bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extradural Contralateral Ventral Root Transfer to Treat Lower Limb Motor Dysfunction in Paraplegia
Authors: Chang Jie , Cao Jiang , Wu Chaoqin , Zhang Sheng , Wang Binyu , Cao Xiaojian , Sui Tao 
Published: July 2022

Study Design.
Eight cadavers were included in this anatomical study.

Objective.
This study aimed to confirm the anatomical feasibility of extradural transfer of the contralateral T11 ventral root (VR) to the ipsilateral L2 level and the contralateral L1 VR to the ipsilateral L3 level to restore lower limb function in cases of paraplegia.

Summary of Background Data.
Motor dysfunction due to hemiplegia significantly affects the daily life of patients. To date, unlike in cases of upper limb dysfunction, there are few studies on the surgical management of lower limb movement dysfunction.

Materials and Methods.
Eight cadavers were included in this study to confirm the feasibility of the nerve transfer. After separating the VR and dorsal root at each level, the VRs at the T11 and L1 levels were anastomosed with the VRs of L2 and L3, respectively. The length of the VRs of donor roots and the distance between the donor and recipient nerves were measured. H&E staining was performed to verify the number of axons and the cross-sectional area of the VRs. Lumbar x-rays of 60 healthy adults were used to measure the distance between the donor and recipient nerves.

Results.
After exposing the bilateral extradural each root, the VRs could be easily isolated from the whole root. The distance between the VRs of T11 and L2, L1, and L3 was significantly longer than the length of the donor nerve. Therefore, the sural nerve was used for grafting. The measurements performed on the lumbar x-rays of the 60 healthy adults confirmed the results. The number of axons and cross-sectional area of the VRs were measured.

Conclusion.
Our study confirmed the anatomical feasibility of transferring the VRs of T11 to L2 and that of L1 to L3 to restore lower limb function in cases of hemiplegia.

Level of Evidence.
5.
Racially Focused LGBQ Pride Events: The Promotion of Psychological Wellbeing Among Cisgender LGBQ People of Color
Authors: Curtis Michael G. 
Published: July 2022

AbstractLesbian, gay, bisexual, and queer/questioning people of color (LGBQ POC) are disproportionately more likely to experience issues related to their mental health when compared to their White counterparts. In spite of this persistent mental health disparity, few studies have been dedicated to identifying mental health-related promotive factors among LGBQ POC adults. The current study examined the extent to which attending LGBQ POC Pride events (e. g., Black Pride Festival) was associated with cisgender LGBQ POC’s psychological wellbeing. I hypothesized that attendance would be positively associated with psychological well-being due to the unique sociocultural resources offered at these events. I further hypothesized that participants’ racial/ethnic identity or gender would modulate these effects. Hypotheses were tested using multiple linear regression with data from the 2013 Social Justice Sexuality Project (n = 2,486). Attending LGBQ POC Pride events was positively associated with cisgender LGBQ POC’s psychological wellbeing. Post hoc multigroup analysis indicated that participants’ racial/ethnic identity or gender did not moderate these effects. Findings suggest that attending racially focused LGBQ Pride events may offer cisgender LGBQ POC’s unique psychological resources that are not provided by general LGBQ Pride events.Public Health SignificanceLGBQ people of color (POC) are a multiply marginalized population vulnerable to increased levels of psychological distress that is unquietly different from their White LGBQ counterparts. Findings suggest that increasing the prevalence of racially focused Pride events may contribute to the psychological wellbeing of LGBQ POC.
Community-orientated primary health care: exploring the interface between community health worker programmes, the health system and communities in South Africa
Authors: Malatji Hlologelo , Griffiths Frances , Goudge Jane 
Published: July 2022

ABSTRACTDue to insufficient number of health workers in low- and middle-income countries, and the evidence of the benefits of community health workers (CHWs), CHWs are being deployed to provide health care services to under-served communities. In this article, we explore to what extent a nation-wide CHW programme in South Africa is attuned to community needs, integrated into the healthcare system and community structures, and also implemented in accordance with community-orientated primary health care principles. Using a case study approach, the study was conducted in seven primary healthcare facilities located in semi-urban and rural areas of Gauteng and Mpumalanga provinces, South Africa. We collected data using in-depth interviews involving facility managers, CHW supervisors and community representatives, and focus groups and observations of CHWs. The implementation of community-orientated community worker programmes remains complex. In the different sites we studied, there were efforts to integrate the views of stakeholders (e.g., political leaders) into the implementation of the programmes. However, many residents were more concerned about access to housing that health services delivery issues. The CHW services’ were found to be generally comprehensive, however inefficient training, supervision and mentorship limited their effectiveness. The multidisciplinary approach to care, as introduced by some sites, helped enhance the knowledge and skills of some of the CHWs on complex health topics. The roll out of community orientated primary health care services is crucial in a resource constrained setting like South Africa. Significant socio-economic issues are barriers to community involvement and the effective provision of services. Governments need to provide sufficient funds for training, supervision, supplies and remuneration to help overcome these barriers.
Views of American Democracy and Society and Support for Political Violence: First Report from a Nationwide Population-Representative Survey
Authors: Wintemute Garen J. , Robinson Sonia , Crawford Andrew , Schleimer Julia P. , Barnhorst Amy , Chaplin Vicka , Tancredi Daniel , Tomsich Elizabeth A. , Pear Veronica A. 
Published: July 2022

