki , Lee Sang-Woong 
Published: May 2024

Abstract
Background
Coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA) is a well-established, safe procedure. However, problems with RGEA grafts in subsequent abdominal surgeries can lead to fatal complications. This report presents the first case of right hepatectomy for hepatocellular carcinoma after CABG using the RGEA.

Case presentation
We describe a case in which a right hepatectomy for an 81-year-old male patient with hepatocellular carcinoma was safely performed after CABG using a RGEA graft. Preoperatively, three-dimensional computed tomography (3D- CT) images were constructed to confirm the run of the RGEA graft. The operation was conducted with the standby of a cardiovascular surgeon if there was a problem with the RGEA graft. The RGEA graft had formed adhesions with the hepatic falciform ligament, necessitating meticulous dissection. After the right hepatectomy, the left hepatic lobe descended into the vacated space, exerting traction on the RGEA. However, this traction was mitigated by suturing the hepatic falciform ligament to the abdominal wall, ensuring stability of the RGEA. There were no intraoperative or postoperative complications.

Conclusion
It is crucial to confirm the functionality and anatomy of the RGEA graft preoperatively, handle it gently intraoperatively, and collaborate with cardiovascular surgeons.
Built and natural environment correlates of physical activity of adults living in rural areas: a systematic review
Authors: Müller Christina , Paulsen Lisa , Bucksch Jens , Wallmann-Sperlich Birgit 
Published: May 2024

AbstractBackgroundAccording to social-ecological models, the built and natural environment has the potential to facilitate or hinder physical activity (PA). While this potential is well researched in urban areas, a current systematic review of how the built and natural environment is related to PA in rural areas is lacking.MethodsWe searched five databases and included studies for adults (18–65 years) living in rural areas. We included quantitative studies investigating the association between any self-reported or objectively measured characteristic of the built or natural environment and any type of self-reported or objectively measured PA, and qualitative studies that reported on features of the built or natural environment perceived as barriers to or facilitators of PA by the participants. Screening for eligibility and quality assessment (using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields) were done in duplicate. We used a narrative approach to synthesize the results.ResultsOf 2432 non-duplicate records, 51 quantitative and 19 qualitative studies were included. Convincing positive relationships were found between the availability and accessibility of places for exercise and recreation and leisure-time PA as well as between the overall environment and leisure-time PA. Possible positive associations were found between the overall environment and total and transport-related PA, between greenness/natural environment and total PA, between cycling infrastructure and aesthetics and MVPA, and between pedestrian infrastructure and total walking. A possible negative relationship was found between safety and security and total walking. Qualitative studies complemented several environmental facilitators (facilities for exercise and recreation, sidewalks or streets with low traffic, attractive natural environment) and barriers (lack of facilities and destinations, lack of sidewalks, speeding traffic and high traffic volumes, lack of street lighting).ConclusionsResearch investigating the relationship between the built and natural environment and PA behaviors of adults living in rural areas is still limited and there is a need for more high-quality and longitudinal studies. However, our most positive findings indicate that investing in places for exercise and recreation, a safe infrastructure for active transport, and nature-based activities are possible strategies that should be considered to address low levels of PA in rural adults.Trial registrationPROSPERO: CRD42021283508.
Tribulations and future opportunities for artificial intelligence in precision medicine
Authors: Carini Claudio , Seyhan Attila A. 
Published: May 2024

AbstractUpon a diagnosis, the clinical team faces two main questions: what treatment, and at what dose? Clinical trials' results provide the basis for guidance and support for official protocols that clinicians use to base their decisions. However, individuals do not consistently demonstrate the reported response from relevant clinical trials. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual's response to the treatment varies with the changes in their condition. In practice, the drug and the dose selection depend significantly on the medical protocol and the medical team's experience. As such, the results are inherently varied and often suboptimal. Big data and Artificial Intelligence (AI) approaches have emerged as excellent decision-making tools, but multiple challenges limit their application. AI is a rapidly evolving and dynamic field with the potential to revolutionize various aspects of human life. AI has become increasingly crucial in drug discovery and development. AI enhances decision-making across different disciplines, such as medicinal chemistry, molecular and cell biology, pharmacology, pathology, and clinical practice. In addition to these, AI contributes to patient population selection and stratification. The need for AI in healthcare is evident as it aids in enhancing data accuracy and ensuring the quality care necessary for effective patient treatment. AI is pivotal in improving success rates in clinical practice. The increasing significance of AI in drug discovery, development, and clinical trials is underscored by many scientific publications. Despite the numerous advantages of AI, such as enhancing and advancing Precision Medicine (PM) and remote patient monitoring, unlocking its full potential in healthcare requires addressing fundamental concerns. These concerns include data quality, the lack of well-annotated large datasets, data privacy and safety issues, biases in AI algorithms, legal and ethical challenges, and obstacles related to cost and implementation. Nevertheless, integrating AI in clinical medicine will improve diagnostic accuracy and treatment outcomes, contribute to more efficient healthcare delivery, reduce costs, and facilitate better patient experiences, making healthcare more sustainable. This article reviews AI applications in drug development and clinical practice, making healthcare more sustainable, and highlights concerns and limitations in applying AI.
Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets
Authors: Xu Mengchen , Hou Yiming , Li Na , Yu Wenqian , Chen Lei 
Published: May 2024

