bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of accounting for loss to follow-up when comparing mortality between immigrants and long-term residents: a population-based retrospective cohort
Authors: Vyas Manav V. , Fang Jiming , Austin Peter C. , Laupacis Andreas , Cheung Matthew C. , Silver Frank L. , Kapral Moira K 
Published: November 2021

ObjectivesTo evaluate the association between immigration status and all-cause mortality in different disease cohorts, and the impact of loss to follow-up on the observed associations.DesignPopulation-based retrospective cohort study using linked administrative health data in Ontario, Canada.SettingWe followed adults with a first-ever diagnosis of ischaemic stroke, cancer or schizophrenia between 2002 and 2013 from index event to death, loss to follow-up, or end of follow-up in 2018.Primary and secondary outcome measuresOur outcomes of interest were all-cause mortality and loss to follow-up. For each disease cohort, we calculated adjusted HRs of death in immigrants compared with long-term residents, adjusting for demographic characteristics and comorbidities, with and without censoring for those who were lost to follow-up. We calculated the ratio of two the HRs and the respective CL using bootstrapping methods.ResultsImmigrants were more likely to be lost to follow-up than long-term residents in all disease cohorts. Not accounting for this loss to follow-up overestimated the magnitude of the association between immigration status and mortality in those with ischaemic stroke (HR of death before vs after accounting for censoring: 0.78 vs 0.83, ratio=0.95; 95% CL 0.93 to 0.97), cancer (0.74 vs 0.78, ratio=0.96; 0.95 to 0.96), and schizophrenia (0.54 vs 0.56, ratio=0.97; 0.96 to 0.98).ConclusionsImmigrants to Canada have a survival advantage that varies by the disease studied. The magnitude of this advantage is modestly overestimated by not accounting for the higher loss to follow-up in immigrants.
COVID-19 Public Stigma Scale (COVID-PSS): development, validation, psychometric analysis and interpretation
Authors: Nochaiwong Surapon , Ruengorn Chidchanok , Awiphan Ratanaporn , Kanjanarat Penkarn , Ruanta Yongyuth , Phosuya Chabaphai , Boonchieng Waraporn , Nanta Sirisak , Chongruksut Wilaiwan , Thavorn Kednapa , Wongpakaran Nahathai , Wongpakaran Tinakon 
Published: November 2021

ObjectiveAmid the COVID-19 pandemic, social stigma towards COVID-19 infection has become a major component of public discourse and social phenomena. As such, we aimed to develop and validate the COVID-19 Public Stigma Scale (COVID-PSS).Design and settingNational-based survey cross-sectional study during the lockdown in Thailand.ParticipantsWe invited the 4004 adult public to complete a set of measurement tools, including the COVID-PSS, global fear of COVID-19, perceived risk of COVID-19 infection, Bogardus Social Distance Scale, Pain Intensity Scale and Insomnia Severity Index.MethodsFactor structure dimensionality was constructed and reaffirmed with model fit by exploratory and confirmatory factor analyses and non-parametric item response theory (IRT) analysis. Psychometric properties for validity and reliability were tested. An anchor-based approach was performed for classifying the proper cut-off scores.ResultsAfter factor analysis, IRT analysis and test for model fit, we created the final 10-item COVID-PSS with a three-factor structure: stereotype, prejudice and fear. Face and content validity were established through the public and experts’ perspectives. The COVID-PSS was significantly correlated (Spearman rank, 95% CI) with the global fear of COVID-19 (0.68, 95% CI 0.66 to 0.70), perceived risk of COVID-19 infection (0.79, 95% CI 0.77 to 0.80) and the Bogardus Social Distance Scale (0.50, 95% CI 0.48 to 0.53), indicating good convergent validity. The correlation statistics between the COVID-PSS and the Pain Intensity Scale and Insomnia Severity Index were <0.2, supporting the discriminant validity. The reliability of the COVID-PSS was satisfactory, with good internal consistency (Cronbach’s α of 0.85, 95% CI 0.84 to 0.86) and test–retest reproducibility (intraclass correlation of 0.94, 95% CI 0.86 to 0.96). The proposed cut-off scores were as follows: no/minimal (≤18), moderate (19–25) and high (≥26) public stigma towards COVID-19 infection.ConclusionsThe COVID-PSS is practical and suitable for measuring stigma towards COVID-19 in a public health survey. However, cross-cultural adaptation may be needed.
Effect of aspirin on HIV disease progression among HIV-infected individuals initiating antiretroviral therapy: study protocol for a randomised controlled trial
Authors: Mwakyandile Tosi , Shayo Grace , Mugusi Sabina , Sunguya Bruno , Sasi Philip , Moshiro Candida , Mugusi Ferdinand , Lyamuya Eligius 
Published: November 2021

