bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normothermic Regional Perfusion in Pediatric Controlled Donation After Circulatory Death Can Lead to Optimal Organ Utilization and Posttransplant Outcomes
Authors: Miñambres Eduardo , Estébanez Belen , Ballesteros Maria Ángeles , Coll Elisabeth , Flores-Cabeza Eva Mercedes , Mosteiro Fernando , Lara Ramón , Domínguez-Gil Beatriz 
Published: October 2022

Background.
The benefits of normothermic regional perfusion (NRP) in posttransplant outcomes after controlled donation after the determination of death by circulatory criteria (cDCD) has been shown in different international adult experiences. However, there is no information on the use of NRP in pediatric cDCD donors.

Methods.
This is a multicenter, retrospective, observational cohort study describing the pediatric (<18 y) cDCD procedures performed in Spain, using either abdominal NRP or thoracoabdominal NRP and the outcomes of recipients of the obtained organs.

Results.
Thirteen pediatric cDCD donors (age range, 2–17 y) subject to abdominal NRP or thoracoabdominal NRP were included. A total of 46 grafts (24 kidneys, 11 livers, 8 lungs, 2 hearts, and 1 pancreas) were finally transplanted (3.5 grafts per donor). The mean functional warm ischemic time was 15 min (SD 6 min)‚ and the median duration of NRP was 87 min (interquartile range, 69–101 min). One-year noncensored for death kidney graft survival was 91.3%. The incidence of delayed graft function was 13%. One-year‚ noncensored-for-death liver graft survival was 90.9%. All lung and pancreas recipients had an excellent evolution. One heart recipient died due to a septic shock.

Conclusions.
This is the largest experience of pediatric cDCD using NRP as graft preservation method. Although our study has several limitations, such as its retrospective nature and the small sample size, its reveals that NRP may increase the utilization of cDCD pediatric organs and offer optimal recipients’ outcomes.
The 2021 WHO classification of central nervous system tumors: what neurologists need to know
Authors: Jamshidi Pouya , Brat Daniel J. 
Published: October 2022

Purpose of review
The recently published WHO Classification of Tumours, Central Nervous System Tumours, Fifth Edition (WHO CNS-5) introduces substantial clinically relevant changes based on improved understanding of the molecular underpinnings of brain tumor types as biological entities. This review highlights pertinent changes for practicing neurologists.

Recent findings
Diffuse gliomas are now divided into adult and pediatric types. Adult types are greatly simplified, being classified into three groups based on IDH and 1p/19q status, with molecular grading criteria now included. Pediatric types are divided into low-grade or high-grade and further classified based on molecular features corresponding to clinical behavior. While still recognizing previous morphological subtypes, meningioma is now a single tumor type, with greatly advanced correlations between molecular alterations, locations, morphologic subtypes, and grades. For the first time, ependymomas are classified based on integration of anatomical location, histopathology, and molecular alterations. Importantly, WHO CNS-5 includes a number of new tumor types that have similar clinicopathologic features and are grouped together by their distinctive molecular characteristics.

Summary
The classification of CNS tumors according to objective, reproducible molecular genetic alterations, provides greater opportunity for neurologists to offer individualized treatment options, enroll homogenous patient populations into clinical trials, and ultimately discover novel therapeutics.
School-located influenza vaccination and community-wide indirect effects: reconciling mathematical models to epidemiologic models
Authors: Arinaminpathy Nimalan , Reed Carrie , Biggerstaff Matthew , Nguyen Anna , Athni Tejas S. , Arnold Benjamin F. , Hubbard Alan , Colford John M. , Reingold Art , Benjamin-Chung Jade 
Published: October 2022