ABSTRACTBackgroundSeveral social trends in the United States (US) suggest an increasing risk for political violence. Little is known about support for and personal willingness to engage in political violence and how those measures vary with lethality of violence, specific circumstances, or specific populations as targets.Design, Setting, ParticipantsCross-sectional nationwide survey conducted May 13 to June 2, 2022; participants were adult members of the Ipsos KnowledgePanel.Main Outcomes and MeasuresWeighted, population-representative proportions endorsing an array of beliefs about American democracy and society and the use of violence, including political violence, and extrapolations to the US adult population.ResultsThe analytic sample included 8,620 respondents; 50.6% (95% Confidence Interval (CI) 49.4%, 51.7%) were female; mean (SD) age was 48.4 (18.0) years. Two-thirds of respondents (67.2%, 95% CI 66.1%, 68.4%) perceived “a serious threat to our democracy,” but more than 40% agreed that “having a strong leader for America is more important than having a democracy” and that “in America, native-born white people are being replaced by immigrants.” Half (50.1%) agreed that “in the next few years, there will be civil war in the United States.” Among 6,768 respondents who considered violence to be at least sometimes justified to achieve 1 or more specific political objectives, 12.2% were willing to commit political violence themselves “to threaten or intimidate a person,” 10.4% “to injure a person,” and 7.1% “to kill a person.” Among all respondents, 18.5% thought it at least somewhat likely that within the next few years, in a situation where they believed political violence was justified, “I will be armed with a gun”; 4.0% thought it at least somewhat likely that “I will shoot someone with a gun.”Conclusions and RelevanceCoupled with prior research, these findings suggest a continuing alienation from and mistrust of American democratic society and its institutions. Substantial minorities of the population endorse violence, including lethal violence, to obtain political objectives. Efforts to prevent that violence, which a large majority of Americans already reject, should proceed rapidly based on the best evidence available. Further research will inform future prevention efforts.
SARS-CoV-2 oral tablet vaccination induces neutralizing mucosal IgA in a phase 1 open label trial
Authors: Johnson Susan , Martinez Clarissa I , Jegede Clara B , Gutierrez Samanta , Cortese Mario , Martinez C Josefina , Garg Shaily J , Peinovich Nadine , Dora Emery G , Tucker Sean N 
Published: July 2022

AbstractBackgroundDespite the plethora of efficacious vaccines to the initial Wuhan strain of SARS-CoV-2, these do not induce robust mucosal immunity, offering limited protection against breakthrough infection and replication in the respiratory tract. The mucosa is the first line of defense, therefore a vaccine that induces a mucosal IgA response could be an important strategy in curbing the global pandemic.MethodsWe conducted a single-site, dose-ranging, open-label clinical trial of an oral SARS-CoV-2 vaccine to determine safety and immunogenicity. This tablet vaccine is comprised of a non-replicating adenoviral vector expressing the SARS-CoV-2 Spike and Nucleocapsid genes and a double-stranded RNA adjuvant. 35 adult subjects meeting inclusion/exclusion criteria received a single low (1×1010 IU) or high (5×1010 IU) dose and 5 subjects received two low doses. Nasal, saliva and serum samples were assessed for the presence of IgA, IgG and surrogate neutralizing antibodies. Convalescent subjects between 1-8 months post infection were recruited to give nasal, saliva, and serum samples for comparison.ResultsThe vaccine was well tolerated without any dose-limiting toxicity observed. No serum neutralizing antibodies were observed, but modest IgA responses were seen in serum post immunization. The majority of vaccine recipients had an increase in mucosal secretory IgA which was highly cross-reactive against all coronaviruses tested and persisted up to 360 days. Furthermore, the nasal IgA induced by vaccination has superior neutralizing activity compared to convalescent nasal samples.ConclusionThe vaccine was safe, well tolerated and generated mucosal immune responses including cross-reactive surrogate neutralizing secretory IgA. These results demonstrate the ability of a mucosal vaccine to induce long-lasting mucosal IgA to SARS-CoV-2.Graphical Abstract
Analysis of a paediatric cohort of dyslipidaemic patients using unsupervised learning methods provides insights into the biochemical phenotypes of familial hypercholesterolemia
Authors: Correia Marta , Bourbon Mafalda , Gama-Carvalho Margarida 
Published: July 2022

