bluuebunny/crossref_metadata_2025_split huggingface dataset:
VGLUT3‐p.A211V variant fuses stereocilia bundles and elongates synaptic ribbons
Authors: Joshi Yuvraj , Petit Chloé P. , Miot Stéphanie , Guillet Marie , Sendin Gaston , Bourien Jérôme , Wang Jing , Pujol Rémy , El Mestikawy Salah , Puel Jean‐Luc , Nouvian Régis 
Published: November 2021

AbstractDFNA25 is an autosomal‐dominant and progressive form of human deafness caused by mutations in the SLC17A8 gene, which encodes the vesicular glutamate transporter type 3 (VGLUT3). To resolve the mechanisms underlying DFNA25, we studied phenotypes of mice harbouring the p.A221V mutation in humans (corresponding to p.A224V in mice). Using auditory brainstem response and distortion product otoacoustic emissions, we showed progressive hearing loss with intact cochlear amplification in the VGLUT3A224V/A224V mouse. The summating potential was reduced, indicating the alteration of inner hair cell (IHC) receptor potential. Scanning electron microscopy examinations demonstrated the collapse of stereocilia bundles in IHCs, leaving those from outer hair cells unaffected. In addition, IHC ribbon synapses underwent structural and functional modifications at later stages. Using super‐resolution microscopy, we observed oversized synaptic ribbons and patch‐clamp membrane capacitance measurements showed an increase in the rate of the sustained releasable pool exocytosis. These results suggest that DFNA25 stems from a failure in the mechano‐transduction followed by a change in synaptic transfer. The VGLUT3A224V/A224V mouse model opens the way to a deeper understanding and to a potential treatment for DFNA25.Key points
The vesicular glutamate transporter type 3 (VGLUT3) loads glutamate into the synaptic vesicles of auditory sensory cells, the inner hair cells (IHCs).
The VGLUT3‐p.A211V variant is associated with human deafness DFNA25.
Mutant mice carrying the VGLUT3‐p.A211V variant show progressive hearing loss.
IHCs from mutant mice harbour distorted stereocilary bundles, which detect incoming sound stimulation, followed by oversized synaptic ribbons, which release glutamate onto the afferent nerve fibres.
These results suggest that DFNA25 stems from the failure of auditory sensory cells to faithfully transduce acoustic cues into neural messages.
Corticothalamic projections deliver enhanced responses to medial geniculate body as a function of the temporal reliability of the stimulus
Authors: Kommajosyula Srinivasa P. , Bartlett Edward L. , Cai Rui , Ling Lynne , Caspary Donald M. 
Published: November 2021

AbstractAgeing and challenging signal‐in‐noise conditions are known to engage the use of cortical resources to help maintain speech understanding. Extensive corticothalamic projections are thought to provide attentional, mnemonic and cognitive‐related inputs in support of sensory inferior colliculus (IC) inputs to the medial geniculate body (MGB). Here we show that a decrease in modulation depth, a temporally less distinct periodic acoustic signal, leads to a jittered ascending temporal code, changing MGB unit responses from adapting responses to responses showing repetition enhancement, posited to aid identification of important communication and environmental sounds. Young‐adult male Fischer Brown Norway rats, injected with the inhibitory opsin archaerhodopsin T (ArchT) into the primary auditory cortex (A1), were subsequently studied using optetrodes to record single‐units in MGB. Decreasing the modulation depth of acoustic stimuli significantly increased repetition enhancement. Repetition enhancement was blocked by optical inactivation of corticothalamic terminals in MGB. These data support a role for corticothalamic projections in repetition enhancement, implying that predictive anticipation could be used to improve neural representation of weakly modulated sounds.Key points
In response to a less temporally distinct repeating sound with low modulation depth, medial geniculate body (MGB) single units show a switch from adaptation towards repetition enhancement.
Repetition enhancement was reversed by blockade of MGB inputs from the auditory cortex.
Collectively, these data argue that diminished acoustic temporal cues such as weak modulation engage cortical processes to enhance coding of those cues in auditory thalamus.
Magmatism and related metamorphism as a response to mountain-root collapse of the Dabie orogen: Constraints from geochronology and petrogeochemistry of metadiorites
Authors: Yang Yang , Liu Yi-Can , Li Yang , Groppo C. , Rolfo F. 
Published: November 2021

