bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression and Brain Morphology in Middle Childhood: Results from the ABCD Study
Authors: Moreau Allison L. , Voss Michaela , Hansen Isabella , Paul Sarah E. , Barch Deanna M. , Rogers Cynthia E. , Bogdan Ryan 
Published: September 2021

ABSTRACTObjectivePrenatal selective serotonin reuptake inhibitor (SSRI) exposure has been inconsistently linked to depression. Potential neural intermediaries remain understudied. We examined whether prenatal SSRI exposure is associated with depressive symptoms and brain structure during middle childhood.MethodsPrenatal SSRI exposure (retrospective caregiver-report), depressive symptoms (caregiver-reported Child Behavior Checklist) and brain structure (MRI-derived subcortical volume; cortical thickness and surface area) were assessed in children (analytic ns=5,420-7,528; 235 with prenatal SSRI exposure; 9-10 years old) who completed the baseline session of the Adolescent Brain and Cognitive DevelopmentSM Study. Covariates included familial (e.g., 1st degree relative depression density), pregnancy (e.g., planned pregnancy), and child (e.g., birthweight) variables. Matrix spectral decomposition was used to address multiple testing.ResultsThere was no evidence that prenatal SSRI exposure was associated with child depression after accounting for recent maternal depressive symptoms. Prenatal SSRI exposure was associated with greater left superior parietal surface area (b=145.3 mm2, p=0.00038) and lateral occipital cortical thickness (b=0.0272 mm, p=0.0000079), neither of which was associated with depressive symptoms.ConclusionsOur findings, combined with adverse associations of prenatal exposure to maternal depression and the utility of SSRIs for treating depression, suggest that risk for child depression during middle childhood should not discourage SSRI use during pregnancy. It will be important for future work to examine associations between prenatal SSRI exposure and depression through young adulthood, when risk for depression increases.
Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Stage II Colon Cancer (DYNAMIC Trial): Statistical Analysis Plan
Authors: Tie Jeanne , Lo Serigne N. , Cohen Joshua D. , Wang Yuxuan , Wong Rachel , Shapiro Jeremy , Harris Sam , Khattak Adnan , Burge Matthew , Vogelstein Bert , Gibbs Peter 
Published: September 2021

ABSTRACTBackgroundDetection of circulating tumour DNA (ctDNA) after curative intent treatment reflects the presence of minimal residual disease and predicts for recurrence. DYNAMIC trial is a randomised phase II investigating the clinical utility of ctDNA-guided adjuvant treatment strategy compared with the standard of care (non-ctDNA based) approach in patients with stage II colon cancer. The primary trial endpoint is recurrence-free survival estimated from Kaplan Meier Method at 2 years. Secondary endpoints include proportion of patients treated with adjuvant chemotherapy, time-to-recurrence, overall survival, ctDNA clearance rate (investigational arm) and quality-adjusted life-years.ObjectiveTo outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis.MethodsThe SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data.Trial RegistrationANZ Clinical Trials Registry, ACTRN12615000381583. Registered on 27th April 2015.
Covid spirals: a phase diagram representation of COVID-19 effective reproduction number Rt
Authors: Pesenti K. W. , Pesenti R. 
Published: September 2021

AbstractIn this paper, we propose a phase diagram representation of COVID-19 effective reproduction number Rt. Specifically, we express Rt as a function of the estimated infected individuals. This function plots a particular clockwise spiral that allows to easily compare the evolution of the number of new infected individuals at different dates and, possibly, provide some hints on the future progression of the infection.
COVID-19 Vaccine Efficacy in a Diverse Urban Healthcare Worker Population
Authors: Iliaki Eirini , Lan Fan-Yun , Christophi Costas A. , Guidotti Guido , Jobrack Alexander D. , Buley Jane , Nathan Neetha , Osgood Rebecca , Bruno-Murtha Lou Ann , Kales Stefanos N. 
Published: September 2021

