bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the role of Large Language Models (LLMs) in hematology: a systematic review of applications, benefits, and limitations
Authors: Mudrik Aya , Nadkarni Girish N , Efros Orly , Glicksberg Benjamin S , Klang Eyal , Soffer Shelly 
Published: April 2024

ABSTRACTRationale and ObjectivesLarge Language Models (LLMs) have the potential to enhance medical training, education, and diagnosis. However, since these models were not originally designed for medical purposes, there are concerns regarding their reliability and safety in clinical settings. This review systematically assesses the utility, advantages, and potential risks of employing LLMs in the field of hematology.Materials and MethodsWe searched PubMed, Web of Science, and Scopus databases for original publications on LLMs application in hematology. We limited the search to articles published in English from December 01 2022 to March 25, 2024, coinciding with the introduction of ChatGPT. To evaluate the risk of bias, we used the adapted version of the Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2).ResultsEleven studies fulfilled the eligibility criteria. The studies varied in their goals and methods, covering medical education, diagnosis, and clinical practice. GPT-3.5 and GPT-4’s demonstrated superior performance in diagnostic tasks and medical information propagation compared to other models like Google’s Bard (currently called Gemini). GPT-4 demonstrated particularly high accuracy in tasks such as interpreting hematology cases and diagnosing hemoglobinopathy, with performance metrics of 76% diagnostic accuracy and 88% accuracy in identifying normal blood cells. However, the study also revealed discrepancies in model consistency and the accuracy of provided references, indicating variability in their reliability.ConclusionWhile LLMs present significant opportunities for advancing clinical hematology, their incorporation into medical practice requires careful evaluation of their benefits and limitations.
Programmes evaluated after teaching infection prevention and control training in health or social care settings: A mapping review
Authors: Brainard Julii , Swindells Isabel Catalina , Hammer Charlotte Christiane , Hornsey Emilio 
Published: April 2024

AbstractObjectiveTo provide an overview of country settings, study designs, pathogens, response stage, outcomes and monitoring periods that were described in studies that may provide evidence about effectiveness of training in infection prevention and control programmes, for health or social care workers.MethodsA systematic review was undertaken to find and summarise aspects of relevant studies published from 2000-2023. Eligible studies had to have pre and post evaluation or post-intervention evaluation in case of trials only. Eligible outcomes were knowledge; adherence/compliance; skills or practice; incidence; case-related mortality. Eligible infectious diseases were those caused by any single cell biological entity (eg virus or protozoa) where vectors were not the primary transmission pathway. Infection prevention settings had to be health/social care (not community or environmental), and participants had to be health or social care staff or trainee staff. Articles from three bibliographic databases were dual-screened independently and key data were extracted and verified. Findings are summarised quantitatively and narratively.FindingsIncluded studies numbered 210, of which 187 were pre-post study design and 23 had concurrent comparator arms. Most studies (n=128) were undertaken in high income country settings, especially in the USA (n=31), and 47 were in European Union member countries. There were 20 studies based in China, and 5 in India. Frequency of phases were preparedness (n=47), readiness (n=29), response (n=146), and recovery (n=4). The most commonly mentioned pathogens were SARS-CoV-2 (n=73) and anti-microbial-resistant organisms (AMROs, n=54). Most settings were health care centres but long-term care facilities (n=13) and healthcare delivered by emergency responders (3) were also mentioned. Dental professionals or students were in just 3 studies and 10 studies had trainee health professionals as participants.ConclusionThe research questions for which the most evidence is likely to exist about effectiveness of IPC training of health care workers would be in response phase in high income countries, especially if the relevant pathogens were AMROs or SARS-CoV-2. In contrast, the prospects are not good for finding evidence that could deliver confident conclusions about optimal IPC training programmes in low income countries, for most specific diseases (eg. cholera or tuberculosis) or in non-response phases.
Cryo-EM captures the coordination of long-range allostery and asymmetric electron transfer by a bi-copper cluster in the nitrogenase-like DPOR complex
Authors: Kashyap Rajnandani , Deveryshetty Jaigeeth , Walsh Natalie , Tokmina-Lukaszewska Monika , Bothner Brian , Bennett Brian , Antony Edwin 
Published: April 2024

