bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Stroke Outcome in Mice Based on Non-Invasive MRI and Behavioral Testing
Authors: Knab Felix , Koch Stefan Paul , Major Sebastian , Farr Tracy D. , Mueller Susanne , Euskirchen Philipp , Eggers Moritz , Kuffner Melanie T.C. , Walter Josefine , Berchtold Daniel , Knauss Samuel , Dreier Jens P. , Meisel Andreas , Endres Matthias , Dirnagl Ulrich , Wenger Nikolaus , Hoffmann Christian J. , Boehm-Sturm Philipp , Harms Christoph 
Published: November 2022

ABSTRACTBackgroundPrediction of post-stroke outcome using the degree of subacute deficit or magnetic resonance imaging is well studied in humans. While mice are frequently used animals in preclinical stroke research, systematic analysis of outcome predictors is lacking.MethodsWe introduced heterogeneity into our study to broaden the applicability of our prediction tools. We analyzed the effect of 30, 45 and 60 minutes of arterial occlusion on the variance of stroke volumes. Next, we built a heterogeneous cohort of 215 mice using data from 15 studies that included 45 minutes of middle cerebral artery occlusion and various genotypes. Motor function was measured using the staircase test of skilled reaching. Phases of subacute and residual deficit were defined. Magnetic resonance images of stroke lesions were co-registered on the Allen Mouse Brain Atlas to characterize stroke topology. Different random forest prediction models that either used motor-functional deficit or imaging parameters were generated for the subacute and residual deficits.ResultsVariance of stroke volumes was increased by 45 minutes of arterial occlusion compared to 60 minutes and including various genotypes. We detected both a subacute and residual motor-functional deficit after stroke and different recovery trajectories. In mice with small cortical lesions, lesion volume was the best predictor of the subacute deficit. The residual deficit was most accurately predicted by the degree of the subacute deficit. When using imaging parameters for the prediction of the residual deficit, including information about the lesion topology increased prediction accuracy. A subset of anatomical regions within the ischemic lesion had particular impact on the prediction of long-term outcome.ConclusionsWe developed and validated a robust tool for the prediction of functional outcome after stroke in mice using a large heterogeneous cohort. Study design and imaging limitations are discussed. In the future, using outcome prediction can improve the design of preclinical studies and guide intervention decisions.
Childhood trauma moderates schizotypy-related brain morphology: Analyses of 1,182 healthy individuals from the ENIGMA Schizotypy working group
Authors: Quidé Yann , Watkeys Oliver J. , Tonini Emiliana , Grotegerd Dominik , Dannlowski Udo , Nenadić Igor , Kircher Tilo , Krug Axel , Hahn Tim , Meinert Susanne , Goltermann Janik , Gruber Marius , Stein Frederike , Brosch Katharina , Wroblewski Adrian , Thomas-Odenthal Florian , Usemann Paula , Straube Benjamin , Alexander Nina , Leehr Elisabeth J. , Bauer Jochen , Winter Nils R. , Fisch Lukas , Dohm Katharina , Rössler Wulf , Smigielski Lukasz , DeRosse Pamela , Moyett Ashley , Houenou Josselin , Leboyer Marion , Gilleen James , Thomopoulos Sophia I. , Thompson Paul M. , Aleman André , Modinos Gemma , Green Melissa J. 
Published: November 2022

ABSTRACTSchizotypy represents an index of psychosis-proneness in the general population often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy. We addressed this question using data from a total of 1,182 healthy adults (age range: 18-65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical grey matter volume and cortical thickness were determined. A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of thicker bilateral medial orbitofrontal gyri, right rostral anterior cingulate gyrus, left temporal pole, left insula, and thinner left paracentral lobule directly associated with increasing levels of schizotypy. In addition, thinner left postcentral, superior parietal and lingual gyri, as well as thicker left caudal middle frontal gyrus and smaller left thalamus and right caudate were associated with increasing levels of childhood trauma exposure. These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.
Defining the Critical Educational Components of Informed Consent for Genetic Testing: Views of US-Based Genetic Counselors and Medical Geneticists
Authors: Hallquist Miranda L. G. , Borensztein Maia J. , Coughlin Curtis R. , Buchanan Adam H. , Faucett W. Andrew , Peay Holly L. , Smith Maureen E. , Tricou Eric P. , Uhlmann Wendy R. , Wain Karen E. ,   the CADRe workgroup, Ormond Kelly E. 
Published: November 2022