AbstractBackgroundMathematical models and empirical epidemiologic studies (e.g., randomized and observational studies) are complementary tools but may produce conflicting results for a given research question. We used sensitivity analyses and bias analyses to explore such discrepancies in a study of the indirect effects of influenza vaccination.MethodsWe fit an age-structured, deterministic, compartmental model to estimate indirect effects of a school-based influenza vaccination program in California that was evaluated in a previous matched cohort study. To understand discrepancies in their results, we used 1) a model with constrained parameters such that projections matched the cohort study; and 2) probabilistic bias analyses to identify potential biases (e.g., outcome misclassification due to incomplete influenza testing) that, if corrected, would align the empirical results with the mathematical model.ResultsThe indirect effect estimate (% reduction in influenza hospitalization among older adults in intervention vs. control) was 22.3% (95% CI 7.6% – 37.1%) in the cohort study but only 1.6% (95% Bayesian credible intervals 0.4 – 4.4%) in the mathematical model. When constrained, mathematical models aligned with the cohort study when there was substantially lower pre-existing immunity among school-age children and older adults. Conversely, empirical estimates corrected for potential bias aligned with mathematical model estimates only if influenza testing rates were 15-23% lower in the intervention vs. comparison site.ConclusionsSensitivity and bias analysis can shed light on why results of mathematical models and empirical epidemiologic studies differ for the same research question, and in turn, can improve study and model design.
Targeted Nano Sized Drug Delivery to Heterogeneous Solid Tumor Microvasculatures: Implications for Immunoliposomes Exhibiting Bystander Killing Effect
Authors: Abazari Mohammad Amin , Soltani Madjid , Kashkooli Farshad Moradi 
Published: October 2022

ABSTRACTTargeted drug delivery to cancer cells utilizing antibodies against oncogenic cell-surface receptors is an emerging therapeutical approach. Here, we developed a computational framework to evaluate the treatment efficacy of free Doxorubicin (Dox) and immunoliposome at different stages of vascular solid tumors. Firstly, three stages of vascularized tumors with different microvascular densities (MVDs) are generated using mathematical modeling of tumor-induced angiogenesis. Secondly, the fluid flow in vascular and interstitial spaces is calculated. Ultimately, convection-diffusion-reaction equations governing on classical chemotherapy (stand-alone Dox) and immunochemotherapy (drug-loaded nanoparticles) are separately solved to calculate the spatiotemporal concentrations of different therapeutic agents. The present model considers the key processes in targeted drug delivery, including association/disassociation of payloads to cell receptors, cellular internalization, linker cleavage, intracellular drug release, and bystander-killing effect. Our results show that reducing MVD decreases the interstitial fluid pressure, allowing higher rates of the drug to enter the tumor microenvironment. Also, immunoliposomes exhibiting bystander-killing effect yield higher drug internalization, which supports a higher intracellular Dox concentration during immunochemotherapy. Bystander-killing effect alongside intracellular Dox release and persistence of immunoliposomes within tumor over a longer period lead to more homogeneous drug distribution and a much greater fraction of killed cancer cells than classical chemotherapy. Our findings also demonstrate drug transport at tumor microvascular networks is increased by decreasing MVD, leading to better treatment outcomes. Present results can be used to improve the treatment efficacy of drug delivery at different stages of vascular tumors.
Evidence of backcross inviability and mitochondrial DNA paternal leakage in sea turtle hybrids
Authors: Vilaça Sibelle T. , Maroso Francesco , Lara Paulo , de Thoisy Benoit , Chevallier Damien , Arantes Larissa Souza , Santos Fabricio R. , Bertorelle Giorgio , Mazzoni Camila J. 
Published: October 2022

ABSTRACTHybridization is known to be part of many species’ evolutionary history. Sea turtles have a fascinating hybridization system in which species separated by as much as 43 million years are still capable of hybridizing. Indeed, the largest nesting populations in Brazil of loggerheads (Caretta caretta) and hawksbills (Eretmochelys imbricata) have a high incidence of hybrids between these two species. A third species, olive ridleys (Lepidochelys olivacea), is also known to hybridize although at a smaller scale. Here we used restriction site-associated DNA sequencing (RAD-Seq) markers, mitogenomes, and satellite-telemetry to investigate the patterns of hybridization and introgression in the Brazilian sea turtle population and their relationship with the migratory behaviors between feeding and nesting aggregations. We also explicitly test if the mixing of two divergent genomes in sea turtle hybrids causes mitochondrial paternal leakage. We developed a new species-specific PCR-assay capable of detecting mitochondrial DNA (mtDNA) inheritance from both parental species and performed ultra-deep sequencing to estimate the abundance of each mtDNA type. Our results show that all adult hybrids are first generation (F1) and most display a loggerhead migratory behavior. We detected paternal leakage in F1 hybrids and different proportions of mitochondria from maternal and paternal species. Although previous studies showed no significant fitness decrease in hatchlings, our results support genetically-related hybrid breakdown possibly caused by cytonuclear incompatibility. Further research on hybrids from other populations besides Brazil and between different species will show if backcross inviability and mitochondrial paternal leakage is observed across sea turtle species.
Running System of Flipped Teaching Based on Video Conference
Authors: Zhang Xiao-Yu 
Published: October 2022

