bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-Chain Acyl-CoA Dehydrogenase as a Therapeutic Target for Cardiac Fibrosis
Authors: Shu Zhaohui , Feng Jingyun , Liu Lanting , Liao Yingqin , Cao Yuhong , Zeng Zhenhua , Qiuju Huang  , Li Zhonghong , Jin Guifang , Yang Zhicheng , Xing Jieyu , Zhou Sigui 
Published: February 2024

Abstract:
Cardiac fibrosis is considered as unbalanced extracellular matrix production and degradation, contributing to heart failure. Short-chain acyl-CoA dehydrogenase (SCAD) negatively regulates pathological cardiac hypertrophy. The purpose of this study was to investigate the possible role of SCAD in cardiac fibrosis. In vivo experiments were performed on spontaneously hypertensive rats (SHR) and SCAD-knockout mice. The cardiac tissues of hypertensive patients with cardiac fibrosis were used for the measurement of SCAD expression. In vitro experiments, with angiotensin II (Ang II), SCAD siRNA and adenovirus-SCAD were performed using cardiac fibroblasts (CFs). SCAD expression was significantly decreased in the left ventricles of SHR. Notably, swim training ameliorated cardiac fibrosis in SHR in association with the elevation of SCAD. The decrease in SCAD protein and mRNA expression levels in SHR CFs were in accordance with those in the left ventricular myocardium of SHR. In addition, SCAD expression was downregulated in CFs treated with Ang II in vitro, and SCAD siRNA interference induced the same changes in cardiac fibrosis as Ang II-treated CFs, while adenovirus-SCAD treatment significantly reduced the Ang II–induced CFs proliferation, alpha smooth muscle actin (α-SMA), and collagen expression. In SHR infected with adenovirus-SCAD, the cardiac fibrosis of the left ventricle was significantly decreased. However, cardiac fibrosis occurred in conventional SCAD-knockout mice. SCAD immunofluorescence intensity of cardiac tissue in hypertensive patients with cardiac fibrosis was lower than that of healthy subjects. Altogether, the current experimental outcomes indicate that SCAD has a negative regulatory effect on cardiac fibrosis and support its potential therapeutic target for suppressing cardiac fibrosis.
Exploring the Promise and Challenges of Artificial Intelligence in Biomedical Research and Clinical Practice
Authors: Altara Raffaele , Basson Cameron J. , Biondi-Zoccai Giuseppe , Booz George W. 
Published: February 2024

Abstract:
Artificial intelligence (AI) is poised to revolutionize how science, and biomedical research in particular, are done. With AI, problem-solving and complex tasks using massive data sets can be performed at a much higher rate and dimensionality level compared with humans. With the ability to handle huge data sets and self-learn, AI is already being exploited in drug design, drug repurposing, toxicology, and material identification. AI could also be used in both basic and clinical research in study design, defining outcomes, analyzing data, interpreting findings, and even identifying the most appropriate areas of investigation and funding sources. State-of-the-art AI-based large language models, such as ChatGPT and Perplexity, are positioned to change forever how science is communicated and how scientists interact with one another and their profession, including postpublication appraisal and critique. Like all revolutions, upheaval will follow and not all outcomes can be predicted, necessitating guardrails at the onset, especially to minimize the untoward impact of the many drawbacks of large language models, which include lack of confidentiality, risk of hallucinations, and propagation of mainstream albeit potentially mistaken opinions and perspectives. In this review, we highlight areas of biomedical research that are already being reshaped by AI and how AI is likely to affect it further in the near future. We discuss the potential benefits of AI in biomedical research and address possible risks, some surrounding the creative process, that warrant further reflection.
Instructional Video of a Standardized Interprofessional Postsimulation Facilitator-guided Debriefing of a Fatality in Plastic Surgery
Authors: Gasteratos Konstantinos , Michalopoulos James , Nona Marven , Morsi-Yeroyiannis Antonios , Goverman Jeremy , Rakhorst Hinne , van der Hulst René R. W. J. 
Published: February 2024

Background:
Postsimulation facilitator-guided debriefing (PSFGD) is the process of intentional discussion of thoughts, actions, and events that took place during simulation amongst the facilitator(s) and trainees. Despite the significance of delivering high-quality debriefings, there is a lack of evidence-based guidelines. Our study aimed to provide an instructional video demonstration of a PSFGD of a fatality.

