bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of anastomotic technique and gastric conduit perfusion with hyperspectral imaging in an experimental model for minimally invasive esophagectomy
Authors: Nickel F. , Studier-Fischer A. , Özdemir B. , Odenthal J. , Müller L.R. , Knödler S. , Kowalewski K.F. , Camplisson I. , Allers M.M. , Dietrich M. , Schmidt K. , Salg G.A. , Kenngott H.G. , Billeter A.T. , Gockel I. , Sagiv C. , Hadar O.E. , Gildenblat J. , Ayala L. , Seidlitz S. , Maier-Hein L. , Müller-Stich B.P. 
Published: October 2021

AbstractObjectiveTo optimize anastomotic technique and gastric conduit perfusion with hyperspectral imaging (HSI) for total minimally invasive esophagectomy (MIE) with linear stapled anastomosis.Summary Background DataEsophagectomy is the mainstay of esophageal cancer treatment but anastomotic insufficiency related morbidity and mortality remain challenging for patient outcome.MethodsA live porcine model (n=50) for MIE was used with gastric conduit formation and linear stapled side-to-side esophagogastrostomy. Four main experimental groups differed in stapling length (3 vs. 6 cm) and anastomotic position on the conduit (cranial vs. caudal). Tissue oxygenation around the anastomotic site was evaluated using HSI and was validated with histopathology.ResultsThe tissue oxygenation (ΔStO2) after the anastomosis remained constant only for the short stapler in caudal position (−0.4± 4.4%, n.s.) while it dropped markedly in the other groups (short-cranial: -15.6± 11.5%, p=0.0002; long-cranial: -20.4± 7.6%, p=0.0126; long-caudal: -16.1± 9.4%, p<0.0001) Tissue samples from deoxygenated stomach as measured by HSI showed correspondent eosinophilic pre-necrotic changes in 35.7± 9.7% of the surface area.ConclusionsTissue oxygenation at the anastomotic site of the gastric conduit during MIE is influenced by stapling technique. Optimal oxygenation was achieved with a short stapler (3 cm) and sufficient distance of the anastomosis to the cranial end of the gastric conduit. HSI tissue deoxygenation corresponded to histopathologic necrotic tissue changes. These findings allow for optimization of gastric conduit perfusion and anastomotic technique in MIE.Level of EvidenceNot applicable. Translational animal science. Original article.
Proteome biology of primary colorectal carcinoma and corresponding liver metastases
Authors: Fahrner Matthias , Bronsert Peter , Fichtner-Feigl Stefan , Jud Andreas , Schilling Oliver 
Published: October 2021

AbstractColorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis-promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how thein vitroinhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.
Signatures of vibration frequency tuning in human neocortex
Authors: Wang Lingyan , Yau Jeffrey M. 
Published: October 2021

ABSTRACTThe spectral content of vibrations produced in the skin conveys essential information about textures and underlies sensing through hand-held tools. Humans can perceive and discriminate vibration frequency, yet the central representation of this fundamental feature is unknown. Using fMRI, we discovered that cortical responses are tuned for vibration frequency. Voxel tuning was biased in a manner that reflects perceptual sensitivity and the response profile of the Pacinian afferent system. These results imply the existence of tuned populations that may encode naturalistic vibrations according to their constituent spectra.
Lamina cribrosa vessel and collagen beam networks are distinct
Authors: Waxman Susannah , Brazile Bryn L. , Yang Bin , Gogola Alexandra L. , Hua Yi , Lam Po , Lee Po-Yi , Voorhees Andrew P. , Rizzo Joseph F. , Jakobs Tatjana C. , Sigal Ian A. 
Published: October 2021

