bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restrictive Versus Liberal Transfusion in Symptomatic Coronary Artery Disease and Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials
Authors: Singh Sahib , Tantry Udaya S. , Bliden Kevin , Gurbel Paul A. , Navarese Eliano , Garg Aakash 
Published: November 2024

Background:
In patients with coronary artery disease (CAD) and/or myocardial infarction (MI), anemia is associated with an increased risk of adverse cardiovascular (CV) outcomes. Transfusion goals in such patients remain unclear.

Study question:
A meta-analysis of the available randomized controlled trials (RCTs) was conducted comparing restrictive and liberal transfusion strategies in patients with symptomatic CAD/MI.

Data sources:
Multiple online databases including Cochrane, Pubmed, Embase, and MEDLINE were searched for RCTs.

Study design:
End points of interest were major adverse CV events (MACEs), MI, all-cause death, CV death, revascularization, heart failure (HF), and infection. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model.

Results:
A total of 5 RCTs with 4518 patients—2258 in the restrictive transfusion group and 2260 in the liberal transfusion group—were included. The mean age was 72 years, and 59% of patients were men. At 30 days, MACE and MI were similar in the 2 transfusion groups. However, at the longest available follow-up, the restrictive strategy was associated with increased risks of MACE (OR 1.18, 95% CI, 1.02–1.37; P = 0.03) and MI (1.27, 95% CI, 1.02–1.58; P = 0.04), along with the higher trend of all-cause death (1.21, 95% CI, 1.00–1.46; P = 0.05) as compared with liberal transfusion. The 2 groups had comparable rates of CV death, revascularization, HF, and infection.

Conclusions:
Liberal transfusion strategy may be associated with improved CV outcomes among patients with symptomatic CAD/MI as compared with a restrictive transfusion strategy.
Treatment With Long-Acting Injectable Aripiprazole During Pregnancy in Bipolar Disorder: A Scoping Review
Authors: Teodorescu Andreea , Dima Lorena , Petric Paula Simina , Necula Ruxandra Mihaela , Banciu Roxana , Moga Marius Alexandru , Marian-Pavlenco Angela , Ifteni Petru 
Published: November 2024

Background:
The management of bipolar disorder during pregnancy presents a significant challenge, particularly regarding the safety and effectiveness of long-acting injectable (LAI) antipsychotics like aripiprazole. Despite the growing use of LAI antipsychotics in psychiatric disorders, data on their use during pregnancy are limited, especially for bipolar disorder. This study aimed to shed light on this issue through a scoping review.

Areas of Uncertainty:
The level of evidence concerning the safety of second-generation antipsychotics during pregnancy is limited. Data on LAI aripirazole are even more limited.

Data Sources:
We conducted a scoping review following the PRISMA-ScR guidelines, systematically searching multiple electronic databases for studies published between January 2008 and February 2024. The review focused on the administration of aripiprazole during pregnancy among patients with psychiatric disorders, examining outcomes related to maternal health, fetal well-being, and neonatal outcomes.

Results:
The scoping review identified 11 case reports that met the inclusion criteria and 4 additional studies (prospective and retrospective cohort studies).

Conclusions:
The scoping review emphasizes the need for further research to confirm its safety and efficacy. The limited data underscore the importance of individualized treatment plans and informed decision-making, considering the unique risks and benefits of LAI antipsychotic use during pregnancy. Further studies are imperative to provide more definitive guidance for managing bipolar disorder with LAI antipsychotics in pregnant patients.
EGb761 Trials for Mild-to-Moderate Dementia—What Have We Learned in the Past 18 years?
Authors: Necula Bogdan-Radu , Necula Radu Dan , Petric Paula Simina , Ifteni Petru Iulian , Irimie Marius , Dima Lorena 
Published: November 2024

Background:
Dementia leads to cognitive decline affecting memory, thinking, and behavior. Current pharmaceutical treatments are symptomatic, with limited efficacy and significant drawbacks. Ginkgo biloba extract (EGb761) is being explored as an adjuvant therapy for dementia because of its potential neuroprotective effects.

Areas of Uncertainty:

Despite decades of study, EGb761 has not been incorporated into treatment guidelines for these conditions. This review evaluates research futility in EGb761 trials for dementia, analyzing efficacy and methodological challenges to inform future research directions.

Data Sources:
In this review, we investigate the efficacy and adverse reactions of Ginkgo biloba extract (EGb761) as a treatment for Alzheimer disease or vascular dementia. We searched the randomized controlled trials published between 2006 and 2023 on PubMed and ScienceDirect.

