bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural population dynamics in dorsal premotor cortex underlying a reach decision
Authors: Boucher Pierre O , Wang Tian , Carceroni Laura , Kane Gary , Shenoy Krishna V , Chandrasekaran Chandramouli 
Published: July 2022

AbstractWe investigated if a dynamical systems approach could help understand the link between decision-related neural activity and decision-making behavior, a fundamentally unresolved problem. The dynamical systems approach posits that neural dynamics can be parameterized by a state equation that has different initial conditions and evolves in time by combining at each time step, recurrent dynamics and inputs. For decisions, the two key predictions of the dynamical systems approach are that 1) initial conditions substantially predict subsequent dynamics and behavior and 2) inputs should combine with initial conditions to lead to different choice-related dynamics. We tested these predictions by investigating neural population dynamics in the dorsal premotor cortex (PMd) of monkeys performing a red-green reaction time (RT) checkerboard discrimination task where we varied the sensory evidence (i.e., the inputs). Prestimulus neural state, a proxy for the initial condition, predicted poststimulus neural trajectories and showed organized covariation with RT. Furthermore, faster RTs were associated with faster pre- and poststimulus dynamics as compared to slower RTs, with these effects observed within a stimulus difficulty. Poststimulus dynamics depended on both the sensory evidence and initial condition, with easier stimuli and “fast” initial conditions leading to the fastest choice-related dynamics whereas harder stimuli and “slow” initial conditions led to the slowest dynamics. Finally, changes in initial condition were related to the outcome of the previous trial, with slower pre- and poststimulus population dynamics and RTs on trials following an error as compared to trials following a correct response. Together these results suggest that decision-related activity in PMd is well described by a dynamical system where inputs combine with initial conditions that covary with eventual RT and previous outcome, to induce decision-related dynamics.
epialleleR: an R/Bioconductor package for sensitive allele-specific methylation analysis in NGS data
Authors: Nikolaienko Oleksii , Lønning Per Eystein , Knappskog Stian 
Published: July 2022

ABSTRACTLow-level mosaic methylation of theBRCA1gene promoter occurs in 5–8% of healthy individuals and is associated with a significantly elevated risk of breast and ovarian cancer. Similar events may also affect other tumour suppressor genes, potentially being a significant contributor to cancer burden. While this opens a new area for translational research, detection of low-level mosaic epigenetic events requires highly sensitive and robust methodology for methylation analysis. We here present epialleleR, a computational framework for sensitive detection, quantification and visualisation of mosaic epimutations in methylation sequencing data. Analysing simulated and real data sets, we provide in-depth assessments of epialleleR performance, and show that linkage to epihaplotype data is necessary to detect low-level methylation events. The epialleleR is freely available athttps://github.com/BBCG/epialleleRandhttps://bioconductor.org/packages/epialleleR/as an open source R/Bioconductor package.
Concurrent gliomas in patients with multiple sclerosis
Authors: Sahm Katharina , Kessler Tobias , Eisele Philipp , Ratliff Miriam , Sperk Elena , König Laila , Breckwoldt Michael O. , Seliger Corinna , Mildenberger Iris , Schrimpf Daniel , Herold-Mende Christel , Zeiner Pia S. , Tabatabai Ghazaleh , Meuth Sven G. , Capper David , Bendszus Martin , von Deimling Andreas , Wick Wolfgang , Sahm Felix , Platten Michael 
Published: July 2022

