bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment and partner notification outcomes for clients diagnosed with chlamydia and gonorrhea through GetCheckedOnline compared to sexually transmitted infection clinics in British Columbia, Canada
Authors: Zamanpour Arina , Grennan Troy , Ablona Aidan , Fairley Christopher K. , Estcourt Claudia , Mema Silvina , Hoyano Dee , Ogilvie Gina , Wong Jason , Gilbert Mark 
Published: November 2022

ABSTRACT

Background
Whether treatment, engagement in partner notification (PN), and PN outcomes differ between clients of internet-based and clinic-based testing services is poorly understood. We compared these outcomes between people diagnosed with chlamydia and/or gonorrhea (CT/GC) through a sexually transmitted infection (STI) clinic service and GetCheckedOnline GCO), an internet based testing service in British Columbia (BC).

Methods
We conducted a retrospective matched cohort study among CT/GC cases where each case diagnosed through GCO in 2016-2017 was matched to two STI clinic cases by diagnosis, gender, age group, and specimen collection date. Data was collected through chart review with outcomes compared using appropriate statistical tests.

Results
Of 257 GCO and 514 matched clinic cases, case treatment was high and did not differ between GCO (254/257, 98.9%) and clinic (513/514, 99.8%) cases, as was engagement in partner notification (250/257 (97.2%) vs. 496/514 (96.5%)). There was no difference in the proportion of notified partners between GCO (159/270, 58.9%) and clinic cases (253/435, 58.2%) although a greater proportion of partners reported by clinic cases were notified by STI nurses (43/435, 9.9%) vs. GCO cases (6/270, 2.2%).

Conclusions
GCO clients diagnosed with CT/GC demonstrated similar treatment uptake and engagement in PN to clinic clients, and PN outcomes did not differ. The greater reliance on STI clinic nurses for partner notification among clinic clients may be related to having had an initial in-person testing visit.
Is Liver Transplant Justified at Any MELD Score?
Authors: Oden-Brunson Hannah , McDonald Malcolm F. , Godfrey Elizabeth , Keeling Stephanie S. , Cholankeril George , Kanwal Fasiha , O’Mahony Christine , Goss John , Rana Abbas 
Published: November 2022

Background.
Assessing the survival benefit of transplantation in patients with end-stage liver disease is critical in guiding the decision-making process for liver allocation. Previous studies established increased mortality risk for those transplanted below Model for End-Stage Liver Disease (MELD) 18 compared with candidates who remained on the waitlist; however, improved outcomes of liver transplantation and a changing landscape in the donor supply warrant re-evaluation of this idea.

Methods.
Using the United Network for Organ Sharing database, we analyzed 160 290 candidates who were waitlisted for liver transplantation within MELD cohorts. We compared patients who were transplanted in a MELD cohort with those listed but not transplanted in that listed MELD cohort with an intent-to-treat analysis.

Results.
Those transplanted at a MELD between 6 and 11 showed a 31% reduction in adjusted mortality (HR = 0.69 [95% confidence interval [CI], 0.66-0.75]; P < 0.001) compared with the intent-to-treat cohort in a Cox multivariate regression. This mortality benefit increased to a 37% adjusted reduction for those transplanted at MELD between 12 and 14 (HR = 0.63 [95% CI, 0.60-0.66]; P < 0.001) and a 46% adjusted reduction for those transplanted at a MELD between 15 and 17 (HR = 0.54 [95% CI, 0.52-0.57]; P < 0.001), effects that remained in sensitivity analyses excluding patients with hepatocellular carcinoma, encephalopathy, ascites, and variceal bleeds. A multivariate analysis of patients transplanted at MELD < 18 found younger age and cold ischemia time were protective, whereas older age, lower functional status, and socioeconomic factors increased mortality risk.

