bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal enteroendocrine cells rely on ryanodine and IP3 calcium store receptors for mechanotransduction
Authors: Knutson Kaitlyn R. , Whiteman Sara T. , Alcaino Constanza , Mercado‐Perez Arnaldo , Finholm Isabelle , Serlin Hannah K. , Bellampalli Shreya S. , Linden David R. , Farrugia Gianrico , Beyder Arthur 
Published: November 2022

AbstractEnteroendocrine cells (EECs) are specialized sensors of luminal forces and chemicals in the gastrointestinal (GI) epithelium that respond to stimulation with a release of signalling molecules such as serotonin (5‐HT). For mechanosensitive EECs, force activates Piezo2 channels, which generate a very rapidly activating and inactivating (∼10 ms) cationic (Na+, K+, Ca2+) receptor current. Piezo2 receptor currents lead to a large and persistent increase in intracellular calcium (Ca2+) that lasts many seconds to sometimes minutes, suggesting signal amplification. However, intracellular calcium dynamics in EEC mechanotransduction remain poorly understood. The aim of this study was to determine the role of Ca2+ stores in EEC mechanotransduction. Mechanical stimulation of a human EEC cell model (QGP‐1) resulted in a rapid increase in cytoplasmic Ca2+ and a slower decrease in ER stores Ca2+, suggesting the involvement of intracellular Ca2+ stores. Comparing murine primary colonic EECs with colonocytes showed expression of intercellular Ca2+ store receptors, a similar expression of IP3 receptors, but a >30‐fold enriched expression of Ryr3 in EECs. In mechanically stimulated primary EECs, Ca2+ responses decreased dramatically by emptying stores and pharmacologically blocking IP3 and RyR1/3 receptors. RyR3 genetic knockdown by siRNA led to a significant decrease in mechanosensitive Ca2+ responses and 5‐HT release. In tissue, pressure‐induced increase in the Ussing short circuit current was significantly decreased by ryanodine receptor blockade. Our data show that mechanosensitive EECs use intracellular Ca2+ stores to amplify mechanically induced Ca2+ entry, with RyR3 receptors selectively expressed in EECs and involved in Ca2+ signalling, 5‐HT release and epithelial secretion.
imageKey points
A population of enteroendocrine cells (EECs) are specialized mechanosensors of the gastrointestinal (GI) epithelium that respond to mechanical stimulation with the release of important signalling molecules such as serotonin.
Mechanical activation of these EECs leads to an increase in intracellular calcium (Ca2+) with a longer duration than the stimulus, suggesting intracellular Ca2+ signal amplification.
In this study, we profiled the expression of intracellular Ca2+ store receptors and found an enriched expression of the intracellular Ca2+ receptor Ryr3, which contributed to the mechanically evoked increases in intracellular calcium, 5‐HT release and epithelial secretion.
Our data suggest that mechanosensitive EECs rely on intracellular Ca2+ stores and are selective in their use of Ryr3 for amplification of intracellular Ca2+.
This work advances our understanding of EEC mechanotransduction and may provide novel diagnostic and therapeutic targets for GI motility disorders.
Oceanic intraplate faulting as a pathway for deep hydration of the lithosphere: Perspectives from the Caribbean
Authors: Bishop Brandon T. , Cho Sungwon , Warren Linda , Soto-Cordero Lillian , Pedraza Patricia , Prieto German A. , Dionicio Viviana 
Published: November 2022