AbstractEnzymes that catalyze long-range electron transfer reactions are often structurally evolved to possess two symmetrical halves. The functional advantages and mechanistic principles for such architecture remain a mystery. Using Cryo-EM we capture snapshots of the nitrogenase-like Dark-operative Protochlorophyllide Oxidoreductase (DPOR) enzyme during substrate recognition and turnover. The structures reveal that asymmetry is enforced upon substrate binding and leads to an allosteric inhibition of protein-protein interactions and electron transfer in one half. Residues that form a conduit for electron transfer are aligned in one half while misaligned in the other. An ATP-turnover coupled switch is triggered once electron transfer is accomplished in one half and relayed through a bi-copper cluster at the oligomeric interface, leading to activation of enzymatic events in the other. The findings provide a mechanistic blueprint for regulation of asymmetric long-range electron transfer.One-Sentence SummaryA bi-copper cluster coordinates electron transfer for substrate reduction in the nitrogenase-like DPOR enzyme and the structures reveal how allostery and asymmetry are enacted over 100Å and utilized for sequential electron transfer.
Dimer-monomer transition defines a hyper-thermostable peptidoglycan hydrolase mined from bacterial proteome by lysin-derived antimicrobial peptide-primed screening
Authors: Zhang Li , Hu Fen , Zhao Zirong , Li Xinfeng , Zhong Mingyue , He Jiajun , Yao Fangfang , Zhang Xiaomei , Mao Yuxuan , Wei Hongping , He Jin , Yang Hang 
Published: April 2024

AbstractPhage-derived peptidoglycan hydrolases (i.e., lysins) are considered promising alternatives to conventional antibiotics due to their direct peptidoglycan degradation activity and low risk of resistance development. The discovery of these enzymes is often hampered by the limited availability of phage genomes. Herein, we report a new strategy to mine active peptidoglycan hydrolases from bacterial proteomes by lysin-derived antimicrobial peptide-primed screening. As a proof-of-concept, fivepeptidoglycanhydrolases from theAcinetobacterbaumanniiproteome (PHAb7-PHAb11) were identified using PlyF307 lysin-derived peptide as a template. Among them, PHAb10 and PHAb11 showed potent bactericidal activity against multiple pathogens even after treatment at 100°C for 1 hour, while the other three were thermosensitive. We solved the crystal structures of PHAb8, PHAb10, and PHAb11 and unveiled that hyper-thermostable PHAb10 underwent a unique folding-refolding thermodynamic scheme mediated by a dimer-monomer transition, while thermosensitive PHAb8 formed a monomer. Two mouse models of bacterial infection further demonstrated the safety and efficacy of PHAb10. In conclusion, our antimicrobial peptide-primed strategy provides new clues for the discovery of promising antimicrobial drugs.
RBC-GEM: a Knowledge Base for Systems Biology of Human Red Blood Cell Metabolism
Authors: Haiman Zachary B. , D’Alessandro Angelo , Palsson Bernhard O. 
Published: April 2024