AbstractObjectiveTo investigate COVID-19 vaccine efficacy (VE) among healthcare workers (HCWs) in an ethnically diverse community healthcare system, during its initial immunization campaign.MethodsHCWs of the system were retrospectively included from the beginning of a COVID-19 vaccination program (December 16, 2020) until March 31, 2021. Those with a prior COVID-19 infection before December 15 were excluded. The Occupational Health department of the system ran a COVID-19 screening and testing referral program for workers, consistently throughout the study period. A master database had been established and updated comprising of the demographics, COVID-19 PCR assays, and vaccinations of each HCW. Andersen-Gill extension of the Cox models were built to estimate the VE of fully/partially vaccinated person-days at risk.ResultsAmong the 4317 eligible HCWs, 3249 (75%) received any vaccination during the study period. Vaccinated HCWs were older, less likely to be Black/African American, Hispanic/Latino or identify as two or more races, and more likely to be medical providers. After adjusting for age, sex, race, and the statewide background incidence at the time of vaccination, we observed a VE of 80.2% (95% CI: 57.5–90.8%) for ≧14 days after the first dose of Pfizer/Moderna, and 95.5% (95% CI: 88.2-98.3%) among those fully vaccinated (i.e. ≧14 days after the second dose of Pfizer/Moderna or the single dose of J&J/Janssen).ConclusionCOVID-19 vaccine effectiveness in the real world is promising, and these data in concert with culturally appropriate may decrease vaccine hesitancy.
A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults
Authors: Williams Katherine V. , Zhai Bo , Alcorn John F. , Nowalk Mary Patricia , Levine Min Z. , Kim Sara S. , Flannery Brendan , Geffel Krissy Moehling , Merranko Amanda Jaber , Nagg Jennifer P. , Collins Mark , Susick Michael , Clarke Karen S. , Zimmerman Richard K. , Martin Judith M. 
Published: September 2021

AbstractBackgroundHemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children and young adult HAI titers against the 2019-2020 LAIV4 and ccIIV4.MethodsParticipants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n =100) or LAIV4 (n=98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers.ResultsGMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p<0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p<0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p<0.05) than cell-grown GMTs [ccIIV4 day 28: egg=205 (95% CI: 178-237); cell=136 (95% CI:113-165); LAIV4 day 28: egg=96 (95% CI: 83-112); cell=63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR.ConclusionThe HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. For both vaccines, the A/H3N2 cell-grown antigen levels were lower than egg-grown, but the GMFR for cell-grown and egg-grown did not differ significantly within vaccine type.Clinical Trials NoNCT03982069
Association Between SARS-CoV-2 RNAemia and Post-Acute Sequelae of COVID-19
Authors: Ram-Mohan Nikhil , Kim David , Rogers Angela J , Blish Catherine A , Nadeau Kari C , Blomkalns Andra L , Yang Samuel 
Published: September 2021

AbstractDeterminants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 75% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, initial disease severity, and length of symptoms.
Brain age as a surrogate marker for information processing speed in multiple sclerosis
Authors: Denissen S , Engemann DA , De Cock A , Costers L , Baijot J , Laton J , Penner IK , Grothe M , Kirsch M , D’hooghe MB , D’Haeseleer M , Dive D , De Mey J , Van Schependom J , Sima DM , Nagels G 
Published: September 2021

BackgroundData from neuro-imaging techniques allow us to estimate a brain’s age. Brain age is easily interpretable as “how old the brain looks”, and could therefore be an attractive communication tool for brain health in clinical practice. This study aimed to investigate its clinical utility.ObjectivesTo investigate the relationship between brain age and information processing speed in MS.MethodsA ridge-regression model was trained to predict age from brain MRI volumetric features and sex in a healthy control dataset (HC_train, n=1690). This model was used to predict brain age in two test sets: HC_test (n=50) and MS_test (n=201). Brain-Predicted Age Difference (BPAD) was calculated as BPAD=brain age minus chronological age. Information processing speed was assessed with the Symbol Digit Modalities Test (SDMT).ResultsBrain age was significantly related to SDMT scores in the MS_test dataset (r=-0.44, p<.001), and contributed uniquely to variance in SDMT beyond chronological age, reflected by a significant correlation between BPAD and SDMT (r=-0.21, p=0.003) and a significant weight (−0.21, p=0.011) in a multivariate regression equation with age.ConclusionsBrain age is a candidate biomarker for information processing speed in MS and an easy to grasp metric for brain health.
UTTARAKHAND COVID-19 CASES AND DEATHS: COMPARING THE DEMOGRAPHICS AND SUGGESTIVE STRATEGY TO PREVENT SIMILAR PANDEMICS IN FUTURE
Authors: Joshi Gaurav , Pande Akshara , Gupta Omdeep , Nautiyal Anoop , Jasola Sanjay , Gahtori Prashant 
Published: September 2021

