bluuebunny/crossref_metadata_2025_split huggingface dataset:
The formation and propagation of human Robertsonian chromosomes
Authors: Gomes de Lima Leonardo , Guarracino Andrea , Koren Sergey , Potapova Tamara , McKinney Sean , Rhie Arang , Solar Steven J , Seidel Chris , Fagen Brandon , Walenz Brian P , Bouffard Gerard G , Brooks Shelise Y , Peterson Michael , Hall Kate , Crawford Juyun , Young Alice C , Pickett Brandon D , Garrison Erik , Phillippy Adam M , Gerton Jennifer L. 
Published: September 2024

AbstractRobertsonian chromosomes are a type of variant chromosome found commonly in nature. Present in one in 800 humans, these chromosomes can underlie infertility, trisomies, and increased cancer incidence. Recognized cytogenetically for more than a century, their origins have remained mysterious. Recent advances in genomics allowed us to assemble three human Robertsonian chromosomes completely. We identify a common breakpoint and epigenetic changes in centromeres that provide insight into the formation and propagation of common Robertsonian translocations. Further investigation of the assembled genomes of chimpanzee and bonobo highlights the structural features of the human genome that uniquely enable the specific crossover event that creates these chromosomes. Resolving the structure and epigenetic features of human Robertsonian chromosomes at a molecular level paves the way to understanding how chromosomal structural variation occurs more generally, and how chromosomes evolve.
Optical Control of Microtubule Accumulation and Dispersion by Tau-Derived Peptide-Fused Photo-Responsive Protein
Authors: Watari Soei , Inaba Hiroshi , Lv Qianru H , Ichikawa Muneyoshi , Iwasaki Takashi , Wang Bingxun , Tadakuma Hisashi , Kakugo Akira , Matsuura Kazunori 
Published: September 2024

ABSTRACTMicrotubules, a major component of the cytoskeleton consisting of tubulin dimers, are involved in various cellular functions, including forming axons and dendrites of neurons and retaining cell shapes by forming various accumulated superstructures such as bundles and doublets. Moreover, microtubule-accumulated structures like swarming microtubule assemblies are attractive components for dynamic materials, such as active matter and molecular robots. Thus, dynamic control of microtubule superstructures is an important topic. However, implementing stimulus-dependent control of superstructures remains challenging. This challenge can be resolved by developing designer protein approaches. We have previously developed a Tau-derived peptide (TP), which binds to the inner or outer surface of microtubules depending on the timing of the incubation. In this report, we designed the TP-fused photo-switchable protein Dronpa (TP-Dronpa) that reversibly photoconverts between monomeric and tetrameric states to photocontrol microtubule assemblies. The formation of microtubule superstructures, including bundles and doublets, was induced by tetrameric TP-Dronpa, whereas monomeric TP-Dronpa ensured that microtubules remained dispersed. Tetrameric TP-Dronpa also induced motile aster-like structures and swarming movement of microtubules on a kinesin-coated substrate. The formation/dissociation of these microtubule superstructures can be controlled by light irradiation. This system can generate and photocontrol various microtubule superstructures and provides an approach to facilitate the assembly of dynamic materials for various applications.
Bulk and selective autophagy cooperate to remodel a fungal proteome in response to changing nutrient availability
Authors: Telusma Bertina , Farre Jean-Claude , Cui Danica S. , Subramani Suresh , Davis Joseph H. 
Published: September 2024