Conclusions.
These findings challenge the current practice of deferring liver transplants below a particular MELD score by demonstrating survival benefits for most transplant patients at the lowest MELD scores and providing insight into who benefits within these subgroups.
Clinical Impact of Spontaneous Portosystemic Shunts in Liver Transplantation: A Comprehensive Assessment Through Total Shunt Area Measurement
Authors: Centonze Leonardo , Gorga Giovanna , De Carlis Riccardo , Bernasconi Davide , Lauterio Andrea , Carbonaro Luca , Vella Ivan , Sgrazzutti Cristiano , Incarbone Niccolò , Rizzetto Francesco , Valsecchi Maria Grazia , Vanzulli Angelo , De Carlis Luciano 
Published: November 2022

Background.
The impact of spontaneous portosystemic shunts (SPSSs) on natural history of cirrhotic patients was recently evaluated through the measurement of total shunt area (TSA), a novel tool that allows a comprehensive assessment of SPSSs extension, identifying a direct correlation of higher TSA with lower patient survival. The role of SPSSs in liver transplant (LT) is still debated: we sought to investigate the clinical impact of TSA on the development of early allograft dysfunction (EAD), acute kidney injury (AKI), postoperative complications, and graft and patient survival following LT.

Methods.
Preoperative imaging of 346 cirrhotic patients undergoing primary LT between 2015 and 2020 were retrospectively revised, recording the size and anatomy of each SPSS to calculate TSA. The impact of TSA and selected patient and donor characteristics on the development of EAD, AKI, and clinically relevant complications was evaluated through univariate and multivariate logistic regression, whereas their effect on graft and patient survival was investigated through Cox regression analysis.

Results.
A TSA exceeding 78.54 mm2 resulted as an independent risk factor for the development of EAD (odds ratio [OR]: 2.327; P = 0.003), grade 3 AKI (OR: 2.093; P = 0.041), and clinically relevant complications (OR: 1.962; P = 0.015). Moreover, higher TSA was significantly related to early graft and patient survivals, emerging as an independent risk factor for 12-mo graft loss (hazard ratio: 3.877; P = 0.007) and patient death (hazard ratio: 2.682; P = 0.018).

Conclusions.
Higher TSA emerged as a significant risk factor for worse postoperative outcomes following LT, supporting the need for careful hemodynamic assessment and management of patients presenting multiple/larger shunts.
Protective Effects of Ursodeoxycholic Acid Against Oxidative Stress and Neuroinflammation Through Mitogen-Activated Protein Kinases Pathway in MPTP-Induced Parkinson Disease
Authors: Jiang Chenggong , Shen Dongfang , Li Kaiyang , Wang Huan , Sang Wenxu , Qi Huiping 
Published: November 2022

Objectives
Parkinson disease (PD) is the second most common neurodegenerative disorder, and no disease-modifying medications are available. Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage; however, the effect of UDCA on PD is unclear. This study aimed to the role of UDCA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced mouse model of PD.

Methods
Mice were divided into 3 experimental groups: the control group, MPTP group, and UDCA-treat group. Mice were tested for behavioral impairments, and slices at the level of the ventral midbrain were collected to perform hematoxylin and eosin and terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling staining and immunohistochemistry. To evaluate the levels of dopamine (DA), serotonin (5-HT), antioxidant markers, and inflammatory cytokines, enzyme-linked immunoassays were carried out. The protein (α-synuclein, p38, phospho-p38, c-Jun N-terminal kinase [JNK], and phospho-JNK) expression was examined adopting Western blot.

Results
We found that UDCA reduced the MPTP-induced degeneration of DA neurons, improved behavioral impairments, and decreased the protein level of α-synuclein, accompanied with increases of DA and 5-HT. In the present study, UDCA prevented DA neurons from MPTP toxicity with increased superoxide dismutase, catalase, glutathione, and decreased malondialdehyde levels. Ursodeoxycholic acid prevented DA neurons from MPTP toxicity with decreased levels of tumor necrosis factor α, interferon γ, and interleukin (IL)-1β, IL-6, and IL-10. Our results demonstrated that UDCA inhibited the phosphorylation of JNK and p38MAPK.

Conclusions
This study revealed protective effects of UDCA against oxidative stress and neuroinflammation through mitogen-activated protein kinases pathways in MPTP-induced PD, suggesting that UDCA may be a novel therapeutic candidate for PD.
Efficacy of Valproic Acid Against Coronavirus Disease 2019 Infection or Severity: A Pilot Study
Authors: Farazdaghi Mohsen , Razavizadegan Seyed Mohammad Ali , Moghimi Mahnoosh , Asadi-Pooya Ali A. 
Published: November 2022

Objectives
The purpose of the current study was to investigate whether taking valproic acid (VPA) was protective against coronavirus disease 2019 (COVID-19) infection or severity in patients with epilepsy.