Results:
The 7 selected studies have shown that the degree of improvement in standard cognitive assessment scores [Mini-Mental State Examination (MMSE), short cognitive performance test (SKT), neuropsychiatric inventory (NPI)] was not significant enough for a substantial proportion of patients. Improvements of the SKT score with at least 3 points in the Alzheimer disease/vascular dementia groups were found only in 2 out of 7 studies, changes of less than 2 points in MMSE score were found in 2 of the studies, while an improvement of at least 4 points in NPI scores was reported in 4 out of 7 studies. We aim to understand why this extract has not reached the level of evidence to be included in guideline recommendation despite extensive research and what have we learned from systematic reviews performed since 2010? Studies included in this review have shown some improvement in outcome scores with EGb761 treatment compared with placebo, but these improvements did not reach the threshold for clinically significant enhancement in MMSE/SKT/NPI scores. Limitations such as small sample sizes, minimal score changes, predominantly placebo comparisons, and short follow-up durations make it challenging to determine the usefulness of EGb761 in dementia treatment. The changes observed and methodological constraints underscore the uncertainty surrounding the efficacy of EGb761.

Conclusion:
The findings do not consistently demonstrate the clinical utility of EGb761, and improved scores on cognitive and neuropsychiatric assessments may not necessarily translate into meaningful clinical outcomes for patients with dementia. Starting from the question “What have we learned in the past 18 years?”, the answer would be: not much. Consequently, the question raised is: how long should we go on with the same conclusion, continuing to spend time and financial resources to replicate these results? Research strategies should be refined to optimize decision making and advance evidence-based care for neurocognitive disorders.
Botox for Sleep Effectiveness
Authors: Getaneh Feven W. , Richter Lee Ann , Dabbas Mai , Chou Jiling , Iglesia Cheryl B. , Dieter Alexis A. 
Published: November 2024

Importance
Nocturia is one of the most bothersome complaints in women with overactive bladder syndrome (OAB). Although small preliminary studies have shown that intradetrusor onabotulinum toxin A (BTX) injections reduce nocturia episodes, it is not known how reduction in nighttime urination affects sleep quality and quality of life.

Objectives
We aimed to assess the effect of BTX on nocturia frequency, sleep quality, and quality of life.

Study Design
This is a prospective observation study of adult women with ≥2 nocturia episodes and OAB planning to undergo treatment with BTX injections. Participants completed a 2-day bladder/sleep diary and sleep-related questionnaires at baseline and 5 weeks post-BTX.

Results
A total of 40 participants were included with a mean age of 71 ± 12 years and most (90%) undergoing 100 units of BTX injection. At baseline, the median nocturia episodes were 3.5 (IQR, 2.5–5.0), and nearly half (43%) of participants reported mild to moderate sleep disturbance. At 5 weeks post-BTX, we found a significant decrease in nocturia episodes (−2/night) and a 59% decrease in mild to moderate sleep disturbance (P = 0.006). There were significant increases in longest sleep interval (+1.5 hours), time to first awakening (+1.6 hours) and average sleep interval (+1.3 hours), and a significant increase in nocturia-related quality of life scores (P < 0.001 for all). Sixteen (40%) of participants had nocturia resolution defined as ≤1 mean nocturia episode post-BTX.

Conclusions
For women with OAB and >2 nocturia episodes/night, BTX injections reduce voids/night and improve sleep quality and nocturia-related quality of life.
Urinary Incontinence and Care Seeking Among Wisconsin Women
Authors: Warner Kristina J. , Schultz Amy A. , Barnet Jodi H. , Brown Heidi W. 
Published: November 2024

Importance
Women who identify as Black or African American are underrepresented in research about pelvic floor disorders.

Objectives
The objectives of this study were to describe the prevalence of and factors associated with urinary incontinence (UI) and UI care-seeking among adult women in a Wisconsin household survey.

Study Design
This was a cross-sectional analysis of data collected by the Survey of the Health of Wisconsin (SHOW). Using community engagement, individuals who identified as Black or African American were purposively oversampled in the 2018–2019 wave. Descriptive analyses compared women with and without UI, and those who had and had not sought care.

Results
Among 237 study participants, 46% (110) had UI: 46% mild, 36% moderate, and 18% severe. Most participants (84%) self-identified as non-Hispanic Black (84%), with a mean age of 49 ± 16 years and mean body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 34 ± 9; 62% were insured by Medicaid. The prevalence of UI was 44% among women who identified as non-Hispanic Black versus 59% (P = 0.085) among other women. Older age, obesity, needing help to read medical instructions, and identifying as a race other than non-Hispanic Black were significantly associated with UI. Among 110 women with UI, 53% had previously sought care. Rates of UI care seeking were similar (P = 0.32) among women who identified as non-Hispanic Black (55%) and those who identified as another race or ethnicity (43%).