Methods:
Fifty surgical interns participated in a burn simulation scenario in two groups. Group 1 (control, or “no exposure,” n = 25) consisted of residents who received oral postsimulation debriefing from an independent faculty member who had no exposure to our instructional video on how to debrief effectively. Group 2 (intervention, or “exposure,” n = 25) consisted of interns who were debriefed by the second faculty member who did watch our instructional video before the simulation and learned about “advocacy and inquiry” techniques. The outcome measures were the Debriefing Assessment for Simulation in Healthcare score and the postdebrief multiple-choice question (MCQ) quiz scores to assess debriefers’ performance and interns’ knowledge consolidation, respectively.

Results:
The “exposure” group presented statistically significantly higher values for the Debriefing Assessment for Simulation in Healthcare score (P < 0.001) and MCQ score (P < 0.001) compared with the “no exposure” group.

Conclusions:
Debriefers who followed the methodology as demonstrated in our instructional video were considered more competent, and the residents achieved higher MCQ scores. The quality of the debriefing ensures improved critical thinking and problem-solving skills. Safer practice and better patient outcomes are achieved by developing debriefing programs for educators.
Improving Skin Paddle Reliability and Muscle Gliding in Free Functional Gracilis Transfers
Authors: Vaile John R. , Struble Sarah L. , Patel Niki K. , Janes Lindsay E. , Park Eugene D. , Levin L. Scott , Mendenhall Shaun D. 
Published: February 2024

Summary:
Free functional muscle transfer is an attractive option within reconstructive surgery when seeking to restore critical muscle function. The gracilis muscle has long been utilized for this purpose due to its expendability and consistent anatomy. Historically, survival of the skin overlying the distal one-third of the myocutaneous gracilis flap has been unpredictable. To address this, the myofasciocutaneous technique was developed, with prior studies demonstrating improved distal skin paddle viability with this approach; however, the mechanism is poorly defined. This study aimed to understand what factors contribute to survival benefit in myofasciocutaneous gracilis flaps. Using cadaveric dissections followed by latex dye injections, we discuss the creation of a deep fascial sheath that contains a rich vascular network and permits adhesion-free excursion at the recipient site. This study advances our understanding of the myofasciocutaneous gracilis flap and provides wider clinical applicability in free functional muscle transfer.
Race-specific associations: inflammatory mediators and chronic low back pain
Authors: Overstreet Demario S. , Strath Larissa J. , Sorge Robert E. , Thomas Pavithra A. , He Jingui , Wiggins Asia M. , Hobson Joanna , Long D. Leann , Meints Samantha M. , Aroke Edwin N. , Goodin Burel R. 
Published: February 2024

Abstract
Chronic low back pain (cLBP) is a global health crisis that disproportionately burdens non-Hispanic Black (NHB) individuals, compared with those who identify as non-Hispanic White (NHW). Despite the growing personal and societal impact of cLBP, its biological underpinnings remain poorly understood. To elucidate the biological factors that underlie the racial disparities in cLBP, this study sought to determine whether inflammatory mediators associated with pain interference (PI), pain at rest (PAR), and movement-evoked pain (MEP) differ as a function of racial identity. Blood samples were collected from 156 individuals with cLBP (n = 98 NHB participants, n = 58 NHW participants). Enzyme-linked immunosorbent assay and multiplex assays were used to quantify concentrations of proinflammatory (fibrinogen, C-reactive protein [CRP], serum amyloid A, tumor necrosis factor α [TNF-α], and interleukin [IL]–1α, IL-1β, and IL-6) and anti-inflammatory markers (IL-4 and IL-13). Spearman rho correlations were used to assess associations among markers of inflammation and PI, PAR, and MEP using the Brief Pain Inventory–Short Form. Analyses revealed that for NHW patients, CRP, serum amyloid A, and IL-6 were positively associated with cLBP outcomes and IL-4 was inversely associated with PAR and MEP. However, for NHB patients, only IL-1α was positively associated with PAR. Our findings suggest that, while there are associations between inflammation and cLBP outcomes, the biomarkers that underlie the inflammation could very well differ as a function of racialized minority group. However, more research with racially inclusive samples is needed to elucidate the mechanisms that may contribute to racial disparities in cLBP.
Pulmonary infections in the returning traveler
Authors: Norman Francesca F. , Gonzalez-Sanz Marta 
Published: February 2024

Purpose of review
The recent COVID-19 pandemic has shaped the epidemiology of other infectious diseases globally. International tourist arrivals are increasing and recovering to prepandemic levels. This review focuses on respiratory infections in travelers, highlighting the characteristics of the main imported viral, bacterial, fungal, and parasitic infections with pulmonary involvement.