ABSTRACTCells remodel their proteomes in response to changing environments by coordinating changes in protein synthesis and degradation. In yeast, such degradation involves both proteasomal and vacuolar activity, with a mixture of bulk and selective autophagy delivering many of the vacuolar substrates. Although these pathways are known to be generally important for such remodeling, their relative contributions have not been reported on a proteome-wide basis. To assess this, we developed a method to pulse-label the methylotrophic yeastKomagataella phaffii(i.e. Pichia pastoris) with isotopically labeled nutrients, which, when coupled to quantitative proteomics, allowed us to globally monitor protein degradation on a protein-by-protein basis following an environmental perturbation. Using genetic ablations, we found that a targeted combination of bulk and selective autophagy drove the vast majority of the observed proteome remodeling activity, with minimal non-autophagic contributions. Cytosolic proteins and protein complexes, including ribosomes, were degraded via Atg11-independent bulk autophagy, whereas proteins targeted to the peroxisome and mitochondria were primarily degraded in an Atg11-dependent manner. Notably, these degradative pathways were independently regulated by environmental cues. Taken together, our new approach greatly increases the range of known autophagic substrates and highlights the outsized impact of autophagy on proteome remodeling. Moreover, the resulting datasets, which we have packaged in an accessible online database, constitute a rich resource for identifying proteins and pathways involved in fungal proteome remodeling.
Intestinal Epithelial PTPN2 Limits Pathobiont Colonization by Immune-Directed Antimicrobial Responses
Authors: Chatterjee Pritha , Spalinger Marianne R. , Acevedo Charly , Gries Casey M. , Manz Salomon M. , Canale Vinicius , Santos Alina N. , Shawki Ali , Sayoc-Becerra Anica , Lei Hillmin , Crawford Meli’sa S. , Eckmann Lars , Borneman James , McCole Declan F. 
Published: September 2024

AbstractBackground and AimsLoss of activity of the inflammatory bowel disease (IBD) susceptibility gene, protein tyrosine phosphatase non-receptor type 2 (PTPN2), is associated with altered microbiome composition in both human subjects and mice. Further, expansion of the bacterial pathobiont, adherent- invasiveE. coli(AIEC), is strongly linked to IBD pathogenesis. The mechanism by which intestinal epithelial cells (IEC) maintain equilibrium between commensal microbiota and immune cells to restrict invading pathobionts is poorly understood. Here, we investigated the role of IEC-specific PTPN2 in regulating AIEC colonization.MethodsTamoxifen-inducible, intestinal epithelial cell-specificPtpn2knockout mice (Ptpn2ΔIEC) and controlPtpn2fl/flmice were infected with either non-invasiveE. coliK12, or fluorescent-taggedmAIEC (mAIECred) for four consecutive days or administered PBS. Subsequently, bacterial colonization in mouse tissues was quantified. mRNA and protein expression were assayed in intestinal epithelial cells (IECs) or whole tissue lysates by PCR and Western blot. Tissue cytokine expression was determined by ELISA. Intestinal barrier function was determined byin vivoadministration of 4 kDa FITC-dextran (FD4) or 70kDa Rhodamine-B dextran (RD70) fluorescent probes. Confocal microscopy was used to determine the localization of tight-junction proteins.ResultsPtpn2ΔIECmice exhibited increasedmAIECred- but not K12 - bacterial load in the distal colon compared to infectedPtpn2fl/flmice. The higher susceptibility tomAIECredinfection was associated with altered levels of antimicrobial peptide (AMPs). Ileal RNA expression of the alpha-defensin AMPs,Defa5andDefa6, as well as MMP7, was significantly lower inPtpn2ΔIECvs.Ptpn2fl/flmice, aftermAIECredbut not K12 infection. Further, we observed increased tight junction-regulated permeability determined by elevatedin vivoFD4 but not RD70 permeability inPtpn2ΔIEC-K12 mice compared to their respective controls. This effect was further exacerbated inPtpn2ΔIECmAIEC-infected mice. Further,Ptpn2ΔIECmice displayed lower IL-22, IL-6, IL-17A cytokine expression postmAIEC infection compared toPtpn2fl/flcontrols. Recombinant IL-22 reversed the FD4 permeability defect and reduced bacterial burden inPtpn2ΔIECmice postmAIEC challenge.Conclusion:Our findings highlight that intestinal epithelial PTPN2 is crucial for mucosal immunity and gut homeostasis by promoting anti-bacterial defense mechanisms involving coordinated epithelial-immune responses to restrict pathobiont colonization.
Impact of residual intimal flap displacement post-TEVAR on TBAD haemodynamics in compliant, patient-specific CFD simulations informed by MRI
Authors: Girardin Louis , Lind Niklas , von Tengg-Kobligk Hendrik , Balabani Stavroula , Díaz-Zuccarini Vanessa 
Published: September 2024

