bluuebunny/crossref_metadata_2025_split huggingface dataset:
CORELSA - Remote stethoscope system for fast and standardized auscultations of large numbers of patients with respiratory syndromes
Authors: Ides Kris , Aerts Arne , Baeyens Rens , Balemans Niels , Bosschaerts Tom , Cazaerck Jonathan , Ceulemans David , De Mey Fons , Jansen Wouter , Kerstens Robin , Laurijssen Dennis , Lauwers Eline , Schenck Anthony , Schouten Girmi , Simon Ralph , Verellen Thomas , Verreycken Erik , Jorens Philippe , Verhulst Stijn , Daems Walter , Steckel Jan 
Published: September 2024

AbstractOne of the major impacts of the current COVID-19 pandemic is the immense strain that is being put on the intensive care units. As a typical SARS-CoV-2 infection often leads to severe acute respiratory syndromes, one of the most basic essential examinations is lung auscultation. There are different categories of lung sounds that can be assessed with a stethoscope like crackles, wheezes, rhonchi and coarse breath sounds. Each of these malicious lung sounds contribute to a clinical assessment and follow-up of the patient’s airways and lungs and can indicate the development of pneumonia. Therefore, auscultation on a regular basis is essential, but it also takes a lot of time for the physicians. Moreover, because of the risk of infection for health care workers, it is becoming increasingly difficult or sometimes impossible to safely use a stethoscope. Here we introduce a remote stethoscope system that can help to reduce the workload of physicians and nurses, diminishes the risk of contamination and leads to more standardized auscultation, which can also be stored and reevaluated. We provide a detailed description of our system, which consists of parts that are low cost, easily available in most parts of the world, or can be 3D printed. We provide instructions and an open source software stack to run such a system for a large number of patients which can be remotely auscultated from a central computer. We believe that the system described in this paper can allow various institutes to replicate the system, and increase the safety and reduce the overall workload in the intensive care units around the world.
CRISPR editing of candidate host factors that impact influenza A virus infection
Authors: Kyawe Pyae Phyo , Liu Ping , Jiang Zhaozhao , Bradley Evan S. , Cicuto Thomas , Trombly Melanie I. , Silverman Neal , Fitzgerald Katherine A. , McDougall William M. , Wang Jennifer P. 
Published: September 2024

AbstractInfluenza A virus (IAV) is a respiratory pathogen with a segmented negative-sense RNA genome that can cause epidemics and pandemics. The host factors required for the complete IAV infectious cycle have not been fully identified. Here, we examined select host factors that were identified by independent CRISPR screens as candidate contributors to IAV infectivity. We performed CRISPR-mediated knockout of cytidine monophosphate N-acetylneuraminic acid synthetase (CMAS) as well as CRISPR-mediated overexpression of beta-1,4 N-acetylgalactosaminyltransferase 2 (B4GALNT2) and adenosine deaminase acting on RNA 1 (ADAR1) in the human bronchial epithelial A549 cell line and evaluated IAV infectivity. We confirmed that the knockout ofCMASor overexpression ofB4GALNT2restricts IAV infection by diminishing binding to the cell surface but has no effect on vesicular stomatitis virus infection. While ADAR1 overexpression does not significantly inhibit IAV replication, it has a pro-viral effect with coxsackie B virus (CVB) infection. This pro-viral effect is not likely secondary to reduced type I interferon (IFN) production, as the induction of the IFN-stimulated genesISG15andCXCL10is negligible in both parent and ADAR1-overexpressing A549 cells following CVB challenge. In contrast,ISG15andCXCL10production is robust and equal for parent and ADAR1-overexpressing A549 cells challenged with IAV. Taken together, these data provide insight into how host factors identified in CRISPR screens can be further explored to understand the dynamics of pro- and anti-viral factors.ImportanceInfluenza A virus (IAV) remains a global threat due to its ability to cause pandemics, making the identification of host factors essential for developing new antiviral strategies. In this study, we utilized CRISPR-based techniques to investigate host factors identified in screens as reducing IAV infectivity. Knockout of CMAS, a key enzyme in sialic acid biosynthesis, significantly reduced IAV binding and infection by disrupting sialic acid production on the cell surface. Overexpression of B4GALNT2 had similar effects, conferring resistance to IAV infection through diminished cell-surface binding. While overexpression of ADAR1, known for its role in RNA editing and immune regulation, slightly reduced IAV replication, it increased coxsackie B virus replication. Such findings reveal the diverse roles of host factors in viral infection, offering insights for targeted therapeutic development against IAV and other pathogens.
Abrogation of presynaptic facilitation at hippocampal mossy fiber synapses impacts neural ensemble activity and spatial memory
Authors: Marneffe Catherine , Grosjean Noelle , Nicolay-Kritter Kyrian , Chatras Cécile , Harrell Evan R. , Kees Ashley , Mulle Christophe 
Published: September 2024

