bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between input connectivity, morphology and orientation tuning of layer 2/3 pyramidal cells in mouse visual cortex
Authors: Weiler Simon , Nilo Drago Guggiana , Bonhoeffer Tobias , Hübener Mark , Rose Tobias , Scheuss Volker 
Published: June 2020

AbstractNeocortical pyramidal cells (PCs) display functional specializations defined by their excitatory and inhibitory circuit connectivity. For layer 2/3 (L2/3) PCs, little is known about the detailed relationship between their neuronal response properties, dendritic structure and their underlying circuit connectivity at the level of single cells. Here, we ask whether L2/3 PCs in mouse primary visual cortex (V1) differ in their functional intra- and interlaminar connectivity patterns, and how this relates to differences in visual response properties. Using a combined approach, we first characterized the orientation and direction tuning of individual L2/3 PCs within vivo2-photon calcium imaging. Subsequently, we performed excitatory and inhibitory synaptic input mapping of the same L2/3 PCs in brain slices using laser scanning photostimulation (LSPS).Our data from this structure-connectivity-function analysis show that the sources of excitatory and inhibitory synaptic input are different in their laminar origin and horizontal location with respect to cell position: On average, L2/3 PCs receive more inhibition than excitation from within L2/3, whereas excitation dominates input from L4 and L5. Horizontally, inhibitory input originates from locations closer to the horizontal position of the soma, while excitatory input arises from more distant locations in L4 and L5. In L2/3, the excitatory and inhibitory inputs spatially overlap on average. Importantly, at the level of individual neurons, PCs receive inputs from presynaptic cells located spatially offset, vertically and horizontally, relative to the soma. These input offsets show a systematic correlation with the preferred orientation of the postsynaptic L2/3 PCin vivo. Unexpectedly, this correlation is higher for inhibitory input offsets within L2/3 than for excitatory input offsets. When relating the dendritic complexity of L2/3 PCs to their orientation tuning, we find that sharply tuned cells have a less complex apical tree compared to broadly tuned cells. These results indicate that the spatial input offsets of the functional input connectivity are linked to orientation preference, while the orientation selectivity of L2/3 PCs is more related to the dendritic complexity.
Internal timing-related dopaminergic dynamics can be explained by reward-prediction errors
Authors: Hamilos Allison E. , Assad John A. 
Published: June 2020

AbstractDopaminergic neurons (DANs) exhibit complex dynamics across a variety of behavioral contexts, often in ways that seem task-specific and even incompatible with results across different paradigms. Dopaminergic signaling during timing tasks has been a prime example. In behavioral timing, dopaminergic dynamics predict the initiation of self-timed movement via a seconds-long ramp up of activity prior to movement onset, similar to ramping seen in visuospatial reward approach and multi-step, goal-directed behaviors. By contrast, in perceptual timing, DANs exhibit more complex dynamics whose direction of modulation seems to be theoppositeof that observed in behavioral timing. Mikhael et al. (2022) recently proposed a formal model in which dopaminergic dynamics encode reward expectation in the form of an “ongoing” reward-prediction error (RPE) that arises from resolving uncertainty of one’s position in the value landscape (i.e., one’s spatial-temporal distance to reward delivery/omission). Here, we show that application of this framework recapitulates and reconciles the seemingly contradictory dopaminergic dynamics observed in behavioralvsperceptual timing. These results suggest a common neural mechanism that broadly underlies timing behavior: trial-by-trial variation in the rate of the internal “pacemaker,” manifested in DAN signals that reflect stretching or compression of the derivative of the subjective value function relative to veridical time. In this view, faster pacemaking is associated with relatively high amplitude dopaminergic signaling, whereas slower pacemaking is associated with relatively low levels of dopaminergic signaling, consistent with findings from pharmacological and lesion studies.
Mathematical modeling of ventilator-induced lung inflammation
Authors: Minucci Sarah , Heise Rebecca L. , Valentine Michael S. , Kamga Gninzeko Franck J. , Reynolds Angela M. 
Published: June 2020