AbstractAdvancements with cost-effective, high-throughput omics technologies have had a transformative effect on both fundamental and translational research in the medical sciences. These advancements have facilitated a departure from the traditional view of human red blood cells (RBCs) as mere carriers of hemoglobin, devoid of significant biological complexity. Over the past decade, proteomic analyses have identified a growing number of different proteins present within RBCs, enabling systems biology analysis of their physiological functions. Here, we introduce RBC-GEM, the most extensive and meticulously curated metabolic reconstruction of a specific human cell type to-date. It was developed through meta-analysis of proteomic data from 28 studies published over the past two decades resulting in a RBC proteome composed of more than 4,600 distinct proteins. Through workflow-guided manual curation, we have compiled the metabolic reactions carried out by this proteome. RBC-GEM is hosted on a version-controlled GitHub repository, ensuring adherence to the standardized protocols for metabolic reconstruction quality control and data stewardship principles. This reconstruction of the RBC metabolic network is a knowledge base consisting of 718 genes encoding proteins acting on 1,590 unique metabolites through 2,554 biochemical reactions: a 700% size expansion over its predecessor. This reconstruction as an up-to-date curated knowledge base can be used for contextualization of data and for the construction of a computational whole-cell model of a human RBC.Author SummaryHuman red blood cells (RBCs) have been studied for decades because of their unique physiology, essential oxygen delivery functions, and general accessibility. RBCs are the simplest yet most numerous of human cell types due to the loss of cellular organelles during their development process. This process has evolved to maximize hemoglobin content per cell to facilitate RBCs’ main function in gas transport. RBCs are integral to a variety of medical applications, such as blood storage for transfusion. Recent advancements in high-throughput data collection have greatly expanded our understanding of RBC metabolism, highlighting important roles and functions for RBCs in maintaining homeostasis in the organism in addition to oxygen transport. Here we provide a knowledge base for the human RBC as a genome-scale metabolic reconstruction. Our results highlight the complexity of RBC metabolism, supported by recent advancements in high-throughput data collection methods for detecting low-abundance proteins in RBCs. We make knowledge about the RBC findable, accessible, interoperable, and reusable (FAIR). As RBC research is likely to see many translational medical advancements, a knowledge base for the contextualization of RBC data will serve as an essential resource for further research and medical application development.
P53 Orchestrates Cancer Metabolism: Unveiling Strategies to Reverse the Warburg Effect
Authors: Abukwaik Roba , Vera-Siguenza Elias , Tennant Daniel , Spill Fabian 
Published: April 2024

AbstractCancer cells exhibit significant alterations in their metabolism, characterised by a reduction in oxidative phosphorylation (OXPHOS) and an increased reliance on glycolysis, even in the presence of oxygen. This metabolic shift, known as the Warburg effect, is pivotal in fuelling cancer’s uncontrolled growth, invasion, and therapeutic resistance. While dysregulation of many genes contributes to this metabolic shift, the tumour suppressor gene p53 emerges as a master player. Yet, the molecular mechanisms remain elusive. This study introduces a comprehensive mathematical model, integrating essential p53 targets, offering insights into how p53 orchestrates its targets to redirect cancer metabolism towards an OXPHOS-dominant state. Simulation outcomes align closely with experimental data comparing glucose metabolism in colon cancer cells with wild-type and mutated p53. Additionally, our findings reveal the dynamic capability of elevated p53 activation to fully reverse the Warburg effect, highlighting the significance of its activity levels not just in triggering apoptosis (programmed cell death) post-chemotherapy but also in modifying the metabolic pathways implicated in treatment resistance. In scenarios of p53 mutations, our analysis suggests targeting glycolysis-instigating signalling pathways as an alternative strategy, whereas targeting solely synthesis of cytochrome c oxidase 2 (SCO2) does support mitochondrial respiration but may not effectively suppress the glycolysis pathway, potentially boosting the energy production and cancer cell viability.
Single-cell data reveal heterogeneity of resource allocation across a bacterial population
Authors: Pavlou Antrea , Cinquemani Eugenio , Pinel Corinne , Giordano Nils , Van Melle-Gateau Mathilde , Mihalcescu Irina , Geiselmann Johannes , de Jong Hidde 
Published: April 2024

