bluuebunny/crossref_metadata_2025_split huggingface dataset:
The changing landscape of nonobstructive azoospermia
Authors: Garabed Laurianne Rita , Flannigan Ryan 
Published: November 2024

Purpose of review
This article aims to describe new developments in the field of nonobstructive azoospermia biology, diagnostics, biomarkers, and therapeutic strategies.

Recent findings
Recent studies have investigated the molecular underpinnings of cellular dysfunction that is contributing to spermatogenic dysfunction and findings suggest abnormalities across both somatic and germ cells. Biomarkers to predict the chances of sperm retrieval are being explored utilizing cell free (cf) DNA and RNA from various body fluids, in addition to a full range of transcripts and epigenetics within seminal fluid. Various approaches are being explored to optimize sperm identification from surgical specimens including microfluidic and machine learning approaches. Finally, approaches to regenerating sperm production from males with nonobstructive azoospermia are evolving to include various 3-dimensional culture techniques with integration of computational modeling.

Summary
The landscape of nonobstructive azoospermia biomarkers, molecular underpinnings, technological approaches to more reliably identify sperm and novel regenerative therapeutic strategies are likely to transform the field of male reproduction in years to come.
Does climate change threaten delivery of HIV care in resource-limited settings?
Authors: Orievulu Kingsley Stephen , Buczkowska Matylda , Iwuji Collins C. 
Published: November 2024

Purpose of review
Extreme weather events (EWEs) pose a challenge to achieving UNAIDS goal of eliminating HIV as a public health threat by 2030. This review summarizes recent findings describing the disruption of HIV services by EWEs and discusses strategies for a resilient HIV care programme in resource-limited settings.

Recent findings
EWEs impact each component of the continuum of care – HIV testing, linkage to treatment, viral suppression and other HIV prevention services. EWEs disrupt healthcare provision either through impacting the ability of the healthcare system to deliver care because of infrastructure damage and increased workload or by limiting people's ability to seek healthcare because of access challenges and forced displacements. This culminates in disengagement from care, poor treatment adherence and increase in HIV disease progression with more vulnerable groups such as women and young people being more adversely impacted.

Summary
Most people affected by or at risk of HIV reside in resource-poor settings which are the region with the least capacity to adapt to climate change. Few recent studies with very limited geographical coverage show that EWEs affect the delivery of HIV care in this setting. Climate adaptation and mitigation policies are required to protect health in resource-limited settings.
Thyroid eye disease and ocular myasthenia gravis
Authors: Shabto Julie M. , Stevens Shanlee , Kazim Michael 
Published: November 2024

Purpose of review
An overview of two ocular diseases, which significantly impact quality of life: thyroid eye disease (TED) and ocular myasthenia gravis (OMG). Additionally, we describe the clinical challenge when they occur simultaneously. We will describe the pathophysiology of both conditions, the currently available diagnostic tools, and the therapies available.

Recent findings
Recent literature has described newer diagnostic modalities, predictors of disease severity and co-occurrence of TED and OMG, and novel therapies. There is also critical analysis of current therapeutics and risk factors.

Summary
The findings from this review suggest a need for heightened clinical awareness and early detection strategies for TED and OMG due to their overlapping clinical presentation. Emerging therapies and diagnostic techniques should be integrated into practice. Further research is warranted to explore the long-term safety and efficacy of novel treatments and the potential genetic links between these conditions.
Farming practices in the landscape have an impact on grassland arthropods, in addition to local conditions and land cover
Authors: Brusse Théo , Thénard Jodie , Marrec Ronan , Caro Gaël 
Published: November 2024