AbstractRespiratory infections, such as the novel coronavirus (SARS-COV-2) and other lung injuries, damage the pulmonary epithelium. In the most severe cases this leads to acute respiratory distress syndrome (ARDS). Due to respiratory failure associated with ARDS, the clinical intervention is the use of mechanical ventilation. Despite the benefits of mechanical ventilators, prolonged or misuse of these ventilators may lead to ventilation-associated/ventilation-induced lung injury (VILI). Damage caused to epithelial cells within the alveoli can lead to various types of complications and increased mortality rates. A key component of the immune response is recruitment of macrophages, immune cells that differentiate into phenotypes with unique pro- and/or anti-inflammatory roles based on the surrounding environment. An imbalance in pro- and anti-inflammatory responses can have deleterious effects on the individual’s health. To gain a greater understanding of the mechanisms of the immune response to VILI and post-ventilation outcomes, we develop a mathematical model of interactions between the immune system and site of damage while accounting for macrophage polarization. Through Latin hypercube sampling we generate a virtual cohort of patients with biologically feasible dynamics. We use a variety of methods to analyze the results, including a random forest decision tree algorithm and parameter sensitivity with eFAST. Analysis shows that parameters and properties of transients related to epithelial repair and M1 activation and de-activation best predicted outcome. Using this new information, we hypothesize inter-ventions and use these treatment strategies to modulate damage in select virtual cases.
Sustained attention and vigilance deficits associated with HIV and a history of methamphetamine dependence
Authors: Pocuca Nina , Young Jared W. , MacQueen David A. , Letendre Scott , Heaton Robert K. , Geyer Mark A. , Perry William , Grant Igor , Minassian Arpi ,   the Translational Methamphetamine AIDS Research Center (TMARC)
Published: June 2020

AbstractBackgroundHuman immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy (ART). One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH+). Such dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, ART initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; ≤50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the independent and combined (additive versus synergistic) effects of HIV and history of METH+ on the sustained attention and vigilance cognitive domain, while controlling for VLS.MethodsParticipants included 205 (median age=44 years; 77% males; HIV-/METH-n=67; HIV+/METH -n=49; HIV-/METH+n=36; HIV+/METH+n=53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners’ and the 5- Choice continuous performance tests (CPTs).ResultsMETH+ participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV-participants. There was no HIV x METH interaction on sustained attention and vigilance.ConclusionsRecent methamphetamine use among METH+ people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of ART, and METH use interventions.
Massively parallel functional testing ofMSH2missense variants conferring Lynch Syndrome risk
Authors: Jia Xiaoyan , Burugula Bala Bharathi , Chen Victor , Lemons Rosemary M. , Jayakody Sajini , Maksutova Mariam , Kitzman Jacob O. 
Published: June 2020

AbstractThe lack of functional evidence for the majority of missense variants limits their clinical interpretability, and poses a key barrier to the broad utility of carrier screening. In Lynch Syndrome (LS), one of the most highly prevalent cancer syndromes, nearly 90% of clinically observed missense variants are deemed “variants of uncertain significance” (VUS). To systematically resolve their functional status, we performed a massively parallel screen in human cells to identify loss-of-function missense variants in the key DNA mismatch repair factorMSH2. The resulting functional effect map is substantially complete, covering 94% of the 17,746 possible variants, and is highly concordant (96%) with existing functional data and expert clinicians’ interpretations. The large majority (89%) of missense variants were functionally neutral, perhaps unexpectedly in light of its evolutionary conservation. These data provide ready-to-use functional evidence to resolve the ∼1,300 extant missense VUSs inMSH2, and may facilitate the prospective classification of newly discovered variants in the clinic.
Sex differences in the progression from NAFL to NASH: a functional meta-analysis of transcriptomic studies
Authors: Català-Senent José F. , Hidalgo Marta R. , Berenguer Marina , Parthasarathy Gopanandan , Malhi Harmeet , Malmierca-Merlo Pablo , de la Iglesia-Vayá María , García-García Francisco 
Published: June 2020