AbstractObjectiveI aimed to provide a basis for the standardized operation of Flipped Teaching based on Video Conference for reference by other institutions or organizations.MethodsThe teaching and research materials of Flipped Teaching with Video Conference as carrier carried out in April and June 2022 were collected. Based on the “Structure-Process-Outcome” theory, the induction method and SWOT analysis method were used for systematic analysis.ResultsA total of 43 residents participated in the teaching project, and 40 of them passed the examination, accounting for 93.0%. And the teaching project had been analyzed and reported in 3 literature. For the successful operation of this project, the following five dimensions were summarized. First, the preparatory dimension of teaching: clear teaching form, objectives, content, reference materials and assignments; Second, the carrier of teaching implementation: the selection, function and debugging of teaching equipment; Third, the teaching management dimension: the management mode, management team, lecturers team, trainees management and emergency response; Fourth, the teaching evaluation dimension: trainees’ systematic evaluation of the teaching; Fifth, the teaching assessment dimension: attendance rate, assignments completion rate and exam pass rate.ConclusionThe core of the running system is to carry out Flipped Teaching with Video Conference as carrier to realize the standardized training for residents, and ensure the smooth progress and the quality of teaching through teaching management, evaluation and assessment.
A causal model of human growth and its estimation using temporally-sparse data
Authors: Bunce John A. , Fernández Catalina I. , Revilla-Minaya Caissa 
Published: October 2022

AbstractExisting models of human growth provide little insight into underlying mechanisms responsible for inter-individual and inter-population variation in children’s growth trajectories. Building on general theories linking growth to metabolic rates, we develop a causal parametric model of height and weight growth incorporating a representation of human body allometry and a process-partitioned representation of ontogeny. This model permits separation of metabolic causes of growth variation, potentially influenced by nutrition and disease, from allometric factors, potentially under stronger genetic control. We estimate model parameters using a Bayesian multilevel statistical design applied to temporally-dense height and weight measurements of U.S. children, and temporally-sparse measurements of Indigenous Amazonian children. This facilitates a comparison of the contributions of metabolism and allometry to observed cross-cultural variation in the growth trajectories of the two populations, and permits simulation of the effects of healthcare interventions on growth. This theoretical model provides a new framework for exploring the causes of growth variation in our species, while potentially guiding the development of appropriate, and desired, healthcare interventions in societies confronting growth-related health challenges, such as malnutrition and stunting.
Newly formed place cells are stabilized by coordinated population activity during REM sleep
Authors: Boyce Richard , Yong Hyun Choong , Carmichael James E , Brandon Mark P , Williams Sylvain 
Published: October 2022

SummaryThe involvement of rapid-eye-movement sleep (REMs) in spatial memory formation was recently demonstrated, although how neural activity during REMs influences newly-formed place field stability remains unclear. Here, we combined large-scale single-unit recordings of mouse hippocampal CA1 with an established optogenetic approach enabling REMs-selective inhibition of medial septum GABAergic neurons (MSGABA), resulting in spatial memory deficits when applied post-learning. Although individual neural activity was unaffected by REMs-selective MSGABA inhibition during a post-learning rest session, both the synchrony of population-level activity bursts observed during REMs occurring in the rest session and place field stability measured during subsequent memory recall testing were reduced vs controls. However, the latter effect was limited to place cells participating in population activity during REMs, as stability of non-participant place cells was relatively weak and indifferent between groups. This suggests that synchronous CA1 population activity during REMs stabilizes spatial representations in a plastic subpopulation of participating CA1 neurons.
Magnetically powered chitosan milliwheels for rapid translation, barrier function rescue, and delivery of therapeutic proteins to the inflamed gut epithelium
Authors: Osmond M.J. , Korthals E. , Zimmermann C.J. , Roth E.J. , Marr D.W.M. , Neeves K.B. 
Published: October 2022

