bluuebunny/crossref_metadata_2025 huggingface dataset:
“You're Poor, so You're Not Going to Do Anything:” Socioeconomic Status and Capital Accumulation as a Means to Access Higher Education for Rural Youth☆
Authors: Grant Phillip D. , Roberts J. Kessa
Published: June 2022

This qualitative phenomenological study sought to understand rural students' college‐going decisions through the lens of socioeconomic status, social capital, and Perna's nested model of college choice. The sample included 18 students who were undergraduates at a selective R1 university in the Southeastern United States. Rural first‐generation students reported that they received little practical advice from adults in their family, school, or community. Rural students' choice to take adult advice seemed to be dependent on their family's education background. Family connection was the most common reason for students to choose to attend a selective university if they were not a first‐generation college student. Distance to institution was not a major factor in the participant's decision to attend the university. The students in this study were highly influenced by the policy environment of the state in which they live; a state‐wide merit‐based scholarship provided all the students, regardless of first‐generation status, a motivation to attend what they considered to be the best public school in the state, while still receiving a significant discount on their tuition.
No increased HIV risk in general population near sex work sites: A nationally representative cross‐sectional study in Zimbabwe
Authors: Kloek Mariёlle , Bulstra Caroline A. , Chabata Sungai T. , Fearon Elizabeth , Taramusi Isaac , de Vlas Sake J. , Cowan Frances M. , Hontelez Jan A. C.
Published: June 2022

Objectives

Sex work sites have been hypothesised to be at the root of the observed heterogeneity in HIV prevalence in sub‐Saharan Africa. We determined if proximity to sex work sites is associated with HIV prevalence among the general population in Zimbabwe, a country with one of the highest HIV prevalence in the world.

Methods

In this cross‐sectional study we use a unique combination of nationally representative geolocated individual‐level data from 16,121 adults (age 15–49 years) from 400 sample locations and the locations of 55 sex work sites throughout Zimbabwe; covering an estimated 95% of all female sex workers (FSWs). We calculated the shortest distance by road from each survey sample location to the nearest sex work site, for all sites and by type of sex work site, and conducted univariate and multivariate multilevel logistic regressions to determine the association between distance to sex work sites and HIV seropositivity, controlling for age, sex, male circumcision status, number of lifetime sex partners, being a FSW client or being a stable partner of an FSW client.

Results

We found no significant association between HIV seroprevalence and proximity to the nearest sex work site among the general population in Zimbabwe, regardless of which type of site is closest (city site adjusted odds ratio [aOR] 1.010 [95% confidence interval {CI} 0.992–1.028]; economic growth point site aOR 0.982 [95% CI 0.962–1.002]; international site aOR 0.995 [95% CI 0.979–1.012]; seasonal site aOR 0.987 [95% CI 0.968–1.006] and transport site aOR 1.007 [95% CI 0.987–1.028]). Individual‐level indicators of sex work were significantly associated with HIV seropositivity: being an FSW client (aOR 1.445 [95% CI 1.188–1.745]); nine or more partners versus having one to three lifetime partners (aOR 2.072 [95% CI 1.654–2.596]).

Conclusions

Sex work sites do not seem to directly affect HIV prevalence among the general population in surrounding areas. Prevention and control interventions for HIV at these locations should primarily focus on sex workers and their clients, with special emphasis on including and retaining mobile sex workers and clients into services.
Quantitative analysis of composition and temperature of semiconductor processing plasmas via terahertz spectroscopy
Authors: Helal Yaser H. , Neese Christopher F. , De Lucia Frank C. , Stout Phillip J. , Craver Barry , Armacost Michael
Published: June 2022

The application of terahertz (THz) absorption spectroscopy was developed for chemical characterization in inductively coupled plasmas. Plasma processing is a complex and important tool of the semiconductor manufacturing industry, which makes use of several diagnostic methods for precise process control. Electronically based THz spectroscopy is a technique with favorable attributes for the characterization of plasmas and process control in semiconductor reactors. These attributes include (1) plasmas are transparent and noise-free for THz transmission/detection, (2) concentration and temperatures of molecules can be calculated from first principles without adjustable variables, and (3) the technique has very high resolution and has absolute specificity. However, rotational spectroscopy requires that the molecule have a permanent dipole moment, precluding direct observation of atomic and symmetric species such as fluorine or CF4. In this work, an electronically based 500–750 GHz absorption spectrometer and a method to accurately and simultaneously determine number densities and temperatures were developed. Density and temperature measurements of molecular species in Ar/CF4/CHF3 and N2/CF4/CHF3 plasmas as a function of flow ratio, power, and pressure will be discussed. In addition, a quantitative survey of spectroscopically measurable molecules and radicals was conducted for plasma mixtures using varying quantities of CF4, CHF3, N2, and O2 feedstock gases.
Brain injury environment critically influences the connectivity of transplanted neurons
Authors: Grade Sofia , Thomas Judith , Zarb Yvette , Thorwirth Manja , Conzelmann Karl-Klaus , Hauck Stefanie M. , Götz Magdalena
Published: June 2022