ABSTRACTPost-collisional mountain-root collapse and subsequent massive partial melting occurred in the high-temperature (HT) ultrahigh-pressure (UHP) metamorphic terrane of the North Dabie complex zone (NDZ), central China. The NDZ was deeply subducted in the Triassic, producing widespread migmatites and various magmatic intrusions in the Cretaceous. Post-collisional metadiorites with distinctive large K-feldspar augen porphyroblasts, locally reported but rarely exposed in the NDZ, underwent a complex evolutional history. In this contribution, integrated studies including field investigation, petrographic observation and mineral analysis, zircon U-Pb geochronological and Hf isotopic analyses, and whole-rock elemental and Sr-Nd-Pb isotopic analyses of the metadiorites were carried out. Our results provide new constraints on the mountain-root collapse in the Dabie orogen. The metadiorites are enriched in large ion lithophile elements and light rare earth elements, whereas they are depleted in high field strength elements and heavy rare earth elements with significant Ba positive anomalies, a composition consistent with the lower continental crust. All the studied samples have moderately enriched initial 87Sr/86Sr ratios (0.707582–0.708099), low εNd(t) values (−15.3 to −20.4), and low initial Pb isotopic ratios (16.0978–16.8452, 15.3167–15.4544, and 37.1778–37.8397 for 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb, respectively). However, they have highly negative εHf(t) values and Paleoproterozoic two-stage Hf model ages, which are only partially consistent with data from the associated UHP metamorphic rocks. Such features suggest the metadiorites resulted from a magma produced by mixing of Triassic UHP mafic lithologies and minor amounts of mantle-derived materials. Zircon morphological analysis and U-Pb sensitive high-resolution ion microprobe dating combined with conventional thermobarometry indicate that these upwelling melts crystallized at pressure-temperature (P-T) conditions of 5.4–5.7 kbar and 750–768 °C at ca. 130 Ma and subsequently suffered HT metamorphism at ca. 125 Ma. We conclude that the metadiorites’ precursors were derived from partial melting of the Triassic subducted Neoproterozoic mafic lower-crustal rocks, with addition of minor amounts of mantle-derived materials in the Early Cretaceous, in response to mountain-root collapse of the orogen. Based on petrographic textures and mineral compositions, it is moreover inferred that formation of the distinctive K-feldspar porphyroblasts is likely related to a two-stage process, i.e., crystallization derived from biotite breakdown after the formation of the metadiorite at T = 640–703 °C and P &lt; 4.5 kbar and coarsening related to shear deformation.
Global red and processed meat trade and non-communicable diseases
Authors: Chung Min Gon , Li Yingjie , Liu Jianguo 
Published: November 2021