AbstractPresynaptic short-term plasticity is thought to play a major role in the process of spike transfer within local circuits. Mossy fiber synapses between the axons of dentate gyrus (DG) granule cells and CA3 pyramidal cells (Mf-CA3 synapses) display a remarkable extent of presynaptic plasticity which endows these synaptic connections with detonator properties. The pattern of action potential firing, in the form of high frequency bursts in the DG, strongly controls the amplitude of synaptic responses and information transfer to CA3. Here we have investigated the role of presynaptic facilitation at Mf-CA3 synapses in the operation of CA3 circuitsin vivoand in memory encoding. Syt7, a calcium sensor necessary for presynaptic facilitation, was selectively abrogated, in DG granule cells using Syt7 conditional KO mice (DG Syt7 KO mice). In hippocampal slices, we extend previous analysis to show that short-term presynaptic facilitation is selectively suppressed at Mf-CA3 synapses in the absence of Syt7, without any impact on basal synaptic properties and long-term potentiation. Short-term plasticity was found to be crucial for spike transfer between the DG and CA3 in conditions of naturalistic patterns of presynaptic firing. At the network level, in awake head-fixed mice, the abrogation of short-term plasticity largely reduced the co-activity of CA3 pyramidal cells. Finally, whereas DG Syt7 KO mice are not impaired in behavioral tasks based on pattern separation, they show deficits in spatial memory tasks which rely on the process of pattern completion. These results shed new light on the role of the detonator properties of DG-CA3 synapses, and give important insights into how this key synaptic feature translate at the population and behavioral levels.
Distinct input-specific mechanisms enable presynaptic homeostatic plasticity
Authors: Chien Chun , He Kaikai , Perry Sarah , Tchitchkan Elizabeth , Han Yifu , Li Xiling , Dickman Dion 
Published: September 2024

ABSTRACTSynapses are endowed with the flexibility to change through experience, but must be sufficiently stable to last a lifetime. This tension is illustrated at theDrosophilaneuromuscular junction (NMJ), where two motor inputs that differ in structural and functional properties co-innervate most muscles to coordinate locomotion. To stabilize NMJ activity, motor neurons augment neurotransmitter release following diminished postsynaptic glutamate receptor functionality, termedpresynaptichomeostaticpotentiation (PHP). How these distinct inputs contribute to PHP plasticity remains enigmatic. We have used a botulinum neurotoxin to selectively silence each input and resolve their roles in PHP, demonstrating that PHP is input-specific: Chronic (genetic) PHP selectively targets the tonic MN-Ib, where active zone remodeling enhances Ca2+influx to promote increased glutamate release. In contrast, acute (pharmacological) PHP selectively increases vesicle pools to potentiate phasic MN-Is. Thus, distinct homeostatic modulations in active zone nanoarchitecture, vesicle pools, and Ca2+influx collaborate to enable input-specific PHP expression.
A Novel Maxillofacial Technology for Drug Administration-A Randomized Controlled Trial Using Metronidazole
Authors: Ramachandran Sajani , Kandasamy Ravichandran , Verma Kavita , Murugan Jayahshri , Sudhakar Jishnu , Adiyeri Janardhanan Hridwik , Anoop U.R 
Published: September 2024

