bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perineural Invasion is an Important Prognostic Factor in Patients With Radically Resected (R0) and Node-negative (pN0) Pancreatic Cancer
Authors: Schouten Thijs J. , Kroon Victor J. , Besselink Marc G. , Bosscha Koop , Busch Olivier R. , Crobach A. Stijn L.P. , van Dam Ronald M. , Doukas Michail , Fariña Sarasquesta Arantza , Festen Sebastiaan , Groot Koerkamp Bas , van der Harst Erwin , Heij Lara R. , de Hingh Ignace H.J.T. , Kazemier Geert , Liem Mike S.L. , de Meijer Vincent E. , Mieog J. Sven D. , Patijn Gijs A. , Raicu G. Mihaela , Roos Daphne , Schreinemakers Jennifer M.J. , Stommel Martijn W.J. , Wilmink Hanneke J. , Wit Fennie , Brosens Lodewijk A.A. , van Santvoort Hjalmar C. , Molenaar I. Quintus , Daamen Lois A. ,   for the Dutch Pancreatic Cancer Group
Published: May 2024

Objective:
To investigate the association between perineural invasion (PNI) and overall survival (OS) in a nationwide cohort of patients with resected pancreatic ductal adenocarcinoma (PDAC), stratified for margin negative (R0) or positive (R1) resection and absence or presence of lymph node metastasis (pN0 or pN1-N2, respectively).

Background:
Patients with R0 and pN0 resected PDAC have a relatively favorable prognosis. As PNI is associated with worse OS, this might be a useful factor to provide further prognostic information for patients counselling.

Methods:
A nationwide observational cohort study was performed including all patients who underwent PDAC resection in the Netherlands (2014-2019) with complete information on relevant pathological features (PNI, R status, and N status). OS was assessed using Kaplan-Meier curves, and Cox-proportional hazard analyses were performed to calculate hazard ratio’s (HR) with corresponding 95% confidence intervals (CI).

Results:
In total, 1630 patients were included with a median follow-up of 43 (interquartile range 33-58) months. PNI was independently associated with worse OS in both R0 patients (HR 1.49 [95%CI 1.18-1.88]; P<0.001) and R1 patients (HR 1.39 [95% CI 1.06-1.83]; P=0.02), as well as in pN0 patients (HR 1.75 [95%CI 1.27-2.41]; P<0.001) and pN1-N2 patients (HR 1.35 [95% CI 1.10-1.67]; P<0.01). In 315 patients with R0N0, multivariable analysis showed that PNI was the strongest predictor of OS (HR 2.24 [95% CI 1.52-3.30]; P<0.001).

Conclusion:
PNI is strongly associated with worse survival in patients with resected PDAC, in particular in patients with relatively favorable pathological features. These findings may aid patient stratification and counselling and help guide treatment strategies.
Impact of Obesity on Midurethral Sling Failure in a Highly Hispanic Population
Authors: Song Jun , Song Xuemei , Wang Zhu , Alas Alexandriah 
Published: May 2024

Importance
Mixed data exist in the literature regarding the impact of obesity on midurethral sling (MUS) failure rates.

Objective
The aim of this study was to evaluate the impact of obesity and Hispanic ethnicity on MUS failure.

Study Design
This was a retrospective cohort study of females who underwent MUS surgery, alone or with concomitant prolapse repair, with at least 1 year of follow-up. Body mass index (BMI) classes were categorized as normal (<25 kg/m2), overweight (25–29.9 kg/m2), obese (30–39.9 kg/m2), and severe obesity (≥40 kg/m2). The primary outcome was MUS failure, defined as a composite of subjectively unchanged or worsened symptoms or need for additional procedures. Secondary outcomes included risk factors related to MUS failure and the effect of ethnicity on MUS failure rates.

Results
A total of 322 women were included for analysis. The mean age was 52.3 years. Increasing BMI was associated with higher MUS failure, with multivariate logistic regression showing a 5% increased risk for each 1 kg/m2 BMI increase. Failure rates were significantly different between normal BMI and severe obesity (16.7% vs 36.4%, P = 0.04). After adjusting for other variables, transobturator slings had a higher risk of failure compared with retropubic slings, whereas surgeon training and patient ethnicity did not affect failure rates.