AbstractThe recycling of water into the Earth’s mantle via hydrated oceanic lithosphere is believed to have an important role in subduction zone seismicity at intermediate depths. Hydration of oceanic lithosphere has been shown to drive double planes of intermediate-depth, Wadati-Benioff zone seismicity at subduction zones. However, observations from trenches show that pervasive normal faulting causes hydration ~25 km into the lithosphere and can explain neither locations where separations of 25–40 km between Wadati-Benioff zone planes are observed nor the spatial variability of the lower plane in these locations, which suggests that an additional mechanism of hydration exists. We suggest that intraplate deformation of &gt;50-m.y.-old lithosphere, an uncommon and localized process, drives deeper hydration. To test this, we relocated the 25 November 2018 6.0 MW Providencia, Colombia, earthquake mainshock and 575 associated fore- and aftershocks within the interior of the Caribbean oceanic plate and compared these with receiver functions (RF) that sampled the fault at its intersection with the Mohorovičić discontinuity. We examined possible effects of velocity model, initial locations of the earthquakes, and seismicphase arrival uncertainty to identify robust features for comparison with the RF results. We found that the lithosphere ruptured from its surface to a depth of ~40 km along a vertical fault and an intersecting, reactivated normal fault. We also found RF evidence for hydration of the mantle affected by this fault. Deeply penetrating deformation of lithosphere like that we observe in the Providencia region provides fluid pathways necessary to hydrate oceanic lithosphere to depths consistent with the lower plane of Wadati-Benioff zones.
Cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in the low endemic setting of Namibia: an analysis alongside a 2×2 factorial design cluster randomised controlled trial
Authors: Ntuku Henry , Smith-Gueye Cara , Scott Valerie , Njau Joseph , Whittemore Brooke , Zelman Brittany , Tambo Munyaradzi , Prach Lisa M , Wu Lindsey , Schrubbe Leah , Kang Dufour Mi-Suk , Mwilima Agnes , Uusiku Petrina , Sturrock Hugh , Bennett Adam , Smith Jennifer , Kleinschmidt Immo , Mumbengegwi Davis , Gosling Roly , Hsiang Michelle 
Published: November 2022

Objectives
To estimate the cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in a low endemic setting.

Setting
The study was part of a 2×2 factorial design cluster randomised controlled trial within the catchment area of 11 primary health facilities in Zambezi, Namibia.

Participants
Cost and outcome data were collected from the trial, which included 8948 community members that received interventions due to their residence within 500 m of malaria index cases.

Outcome measures
The primary outcome was incremental cost effectiveness ratio (ICER) per in incident case averted. ICER per prevalent case and per disability-adjusted life years (DALY) averted were secondary outcomes, as were per unit interventions costs and personnel time. Outcomes were compared as: (1) rfMDA versus RACD, (2) RAVC versus no RAVC and (3) rfMDA+RAVC versus RACD only.

Results
rfMDA cost 1.1× more than RACD, and RAVC cost 1.7× more than no RAVC. Relative to RACD only, the cost of rfMDA+RAVC was double ($3082 vs $1553 per event). The ICERs for rfMDA versus RACD, RAVC versus no RAVC and rfMDA+RAVC versus RACD only were $114, $1472 and $842, per incident case averted, respectively. Using prevalent infections and DALYs as outcomes, trends were similar. The median personnel time to implement rfMDA was 20% lower than for RACD (30 vs 38 min per person). The median personnel time for RAVC was 34 min per structure sprayed.

Conclusion
Implemented alone or in combination, rfMDA and RAVC were cost effective in reducing malaria incidence and prevalence despite higher implementation costs in the intervention compared with control arms. Compared with RACD, rfMDA was time saving. Cost and time requirements for the combined intervention could be decreased by implementing rfMDA and RAVC simultaneously by a single team.

Trial registration number

NCT02610400; Post-results.
Temporal trends in anticoagulation management for US active duty personnel with atrial fibrillation
Authors: Keithler Andrea Nichole , Wilson Andrew S , Yuan Alexander , Sosa Jose M , Bush Kelvin N V 
Published: November 2022