AbstractAimTo compare the efficacy of a novel maxillofacial drug delivery technology with that of oral administration by analyzing the presence of administered metronidazole in plasma.Material & MethodsThe patients reporting to the Dental outpatient department with acute pulpitis in relation to maxillary molar were examined and recruited for the study. All consenting patients fulfilling the inclusion criteria during the study period were included.The selected patients were randomly divided into two groups using computer generated sequence of random numbers.Group I: In the control group patients, a single dose of 400 mg of metronidazole in the form of a tablet was administered through the oral route, after biomechanical preparation of root canals.Group II: In the experimental group patients, 5mg of metronidazole in the form of an infusion solution was administered into the pulp cavity of a maxillary molar using the maxillofacial route and technology, after biomechanical preparation of root canals.The blood samples were collected at 15 minutes and 30 minutes after administration of metronidazole. The plasma samples were then analysed for the presence of metronidazole using high performance liquid chromatography (HPLC).ResultsOut of ten, 5 (50%) samples in the oral route group and all 9 (100%) samples in the maxillofacial route group had the presence of the drug (p = 0.033). There was no statistically significant difference in presence of the drug between 15 minutes and 30 minutes in the oral route (p = 1.0) and in the maxillofacial route (p = 0.687). Further, the mean value of the area under the HPLC curve after 15 minutes was found to be similar in both the groups (p = 0.4). At 30 minutes also the area under the HPLC curve between the groups was not statistically significant (p = 0.156)ConclusionThe maxillofacial drug delivery technique can be an effective alternate route for painless and controlled drug delivery.
In-hospital stay of anemic patients (70-90 g.L-1) in the ED with/without transfusion: a single-center propensity-matched study
Authors: Coisy Fabien , Anselme Clémence , Goulabchand Radjiv , Grau-Mercier Laura , Markarian Thibaut , Bobbia Xavier , Genre-Grandpierre Romain 
Published: September 2024

AbstractBackground and importanceA quarter of patients presenting to the emergency department (ED) have anemia. Although red blood cell (RBC) transfusion is routinely used in symptomatic anemia, there is no evidence on the benefit of blood transfusion in hemodynamically stable patients in the ED for patients requiring hospitalization.ObjectiveThe study aimed to compare in-hospital length of stay (LOS) of patients with anemia between 70 and 90 g.L-1transfused or not in ED.DesignRetrospective single-center studySettings and participantsAll adult patients admitted to the ED of our university hospital with an initial hemoglobin level between 70 and 90 g.L-1, without hemorrhagic shock, who were hospitalized after ED admission.Outcome measures and analysisA propensity score, comprising hemoglobin level, Charlson’s comorbidity index, clinical signs of anemia, the chronicity of anemia and hospitalization department was used to compare the LOS of patients transfused versus non-transfused in the ED.InterventionRBC transfusion in the EDMain resultsFrom January 1st to December 31st, 2022, 1 169 patients were screened of whom 569 (49%) were excluded, mostly due to discharge without hospitalization. The remaining 564 (48%) patients had a median age of 77 [68; 85] and 240 (43%) were women. Finally, 127 (23%) patients were transfused in ED. Transfused patients received more units of RBC during the whole hospitalization period (4 [3; 5] versus 2 [1; 3] than non-transfused patients (p< 0.01)). After propensity score matching, median LOS was 9 [5; 19] days for ED transfused patients and 8 [5; 15] days for non-ED transfused patients (median difference= -1 95% CI [-3; 2]; p=0.45).ConclusionIn patients with non-life-threatening anemia, RBC transfusion in the ED does not appear to reduce in-hospital LOS compared with transfusion in inpatient departments. Further studies are needed to identify patients requiring transfusion in ED.
Computed tomography radiomics-based cross-sectional detection of mandibular osteoradionecrosis in head and neck cancer survivors
Authors:   MD Anderson Head and Neck Cancer Symptom Working Group, Kamel Serageldin , Humbert-Vidan Laia , Kaffey Zaphanlene , Abusaif Abdulrahman , Fuentes David T. A. , Wahid Kareem , Dede Cem , Naser Mohamed A. , He Renjie , Moawad Ahmed W. , Elsayes Khaled M. , Chen Melissa M. , Otun Adegbenga O. , Rigert Jillian , Chambers Mark , Hope Andrew , Watson Erin , Brock Kristy K. , Hutcheson Katherine , van Dijk Lisanne , Moreno Amy C. , Lai Stephen Y. , Fuller Clifton D. , Mohamed Abdallah S. R. 
Published: September 2024