AbstractOur goal was to analyze the spatial interrelation between vascular and collagen networks in the lamina cribrosa (LC). Specifically, we quantified the percentages of collagen beams with/without vessels and of vessels inside/outside of collagen beams. To do this, the vasculature of six normal monkey eyes was labelled by perfusion post-mortem. After enucleation, coronal cryosections through the LC were imaged using fluorescence and polarized light microscopy to visualize the blood vessels and collagen beams, respectively. The images were registered to form 3D volumes. Beams and vessels were segmented, and their spatial interrelationship was quantified in 3D. We found that 22% of the beams contained a vessel (range 14% to 32%), and 21% of vessels were outside beams (13% to 36%). Stated differently, 78% of beams did not contain a vessel (68% to 86%), and 79% of vessels were inside a beam (64% to 87%). Individual monkeys differed significantly in the fraction of vessels outside beams (p<0.01 by linear mixed effect analysis), but not in the fraction of beams with vessels (p>0.05). There were no significant differences between contralateral eyes in the percent of beams with vessels and of vessels outside beams (p>0.05). Our results show that the vascular and collagenous networks of the LC in monkey are clearly distinct, and the historical notions that each LC beam contains a vessel and all vessels are within beams are inaccurate. We postulate that vessels outside beams may be relatively more vulnerable to mechanical compression by elevated IOP than are vessels shielded inside of beams.Research highlights- We combined fluorescence and polarized light microscopy to map in 3D the lamina cribrosa vessels and collagen beams of three pairs of monkey eyes- Collagen beam and vessel networks of the lamina cribrosa have distinct topologies- Over half of lamina cribrosa collagen beams did not contain a blood vessel- One fifth of blood vessels in the lamina cribrosa were outside collagen beams- Beams with/without vessels and vessels inside/outside beams may respond differently to IOP
Th2 single-cell heterogeneity and clonal interorgan distribution in helminth-infected mice
Authors: Radtke Daniel , Thuma Natalie , Kirchner Philipp , Ekici Arif B , Voehringer David 
Published: October 2021

AbstractTh2 cells provide effector functions in type 2 immune responses to helminths and allergens. Despite knowledge about molecular mechanisms of Th2 cell differentiation, there is little information on Th2 cell heterogeneity and clonal distribution between organs. To address this, we performed combined single-cell transcriptome and TCR clonotype analysis on murine Th2 cells in mesenteric lymph nodes (MLN) and lung after infection withNippostrongylus brasiliensis(Nb) as a human hookworm infection model. We find organ-specific expression profiles, but also populations with conserved migration or effector/resident memory signatures that unexpectedly cluster with potentially regulatoryIl10posFoxp3negcells. A substantial MLN subpopulation with an interferon response signature suggests a role for interferon-signaling in Th2 differentiation or diversification. Further RNA-inferred developmental directions indicate proliferation as a hub for differentiation decisions. We also link long notedCxcr3expression in the Th2 compartment to a population ofIl4posNKT cells. Although the TCR repertoire is highly heterogeneous, we identified expanded clones and CDR3 motifs. Clonal relatedness between distant organs confirmed effective exchange of Th2 effector cells, although locally expanded clones dominated the response. These results provide new insights in Th2 cell subset diversity and clonal relatedness in distant organs.
F-Actin Bending Facilitates Net Actomyosin Contraction By Inhibiting Expansion With Plus-End-Located Myosin Motors
Authors: Tam Alexander K. Y. , Mogilner Alex , Oelz Dietmar B. 
Published: October 2021

AbstractContraction of actomyosin networks underpins important cellular processes including motility and division. The mechanical origin of actomyosin contraction is not fully-understood. We investigate whether contraction arises on the scale of individual filaments, without needing to invoke network-scale interactions. We derive discrete force-balance and continuum partial differential equations for two symmetric, semi-flexible actin filaments with an attached myosin motor. Assuming the system exists within a homogeneous background material, our method enables computation of the stress tensor, providing a measure of contractility. After deriving the model, we use a combination of asymptotic analysis and numerical solutions to show how F-actin bending facilitates contraction on the scale of two filaments. Rigid filaments exhibit polarity-reversal symmetry as the motor travels from the minus to plus-ends, such that contractile and expansive components cancel. Filament bending induces a geometric asymmetry that brings the filaments closer to parallel as a myosin motor approaches their plus-ends, decreasing the effective spring force opposing motor motion. The reduced spring force enables the motor to move faster close to filament plus-ends, which reduces expansive stress and gives rise to net contraction. Bending-induced geometric asymmetry provides both new understanding of actomyosin contraction mechanics, and a hypothesis that can be tested in experiments.
Stepwise progression of β-selection during T cell development as revealed by histone deacetylation inhibition
Authors: Chann Anchi S , Charnley Mirren , Newton Lucas M. , Newbold Andrea , Wiede Florian , Tiganis Tony , Humbert Patrick O , Johnstone Ricky W , Russell Sarah M 
Published: October 2021