AbstractArthropods deliver vital ecosystem services in agricultural landscapes, but their diversity is threatened by intensified farming and landscape simplification. Despite this, the relative impacts of farming practices at the landscape level remain underexplored compared to local and land cover effects. In this study, we dissect the influence of local and landscape factors, including farming practices, on arthropod communities. By sampling 18 grasslands in northeastern France during spring and autumn 2021, we collected 14 arthropod families, identifying all species of carabids and spiders. We conducted surveys of farming practices to estimate their intensity at landscape level. Our results highlight that environmental factors affect arthropod communities differently between seasons. Intensity of farming practices at landscape level was less explanatory of arthropod communities, but this impact is additional to that of local conditions and land cover. Our study underscores the critical need to integrate farming practices into landscape-level management strategies to safeguard arthropod diversity.
Sex Differences in Middle Cerebral Artery Reactivity and Hemodynamics Independent from Changes in Systemic Arterial Stiffness in Adult Sprague-Dawley Rats
Authors: Ray Jonathan W. , Sun Xuming , Diaz Nildris Cruz , Pulgar Victor M. , Yamaleyeva Liliya M. 
Published: November 2024

ABSTRACTYoung women are protected against cerebrovascular disease compared with men. However, the underlying mechanisms of sex differences in cerebrovascular function are not well understood. In this study, we determined whether sex differences in middle cerebral artery (MCA) reactivity are accompanied with changes in cerebral or systemic arterial resistance and stiffness in adult 25-week-old Sprague-Dawley (SD) rats. No differences in systolic or diastolic blood pressures were observed between sexes. Heart rate was higher in the female versus male SD. Left MCA pulsatility index (PI) was lower in female versus male SD, while no differences in left intracranial internal carotid artery (ICA) PI was observed between sexes. There were no differences in thoracic aorta or left common carotid artery pulse wave velocity (PWV) between sexes. In isolated MCA segments, female left MCA had lower contraction to potassium, but similar maximal contraction and sensitivity to thromboxane A2 receptor agonist U46619. Pre-incubation with indomethacin lowered maximal response and sensitivity to U46619 in male MCA but not female MCA suggesting that vasoconstrictor prostaglandins may have a greater role in male MCA vs. female MCA. Endothelial nitric oxide synthase (eNOS) and vascular smooth muscle layer thromboxane A2 receptor immunoreactivity were greater in female versus male SD. We conclude that sex differences in the MCA reactivity are associated with a differential functional profile of MCA in adult SD rats independent from changes in systemic PWV.NEW & NOTEWORTHYDespite the debilitating effects of cerebrovascular disease in women, the basis for sex differences in cerebrovascular dysfunction remains incompletely understood. Our study demonstrated that middle cerebral artery reactivity and hemodynamics are not accompanied by changes in central pulse wave velocity in mature adult Sprague-Dawley rats suggesting different mechanisms underlying baseline vascular reactivity of cerebral versus systemic arterial beds.
White matter hyperintensities and microplastics
Authors: Bearer Elaine L. , Garcia Marcus A. , Adolphi Natalie , Campen Matthew J. 
Published: November 2024

ABSTRACTSynopsisWhite matter hyperintensities are abnormalities that appear in MRI scans of living patients but are not apparent in MRI post-mortem.GoalOur goal is to understand the cellular/biological basis of white matter hyperintensities (WMH).ApproachWe aligned post-mortem MR scans with those collected ante-mortem and performed histopathology and pyrGC/MS for plastics on regions with WMH.ResultPyrGC/MS detected large amounts of plastics and we determined their cellular locations with a novel optical imaging approach in regions with small vessel disease and Abeta plaques.ImpactMicroplastics in the brains of people with cognitive impairment may be due to pre-existing vascular injury or contribute to it. Many questions remain: Where do they come from, do they impair function? Can they be diagnosed by MRI ante-mortem?
pnetr: An R package for the PnET family of forest ecosystem models
Authors: Gao Xiaojie , Zhou Zaixing , Ollinger Scott V. , Matthes Jaclyn Hatala , Jiao Wenzhe , Thompson Jonathan R. 
Published: November 2024