AbstractBackgroundConcurrent malignant brain tumors in patients with multiple sclerosis (MS) constitute a rare but paradigmatic phenomenon for studying neuroimmunological mechanisms from both molecular and clinical perspectives.MethodsA multicenter cohort of 26 patients diagnosed with both primary brain tumors and multiple sclerosis was studied for disease localization, tumor treatment-related MS activity, and molecular characteristics specific for diffuse glioma in MS patients.ResultsMS neither predisposes nor protects from the development of gliomas. Patients with glioblastoma WHO grade IV without IDH mutations had a longstanding history of MS, whereas patients diagnosed with IDH-mutant astrocytoma WHO grade II received multiple sclerosis diagnosis mostly at the same time or later. Concurrent MS was associated with a lesser extent of tumor resection and a worse prognosis in IDH-mutant glioma patients (PFS 32 vs. 64 months, p=0.0206). When assessing tumor-intrinsic differences no distinct subgroup-defining methylation pattern was identified in gliomas of MS patients compared to other glioma samples. However, differential methylation of immune-related genetic loci including human leukocyte antigen locus on 6p21 and interleukin locus on 5q31 was found in MS patients vs. matched non-MS patients. In line, inflammatory disease activity increased in 42% of multiple sclerosis patients after brain tumor radiotherapy suggesting a susceptibility of multiple sclerosis brain tissue to pro-inflammatory stimuli such as ionizing radiation.ConclusionsConcurrent low-grade gliomas should be considered in multiple sclerosis patients with slowly progressive, expansive T2/FLAIR lesions. Our findings of typically reduced extent of resection in MS patients and increased MS activity after radiation inform future treatment decisions.Key points–Disease history and sequence of diagnosis differ in MS patients with high-vs low-grade glioma–Gliomas of MS patients harbor subtle methylation changes in immune-related genetic regions–Brain tumor radiotherapy is followed by MS disease activityImportance of the studyImmune escape is a hallmark of diffuse glioma, while inflammation is the underlying mechanism of multiple sclerosis. These opposing mechanisms concur in patients that suffer in parallel from multiple sclerosis and glioma. This study is the first to investigate the tumor characteristics, tumor treatment responses and effect on multiple sclerosis activity of a cohort of patients with both diseases. The data warrant caution in the interpretation of suspicious lesions in imaging and suggests risk loci for the observed detrimental effects of radiation specific to MS patients.
Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi
Authors: Wadhwa Bharti , Malhotra Vikas , Kerai Sukhyanti , Husain Farah , Pandey Nalini Bala , Saxena Kirti N , Singh Vinay , Quinn Tom M , Li Feng , Gaughan Erin , Shankar-Hari Manu , Mills Bethany , Antonelli Jean , Bruce Annya , Finlayson Keith , Moore Anne , Dhaliwal Kevin , Edwards Christopher 
Published: July 2022

ABSTRACTBackgroundIn this phase 2 randomised placebo-controlled clinical trial, we hypothesised that blocking mineralocorticoid receptors with spironolactone in patients with COVID-19 is safe and may reduce illness severity.MethodsHospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50mg day 1, then 25mg once daily for 21 days) or standard care in a 2:1 ratio. Both groups received dexamethasone 6mg for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category ≤ 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF).Results120 patients were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had lower aldosterone levels on day 7 and lower D-dimer levels on days 4 and 7 (day 7 D-dimer mean SpiroDex 1.15µg/mL, Dex 3.15 µg/mL, p = 0.0004). There was no increase in adverse events in patients receiving SpiroDex.Post hocanalysis demonstrated reduced clinical deterioration (pre specified as escalating to WHO OS category >4) in the SpiroDex group vs Dex group (5.4% vs 19.6%).ConclusionLow dose oral spironolactone in addition to dexamethasone was safe and reduced D-Dimer and aldosterone. Although time to recovery was not significantly reduced, fewer patients progressed to severe disease. Phase 3 randomised controlled trials with spironolactone should be considered.
Kinematic and neuromuscular characterization of cognitive involvement in gait control in healthy young adults
Authors: Lana Valentin , Frère Julien , Cabibel Vincent , Réguème Tristan , Lefèvre Nicolas , Vlamynck Elodie , Decker Leslie M. 
Published: July 2022

