bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV
Authors: Coburn Sally B. , Pimentel Noel , Leyden Wendy , Kitahata Mari M. , Moore Richard D. , Althoff Keri N. , Gill M. John , Lang Raynell , Horberg Michael A. , D'Souza GypsyAmber , Hussain Shehnaz K. , Dubrow Robert , Novak Richard M. , Rabkin Charles S. , Park Lesley S. , Sterling Timothy R. , Neugebauer Romain S. , Silverberg Michael J. ,   for the North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS
Published: April 2024

Background:
The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.

Setting:
A cohort study of 36,322 PWH enrolled (1996–2014) in the North American AIDS Cohort Collaboration on Research and Design.

Methods:
We followed individuals from ART initiation (protease inhibitor [PI]-based, nonnucleoside reverse transcriptase inhibitor [NNRTI]-based, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, December 31, 2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (nonmutually exclusive) as follows: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials.

Results:
We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up), and 1782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85-month follow-up indicated no cancer risk differences. In truncated analyses, the risk of ADCs (aHR 1.33; 95% CI: 1.00, 1.77 [PP analysis]) and NADCs (aHR 1.23; 95% CI: 1.00 to 1.51 [ITT analysis]) was higher comparing PIs vs. NNRTIs.

Conclusions:
Results with longer-term follow-up suggest being on a PI-based versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with a longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk.
MORTALITY AND ASSOCIATED FACTORS AMONG INTENSIVE CARE UNIT ADMITTED ADULT PATIENTS WITH MECHANICAL VENTILATION IN ETHIOPIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Alamaw Addis Wondmagegn , Abebe Gebremeskel Kibret , Abate Biruk Beletew , Tilahun Befkad Derese , Yilak Gizachew , Birara Wagaw Abebe , Azmeraw Molla , Habtie Tesfaye Engdaw , Zemariam Alemu Birara 
Published: April 2024

ABSTRACT

Introduction: The global demand for intensive care has risen, given its effectiveness in lowering mortality rates. Mechanical ventilation (MV) is integral to intensive care but introduces risks such as ventilator-associated complications. Ethiopia experiences a high intensive care unit (ICU) mortality rate. Objective: This systematic review and meta-analysis aim to comprehensively synthesize evidence on the mortality of adults undergoing MV in Ethiopia and identify associated factors. Methods: The study extensively searched databases and gray literature for research on MV outcomes, trends, and associated factors in adult ICUs. Adhering to the 2020 PRISMA checklist, a systematic review and meta-analysis sought to establish the mortality rate and key determinants among adult ICU patients on MV. The search incorporated keywords and MeSH terms, excluding studies with unsound methodologies or missing data. Data extraction, quality assessment, and analysis followed established protocols, including the JBI tool for methodological quality evaluation. STATA version 17.0 facilitated analysis, assessing heterogeneity, publication bias, and performing sensitivity and meta-regression analyses. Results: The pooled mortality rate among adult ICU patients undergoing MV was 48.61% (95% CI: 40.82, 56.40%). Significant mortality-contributing factors included medical diagnosis, Glasgow Coma Scale score, sepsis/septic shock, sedation use, multiple-organ dysfunction syndrome, and cardiovascular disease. Although some pooled odds ratios seemed insignificant, closer examination revealed significant associations in individual studies. Conclusion: The study underscores the urgent need for further research, improved ICU infrastructure, and healthcare personnel training in Ethiopia to enhance outcomes for mechanically ventilated patients. Identified factors offer valuable insights for targeted interventions, guiding tailored treatment strategies to reduce mortality. This study contributes to understanding mortality and associated factors in MV patients, informing initiatives to improve critical care outcomes in Ethiopia.
CIRCVMA21-RELATED PATHWAY ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HK-2 CELL INJURY
Authors: Li Fuzhu , Fu Hongyun , Zeng Linna , Liu Pingping 
Published: April 2024