Cell transplantation is a promising approach for the reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries of the mouse cerebral cortex affected by neuronal ablation. However, it remains unclear how neurons perform in a local environment undergoing reactive gliosis, inflammation, macrophage infiltration, and scar formation, as in traumatic brain injury (TBI). To elucidate this, we transplanted cells from the embryonic mouse cerebral cortex into TBI-injured, inflamed-only, or intact cortex of adult mice. Brain-wide quantitative monosynaptic rabies virus (RABV) tracing unraveled graft inputs from correct regions across the brain in all conditions, with pronounced quantitative differences: scarce in intact and inflamed brain versus exuberant after TBI. In the latter, the initial overshoot is followed by pruning, with only a few input neurons persisting at 3 months. Proteomic profiling identifies candidate molecules for regulation of the synaptic yield, a pivotal parameter to tailor for functional restoration of neuronal circuits.
Multiscale topology characterizes dynamic tumor vascular networks
Authors: Stolz Bernadette J. , Kaeppler Jakob , Markelc Bostjan , Braun Franziska , Lipsmeier Florian , Muschel Ruth J. , Byrne Helen M. , Harrington Heather A.
Published: June 2022

Advances in imaging techniques enable high-resolution three-dimensional (3D) visualization of vascular networks over time and reveal abnormal structural features such as twists and loops, and their quantification is an active area of research. Here, we showcase how topological data analysis, the mathematical field that studies the “shape” of data, can characterize the geometric, spatial, and temporal organization of vascular networks. We propose two topological lenses to study vasculature, which capture inherent multiscale features and vessel connectivity, and surpass the single-scale analysis of existing methods. We analyze images collected using intravital and ultramicroscopy modalities and quantify spatiotemporal variation of twists, loops, and avascular regions (voids) in 3D vascular networks. This topological approach validates and quantifies known qualitative trends such as dynamic changes in tortuosity and loops in response to antibodies that modulate vessel sprouting; furthermore, it quantifies the effect of radiotherapy on vessel architecture.
Irradiation-induced grain boundary facet motion: In situ observations and atomic-scale mechanisms
Authors: Barr Christopher M. , Chen Elton Y. , Nathaniel James E. , Lu Ping , Adams David P. , Dingreville Rémi , Boyce Brad L. , Hattar Khalid , Medlin Douglas L.
Published: June 2022

Metals subjected to irradiation environments undergo microstructural evolution and concomitant degradation, yet the nanoscale mechanisms for such evolution remain elusive. Here, we combine in situ heavy ion irradiation, atomic resolution microscopy, and atomistic simulation to elucidate how radiation damage and interfacial defects interplay to control grain boundary (GB) motion. While classical notions of boundary evolution under irradiation rest on simple ideas of curvature-driven motion, the reality is far more complex. Focusing on an ion-irradiated Pt Σ3 GB, we show how this boundary evolves by the motion of 120° facet junctions separating nanoscale {112} facets. Our analysis considers the short- and mid-range ion interactions, which roughen the facets and induce local motion, and longer-range interactions associated with interfacial disconnections, which accommodate the intergranular misorientation. We suggest how climb of these disconnections could drive coordinated facet junction motion. These findings emphasize that both local and longer-range, collective interactions are important to understanding irradiation-induced interfacial evolution.
Daily changes in light influence mood via inhibitory networks within the thalamic perihabenular nucleus
Authors: Weil Tenley , Daly K. M. , Yarur Castillo Hector , Thomsen Michael B. , Wang Huikun , Mercau Maria E. , Hattar Samer , Tejeda Hugo , Fernandez Diego C.
Published: June 2022

Exposure to irregular lighting schedules leads to deficits in affective behaviors. The retino-recipient perihabenular nucleus (PHb) of the dorsal thalamus has been shown to mediate these effects in mice. However, the mechanisms of how light information is processed within the PHb remains unknown. Here, we show that the PHb contains a distinct cluster of GABAergic neurons that receive direct retinal input. These neurons are part of a larger inhibitory network composed of the thalamic reticular nucleus and zona incerta, known to modulate thalamocortical communication. In addition, PHb
GABA
neurons locally modulate excitatory-relay neurons, which project to limbic centers. Chronic exposure to irregular light-dark cycles alters photo-responsiveness and synaptic output of PHb
GABA
neurons, disrupting daily oscillations of genes associated with inhibitory and excitatory PHb signaling. Consequently, selective and chronic PHb
GABA
manipulation results in mood alterations that mimic those caused by irregular light exposure. Together, light-mediated disruption of PHb inhibitory networks underlies mood deficits.
Time-constrained multiphase brittle tectonic evolution of the onshore mid-Norwegian passive margin
Authors: Tartaglia Giulia , Ceccato Alberto , Scheiber Thomas , van der Lelij Roelant , Schönenberger Jasmin , Viola Giulio
Published: June 2022