ABSTRACTThe signature of cognitive involvement in gait control has rarely been studied using both kinematic and neuromuscular features. The present study aimed to address this gap. Twenty-four healthy young adults walked on an instrumented treadmill in a virtual environment under two optic flow conditions: normal (NOF) and perturbed (POF, continuous mediolateral pseudorandom oscillations). Each condition was performed under single-task and dual-task conditions of increasing difficulty (1-, 2-, 3-back). Subjective mental workload (raw NASA-TLX), cognitive performance (mean reaction time and d-prime), kinematic (steadiness, variability and complexity in the mediolateral and anteroposterior directions) and neuromuscular (duration and variability of motor primitives) control of gait were assessed. The cognitive performance and the number and composition of motor modules were unaffected by simultaneous walking, regardless of the optic flow condition. Kinematic and neuromuscular variability was greater under POF compared to NOF conditions. Young adults sought to counteract POF by rapidly correcting task-relevant gait fluctuations. The depletion of cognitive resources through dual-tasking led to reduced kinematic and neuromuscular variability and this occurred to the same extent regardless of simultaneous working memory (WM) load. Increasing WM load led to a prioritization of gait control in the mediolateral direction over the anteroposterior direction. The impact of POF on kinematic variability (step velocity) was reduced when a cognitive task was performed simultaneously, but this phenomenon was no modulated by WM load. Collectively, these results shed important light on how young adults adjust the processes involved in goal-directed locomotion when exposed to varying levels of task and environmental constraints.NEW & NOTEWORTHYThe kinematic and neuromuscular signatures of cognitive involvement in gait control have rarely been studied jointly. We sought to address this issue using gait perturbation and dual-task paradigms. The protocol consisted of a fixed-speed treadmill walk to which visual and cognitive constraints were applied separately and together. The results revealed that young adults optimally regulated their gait to cope with these constraints by maintaining relatively stable muscle synergies and flexibly allocating attentional resources.
RORc expressing immune cells negatively regulate tertiary lymphoid structure formation and support their pro-tumorigenic functions
Authors: Cinnamon Einat , Stein Ilan , Zino Elvira , Rabinovich Stav , Shovman Yehuda , Schlesinger Yehuda , Salame Tomer-Meir , Reich-Zeliger Shlomit , Lotem Michal , Ben-Neriah Yinon , Parnas Oren , Pikarsky Eli 
Published: July 2022

AbstractTertiary lymphoid structures (TLSs) are formed in many cancer types and have been correlated with better prognosis and response to immunotherapy. In liver cancer, TLSs have been reported to be pro-tumorigenic as they harbor tumor progenitor cells and nurture their growth. The processes involved in TLS development and the acquisition of a pro- or anti-tumorigenic phenotype in cancer are largely unknown. RORc expressing immune cells have been previously implicated in TLS formation, however we find that they are not necessary for TLS neogenesis in the context of inflammation-associated liver cancer. On the contrary, RORc expressing cells negatively regulate TLS formation, since in their absence TLSs form in excess. CD4 cells are essential for liver TLS formation whereas B cells are required for TLS formation specifically in the absence of RORc expressing cells. Importantly, in chronically inflamed livers lacking RORc expressing cells, TLSs become anti-tumorigenic, resulting in reduced tumor load. Comparing liver pro- and anti-tumorigenic TLSs by transcriptional, proteomic and immunohistochemical analyses, revealed enrichment of exhausted CD8 cells that retained effector functions as well as germinal center B cells and plasma cells in anti-tumorigenic TLSs. Cell depletion experiments revealed a role mainly for B cells in limiting tumor development, possibly via tumor directed antibodies. Thus, RORc expressing cells negatively regulate B cell responses, and facilitate the pro-tumorigenic functions of hepatic TLSs.
Predator-Prey Interactions Give Rise to Scale-Invariant Ecosystems
Authors: Salahshour Mohammad 
Published: July 2022

