bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of HPV-related Anogenital Intraepithelial Neoplasia and Cancer in Men With Diabetes Compared With the General Population
Authors: Reinholdt Kristian , Thomsen Louise Thirstrup , Munk Christian , Dehlendorff Christian , Carstensen Bendix , Jørgensen Marit Eika , Kjaer Susanne Krüger 
Published: May 2021

Background:
Diabetes may increase risk of human papillomavirus (HPV)–related precancer and cancer. We estimated incidence of penile and anal high-grade intraepithelial neoplasia (hgPeIN, hgAIN) and squamous cell carcinoma (SCC) in men with diabetes compared with the entire Danish male population without diabetes.

Methods:
In this registry-based cohort study, we included all men born 1916–2001 and residing in Denmark (n = 2,528,756). From nationwide registries, we retrieved individual-level information on diabetes, educational level, and diagnoses of hgPeIN, hgAIN, penile SCC, and anal SCC. We used Poisson regression models to estimate incidence of hgPeIN, hgAIN, penile SCC, and anal SCC as a function of diabetes status, attained age, calendar period, and education. We estimated incidence rate ratios (IRRs) of each outcome in men with diabetes compared with nondiabetic men, both for diabetes overall and separately for type 1 (T1D) and type 2 diabetes (T2D).

Results:
Men with diabetes had increased incidence rate of penile SCC compared with nondiabetic men (IRR = 1.5, 95% CI = 1.2, 1.9). We saw similar trends for anal SCC, hgPeIN, and hgAIN. The combined incidence rate of penile and anal SCC was increased in men with T2D (IRR = 1.5, 95% CI = 1.3, 1.8), but not with T1D (IRR = 0.53, 95% CI = 0.20, 1.4) compared with men without diabetes.

Conclusion:
The incidence of penile and anal high-grade intraepithelial neoplasia and SCC in men with diabetes was increased compared with men without diabetes. For penile and anal SCCs, this was primarily due to an increased risk in men with T2D.
Safe balloon inflation parameters for resuscitative endovascular balloon occlusion of the aorta
Authors: Maleckis Kaspars , Keiser Courtney , Jadidi Majid , Anttila Eric , Desyatova Anastasia , MacTaggart Jason , Kamenskiy Alexey 
Published: May 2021

BACKGROUND
Noncompressible hemorrhage is a leading cause of preventable death in civilian and military trauma populations. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising method for controlling noncompressible hemorrhage, but safe balloon inflation parameters are not well defined. Our goal was to determine the balloon inflation parameters associated with benchtop flow occlusion and aortic/balloon rupture in ex vivo human aortas and test the hypothesis that optimal balloon inflation characteristics depend on systolic pressure and subject demographics.

METHODS
Aortic occlusion parameters in human thoracic aortas (TAs) and abdominal aortas (AAs) from 79 tissue donors (median ± SD age, 52 ± 18 years [range, 13–75 years]; male, 52; female, 27) were recorded under 100/40, 150/40, and 200/40 mm Hg flow pressures for ER-REBOA and Coda balloons. Rupture tests were done with Coda balloons only without flow.

RESULTS
In the TA, the average balloon inflation volumes and pressures resulting in 100/40 mm Hg flow occlusion were 11.7 ± 3.8 mL and 174 ± 65 mm Hg for the ER-REBOA, and 10.6 ± 4.3 mL and 94 ± 57 mm Hg for the Coda balloons. In the AA, these values were 6.2 ± 2.6 mL and 110 ± 47 mm Hg for the ER-REBOA, and 5.9 ± 2.2 mL and 71 ± 30 mm Hg for the Coda. The average balloon inflation parameters associated with aortic/Coda balloon rupture were 39.1 ± 6.5 mL and 1,284 ± 385 mm Hg in the TA, and 27.7 ± 7.7 mL and 1,410 ± 483 mm Hg in the AA. Age, sex, and systolic pressure all had significant effects on balloon occlusion and rupture parameters.