AbstractThe Clinical Genome Resource (ClinGen)ConsentandDisclosureRecommendation (CADRe) framework proposes that key components of informed consent for genetic testing can be covered with a targeted discussion for many conditions rather than a time-intensive traditional genetic counseling approach. We surveyed US genetics professionals (medical geneticists and genetic counselors) on their response to scenarios that proposed core informed consent concepts for clinical genetic testing developed in a prior expert consensus process. The anonymous online survey included responses to 3 (of 6 possible) different clinical scenarios that summarized the application of the core concepts. There was a binary (yes/no) question asking respondents whether they agreed the scenarios included the minimum necessary and critical educational concepts to allow an informed decision. Respondents then provided open-ended feedback on what concepts were missing or could be removed. At least one scenario was completed by 238 respondents. For all but one scenario, over 65% of respondents agreed that the identified concepts portrayed were sufficient for an informed decision; the exome scenario had the lowest agreement (58%). Qualitative analysis of the open-ended comments showed no consistently mentioned concepts to add or remove. The level of agreement with the example scenarios suggests that the minimum critical educational components for pre-test informed consent proposed in our prior work is a strong starting place for clinicians to provide targeted pre-test discussions. This may be helpful in providing consistency to the clinical practice of both genetics and non-genetics providers, and in future guideline development.
Pre- and asymptomatic viral shedding in high-risk contacts of monkeypox cases: a prospective cohort study
Authors: Brosius Isabel , Van Dijck Christophe , Coppens Jasmine , Vandenhove Leen , Bangwen Eugene , Vanroye Fien , Verschueren Jacob , Zange Sabine , Bugert Joachim , Michiels Johan , Bottieau Emmanuel , Soentjens Patrick , van Griensven Johan , Kenyon Chris , Ariën Kevin K. , Van Esbroeck Marjan , Vercauteren Koen , Liesenborghs Laurens ,   the ITM MPX consortium
Published: November 2022

AbstractEpidemiological data suggest that clade IIb monkeypox virus (MPXV) is readily transmitted during sexual contact, even before symptom onset. However, presymptomatic shedding of MPXV remains to be demonstrated. Here, we prospectively followed up 25 individuals after high-risk exposure to MPXV. Daily anorectal, genital, and saliva samples and weekly blood and oropharyngeal samples were collected along with clinical information. During follow-up, 12/18 (66.0%) sexual and 1/7 (14.0%) non-sexual contacts showed evidence of MPXV infection by PCR, five of whom had low viral loads and no typical MPXV symptoms. In 5/6 (83.3%) patients with typical symptoms, viral DNA was detected as early as four days before symptom onset and in three of them, replication-competent virus was found. These findings emphasize the high risk of MPXV transmission during sexual contact and confirm the existence of presymptomatic viral shedding of MPXV. Sexual contacts of an MPXV-infected partner should abstain from sex irrespective of symptoms.
The potential impact of novel tuberculosis vaccine introduction on economic growth in low- and middle-income countries
Authors: Portnoy Allison , Arcand Jean-Louis , Clark Rebecca A. , Weerasuriya Chathika K. , Mukandavire Christinah , Bakker Roel , Patouillard Edith , Gebreselassie Nebiat , Zignol Matteo , Jit Mark , White Richard G. , Menzies Nicolas A. 
Published: November 2022

AbstractMost individuals who develop tuberculosis (TB) are working-age adults living in low- and middle-income countries (LMICs). The resulting disability and death impacts economic productivity and burdens health systems. New TB vaccine candidates may reduce this burden. In this study, we estimated the impact of introducing novel TB vaccines on GDP growth in 105 LMICs, using a macroeconomic model to simulate country-level GDP trends between 2020 and 2080, in 2020 USD. We compared scenarios for introduction of infant and adolescent/adult vaccine candidates to a no-new-vaccine counterfactual. Compared to the no-new-vaccine counterfactual, both vaccination scenarios produced greater cumulative GDP in the modelled countries over the study period, equivalent to $1.6 (95% uncertainty interval: $0.8–3.0) trillion for the adolescent/adult vaccine, and $0.2 ($0.1–0.4) trillion for the infant vaccine. These GDP gains were substantially lagged relative to the time of vaccine introduction, and concentrated in countries with higher current TB incidence.
Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants
Authors: Wang Qian , Iketani Sho , Li Zhiteng , Liu Liyuan , Guo Yicheng , Huang Yiming , Bowen Anthony D. , Liu Michael , Wang Maple , Yu Jian , Valdez Riccardo , Lauring Adam S. , Sheng Zizhang , Wang Harris H. , Gordon Aubree , Liu Lihong , Ho David D. 
Published: November 2022

SUMMARYThe SARS-CoV-2 Omicron variant continues to evolve, with new BQ and XBB subvariants now rapidly expanding in Europe/US and Asia, respectively. As these new subvariants have additional spike mutations, they may possess altered antibody evasion properties. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals who were boosted with a WA1/BA.5 bivalent mRNA vaccine. Compared to the ancestral strain D614G, serum neutralizing titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with Emergency Use Authorization, were largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained. Finally, the ACE2-binding affinities of the spike proteins of these novel subvariants were found to be similar to those of their predecessors. Taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.
NewSNCAmutation and structures of α-synuclein filaments from juvenile-onset synucleinopathy
Authors: Yang Yang , Garringer Holly J. , Shi Yang , Lövestam Sofia , Zhang Xianjun , Kotecha Abhay , Bacioglu Mehtap , Koto Atsuo , Takao Masaki , Spillantini Maria Grazia , Ghetti Bernardino , Vidal Ruben , Murzin Alexey G. , Scheres Sjors H.W. , Goedert Michel 
Published: November 2022