ABSTRACT

Background: It is reported that circVMA21 has an inhibition effect on sepsis-induced acute kidney injury (AKI). Therefore, the underlying molecular mechanisms of circVMA21 in AKI are worthy of further investigation. Material and Methods: Lipopolysaccharide (LPS) was used to induce HK2 cell injury. CircVMA21, miR-337-3p and ZEB2 expression was tested by qRT-PCR. Cell growth was detected by CCK8 assay, EdU assay, and flow cytometry. Protein levels were examined by western blot. The levels of inflammatory factors and oxidative stress markers were measured to evaluate cell inflammatory response and oxidative stress. RNA relationship as verified by dual-luciferase reporter assay, RIP assay, and RNA pull-down assay. Results: CircVMA21 had decreased expression in AKI patients. Overexpressed circVMA21 alleviated LPS-induced HK2 cell inflammation, apoptosis, and oxidative stress. Moreover, circVMA21 sponged miR-337-3p, and miR-337-3p targeted ZEB2. The inhibitory effect of circVMA21 on LPS-induced HK2 cell injury was reversed by miR-337-3p overexpression, and ZEB2 overexpression abolished the promotion effect of miR-337-3p on LPS-induced HK2 cell injury. Conclusions: CircVMA21 could inhibit LPS-induced HK2 cell injury via miR-337-3p/ZEB2 axis.
DEVELOPMENT AND VALIDATION OF A MODEL FOR PREDICTION OF SEPTIC SHOCK IN NEONATES WITH SEPSIS
Authors: Liu Chunmei , Wang Yanggan 
Published: April 2024

ABSTRACT

Purpose: This study aimed to develop and validate a model for prediction of septic shock in neonates with sepsis. Materials and methods: This retrospective study included early-onset septic neonates in the Renmin Hospital of Wuhan University between January 2017 and June 2021. The neonates were divided into the training set and the validation set in a ratio of 7:3 and further categorized into septic shock group and none-shock group according to presence or absence of shock symptoms. Results: A total of 406 septic neonates were enrolled, including 217 in septic shock group. Sex (odds ratio [OR] = 0.092, 95% confidence interval [CI]: 0.012 to 0.683, P = 0.020), C-reactive protein at 6 h (OR = 8.475, 95% CI: 3.154 to 22.774, P < 0.001), serum amyloid A at 6 h (OR = 1.179, 95% CI: 1.094 to 1.269, P < 0.01), white blood cells at 6 h (OR = 0.173, 95% CI: 0.092 to 0.326, P < 0.001), platelets at 6 h (OR = 0.985, 95% CI: 0.975 to 0.995, P < 0.001), and Ca2+ at 6 h (OR = 1.44 × 1011, 95% CI: 2.70 × 106 to 7.70 × 1015, P < 0.001) were identified as independent risk factors for septic shock and were further included in the nomogram. The areas under the receiver operator characteristic curve were 0.873 and 0.920 in training and validation sets, respectively. Conclusions: A predictive model for early diagnosis of septic shock in neonates was developed and initially validated in this study, allowing for timely intervention.
Somatostatin Versus Octreotide for Prevention of Postoperative Pancreatic Fistula: The PREFIPS Randomized Clinical Trial
Authors: Gaujoux Sébastien , Regimbeau Jean-Marc , Piessen Guillaume , Truant Stéphanie , Foissac Frantz , Barbier Louise , Buc Emmanuel , Adham Mustapha , Fuks David , Deguelte Sophie , Muscari Fabrice , Sulpice Laurent , Vaillant Jean-Christophe , Schwarz Lilian , Sa Cunha Antonio , Muzzolini Milena , Dousset Bertrand , Sauvanet Alain ,   Collaborators
Published: April 2024

Objective:
Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment.

Methods:
Multicentric randomized controlled open study in patient’s candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 μg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis.

Results:
Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a nondilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 days). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ2 test, P=0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.

Conclusion:
Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy.