Conclusion
Needing help to read medical instructions emerged as a factor associated with UI diagnosis in this sample that included almost 200 women who identified as non-Hispanic Black.
Enhancing Gene Set Overrepresentation Analysis with Large Language Models
Authors: Zhu Jiqing , Wang Rebecca Y. , Wang Xiaoting , Azevedo Ricardo , Moreno Alexander , Kuhn Julia A. , Khan Zia 
Published: November 2024

AbstractGene set overrepresentation analysis is widely used to interpret high-throughput transcriptomics and proteomics data, but traditional methods rely on static, human-curated gene set databases that lack flexibility. We introducellm2geneset, a framework that leverages large language models (LLMs) to dynamically generate gene set databases tailored to input query genes, such as differentially expressed genes (DEGs) and a biological context specified in natural language. These databases integrate with methods, such as overrepresentation analysis (ORA), to assign biological functions to input genes. Benchmarking against human-curated gene sets demonstrates that LLMs generate gene sets comparable in quality to those curated by humans.llm2genesetalso identifies biological processes represented by input gene sets, outperforming traditional ORA and direct LLM prompting. Applying the framework to RNA-seq data from iPSC-derived microglia treated with a TREM2 agonist highlights its potential for flexible, context-aware gene set generation and improved interpretation of high-throughput biological data.llm2genesetis available as open source athttps://github.com/Alector-BIO/llm2genesetand via a web interface athttps://llm2geneset.streamlit.app.
Mu and beta power effects of fast response trait double dissociate during precue and movement execution in the sensorimotor cortex
Authors: Kamali Sara , Baroni Fabiano , Varona Pablo 
Published: November 2024

AbstractA better understanding of the neural and muscular mechanisms underlying motor responses is essential for advancing neurorehabilitation protocols, brain-computer interfaces (BCI), feature engineering for biosignal classification algorithms, and identifying biomarkers of disease and performance enhancement strategies. In this study, we examined the neuromuscular dynamics of healthy individuals during a sequential finger-pinching task, focusing on the relationships between cortical oscillations and muscle activity in simultaneous electroencephalography (EEG) and electromyography (EMG) recordings. We contrasted two pairs of subsets of the dataset based on the latency of EMG onset: an across-subjects trait-based comparison and a within-subjects state-based comparison. Trait-based analyses showed that fast responders had higher baseline beta power, indicating stronger motor inhibition and efficient resetting of motor networks, and greater mu desynchronization during movement, reflecting enhanced motor cortex activation. Visual association areas also displayed more pronounced changes in different phases of the task in subjects with lower latency. Fast responders exhibited lower baseline EMG activity and stronger EMG power during movement initiation, showing effective motor inhibition and rapid muscle activation. State-based analyses revealed no significant EEG differences between fast and slow trials, while EMG differences were only detected after movement onset. These results highlight that fast response trait is related to electro-physiological differences at specific frequency bands and task phases, offering insights for enhancing motor function in rehabilitation, biomarker identification and BCI applications.HighlightsWe analyzed simultaneous EEG and EMG recordings during a sequential finger movement taskWe identified neural correlates of response latency trait, but not stateFast responders show higher baseline beta power, indicating stronger motor inhibitionLower latency trait was linked to a sharper postcue sensorimotor mu power decreaseFast responders have lower pre-movement EMG and higher EMG onset power
Regulating of Koisio technology-produced fluid on Vascular Adventitial Interstitial Fluid flow and its Effect on heart rate by delivering Esmolol
Authors: Li Bei , Cai Jin , Ma Chao , Hu Jun , Li Hongyi 
Published: November 2024

AbstractAcupoint-originated interstitial fluid (ISF) circulatory network along the vasculature has been demonstrated to play a role as an extravascular drug delivery pathway. We aim to reveal the regulation of Koisio technology-produced fluid (KF), which is rich in Ultra-small Particle Size Nanobubbles (UsNBs), on vascular adventitial ISF flow and its Effect on heart rate by delivering Esmolol. In animal experiments, using real-time fluorescent imaging technology, it was found that: when normal saline-fluorescent liquid was given at Kunlun acupoint, the velocity of the adventitial ISF along the femoral vein was measured to be about 600 μm/sec, and the width of the tunica ISF channel on the adventitia surface of the femoral vein was about 210μm; when KF-fluorescent liquid was injected into the subcutaneous tissue of Kunlun acupoint, the velocity of the adventitia ISF slowed down by about 24% compared with before; the width of the tunica ISF channel on the adventitia surface of the femoral vein increased by about 35% compared with before; When 150μL of KF with high-concentration UsNBs was injected into Kunlun acupoint, it was observed that the adventitial ISF flow velocity was decreased by 43%, and recovered after 30 minutes. Administration of normal saline-esmolol solution at Kunlun acupoint caused the heart rate to drop from 410 bpm to 380 bpm, a decrease of 7.3%, which continued for 5 minutes before recovery. Administration of KF-esmolol solution at Kunlun acupoint caused the heart rate to drop from 410 bpm to 371 bpm, a decrease of 9.5%, which continued for 15 minutes before recovery. Thus, acupoint injection of KF can regulate the velocity of the adventitia ISF flow along the femoral vein and increase the width of the tunica ISF channel. These results may reveal a new mechanism of the physiological effect of Koisio drinking water rich in ultra-small particle size nanobubbles. KF may not only regulate the acupoint-originated ISF circulatory system, but also play a role in adventitial drug delivery, nutrient supply, and waste removal.
Poplar: A Phylogenetics Pipeline
Authors: Koning Elizabeth , Krishnakumar Raga 
Published: November 2024