AbstractWe propose a novel formulation of a moving boundary method to account for the motion of the intimal flap (IF) in a TBAD post-thoracic endovascular aortic repair using patient-specific compliant computational fluid dynamics simulations. The simulations were informed by non-invasive 4DMRI sequences. Predicted flow waveforms, aortic wall and IF displacements were validated against in vivo 4DMRI and cine MRI data. The patient-specific simulation showed that at peak systole, the dynamic interplay between high IF displacement and high transmural pressures promoted true lumen compression and false lumen expansion, while luminal patterns were reversed at the deceleration phase. High vorticity and swirling flow patterns were observed throughout the cardiac cycle at the primary entry tear, the descending aorta and proximal to the visceral aortic branches, correlating with high relative residence time, which could indicate an increased localised risk of aortic growth proximal to the IF. A rigid IF simulation revealed significant discrepancies in haemodynamic metrics, highlighting the potential mispredictions when using a rigid wall assumption to assess disease progression. Simulations assuming a more compliant IF highlighted increased risks of visceral branches malperfusion and localised aortic wall degeneration. The study underscores the necessity of patient-specific-compliant IF simulations for accurate TBAD hemodynamic assessments. These insights can improve disease understanding and inform future treatment strategies.
Antibody response toPlasmodium vivaxin the context of Epstein-Barr virus (EBV) co-infection: A 14-year follow-up study in the Amazon rainforest
Authors: Guimarães Luiz F. F. , Rodrigues Bárbara A. , Dias Michelle H. F. , Barcelos Matheus G. , Nascimento Maria F. A. , Moreira-Nascimento Sâmick L. , Afonso Sofia L. , Abreu Barbara G. S. , Middeldorp Jaap. M. , Ntumngia Francis B. , Adams John H. , Fabbri Camila , Lopes Stefanie , Fernandes Cor J. F. , Kano Flora S. , Carvalho Luzia H. 
Published: September 2024

AbstractBackgroundTo develop an effective vaccine againstPlasmodium vivax, the most widely dispersed human malaria parasite, it is critical to understand how coinfections with other pathogens could impact malaria-specific immune response. A recent conceptual study proposed that Epstein-Barr virus (EBV), a highly prevalent human herpesvirus that establishes lifelong persistent infection, may influenceP. vivaxantibody responses. Here, it was investigated whether EBV could impact the longevity of humoral immune response toP. vivax.Methodology/principal findingsA 14-year follow-up study was carried out among long-termP. vivax-exposed Amazonian individuals (272, median age 35 years), and included 9 cross-sectional surveys at periods of high and low malaria transmission. The experimental approach focused on monitoring antibodies to the major blood-stageP. vivaxvaccine candidate, the Duffy binding protein region II (DBPII-Sal1), including a novel engineered DBPII-based vaccine targeting conserved epitopes (DEKnull-2). In parallel, the status of EBV infection was determined over time by the detection of circulating EBV DNA (EBV-DNAemia) and EBV-specific antibodies to lytic (VCAp18) or latent (EBNA1) antigens. Regardless of the malaria transmission period, the results demonstrated that one or multiple episodes of EBV-DNAemia did not influence the longevity of DBPII immune responses to both strain-specific (Sal-1) or strain-transcending (DEKnull-2) antibodies. Also, the average time in which DBPII-responders lost their antibodies was unrelated to the EBV serostatus. Considering all malaria cases detected during the study, there was a predominance ofP. vivaxmono-infection (76%), with a positive association between malaria infection and detectable EBV-DNAemia.Conclusions/significanceIn an immunocompetentP. vivax-exposed adult population neither sporadic episodes of EBV-DNAemia nor antibody responses to lytic/latent EBV antigens influence the longevity of both strain-specific and strain-transcending DBPII immune responses. Further studies should investigate the role of acuteP. vivaxinfection in the activation of EBV replication cycle.
Prevalence and Factors Associated with Puerperal Sepsis among Postnatal Women at a Tertiary Referral Hospital in Western Uganda
Authors: Nabawanuka Brenda , Asiimwe Moses , Irumba Pauline , Aryampa Julian , George Wasswa , Muhoozi Michael , Acen Joy , Amumpaire Peterson , Katusabe Shamim , Tusabe Joan , Joshua Epuitai 
Published: September 2024