AbstractCoronavirus disease 19 (Covid-19) is causing a dramatic impact on human life worldwide. As of June 11 2021, later one has attributed more than 174 million confirmed cases and over 3.5 million deaths globally. Nonetheless, a World Bank Group flagship report features Covid-19 induced global crisis as the strongest post-recession since World WarII. Currently, all approved therapeutics or vaccines are strictly allowed for emergency use. Hence, in the absence of pharmaceutical interventions, it is vital to analyze data set covering the growth rates of positive human cases, number of recoveries, other factors, and future strategies to manage the growth of fatal Covid-19 effectively. The Uttarakhand state of India is snuggled in the lap of the Himalayas and occupies more people than Israel, Switzerland, Hong Kong, etc. This study analyzed state Covid-19 data, fetched from an authenticated government repository using Python 3.9 from April 1, 2020, to February 28, 2021. In the first wave, plain areas of Uttarakhand covering the districts Dehradun, Haridwar, Nainital, and U. S. Nagar were severely affected and reported peak positive cases during the 21st – 26th week. Other hands, the hilly terrains of Uttarakhand districts, including Chamoli, Pauri Garhwal, and Rudraprayag, reported a high number of positive cases between the 30th and 31st week, and other hilly districts reported an increase in Covid-19 cases during the 34th to 38th week. The highest recovery rate was attributed to the hilly district Rudraprayag. The analysis also revealed that a very high doubling rate was seen during the last week of May to the first week of Jun 2020. At last, based on this blueprint, we have suggested 6-points solutions for preventing the next pandemic.
Unraveling the COVID-19 hospitalization dynamics in Spain using publicly available data
Authors: Aleta Alberto , Blas-Laína Juan Luis , Anglés Gabriel Tirado , Moreno Yamir 
Published: September 2021

SummaryBackgroundOne of the main challenges of the ongoing COVID-19 pandemic is to be able to make sense of available, but often heterogeneous and noisy data, to characterize the evolution of the SARS-CoV-2 infection dynamics, with the additional goal of having better preparedness and planning of healthcare services. This contribution presents a data-driven methodology that allows exploring the hospitalization dynamics of COVID-19, exemplified with a study of 17 autonomous regions in Spain.MethodsWe use data on new daily cases and hospitalizations reported by the Ministry of Health of Spain to implement a Bayesian inference method that allows making short and mid-term predictions of bed occupancy of COVID-19 patients in each of the autonomous regions of the country.FindingsWe show how to use given and generated temporal series for the number of daily admissions and discharges from hospital to reproduce the hospitalization dynamics of COVID-19 patients. For the case-study of the region of Aragon, we estimate that the probability of being admitted to hospital care upon infection is 0·090 [0·086-0·094], (95% C.I.), with the distribution governing hospital admission yielding a median interval of 3·5 days and an IQR of 7 days. Likewise, the distribution on the length of stay produces estimates of 12 days for the median and 10 days for the IQR. A comparison between model parameters for the regions analyzed allows to detect differences and changes in policies of the health authorities.InterpretationThe amount of data that is currently available is limited, and sometimes unreliable, hindering our understanding of many aspects of this pandemic. We have observed important regional differences, signaling that to properly compare very different populations, it is paramount to acknowledge all the diversity in terms of culture, socio-economic status and resource availability. To better understand the impact of this pandemic, much more data, disaggregated and properly annotated, should be made available.
Impact and Equality of Expanding Pre-Exposure Prophylaxis (PrEP) for Men who have Sex with Men in Los Angeles County
Authors: Nguyen Anthony , Drabo Emmanuel Fulgence , Garland Wendy , Moucheraud Corrina , Holloway Ian W , Leibowitz Arleen , Suen Sze-chuan 
Published: September 2021