AbstractPurposeThis study aims to identify radiomic features extracted from contrast-enhanced CT scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in patients with head and neck cancer (HNC) treated with radiotherapy (RT).Materials and MethodsContrast-enhanced CT (CECT) images were collected for 150 patients (80% train, 20% test) with confirmed ORN diagnosis at The University of Texas MD Anderson Cancer Center between 2008 and 2018. Using PyRadiomics, radiomic features were extracted from manually segmented ORN regions and the corresponding automated control regions, the later defined as the contralateral healthy mandible region. A subset of pre-selected features was obtained based on correlation analysis (r > 0.95) and used to train a Random Forest (RF) classifier with Recursive Feature Elimination. Model explainability SHapley Additive exPlanations (SHAP) analysis was performed on the 20 most important features identified by the trained RF classifier.ResultsFrom a total of 1316 radiomic features extracted, 810 features were excluded due to high collinearity. From a set of 506 pre-selected radiomic features, the optimal subset resulting on the best discriminative accuracy of the RF classifier consisted of 67 features. The RF classifier was well calibrated (Log Loss 0.296, ECE 0.125) and achieved an accuracy of 88% and a ROC AUC of 0.96. The SHAP analysis revealed that higher values of Wavelet-LLH First-order Mean and Median were associated with ORN of the jaw (ORNJ). Conversely, higher Exponential GLDM Dependence Entropy and lower Square First-order Kurtosis were more characteristic of normal mandibular tissue.ConclusionThis study successfully developed a CECT-based radiomics model for differentiating ORNJ from healthy mandibular tissue in HNC patients after RT. Future work will focus on the detection of subclinical ORNJ regions to guide earlier interventions.
Exploiting the Achilles’ Heel of Viral RNA Processing to Develop Novel Antivirals
Authors: Amiri Ali Zahedi , Ahmed Choudhary , Dahal Subha , Grosso Filomena , Leng Haomin , Stoilov Peter , Mangos Maria , Toutant Johanne , Shkreta Lulzim , Attisano Liliana , Chabot Benoit , Brown Martha , Huesca Mario , Cochrane Alan 
Published: September 2024

AbstractViruses continue to pose a significant health burden to the human population, and recent history has shown a concerning surge in viral threats. Treatment options for viral infections are limited, and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Many viruses depend on the host cell’s RNA splicing machinery, and small alterations to this host process results in catastrophic changes in viral protein production, ultimately inhibiting virus replication. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression. In this report, we document 5342191 as a potent inhibitor of adenovirus, coronavirus, and influenza replication. In each case, 5342191-mediated reduction in virus replication was associated with altered viral RNA accumulation and loss of viral structural protein expression. Interestingly, while resistant viruses were rapidly isolated for compounds targeting either virus-encoded proteases or polymerases, we have not yet isolated 534219-resistant variants of coronavirus or influenza. As with HIV-1, 5342191’s inhibition of coronaviruses and influenza is mediated through the activation of specific cell signaling networks, including GPCR and/or MAPK signaling pathways that ultimately affect SR kinase expression. Together, these studies highlight the therapeutic potential of compounds that target cellular processes essential for the replication of multiple viruses. Not only do these compounds hold promise as broad-spectrum antivirals, but they also offer the potential of greater resilience in combating viral infections.
Molecular mechanisms of uric acid transport by the native human URAT1 and its inhibition by anti-gout drugs
Authors: Wu Canrong , Zhang Chao , Jin Sanshan , Wang James Jiqi , Dai Antao , Xu Jiuyin , Zhang Heng , Yang Xuemei , He Xinheng , Yuan Qingning , Hu Wen , Xu Youwei , Wang Mingwei , Jiang Yi , Yang Dehua , Xu H. Eric 
Published: September 2024

AbstractGout, a common and painful disease, stems from hyperuricemia, where elevated blood uric acid levels lead to urate crystal formation in joints and kidneys. The human urate transporter 1 (hURAT1) plays a critical role in urate homeostasis by facilitating urate reabsorption in the renal proximal tubule, making it a key target for gout therapy. Pharmacological inhibition of hURAT1 with drugs such as dotinurad, benzbromarone, lesinurad, and verinurad promotes uric acid excretion and alleviates gout symptoms. Here we present cryo-electron microscopy structures of native hURAT1 bound with these anti-gout drugs in the inward-open state, and with uric acid in inward-open, outward-open, and occluded states. Complemented by mutagenesis and cell-based assays, these structures reveal the mechanisms of uric acid reabsorption and hURAT1 inhibition. Our findings elucidate the molecular basis of uric acid transport and anti-gout medication action, and provide a structural framework for the rational design of next-generation therapies for hyperuricemia and gout.
A conserved hub protein for coordinating peptidoglycan turnover that activates cell division amidases inAcinetobacter baumannii
Authors: Simpson Brent W. , McLean Amanda B. , Trent M. Stephen 
Published: September 2024