AbstractBackground & aimsSex differences in non-alcoholic fatty liver disease (NAFLD) are well known and yet, most of the studies available in the literature do not include this factor when analysing the data. Here we present a functional meta-analysis of NAFLD studies to detect the molecular mechanisms involved in its progression, distinguishing any differences relative to patient sex.MethodsWe systematically reviewed the Gene Expression Omnibus (GEO) database functional Gene Ontology (GO) terms detailed in transcriptomic studies, following the PRISMA statement guidelines. For each study, we compared the progression from steatosis (NAFL) to steatohepatitis (NASH) in premenopausal women and men using a dual strategy: a gene-set analysis and a pathway activity analysis. The functional results of all the studies were integrated in a meta-analysis.ResultsA total of 114 abstracts were reviewed and 7 studies, which included 323 eligible patients, were finally analysed. The meta-analyses highlighted significant functions in both sexes. In premenopausal women, the overrepresented functions referred to DNA regulation, vinculin binding, IL-2 responses, negative regulation of neuronal death, and the transport of ions and cations. In men, they referred to the negative regulation of IL-6 and the establishment of planar polarity involved in neural tube closure.ConclusionsOur meta-analysis of this transcriptomic data provides a powerful approach to identify sex differences in the progression from NAFL to NASH. We detected relevant biological functions and molecular terms that were affected differently between premenopausal women and men. Changes in the immune responsiveness between men and women with NAFLD suggested that women have a more immune tolerant milieu while men have an impaired liver regenerative response.Introductory StatementProgression from NAFL to NASH differently affects cellular functions in women and men. Here we systematically reviewed publicly available transcriptomic data and then performed a meta-analysis to find these affected functions. Thus, we identified 13 biological functions implicated in the progression of NAFLD that were differentially affected by sex.Graphical abstract
The psychological effects of COVID-19 on frontline healthcare workers and how they are coping: a web-based, cross-sectional study from Pakistan
Authors: Salman Muhammad , Raza Muhammad Husnnain , Ul Mustafa Zia , Khan Tahir Mehmood , Asif Noman , Tahir Humera , Shehzadi Naureen , Hussain Khalid 
Published: June 2020

AbstractBackgroundHigh level stress is expected when crises starts affecting people’s lives and communities which is witnessed in the past epidemics. Infectious diseases outbreaks like the ongoing COVID19 pandemic have negative impact on healthcare workers’ (HCWs) mental health, which needs to be investigated. Therefore, we aimed to assess the psychological impact of COVID-19 on frontline HCWs and their coping strategies.MethodsA web-based, cross-sectional study was conducted among HCWs of the Punjab province of Pakistan. The generalized anxiety scale (GAD-7), patient health questionnaire (PHQ-9) and Brief-COPE were used to assess anxiety, depression and coping strategies.ResultsThe mean age of respondents (N = 398) was 28.67 ± 4.15 years, with majority of medical doctors (52%). The prevalence of anxiety and depression were 21.4% and 21.9%, respectively. There was no significant difference of anxiety and depression scores among doctors, nurses and pharmacists. Females had significantly higher anxiety (p = 0.003) and depression (p = 0.001) scores than males. Moreover, HCWs performing duties in COVID-19 ICU had significantly higher anxiety score than those from isolation wards (p = 0.020) and other departments (p = 0.014). Depression, not anxiety, score were higher among those who did not receive the infection prevention training. Most frequently adopted coping strategy was religious coping (5.98 ± 1.73) followed by acceptance (5.59 ± 1.55) and coping planning (4.91 ± 1.85).ConclusionA considerable proportion of HCWs are having generalized anxiety and depression during the ongoing COVID-19 pandemic. Our findings call for interventions to mitigate mental health risks in HCWs.
Strength of attention-sampling parietal EEG theta rhythm is linked to impaired inhibition in adult ADHD
Authors: Juurmaa Kristiina , Palomäki Jussi , Cowley Benjamin Ultan 
Published: June 2020