CONCLUSION
Optimal balloon inflation parameters depend on anatomical, physiological, and demographic characteristics. Pressure-guided rather than volume-guided balloon inflation may reduce the risk of aortic rupture. These results can be used to help improve the safety of REBOA procedures and devices.
Pain management for casualties receiving lifesaving interventions in the prehospital scenario: Raising awareness of our human nature
Authors: Betelman Mahalo Yaar , Avital Guy , Radomislensky Irina , Vysokovsky Moshe , Avital-Cohen Rotem , Gelikas Shaul , Tsur Avishai M. , Nadler Roy , Bodas Moran ,   Israel Trauma Group, Chen Jacob , Glassberg Elon , Benov Avi 
Published: May 2021

BACKGROUND
Lifesaving interventions (LSIs) are the hallmark of medical care in trauma casualties, reducing mortality and morbidity. Analgesia is another essential treatment, which has been shown to improve outcomes and decrease long-term complications. However, oligoanalgesia is common, and information regarding its relation to the performance of LSIs is scarce. The purpose of this study was to assess the relation between the performance of LSIs and analgesia administration in the prehospital environment.

METHODS
A retrospective database-based study was performed, including all trauma casualties treated by Israeli Defense Forces physicians and paramedics during 2006 to 2017 and admitted to hospitals participating in the Israeli National Trauma Registry. Included LSIs were tourniquet application, administration of tranexamic acid and freeze-dried plasma, and administration of chest decompression. Casualties treated with endotracheal intubation or cricothyroidotomy were excluded.

RESULTS
In the multivariable logistic regression analysis, LSIs were associated with prehospital analgesia administration (odds ratio [OR], 3.59; confidence interval [CI], 2.56–5.08; p < 0.001). When assessing for the different LSIs, tourniquet application (OR, 2.83; CI, 1.89–4.27; p < 0.001) and tranexamic acid administration (OR, 4.307; CI, 2.42–8.04; p < 0.001) were associated with prehospital analgesia administration.

CONCLUSION
A positive association exists between performance of LSIs and administration of analgesia in the prehospital environment. Possible explanations may include cognitive and emotional biases affecting casualty care providers.

LEVEL OF EVIDENCE
Retrospective study, level IV.
Recommended primary outcomes for clinical trials evaluating hemostatic blood products and agents in patients with bleeding: Proceedings of a National Heart Lung and Blood Institute and US Department of Defense Consensus Conference
Authors: Spinella Philip C. , El Kassar Nahed , Cap Andrew P. , Kindzelski Andrei L. , Almond Christopher S. , Barkun Alan , Gernsheimer Terry B. , Goldstein Joshua N. , Holcomb John B. , Iorio Alfonso , Jensen Dennis M. , Key Nigel S. , Levy Jerrold H. , Mayer Stephan A. , Moore Ernest E. , Stanworth Simon J. , Lewis Roger J. , Steiner Marie E. ,   for the Hemostasis Trials Outcomes Working Group
Published: May 2021

ABSTRACT
High-quality evidence guiding optimal transfusion and other supportive therapies to reduce bleeding is needed to improve outcomes for patients with either severe bleeding or hemostatic disorders that are associated with poor outcomes. Alongside challenges in performing high-quality clinical trials in patient populations who are at risk of bleeding or who are actively bleeding, the interpretation of research evaluating hemostatic agents has been limited by inconsistency in the choice of primary trial outcomes. This lack of standardization of primary endpoints or outcomes decreases the ability of clinicians to assess the validity of endpoints and compare research results across studies, impairs meta-analytic efforts, and, ultimately, delays the translation of research results into clinical practice. To address this challenge, an international panel of experts was convened by the National Heart Lung and Blood Institute and the US Department of Defense on September 23 and 24, 2019, to develop expert opinion, consensus-based recommendations for primary clinical trial outcomes for pivotal trials in pediatric and adult patients with six categories in various clinical settings. This publication documents the conference proceedings from the workshop funded by the National Heart Lung and Blood Institute and the US Department of Defense that consolidated expert opinion regarding clinically meaningful outcomes across a wide range of disciplines to provide guidance for outcomes of future trials of hemostatic products and agents for patients with active bleeding.
Multi-level multi-state modelling applied to hospital admission in mexican patients with COVID-19
Authors: Martinez Juan Pablo Diaz , Becerril Karen Janik Orozco , Herrada Marco Antonio Gallegos , Garcia Mayra Alejandra Gutierrez , Espin-Garcia Osvaldo , Garcia Ruth Fuentes 
Published: May 2021