AbstractRibosomes are responsible for the synthesis of proteins, the major component of cellular biomass. Classical experiments have established a linear relationship between the fraction of resources invested in ribosomal proteins and the rate of balanced growth of a microbial population. We extended the study of ribosomal resource allocation from populations to single cells, using a combination of time-lapse fluorescence microscopy and statistical inference. We found a large variability of ribosome concentrations and growth rates in conditions of balanced growth of the model bacterium Escherichia coli. Moreover, the ribosome concentrations and growth rates of individual cells are uncorrelated, contrary to what would be expected from the population-level growth law. A similar large heterogeneity was found during the transition of the bacteria from a poor to a rich growth medium. Whereas some cells immediately adapt ribosomal resource allocation to the new environment, others do so only gradually. Our results thus reveal distinct strategies for investing resources in the molecular machines at the heart of cellular self-replication. This raises the interesting question whether the observed variability is an intrinsic consequence of the stochastic nature of the underlying biochemical processes or whether it improves the fitness of Escherichia coli in its natural environment.
An inflection point in high-throughput proteomics with Orbitrap Astral: analysis of biofluids, cells, and tissues
Authors: Hendricks Nathan G. , Bhosale Santosh D. , Keoseyan Angel J. , Ortiz Josselin , Stotland Aleksandr , Seyedmohammad Saeed , Nguyen Chi D. L. , Bui Jonathan , Moradian Annie , Mockus Susan M. , Van Eyk Jennifer E 
Published: April 2024

AbstractThis technical note presents a comprehensive proteomics workflow for the new combination of Orbitrap and Astral mass analyzers across biofluids, cells, and tissues. Central to our workflow is the integration of Adaptive Focused Acoustics (AFA) technology for cells and tissue lysis, to ensure robust and reproducible sample preparation in a high-throughput manner. Furthermore, we automated the detergent-compatible single-pot, solid-phase-enhanced sample Preparation (SP3) method for protein digestion, a technique that streamlines the process by combining purification and digestion steps, thereby reducing sample loss and improving efficiency. The synergy of these advanced methodologies facilitates a robust and high-throughput approach for cells and tissue analysis, an important consideration in translational research. This work disseminates our platform workflow, analyzes the effectiveness, demonstrates reproducibility of the results, and highlights the potential of these technologies in biomarker discovery and disease pathology. For cells and tissues (heart, liver, lung, and intestine) proteomics analysis by data-independent acquisition mode, identifications exceeding 10,000 proteins can be achieved with a 24-minute active gradient. In 200ng injections of HeLa digest across multiple gradients, an average of more than 80% of proteins have a CV less than 20%, and a 45-minute run covers ∼90% of the expressed proteome. In plasma samples including naive, depleted, perchloric acid precipitated, and Seer nanoparticle captured, all with a 24-minute gradient length, we identified 87, 108, 96 and 137 out of 216 FDA approved circulating protein biomarkers, respectively. This complete workflow allows for large swaths of the proteome to be identified and is compatible across diverse sample types.Graphical abstract created with biorender.com
Single-Cell Transcriptomics Reveals the Molecular Logic Underlying Ca2+Signaling Diversity in Human and Mouse Brain
Authors: Al Rayyes Ibrahim , Louhivuori Lauri , Ellström Ivar Dehnisch , Smedler Erik , Uhlén Per 
Published: April 2024

AbstractThe calcium ion (Ca2+) is a ubiquitous intracellular signaling molecule that plays a critical role in the adult and developing brain. However, the principles governing the specificity of Ca2+signaling remain unresolved. In this work, we comprehensively analyzed the Ca2+signaling transcriptome in the adult mouse brain and developing human brain. We found that neurons form non-stochastic Ca2+-states that are reflective of their cell types and functionality, with evidence suggesting that the diversity is driven by lineage-specific developmental changes. Focusing on the neocortical development, we reveal that an unprecedented number of Ca2+genes are tightly regulated and evolutionarily conserved, capturing functionally driven differences within radial glia and neuronal progenitors. In summary, our study provides an in-depth understanding of the cellular and temporal diversity of Ca2+signaling and suggests that Ca2+signaling is dynamically tailored to specific cell states.One Sentence SummaryThe expression of Ca2+signaling genes is finely tuned to cellular states, reflecting a spectrum of differences that range from lineage specificity to subtle functional distinctions within cortical radial glia.
The forgotten wine: understanding the ecology and composition of palm wine fermentation
Authors: Sumerta I Nyoman , Ruan Xinwei , Howell Kate 
Published: April 2024