AbstractDuring T cell development, the first step in creating a unique T Cell Receptor (TCR) is the genetic recombination of the TCRβ chain. The quality of the newly recombined TCRβ is assessed at the β-selection checkpoint. Most cells fail this checkpoint and die, but the coordination of the complex events that control fate at the β-selection checkpoint is not yet understood. We shed new light on fate determination during β-selection using a selective inhibitor of histone deacetylase 6, ACY1215. ACY1215 disrupted the β-selection checkpoint. Characterising the basis for this disruption revealed a new, pivotal stage in β-selection, bookended by upregulation of the TCR co-receptors, CD28 and CD2 respectively. Within this ‘DN3bPre’stage, CD5 and Lef1 are upregulated to reflect pre-TCR signalling and their expression correlates with proliferation. During this phase, ACY1215-mediated disruption of the organisation of the β-selection immunological synapse is associated with a breakdown in connectivity of expression of pre-TCR, CD5 and Lef1. Subsequent deregulation of pre-TCR-induced proliferation leads to bypass of the β-selection checkpoint and subsequent failure to progress. We propose that the progressive expression of CD28, CD5 and Lef1, then CD2 reports and modulates the pre-TCR signal to orchestrate passage through the β-selection checkpoint. These findings suggest a refined model of β-selection in which a coordinated increase in expression of pre-TCR, CD28, CD5 and Lef1 allows for modulating TCR signalling strength, and culminates in the expression of CD2 to enable exit from the β-selection checkpoint.
LOCOM: A logistic regression model for testing differential abundance in compositional microbiome data with false discovery rate control
Authors: Hu Yingtian , Satten Glen A. , Hu Yi-Juan 
Published: October 2021

AbstractMotivationCompositional analysis is based on the premise that a relatively small proportion of taxa are “differentially abundant”, while the ratios of the relative abundances of the remaining taxa remain unchanged. Most existing methods of compositional analysis such as ANCOM or ANCOM-BC use log-transformed data, but log-transformation of data with pervasive zero counts is problematic, and these methods cannot always control the false discovery rate (FDR). Further, high-throughput microbiome data such as 16S amplicon or metagenomic sequencing are subject to experimental biases that are introduced in every step of the experimental workflow. McLaren, Willis and Callahan [1] have recently proposed a model for how these biases affect relative abundance data.MethodsMotivated by [1], we show that the (log) odds ratios in a logistic regression comparing counts in two taxa are invariant to experimental biases. With this motivation, we propose LOCOM, a robust logistic regression approach to compositional analysis, that does not require pseudocounts. We use a Firth bias-corrected estimating function to account for sparse data. Inference is based on permutation to account for overdispersion and small sample sizes. Traits can be either binary or continuous, and adjustment for continuous and/or discrete confounding covariates is supported.ResultsOur simulations indicate that LOCOM always preserved FDR and had much improved sensitivity over existing methods. In contrast, ANCOM often had inflated FDR; ANCOM-BC largely controlled FDR but still had modest inflation occasionally; ALDEx2 generally had low sensitivity. LOCOM and ANCOM were robust to experimental biases in every situation, while ANCOM-BC and ALDEx2 had elevated FDR when biases at causal and non-causal taxa were differentially distributed. The flexibility of our method for a variety of microbiome studies is illustrated by the analysis of data from two microbiome studies.Availability and implementationOur R package LOCOM is available on GitHub athttps://github.com/yijuanhu/LOCOMin formats appropriate for Macintosh or Windows.
Clinical utility of Elecsys Anti-SARS-CoV-2 S assay in COVID-19 vaccination: An exploratory analysis of the mRNA-1273 phase 1 trial
Authors: Jochum Simon , Kirste Imke , Hortsch Sayuri , Grunert Veit Peter , Legault Holly , Eichenlaub Udo , Kashlan Basel , Pajon Rolando 
Published: October 2021