Conclusions
We found that increasing BMI was associated with higher MUS failures, with significantly higher failure rates in the severely obese population. Although MUS remains the standard of care for treatment of SUI, based on our findings, counseling should be individualized to the patient, taking into account each patient’s unique characteristics.
Comparison of shelf-stable and conventional resuscitation products in a canine model of hemorrhagic shock
Authors: Edwards Thomas H. , Venn Emilee C. , Le Tuan D. , Grantham Lonnie E. , Hogen Talli , Ford Rebekah , Ewer Nicole , Gunville Ranger , Carroll Calli , Taylor Amy , Hoareau Guillaume L. 
Published: May 2024

BACKGROUND
Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available.

METHODS
Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product.

RESULTS
At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB (p < 0.01).

CONCLUSION
Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma.
Myeloid cell networks determine reinstatement of original immune environments in recurrent ovarian cancer
Authors: Ghisoni Eleonora , Benedetti Fabrizio , Minasyan Aspram , Cunnea Paula , Grimm Alizée J. , Fahr Noémie , Desbuisson Mathieu , Capt Charlotte , Rayroux Nicolas , Gulhan Doga C. , Dagher Julien , Barras David , Morotti Matteo , Marín-Jiménez Juan A. , De Carlo Flavia , Chap Bovannak Stewen , Spagnol Giulia , Fleury Mapi , Fortis Katerina , Dorier Julien , Tissot Stephanie , Rusakiewicz Sylvie , Ferreira Humberto J. , Bassani-Stenberg Michal , Swisher Elizabeth M. , Kandalft Lana , Mastroyannis Spyridon A. , Montone Kathleen T. , Powell Daniel , Pittet Mikaël J. , Tanyi Janos L. , Coukos George , Fotopoulou Christina , Conejo-Garcia Jose R. , Laniti Denarda Dangaj 
Published: May 2024

SummaryImmunotherapy has produced disappointing results in recurrent ovarian cancer (OC). However, the prognostic value of tumour-infiltrating lymphocytes (TILs) is largely based on the analysis of treatment-naive tumours. To understand the immunobiology of recurrent cancers, and their evolution, we profiled 170 patient-matched primary-recurrent OC samples from 69 patients of two independent cohorts. By capturing heterogeneous TIL distributions, we identified four immune phenotypes associated with differential prognosis, TILs states and TILs:myeloid networks, which dictate malignant evolution after chemotherapy and recurrence. Notably, recurrent tumours recapitulate the immunogenic patterns of original cancers. Mirroring inflamed human OC, preclinical recurrentBrca1muttumours maintained activated TILs:dendritic cells (DCs) niches and immunostimulatory tumour-associated macrophages (TAMs). Conversely, recurrentBrca1wttumours displayed loss of TILs:DCs niches and accumulated immunosuppressive myeloid networks featuringTrem2/ApoEhighTAMs andNduf4l2high/Galectin3highmalignant states. Our study highlights that persistent immunogenicity in recurrent OC is governed by the crosstalk between dissimilar myeloid cells and TILs, which is BRCA-dependent.
Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice
Authors: Khosravi-Maharlooei Mohsen , Vecchione Andrea , Danzl Nichole , Li Hao Wei , Nauman Grace , Madley Rachel , Waffarn Elizabeth , Winchester Robert , Ruiz Amanda , Ding Xiaolan , Fousteri Georgia , Sykes Megan 
Published: May 2024