Recent findings
A recent systematic review estimated a prevalence of respiratory symptoms in travelers of around 35%, increasing to nearly 65% in the context of mass gatherings. Common viral and bacterial pathogens account for the majority of respiratory infections with an identified cause; however, recent data focus on the need for surveillance of emerging infections such as MERS-CoV, henipaviruses and multidrug resistant bacteria, which may be spread through travel. Fungal and parasitic respiratory infections are less common, and acquisition is usually associated with specific risk factors or exposure in endemic areas. Special risk groups, such as immunocompromised travelers, may be particularly vulnerable, presenting with severe disease or reactivation of latent infections.

Summary
The next significant international epidemic could involve another new infectious agent causing respiratory disease and spreading via mobile populations. Official protocols should be adhered to, and public health interventions implemented for effective control. Continued and globally coordinated investments in research for new vaccines, therapeutic agents, disease modeling, and digital tracking strategies are essential.
Thoracic empyema: aetiology, diagnosis, treatment, and prevention
Authors: Merchant Na’im , Liu Chantal 
Published: February 2024

Purpose of review
The aim of this study was to review current key points in the aetiology, diagnosis, treatment, and prevention of empyema thoracis. Early postpandemic trends have seen an increasing global incidence and evolution in the aetiology of empyema. Due to varied aetiology and typically lengthy treatment, empyema will be disproportionately affected by the rising tide of antimicrobial resistance (AMR), thus warranting attention and further research.

Recent findings
Multiple novel biomarkers (e.g. IL-36γ) are under investigation to aid diagnosis, while oral health assessment tools are now available for prognosticating and risk-stratifying patients with thoracic empyema. There exists an ongoing lack of evidence-based guidance surrounding antibiotic treatment duration, surgical intervention indication, and prognostic scoring utility.

Summary
Understanding aetiologies in different global regions and settings is pivotal for guiding empirical treatment. Antimicrobial resistance will make thoracic empyema increasingly challenging to treat and should prompt increased awareness of prescribing practices. Novel biomarkers are under investigation which may speed up differentiation of pleural effusion types, allowing faster cohorting of patients.
Although newly identified predictors of morbidity and mortality have been suggested to be beneficial for incorporation into clinical practice, further work is required to prognosticate, risk-stratify, and standardize treatment.
Rural trauma team development training amongst medical trainees and traffic law enforcement professionals in a low-income country: a protocol for a prospective multicenter interrupted time series
Authors: Lule Herman , Mugerwa Michael , SSebuufu Robinson , Kyamanywa Patrick , Posti Jussi P. , Wilson Michael L. 
Published: February 2024

Background:
Road traffic injuries and their resulting mortality disproportionately affect rural communities in low-middle-income countries (LMICs) due to limited human and infrastructural resources for postcrash care. Evidence from high-income countries show that trauma team development training could improve the efficiency, care, and outcome of injuries. A paucity of studies have evaluated the feasibility and applicability of this concept in resource constrained settings. The aim of this study protocol is to establish the feasibility of rural trauma team development and training in a cohort of medical trainees and traffic law enforcement professionals in Uganda.