AbstractBackgroundPuerperal sepsis remains one of the leading causes of maternal mortality and morbidity in Uganda.AimThis study assessed the prevalence and factors associated with puerperal sepsis among postpartum women at Fort portal Regional Referral Hospital located in western Uganda.MethodsA cross-sectional design was employed in the study. We conducted a records review of the patient files of 180 postnatal mothers who were admitted at Fort Portal Regional Referral Hospital from 20 February, 2024 to 01 April, 2024. A data abstraction checklist was used to collect data from participant files based on strict inclusion and exclusion criteria. Data was entered in Microsoft Excel and exported to STATA17 for data analysis. Descriptive analysis and logistic regression analysis were performed to determine the prevalence of puerperal sepsis and determinants. Bivariate and multivariate logistic regression analysis was conducted for significant factors presented as Adjusted Odds Ratios (aOR) atp≤0.05.ResultsThe median age of participants was 25.5 years (1QR=20-30) and the majority (77%) had primary education. The prevalence of postnatal sepsis was 24%. Duration of hospital stay [aOR=2.30; 95%CI (1.552-3.398);p=<0.001], history of antepartum hemorrhage [aOR=29.09; 95% CI (1.182-716.38);p=0.039] and Anemia [aOR=0.01; 95% CI (0.001-0.218);p=0.004] were identified as factors associated with puerperal sepsis among postnatal women upon multivariate logistic regression.ConclusionPuerperal sepsis was common in our setting. This study found that mode of delivery, duration of hospital stay, anemia, and Antepartum hemorrhage, were the determining factors contributing to puerperal sepsis, infection prevention measures during cesarean sections, and reducing the length of hospital stay would prove to be beneficial in the prevention of sepsis.
Impact of Losartan on Portal hypertension and Liver Cirrhosis: A Systematic Review
Authors: Avasthi Deepti , Avasthi Salil 
Published: September 2024

AbstractBackgroundPortal hypertension, a complication of chronic liver disease, results from elevated pressure between the portal vein and the inferior vena cava. While non-selective beta-blockers are established for reducing portal pressure, the efficacy of losartan, an angiotensin II receptor blocker, remains debated. This study evaluated losartan’s impact on portal pressure and clinical outcomes in patients with cirrhosis and portal hypertension.ObjectivesTo appraise evidence on the role of losartan in reducing portal pressure and associated clinical outcomes in cirrhotic patients with portal hypertension.MethodsA comprehensive literature search was conducted in PubMed, Cochrane Library, Medline, and Web of Science. All the research and review of literature was conducted within the time period from August 20th, 2024 till August 31st, 2024 (within 1 month of submission of the paper). The Risk of Bias Visualization Tool (Robvis 2.0) and ROBINS-I were used to assess study quality. Data was extracted and analyzed using Microsoft Excel.ResultsAmong 426 potential studies, 12 met the inclusion criteria. Both losartan and propranolol reduced hepatic venous pressure gradient (HVPG), with some studies suggesting a more pronounced effect of losartan. Meta-analysis found no significant difference in HVPG reduction (p = 0.22), but losartan significantly reduced wedged hepatic venous pressure (WHVP) compared to propranolol (p = 0.03). Losartan also affected mean arterial pressure, renal function, and hepatic fibrosis.ConclusionsLosartan shows potential in treating portal hypertension by reducing portal pressure and fibrosis. It may be particularly beneficial for patients unresponsive to beta-blockers, addressing both hemodynamic and structural components, and improving sodium handling in complex cases.
Effects of respite services on fluctuations in caregivers’ stress: A pilot study using a daily diary
Authors: Abe Koji , Kubota Wataru 
Published: September 2024

AbstractObjectivesFamily caregivers for people with dementia report daily fluctuations in stress levels. Much prior research on caregivers’ daily stress fluctuations has used a daily diary method. However, only a few studies have used this method with family caregivers to examine the effects of respite services. This study aimed to use a daily diary method to assess the effects of respite services on stress and depression in family caregivers.MethodsParticipants included 13 family caregivers of persons with dementia using respite services in rural areas of Japan. Participants completed self-administered questionnaires every day for seven days, including the use or non-use of respite services, cognitive and daily living function, depression, and stress appraisal. Generalized linear mixed models with data nested within persons were used for the analysis.ResultsFew significant effects of services were found on caregivers’ depression and stress appraisals at the between-person level. However, within-person level analyses using generalized mixed models showed that respite services significantly reduced stress appraisal.ConclusionThe findings demonstrate the stress-buffering effect of respite service for caregivers and the applicability of a daily diary method to the small sample.
Pulsed Field Ablation of Small Vessel-Related Arrhythmias: A New Catheter and Methods
Authors: Xuan Fengqi , Li Yunhao , Zhang Jie , Lin Long , Zhang Daoyang , Zhang Qi , Zhang Ping , Zhang Yujie , Ma Wei , Wang Zulu , Han Yaling , Liang Ming 
Published: September 2024