Methods
This was a questionnaire study of 150 people who were taking VPA in monotherapy or polytherapy (since the start of the pandemic or longer) and also 150 people who were not taking VPA (since the start of the pandemic), registered in our epilepsy database. The data compared rates of the seropositivity and severity of infection of COVID-19 between the 2 groups. The latter was assessed, by proxy, vis-à-vis rates of hospital admission and intensive care unit admission.

Results
Two hundred forty-one patients were studied, including 130 (53.9%) male and 111 (46.1%) female patients. The mean age of the patients was 30.7 ± 11.4 years. The infection rate and severity of COVID-19 did not significantly differ among patients who were taking VPA and those who were not taking VPA (P = 0.587) and (P = 0.648), respectively.

Conclusions
In this pilot study, no support was found for the hypothesis of a protective effect of VPA against the infectivity rate of COVID-19. Neither was there any indication of a disease-modulating effect of VPA in people with active COVID-19 infection. Larger, randomized controlled trials would be warranted to substantiate our conclusion.
GlioMod: Spatiotemporal-Aware Glioblastoma Multiforme Tumor Growth Modeling with Deep Encoder-Decoder Networks
Authors: Jain Rishab K. , Gupta Abhinav , Ali Wael H. , Lermusiaux Pierre F. J. 
Published: November 2022

AbstractGlioblastoma multiforme is an aggressive brain tumor with the lowest survival rate of any human cancer due to its invasive growth dynamics. These dynamics result in recurrent tumor pockets hidden from medical imaging, which standard radio-treatment and surgical margins fail to cover. Mathematical modeling of tumor growth via partial differential equations (PDE) is well-known; however, it remains unincorporated in clinical practice due to prolonged run-times, inter-patient anatomical variation, and initial conditions that ignore a patient’s current tumor. This study proposes a glioblastoma multiforme tumor evolution model, GlioMod, that aims to learn spatiotemporal features of tumor concentration and brain geometry for personalized therapeutic planning. A dataset of 6,000 synthetic tumors is generated from real patient anatomies using PDE-based modeling. Our model employs image-to-image regression using a novel encoder-decoder architecture to predict tumor concentration at future states. GlioMod is tested in its simulation of forward tumor growth and reconstruction of patient anatomy on 900 pairs of unseen brain geometries against their corresponding PDE-solved future tumor concentrations. We demonstrate that spatiotemporal context achieved via neural modeling yields tumor evolution predictions personalized to patients and still generalizable to unseen anatomies. Its performance is measured in three areas: (1) regression error rates, (2) quantitative and qualitative tissue agreement, and (3) run-time compared to state-of-the-art numerical solvers. The results demonstrate that GlioMod can predict tumor growth with high accuracy, being 2 orders of magnitude faster and therefore suitable for clinical use. GlioMod is provided as an open-source software package, which includes the synthetic tumor data generated from the patients in our study.
The Blood-Brain Barrier in Bipolar Disorders: A Systematic Review
Authors: Alonso Clara Wakonigg , McElhatton Frances , O’Mahony Brian , Pollak Thomas , Stokes Paul R.A. 
Published: November 2022

AbstractBackgroundBipolar disorders (BD) are chronic, debilitating disorders. Our understanding of the pathogenesis and functional biomarkers in BD remains limited. The blood-brain barrier (BBB), a highly selective, protective physical barrier which separates the central nervous system from the peripheral circulation, has been increasingly investigated in the BD. This systematic review aimed to assess the relationship between BD and markers of BBB dysfunction.MethodsStudies were identified in PubMed and Medline databases in January 2021. Articles were limited to full-length peer-reviewed journal publications with no date restrictions. Included studies compared blood, CSF, post-mortem, genetic and imaging measures of BBB function in people with BD compared to healthy controls.Results49 studies were identified, 34 of which found an association between BD and markers of BBB dysfunction. Blood QAlb, S100B and MMP levels were found to be increased in BD participants compared to controls in 57% of the studies. In post-mortem BD studies, ICAM, neurexin, claudin-5, and chondroitin sulphate proteoglycans were increased in the anterior cingulate cortex (ACC), prefrontal grey matter, occipital cortex and cerebellum, and lateral nucleus of the entorhinal cortex respectively compared to controls. Additionally, a study of BBB leakage measured by MRI found that nearly 30% of BD participants had extensive BBB leakage compared to controls. The mood state of BD participants was also associated with markers of BBB dysfunction, with participants experiencing mania generally having increased BBB marker levels compared to participants who were depressed or in remission.ConclusionsThis review suggests an association between BD and markers of BBB dysfunction. Further research is needed to control for a number of confounding factors, and to clarify whether this association provides a pathogenic mechanism, or is an epiphenomenon of BD.
Sodium channel endocytosis drives axon initial segment plasticity
Authors: Fréal Amélie , Jamann Nora , Bos Jolijn Ten , Jansen Jacqueline , Petersen Naomi , Ligthart Thijmen , Hoogenraad Casper C. , Kole Maarten H. P. 
Published: November 2022