ObjectivesThis study aims to investigate US active duty (AD) military members diagnosed with atrial fibrillation (AF) and the temporal trends of systemic anticoagulation (AC). Our secondary objective is to study the AC prescriptions in AD military members diagnosed with AF and associated military dispositions and deployment rates.Design and settingA retrospective investigation of Tricare pharmacy AC prescriptions within the San Antonio Military Health System from January 2004 to July 2019 for AD individuals diagnosed with AF was performed.Participants386 AD personnel with non-valvular AF were analysed (mean age 35.0±9.4 years; mean body mass index, 28.3±4.3 kg/m2; 93% male; 57% Caucasian, 94% paroxysmal AF).OutcomesThe temporal trends of systemic AC prescriptions were the primary outcome measures. The association between AC prescriptions and military dispositions and deployments were secondary outcomes of interest.Statistical analysisThe association between AC management, future deployments and military disposition was analysed using χ2and Fisher’s exact test for categorical variables. The t-test was used for comparison of continuous variables.ResultsCHA2DS2-VASc and HAS-BLED scores were low (0.39±0.65 and 0.86±0.63, respectively). 127 (33%) members received warfarin and 58 (15%) received direct oral anticoagulants (DOACs). Rates of military retention were not different between AC histories (no AC (64%) vs warfarin (75%) vs DOAC (65%); p=0.425). There was a significant trend of more recent utilisation of DOACs compared with warfarin (p<0.0001). When adjusted for temporal changes in deployment rates, there was no significant difference in deployment between AC groups (no AC (39%) vs warfarin (49%) vs DOAC (27%); p=0.9472).ConclusionsThis is the first report describing AC utilisation in US AD military members with AF. Young AD personnel with low stroke and bleeding risks do not commonly receive AC prescriptions. DOAC prescription rates are increasing and predominate over warfarin for AC indications.
Usability assessment of an interactive health technology for kidney living donors: protocol for a prospective cross-sectional survey
Authors: Ortiz Fernanda , Giunti Guido 
Published: November 2022

Introduction
Several web portals for kidney patients are available, but assessments of their performance are scarce. A crucial aspect of living donation is to provide standardised information about the risks of the procedure. This is of particular interest among candidates for kidney living donation. In 2019, the Digital Care Path for Living Kidney Donor Candidates was launched in Finland as part of the Health Village portal, containing information about the donation process and facilitating communication between clinicians, transplant coordinators and patients. The performance of this eHealth service has not yet been studied. The present study will investigate living donor candidates’ experience with the Health Village and Digital Care Path for Living Kidney Donor Candidates. Participants’ general attitudes towards the use of eHealth services will also be explored as a secondary objective.

Methods and analysis
A prospective cross-sectional survey study will take place. Participants will be kidney donor candidates who have used the digital care path since its implementation in January 2019 up to 1 March 2021 (N=122). The surveys will include demographic data, electronic device ownership and digital health literacy. Platform’s ease of use will be assessed with the System Usability Scale. Open-ended questions will be used to gather suggestions.

Ethics and dissemination
The research protocol has been approved by the Helsinki University Hospital ethical committee (HUS/501/2021) to ensure that the work is done in accordance with the declaration of Helsinki and Declaration of Istanbul. Recruitment will start during the first semester of 2021. Initial results are expected during the second semester of 2021.

Trial registration number

NCT04791670; Pre-results.
STAndardised DIagnostic Assessment for children and young people with emotional difficulties (STADIA): protocol for a multicentre randomised controlled trial
Authors: Day Florence , Wyatt Laura , Bhardwaj Anupam , Dubicka Bernadka , Ewart Colleen , Gledhill Julia , James Marilyn , Lang Alexandra , Marshall Tamsin , Montgomery Alan , Reynolds Shirley , Sprange Kirsty , Thomson Louise , Bradley Ellen , Lathe James , Newman Kristina , Partlett Chris , Starr Kath , Sayal Kapil 
Published: November 2022

Introduction
Emotional disorders (such as anxiety and depression) are associated with considerable distress and impairment in day-to-day function for affected children and young people and for their families. Effective evidence-based interventions are available but require appropriate identification of difficulties to enable timely access to services. Standardised diagnostic assessment (SDA) tools may aid in the detection of emotional disorders, but there is limited evidence on the utility of SDA tools in routine care and equipoise among professionals about their clinical value.

Methods and analysis
A multicentre, two-arm, parallel group randomised controlled trial, with embedded qualitative and health economic components. Participants will be randomised in a 1:1 ratio to either the Development and Well-Being Assessment SDA tool as an adjunct to usual clinical care, or usual care only. A total of 1210 participants (children and young people referred to outpatient, specialist Child and Adolescent Mental Health Services with emotional difficulties and their parent/carers) will be recruited from at least 6 sites in England. The primary outcome is a clinician-made diagnosis about the presence of an emotional disorder within 12 months of randomisation. Secondary outcomes include referral acceptance, diagnosis and treatment of emotional disorders, symptoms of emotional difficulties and comorbid disorders and associated functional impairment.