The mid-Norwegian passive margin is a multiphase rifted margin that developed since the Devonian. Its geometry is affected by the long-lived activity of the Møre-Trøndelag fault complex, an ENE-WSW–oriented regional tectonic structure. We propose a time-constrained evolutionary scheme for the brittle history of the mid-Norwegian passive margin. By means of remote-sensing lineament detection, field work, microstructural analysis, paleostress inversion, mineralogical characterization, and K-Ar dating of fault rocks, six tectonic events have been identified: (1) Paleozoic NE-SW compression forming WNW-ESE–striking thrust faults; (2) Paleozoic NW-SE transpression forming conjugate strike-slip faults; (3) Carboniferous protorifting forming NW-SE– and NE-SW–striking faults; (4) Late Triassic–Jurassic (ca. 202 and 177 Ma) E-W extension forming approximately N-S–striking epidote- and quartz-coated normal faults and widespread alteration; (5) renewed rifting in the Early Cretaceous (ca. 122 Ma) with a NW-SE extension direction; and (6) Late Cretaceous extensional pulses (ca. 71, 80, 86, 91 Ma ago) reactivating preexisting faults and crystallizing prehnite and zeolite. Our multidisciplinary and multiscalar study sheds light onto the structural evolution of the mid-Norwegian passive margin and confirms the active role of the Møre-Trøndelag fault complex during the rifting stages. Our 62 new radiometric K-Ar ages define discrete episodes of faulting along the margin. The proposed workflow may assist in the interpretation of the structural framework of the mid-Norwegian passive margin offshore domain and also help to better understand fault patterns of fractured passive margins elsewhere.
Monoclonal gammopathy of undetermined significance causing large vessel vasculitis
Authors: Alcorn Edward George , Floyd Lauren , Dhaygude Ajay
Published: June 2022

A man in his late 50s presented with unilateral pain and discolouration of his fourth and fifth toes suggestive of digital ischaemia. He had a medical history of two unprovoked venous thromboembolisms in the preceding 18 months and a history of monoclonal gammopathy of undetermined significance (MGUS). A CT scan showed evidence of large vessels vasculitis in the absence of circulating antineutrophil cytoplasmic antibodies. Biopsy of the toes showed evidence of light chain and immunoglobulin deposition on immunofluorescence suggesting vasculitis secondary to his haematological diagnosis of MGUS. The patient was treated with high dose glucocorticoids and immunosuppressive treatment with a significant improvement in his symptoms and features of digital ischaemia.
Case of bilateral Bell’s palsy
Authors: Otaka Yumi , Harada Yukinori , Shimizu Taro
Published: June 2022

A man in his 70s presented with a 4-day history of bilateral frontal headache and heaviness of the face. He was unable to close either of his eyes, to wrinkle his forehead bilaterally and to raise either corner of his mouth. The patient was admitted with a diagnosis of bilateral facial palsy. From history, epidemiology, physical and laboratory findings, Bell’s palsy was considered more probable than viral infection, Guillain-Barré syndrome and sarcoidosis. Oral administration of prednisolone, valacyclovir and mecobalamin were initiated promptly, which improved his symptoms. In areas in which Lyme disease is not endemic, we believe that Bell’s palsy is the most probable cause of isolated bilateral facial palsy. Patients with bilateral facial paralysis under the suspicion of Bell’s palsy should be immediately started on steroid therapy.
Effect of eHealth-delivered exercise programmes on balance in people aged 65 years and over living in the community: a systematic review and meta-analysis of randomised controlled trials
Authors: Ambrens Meghan , Alley Stephanie , Oliveira Juliana S , To Quyen , Delbaere Kim , Vandelanotte Corneel , Tiedemann Anne
Published: June 2022

Introduction

Exercise that challenges balance is proven to prevent falls in community-dwelling older people, yet widespread implementation and uptake of effective programmes is low. This systematic review and meta-analysis synthesised the evidence and evaluated the effect of eHealth-delivered exercise programmes compared with control on balance in community-dwelling people aged ≥65 years.

Methods

Nine databases including MEDLINE, CINAHL and Embase, were searched from inception to January 2022 to identify randomised controlled trials evaluating eHealth-delivered exercise programmes for community-dwelling people aged ≥65 years, published in English that included a balance outcome. Primary outcomes were static and dynamic balance. Secondary outcomes included fall risk and fear of falling. We calculated standardised mean differences (SMDs, Hedges’ g) with 95% CIs from random effects meta-analyses.

Results

We identified 14 eligible studies that included 1180 participants. Methodological quality ranged from 3 to 8 (mean, 5). The pooled effect indicated that eHealth-delivered exercise programmes have a medium significant effect on static balance (11 studies; SMD=0.62, 95% CI 0.27 to 0.72) with very low-quality evidence. There was small statistically significant effect on dynamic balance (14 studies; SMD=0.42, 95% CI 0.11 to 0.73) with very low-quality evidence, and fall risk (5 studies; SMD=0.32, 95% CI 0.00 to 0.64) with moderate-quality evidence. No significant effect of eHealth programmes on fear of falling was found (four studies; SMD=0.10, 95% CI −0.05 to 0.24; high-quality evidence).

Conclusion

This review provides preliminary evidence that eHealth-delivered exercise programmes improved balance and reduced fall risk in people aged ≥65 years. There is still uncertainty regarding the effect of eHealth delivered exercise programmes on fear of falling.