ABSTRACTHuman immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants and immunotherapies. In HIS mice that generate T cellsde novofrom hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg-PrkdcscidIl2rgtm1Wjl(NSG) mouse thymus, where negative selection is abnormal. Disease develops very late when human T cells develop in human fetal thymus grafts, where robust negative selection is observed. We demonstrate here that PD-1+CD4+peripheral (Tph) helper-like and follicular (Tfh) helper-like T cells developing in HIS mice can induce autoimmune disease. Tfh- like cells were more prominent in HIS mice with a mouse thymus, in which the highest levels of IgG were detected in plasma, compared to those with a human thymus. While circulating IgG and IgM antibodies were autoreactive to multiple mouse antigens, in vivo depletion of B cells and antibodies did not delay the development of autoimmune disease. Conversely, adoptive transfer of enriched Tfh- or Tph-like cells induced disease and autoimmunity-associated B cell phenotypes in recipient mice containing autologous human APCs without T cells. Tfh/Tph cells from mice with a human thymus expanded and induced disease more rapidly than those originating in a murine thymus, implicating HLA-restricted T cell-APC interactions in this process. Since Tfh, Tph, autoantibodies and lymphopenia-induced proliferation (LIP) have all been implicated in various forms of human autoimmune disease, the observations here provide a platform for the further dissection of human autoimmune disease mechanisms and therapies.
Contrasting patterns of spatial genetic structure in endangered southern damselfly (Coenagrion mercuriale) populations facing habitat fragmentation and urbanisation
Authors: Lévêque Agathe , Duputié Anne , Vignon Vincent , Duez Fabien , Godé Cécile , Vanappelghem Cédric , Arnaud Jean-François 
Published: May 2024

AbstractAimHuman-induced environmental changes result in habitat loss and fragmentation, impacting wildlife population genetic structure and evolution. Urbanised and geographically peripheral areas often represent unfavourable environments, reducing connectivity among populations and causing higher population genetic differentiation and lower intra-population genetic diversity. We examined how geographic peripherality and anthropogenic pressures affect genetic diversity and genetic differentiation in the protected southern damselfly (Coenagrion mercuriale, Odonata), which has low dispersal capabilities and specific habitat requirements and whose populations are declining.LocationWe studied two areas: one in semi-natural habitats at the periphery of the species geographic range (northern France) and the other more central to the species’ range, in an urbanised area surrounding the city of Strasbourg (Alsace, eastern France).MethodsWe genotyped 2743 individuals from 128 populations using eleven microsatellite loci. We analysed the spatial distribution of neutral genetic diversity (allelic richness, heterozygosity, levels of inbreeding, genetic relatedness), the extent of genetic differentiation, and population affiliations (sPCA analyses) within the two areas. We also examined fine-scale patterns of gene flow in the urbanised area of Alsace by investigating patterns of isolation by distance and estimating effective migration surfaces (EEMS method).ResultsNorthern peripheral populations showed lower levels of genetic diversity and higher levels of genetic differentiation than central Alsacian populations. Although located in anthropised habitats, geographically central Alsacian populations showed high levels of gene flow, with dispersal events mainly occurring overland and not restricted to watercourses. However, the highly urbanised city of Strasbourg negatively impacted nearby populations by reducing levels of genetic diversity and increasing population genetic differentiation.Main conclusionsThese results showed the need for management action by restoring breeding sites and creating migratory corridors for peripheral southern damselfly populations. However, our results also highlighted the resilience of southern damselfly in central range populations facing strong urbanisation pressures.
Long-read sequencing reveals aberrant fragmentation patterns and origins of circulating DNA in cancer
Authors: Berman Benjamin P. , Erdman Sarah A. , Turatsinze Jean-Valery , Cayford Justin , Kelly Theresa K. 
Published: May 2024

AbstractCirculating cell-free DNA (cfDNA), which includes tumor and immune-derived fragments, is often elevated in cancer patients relative to healthy individuals. This can be accompanied by changes in cfDNA fragmentation patterns, including fragment length distributions, fragment end sequences, and genomic context. Here, we survey fragmentation changes across 12 cancer types using Oxford Nanopore Technologies (ONT) shallow whole-genome sequencing. We confirm a hyperfragmentation pattern across a large fraction of the cancers and associate this with markers of altered DNase activity and elevation of circulating DNA and nucleosome levels. We also identify a cluster of cancers with fragments greater than 1 kilobase and distinguish these long fragments from genomic contamination based on length distribution and a DNASE1L3 fragmentation signature. Future studies using ONT sequencing will determine the prevalence and implications of this hypofragmentation phenotype across cancer.
Invasive adult jumping worms in Atlantic Canada are chill-susceptible
Authors: Adams Victoria E. , Chettiar Subash Raj , Clow Tanner M. , Gendron Emily , Gough Amber L. , Stewart Brianna E. M. , Cameron Erin K. , Toxopeus Jantina 
Published: May 2024