AbstractA large body of empirical evidence has shown that scaling laws and power-law distributions are ubiquitous features of ecological systems. However, it is not clear what factors give rise to such universal regularities and how scaling laws and scale-invariant distributions relate to each other. Here, I show scaling laws can be a simple consequence of scale-invariant distributions, and both result from simple commonalities of apparently different ecosystems. I introduce a simple model of predator-prey interactions in which predators and prey move on a two-dimensional space in search of resources that they use to survive and reproduce. The model predicts predator-prey systems can be found in different phases: as primary resources increase, the system exhibits a series of consecutive transitions to different phases with equilibrium dynamics and top-down control of the food web, non-equilibrium dynamics with bottom-up control, or unstable dynamics. While unstable predator-prey dynamics can result in a homogeneous environment by enrichment of resources, resource heterogeneity restores the stability of the system. Scale-invariant group size distribution and a rich set of scaling laws result in the non-equilibrium phase. By developing a general theory, I argue scaling laws can result from the scale-invariance of group size distributions under broad conditions. While some of the scaling laws predicted by the model await empirical examination, consistently with a recently discovered empirical pattern, the model shows predator abundance and prey production show a sublinear scaling with prey abundance. The model links the nature of the control in the food web, prey’s and predators’ behavioral responses to each other, and their life histories. While in small densities, mass-action law holds, and a weak density dependence and top-down control follows, in large densities, a shelter effect - the benefit of living in groups for preys - plays a role and makes prey production non-invariant to density fluctuations. Due to higher density fluctuations in higher densities, prey per-capita production in large densities decreases. This leads to a longer lifespan and lower population turnover of prey, and a scale-invariant ecosystem with bottom-up control in large densities.
Single cell multi-omic mapping of subclonal architecture and pathway phenotype in primary gastric and metastatic colon cancers
Authors: Bai Xiangqi , Lau Billy , Grimes Susan M. , Sathe Anuja , Ji Hanlee P. 
Published: July 2022

ABSTRACTSingle cell genomics provides a high-resolution profile of intratumoral heterogeneity and subclonal structure in primary and metastatic tumors. Notably, metastases and therapeutic resistant tumors often originate from distinct subclones. These distinct cellular populations are an important contributor to adaptation and resistance to ongoing therapy. Single cell DNA-sequencing (scDNA-seq) defines subclones but does not provide biological information about cell types. Single cell RNA-sequencing (scRNA-seq) provides biological information but is less useful for identifying different subclones. The integrated scDNA-seq and scRNA-seq data from the same tumor cell population provides both subclone structure and biology. To understand the cellular genomic variation of different subclones in primary and metastatic cancers, we developed an approach to integrate multi-omics data from both types of single cells. This joint data set represented thousands of normal and tumor cells derived from a set of primary gastric and metastatic colorectal cancers. The extensive cellular sampling provided robust characterization of the subclonal architecture of gastric and colorectal cancers. We reconstructed the subclonal architecture using the cells in G0/G1 phase. The scDNA-seq provided a ground truth for copy number-based subclones. From the scRNA-seq data, the epithelial cells in G0/G1 were identified and assigned to specific subclones by a correlation algorithm based on gene dosage. The inferred CNV profiles from the scRNA-seq epithelial cells were assigned subclones identified from the scDNA-seq. Afterward, we determined the biological pathway activities of specific clones. Overall, integrative multi-omics analysis of single-cell datasets is more informative than any individual genomic modality, provides deep insights into the intratumoral heterogeneity, and reveals subclonal biology.
Status of Genome Function Annotation in Model Organisms and Crops
Authors: Xue Bo , Rhee Seung Y 
Published: July 2022

AbstractSince entry into genome-enabled biology several decades ago, much progress has been made in determining, describing, and disseminating functions of genes and their products. Yet, this information is still difficult to access for many scientists and for most genomes. To provide easy access and graphical summary to the status of genome function annotation for model organisms and bioenergy and food crop species, we created a web application (https://genomeannotation.rheelab.org) to visualize, search, and download genome annotation data for 28 species. The summary graphics and data tables will be updated semi-annually and snapshots will be archived to provide a historical record of the progress of genome function annotation efforts. Clear and simple visualization of updated gene function annotation, including the extent of what is unknown, will help address the grand challenge of elucidating functions of all genes in organisms.
Monanthotaxis bali (Annonaceae) a new Critically Endangered (possibly extinct) montane forest treelet from Bali Ngemba, Cameroon
Authors: Cheek Martin , Darbyshire Iain , Onana Jean Michel 
Published: July 2022