Methods:
Muticenter interrupted time series of prospective interventional trainings, using the rural trauma team development course (RTTDC) model of the American College of Surgeons. A team of surgeon consultants will execute the training. A prospective cohort of participants will complete a before and after training validated trauma related multiple choice questionnaire during September 2019-November 2023. The difference in mean prepost training percentage multiple choice questionnaire scores will be compared using ANOVA-test at 95% CI. Time series regression models will be used to test for autocorrelations in performance. Acceptability and relevance of the training will be assessed using 3 and 5-point-Likert scales. All analyses will be performed using Stata 15.0. Ethical approval was obtained from Research and Ethics Committee of Mbarara University of Science and Technology (Ref: MUREC 1/7, 05/05-19) and Uganda National Council for Science and Technology (Ref: SS 5082). Retrospective registration was accomplished with Research Registry (UIN: researchregistry9490).
Optic Neuropathy and Myelopathy in a Teenager With Biotinidase Deficiency
Authors: Chodnicki Kevin D. , Aksamit Allen J. , Gavrilova Ralitza H. , Farnsworth Paul J. , McClelland Collin M. 
Published: February 2024

Abstract:
A 19-year-old man presented with 3 years of gradually progressive, painless vision loss in both eyes. The ophthalmic examination showed bilateral diminished visual acuity, dyschromatopsia, and temporal optic nerve pallor. The neurological examination was consistent with a mild myelopathy with decreased pin-prick sensation starting at T6–T7 and descending through the lower extremities. Hyperreflexia was also present in the lower more than upper extremities. Infectious, inflammatory, and nutritional serum workup and cerebrospinal fluid analysis were both unrevealing. MRI of the brain and spinal cord showed abnormal T2 hyperintensity of the fornix, corpus callosum, optic nerves, and lateral columns of the cervical and thoracic spine, with diffusion restriction in the inferior–posterior corpus callosum and fornix. Biotinidase serum enzyme activity was tested and showed a decreased level of activity. Biotinidase gene testing showed a homozygous pathogenic variant, c.424C>A (p.P142T), confirming the diagnosis of biotinidase deficiency and prompting oral biotin supplementation. Three months after starting treatment, the patient's visual acuity, color vision, visual fields, and MRI spine abnormalities all improved significantly. Biotinidase deficiency is an important diagnostic consideration in patients with unexplained optic neuropathy and/or myelopathy.
Proposal for Prognosis-Oriented Definition of Borderline Resectable Hepatocellular Carcinoma
Authors: Haruki Koichiro , Harimoto Norifumi , Furukawa Kenei , Taniai Tomohiko , Yanagaki Mitsuru , Igarashi Yosuke , Tsunematsu Masashi , Shirai Yoshihiro , Shirabe Ken , Ikegami Toru 
Published: February 2024

BACKGROUND:
Owing to advances in the multidisciplinary treatment of hepatocellular carcinoma (HCC), a conceptualization and definition for borderline resectable (BR) HCC, which carries a high risk of recurrence, is warranted. In this study, we aimed to define BR-HCC using a prognosis-oriented approach.

STUDY DESIGN:
The study included an original cohort of 221 patients and an independent validation cohort of 181 patients who had undergone primary hepatic resection for HCC. To define biological BR-HCC, we evaluated the risk factors for early recurrence beyond the Milan criteria within 1 year after hepatic resection using multivariable logistic regression models. Subsequently, we developed high-risk scores using the identified risk factors and defined BR-HCC. The utility of high-risk score was validated in the validation cohort.

RESULTS:
In the original cohort (hepatitis B virus:hepatitis C virus = 20%:29%), recurrence beyond the Milan criteria within 1 year was observed in 28 patients (13%), with a 5-year survival rate of 25%. Multivariable analysis identified risk factors for recurrence beyond the Milan criteria within 1 year, including serum alpha-fetoprotein levels of 12 ng/mL or more (p = 0.02), tumor diameters less than 5 cm (p = 0.02), tumor number 3 or more (p = 0.001), and macrovascular invasion (p = 0.04). BR-HCC was defined as a tumor with 2 or more identified risk factors, and 42 patients (19%) were diagnosed with BR-HCC, with a 5-year survival rate of 51%. In the validation cohort, 45 (25%) patients had BR-HCC, with a 5-year survival rate of 42%.