Attention-deficit hyperactivity disorder (ADHD) in adults is understudied, especially regarding neural mechanisms such as oscillatory control of attention sampling. We report an EEG study of such cortical oscillations, in ADHD-diagnosed adults taking a continuous performance test that measures the ability to sustain attention and inhibit impulsivity for a prolonged period of time.We recorded 53 adults (28f, 25m, aged 18-60), and 18 matched healthy controls, using 128-channel EEG. We analysed features with established links to neural correlates of attention: event-related (de)synchronisation (ERS), alpha and theta frequency band activation, and stimulus-locking indices; in frontal and parietal scalp regions.Test performance distinguished healthy controls from ADHD adults. The ADHD group manifested significantly less parietal 4 Hz theta ERS during correct inhibition trials, in addition to having greater sensitivity to targets in stimulus-locking measures.Our results suggest that ADHD adults have impaired attention sampling in relational categorisation tasks.
Attitudes of multimorbid patients to surviving future acute illness and subsequent functional disability: A systematic review
Authors: McNelly Angela S , Flower Luke , Stephens Timothy J , Fowler AJ , Pearse Rupert M , Prowle John , Puthucheary Zudin A 
Published: June 2020

AbstractBACKGROUNDMultimorbid patients have worse outcomes following acute hospitalisation. These include increased mortality as an in-patient and after hospital discharge, and increased morbidity and dependence requiring greater use of care facilities. The literature is unclear on the views and wishes of multimorbid patients regarding the outcomes of acute hospitalisation, specifically regarding survival with additional functional disability following acute illness. This is increasingly relevant, with the recent National Institute for Health and Care Excellence (NICE) guidance on admission to hospital and critical care being based on the presence of comorbidities and function as opposed to numerical age.ObjectivesWe performed a systematic review to assess the current qualitative literature exploring attitudes, wishes and perspectives of adult patients with multimorbidity on surviving future acute illness and subsequent acquired functional disability.METHODSEligibility criteriaEligible studies addressed the attitudes, wishes and perspectives of multimorbid adults to illness and treatment-acquired disability using qualitative methods.Information sources: A search of PubMed, Embase, and CINAHL databases was conducted from database inception through April 2020. References lists from selected papers and NICE Guidelines on Multimorbidity (NG56) were searched iteratively for additional relevant articles.Review methodsTwo researchers reviewed candidate full texts independently. Relevant data was extracted to an evidence table. The risk of bias was avoided by adhering to the previously published extensive search strategy and use of qualitative methodology.RESULTSFrom 35606 records of which 6370 were duplicates, 20 full texts were reviewed for inclusion, but none met the eligibility criteria. Coverage of domains of importance to multimorbid adults and those highlighted in the NICE guidelines on multimorbidity (NG56) by the 20 short-listed papers was determined; no publications were found to address all domains.DISCUSSIONNo studies were identified which have applied appropriate qualitative methodology to understand the wishes, attitudes, and preferences of multimorbid adults regarding treatment and outcomes of acute illness. Such enquiries need to be urgently undertaken to inform and progress policy and clinical practice relating to decisions around admission to hospital and critical care.OTHERFundingNational Institute of Health Research (NIHR) Research for Patient Benefit grant; NIHR Programme grant; NIHR Doctoral Research Fellowship.RegistrationPROSPERO International Prospective Register of systematic reviews (CRD: 42019155028) https://www.crd.vork.ac.uk/PROSPERO/
Titanium Fasteners In Endoscopic Mitral Valve Surgery
Authors: Margaryan Rafik , Bianchi Giacomo , Gasbarri Tommaso , Concistre Giovanni , Solinas Marco 
Published: June 2020