AbstractThe onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, there is limited knowledge regarding the role of HDACs in HNSCC. Consequently, this review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on therapeutic approaches targeting HDACs that could potentially enhance the efficacy of HNSCC treatment. Additionally, the Cancer Genome Atlas (TCGA) dataset, CPTAC, HPA, OmicShare, GeneMANIA and STRING databases are utilized to provide supplementary evidence on the differential expression of HDACs, their prognostic significance and predicting functions in HNSCC patients.
Graphical Abstract
Immune checkpoint inhibitors induce acute interstitial nephritis in mice with increased urinary MCP1 and PD-1 glomerular expression
Authors: Martinez Valenzuela Laura , Gómez-Preciado Francisco , Guiteras Jordi , Antón Pampols Paula , Gomà Montserrat , Fulladosa Xavier , Cruzado Josep Maria , Torras Joan , Draibe Juliana 
Published: May 2024

Abstract
Introduction
Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2–5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients.

Methods
Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression.

Results
Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity.

Conclusions
Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.
Changes in the hippocampal level of tau but not beta-amyloid may mediate anxiety-like behavior improvement ensuing from exercise in diabetic female rats
Authors: Khoramipour Kayvan , Rezaei Maryam Hossein , Moslemizadeh Amirhossein , Hosseini Mahdieh Sadat , Ebrahimnezhad Narjes , Bashiri Hamideh 
Published: May 2024

AbstractBackgroundIn the present study, we investigated the effect of high-intensity interval training (HIIT) on cognitive behaviors in female rats with a high-fat diet + streptozotocin (STZ)-induced type 2 diabetes.MethodsTwenty-four female rats were divided into four groups randomly (n = 6): control (C), control + exercise (Co + EX), diabetes mellitus (type 2) (T2D), and diabetes mellitus + exercise (T2D + EX). Diabetes was induced by a two-month high-fat diet and a single dose of STZ (35 mg/kg) in the T2D and T2D + EX groups. The Co + EX and T2D + EX groups performed HIIT for eight weeks (five sessions per week, running on a treadmill at 80–100% of VMax, 4–10 intervals). Elevated plus maze (EPM) and open field test (OFT) were used for assessing anxiety-like behaviors, and passive avoidance test (PAT) and Morris water maze (MWM) were applied for evaluating learning and memory. The hippocampal levels of beta-amyloid (Aβ) and Tau were also assessed using Western blot.ResultsAn increase in fasting blood glucose (FBG), hippocampal level of Tau, and a decrease in the percentage of open arm time (%OAT) as an index of anxiety-like behavior were seen in the female diabetic rats which could be reversed by HIIT. In addition, T2D led to a significant decrease in rearing and grooming in the OFT. No significant difference among groups was seen for the latency time in the PAT and learning and memory in the MWM.ConclusionsHIIT could improve anxiety-like behavior at least in part through changes in hippocampal levels of Tau.
Colour-analyzer: a new dual colour model-based imaging tool to quantify plant disease
Authors: Loranger Mackenzie Eli William , Yim Winfield , Accomazzi Vittorio , Morales-Lizcano Nadia , Moeder Wolfgang , Yoshioka Keiko 
Published: May 2024

Abstract
Background
Despite major efforts over the last decades, the rising demands of the growing global population makes it of paramount importance to increase crop yields and reduce losses caused by plant pathogens. One way to tackle this is to screen novel resistant genotypes and immunity-inducing agents, which must be conducted in a high-throughput manner.

Results
Colour-analyzer is a free web-based tool that can be used to rapidly measure the formation of lesions on leaves. Pixel colour values are often used to distinguish infected from healthy tissues. Some programs employ colour models, such as RGB, HSV or L*a*b*. Colour-analyzer uses two colour models, utilizing both HSV (Hue, Saturation, Value) and L*a*b* values. We found that the a* b* values of the L*a*b* colour model provided the clearest distinction between infected and healthy tissue, while the H and S channels were best to distinguish the leaf area from the background.

Conclusion
By combining the a* and b* channels to determine the lesion area, while using the H and S channels to determine the leaf area, Colour-analyzer provides highly accurate information on the size of the lesion as well as the percentage of infected tissue in a high throughput manner and can accelerate the plant immunity research field.