AbstractThe jumping wormAmynthas tokioensisis invasive in North America, and it has been expanding its range northward in recent years. Because low temperatures typically restrict the geographic distribution of organisms, our goal was to characterize the cold tolerance physiology of adult jumping worms from a site in New Brunswick, Canada (c. 45°N), with the intent of better understanding their geographic range limits. Most of our experiments supported the conclusion that these worms are chill-susceptible: they die during or after exposure to relatively mild low temperatures. When gradually cooled, adult worms lost neuromuscular coordination at approximately 0 °C and froze at a mean temperature of −4.5 °C. They did not survive freezing and showed poor survival following 1 h exposures to 0 °C and subzero temperatures. At higher mild temperatures (5 °C), the worms could survive short (up to 6 h) but not long (e.g., 48 h) chilling durations. We attempted to induce improved cold tolerance via a five-week gradual acclimation to fall-like temperatures, but fall-acclimated worms showed poor survival during and after this acclimation. Acclimation also did not induce accumulation of glucose, a typical cryoprotectant in earthworms. We suggest thatA. tokioensiscan likely persist wherever the growing season is sufficiently warm and long enough for the adults to mature, reproduce, and lay cocoons prior to the chilling temperatures associated with early fall. Future work examining the cold tolerance of the overwintering cocoons will be important for fully understanding the northern range limits of these jumping worms.
HiMoRNA and RNA-Chrom integration: Chromatin-Associated LncRNAs in Genome-Wide Epigenetic Regulation
Authors: Ilnitskiy Ivan S. , Ryabykh Grigory K. , Marakulina Daria A. , Mironov Andrey A. , Medvedeva Yulia A. 
Published: May 2024

AbstractLong non-coding RNAs (lncRNAs) significantly contribute to genome structure and regulation. Many lncRNAs are known to interact with chromatin and in this way to affect gene expression patterns through epigenetic regulation. Still, experimental protocols for lncRNA-chromatin interactions do not provide any insight into the mechanisms of lncRNA-based genome-wide regulation. Here we present an integration of HiMoRNA – a resource containing correlated lncRNA-epigenetic changes in specific genomic locations genome-wide, – and RNA-Chrom, a resource featuring uniformly processed experimental data on RNA-chromatin interactions. Our integration approach allows generating interpretable and experimentally supported hypotheses on the mechanisms of lncRNA epigenetic regulation of gene expression. For this integration we have tailored the interface of HiMoRNA such that for many lncRNAs experimentally detected RNA-chromatin contacts are available from RNA-Chrom for browsing, analysis and downloading. HiMoRNA peaks supported by RNA-Chrom contacts can be explained by external experimental data. We believe that the integration of HiMoRNA and RNA-Chrom is a convenient and valuable approach that can provide experimental and mechanistic insights and greatly facilitate functional annotation of lncRNAs.
TNF signaling mediates cellular immune function and promotes malaria parasite killing in the mosquitoAnopheles gambiae
Authors: Samantsidis George-Rafael , Kwon Hyeogsun , Wendland Megan , Fonder Catherine , Smith Ryan C. 
Published: May 2024