AbstractInflammatory bowel disease (IBD) is mediated by an overexpression of tumor necrosis factor-α (TNF) by mononuclear cells in the intestinal mucosa. Intravenous delivery of neutralizing anti-TNF antibodies can cause systemic immunosuppression and up to one-third of people are non-responsive to treatment. Oral delivery of anti-TNF could reduce adverse effects; however, it is hampered by antibody degradation in the harsh gut environment during transit and poor bioavailability. To overcome these shortcomings, we demonstrate magnetically powered hydrogel particles that roll along mucosal surfaces, provide protection from degradation, and sustain local release of anti-TNF. Iron oxide nanoparticles are embedded into a crosslinked chitosan hydrogel and sieved to produce 100-200 μm particles called milliwheels (m-wheels). Once loaded with anti-TNF, these m-wheels release 10% to 80% of their payload over one week at a rate that depends on crosslinking density and pH. A rotating magnetic field induces a torque on the m-wheels that results in rolling velocities greater than 500 μm/s on glass and mucus-secreting cells. The permeability of TNF challenged gut epithelial cell monolayers was rescued in the presence of anti-TNF carrying m-wheels which both neutralized the TNF and created an impermeable patch over leaky cell junctions. With the ability to translate over mucosal surfaces at high speed, provide sustained release directly to the inflamed epithelium, and provide barrier rescue, m-wheels demonstrate a potential strategy to deliver therapeutic proteins for the treatment of IBD.
Correlating basal gene expression across chemical sensitivity data to screen for novel synergistic interactors of HDAC inhibitors in pancreatic carcinoma
Authors: Djokovic Nemanja , Djuric Ana , Ruzic Dusan , Srdic-Rajic Tatjana , Nikolic Katarina 
Published: October 2022

AbstractPancreatic ductal adenocarcinoma (PDAC) is considered as one of the most aggressive and lethal malignancies. Development of chemoresistance in PDAC is one of the key contributors for the poor survival outcomes of PDAC patients and the major reason for urgent development of novel pharmacological approaches for effective treatment of PDAC. Systematically tailored combination therapy holds the promise for advancing the treatment of PDAC, but number of possible combinations considering all approved drugs and drug candidates is too large to be explored empirically. In respect to the many epigenetic alterations in PDAC, epigenetic drugs including histone deacetylase inhibitors (HDACi) could be seen as a game changer but available data indicates their efficacy only in combined therapy settings. In this work, we explored possibility of using drug-sensitivity data together with basal gene expression data on pancreatic cell lines to predict the combinatorial options available for HDACi and developed bioinformatics screening protocol for predictions of synergistic drug combinations in PDAC. Our results identified sphingolipid signaling pathway with associated downstream effectors as a promising novel target for future development of multi-target therapeutics or combined therapy with HDACi. Through the experimental validation, we have characterized novel synergism between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, and HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod.
On the Origin of Obligate Parthenogenesis inDaphnia pulex
Authors: Snyman Marelize , Xu Sen 
Published: October 2022

AbstractDespite the presence of obligately parthenogenetic (OP) lineages derived from sexual ancestors in diverse phylogenetic groups, the genetic mechanisms giving rise to the OP lineages remain poorly understood. The freshwater microcrustaceanDaphnia pulextypically reproduces via cyclical parthenogenesis. However, some populations of OPD. pulexhave emerged due to ancestral hybridization and introgression events between two cyclically parthenogenetic (CP) speciesD. pulexandD. pulicaria. These OP hybrids produce both subitaneous and resting eggs parthenogenetically, deviating from CP isolates where resting eggs are produced via conventional meiosis and mating. This study examines the genome-wide expression and alternative splicing patterns of early subitaneous versus early resting egg production in OPD. pulexisolates to gain insight into the genes and mechanisms underlying this transition to obligate parthenogenesis. Our differential expression and functional enrichment analyses revealed a downregulation of meiosis and cell cycle genes during early resting egg production, as well as divergent expression patterns of metabolism, biosynthesis, and signaling pathways between the two reproductive modes. These results provide important gene candidates for future experimental verification, including the CDC20 gene that activates the anaphase-promoting complex in meiosis.
Developmental Validation of the Illumina Infinium Assay using the Global Screening Array (GSA) on the iScan System for use in Forensic Laboratories
Authors: Russell David A. , Gorden Erin M. , Peck Michelle A. , Neal Christina M. , Heaton Mary C. , Bouchet Jessica , Koeppel Alexander F. , Ciuzio Elayna , Turner Stephen D. , Reedy Carmen R. 
Published: October 2022