AbstractEcosystem models offer a rigorous way to formalize scientific theories and are critical to evaluating complex interactions among ecological and biogeochemical processes. In addition to simulation and prediction, ecosystem models are a valuable tool for testing hypotheses about mechanisms and empirical findings because they reveal critical internal processes that are difficult to observe directly.However, many ecosystem models are difficult to manage and apply by scientists who lack advanced computing skills due to complex model structures, lack of consistent documentation, and low-level programming implementation, which facilitates computing but reduces accessibility.Here, we present the ‘pnetr’ R package, which is designed to provide an easy-to-manage ecosystem modeling framework and detailed documentation in both model structure and programming. The framework implements a family of widely used PnET (net photosynthesis, evapotranspiration) ecosystem models, which are relatively parsimonious but capture essential biogeochemical cycles of water, carbon, and nutrients. We chose the R programming language since it is familiar to many ecologists and has abundant statistical modeling resources. We showcase examples of model simulations and test the effects of phenology on carbon assimilation and wood production using data measured by the Environmental Measurement Station (EMS) eddy-covariance flux tower at Harvard Forest, MA.We hope ‘pnetr’ can facilitate further development of ecological theory and increase the accessibility of ecosystem modeling and ecological forecasting.
Characterization of Soybean Vein Necrosis Virus (SVNV) Proteins: Sequence Analysis of Field Strains and Comparison of Localization Patterns in Differing Cell Types
Authors: Shehata Abdelaal H.A. , Mayfield Michael A. , Sikora Edward J. , Martin Kathleen M. 
Published: November 2024

AbstractSoybean vein necrosis virus(SVNV) is a persistent, propagative, ambisense-ssRNA virus in the genus Orthotospovirus transmitted byNehydratothrips variabilis. In this study, five open reading frames (ORFs) (N, NSs, NSm, GN, and GC) were fused in frame to GFP for use in both plant and insect cells. N and NSs localize in plants to the cell periphery and nucleus. NSm causes cell death to plant cells but not in insect cells where cytoplasmic localization is seen. GNand GCglycoproteins localize to the membranes and accumulate with more cytoplasmic localization seen in insect cells. To understand SVNV in the field, we collected 33 samples expressing symptoms of SVNV. The N, NSs, and NSm ORFs were sequenced and amino acid mutations in each gene were seen. The findings of this study capture sequence changes which have occurred over the past fifteen years compared to the localization of proteins never before conducted.
A contextual fear conditioning paradigm in head-fixed mice exploring virtual reality
Authors: Krishnan Seetha , Dong Can , Ratigan Heather , Morales-Rodriguez Denisse , Cherian Chery , Sheffield Mark 
Published: November 2024

ABSTRACTContextual fear conditioning is a classical laboratory task that tests associative memory formation and recall. Techniques such as multi-photon microscopy and holographic stimulation offer tremendous opportunities to understand the neural underpinnings of these memories. However, these techniques generally require animals to be head-fixed. There are few paradigms that test contextual fear conditioning in head-fixed mice, and none where the behavioral outcome following fear conditioning is freezing, the most common measure of fear in freely moving animals. To address this gap, we developed a contextual fear conditioning paradigm in head-fixed mice using virtual reality (VR) environments. We designed an apparatus to deliver tail shocks (unconditioned stimulus, US) while mice navigated a VR environment (conditioned stimulus, CS). The acquisition of contextual fear was tested when the mice were reintroduced to the shock-paired VR environment the following day. We tested three different variations of this paradigm and, in all of them, observed an increased conditioned fear response characterized by increased freezing behavior. This was especially prominent during the first trial in the shock-paired VR environment, compared to a neutral environment where the mice received no shocks. Our results demonstrate that head-fixed mice can be fear conditioned in VR, discriminate between a feared and neutral VR context, and display freezing as a conditioned response, similar to freely behaving animals. Furthermore, using a two-photon microscope, we imaged from large populations of hippocampal CA1 neurons before, during, and following contextual fear conditioning. Our findings reconfirmed those from the literature on freely moving animals, showing that CA1 place cells undergo remapping and show narrower place fields following fear conditioning. Our approach offers new opportunities to study the neural mechanisms underlying the formation, recall, and extinction of contextual fear memories. As the head-fixed preparation is compatible with multi-photon microscopy and holographic stimulation, it enables long-term tracking and manipulation of cells throughout distinct memory stages and provides subcellular resolution for investigating axonal, dendritic, and synaptic dynamics in real-time.
Physioxia-modulated mesenchymal stem cells secretome has higher capacity to preserve neuronal network and translation processes in hypoxic-ischemic encephalopathy in vitro model
Authors: Caramelo Inês , Anjo Sandra I. , Mendes Vera M. , Salazar Ivan L. , Dinis Alexandra , Cardoso Carla M.P. , Duarte Carlos B. , Grãos Mário , Manadas Bruno 
Published: November 2024