Findings:
In the PREFIPS Randomized Clinical Trial including 651 patients, a total of 153 patients (23.5%) developed a grade B/C POPF with no significant difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ2 test, P=0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.
Large Language Models to process, analyze, and synthesize biomedical texts – a scoping review
Authors: Doneva Simona Emilova , Qin Sijing , Sick Beate , Ellendorff Tilia , Goldman Jean-Philippe , Schneider Gerold , Ineichen Benjamin Victor 
Published: April 2024

ABSTRACTThe advent of large language models (LLMs) such as BERT and, more recently, GPT, is transforming our approach of analyzing and understanding biomedical texts. To stay informed about the latest advancements in this area, there is a need for up-to-date summaries on the role of LLM in Natural Language Processing (NLP) of biomedical texts. Thus, this scoping review aims to provide a detailed overview of the current state of biomedical NLP research and its applications, with a special focus on the evolving role of LLMs. We conducted a systematic search of PubMed, EMBASE, and Google Scholar for studies and conference proceedings published from 2017 to December 19, 2023, that develop or utilize LLMs for NLP tasks in biomedicine. LLMs are being applied to a wide array of tasks in the biomedical field, including knowledge management, text mining, drug discovery, and evidence synthesis. Prominent among these tasks are text classification, relation extraction, and named entity recognition. Although BERT-based models remain prevalent, the use of GPT-based models has substantially increased since 2023.
Cross species modeling reveals a role for the unfolded protein response in shaping the transcriptional reaction toMycobacterium tuberculosisinfection
Authors: Pullen Krista M. , Finethy Ryan , Ko Seung-Hyun B. , Reames Charlotte J. , Sassetti Christopher M. , Lauffenburger Douglas A. 
Published: April 2024

AbstractNumerous blood mRNA signatures have been developed to diagnose tuberculosis (TB) disease. The utility of these signatures in diverse populations depends on the inclusion of ubiquitously expressed features, such as type 1 interferon (IFN) production and innate immune cell activities. As a result, these signatures are generally insensitive to heterogeneous responses between individuals. Designing more effective therapies will require understanding the diverse mechanisms underlying pathogenesis by associating them with appropriate preclinical animal models. To address this critical animal-to-human gap, we applied a modeling framework, Translatable Components Regression, which is designed to account for biological heterogeneity by identifying multiple orthogonal axes of variation that are common to humans and animal models. Our framework was capable of distinguishing human active TB from latent TB infection using a model derived from murine data. This discrimination was based on differential expression of numerous biological pathways in addition to the common IFN and neutrophil signatures. Prominent among these predictive pathways was protein translation, which we show is a feature of the Mtb infection-induced Unfolded Protein Response (UPR) in macrophages. We show that this cellular stress pathway controls a variety of immune-related functions in Mtb-infected mouse macrophages, suggesting a possible causative role during the development of TB disease.Significance StatementDespite tuberculosis being one of the top causes of global mortality, the mechanisms that control the progression of disease are still not fully understand. Here we leverage a systems-level modeling approach that incorporates transcriptomics data across thousands of genes from both a traditional tuberculosis mouse model and human clinical samples to implicate a previously unappreciated mechanism in pathogenesis, the unfolded protein response. We validate these findings in a mouse macrophage model and pinpoint which branch of the unfolded protein response might be activated during tuberculosis infection. These insights, originally derived from our cross-species model, may allow us to better understand human tuberculosis pathogenesis and potentially identify therapeutic targets to prevent active tuberculosis.
Real-time visualization reveals Mycobacterium tuberculosis ESAT-6 disrupts phagosome via fibril-mediated vesiculation
Authors: Koiri Debraj , Nandi Mintu , Abik Hameem P M , Bhausaheb Aher Jayesh , Meher Geetanjali , Behura Assirbad , Kumar Akhil , Choudhary Vineet , Choubey Sandeep , Saleem Mohammed 
Published: April 2024