PROSPERO registration number

CRD42018115098.
Risky sexual behaviour and HIV testing uptake among male college students: a cross-sectional study in China
Authors: Zhao Gang , Luo Yan , Xu Junfang
Published: June 2022

Objective

To understand the sexual behaviours and HIV testing uptake of sexually experienced male college students in China.

Design

A cross-sectional study was conducted between September and November of 2020 among male college students.

Setting

Hangzhou, China.

Participants

Male students who had sexual experience in the previous year were investigated.

Outcome measures

Sexual risk behaviour was defined as having multiple sexual partners or having unprotected sex.

Results

More than half of the sexually experienced male students (556, 53.2%) had their first sexual intercourse under the age of 18 years old. Among participants, 32.82% (343/1045) had causal sex in the last 6 months; 4.21% (44/1045) had paid sex; 37.32% (390/1045) had sex with other men and had two or more sexual partners in last half year; and 33.33% (130/390) used psychoactive drugs during same-sex intercourse. Only 33.5% (350/1045) of male students had undertaken an HIV test before.

Conclusion

Male college students especially men who have sex with men were at risk because they tended to be sexually adventurous, have sex at an early age, have sex with multiple sexual partners and practice unprotected sex. Furthermore, they had a low HIV testing uptake. This highlights the importance of carrying out targeted and timely HIV risk education towards college students.
Portable wide-field digital imaging for screening of neonatal visual impairment causes in Rio de Janeiro, Brazil: a budget impact analysis
Authors: Haefeli Lorena M , Neves Luiza M , Zin Andrea , Costa Ana Carolina Carioca , Farias Meira de Vasconcelos Zilton , Pinto Marcia
Published: June 2022

Objective

To estimate the budget impact of portable wide-field digital imaging incorporation on screening neonatal causes of childhood blindness and visual impairment in Rio de Janeiro, Brazil.

Design

Budget impact analysis.

Setting

Rio de Janeiro, Brazil.

Primary and secondary outcome measures

The primary outcome was the direct cost of indirect binocular ophthalmoscopy, red reflex test and portable wide-field digital image screening comprising all babies born in Rio de Janeiro’s government maternity wards. The secondary outcome was the budget impact of implementing portable wide-field digital image screening in Rio de Janeiro, Brazil.

Results

Considering 100% coverage of maternity wards, the total budget impact between 2020 and 2024 would be US$3 820 706.04, ranging from US$3 139 844.34 to US$6 099 510.35. The additional cost would be US$3 124 457.28, ranging from US$2 714 492.26 to US$4 880 608.63.

Conclusion

The cost of universal digital imaging screening corresponds to less than 1% of the government health budget of the city of Rio de Janeiro. The information provided in this study may help government decision-makers evaluate the feasibility of implementing this new strategy in the municipal setting. Further health economic evaluations should be performed to verify the affordability of the implementation of this screening strategy in the Brazilian scenario, taking into account scarce human resources.
Are deprivation-specific cancer survival patterns similar according to individual-based and area-based measures? A cohort study of patients diagnosed with five malignancies in England and Wales, 2008–2016
Authors: Woods Laura M , Belot Aurélien , Atherton Iain M , Elliss-Brookes Lucy , Baker Matthew , Ingleby Fiona C
Published: June 2022

Objective

To investigate if measured inequalities in cancer survival differ when using individual-based (‘person’) compared with area-based (‘place’) measures of deprivation for three socioeconomic dimensions: income, deprivation and occupation.

Design

Cohort study.

Setting

Data from the Office for National Statistics Longitudinal Study of England and Wales, UK, linked to the National Cancer Registration Database.

Participants

Patients diagnosed with cancers of the colorectum, breast, prostate, bladder or with non-Hodgkin’s lymphoma during the period 2008–2016.

Primary and secondary outcome measures

Differentials in net survival between groups defined by individual wage, occupation and education compared with those obtained from corresponding area-level metrics using the English and Welsh Indices of Multiple Deprivation.

Results

Survival was negatively associated with area-based deprivation irrespective of the type analysed, although a trend from least to most deprived was not always observed. Socioeconomic differences were present according to individually-measured socioeconomic groups although there was an absence of a consistent ‘gradient’ in survival. The magnitude of differentials was similar for area-based and individually-derived measures of deprivation, which was unexpected.