ABSTRACTFamilial hypercholesterolaemia (FH) is a highly prevalent silent disease with known genetic causes and poor prognosis if undiagnosed into adulthood. Characterised by high levels of total cholesterol and low-density lipoprotein cholesterol from birth, the majority of cases that fit the clinical criteria for FH do not present mutations in the disease associated genes and seem to result from polygenic and/or environmental causes. In this study we have addressed the heterogeneity of extended blood biochemical and genetic parameters across a cohort of children using an unsupervised hierarchical clustering approach. In addition to correctly classifying individuals into the two classes recognized in clinical studies for familial hypercholesterolaemia (with and without genetic diagnosis), a subset of patients with mixed characteristics was systematically identified as representing a third category. The careful analysis of biochemical, genetic, and anthropomorphic characteristics that constitute hallmarks of each group provides detailed insights into the characteristics of each group, contributing to unravel the complexity of FH and dyslipidaemic phenotypes. The results presented here may assist in the future identification of novel biomarkers to efficiently identify FH+ individuals.
Adaptive sentinel testing in workplace for COVID-19 pandemic
Authors: Li Yi , Chen Mandy , George Joshy , Liu Edison T. , Murthy Karuturi R. Krishna 
Published: July 2022

AbstractTesting and isolation of infectious employees is one of the critical strategies to make the workplace safe during the pandemic for many organizations. Adaptive testing frequency reduces cost while keeping the pandemic under control at the workplace. However, most models aimed at estimating test frequencies were structured for municipalities or large organizations such as university campuses of highly mobile individuals. By contrast, the workplace exhibits distinct characteristics: employee positivity rate may be different from the local community because of rigorous protective measures at workplace, or self-selection of co-workers with common behavioral tendencies for adherence to pandemic mitigation guidelines. Moreover, dual exposure to COVID19 occurs at work and home that complicates transmission modelling, as does transmission tracing at the workplace. Hence, we developed bi-modal SEIR model and R-shiny tool that accounts for these differentiating factors to adaptively estimate the testing frequency for workplace. Our tool uses easily measurable parameters: community incidence rate, risks of acquiring infection from community and work-place, workforce size, and sensitivity of testing. Our model is best suited for moderate-sized organizations with low internal transmission rates, no-outward facing employees whose position demands frequent in-person interactions with the public, and low to medium population positivity rates. Simulations revealed that employee behavior in adherence to protective measures at work and in their community, and the onsite workforce size have large effects on testing frequency. Reducing workplace transmission rate through workplace mitigation protocols and higher sensitivity of the test deployed, though to a lesser extent. Furthermore, our simulations showed that sentinel testing leads to only marginal increase in the number of infections even for high community incidence rates, suggesting that this may be a cost-effective approach in future pandemics. We used our model to accurately guide testing regimen for three campuses of The Jackson Laboratory.
Accounting for endogenous effects in decision-making with a non-linear diffusion decision model
Authors: Hoxha Isabelle , Chevallier Sylvain , Ciarchi Matteo , Glasauer Stefan , Delorme Arnaud , Amorim Michel-Ange 
Published: July 2022

ABSTRACTThe Drift-Diffusion Model (DDM) is widely accepted for two-alternative forced-choice decision paradigms thanks to its simple formalism and close fit to behavioral and neurophysiological data. However, this formalism presents strong limitations in capturing inter-trial dynamics at the single-trial level and endogenous influences. We propose a novel model, the non-linear Drift-Diffusion Model (nl-DDM), that addresses these issues by allowing the existence of several trajectories to the decision boundary. We show that the non-linear model performs better than the drift-diffusion model for an equivalent complexity. To give better intuition on the meaning of nl-DDM parameters, we compare the DDM and the nl-DDM through correlation analysis. This paper provides evidence of the functioning of our model as an extension of the DDM. Moreover, we show that the nl-DDM captures time effects better than the DDM. Our model paves the way toward more accurately analyzing across-trial variability for perceptual decisions and accounts for peri-stimulus influences.
Evidence for intercellular bridges and radial patterning of meiotic initiation in the human fetal ovary
Authors: Soygur Bikem , Derpinghaus Amber , Cunha Gerald R. , Baskin Laurence S. , Laird Diana J 
Published: July 2022