AbstractHypoxic-ischemic encephalopathy (HIE) is one of the leading causes of child death worldwide. Most of the survivors develop various neurological diseases, such as cerebral palsy, seizures, and/or motor and behavioral problems. HIE is caused by an episode of perinatal asphyxia, which interrupts the blood supply to the brain. Due to its high energy demands, this interruption initiates glutamate excitotoxic pathways, leading to cell death. Umbilical cord mesenchymal stem cells (UC-MSCs) are gaining attention as a promising complement to the current clinical approach, based on therapeutic hypothermia, which has shown limited efficacy. Previous data have shown that priming MSCs under physiological culture conditions, namely soft platforms (3kPa) – mechanomodulated – or physiological oxygen levels (5% O2) – physioxia – leads to changes in the cellular proteome and their secretome. To evaluate how exposing MSCs’ to these culture conditions could impact their therapeutic potential, physiologically primed UC-MSCs or their secretome were added to anin vitroHIE model using cortical neurons primary cultures subjected to oxygen and glucose deprivation (OGD) insult. By comparing the neuronal proteome of sham, OGD insulted, and OGD-treated neurons, it was possible to identify proteins whose levels were restored in the presence of UC-MSCs or their secretome. Despite the different approaches that differentially altered UC-MSCs’ proteome and secretome, the effects converged on the re-establishment of the levels of proteins involved in translation mechanisms (such as the 40S and 60s ribosomal subunits), possibly stabilizing proteostasis, which is known to be essential for neuronal recovery. Interestingly, treatment with the secretome of UC-MSC modulated under physioxic conditions sustained part of the neuronal network integrity and modulated several mitochondrial proteins, including those proteins involved in ATP production. This suggests that the unique composition of the physioxia-modulated secretome may offer a therapeutical advantage in restoring essential cellular processes that help neurons maintain their function, compared to traditionally expanded UC-MSCs. These findings suggest that both the presence of UC-MSCs and their secretome alone can influence multiple targets and signaling pathways, collectively promoting neuronal survival following an OGD insult.
Stage-Specific Transcriptome Landscape of Hepatocellular Carcinoma: Insights from Super and Poor Survivors with Prognostic Signature Identification
Authors: Xu Xiao-Qian , Wang Hao , Shi Li-Chen , Huang Cheng , You Hong , Jia Ji-Dong , He You-Wen , Kong Yuan-Yuan 
Published: November 2024

AbstractBackgroundThe prognosis for hepatocellular carcinoma (HCC) patients can vary significantly even within the same clinical stage. This study aims to characterize the stage-specific transcriptomic landscape of super survivors with HCC and identify a prognostic gene signature.MethodsWe analyzed data from The Cancer Genome Atlas (TCGA) for 76 matched super survivors (alive at 5 years) and poor survivors (deceased within 1 year) with HCC. Gene set enrichment analysis stratified by stage was conducted and a key prognostic gene signature was developed. The signature was then applied to the full TCGA cohort and independently validated in International Cancer Genome Consortium (ICGC) data.FindingsStage-specific transcriptomic profiling revealed distinct patterns in super survivors. Stage I and II showed positive enrichment in immune response pathways, while stage III exhibited enhanced catabolic activities and reduced glycolysis. Across all stages, cell cycle processes were less active in super survivors. A 19-gene signature, incorporating immune, metabolic, and cell cycle genes, accurately distinguished super from poor survivors with 91% accuracy (69/76). The signature reliably predicted overall survival in both the verification cohort (1-year, 3-year, and 5-year AUROCs of 0.82, 0.80, and 0.78) and the independent validation cohort (1-year and 3-year AUROCs of 0.80 and 0.83). Consistent AUROCs were observed across all tumor stages.InterpretationOur findings reveal a dynamic shift in HCC progression, with immune dominance in early stages and metabolic dominance in later stages, alongside reduced cell cycle activity across all stages. Integrating stage-specific transcriptomic profiles offers a promising approach to enhancing individualized management for HCC patients.
Insulin resistance, cognition, and functional brain network topology in older adults with obesity
Authors: McIntyre Clayton C. , Lyday Robert G. , Su Yixin , Nicklas Barbara , Simpson Sean L. , Deep Gagan , Macauley Shannon L. , Hugenschmidt Christina E. 
Published: November 2024