CONCLUSIONS:
The prognosis-oriented definition of BR-HCC enabled us to identify patients who are susceptible to early unresectable recurrence and have poor survival after hepatic resection for HCC. For patients with BR-HCC, preoperative systemic therapy may be a viable option to improve postresection outcomes.
A HOSPITAL BASED OBSERVATIONAL STUDY ON HIV-TB COINFECTION
Authors: Soni Akansha , Jain Parul , Venkatesh Vimala , JAIN AMITA , HIMANSHU D , GUPTA NEETU , TANDON RITU 
Published: February 2024

ABSTRACT

BACKGROUND:
HIV is the leading cause of failure to reach TB control targets in high-HIV settings. TB on the other hand enhances progression of HIV infection to AIDS.
MATERIAL AND METHODS :
An observational study was conducted in which a total of 573 newly diagnosed HIV-positive patients enrolled at ART center, KGMU, Lucknow between May 2021 to June 2022 were taken of which 80 patients had newly diagnosed TB. These HIV-TB co-infected patients were analyzed for demographic factors. Also, CD4 counts were done at the time of enrolment on ART and then about six to eight months later. For comparision, of the 493 HIV only patients, 50 age and sex matched consecutive patients for whom baseline and follow up CD4 counts were available were enrolled as controls. The change from baseline CD4 count was calculated using paired t-test and Wilcoxon signed rank test.
RESULTS :
In present study,among HIV-TB coinfected patients, baseline CD4 levels were 194.52±162.27, and follow up CD4 levels were 285.09±170.33. An increment of 90.57±165.60 in mean CD4 levels was observed which was statistically significant(t=4.019; p<0.001 ).
CONCLUSION :
Significant rise in CD4 counts was observed in HIV-TB coinfected patients started on ART and ATT.
Assessing NGS-based computational methods for predicting transcriptional regulators with query gene sets
Authors: Lu Zeyu , Xiao Xue , Zheng Qiang , Wang Xinlei , Xu Lin 
Published: February 2024

AbstractThis article provides an in-depth review of computational methods for predicting transcriptional regulators with query gene sets. Identification of transcriptional regulators is of utmost importance in many biological applications, including but not limited to elucidating biological development mechanisms, identifying key disease genes, and predicting therapeutic targets. Various computational methods based on next-generation sequencing (NGS) data have been developed in the past decade, yet no systematic evaluation of NGS-based methods has been offered. We classified these methods into two categories based on shared characteristics, namely library-based and region-based methods. We further conducted benchmark studies to evaluate the accuracy, sensitivity, coverage, and usability of NGS-based methods with molecular experimental datasets. Results show that BART, ChIP-Atlas, and Lisa have relatively better performance. Besides, we point out the limitations of NGS-based methods and explore potential directions for further improvement.Key pointsAn introduction to available computational methods for predicting functional TRs from a query gene set.A detailed walk-through along with practical concerns and limitations.A systematic benchmark of NGS-based methods in terms of accuracy, sensitivity, coverage, and usability, using 570 TR perturbation-derived gene sets.NGS-based methods outperform motif-based methods. Among NGS methods, those utilizing larger databases and adopting region-centric approaches demonstrate favorable performance. BART, ChIP-Atlas, and Lisa are recommended as these methods have overall better performance in evaluated scenarios.
Persistent tailoring of MSC activation through genetic priming
Authors: Beauregard Michael A. , Bedford Guy C. , Brenner Daniel A. , Sanchez Solis Leonardo D. , Nishiguchi Tomoki , Abhimanyu  , Carrero Longlax Santiago , Mahata Barun , Veiseh Omid , Wenzel Pamela L. , DiNardo Andrew R. , Hilton Isaac B. , Diehl Michael R. 
Published: February 2024

ABSTRACTMesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molecules. Yet, MSCs are well known to require preconditioning or priming to boost their therapeutic efficacy. Current priming methods offer limited control over MSC activation, yield transient effects, and often induce expression of pro-inflammatory effectors that can potentiate immunogenicity. Here, we describe a ‘genetic priming’ method that can both selectively and sustainably boost MSC potency via the controlled expression of the inflammatory-stimulus-responsive transcription factor IRF1 (interferon response factor 1). MSCs engineered to hyper-express IRF1 recapitulate many core responses that are accessed by biochemical priming using the proinflammatory cytokine interferon-γ (IFNγ). This includes the upregulation of anti-inflammatory effector molecules and the potentiation of MSC capacities to suppress T cell activation. However, we show that IRF1-mediated genetic priming is much more persistent than biochemical priming and can circumvent IFNγ-dependent expression of immunogenic MHC class II molecules. Together, the ability to sustainably activate and selectively tailor MSC priming responses creates the possibility of programming MSC activation more comprehensively for therapeutic applications.GRAPHICAL ABSTRACT