ABSTRACTBackgroundRacial and ethnic minority men who have sex with men (MSM) are disproportionately affected by HIV/AIDS in Los Angeles County (LAC), an important epicenter in the battle to end HIV.ObjectiveTo examine tradeoffs between effectiveness and equality of PrEP allocation strategies among different racial and ethnic groups of MSM in LAC.Design, Setting, and PopulationWe developed a microsimulation model of HIV among MSM in LAC using county epidemic surveillance and survey data to capture demographic trends and subgroup-specific partnership patterns, disease progression, patterns of PrEP use, and patterns for viral suppression.InterventionWe simulated interventions where an additional 3000, 6000, or 9000 PrEP prescriptions are provided annually in addition to current levels, following different allocation scenarios to each racial/ethnic group (Black, Hispanic, or White).MeasurementsWe estimated cumulative infections averted and measures of equality, after 15 years (2021-2035), relative to base case (no intervention).ResultsOf the policies evaluated, targeting PrEP preferentially to Black individuals would result in the largest reductions in incidence and disparities. This outcome was robust to different partnership preference assumptions, though the magnitude of impact differs.LimitationsWe limit analysis to MSM, who bear the majority of HIV/AIDS burden in LAC. We do not consider transmission via injection drug use or mother-to-child transmission, nor do we capture individual network transmission effects. We assume no improvements in the prevention-diagnosis-treatment cascade besides increased PrEP use.ConclusionsWe find there is little trade-off between effectiveness and equality of outcome when choosing groups to target for PrEP in LAC – by focusing on MSM with the highest HIV incidence (Black), we can reduce both overall infections and racial/ethnic disparities.
Synaptic and intrinsic mechanisms impair reticular thalamus and thalamocortical neuron function in a Dravet syndrome mouse model
Authors: Studtmann Carleigh , Ladislav Marek , Topolski Mackenzie A. , Safari Mona , Swanger Sharon A. 
Published: September 2021

ABSTRACTThalamocortical network dysfunction contributes to seizures and sleep deficits in Dravet syndrome (DS), an infantile epileptic encephalopathy, but the underlying molecular and cellular mechanisms remain elusive. DS is primarily caused by mutations in the SCN1A gene encoding the voltage-gated sodium channel NaV1.1, which is highly expressed in GABAergic reticular thalamus (nRT) neurons as well as glutamatergic thalamocortical neurons. We hypothesized that NaV1.1 haploinsufficiency alters somatosensory corticothalamic circuit function through both intrinsic and synaptic mechanisms in nRT and thalamocortical neurons. Using Scn1a heterozygous mice of both sexes aged P25-P30, we discovered reduced intrinsic excitability in nRT neurons and thalamocortical neurons in the ventral posterolateral (VPL) thalamus, while thalamocortical ventral posteromedial (VPM) neurons exhibited enhanced excitability. NaV1.1 haploinsufficiency enhanced GABAergic synaptic input and reduced ascending glutamatergic sensory input to VPL neurons, but not VPM neurons. In addition, glutamatergic cortical input to nRT neurons was reduced in Scn1a heterozygous mice, whereas cortical input to VPL and VPM neurons remained unchanged. These findings introduce input-specific alterations in glutamatergic synapse function and aberrant glutamatergic neuron excitability in the thalamus as disease mechanisms in Dravet syndrome, which has been widely considered a disease of GABAergic neurons. This work reveals additional complexity that expands current models of thalamic dysfunction in Dravet syndrome and identifies new components of corticothalamic circuitry as potential therapeutic targets.HIGHLIGHTSGABAergic reticular thalamus neurons have impaired tonic and burst firing properties in a NaV1.1 haploinsufficiency mouse model of Dravet syndrome.NaV1.1 haploinsufficiency has opposing effects on spike firing in two distinct glutamatergic thalamocortical neuron populations.NaV1.1 haploinsufficiency alters glutamatergic synaptic connectivity in an input-specific manner in the thalamus.Dysregulation of both intrinsic and synaptic mechanisms contribute to imbalanced thalamic excitation and inhibition in this Dravet syndrome mouse model.
A subset of nucleus accumbens neurons receiving dense and functional prelimbic cortical input are required for cocaine seeking
Authors: Siemsen Benjamin M. , Barry Sarah M. , Vollmer Kelsey , Green Lisa M. , Brock Ashley G. , Westphal Annaka M. , King Raven A. , DeVries Derek M. , Otis James M. , Cowan Christopher W. , Scofield Michael D. 
Published: September 2021

AbstractBackgroundPrelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown.MethodsMale Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resolution confocal microscopy were used to identify and characterize a small population of nucleus accumbens core neurons that receive dense prelimbic cortical input to determine their role in regulating cue-induced cocaine and natural reward seeking.ResultsChemogenetic inhibition of prelimbic cortical projections to the nucleus accumbens core suppressed cue-induced cocaine relapse and normalized real-time cue-evoked increases in accumbens glutamate release to that of sucrose seeking animals. Furthermore, chemogenetic inhibition of the population of nucleus accumbens core neurons receiving the densest prelimbic cortical input suppressed cocaine, but not sucrose seeking. These neurons also underwent morphological plasticity during the peak of cocaine seeking in the form of dendritic spine expansion and increased ensheathment by astroglial processes at large spines.ConclusionsWe identified and characterized a unique subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. The functional specificity of this subpopulation is underscored by their ability to mediate cue-induced cocaine relapse, but not sucrose seeking. This subset of cells represents a novel target for addiction therapeutics revealed by anterograde targeting to interrogate functional circuits imbedded within a known network.
Comments on a small sabretooth cat in the Abismo Ponta de Flecha Cave, Vale do Ribeira, southeastern Brazil
Authors: Chahud Artur 
Published: September 2021

AbstractThe Vale do Ribeira, located in southeastern Brazil, is known for many caves with osteological material, including several extinct species. The saber-tooth cat Smilodon populator was a large predator that inhabited the Pleistocene and Holocene of South America. A specimen found in the Abismo Ponta de Flecha Cave based on small bones (metacarpals and phalanges) is commented here. The metacarpals have morphological characteristics of S. populator, but are smaller than that of S. fatalis and Panthera onca and larger than that of S. gracilis. The specimen is among the smallest ever found and is comparable in size to an adult lion.
Electrical impulse characterization along actin filaments in pathological conditions
Authors: Hunley Christian , Mohsin Md , Marucho Marcelo 
Published: September 2021

AbstractWe present an interactive Mathematica notebook that characterizes the electrical impulses along actin filaments in both muscle and non-muscle cells for a wide range of physiological and pathological conditions. The program is based on a multi-scale (atomic → monomer → filament) approach capable of accounting for the atomistic details of a protein molecular structure, its biological environment, and their impact on the travel distance, velocity, and attenuation of monovalent ionic wave packets propagating along microfilaments. The interactive component allows investigators to conduct original research by choosing the experimental conditions (intracellular Vs in vitro), nucleotide state (ATP Vs ADP), actin isoform (alpha, gamma, beta, and muscle or non-muscle cell), as well as, a conformation model that covers a variety of mutants and wild-type (the control) actin filament. The simplicity of the theoretical formulation and the high performance of the Mathematica software enable the analysis of multiple conditions without computational restrictions. These studies may provide an unprecedented molecular understanding of why and how age, inheritance, and disease conditions induce dysfunctions in the biophysical mechanisms underlying the propagation of electrical signals along actin filaments.