AbstractGram-negative bacteria produce a multilayered cell envelope in which their peptidoglycan is sandwiched between two membranes, an inner membrane made of glycerophospholipids and an asymmetric outer membrane with glycerophospholipids in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet. TheAcinetobacter baumanniiouter membrane contains lipooligosaccharide (LOS), a variant of LPS lacking O-antigen. LPS/LOS is typically essential, butA. baumanniican survive without LOS. Previously, we found that the peptidoglycan biogenesis protein NlpD becomes essential during LOS-deficiency. NlpD is typically redundant and is one of the cell’s amidase activators for regulating peptidoglycan degradation, a process critical for cell division. We found that NlpD is essential under these conditions because a second putative amidase activator, termed WthA (cellwall turnoverhub proteinA), no longer functions in LOS-deficient cells. Mutants lacking WthA had severe cell division defects and were synthetically sick with loss of NlpD. BothAcinetobacterWthA and NlpD were found to activate an amidase activity of Oxa51, a chromosomally encodedβ-lactamase. Further, WthA is homologous toPseudomonasLbcA that impacts two other classes of peptidoglycan degradation enzymes, endopeptidases and lytic transglycosylases. WthA/LbcA homologs were identified across Proteobacteria, Bacteroidota, and Chlorobiota, suggesting they belong to a conserved family involved in regulation of peptidoglycan turnover. WhileAcinetobacterWthA may share functions ofPseudomonasLbcA, we found no evidence that LbcA is an amidase activator. Altogether, we have identified a missing player inAcinetobacterpeptidoglycan biogenesis, a conserved hub protein that regulates multiple peptidoglycan turnover enzymes including cell division amidases.Significance StatementPeptidoglycan is a rigid layer that provides structural support to bacterial cells. Peptidoglycan must be degraded to make room for new synthesis and for cells to divide, a process termed turnover. Turnover enzymes are tightly regulated to prevent their activities from lysing the cell. The critical pathogenAcinetobacter baumanniiwas missing known peptidoglycan amidases, a class of turnover enzymes, and the key activator that controls their activity during cell division. We have identified WthA as having a role in cell division most likely as an amidase activator. WthA homologs were widely distributed in bacteria and the closely related LbcA inPseudomonasimpacts two other types of turnover enzymes. We explore the possible functions of this new family of proteins that serves as a hub for impacting peptidoglycan turnover.
Influenza A virus exploits the motility of membrane cytoskeletal actomyosin filaments for its genome packaging in the host cell
Authors: Wang I-Hsuan , Usukura Jiro , Miyake Yasuyuki , Usukura Eiji , Narita Akihiro , Yamauchi Yohei , Kawaoka Yoshihiro 
Published: September 2024

AbstractInfluenza A virus encodes its genome in eight segments of viral ribonucleoproteins (vRNPs) replicated in the host cell nucleus. Our understanding of host factors involved in driving vRNP selective packaging remains incomplete. To address this, we used advanced immuno-freeze-etch electron microscopy to visualise the vRNP packaging process and atomic force live-cell imaging (AFM) to examine the motility of membrane cytoskeletal actin filaments. In the cytoplasm, vRNPs were mainly localised on mottled membrane-like structures, suggesting intracellular trafficking through such structures. After reaching the cytoplasmic side surface of the plasma membrane, vRNPs formed many aggregates while associating with actin filaments. Antibody labelling also detected myosin along actin filaments entangled in vRNPs. Blocking myosin activity with blebbistatin prevented the active movement of membrane cytoskeletal actin filaments just below the plasma membrane visualised by AFM and abrogated proper aggregation of vRNPs. Thus, actomyosin motility appears to be crucial for the selective packaging of vRNPs.