AbstractSince the beginning of the SARS-CoV 2 pandemic, healthcare authorities have made clear that it is crucial to track and identify COVID-19 symptoms and seek medical attention in the presence of the first warning signs, as immediate medical attention can improve the patient’s prognosis. Therefore the present work aims to analyze the risks associated with the time between the patient’s first symptoms and hospitalization followed by death. A cross-sectional study was performed among Mexican population diagnosed with COVID-19 and hospitalized from March to January 2021. Four different Bayesian models were developed to asses the risk associated with different patient trajectories: symptoms-hospitalization and hospitalization-death. Comorbidities that could worsen the patient outcome were included as linear predictions; these analyses were further broken down to the different states of the Mexican Republic and the healthcare providers within. Model III was chosen as the best performance through a validation of leaving one out (LOO). Increased risk for hospitalization was observed at the global population level for chronic renal disease, whereas for death such was the case for COPD and the interaction of diabetes:hypertension:obesity. Our results show that there are differences in mortality between the states without accounting for institution and it is related to the prompt time of death or viceversa. Regarding the 6 healthcare providers included in the analysis differences were also found. While state-managed hospitals and private sector showed lower risks, in contrast the IMSS seems to be the one with the highest risk. The proposed modelling can be helpful to improve healthcare assistance at a regional level, additionally it could inform statistical parameter inference in epidemiological models.
Early transfusion of convalescent plasma improves the clinical outcome in severe SARS-CoV2 infection
Authors: Fodor Eszter , Müller Veronika , Iványi Zsolt , Berki Tímea , Olga Kuten Pella , Ambrus Mira , Sárkány Ágnes , Skázel Árpád , Madár Ágnes , Kardos Dorottya , Kemenesi Gábor , Földes Fanni , Nagy Sándor , Matusovits Andrea , János Nacsa , Tordai Attila , Jakab Ferenc , Lacza Zsombor 
Published: May 2021

AbstractPlasma harvested from convalescent COVID-19 patients (CCP) has been applied as first-line therapy in the early phase of the SARS-CoV2 pandemic through clinical studies using various protocols. We present data from a cohort of 267 hospitalized, severe COVID-19 patients who received CCP. No transfusion-related complications were reported, indicating the overall safety of CCP therapy. Patients who eventually died from COVID-19 received CCP significantly later (3.95 versus 5.22 days after hospital admission) and had higher interleukin 6 (IL-6) levels (28.9 pg/ml versus 102.5 pg/ml) than those who survived. In addition, CCP-transfusion caused a significant reduction in the overall inflammatory status of the patients regardless of the severity of disease or outcome, as evidenced by decreasing C-reactive protein, IL6 and ferritin levels. We conclude that, CCP-transfusion is a safe and effective supplementary treatment modality for hospitalized COVID-19 patients characterized by better expected outcome if applied as early as possible. We also observed that, IL-6 may be a suitable laboratory parameter for patient selection and monitoring of CCP therapy effectiveness.
On the inference of positive and negative species associations and their relation to abundance
Authors: Rominger Andrew J. 
Published: May 2021

AbstractThe prevalence of rare species in ecosystems begs the question of how they persist. In a recent paper, Calatayuda et al. (CEA) provided a new hypothesis that rare species, in contrast to common species, share unique microhabitats and/or preferentially engage in mutualistic interactions. CEA support this hypotheses by reconstructing association networks from spatially replicated abundance data finding that rare species are over-representing in positive association networks while common species are over-representing in negative association networks. However, the use of abundance and co-occurrence data to infer true species associations is difficult and often inaccurate. Here, I show that the finding of rare species being more represented in positive association networks can be explained by statistical artifacts in the inference of species associations from abundance data. I caution against the inference of ecological association networks from abundance data alone.
Neural coding of visual objects rapidly reconfigures to reflect sub-trial shifts in attentional focus
Authors: Barnes Lydia , Goddard Erin , Woolgar Alexandra 
Published: May 2021