SummaryMonanthotaxis bali is the only known, solely montane (occurring solely above 2000 m alt.) species of the genus. It joins Monanthotaxis orophila (Rwanda) and M. discolor (Tanzania), two other species that can also occur above 2000 m alt. Monanthotaxis bali is an addition to the small number (28) of the tree species of the surviving montane forests of the Cameroon Highlands of which only eight other species are endemic.Due to its supra-axillary inflorescences, and petals arranged in one whorl but with the outer petals overlapping the inner petals distally, and rounded flower buds, the new species is placed in Hoekstra’s clade B of Monanthotaxis. The new species is unusual in being a treelet in a predominantly lianescent genus, and in lacking the glaucous underside of the leaf-blades that usually characterises the genus. Monanthotaxis bali takes the number of continental African species of the genus to 80, and makes Cameroon, with 30 species, the most species-diverse country for the genus.Monanthotaxis bali is known only from the Bali Ngemba Forest Reserve, a forest remnant under pressure of degradation and clearance in the Bamenda Highlands of Cameroon. It may already be extinct due to logging and agricultural activities. Here it is described, illustrated, mapped and assessed as Critically Endangered (Possibly Extinct) using the IUCN 2012 criteria.
CometAnalyser: a user-friendly, open-source deep-learning microscopy tool for quantitative comet assay analysis
Authors: Beleon Attila , Pignatta Sara , Arienti Chiara , Carbonaro Antonella , Horvath Peter , Martinelli Giovanni , Castellani Gastone , Tesei Anna , Piccinini Filippo 
Published: July 2022

ABSTRACTComet assay provides an easy solution to estimate DNA damage in single cells through microscopy assessment. It is widely used in the analysis of genotoxic damages induced by radiotherapy or chemotherapeutic agents. DNA damage is quantified at the single-cell level by computing the displacement between the genetic material within the nucleus, typically called “comet head”, and the genetic material in the surrounding part of the cell, considered as the “comet tail”. Today, the number of works based on Comet Assay analyses is really impressive. In this work, besides revising the solutions available to obtain reproducible and reliable quantitative data, we developed an easy-to-use tool named CometAnalyser. It is designed for the analysis of both fluorescent and silver-stained wide-field microscopy images and allows to automatically segment and classify the comets, besides extracting Tail Moment and several other intensity/morphological features for performing statistical analysis. CometAnalyser is an open-source deep-learning tool. It works with Windows, Macintosh, and UNIX-based systems. Source code, standalone versions, user manual, sample images, video tutorial and further documentation are freely available at: https://sourceforge.net/p/cometanalyser.HIGHLIGHTSComet assay provides an easy solution to estimate DNA damage in single cells.Today, an impressive number of works are based on Comet Assay analyses, especially in the field of cancer research.Comet assay was originally performed as a qualitative analysis.None of the free tools today available work on both fluorescent- and silver-stained images.We developed CometAnalyser, an open-source deep-learning tool designed for easy segmentation and classification of comets in fluorescent- and silver-stained images.
Zinc ions prevent α-synuclein aggregation by enhancing chaperone function of human serum albumin
Authors: Al-Harthi Samah , Kharchenko Vladlena , Mandal Papita , Gourdoupis Spyridon , Jaremko Lukasz 
Published: July 2022

ABSTRACTMetal ions present in cellular microenvironment have been implicated as drivers of aggregation of amyloid forming proteins. Zinc (Zn2+) ions have been reported to directly interact with α-synuclein (AS), a causative agent of Parkinson’s disease and other neurodegenerative diseases, and promote its aggregation. AS is a small intrinsically disordered protein (IDP) i.e., understanding molecular factors that drive its misfolding and aggregation has been challenging since methods used routinely to study protein structure are not effective for IDPs. Here, we report the atomic details of Zn2+ binding to AS at physiological conditions using proton-less NMR techniques that can be applied to highly dynamic systems like IDPs. We also examined how human serum albumin (HSA), the most abundant protein in human blood, binds to AS and whether Zn2+ and/or ionic strength affect this. We conclude that Zn2+ enhances the anti-aggregation chaperoning role of HSA that relies on protecting the hydrophobic N-terminal and NAC regions of AS, rather than polar negatively charged C-terminus. This suggested a previously undocumented role of Zn2+ in HSA function and AS aggregation.