AbstractPalm wine is an alcoholic beverage that has existed for centuries and has important economic and socio-culture values in many tropical and sub-tropical countries. Lesser known than other types of wines, palm wine is made by spontaneous fermentation of palm sap by naturally occurring microbial communities. The palm sap ecosystem has unique microbial composition and diversity, which determines the composition of the eventual wine and is likely affected by geographical distinctiveness. While these features are well understood in grape and rice wine, these features have not been understood in palm wine. In this review, we gather information of microbial communities and metabolite profiles from published studies, covering a wide range of methodologies and regions, to better understand the causal links between the principal microbial species and major metabolites of palm wine. We assess palm wine quality across production regions and local practices to provide general characteristics of palm wine and identify specific regional information. These will provide better understandings to the function of microbial communities and metabolite diversity, the contribution of regional variations and to ensure product quality in this important and widespread, yet overlooked, fermented beverage.One sentence summaryreview and synthesis of microbial ecology and metabolites in palm wine fermentation across geography and their contribution to cultural food systems
A programmable seeker RNA guides target selection by IS1111and IS110type insertion sequences
Authors: Siddiquee Rezwan , Pong Carol H. , Hall Ruth M. , Ataide Sandro F. 
Published: April 2024

SUMMARYIS1111and IS110insertion sequence (IS) family members encode an unusual DEDD transposase type and exhibit specific target site selection. The IS1111group include identifiable subterminal inverted repeats (sTIR) not found in the IS110type [1]. IS in both families include a noncoding region (NCR) of significant length and, as each individual IS or group of closely related IS selects a different site, we had previously proposed that an NCR-derived RNA was involved in target selection [2]. Here, we found that the NCR is usually downstream of the transposase gene in IS1111family IS and upstream in the IS110type. Four IS1111and one IS110family members that target different sequences were used to demonstrate that the NCR determines a short seeker RNA (seekRNA) that co-purified with the transposase. The seekRNA was essential for transposition of the IS or a cargo flanked by IS ends from and to the preferred target. Short sequences matching both top and bottom strands of the target were identified in the seekRNA but their order in IS1111and IS110family IS was reversed. Reprogramming the seekRNA and donor flank to target a different site was demonstrated, indicating future biotechnological potential for these systems.
Interplay of hierarchical dynamics and their microscopic structures of polyampholyte gels and proteins
Authors: Zhao Yi Hui , Muthukumar Murugappan , Jia Di 
Published: April 2024

AbstractPolyampholyte gel is a perfect physics model to mimic condensed state of proteins. We have studied the hierarchical dynamics of polyampholyte gels by dynamic light scattering. In addition to the normal gel mode, which indicates the gel elasticity, we also discovered a new mode with a stretched exponential decay with the stretched exponent β = 1/3, and a diffusive exponential decay, which indicates the coupled motion between counterion and the polyampholyte backbone. After dialysis to low salt concentration, the coupled motion of the counterion will go away, so that there are only two modes. Combined with a newly developed theory, we attribute this stretched exponential mode to hierarchical dynamics of the segments between two crosslinking junctions, whose segmental distribution obeys Poisson distribution. As salt concentration inside the gel increases, β decreases from 0.38 to 0.33, which is consistent with theoretical results. The gel with the molar charge ratio R=1, which is at the charge balance point, has the highest value β = 0.38. As long as R deviates further away from the charge balance point from either side, the β values decrease. When the gel is 100% positive charged, their dynamic light scattering results will go back to that of the normal polyelectrolyte gels.