Conclusion

These unique data suggest that the socioeconomic influence of ‘person’ is different to that of ‘place’ with respect to cancer outcomes. This has implications for health policy aimed at reducing inequalities. Further research could consider the separate and additional influence of area-based deprivation over individual-level characteristics (contextual effects) as well as investigate the geographic, socioeconomic and healthcare-related characteristics of areas with poor outcomes in order to inform policy intervention.
Community-based culturally tailored education programmes for black adults with cardiovascular disease, diabetes, hypertension and stroke: a systematic review protocol of primary empirical studies
Authors: Fulton Joseph IV , Singh Hardeep , Pakkal Oya , Uleryk Elizabeth M , Nelson Michelle LA
Published: June 2022

Introduction

Chronic conditions and stroke disproportionately affect black adults in communities all around the world partly due to patterns of systemic racism, disparities in care, and lack of resources. Culturally tailored programmes can potentially meet the needs of the communities they serve, including black adults who may experience reduced access to postacute services. To address unequal care received by black communities, a shift to community-based programmes that deliver culturally tailored programmes may give an alternative to a healthcare model which reinforces health inequities. The objectives of this review are to: (1) synthesise key programme characteristics and outcomes of culturally tailored community-based (CBCT) programmes that are designed to improve health outcomes in black adults with cardiovascular disease, hypertension, diabetes, or stroke and (2) identify which of the five categories of culturally appropriate programmes from Kreuter and colleagues have been used to implement CBCT programmes.

Methods and analysis

This is a protocol for a systematic review that will search Medline, Embase and Cumulative Index to Nursing and Allied Health Literature databases to identify studies of CBCT programmes for black adults with cardiovascular disease, hypertension, diabetes, or stroke between 2000 and 2021. Two reviewers will assess each study based on the inclusion criteria and any disagreements will be resolved by a third reviewer. Data will be extracted using a customised data extraction form to identify programme characteristics and the strategies used to develop culturally appropriate programmes. AMSTAR will be used to evaluate the articles included in the study. The aggregated data will be presented through textual descriptions of programme characteristics and outcomes.

Ethics and dissemination

This systematic review protocol does not require ethics approval without the inclusion of human participants and will use studies that have previously obtained informed consent. The systematic review findings will be disseminated in a peer-reviewed journal and used to inform future research led by JF and HS.

Trial registration number

PROSPERO CRD42021245772.
Comparing propofol anaesthesia guided by Bispectral Index monitoring and frontal EEG wave analysis with standard monitoring in laparoscopic surgery: protocol for the ‘EEG in General Anaesthesia - More Than Only a Bispectral Index’ Trial, a multicentre, double-blind, randomised controlled trial
Authors: Gruber Bettina U , Girsberger Valerie , Kusstatscher Lukas , Funk Simon , Luethy Anita , Jakus Lien , Maillard Julien , Steiner Luzius A , Dell-Kuster Salome , Burkhart Christoph S
Published: June 2022

Introduction

The use of Bispectral Index (BIS) monitors for assessing depth of sedation has led to a reduction in both the incidence of awareness and anaesthetic consumption in total intravenous anaesthesia. However, these monitors are vulnerable to artefacts. In addition to the processed number, the raw frontal electroencephalogram (EEG) can be displayed as a curve on the same monitor. Anaesthesia practitioners can learn to interpret the EEG in a short tutorial and may be quicker and more accurate thanBIS in assessing anaesthesia depth by recognising EEG patterns. We hypothesise that quality of recovery (QoR) in patients undergoing laparoscopic surgery is better, if propofol is titrated by anaesthesia practitioners able to interpret the EEG.

Methods and analysis

This is a multicentre, double-blind (patients and outcome assessors) randomised controlled trial taking place in four Swiss hospitals. Patients aged 18 years or older undergoing laparoscopic procedures with general anaesthesia using propofol and anaesthesia practitioners with more than 2 years experience will be eligible. The primary study outcome is the difference in QoR 24 hours after surgery. Secondary outcomes are propofol consumption, incidence of postoperative nausea and vomiting (PONV) and postoperative delirium.

QoR and propofol consumption are compared between both groups using a two-sample t-test. Fisher’s exact test is used to compare the incidences of PONV and delirium. A total of 200 anaesthesia practitioners (and 200 patients) are required to have an 80% chance of detecting the minimum relevant difference for the QoR-15 as significant at the 5% level assuming a SD of 20.

Ethics and dissemination

Ethical approval has been obtained from all responsible ethics committees (lead committee: Ethikkommission Nordwest- und Zentralschweiz, 16 January 2021). The findings of the trial will be published in a peer-reviewed journal, presented at international conferences, and may lead to a change in titrating propofol in clinical practice.

Trial registration number

www.clinicaltrials.gov:NCT04105660
Feasibility of Cognitive Training in Combination With Transcranial Direct Current Stimulation in a Home-Based Context (TrainStim-Home): study protocol for a randomised controlled trial
Authors: Thams Friederike , Rocke Merle , Malinowski Robert , Nowak Rafal , Grittner Ulrike , Antonenko Daria , Flöel Agnes
Published: June 2022

Introduction

With the worldwide increase of life expectancy leading to a higher proportion of older adults experiencing age-associated deterioration of cognitive abilities, the development of effective and widely accessible prevention and therapeutic measures has become a priority and challenge for modern medicine. Combined interventions of cognitive training and transcranial direct current stimulation (tDCS) have shown promising results for counteracting age-associated cognitive decline. However, access to clinical centres for repeated sessions is challenging, particularly in rural areas and for older adults with reduced mobility, and lack of clinical personnel and hospital space prevents extended interventions in larger cohorts. A home-based and remotely supervised application of tDCS would make the treatment more accessible for participants and relieve clinical resources. So far, studies assessing feasibility of combined interventions with a focus on cognition in a home-based setting are rare. With this study, we aim to provide evidence for the feasibility and the effects of a multisession home-based cognitive training in combination with tDCS on cognitive functions of healthy older adults.