AbstractObjectiveCross-sectional data from a sample of older adults with obesity was used to determine how peripheral and neuronal insulin resistance (IR) relate to executive function and functional brain network topology.MethodsOlder adults (n=71) with obesity but without type 2 diabetes were included. Peripheral IR was quantified by HOMA2-IR. Neuronal IR was quantified according to a proposed neuron-derived exosome-based method (NDE-IR). An executive function composite score, summed scores to the Auditory Verbal Learning Test (AVLT) trials 1-5, and functional brain networks generated from resting-state functional magnetic resonance imaging were outcomes in analyses. We used general linear models and a novel regression framework for brain network analysis to identify relationships between IR measures and brain-related outcomes.ResultsHOMA2-IR, but not NDE-IR, was negatively associated with executive function. Neither IR measure was associated with AVLT score. Peripheral IR was also related to hippocampal network topology in participants who had undergone functional neuroimaging. Neither peripheral nor neuronal IR were significantly related to network topology of the central executive network.ConclusionsCognitive and functional imaging effects were observed from HOMA2-IR, but not NDE-IR. The hippocampus may be particularly vulnerable to effects of peripheral IR.
Visualizing turnover of synaptic vesicle protein Synaptogyrin/SNG-1 in vivo using a new method, ARGO (Analysis of Red Green Offset)
Authors: Shiliaev Nikita , Baumberger Sophie , Richardson Claire E. 
Published: November 2024

AbstractProteostasis is critical for cellular function and longevity, especially in long-lived cells including neurons. A major component of proteostasis is the regulated degradation and replacement of proteins to ensure their quality and appropriate abundance. The regulation of synaptic vesicle protein turnover in neurons is important for understanding synaptic communication, yet it is incompletely understood, partly due to limited tools for assessing protein turnoverin vivo. Here, we present ARGO (Analysis of Red-Green Offset), a fully genetically encoded, ratiometric fluorescence imaging method that visualizes and quantifies protein turnover with subcellular resolutionin vivo. ARGO involves cell-specific labeling of the protein-of-interest with both RFP and GFP, followed by Cre/Lox-mediated removal of GFP (pulse) and periodic ratiometric imaging to track protein turnover (chase). This approach is inexpensive, modular, and scalable for use in genetically tractable experimental organisms. Using ARGO, we examined the turnover of Synaptogyrin/SNG-1, an evolutionarily conserved, integral SV protein, in adultCaenorhabditis elegansneurons. Our findings support the model that SV proteins are sorted for degradation at the synapse, then trafficked to the neuron cell body to complete degradation. We show that the rate of presynaptic SNG-1 turnover is consistent across synapses within a single neuron, indicating a cell-wide super-pool for SV protein degradation. Our results further suggest that, contrary to prevailing models, neither the surveillance nor the sorting of SV proteins for degradation is a rate-limiting step for SNG-1 turnover; rather, the rate-limiting step is the clearance of sorted-for-degradation SNG-1 from the presynapse.Article SummaryHow proteins are turned over within subcellular compartments is not well understood, in part because the phenomenon is difficult to quantify. The authors developed a simple, genetically encoded method to quantify the turnover of a protein-of-interest using fluorescence microscopy. They used this method to begin to assess synaptic vesicle protein turnoverin vivo, as this is important for synaptic function. They found that synaptic vesicle protein Synaptogyrin/SNG-1 is sorted for degradation at the synapse but degraded in the neuron cell body, and the turnover rate depends on animal age but is constant across presynapses within a neuron.