AbstractMycobacterium tuberculosis (Mtb)evades host defense by hijacking and rupturing the phagosome, enabling it to escape to the host cytosol for its survival. ESAT-6, a secreted virulence protein ofMtb, is known to be critical for phagosome rupture. However, the mechanism of ESAT-6-mediated disruption of the phagosomal membrane remains unknown. Usingin vitroreconstitution and numerical simulations, we discover that ESAT-6 polymerization remodels and vesiculates phagosomal membrane. In contrast to the pore formation triggered by a bilayer-spanning conformation, we find that the binding of ESAT-6 to the phagosomal membrane is shallow. Such shallow insertion leads to membrane shape transition leading to tubular and bud-like deformations on the membrane in a concentration-dependent manner, facilitated by the reduction in membrane tension and compressibility modulus. Strikingly, our observations suggest that ESAT-6 polymerizes in bulk and on the membrane, bothin vitroand in macrophage. Numerical simulations demonstrate that growing fibrils generate both radial and tangential forces causing local remodeling and shape transition of the membrane. Using micropipette aspiration, we quantitatively show that ESAT-6 bound tensed membrane undergoes local changes in membrane curvature and lipid phase separation, also facilitated by the direct contact of the bacteria inside the phagosome. Nonetheless, the vesiculation of the buds is primarily driven by the forces exerted by the polymerization of ESAT-6. Such ESAT-6 mediated vesiculation induces apoptosis and host cell death in a concentration and time-dependent manner that promotes infection. Overall, the findings provide mechanistic insights into the long-standing question of phagosome disruption byMtbfor its escape.
MetaX: A peptide centric metaproteomic data analysis platform using Operational Taxa-Functions (OTF)
Authors: Wu Qing , Ning Zhibin , Zhang Ailing , Zhang Xu , Sun Zhongzhi , Figeys Daniel 
Published: April 2024

AbstractMetaproteomics analyzes the functional dynamics of microbial communities by identifying peptides and mapping them to the most likely proteins and taxa. The challenge in this field lies in seamlessly integrating taxonomic and functional annotations to accurately represent the contributions of individual microbial taxa to functional diversity. We introduce MetaX, a comprehensive tool for analyzing taxa-function relationships in metaproteomics by mapping peptides to their lowest common ancestors and assigning functions based on proportional thresholds, ensuring accurate peptide-level mappings. Importantly, MetaX introduces the Operational Taxa-Functions (OTF), a new conceptual unit for exploring microbial roles and interactions within ecosystems. Additionally, MetaX extends traditional taxonomic classification by adding a genome level below the species level, enhancing the accuracy of function attribution to specific genomes. We demonstrated MetaX by reanalyzing metaproteomic data from gut microbiomes exposed to various sweeteners, achieving results similar to traditional protein analysis. Furthermore, using the peptide-centric approach and OTF, we observed thatParabacteroides distasonissignificantly responds to certain sweeteners, highlighting its role in modifying specific metabolic functions. With its intuitive, user-friendly interface, MetaX facilitates detailed study of the complex interactions between microbial taxa and their functions in metaproteomics. It enhances our understanding of microbial roles in ecosystems and health.
Behavioral and cortical arousal from sleep, muscimol-induced coma, and anesthesia by direct optogenetic stimulation of cortical neurons
Authors: Mao Rong , Cavelli Matias Lorenzo , Findlay Graham , Driessen Kort , Peterson Michael J , Marshall William , Tononi Giulio , Cirelli Chiara 
Published: April 2024