AbstractActivity-dependent plasticity of the axon initial segment (AIS) endows neurons with the ability to adapt action potential output to changes in network activity. Action potential initiation at the AIS highly depends on the clustering of voltage-gated sodium channels, however the molecular mechanisms regulating their plasticity remain largely unknown. Here, we used novel genetic tools to endogenously label sodium channels and their scaffolding protein, to reveal their nanoscale organization and longitudinally image AIS plasticity in hippocampal neurons, in slices and primary cultures. We find that induction of NMDA receptor-mediated long-term synaptic depression is linked to a rapid and local endocytosis of sodium channels from the distal AIS. These data reveal a novel fundamental mechanism for rapid activity-dependent AIS reorganization sharing conserved features with synaptic plasticity.
Genetic manipulation of stress-induced mitogen-activated protein kinase modulates early stages of the nodulation process inMedicago sativa
Authors: Hlaváčková Kateřina , Šamajová Olga , Hrbáčková Miroslava , Šamaj Jozef , Ovečka Miroslav 
Published: November 2022

AbstractLeguminous plants have established a mutualistic endosymbiotic interaction with nitrogen-fixing rhizobia to secure nitrogen sources in new specialized organs called root nodules. Before nodule formation, the development of early symbiotic structures is essential for rhizobia docking, internalization, targeted delivery, and intracellular accommodation. We have recently reported that overexpression of stress-induced mitogen-activated protein kinase (SIMK) in alfalfa affects root hair, nodule and shoot formation. However, detailed subcellular spatial distribution, activation, and developmental relocation of SIMK during the early stages of alfalfa nodulation remain unclear. Here, we qualitatively and quantitatively characterized SIMK distribution patterns in rhizobium-infected root hairs using live-cell imaging and immunolocalization, employing alfalfa stable transgenic lines with genetically manipulated SIMK abundance and kinase activity. In theSIMKK-RNAiline, showing downregulation ofSIMKKandSIMK, we found a considerably decreased accumulation of phosphorylated SIMK around infection pockets and infection threads, which was strongly increased in the GFP-SIMK line, constitutively overexpressing GFP-tagged SIMK. Thus, genetically manipulated SIMK modulates root hair capacity to form infection pockets and infection threads. These results shed new light on SIMK spatio-temporal participation in the early interactions between alfalfa and rhizobia, and its internalization into root hairs, showing that local accumulation of active SIMK indeed modulates nodulation in alfalfa.One sentence summaryGenetic manipulation of SIMK in alfalfa revealed that SIMK modulates root hair capacity to form infection pockets and infection threads during the early interactions between alfalfa and rhizobia.
Cytotoxic CD8+T cells target citrullinated antigens in rheumatoid arthritis
Authors: Moon Jae-Seung , Younis Shady , Ramadoss Nitya S. , Iyer Radhika , Sheth Khushboo , Sharpe Orr , Rao Navin L. , Becart Stephane , Carman Julie A. , James Eddie A. , Buckner Jane H. , Deane Kevin D. , Holers V. Michael , Goodman Susan M. , Donlin Laura T. , Davis Mark M. , Robinson William H. 
Published: November 2022