IntroductionAn increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression.Methods and analysisA single-centre phase IIA double-blind, parallel-group randomised controlled trial intends to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants are randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of <50 copies/mL by 8, 12 and 24 weeks. Secondary outcomes include proportions of participants with HVL of >1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes.Ethics and disseminationEthical approval has been obtained from institutional and national ethics review committees. Findings will be submitted to peer-reviewed journals and presented in scientific conferences.Trial registration numberPACTR202003522049711.
A co-design study to develop supportive interventions to improve psychological and social adaptation among adults with new-onset type 1 diabetes in Denmark and the UK
Authors: Due-Christensen Mette , Joensen Lene Eide , Sarre Sophie , Romanczuk Ewa , Wad Julie Lindberg , Forde Rita , Robert Glenn , Willaing Ingrid , Forbes Angus 
Published: November 2021

ObjectiveTo develop supportive interventions for adults with new-onset type 1 diabetes (T1D) to facilitate positive adaptive strategies during their transition into a life with diabetes.DesignThe study used a co-design approach informed by Design Thinking to stimulate participants’ reflections on their experiences of current care and generate ideas for new supportive interventions. Visual illustrations were used to depict support needs and challenges. Initial discussions of these needs and challenges were facilitated by researchers and people with diabetes in workshops. Data comprising transcribed audio recordings of the workshop discussions and materials generated during the workshops were analysed thematically.SettingsSpecialised diabetes centres in Denmark and the United Kingdom.ParticipantsAdults with new-onset T1D (n=24) and healthcare professionals (HCPs) (n=56) participated in six parallel workshops followed by four joint workshops with adults (n=29) and HCPs (n=24) together.ResultsThe common solution prioritised by both adults with new-onset T1D and HCP participants was the development of an integrated model of care addressing the psychological and social elements of the diagnosis, alongside information on diabetes self-management. Participants also indicated a need to develop the organisation, provision and content of care, along with the skills HCPs need to optimally deliver that care. The co-designed interventions included three visual conversation tools that could be used flexibly in the care of adults with new-onset T1D to support physical, psychological and social adaptation to T1D.ConclusionThis co-design study has identified the care priorities for adults who develop T1D, along with some practical conversational tools that may help guide HCPs in attending to the disruptive experience of the diagnosis and support adults in adjusting into a life with diabetes.
Oxford Understanding Relationships, Sex, Power, Abuse and Consent Experiences (OUR SPACE) cross-sectional survey: a study protocol
Authors: Steele Bridget , Degli Esposti Michelle , Mandeville Pete , Hamnett Gillian , Nye Elizabeth , Humphreys David K 
Published: November 2021