AbstractTumor Necrosis Factor-α (TNF-α) is a proinflammatory cytokine and a master regulator of immune cell function in vertebrates. While previous studies have implicated TNF signaling in invertebrate immunity, the roles of TNF in mosquito innate immunity and vector competence have yet to be explored. Herein, we confirm the identification of a conserved TNF-α pathway inAnopheles gambiaeconsisting of the TNF-α ligand, Eiger, and its cognate receptors Wengen and Grindelwald. Through gene expression analysis, RNAi, andin vivoinjection of recombinant TNF-α, we provide direct evidence for the requirement of TNF signaling in regulating mosquito immune cell function by promoting granulocyte midgut attachment, increased granulocyte abundance, and oenocytoid rupture. Moreover, our data demonstrate that TNF signaling is an integral component of anti-Plasmodiumimmunity that limits malaria parasite survival. Together, our data support the existence of a highly conserved TNF signaling pathway in mosquitoes that mediates cellular immunity and influencesPlasmodiuminfection outcomes, offering potential new approaches to interfere with malaria transmission by targeting the mosquito host.
Device-free isolation of photoreceptor cells from patient iPSC-derived retinal organoids
Authors: Stone Nicholas E. , Bohrer Laura R. , Mullin Nathaniel K. , Cooke Jessica , Wright Allison T. , Stone Edwin M. , Mullins Robert F. , Tucker Budd A. 
Published: May 2024

AbstractAutologous photoreceptor cell replacement therapy shows great promise for treating patients with multiple forms of inherited retinal degenerative blindness. Specifically, in disorders such as retinitis pigmentosa and Stargardt’s disease, selective death of photoreceptor cells results in irreversible blindness. Induced pluripotent stem cell (iPSC) derived retinal organoids, which faithfully recapitulate the structure of the neural retina, are an ideal source of photoreceptor cells required for these therapies. However, in addition to photoreceptor cells, retinal organoids also contain many other retinal cell types. Therefore, approaches for isolating fate committed photoreceptors from dissociated retinal organoids are desirable to produce photoreceptor cell replacement therapies. In this work, we present a partial dissociation strategy, which leverages the high level of organization found in retinal organoids to enable selective enrichment of photoreceptor cells without the use of specialized equipment or reagents such as antibody labels. Given that this technique can be performed with only standard plasticware and cGMP compliant reagents, it is an ideal candidate for use in the preparation of clinical cell therapies.
Multi-omics delineate growth factor network underlying exercise effects in an Alzheimer’s mouse model
Authors: Li Xin , Liu Chaozhong , Li Wenbo , Dai Yanwan , Gu Chaohao , Zhou Wenjun , Ciliberto Veronica C. , Liang Jing , S Udhaya Kumar. , Guan Dongyin , Hu Zhaoyong , Zheng Hui , Chen Hu , Liu Zhandong , Wan Ying-Wooi , Sun Zheng 
Published: May 2024

ABSTRACTPhysical exercise represents a primary defense against age-related cognitive decline and neurodegenerative disorders like Alzheimer’s disease (AD). To impartially investigate the underlying mechanisms, we conducted single-nucleus transcriptomic and chromatin accessibility analyses (snRNA-seq and ATAC-seq) on the hippocampus of mice carrying AD-linked NL-G-F mutations in the amyloid precursor protein gene (APPNL-G-F) following prolonged voluntary wheel-running exercise. Our study reveals that exercise mitigates amyloid-induced changes in both transcriptomic expression and chromatin accessibility through cell type-specific transcriptional regulatory networks. These networks converge on the activation of growth factor signaling pathways, particularly the epidermal growth factor receptor (EGFR) and insulin signaling, correlating with an increased proportion of immature dentate granule cells and oligodendrocytes. Notably, the beneficial effects of exercise on neurocognitive functions can be blocked by pharmacological inhibition of EGFR and the downstream phosphoinositide 3-kinases (PI3K). Furthermore, exercise leads to elevated levels of heparin-binding EGF (HB-EGF) in the blood, and intranasal administration of HB-EGF enhances memory function in sedentary APPNL-G-Fmice. These findings offer a panoramic delineation of cell type-specific hippocampal transcriptional networks activated by exercise and suggest EGF-related growth factor signaling as a druggable contributor to exercise-induced memory enhancement, thereby suggesting therapeutic avenues for combatting AD-related cognitive decline.