AbstractThe immune mechanisms that mediate synovitis and joint destruction in rheumatoid arthritis (RA) remain poorly defined. Although increased levels of CD8+T cells have been described in RA, their role in pathogenesis remains unclear. Here we perform single cell transcriptome and T cell receptor (TCR) sequencing of CD8+T cells derived from anti-citrullinated protein antibodies (ACPA)+ RA blood. We identifyGZMB+CD8+subpopulations containing large clonal lineage expansions that express cytotoxic and tissue homing transcriptional programs, while aGZMK+CD8+memory subpopulation comprises of smaller clonal expansions that express effector T cell transcriptional programs. We demonstrate RA citrullinated autoantigens presented by MHC class I activate RA blood-derivedGZMB+CD8+T cells to expand, express cytotoxic mediators, and mediate killing of target cells. We also demonstrate that these clonally expandedGZMB+CD8+cells are present in RA synovium. These findings suggest that cytotoxic CD8+T cells targeting citrullinated antigens have a role in contributing to synovitis and joint tissue destruction in ACPA+ RA.
Identification of leaf rust resistance loci in a geographically diverse panel of wheat using genome-wide association analysis
Authors: Kaur Shivreet , Gill Harsimardeep , Breiland Matthew , Kolmer James , Gupta Rajeev , Sehgal Sunish , Gill Upinder 
Published: November 2022

AbstractLeaf rust, caused byPuccinia triticina (Pt)is among the most devastating diseases posing a significant threat to global wheat production. The continuously evolving virulentPtraces in North America calls for exploring new sources of leaf rust resistance. A diversity panel of 365 bread wheat accessions selected from a worldwide population of landraces and cultivars was evaluated at the seedling stage against fourPtraces (TDBJQ, TBBGS, MNPSD and, TNBJS). A wide distribution of seedling responses against the fourPtraces was observed. Majority of the genotypes displayed a susceptible response with only 28 (9.8%), 59 (13.5%), 45 (12.5%), and 29 (8.1%) wheat accessions exhibiting a highly resistant response to TDBJQ, TBBGS, MNPSD and, TNBJS, respectively. Further, we conducted a high-resolution multi-locus genome-wide association study (GWAS) using a set of 302,524 high-quality single nucleotide polymorphisms (SNPs). The GWAS analysis identified 27 marker-trait associations (MTAs) for leaf rust resistance on different wheat chromosomes of which 20 MTAs were found in the vicinity of knownLrgenes, MTAs, or quantitative traits loci (QTLs) identified in previous studies. The remaining seven significant MTAs identified represent genomic regions that harbor potentially novel genes for leaf rust resistance. Furthermore, the candidate gene analysis for the significant MTAs identified various genes of interest that may be involved in disease resistance. The identified resistant lines and SNPs linked to the QTLs in this study will serve as valuable resources in wheat rust resistance breeding programs.
Allele surfing causes maladaptation in a Pacific salmon of conservation concern
Authors: Rougemont Quentin , Leroy Thibault , Rondeau Eric B. , Koop Ben , Bernatchez Louis 
Published: November 2022

AbstractHow various factors, including demography, recombination or genome duplication, may impact the efficacy of natural selection and the burden of deleterious mutations,is a central question in evolutionary biology and genetics. In this study, we show that key evolutionary processes, including variations ini) effective population size (Ne)ii) recombination rates andiii) chromosome inheritance, have influenced the genetic load and efficacy of selection in Coho salmon (Oncorhynchus kisutch), a widely distributed salmonid species on the west coast of North America. Using whole genome resequencing data from 14 populations at different migratory distances from their southern glacial refugium, we found evidence supporting gene surfing, wherein reducedNeat the postglacial recolonization front, leads to a decrease in the efficacy of selection and a surf of deleterious alleles in the northernmost populations. Furthermore, our results indicate that recombination rates play a prime role in shaping the load along the genome. Additionally, we identified variation in polyploidy as a contributing factor to within-genome variation of the load. Overall, our results align remarkably well with expectations under the nearly neutral theory of molecular evolution. We discuss the fundamental and applied implications of these findings for evolutionary and conservation genomics.Author SummaryUnderstanding how historical processes, such as past glaciations, may have impacted variations in population size and genetic diversity along the genome is a fundamental question in evolution. In this study, we investigated how recent postglacial demographic expansion has affected the distribution of deleterious genetic variants and the resulting deleterious mutation load in Coho salmon (Oncorhynchus kisutch), throughout its native range in North America. By sequencing the entire genome of 71 Coho salmon, we reveal that postglacial expansion has led to allele surfing, a process where alleles increase in frequency in populations that are expanding or colonizing new environments. Here, allele surfing resulted in an increased deleterious mutation load at the colonization front. Furthermore, we demonstrated that the efficacy of natural selection scales with variation in effective population size among populations. We showed that the specific genomic features of Coho salmon, namely variation in local recombination rate and variation in chromosomal inheritance, strongly impacted the segregation of deleterious mutations.