SummaryThe cerebral cortex is widely considered part of the neural substrate of consciousness. However, while several studies have demonstrated that stimulation of subcortical nuclei can produce EEG activation and restore consciousness, so far no direct causal evidence has been available for the cortex itself. Here we tested in mice whether optogenetic activation of cortical neurons in posterior parietal cortex (PtA) or medial prefrontal cortex (mPFC) is sufficient for arousal from three behavioral states characterized by progressively deeper unresponsiveness: sleep, a coma-like state induced by muscimol injection in the midbrain, and deep sevoflurane-dexmedetomidine anesthesia. We find that cortical stimulation always awakens the mice from both NREM sleep and REM sleep, with PtA requiring weaker/shorter light pulses than mPFC. Moreover, in most cases light pulses produce both cortical activation (decrease in low frequencies) and behavioral arousal (recovery of the righting reflex) from brainstem coma, as well as cortical activation from anesthesia. These findings provide evidence that direct activation of cortical neurons is sufficient for behavioral and/or cortical arousal from sleep, brainstem coma, and anesthesia.
Divergence in a Eukaryotic Transcription Factor’s co-TF Dependence Involves Multiple Intrinsically Disordered Regions Affecting Activation and Autoinhibition
Authors: Snyder Lindsey F. , O’Brien Emily M. , Zhao Jia , Liang Jinye , Bruce Baylee J. , Zhang Yuning , Zhu Wei , Cassier Thomas J. , Schnicker Nicholas J. , Zhou Xu , Gordân Raluca , He Bin Z. 
Published: April 2024

ABSTRACTCombinatorial control by multiple transcription factors (TFs) is a hallmark of eukaryotic gene regulation. Despite its prevalence and crucial roles in enhancing specificity and integrating information, the mechanisms behind why eukaryotic TFs depend on one another, and whether such interdependence evolves, are not well understood. We exploit natural variation in co-TF dependence in the yeast phosphate starvation (PHO) response to address this question. In the model yeastSaccharomyces cerevisiae, the main TF, Pho4, relies on the co-TF Pho2 to regulate ∼28 genes. In a related yeast pathogen,Candida glabrata, its Pho4 exhibits significantly reduced Pho2 dependence and has an expanded target set of ∼70 genes. Biochemical analyses showedC. glabrataPho4 (CgPho4) binds to the same consensus motif with 3-4-fold higher affinity than ScPho4 does. A machine-learning-based prediction and yeast one-hybrid assay identified two Intrinsically Disordered Regions (IDRs) in CgPho4 that boost the activity of the main activation domain but showed little to no activity on their own. We also found evidence for autoinhibition behind the co-TF dependence in ScPho4. An IDR in ScPho4 next to its DNA binding domain was found to act as a double-edged sword: it both allows for enhanced activity with Pho2, and inhibits Pho4’s activity without Pho2. This study provides a detailed molecular picture of how co-TF dependence is mediated and how its evolution, mainly driven by IDR divergence, can lead to significant rewiring of the regulatory network.
Linear infrastructure and associated wildlife accidents create an ecological trap for an apex predator and scavenger
Authors: Singh Navinder J , Etienne Michelle , Spong Göran , Ecke Frauke , Hörnfeldt Birger 
Published: April 2024

AbstractAnimals can be caught in an “ecological trap” when they select for seemingly attractive habitats at the expense of their fitness. Such maladaptive behaviour is often a consequence of human induced rapid changes in animals’ natal environment such as building of energy and transportation infrastructure. We tested the ecological trap hypotheses for human created linear infrastructure on a widely distributed apex predator and a scavenger – the Golden eagle (Aquila chrysaetos), whose range spans across the entire northern hemisphere. Roads and railways create novel and attractive feeding subsidies through traffic induced mortality of other species, while powerline areas provide perching or nesting sites and scavenging opportunities from electrocuted or collision-killed birds. These conditions lead to negative demographic consequences for eagles. We used integrated step selection functions for habitat selection and movement behaviour with ten years of data from 74 GPS-tracked Golden Eagles (36 adult and 38 immature) in Fennoscandia. To measure habitat attractiveness, we use wildlife traffic accident statistics on major wildlife species including the eagles, and mortality of five GPS- tracked eagles to show demographic consequences. Eagles selected for linear features all year round and across entire study region. Individuals also searched and sat alongside roads and railway lines more frequently. Immature eagles selected roads and railway sites more consistently compared to adults and showed learning behaviour with age. We discuss implications of these findings for conservation and population ecology of apex predators and scavengers and their potential evolutionary implications. We suggest that rapid removal of carcasses from roads and tracks is urgently needed to avoid this trap for many raptor and scavenger species throughout the world and develop methods and approaches to reduce wildlife traffic accidents all together.