Ethics and dissemination
The study received favourable opinion from the South Birmingham Research Ethics Committee (Ref. 19/WM/0133). Results of this trial will be reported to the funder and published in full in the Health Technology Assessment (HTA) Journal series and also submitted for publication in a peer reviewed journal.

Trial registration number

NCT15748675; Pre-results.
Endoscopic third ventriculostomy for adults with hydrocephalus: creating a prognostic model for success: protocol for a retrospective multicentre study (Nordic ETV)
Authors: Tefre Sondre , Lilja-Cyron Alexander , Arvidsson Lisa , Bartek Jiri , Corell Alba , Forsse Axel , Glud Andreas Nørgaard , Hamdeh Sami Abu , Hansen Frederik Lundgaard , Huotarinen Antti , Johansson Conny , Kämäräinen Olli-Pekka , Korhonen Tommi , Kotkansalo Anna , Mansoor Nadia Mauland , Mendoza Mireles Eduardo Erasmo , Miscov Rares , Munthe Sune , Nittby-Redebrandt Henrietta , Obad Nina , Pedersen Lars Kjelsberg , Posti Jussi , Raj Rahul , Satopää Jarno , Ståhl Nils , Tetri Sami , Tobieson Lovisa , Juhler Marianne 
Published: November 2022

Introduction
Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarniet alcreated the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for ETV and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients.

Methods and analysis
The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients≥18 years of age treated with ETV at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots.

Ethics and dissemination
The study is approved by appropriate ethics or patient safety boards in all participating countries.

Trial registration number

NCT04773938; Pre-results.
Multicentre collection of uniform data on patients hospitalised for transient ischaemic attack or stroke in the Philippines: the Philippine Neurological Association One Database-Stroke (PNA1DB-Stroke) protocol
Authors:   Philippine Neurological Association One Database - Stroke, Disease Study Management Group
Published: November 2022

Introduction
For scientific advances to translate into improved patient outcomes, systems of care must be in place to facilitate delivery of care. There is scarce information on quality of care and clinical outcome in our stroke patients. We aim to collect uniform data from patients with first or recurrent transient ischaemic attack (TIA) or ischaemic or haemorrhagic stroke to determine in-patient caseload, patient profile, types of diagnostic and therapeutic procedures, outcomes and overall quality of care among patients hospitalised for acute stroke in the Philippines.

Methods and analysis
This multicentre observational study and standing database will include patients diagnosed with first or recurrent TIA, ischaemic or haemorrhagic stroke or cerebral venous thrombosis, ≥18 years old, and admitted in any of the country’s 11 accredited adult neurology residency training institutions. Anonymised data on sociodemographics, medical history, stroke subtype, in-hospital management and discharge outcomes will be collected and entered in a database using a secure online data platform. Outcomes include in-hospital complications, functional, neurological and vital (alive or dead) status at discharge.
We intend to capture data from all TIA and stroke cases in participating sites. Based on 2017–2019 census, approximately 10 000 cases each year may be included. Collective data spanning 3 years will be extracted, summarised and analysed every year.

Ethics and dissemination
Approval from ethics committees or institutional review boards (EC/IRB) was obtained from the Single Joint Research Ethics Board and all participating institutions. As this study involves no more than minimal risk to patients, waiver of informed consent was requested. Written information about the study will be provided to patients or legal representative. If site EC/IRB requires written consent, only approved consent forms will be used.
To identify areas of improvement and guide public health policies, data on ‘real-world’ situation are needed. The Philippine Neurological Association One Database-Stroke initiative may become a model that can be implemented in other designated stroke-ready hospitals.