AbstractObjectiveWe sought to review our experience of new titanium knot fastener devices. We hypothesized that it might reduce the cardiop-polmonary bypass time, aortic cross-clamping time and intervention time.MaterialsWe reviewed our electronic records in order identify the patients who underwent mitral valve (MV) repair and replacement in totally endoscopic setup. Surgical approach was trough limited right periareolar or inframmamary thoracotomy with mainly femoro-femoral arterio-venous cannulation. A part of patients underwent interventions using fast knotting system (FK group, Cor-Knot Device, ISL Solutions Inc) and remaining patients served as control group (conventional hand knotting, HK). We identified the FK patients and performed propensity score matching to match 1:1 ratio from main cohort using FK versus HK.ResultsA total of 306 patients underwent mitral valve repair or replacement on via right thoracotomy, 265 (87%) patients underwent using FK, remaining. There were on average 2.6 minutes of CPB time reduction (p = 0.64), and 3.1 minutes of CXC time reduction (p = 0.47). However, when dividing into procedures based on complexity, there were on average 8.6 minutes of CPB time reduction (p = 0.18), and 6.9 minutes of CXC time reduction (p = 0.16) in simple cases; on average in complex cases 12 minutes of CPB time was augmented (p = 0.24), and 2.5 minutes of CXC time was augmented(p = 0.76).In propensity matched population the effect of CPB and CXC reduction was consistent and repeated and there were on average 0.5 minutes of CPB time reduction (p = 0.12), and 3.6 minutes of CXC time augmentation (p = 0.05). However, when dividing into procedures based on complexity, there were on average 0.2 minutes of CPB time reduction (p = 0.16), and 2.7 minutes of CXC time augmentation (p = 0.06) in simple cases; on average 5 minutes of CPB time augmentation (p = 0.34), and 14.2 minutes of CXC time augmentation (p = 0.58) in complex cases.ConclusionsTitanium fasteners are useful tool to have in minimally invasive approaches, especially in complex cases and redo interventions. Titanium are comfortable and fast in many cases then conventional knot tying, but it is also expensive the traditional knotting. The titanium fasteners do not offer significant time reduction. In matched group the pattern of time saving were identical to main cohort.
Detection of SARs-CoV-2 in wastewater, using the existing environmental surveillance network: An epidemiological gateway to an early warning for COVID-19 in communities
Authors: Sharif Salmaan , Ikram Aamer , Khurshid Adnan , Salman Muhammad , Mehmood Nayab , Arshad Yasir , Ahmad Jamal , Safdar Rana Muhammad , Angez Mehar , Alam Muhammad Masroor , Rehman Lubna , Mujtaba Ghulam , Hussain Jaffar , Ali Johar , Akthar Ribqa , Malik Muhammad Wasif , Baig Zeeshan Iqbal , Rana Muhammad Suleman , Usman Muhammad , Ali Muhammad Qaisar , Ahad Abdul , Badar Nazish , Umair Massab , Tamim Sana , Ashraf Asiya , Tahir Faheem , Ali Nida 
Published: June 2020

AbstractBackgroundThe ongoing COVID-19 pandemic caused by SARs-CoV-2 was transmitted person to person via droplet infections and fecal-oral transmission. This illustrates the probability of environmentally facilitated transmission, mainly the sewage.MethodWe used existing Pakistan polio environment surveillance network to investigate presence of SARs-CoV-2 using three commercially available kits and E-Gene detection published assay for surety and confirmatory of positivity. A Two-phase separation method is used for sample clarification and concentration. An additional high-speed centrifugation (14000Xg for 30 min) step was introduced, prior RNA extraction, to increase viral RNA yield resulting a decrease in Cq value.ResultsA total of 78 wastewater samples collected from 38 districts across Pakistan, 74 wastewater samples from existing polio environment surveillance sites, 3 from drains of COVID-19 infected areas and 1 from COVID 19 quarantine center drainage, were tested for presence of SARs-CoV-2. 21 wastewater samples (27%) from 13 districts turned to be positive on RT-qPCR. SARs-COV-2 RNA positive samples from areas with COVID patients and COVID 19 patient quarantine center drainage strengthen the findings and use of wastewater surveillance in future. Furthermore, sequence data of partial ORF 1a generated from COVID 19 patient quarantine center drainage sample also reinforce our findings that SARs-CoV-2 can be detected in wastewater.DiscussionThis study finding indicates that SARs-CoV-2 detection through wastewater surveillance has an epidemiologic potential that can be used as early warning system to monitor viral tracking and circulation in cities with lower COVID-19 disease burden or heavily populated areas where door-to-door tracing may not be possible. However, attention needed on virus concentration and detection assay to increase the sensitivity. Development of highly sensitive assay will be an indicator for virus monitoring and to provide early warning signs.