ABSTRACTA 21-nucleotide duplication in one allele ofSNCAwas identified in a previously described disease with abundant α-synuclein inclusions that we now call juvenile-onset synucleinopathy (JOS). Both wild-type α-synuclein and its insertion mutant containing seven additional residues (MAAAEKT) after residue 22 were present in sarkosyl-insoluble material that was extracted from frontal cortex of the individual with JOS and examined by electron cryo-microscopy. The structures of JOS filaments, comprising either a single protofilament, or a pair of protofilaments, revealed a new α-synuclein fold that differs from the folds of Lewy body diseases and multiple system atrophy (MSA). The JOS fold consists of a compact core, the sequence of which (residues 36-100 of wild-type α-synuclein) is unaffected by the mutation, and two disconnected density islands (A and B) of mixed sequences. There is a non-proteinaceous cofactor bound between the core and island A. The JOS fold resembles the common substructure of MSA type I and type II dimeric filaments, with its core segment approximating the C-terminal body of MSA protofilaments B and its islands mimicking the N-terminal arm of MSA protofilaments A. The partial similarity of JOS and MSA folds extends to the locations of their cofactor-binding sites. Our findings provide insight into a likely mechanism of JOS fibrillation in which mutant α-synuclein of 147 amino acids forms a nucleus with the JOS fold, around which wild-type and mutant proteins assemble during elongation.
Genetics and resource availability shape divergence in life history and behavior between locally-adapted populations of Atlantic mollies (Poecilia mexicana, Poeciliidae)
Authors: Coffin John L. , Williams Bethany L. , Tobler Michael 
Published: November 2022

AbstractPhenotypic variation is common along environmental gradients, but it is often unknown to what extent it results from genetic differentiation between populations or phenotypic plasticity. We studied populations of a livebearing fish that have colonized streams rich in toxic hydrogen sulfide (H2S). In nature, there is strong phenotypic differentiation between adjacent sulfidic and nonsulfidic populations. In this study, we varied food availability to pregnant mothers from different populations to induce maternal effects, a form of plasticity, and repeatedly measured life-history and behavioral traits throughout the offspring’s ontogeny. Genetic differentiation affected most of the traits we measured, as sulfidic offspring tended to be born larger, mature later, have lower burst swimming performance, be more exploratory, and feed less accurately. In contrast, maternal effects impacted few traits and at a smaller magnitude, even though offspring from poorly provisioned mothers tended to be born larger and be more exploratory. Population differences and maternal effects (when both were present) acted synergistically, and there was no evidence for population differences in plasticity. Overall, our study suggests that phenotypic divergence between these populations in nature is primarily caused by genetic differentiation, and that plasticity mediated by maternal effects accentuates—but does not cause—differences between populations.
BiallelicSTAB1pathogenic variants cause hereditary hyperferritinemia
Authors: Monfrini Edoardo , Pelucchi Sara , Hollmén Maija , Viitala Miro , Mariani Raffaella , Bertola Francesca , Majore Silvia , Fonzo Alessio Di , Piperno Alberto 
Published: November 2022

AbstractSerum ferritin measurement is a routine laboratory test to indirectly evaluate body iron content. However, many additional factors may elevate serum ferritin levels disproportionally to iron stores. Hyperferritinemia is a frequent finding in several conditions, both genetic and acquired. Despite the long history of clinical use, fundamental aspects of the biology of serum ferritin are still unclear. We studied eleven healthy subjects from eight different families presenting unexplained hyperferritinemia without iron overload. To detect the genetic cause of hyperferritinemia we carried out whole-exome sequencing. Immunohistochemistry and flow cytometry assays were performed on patient liver biopsies and monocyte-macrophages to confirm the pathogenic role of the identified candidate variants. Through a combined approach of whole-exome sequencing and homozygosity mapping, we found biallelic candidateSTAB1variants in ten subjects from seven families.STAB1encodes the multifunctional scavenger receptor stabilin-1. Immunohistochemical studies and flow cytometry analyses showed absent or markedly reduced stabilin-1 in patient liver samples, monocytes and monocyte-derived macrophages. We present biallelicSTAB1mutations as a new cause of inherited hyperferritinemia without iron overload suggesting the existence of new and unexpected function of stabilin-1 in ferritin metabolism.In conclusion, our findings strongly support biallelicSTAB1mutations as a novel genetic cause of inherited hyperferritinemia without iron overload and suggest the existence of a new and unexpected function of stabilin-1 in ferritin metabolism.
Trends and predictors of unmet need for family planning among women living with HIV in Zambia: implications for elimination of Mother to Child Transmission of HIV
Authors: Lungu Edgar Arnold , Chewe Mwimba 
Published: November 2022