AbstractBackgroundThe ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461).MethodsSamples from 30 healthy participants, aged 18–55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL – equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80), live-virus (PRNT80), and a pseudovirus neutralizing antibody assay (PsVNA50).ResultsRBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but 2 participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels were 3.27–7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson’s r=0.938; p<0.0001) and S-2P ELISA (r=0.918; p<0.0001). For both ELISAs, heterogeneous baseline results and smaller increases in antibody levels following the second vs first vaccination compared with ACOV2S were observed. ACOV2S showed absence of any baseline noise indicating high specificity detecting vaccine-induced antibody response. Moderate–strong correlations were observed between ACOV2S and neutralization tests (nLUC80 r=0.933; PsVNA50, r=0.771; PRNT80, r=0.672; all p≤0.0001).ConclusionThe Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination, and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response.
Ptbp1 deletion does not induce glia-to-neuron conversion in adult mouse retina and brain
Authors: Hoang Thanh , Kim Dong Won , Appel Haley , Pannullo Nicole A. , Leavey Patrick , Ozawa Manabu , Zheng Sika , Yu Minzhong , Peachey Neal S. , Kim Juhyun , Blackshaw Seth 
Published: October 2021

AbstractDirect reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Müller glia and brain astrocytes into functional neurons. However, genetic analysis of Ptbp1 function in adult glia has not been conducted. Here, we use a combination of genetic lineage tracing, scRNA-Seq, and electrophysiological analysis to show that specific deletion of Ptbp1 in adult retinal Müller glia and brain astrocytes does not lead to any detectable level of glia-to-neuron conversion. Only a few changes in gene expression are observed in glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage tracing methods in studying cell type conversion.
Projected dynamics of breeding habitat suitability for a steppe-land bird warrant anticipatory conservation actions
Authors: Simoncini Andrea , Ramellini Samuele , Martineau Alexis , Massolo Alessandro , Giunchi Dimitri 
Published: October 2021

ABSTRACTUnderstanding spatial and temporal variations of habitat suitability is fundamental for species’ conservation under global change. Steppic species are particularly sensitive to anthropogenic change and have undergone large declines in the last decades. We aimed to describe current and future breeding habitat suitability for the Eurasian stone-curlew Burhinus oedicnemus, a steppic species of conservation concern, and to identify critical areas for its conservation. We collected 1628 presence records covering the period 1992-2016. We developed a species distribution model using a dynamic Maxent algorithm and a set of pseudo-absences with a spatial density weighted on a fixed kernel density estimated on the presences, to mitigate the potential sampling bias. We projected this model under a set of carbon emission, socioeconomic and land-use/land-cover scenarios for the years 2030, 2050, 2070 and 2090. Finally, we described the cell-wise and mean change of breeding habitat suitability through consecutive time intervals and identified the areas critical for the species’ conservation.All scenarios predicted a short-term northward shift of suitable areas, followed by a period of stability. We found no consistent trends in the mean change of breeding habitat suitability, and similar extents of suitable areas under current and future scenarios. Critical areas for the conservation of the species are mainly located in Northern Europe, Israel and parts of North Africa, the Iberian Peninsula and Italy. According to our results, the Eurasian stone-curlew has the potential to maintain viable populations in the Western Palearctic, but dispersal limitations might hinder the colonization of shifted suitable areas. Targeted conservation interventions in the critical areas are therefore recommended to secure the future of the species under global change.
Using bootstrap procedures for testing the modular partition inferred via leading eigenvector community detection algorithm
Authors: Vertsimakha Oksana , Dzeverin Igor 
Published: October 2021

AbstractModularity and modular structures can be recognized at various levels of biological organization and in various domains of studies. Recently, algorithms based on network analysis came into focus. And while such a framework is a powerful tool in studying modular structure, those methods usually pose a problem of assessing statistical support for the obtained modular structures. One of the widely applied methods is the leading eigenvector, or Newman’s spectral community detection algorithm. We conduct a brief overview of the method, including a comparison with some other community detection algorithms and explore a possible fine-tuning procedure. Finally, we propose an adapted bootstrap-based procedure based on Shimodaira’s multiscale bootstrap algorithm to derive approximately unbiased p-values for the module partitions of observations datasets. The proposed procedure also gives a lot of freedom to the researcher in constructing the network construction from the raw numeric data, and can be applied to various types of data and used in diverse problems concerning modular structure. We provide an R language code for all the calculations and the visualization of the obtained results for the researchers interested in using the procedure.