AbstractMeiosis is the hallmark of reproduction. Our understanding of early oocyte development was improved by studying the spatiotemporal dynamics and mechanisms governing meiosis in mice, however, our knowledge of the meiotic initiation process in humans remains limited. Here, we utilized three-dimensional (3D) analysis to determine spatiotemporal dynamics of meiotic initiation in fetal human ovaries. Similar to mice, we found that the first meiotic cells appear in clusters in the center of human fetal ovaries as early at 9 weeks and that the initiation of meiosis propagates as a radial wave. Between developing germ cells in fetal human ovaries, we detected a component of the intercellular bridge, TEX14 protein. 3D quantification of germ cells in ovaries collected at the end of first trimester revealed, for the first time, considerable variation in the number of meiotic cells between individuals and asynchronous mitotic-meiotic transition. In addition to illustrating the geography of meiotic initiation in ovaries from the first trimester, we extended our 3D analysis approach to second trimester and showed heterogeneous spatial distribution of meiotic and non-meiotic germ cells in human fetal ovaries. This study is an important step towards better understanding of 3D structure of developing ovary and early stages of meiosis in humans.Highlights-Organic solvent-based clearing methods and confocal microscopy can be implemented to visualize and quantify germ cells in the intact human fetal ovary.-Identification of a new, radial, pattern of meiotic initiation in the ovaries from the first trimester.-Immunolocalization of the intercellular bridge component TEX14 between developing germ cells in the fetal ovary-Maintenance of pre-meiotic germ cells in second trimester ovaries suggests less synchronous mitotic-meiotic stage transition.
Wnt5A Signaling Regulates Gut Bacterial Survival and T cell Homeostasis
Authors: Sengupta Soham , Jati Suborno , Maity Shreyasi , Sen Malini 
Published: July 2022

AbstractIn light of the demonstrated antagonism of Wnt5A signaling toward the growth of several bacterial pathogens, it was important to study the influence of Wnt5A on gut resident bacteria, and its outcome. Here we demonstrate that in contrast to inhibiting the survival of the established gut pathogen Salmonella enterica, Wnt5A clearly promotes the survival of the common gut commensals Enterococcus faecalis and Lactobacillus rhamnosus within macrophages through a self-perpetuating Wnt5A-Actin axis. A Wnt5A – Actin axis furthermore regulates the subsistence of the natural bacterial population of the Peyer’s patches, as is evident from the diminution in the countable bacterial colony forming units therein through the application of Wnt5A signaling and actin assembly inhibitors. Wnt5A dependency of the gut resident bacterial population is also manifested in the notable difference between the bacterial diversities associated with the feces and Peyer’s patches of Wnt5A heterozygous mice, which lack a functional copy of the Wnt5A gene, and the wild type counterparts. Alterations in gut commensal bacterial population resulting from either the lack of a copy of the Wnt5A gene or inhibitor mediated attenuation of Wnt5A signaling correlate with significantly different ratios of regulatory vs. activated CD4 T cells associated with the Peyer’s patches. Taken together, our study reveals the importance of Wnt5A signaling in shaping the gut commensal bacterial population and the T cell repertoire linked to it, thus unveiling a crucial control device for the maintenance of gut bacterial diversity and T cell homeostasis.Significance StatementGut commensal bacterial diversity and T cell homeostasis are crucial entities of the host innate immune network. Yet molecular details of host directed signaling pathways that sustain the steady state of gut bacterial colonization and T cell activation remain unclear. Here we describe the protective role of a Wnt5A-Actin axis in the survival of several gut bacterial commensals, and its importance in shaping gut bacterial colonization and the associated T cell repertoire. This study opens up new avenues of investigation into the role of the Wnt5A-Actin axis in protection of the gut from dysbiosis related inflammatory disorders.
Topological screen identifies hundreds of Cp190 and CTCF dependent Drosophila chromatin insulator elements
Authors: Kahn Tatyana G. , Savitsky Mikhail , Kuong Chikuan , Jacquer Caroline , Cavalli Giacomo , Chang Jia-Ming , Schwartz Yuri B. 
Published: July 2022

AbstractDrosophila insulators were the first DNA elements discovered to regulate gene expression by delimiting chromatin contacts. Remarkably, it is still unclear how many of them exist in the Drosophila genome and whether they have a pervasive impact on the genome folding. Contrary to vertebrates, there is no evidence that fly insulators block cohesin-mediated chromatin loop extrusion. Therefore, their mechanism of action remains an open question. To bridge these gaps, we mapped genomic contacts, transcriptomes and binding landscapes of insulator associated proteins in Drosophila cells deficient for CTCF and Cp190. With this approach, we discovered hundreds of chromatin insulator elements. Their study indicates that Drosophila insulators play a minor role in shaping the overall chromosome folding patterns but impact chromatin contacts locally at many individual loci. Our observations argue that Cp190 promotes co-binding of other insulator proteins and that the model, where Drosophila insulators block chromatin contacts by forming loops, needs revision. The extended catalogue of insulator elements presented here provides a significant new resource to study mechanisms that shape the folding of eukaryotic genomes.