Trial registration

NCT04972058; ClinicalTrials.gov.
Effect of a specific exercise programme during pregnancy on diastasis recti abdominis: study protocol for a randomised controlled trial
Authors: Theodorsen Nina-Margrethe , Fersum Kjartan Vibe , Moe-Nilssen Rolf , Bo Kari , Haukenes Inger 
Published: November 2022

Introduction
Diastasis recti abdominis (DRA) is a common condition in pregnant and postpartum women.
Evidence for the treatment of DRA is both sparse and weak. As this
condition occurs during the last two trimesters of pregnancy and there is a paucity of high-quality studies on a pregnant population, we will conduct a randomised trial on the effect of
a specific exercise programme during pregnancy on DRA.

Methods and analysis
This is an exploratory, assessor-blinded, randomised parallel group trial carried out in a
primary healthcare setting in a Norwegian city. 100 pregnant women, both primigravida and
multigravida, in gestation week 24 presenting with DRA of ≥28 mm will
be included. Participants will be allocated to either an intervention group or a control group
by block randomisation. The intervention group will participate in a 12-week specific exercise
programme. The control group will not participate in any exercise intervention. Data collection
will take place prior to intervention, postintervention at gestation week 37, and 6 weeks, 6
and 12 months postpartum. The primary outcome measure will be change in the inter-recti
distance, measured by two-dimensional ultrasonography. Data will be analysed and presented
in accordance with international Consolidated Standards of Reporting Trials guidelines and analysed according to the intention-to-treat principle.

Ethics and dissemination
Ethical approval has been obtained by the regional ethical committee (76296), and all
procedures will be performed in adherence to the Helsinki declaration. The study has been
registered with ClinicalTrials.gov. Results from this study will be presented at
scientific conferences and in peer-reviewed scientific journals.

Trial registration number

NCT04960800; Pre-results.
Factors associated with anti-SARS-CoV-2 antibody titres 3 months post-vaccination with the second dose of BNT162b2 vaccine: a longitudinal observational cohort study in western Greece
Authors: Parthymou Anastasia , Habeos Evagelia E , Habeos George I , Deligakis Apostolos , Livieratos Ektoras , Marangos Markos , Chartoumpekis Dionysios V 
Published: November 2022

Objectives
Vaccination against SARS-CoV-2 has been extensively deployed during COVID-19 pandemic. One efficient method to evaluate response to vaccination is the assessment of humoral immunity by measuring SARS-CoV-2 antibody titres. We investigated the association between anthropometric parameters (age, body mass index), smoking, diabetes, statin use, hypertension, levels of 25(OH)D and dehydroepiandrosterone sulfate (DHEAS), and SARS-CoV-2 antibody titres after vaccination.

Design
In this longitudinal observational cohort study, 712 subjects were tested for SARS-CoV-2 antibodies 3 months after the second dose of BNT162b2 vaccine. Multiple linear regression analysis was performed to identify which factors are associated with the antibody titres.

Setting
Healthcare units of western Greece (University Hospital of Patras and “St Andrews” State General Hospital of Patras).

Participants
All adults receiving their second dose of BNT162b2 vaccine at the participating healthcare units were eligible to participate in the study. Exclusion criteria were SARS-CoV-2 infection or positive SARS-CoV-2 antibody titre at baseline. Patients who did not provide all necessary information were excluded from our analyses.

Results
We found age to be negatively associated with antibody titre (−0.005; 95% CI −0.009 to −0.001, p=0.0073), as was male gender (−0.11; 95% CI −0.1738 to −0.04617, p=0.0008). The interaction of age and gender was significant (−0.01090; 95% CI −0.01631 to −0.005490, p<0.0001), highlighting that the rate of decline in antibody titre with increasing age tends to be higher in men rather than in women. No linear trend was found between DHEAS levels and antibody titres when the lower quartile of DHEAS levels was used as reference. Tobacco use was associated with low antibody titre (−0.1097; 95% CI −0.174 to −0.046, p=0.0008) but overweight, obese or underweight subjects had similar antibody responses to normal-weight individuals. Although subjects with diabetes and hypertension had numerically lower antibody titres, this association was not statistically significant. Vitamin D levels showed no clear relationships with antibody titres.

Conclusions
Age, male gender and tobacco use are negatively associated with antibody titres after COVID-19 vaccination, but our data showed no clear correlation with vitamin D levels.

Trial registration number

NCT04954651; Results.