IntroductionRapid increases in the trade of global red and processed meat impede international efforts toward sustainable diets by increasing meat consumption. However, little research has examined cross-country variations in diet-related non-communicable diseases (NCDs) because of meat trade. We aimed to examine the impact of red and processed meat trade on diet-related NCDs and to identify which countries are particularly vulnerable to diet-related NCDs due to red and processed meat trade.MethodsBy selecting 14 red meat and six processed meat items, we investigated bilateral meat trade flows across 154 countries. Then, we integrated health data and information on red and processed meat trade to quantify the country-specific burden of diet-related NCDs attributable to the meat trade using a comparative risk assessment framework.ResultsResults show that global increases in red and processed meat trade contributed to the abrupt increase of diet-related NCDs, and the attributable burden of diet-related NCDs had large geographical variations among countries. We also identified responsible exporting countries that increase diet-related NCD risks in importing countries. Over the period from 1993 to 2018, island countries in the Caribbean and Oceania were particularly vulnerable to diet-related NCD incidents and mortality due to large meat imports. In addition, countries in Northern and Eastern Europe have exceedingly increased attributable death and disability-adjusted life year rates via meat imports.ConclusionOur findings suggest that both exporters and importers must urgently undertake cross-sectoral actions to reduce the meat trade’s health impacts. To prevent unintended health consequences due to red and processed meat trade, future interventions need to integrate health policies with agricultural and trade policies by cooperating with both responsible exporting and importing countries.
Trends and causes of adult mortality from 2007 to 2017 using verbal autopsy method, Addis Ababa, Ethiopia
Authors: Fenta Esete Habtemariam , Sisay Binyam Girma , Gebreyesus Seifu H , Endris Bilal Shikur 
Published: November 2021

ObjectivesWe aim to analyse the trends and causes of mortality among adults in Addis Ababa.SettingThis analysis was conducted using verbal autopsy data from the Addis Ababa Mortality Surveillance in Addis Ababa, Ethiopia.ParticipantsAll deceased adults aged 15 years and above between 2007–2012 and 2015–2017 were included in the analysis.Outcome measuresWe collected verbal autopsy and conducted physician review to ascertain cause of death.ResultA total of 7911 data were included in this analysis. Non-communicable disease (NCD) accounted for 62.8% of adult mortality. Mortality from communicable diseases, maternal conditions and nutritional deficiencies followed this by accounting for 30.3% of total mortality. Injury accounted for 6.8% of total mortality. We have observed a significant decline in mortality attributed to group one cause of death (43.25% in 2007 to 12.34% in 2017, p<0.001). However, we observed a significant increase in mortality attributed to group II cause of death (from 49.95% in 2007 to 81.17% in 2017, p<0.001). The top five leading cause of death in 2017 were cerebrovascular disease (12.8%), diabetes mellitus (8.1%), chronic liver disease (6.3%), hypertension (5.7%), ischaemic heart disease (5.7%) and other specified neoplasm (5.2%).ConclusionWe documented an epidemiological shift in cause of mortality from communicable diseases to NCD over 10 years. There is a great progress in reducing mortality due to communicable diseases over the past years. However, the burden of NCDs call for actions for improving access to quality health service, improved case detection and community education to increase awareness. Integrating NCD intervention in to a well-established and successful programme targeting communicable diseases in the country might be beneficial for improving provision of comprehensive healthcare.
How do health professionals translate evidence on early childhood allergy prevention into health literacy-responsive practice? A protocol for a mixed-method study on the views of German health professionals
Authors: Curbach Janina , Lander Jonas , Dierks Marie Luise , Grepmeier Eva-Maria , von Sommoggy Julia 
Published: November 2021

IntroductionPaediatricians, general practitioners (GPs) and midwives in primary care are important sources of information for parents on early childhood allergy prevention (ECAP). Research has shown that preventive counselling by health professionals can be effective in improving patients’ health literacy (HL) and health behaviour. Providing effective advice relies on two factors. First, health professionals need be up-to-date with research evidence on ECAP, to consider popular misconceptions and fears and to translate this knowledge into clear recommendations for parents (knowledge translation). Second, they need to know and apply counselling techniques and create a practice setting which accommodates parental HL needs (health literacy-responsive care). The objective of this study is to explore and assess how German health professionals take up and translate ECAP evidence into appropriate recommendations for parents, how they consider HL in counselling and practice organisation and what barriers and enablers they find in their performance of HL-responsive ECAP.Methods and analysisThe study has a sequential mixed-method design, in two phases. In the first phase, qualitative semi-structured expert interviews will be conducted with health professionals (paediatricians, GPs and midwives) at primary care level and professional policy level. Data collection is ongoing until January 2022. In the second phase, based on the qualitative results, a standardised questionnaire will be developed, and pilot-tested in a wider population of German health professionals. The findings of both phases will be integrated.Ethics and disseminationThe study has received ethical approval from the Ethics Committee of the University of Regensburg (18-1205-101). The results will be published in international peer-reviewed open access journals and via presentations at scientific conferences. The results will also be shared with German health professionals, decision-makers and potential funders of interventions.
Efficacy of tofacitinib in reduction of inflammation detected on MRI in patients with Psoriatic ArthritiS presenTing with axial involvement (PASTOR): protocol of a randomised, double-blind, placebo-controlled, multicentre trial
Authors: Proft Fabian , Torgutalp Murat , Muche Burkhard , Rios Rodriguez Valeria , Verba Maryna , Poddubnyy Denis 
Published: November 2021