Methods and analysis

The TrainStim-Home trial is a monocentric, randomised, double-blind, placebo-controlled study. Thirty healthy participants, aged 60–80 years, will receive 2 weeks of combined cognitive training and anodal tDCS over left dorsolateral prefrontal cortex (target intervention), compared with cognitive training plus sham stimulation. The cognitive training will comprise a letter updating task, and the participants will be stimulated for 20 min with 1.5 mA. The intervention sessions will take place at the participants’ home, and primary outcome will be the feasibility, operationalised by two-thirds successfully completed sessions per participant. Additionally, performance in the training task and an untrained task will be analysed.

Ethics and dissemination

Ethical approval was granted by the ethics committee of the University Medicine Greifswald. Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.

Trial registration number

NCT04817124.
Nissen-Sleeve procedure versus laparoscopic Roux-en-Y gastric bypass in patients with morbid obesity and gastro-oesophageal reflux disease: protocol for a non-inferiority randomised trial (GINSBY)
Authors: 't Hart Judith W H , Noordman Bo J , Biter Laser U , Leeuwenburgh Ivonne , Dunkelgrun Martin , Apers Jan A
Published: June 2022

Introduction

Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are the most frequently performed procedures in bariatric surgery. In patients with morbid obesity and gastro-oesophageal reflux disease (GORD), LRYGB is the most accepted procedure. For patients with a contraindication for LRYGB or a strong preference for LSG, the Nissen-Sleeve procedure may be a viable new option. The aim of this study is to compare effectiveness of Nissen-Sleeve with LRYGB.

Method and analysis

This is a single-centre, phase III, parallel-group randomised controlled trial in a high-volume bariatric centre in the Netherlands. A total of 88 patients with morbid obesity and GORD will be randomised to evaluate non-inferiority of Nissen-Sleeve versus LRYGB (non-inferiority margin 15%, power 80%, one-sided α 0.025, 9% drop out). Patients with morbid obesity aged 18 years and older with GORD according to the Montreal definition will be included after obtaining informed consent. Exclusion criteria are achalasia, neoplastic abnormalities diagnosed during endoscopy, super obesity (body mass index ≥50 kg/m2), Crohn’s disease and medical history of major abdominal surgery. After randomisation, all patients will undergo an upper gastrointestinal endoscopy. Patients in the Nissen-Sleeve arm will undergo a timed barium oesophagram to exclude oesophageal motility disorders. Patients will complete six questionnaires at baseline and every year until 5 years of follow-up. At day 1 postoperative, patients in the Nissen-Sleeve arm will undergo a swallow X-ray to confirm passage. At 1 year, all patients will undergo another endoscopy. The primary outcome is GORD status. Absence of GORD is defined as <8 points on the GORD questionnaire. Secondary outcome measures are long-term GORD improvement; failure rate of procedure; health-related quality of live; weight loss; proton pump inhibitor use; postoperative complications <30 days and >30 days; length of hospital stay; duration of primary surgery; effect on comorbidities; presence and grade of oesophagitis (grade A–D) and/or presence of Barrett’s oesophagus and cost-effectiveness.

Ethics and dissemination

The protocol was approved by the Medical Research Ethics Committees United (MEC-U), Nieuwegein, on 15 September 2021. Written informed consent will be obtained for all participants in the study. The study results will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

NL9789; The Netherlands Trial Registry.
Effects of a nurse-led peer support intervention for stroke survivors: protocol for a randomised controlled trial
Authors: Wan Xiaojuan , Chau Janita Pak Chun , Wu Ying , Xu Limei , Gong Weijuan
Published: June 2022

Introduction

Many stroke survivors have unmet psychosocial needs during the recovery phase following a stroke. There is emerging evidence that peer support interventions may play a valuable role in managing stroke. However, evidence regarding the effectiveness of peer support interventions on the psychosocial outcomes of stroke survivors is uncertain. This study aims to develop a nurse-led peer support intervention for stroke survivors based on the Person–Environment–Occupation–Performance Model and evaluate its effects on the psychosocial outcomes of stroke survivors.

Methods and analysis

This is an assessor-blinded two-arm randomised controlled trial. A convenience sample of 120 stroke survivors will be recruited from two community centres and one rehabilitation unit in Yangzhou, a medium-sized city in eastern China, with 60 participants each in the intervention and control groups. The participants allocated to the intervention group will receive the nurse-led peer support intervention, which includes 6 weekly peer support sessions facilitated by a nurse and at least one peer facilitator. Participants randomised to the control group will receive the same dose of interpersonal interaction as intervention participants, including weekly individual face-to-face session for 6 weeks. The primary outcomes are social participation and participation self-efficacy. The secondary outcomes are psychosocial distress, social support, stigma towards disease, self-efficacy in managing chronic conditions and quality of life. Data will be collected at baseline, immediately after the intervention and 3 months after the intervention. A process evaluation will be conducted qualitatively and quantitively to examine the mechanism by which the intervention impacts the psychosocial outcomes of stroke survivors. All outcomes will be analysed following the intention to treat principle. Generalised Estimation Equation models will be used to assess the intervention effect.