AbstractMotivationGenerating phylogenetic trees from genomic data is essential in understanding biological systems. Each step of this complex process has received extensive attention in the literature, and has been significantly streamlined over the years. Given the volume of publicly available genetic data, obtaining genomes for a wide selection of known species is straightforward. However, analyzing that same data in order to generate a phylogenetic tree is a multi-step process with legitimate scientific and technical challenges, and often requires a significant input from a domain-area scientist.ResultsWe present Poplar, a new, streamlined computational pipeline, to address the computational logistical issues that arise when constructing phylogenetic trees. It provides a framework that runs state-of-the-art software for essential steps in the phylogenetic pipeline, beginning from a genome with or without an annotation, and resulting in a species tree. Running Poplar requires no external databases. In the execution, it enables parallelism for execution for clusters and cloud computing. The trees generated by Poplar match closely with state-of-the-art published trees. The usage and performance of Poplar is far simpler and quicker than manually running a phylogenetic pipeline.Availability and ImplementationFreely available on GitHub athttps://github.com/sandialabs/poplar. Implemented using Python and supported on Linux.Supplementary InformationNewick versions of the reference and generated trees.
Sulfur-species in Zinc-specific Condylar Zones of a Rat Temporomandibular Joint
Authors: Lee Brandon H. , Yang Zhiyuan , Ho Tiffany , Wang Yongmei , Tamura Nobumichi , Webb Samuel , Bone Sharon , Ho Sunita P. 
Published: November 2024

ABSTRACTIn this study, we performed synchrotron-based micro-X-ray fluorescence (μ-XRF) imaging of elements Zn and S, and X-ray absorption near edge spectroscopy (XANES) coupled with μ-XRF for identification of Zn and S species in the condylar zones of a rat temporomandibular joint (TMJ). Histologic localization of Zn and hypoxia-inducible factor-1α (HIF-1α) were mapped using an optical microscope. These data were visually correlated with μ-XRF and XANES data to provide insights into plausible biological S-species in Z-enriched condylar zones of a rat TMJ. Furthermore, μ-XRF coupled with micro-X-ray diffraction (μ-XRD) was used to underline Z-incorporated biological apatite in the subchondral bone and bone of the rat TMJ.Results illustrated the potential dependence between biometal Zn and nonmetal S and their collective governance of cell and tissue functions in a zone-specific manner. Elemental Zn with organic and inorganic S-species at the cartilage-bone interface and transformation of plausible Zn-enriched mineralization kinetics of biological apatite from subchondral bone to condylar bone were ascertained using μ-XRF-XANES and μ-XRD. The coupled μ-XRF-XANES complementing with μ-XRD and immunohistology provided an informative view of S and Zn and their association with zone-specific biological pathwaysin situ. Understanding the spatial distributions of the main S-species with redox-inert Zn in regions of cartilage, bone, and the interface is essential for further unlocking questions surrounding formation and resorption-related biomineralization pathways as related to osteoarthritis or genetically inherited diseases. Using these complementary techniques with microspectroscopic spatial information provided insights into the associations between biometal Zn and nonmetal S and a window into detecting the plausible early-stage diagnostic biomarkers for humans with TMJ osteoarthritis.
Protein-protein interaction is a major source of epistasis in genetic interaction networks
Authors: Castellanos-Girouard Xavier , Serohijos Adrian WR , Michnick Stephen W 
Published: November 2024

AbstractGenetic interaction (GI) and protein-protein interaction (PPI) networks have proved among the most important tools for inference of gene function and genotype-phenotype relationship1–6. It remains unclear, however, how these two networks are related to each other. Here we demonstrate that the strengths of epistatic genetic interactions between two genes strongly correlate with the binding free energies of interactions between their cognate proteins, for both yeast and human genomes. Consequently, we show that GI and PPI networks can reciprocally predict each other. Further, we observe that functional divergence and redundancy in duplicated genes (paralogs) are reflected in the binding affinity of their interactions with other proteins and in their genetic interaction strengths. Finally, we demonstrate that the overall topologies of GI and PPI networks significantly overlap in two topological features: Modules, in which genes/proteins are organized by common function, and connectors, which link modules to each other. This opens avenues for new integrated network approaches in understanding cellular processes and flow of genomic information.