IntroductionPsoriatic arthritis (PsA) is an inflammatory disease characterised by synovitis, enthesitis, dactylitis and axial involvement. The prevalence of axial involvement ranges from 25% to 70% in this patient group. Treatment recommendations for axial PsA were mainly extrapolated from guidelines for axial spondyloarthritis, and the main treatment options are non-steroidal anti-inflammatory drugs and biological disease-modifying antirheumatic drugs (tumour necrosis factor, IL-17 and IL-23 inhibitors). Tofacitinib was approved for the treatment of PsA and its efficacy on axial inflammation has been demonstrated in a phase II study of ankylosing spondylitis (AS). This prospective study aims to evaluate the efficacy of tofacitinib in reducing inflammation in the sacroiliac joints (SIJs) and spine on MRI in patients with axial disease of their PsA presenting with active axial involvement compatible with axial PsA.Methods and analysesThis is a randomised, double-blind, placebo-controlled, multicentre clinical trial in patients with axial PsA who have evidence of axial involvement, active disease as defined by a Bath AS Disease Activity Index score of ≥4 and active inflammation on MRI of the SIJs and/or spine as assessed by and independent central reader. The study includes a 6-week screening period, a 24-week treatment period, which consist of a 12-week placebo-controlled double-blind treatment period followed by a 12-week active treatment period with tofacitinib for all participants, and a safety follow-up period of 4 weeks. At baseline, 80 subjects shall be randomised (1:1) to receive either tofacitinib or matching placebo for a 12-week double-blind treatment period. At week 12, an MRI of the whole spine and SIJs will be performed to evaluate the primary study endpoint.Ethics and disseminationThe study will be performed according to the ethical principles of the Declaration of Helsinki and the German drug law. The independent ethics committees of each centre approved the ethical, scientific and medical appropriateness of the study before it was conducted.Trial registration numberNCT04062695; ClinicalTrials.gov and EudraCT No: 2018-004254-22; European Union Clinical Trials Register.
Integrated system responses for families impacted by violence: a scoping review protocol
Authors: Gear Claire , Ting Chien-Ju , Eraki Manarah , Eppel Elizabeth , Koziol-McLain Jane 
Published: November 2021

IntroductionThe impacts of violence have a significant effect on health and well-being, particularly for women and children. Violence within families is widely recognised as a complex problem constituted by constantly interacting and evolving social, economic, health and cultural elements. Calls for integrated services have arisen from growing understanding about the implications of this complexity, which suggest family violence and solutions to it are generated endogenously from the reflexive nonlinear interactions of system agents. Despite these calls for integration, services designed to support families impacted by violence and the systems that design and fund them are often responsive only to one part of the problem and might not pay attention to agent interactions and their adaptive reflexivity. This paper outlines a scoping protocol to explore how integrated approaches to family violence are conceptualised in current literature, with innovative use of a complexity theory lens.MethodOur scoping review protocol follows the framework outlined by Arksey and O’Malley and refined by Levac. It searches 6 databases, 3 journals and 10 websites using keywords to capture the notion of integration and a complex adaptive system, namely the participant (system agents), concept (system agent interaction) and the context (family violence). Selection criteria require the articles to be written in English, have full-text article available, and were published after 2010. Items selected also need to be evidence based showing interaction between system agents. Applying complexity theory, sensitises us to the reflexive patterns of interaction between system elements and routine ways of interacting.Ethics and disseminationThe nature of this review means that ethics approval is not required. Findings will be disseminated via academic publications, conferences and discussions with policy decision-makers. The findings will be used to develop a plan for stakeholder consultation to share and validate learnings and inform future research.
Developing a preference-based measure for weight-specific health-related quality of life in adolescence: the WAItE UK valuation study protocol
Authors: Robinson Tomos , Hill Sarah , Oluboyede Yemi 
Published: November 2021