AbstractEvery day, we respond to the dynamic world around us by flexibly choosing actions to meet our goals. This constant problem solving, in familiar settings and in novel tasks, is a defining feature of human behaviour. Flexible neural populations are thought to support this process by adapting to prioritise task-relevant information, driving coding in specialised brain regions toward stimuli and actions that are important for our goal. Accordingly, human fMRI shows that activity patterns in frontoparietal cortex contain more information about visual features when they are task-relevant. However, if this preferential coding drives momentary focus, for example to solve each part of a task, it must reconfigure more quickly than we can observe with fMRI. Here we used MVPA with MEG to test for rapid reconfiguration of stimulus information when a new feature becomes relevant within a trial. Participants saw two displays on each trial. They attended to the shape of a first target then the colour of a second, or vice versa, and reported the attended features at a choice display. We found evidence of preferential coding for the relevant features in both trial phases, even as participants shifted attention mid-trial, commensurate with fast sub-trial reconfiguration. However, we only found this pattern of results when the task was difficult, and the stimulus displays contained multiple objects, and not in a simpler task with the same structure. The data suggest that adaptive coding in humans can operate on a fast, sub-trial timescale, suitable for supporting periods of momentary focus when complex tasks are broken down into simpler ones, but may not always do so.
LMO2 is critical for early metastatic events in breast cancer
Authors: Sikandar Shaheen , Antony Jane , Gulati Gunsagar S. , Kuo Angera H. , Dang Ho William Hai , Das Soumyashree , Steen Chloé B. , Pereira Thiago Almeida , Qian Dalong , Beachy Philip A. , Dirbas Fredrick , Red-Horse Kristy , Rabbitts Terence H. , Thiery Jean Paul , Newman Aaron M. , Clarke Michael F. 
Published: May 2021

SUMMARYMetastasis is responsible for the majority of breast cancer-related deaths, however identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immatureTHY1+/VEGFA+tumor epithelial cells in human breast tumor biopsies that display angiogenic features and are marked by the expression of the oncogene,LMO2. Higher abundance ofLMO2+basal cells correlated with tumor endothelial content and predicted poor distant recurrence-free survival in patients. UsingMMTV-PyMT/Lmo2CreERT2mice, we demonstrated thatLmo2lineage- traced cells have a higher propensity to metastasize. LMO2 knockdown in human breast tumors reduced lung metastasis by impairing intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 binds to STAT3 and is required for STAT3 activation by TNFα and IL6. Collectively, our study identifies a population of metastasis-initiating cells with angiogenic features and establishes the LMO2-STAT3 signaling axis as a therapeutic target in breast cancer metastasis.One sentence summaryLMO2 modulates STAT3 signaling in breast cancer metastasis.
Mechanosensitive Osteogenesis on Native Cellulose Scaffolds for Bone Tissue Engineering
Authors: Latour Maxime Leblanc , Pelling Andrew E. 
Published: May 2021

AbstractIn recent years, plant-derived cellulosic biomaterials have become a popular way to create scaffolds for a variety of tissue engineering applications. Moreover, such scaffolds possess similar physical properties (porosity, stiffness) that resemble bone tissues and have been explored as potential biomaterials for tissue engineering applications. Here, plant-derived cellulose scaffolds were seeded with MC3T3-E1 pre-osteoblast cells. Moreover, to assess the potential of these biomaterials, we also applied cyclic hydrostatic pressure (HP) to the cells and scaffolds over time to mimic a bone-like environment more closely. After one week of proliferation, cell-seeded scaffolds were exposed to HP up to 270 KPa at a frequency of 1Hz, once per day, for up to two weeks. Scaffolds were incubated in osteogenic inducing media (OM) or regular culture media (CM). The effect of cyclic HP combined with OM on cell-seeded scaffolds resulted in an increase of differentiated cells. This corresponded to an upregulation of alkaline phosphatase activity and scaffold mineralization. Importantly, the results reveal that well known mechanosensitive pathways cells which regulate osteogenesis appear to remain functional even on novel plant-derived cellulosic biomaterials.
EVL and MIM/MTSS1 regulate actin cytoskeletal remodeling to promote dendritic filopodia in developing neurons
Authors: Parker SS , Ly KT , Grant AD , Wang A , Parker JD , Roman MR , Padi M , Wolgemuth CW , Langlais PR , Mouneimne G 
Published: May 2021