IntroductionSexual violence among higher education students is a public health concern, threatening the general safety of students, often with significant physical and mental health implications for victims. Establishing the prevalence estimates of sexual violence at higher education institutions (HEIs) is essential for designing and resourcing responses to sexual violence, including monitoring the effectiveness of prevention initiatives and institutional programmes. Yet, to date, there have been no rigorous studies assessing prevalence of sexual violence at HEIs in the UK.Methods and analysisInformed by guidance from Universities UK, the University of Oxford administration and the related student advocacy groups working within the University, Oxford Understanding Relationships, Sex, Power, Abuse and Consent Experiences is a cross-sectional survey of all undergraduate and graduate students over the age of 18 enrolled at the University of Oxford, UK. The survey design uses a complete sampling approach and measures adapted from previous campus climate surveys in the USA as well as the Sexual Experiences Survey (USA). The analysis will estimate the prevalence of sexual harassment and sexual violence perpetration and victimisation, and will examine whether ethnicity, gender identity, and sexual orientation are associated with these primary outcomes.Ethics and disseminationEthical approval was obtained by the Social Sciences and Humanities Interdivisional Research Ethics Committee at the University of Oxford which is a subcommittee of the Central University Research Ethics Committee (ref no.: R73805/RE001). The research team will disseminate findings through peer-reviewed journal articles and conference presentations. A report cowritten by authors and stakeholders will be shared with Oxford University students.
Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study
Authors: Dietl Alexander , Zimmermann Martina E , Brandl Caroline , Wallner Stefan , Burkhardt Ralph , Maier Lars S , Luchner Andreas , Heid Iris M , Stark Klaus J 
Published: November 2021

ObjectiveEuropean guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference distribution and to assess the specificity of the 14 ng/L cut-off value in the mobile population ≥70 years of age.DesignA cross-sectional analysis was performed in the German AugUR study (AltersbezogeneUntersuchungen zurGesundheit derUniversity ofRegensburg).SettingStudy population was the mobile population aged 70+ years living in the city and county of Regensburg, Germany.ParticipantsA random sample was derived from the local population registries of residence. Of the 5644 individuals invited, 1133 participated (response ratio=20.1%). All participants came to the study centre and were mentally and physically mobile to conduct the protocol (face-to-face interview, blood draw and standardised transthoracic echocardiography). None of the participants was in an acute state of myocardial infarction.ResultsAmong the 1129 individuals with hsTnT measurements (overall median=10.0 ng/L(25th, 75th percentile)=(7.0, 15.0 ng/L)), hsTnT was higher among the older individuals and higher among men (men 70–74 years median=9.6 ng/L (7.2, 13.1 ng/L); men 90–95 years median=21.2 ng/L (14.6, 26.0 ng/L); women 70–74 years median=6.3 ng/L (4.7, 8.7 ng/L); and women 90–95 years median=18.0 ng/L (11.0, 21.0 ng/L)). In participants with impaired kidney function (eGFRcrea<60 mL/min/1.73 m2), hsTnT was elevated (median=13.6 ng/L (9.4, 20.6 ng/L)).Specificity of recommended upper reference limit, 14 ng/L, is 68%. Most false positives were among men aged >79 years (specificity=34%). In a healthy subgroup (n=96, none of the following: overt heart disease, impaired renal function, blood pressure >160/100 mm Hg, left ventricular hypertrophy and diastolic/systolic dysfunction), specificity was 90%.ConclusionIn the elderly population without acute myocardial infarction, hsTnT further increases with age showing different levels for men and women. The specificity of the 14 ng/L cut-off is considerably lower than 99%, even in healthy subjects.
Incidence of post-traumatic epilepsy following paediatric traumatic brain injury: protocol for systematic review and meta-analysis
Authors: Mariajoseph Frederick P , Rewell Sarah S , O"Brien Terence J , Semple Bridgette D , Antonic-Baker Ana 
Published: November 2021