Ethics and dissemination

This protocol was approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No.: 2021.196-T). All participants will be required to provide written informed consent. Results of the study will be disseminated through publication in peer-reviewed journals and presentation at local or international conferences.

Trial registration number

ChiCTR2100050853.
Prognostic implications of left ventricular diastolic dysfunction in moderate aortic stenosis
Authors: Stassen Jan , Ewe See Hooi , Butcher Steele C , Amanullah Mohammed R , Mertens Bart J , Hirasawa Kensuke , Singh Gurpreet K , Sin Kenny Y , Ding Zee Pin , Pio Stephan M , Sia Ching-Hui , Chew Nicholas , Kong William , Poh Kian Keong , Cohen David , Généreux Philippe , Leon Martin B , Ajmone Marsan Nina , Delgado Victoria , Bax Jeroen J
Published: June 2022

Objective

To investigate the prognostic impact of left ventricular (LV) diastolic dysfunction in patients with moderate aortic stenosis (AS) and preserved LV systolic function.

Methods

Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm2) and preserved LV systolic function (LV ejection fraction ≥50%) were identified. LV diastolic function was evaluated using echocardiographic criteria according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as all-cause mortality and a composite of all-cause mortality and aortic valve replacement (AVR).

Results

Of 1247 patients (age 74±10 years, 47% men), 535 (43%) had LV diastolic dysfunction at baseline. Patients with LV diastolic dysfunction showed significantly higher mortality rates at 1-year, 3-year and 5-year follow-up (13%, 30% and 41%, respectively) when compared with patients with normal LV diastolic function (6%, 17% and 29%, respectively) (p<0.001). On multivariable analysis, LV diastolic dysfunction was independently associated with all-cause mortality (HR 1.368; 95% CI 1.085 to 1.725; p=0.008) and the composite endpoint of all-cause mortality and AVR (HR 1.241; 95% CI 1.035 to 1.488; p=0.020).

Conclusions

LV diastolic dysfunction is independently associated with all-cause mortality and the composite endpoint of all-cause mortality and AVR in patients with moderate AS and preserved LV systolic function. Assessment of LV diastolic function therefore contributes significantly to the risk stratification of patients with moderate AS. Future clinical trials are needed to investigate whether patients with moderate AS and LV diastolic dysfunction may benefit from earlier valve intervention.
A signature for pan-cancer prognosis based on neutrophil extracellular traps
Authors: Zhang Yi , Guo Liping , Dai Qichen , Shang Bingqing , Xiao Ting , Di Xuebing , Zhang Kaitai , Feng Lin , Shou Jianzhong , Wang Yipeng
Published: June 2022

Background

Neutrophil extracellular traps (NETs) were originally thought to be formed by neutrophils to trap invading microorganisms as a defense mechanism. Increasing studies have shown that NETs play a pivotal role in tumor progression and diffusion. In this case, transcriptome analysis provides an opportunity to unearth the association between NETs and clinical outcomes of patients with pan-cancer.

Methods

The transcriptome sequencing data of The Cancer Genome Atlas pan-cancer primary focus was obtained from UCSC Xena, and a 19-gene NETs score was then constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model based on the expression levels of 69 NETs initial biomarkers we collected from multistudies. In addition, multiple datasets covering multiple cancer types from other databases were collected and used to validate the signature. Gene ontology enrichment analyses were used to annotate the functions of NETs-related pathways. Immunohistochemistry (IHC) was implemented to evaluate the role of NETs-related genes in clinical patients across types of tumors, including lung adenocarcinoma (n=58), colorectal carcinoma (n=93), kidney renal clear cell carcinoma (n=90), and triple-negative breast cancer (n=80).

Results

The NETs score was calculated based on 19-NETs related genes according to the LASSO Cox model. The NETs score was considered a hazardous factor in most cancer types, with a higher score indicating a more adverse outcome. In addition, we found that NETs were significantly correlated to various malignant biological processes, such as the epithelial to mesenchymal transition (R=0.7444, p<0.0001), angiogenesis (R=0.5369, p<0.0001), and tumor cell proliferation (R=0.3835, p<0.0001). Furthermore, in IHC cohorts of a variety of tumors, myeloperoxidase, a gene involved in the model and a classical delegate of NETs formation, was associated with poor clinical outcomes.