SUMMARYDendritic spines are the postsynaptic compartment of a functional neuronal synapse, and are critical for synaptic connectivity and plasticity. The developmental precursor to dendritic spines, dendritic filopodia, are highly motile protrusions that facilitate synapse formation by sampling the environment for suitable axon partners during development and learning. Despite the significance of the actin cytoskeleton in driving these protrusions, the actin remodeling factors involved in this process are not fully characterized. In this work, we identify a critical function for the Ena/VASP protein EVL in the regulation of dendritic filopodia. Amongst the Ena/VASP proteins, EVL is uniquely required for the characteristic morphology and dynamics of dendritic filopodia. Using a combination of genetic and optogenetic manipulations, we demonstrate that EVL promotes protrusive motility through membrane-direct actin polymerization at dendritic filopodia tips. EVL forms a complex at nascent protrusions and dendritic filopodia tips with MIM/MTSS1, an I-BAR protein recently discovered to be important for initiation of dendritic filopodia. We propose a model in which EVL cooperates with MIM to elongate and coalesce branched actin filaments, establishing the dynamic lamellipodia-like architecture of dendritic filopodia in developing neurons.
The parasitic nematode Strongyloides ratti exists as populations of long-lived asexual lineages
Authors: Cole Rebecca , Holroyd Nancy , Tracey Alan , Berriman Matt , Viney Mark 
Published: May 2021

AbstractNematodes are important parasites of people and animals and in natural ecosystems they are a major ecological force. Strongyloides ratti is a common parasitic nematode of wild rats and we have investigated its population genetics using single worm, whole genome sequencing. We find that S. ratti populations in the UK consist of mixtures of asexual lineages that are widely dispersed across a host population. These parasite lineages are likely very old and may have originated in Asia from where rats originated. Genes that underly the parasitic phase of the parasite’s life cycle are hyperdiverse, compared with the rest of the genome, and this may allow the parasites to maximise their fitness in a diverse host population. These patterns of parasitic nematode population genetics have not been found before and may also apply to Strongyloides spp. that infect people, which will affect how we should approach their control.
Sir3 Heterochromatin Protein Promotes NHEJ by Direct Inhibition of Sae2
Authors: Bordelet Hélène , Costa Rafaël , Brocas Clémentine , Dépagne Jordane , Veaute Xavier , Busso Didier , Batté Amandine , Guérois Raphaël , Marcand Stéphane , Dubrana Karine 
Published: May 2021

AbstractHeterochromatin is a conserved feature of eukaryotic chromosomes, with central roles in gene expression regulation and maintenance of genome stability. How heterochromatin proteins regulate DNA repair remains poorly described. In Saccharomyces cerevisiae, the Silent Information Regulator (SIR) complex assembles heterochromatin-like chromatin at subtelomeres. SIR-mediated repressive chromatin limits double strand break (DSB) resection protecting damaged chromosome ends during HR. As resection initiation marks the cross-road between repair by non-homologous end joining (NHEJ) or HR, we asked whether SIR- mediated heterochromatin regulates NHEJ. We show that SIRs promote NHEJ through two pathways, one depending on repressive chromatin assembly, and the other relying on Sir3 in a manner that is independent of its heterochromatin-promoting function. Sir3 physically interacts with Sae2 and this interaction impairs Sae2-dependent MRX functions. As a consequence, Sir3 limits Mre11-mediated resection, delays MRX removal from DSB ends and promotes NHEJ.