IntroductionAdolescent obesity is a public health problem in the UK. The Weight-Specific Adolescent Instrument for Economic Evaluation (WAItE) has been developed as the first weight-specific health-related quality of life measure appropriate for economic evaluation, but currently cannot be used to generate quality-adjusted life years (QALYs), which are the basis of cost-utility analysis. Generic measures (such as the EQ-5D-Y or CHU-9D) may be insensitive to small but important health changes in overweight or obese adolescents. This study aims to generate a preference-based scoring algorithm for the WAItE.Methods and analysisA discrete choice experiment (DCE) will be administered to value health states described by the WAItE classification system. These health states will be presented to members of the adult general population of the UK via an online survey. A range of regression models will be used to produce the utility algorithm for the WAItE. The DCE-visual analogue scale and time trade-off (TTO) anchoring methods will be used anchor the value set on to the 0–1 QALY scale.Ethics and disseminationThe Newcastle University Medical School Ethics Committee approved the study (references 4772/2020 (DCE) and 9978/2020 (TTO)). The developed algorithm can be applied to future economic evaluations of weight management interventions and treatments for adolescents.
Patient perspectives on integrated healthcare for HIV, hypertension and type 2 diabetes: a scoping review
Authors: Singh Sabine , Kirk Ole , Jaffar Shabbar , Karakezi Catherine , Ramaiya Kaushik , Kallestrup P , Kraef Christian 
Published: November 2021

IntroductionAntiretroviral therapy has reduced mortality and led to longer life expectancy in people living with HIV. These patients are now at an increased risk of non-communicable diseases (NCDs). Integration of care for HIV and NCDs has become a focus of research and policy. In this article, we aim to review patient perspectives on integration of healthcare for HIV, type 2 diabetes and hypertension.MethodsThe framework for scoping reviews developed by Arksey and O'Malley and updated by Peteret alwas applied for this review. The databases PubMed, Web of Science and Cochrane library were searched. Broad search terms for HIV, NCDs (specifically type 2 diabetes and hypertension) and healthcare integration were used. As the review aimed to identify definitions of patient perspectives, they were not included as an independent term in the search strategy. References of included publications were searched for relevant articles. Titles and abstracts for these papers were screened by two independent reviewers. The full texts for all the publications appearing to meet the inclusion criteria were then read to make the final literature selection.ResultsOf 5502 studies initially identified, 13 articles were included in this review, of which 11 had a geographical origin in sub-Saharan Africa. Nine articles were primarily focused on HIV/diabetes healthcare integration while four articles were focused on HIV/hypertension integration. Patient’s experiences with integrated care were reduced HIV-related stigma, reduced travel and treatment costs and a more holistic person-centred care. Prominent concerns were long waiting times at clinics and a lack of continuity of care in some clinics due to a lack of healthcare workers. Non-integrated care was perceived as time-consuming and more expensive.ConclusionPatient perspectives and experiences on integrated care for HIV, diabetes and hypertension were mostly positive. Integrated services can save resources and allow for a more personalised approach to healthcare. There is a paucity of evidence and further longitudinal and interventional evidence from a more diverse range of healthcare systems are needed.