AbstractMicroarray processing, which interrogates hundreds of thousands of single nucleotide polymorphisms (SNPs) across the human genome, has recently gained traction in forensics due to its use in forensic genetic genealogy, which is based on analysis using SNPs to compare distant relatives in publicly curated databases for the purposes of developing investigative leads or identifying human remains. To date, there has been no published developmental validation of microarray processing using the Scientific Working Group on DNA Analysis Methods (SWGDAM) Validation Guidelines for DNA Analysis Methods and Federal Bureau of Investigation Quality Assurance Standards. Validation of these methods are warranted to identify samples suitable for microarray analysis and to assess the quality of the data obtained prior to upload to genealogical databases. In this study, we validated the Global Screening Array (GSA) for use in forensic investigations according to SWGDAM guidelines, including the following studies: precision and accuracy, sensitivity, contamination, degradation, species specificity, mock case-type samples, mixtures, repeatability and reproducibility, and stability. Results indicated accurate genotype calls with SNP call rates >95% at DNA input as low as 0.20 ng. In addition to SNP call rate, we developed interpretation thresholds for signal intensity and heterozygosity to allow for sample quality assessment and identification of highly degraded and/or non-human DNA. This study demonstrates that high quality data can be generated from multiple sample types, including mock forensic evidence that simulated the challenges that are often encountered in forensic cold cases.
Statistical challenges for inferring multiple SARS-CoV-2 spillovers with early outbreak phylodynamics
Authors: Washburne Alex , Jones Adrian , Zhang Daoyu , Deigin Yuri , Quay Steven , Massey Steven E 
Published: October 2022

AbstractUnderstanding how SARS-CoV-2 entered the human population, thereby causing the COVID-19 pandemic, is one of the most urgent questions in science today. Two hypotheses are widely acknowledged as being most likely to explain the pandemic’s origin in late 2019: (i) the “natural origin” hypothesis that one or more cross-species transmissions from animals into humans occurred, most likely at the Huanan Seafood Market in Wuhan, China; (ii) the “laboratory origin” hypothesis, that scientific research activities led to the unintentional leak of SARS-CoV-2 from a laboratory into the general population.A recent analysis of SARS-CoV-2 genomes by Pekar et al. [Science377:960-966 (2022)] claims to establish at least two separate spillover events from animals into humans, thus claiming to provide strong evidence for the natural origin hypothesis. However, here we use outbreak simulations to show that the findings of Pekar et al. are heavily impacted by two methodological artifacts: the dubious exclusion of informative SARS-CoV-2 genomes, and their reliance on unrealistic phylodynamic models of SARS-CoV-2. Absent models that incorporate these effects, one cannot conclude multiple SARS-CoV-2 spillovers into humans. Our results cast doubt on a primary point of evidence in favor of the natural origin hypothesis.Lay SummaryIt is not known if SARS-CoV-2 spilled over from animals into humans at the Huanan Seafood Market, or arose as a result of research activities studying bat coronaviruses. Two recent papers had claimed to answer this question, but here we show those papers are both inconclusive as they fail to account for biases in how medical managers became alerted to SARS-CoV-2 and how public health authorities sampled early cases. Additionally, key data points conflicting with the authors’ conclusions were improperly excluded from the analysis. The papers’ methods do not justify their conclusions, and the origin of SARS-CoV-2 remains an urgent, open question for science.