AbstractIntroductionPrevention of Mother To Child Transmission (PMTCT) of HIV is one of the key strategies towards HIV epidemic control. Despite considerable progress in PMTCT of HIV over the past decade in Zambia, the country is yet to reach global and national target for elimination of Mother To Child Transmission of HIV. Avoidance of unintended pregnancy among women living with HIV provides is one of the cost-effective interventions in a comprehensive PMTCT of HIV approach. This study therefore aimed at ascertaining trends in and predictors of unmet need for family planning among women living with HIV in ZambiaMethodsThe study employed a repeated cross sectional (RCS) study design, using data from the three (3) most recent consecutive rounds of the Zambia Demographic and Health Survey (ZDHS) conducted in 2007, 2013/2014 and 2018. The study used data from a total of 34,204 women aged 15-49 years from the three survey points, 2007, 2013/14 and 2018, among whom 4,985 were HIV positive, with a final sample size constituting 2,675 married women living with HIV. We used descriptive statistics and logistic regression analyses to respectively ascertain trends in and predictors of unmet need for family planning among married women living with HIV.ResultsOver the three survey points, unmet need for family planning among married women living with HIV has hardly declined, registering 22% in both the 2007 and 2018. Residence, age of women, household wealth, woman’s parity, employment, and age of spouse emerged as significant predictors of unmet need for family planning among women living with HIV in ZambiaConclusionPreventing one HIV infection in a child is averting lifetime costs of HIV treatment and associated healthcare costs. There is need to consider optimization of PMTCT interventions including shaping programming regarding prong 2 in a way that it responds to main causes of mother to child transmission of HIV in Zambia. Among other aspects, policy and practice needs to strengthen SRH/HIV integration and better target rural residents, younger women, those with high parity and consider positive male engagement to reduce unmet need for family planning among women living with HIV.
Women’s mortality following pregnancy affected by vaginal bleeding due to threatened miscarriage: a Danish cohort study
Authors: Dudukina Elena , Horváth-Puhó Erzsébet , Sørensen Henrik Toft , Ehrenstein Vera 
Published: November 2022

AbstractBackgroundWomen with only pregnancy terminations or only miscarriages have an increased mortality risk. We investigated the association between vaginal bleeding (VB) in pregnancy ending in childbirth and women’s mortality.MethodsWe conducted a cohort study in Denmark, which included 1,354,181 women and their 3,162,317 pregnancies (1979-2017) followed through 2018. We ascertained 70,835 VB-affected pregnancies and comparators: 2,236,359 VB-unaffected pregnancies ending in childbirth; 589,697 terminations; and 265,940 miscarriages. We computed all-cause and cause-specific mortality rates per 10,000 person-years (PY) and hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox proportional hazards regression adjusted for age, calendar year, preexisting conditions, and socioeconomic factors.ResultsThere were 2,320 deaths from any cause among women following VB-affected pregnancy (mortality rate: 15.2, 95% CI: 14.6-15.9 per 10,000 PY); 55,030 deaths following VB-unaffected pregnancy (12.7, 12.6-1.28); 27,500 deaths following a termination (21.9, 21.6-22.1), and 10,865 deaths following a miscarriage (19.2, 18.8-19.6).For comparison of VB-affected vs VB-unaffected pregnancies, associations with all-cause (HR: 1.14, 95% CI: 1.09-1.19), natural-causes (HR: 1.15, 95% CI: 1.09-1.22) and non-natural causes (HR: 1.27, 95% CI: 1.08-1.48) mortality attenuated in a sensitivity analysis of pregnancies recorded in 1994-2017 (HR: 1.00, 95% CI: 0.90-1.12, HR: 0.98, 95% CI: 0.85-1.14, and HR: 1.04, 95% CI: 0.71-1.51, respectively). Contrasts with remaining comparators did not suggest increased risks of all-cause, natural, or non-natural mortality causes.ConclusionsWe found no evidence of an increased risk of mortality in women following VB-affected vs VB-unaffected pregnancy, termination, or miscarriage.Key MessagesPrevious studies mostly focused on short-term outcomes of the newborns and mothers following the vaginal bleeding-affected pregnancy. This study investigated the association between vaginal bleeding in pregnancy ending in childbirth and women’s mortality.This registry-based cohort study found no evidence of an increased risk of all-cause or cause-specific mortality from natural or non-natural causes in women following vaginal bleeding-affected pregnancy compared with vaginal bleeding-unaffected pregnancy, termination, or miscarriage