Conclusions

Collectively, these constitutive and complementary biomarkers represented the ability of NETs formation to predict the development of patients’ progression. Integrative transcriptome analyses plus clinical sample validation may facilitate the biomarker discovery and clinical transformation.
Higher proportions of CD39+ tumor-resident cytotoxic T cells predict recurrence-free survival in patients with stage III melanoma treated with adjuvant immunotherapy
Authors: Attrill Grace Heloise , Owen Carina N , Ahmed Tasnia , Vergara Ismael A , Colebatch Andrew J , Conway Jordan W , Nahar Kazi J , Thompson John F , Pires da Silva Ines , Carlino Matteo S , Menzies Alexander M , Lo Serigne , Palendira Umaimainthan , Scolyer Richard A , Long Georgina V , Wilmott James S
Published: June 2022

Background

Adjuvant immune checkpoint inhibitor (ICI) immunotherapies have significantly reduced the recurrence rate in high-risk patients with stage III melanoma compared with surgery alone. However, 48% of anti-PD-1-treated patients will develop recurrent disease within 4 years. There is a need to identify biomarkers of recurrence after adjuvant ICI to enable identification of patients in need of alternative treatment strategies. As cytotoxic T cells are critical for the antitumor response to anti-PD-1, we sought to determine whether specific subsets were predictive of recurrence in anti-PD-1-treated high-risk patients with stage III melanoma.

Methods

Associations with recurrence in patients with stage III melanoma were sought by analyzing resection specimens (n=103) taken prior to adjuvant nivolumab/pembrolizumab±low-dose/low-interval ipilimumab. Multiplex immunohistochemistry was used to quantify intratumoral CD8+ T-cell populations using phenotypical markers CD39, CD103, and PD-1.

Results

With a median follow-up of 19.3 months, 37/103 (36%) of patients had a recurrence. Two CD8+ T-cell subpopulations were significantly associated with recurrence. First, CD39+ tumor-resident memory cells (CD39+CD103+PD-1+CD8+ (CD39+ Trm)) comprised a significantly higher proportion of CD8+ T cells in recurrence-free patients (p=0.0004). Conversely, bystander T cells (CD39−CD103−PD-1−CD8+) comprised a significantly greater proportion of T cells in patients who developed recurrence (p=0.0002). Spatial analysis identified that CD39+ Trms localized significantly closer to melanoma cells than bystander T cells. Multivariable analysis confirmed significantly improved recurrence-free survival (RFS) in patients with a high proportion of intratumoral CD39+ Trms (1-year RFS high 78.1% vs low 49.9%, HR 0.32, 95% CI 0.15 to 0.69), no complete lymph node dissection performed, and less advanced disease stage (HR 2.85, 95% CI 1.13 to 7.19, and HR 1.29, 95% CI 0.59 to 2.82). The final Cox regression model identified patients who developed recurrence with an area under the curve of 75.9% in the discovery cohort and 69.5% in a separate validation cohort (n=33) to predict recurrence status at 1 year.

Conclusions

Adjuvant immunotherapy-treated patients with a high proportion of CD39+ Trms in their baseline melanoma resection have a significantly reduced risk of melanoma recurrence. This population of T cells may not only represent a biomarker of RFS following anti-PD-1 therapy, but may also be an avenue for therapeutic manipulation and enhancing outcomes for immunotherapy-treated patients with cancer.
IVIg-exposure and thromboembolic event risk: findings from the UK Biobank
Authors: Kapoor Mahima , Hunt Ian , Spillane Jennifer , Bonnett Laura Jayne , Hutton Elspeth Jane , McFadyen James , Westwood John-Paul , Lunn Michael P , Carr Aisling S , Reilly Mary M
Published: June 2022

Background

Arterial and venous thromboembolic events (TEEs) have been associated with intravenous Ig use, but the risk has been poorly quantified. We aimed to calculate the risk of TEEs associated with exposure to intravenous Ig.

Methods

We included participants from UK Biobank recruited over 3 years, data extracted September 2020.

The study endpoints were incidence of myocardial infarction, other acute ischaemic heart disease, stroke, pulmonary embolism and other venous embolism and thrombosis.

Predictors included known TEE risk factors: age, sex, hypertension, smoking status, type 2 diabetes mellitus, hypercholesterolaemia, cancer and past history of TEE. Intravenous Ig and six other predictors were added in the sensitivity analysis.

Information from participants was collected prospectively, while data from linked resources, including death, cancer, hospital admissions and primary care records were collected retrospectively and prospectively. 

Findings

14 794 of 502 492 individuals had an incident TEE during the study period. The rate of incident events was threefold higher in those with prior history of TEE (8 .7%) than those without previous history of TEE (3.0%).

In the prior TEE category, intravenous Ig exposure was independently associated with increased risk of incident TEE (OR=3.69 (95% CI 1.15 to 11.92), p=0.03) on multivariate analysis. The number needed to harm by exposure to intravenous Ig in those with a history of TEE was 5.8 (95% CI 2.3 to 88.3).

Intravenous Ig exposure did not increase risk of TEE in those with no previous history of TEE.

Interpretation

Intravenous Ig is associated with increased risk of further TEE in individuals with prior history of an event with one further TEE for every six people exposed. In practice, this will influence how clinicians consent for and manage overall TEE risk on intravenous Ig exposure.
Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis
Authors: Etemadifar Masoud , Nouri Hosein , Pitzalis Maristella , Idda Maria Laura , Salari Mehri , Baratian Mahshid , Mahdavi Sepide , Abhari Amir Parsa , Sedaghat Nahad
Published: June 2022

Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines’ immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS—although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters’ immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20—unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.