AbstractObjectivesSome arrhythmia targets are located in the epicardium or deep myocardium, which could be reached through the vascular approach. However, it is difficult to deliver ablation catheters to the distal vessels and their branches. In small vessels, the energy released is limited, and the risk of ablation is increased. The objective of this study was to design a linear catheter with pulsed field energy that is suitable for ablation in the distal vessels and to verify its efficacy and safety in canines.MethodsA total of eight canines were randomly assigned to two observation groups: a 48-hour group (N=4) and a 30-day group (N=4). A 3 F 10-pole pulsed field ablation catheter was employed to ablate in the great cardiac vein, the middle cardiac vein, the anterior interventricular vein, and the distal small branches of the cardiac venous system. The characteristics of the ablation lesions were observed both grossly and microscopically.ResultsThe surgical procedure was completed successfully. Pulsed field energy can travel through the fatty tissue to form a lesion in the cardiomyocytes. The mean depth of the lesion in the 30-day group (2.37±0.53 mm) was found to be reduced by 39% (P<0.001) in comparison to that observed in the 48-hour group (3.92±0.62 mm). Additionally, a transition zone of incomplete injury was discerned in the junction area of the 48-hour group. Canines exhibited no adverse effects intraoperatively nor postoperatively, and no appreciable damage was observed in the adjacent small arteries or the surrounding organs.ConclusionThe pulsed field energy from small blood vessels can cause lasting, continuous lesions to the myocardium and is safe to use. The 3 F liner pulsed field ablation catheter has been proven to be efficacious and safe, with promising indications for future application.
Prevalence and Determinants of Prehospital Impression of Stroke in Ischemic Stroke Patients
Authors: Caffarelli Mauro , Wood Andrew J. , Crowe Remle P , Amorim Edilberto , Kamel Hooman , Kim Anthony S. , Guterman Elan L. 
Published: September 2024

ABSTRACTBACKGROUNDEmergency Medical Services (EMS) clinicians are front-line in evaluating patients with stroke in the community. Their ability to correctly identify stroke influences downstream management decisions. We sought to use a large national database of prehospital clinical data to determine risk factors associated with missed EMS stroke identification.METHODSRetrospective study examining EMS evaluation of adults with Emergency Department (ED) stroke diagnosis. We leveraged the ESO Data Collaborative research dataset containing EHR data from 2019-2022 that has a subset of encounters with linked hospital diagnostic codes. Our primary outcome was the presence of an EMS diagnosis of stroke. We evaluated the association between demographic and clinical variables with EMS stroke identification using Pearson χ2 test for demographic variables and multivariable GLM for clinical variables with adjustment for demographic variables.RESULTSWe identified 34,504 EMS encounters for patients with ED stroke diagnosis. Of these, 11,077 (32.1%) strokes had missed EMS stroke identification and instead had an EMS impression of “Generalized Weakness” (25.9%), “Altered Level of Consciousness” (24.9%), and “Dizziness” (7.2%). Patients more likely to have missed prehospital stroke identification were of Black race (p=0.0001) and Hispanic ethnicity (p=0.0001). Clinical variables associated with higher risk of missed EMS stroke identification were suspected alcohol or drug use (RR 1.48, 95% CI 1.37-1.59), low GCS (RR 1.17, 95% CI 1.10-1.24), tachycardia (RR 1.05, 95% CI 1.01-1.09), and hypotension (RR 1.47, 95% CI 1.34-1.61).CONCLUSIONSApproximately 1-in-3 patients transported by EMS did not have their stroke identified in the prehospital setting. Factors associated with lower odds of missed EMS stroke identification provide a starting point for future performance improvement initiatives.