IntroductionPost-traumatic epilepsy (PTE) is a recognised complication of traumatic brain injury (TBI), and is associated with higher rates of mortality and morbidity when compared with patients with TBI who do not develop PTE. The majority of the literature on PTE has focused on adult populations, and consequently there is a paucity of information regarding paediatric cohorts. Additionally, there is considerable heterogeneity surrounding the reported incidence of PTE following childhood TBI in the current literature. The primary aim of our study is to summarise reported PTE incidences in paediatric populations to derive an accurate estimate of the global incidence of PTE following childhood TBI. Our secondary aim is to explore risk factors that increase the likelihood of developing PTE.Methods and analysisA systematic literature search of Embase (1947–2021), PubMed (1996–2021) and Web of Science (1900–2021) will be conducted. Publications in English that report the incidence of PTE in populations under 18 years of age will be included. Publications that evaluate fewer than 10 patients, report an alternative cause of epilepsy, or in which a paediatric cohort is not discernable, will be excluded. Independent investigators will identify the relevant publications, and discrepancies will be adjudicated by a third independent investigator. Data extracted will include incidence of PTE, time intervals between TBI and PTE, seizure characteristics, injury characteristics, patient demographics and clinical data. Data extraction will be performed by two independent investigators and cross-checked by a third investigator. A descriptive analysis of PTE incidence will be conducted and a weighted mean will be calculated. If sufficient data are available, stratified meta-analysis of subgroups will also be conducted.Ethics and disseminationEthics approval was not required for this study. We intend to publish our findings in a high-quality peer-reviewed journal on completion.PROSPERO registration numberCRD42021245802.
Enhanced airway sensory nerve reactivity in non-eosinophilic asthma
Authors: Ali Hajar , Brooks Collin , Crane Julian , Beasley Richard , Holgate Stephen , Gibson Peter , Pattemore Philip , Tzeng Yu-Chieh , Stanley Thorsten , Pearce Neil , Douwes Jeroen 
Published: November 2021

BackgroundNeural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics.MethodsThirty-eight asthmatics and 19 non-asthmatics (aged 14–21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV1during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs.ResultsNon-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0; p<0.05). NEA tended to also have greater capsaicin sensitivity than EA, with the difference in capsaicin sensitivity between NEA and EA being of similar magnitude (58.3 µM, 24.1 to 141.5 vs 191.0 µM, 70.9 to 514.0) to that observed between NEA and non-asthmatics; however, this did not reach statistical significance (p=0.07). FEV1was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control or treatment were observed.ConclusionNEA, but not EA, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of NEA.
Defining hypoxaemia from pulse oximeter measurements of oxygen saturation in well children at low altitude in Bangladesh: an observational study
Authors: McCollum Eric D , King Carina , Ahmed Salahuddin , Hanif Abu A M , Roy Arunangshu D , Islam ASMD Ashraful , Colbourn Tim , Schuh Holly B , Ginsburg Amy Sarah , Hooli Shubhada , Chowdhury Nabidul H , Rizvi Syed J R , Begum Nazma , Baqui Abdullah H , Checkley William 
Published: November 2021

BackgroundWHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO2), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO2threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO2threshold for hypoxaemia from well children in Bangladesh residing at low altitude.MethodsWe prospectively enrolled well, children aged 3–35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO2of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO2distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO2as possible lower thresholds for hypoxaemia.ResultsOur primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO2was 98% (IQR 96%–99%), and the 2.5th, 5th and 10th percentile SpO2was 91%, 92% and 94%. No child had a SpO2<90%. Children 3–11 months had a lower median SpO2(97%) than 12–23 months (98%) and 24–35 months (98%) (p=0.039). The SpO2distribution did not differ by sex (p=0.959).ConclusionA SpO2threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO2must also consider the child’s clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO2thresholds for hypoxaemia is a key next step.
Temporal variability of soil fertility indicators and sampling periods in Québec
Authors: Chelabi Hakima , Khiari Lotfi , Gallichand Jacques 
Published: November 2021

An inadequate soil sampling time leads to difficulties in interpreting soil tests, to incorrect recommendations for soil amendments and fertilizers, and to inappropriate environmental protection restrictions. Soil samples may be collected from agricultural fields before, during, or after the crop growth period. Since the time of soil sample collection can affect soil tests results, the objective of this study was to evaluate the effect of sampling time on measurements representativity of 15 fertility indicators in two fields located in La Pocatière (Québec, Canada). The soils were of fine (G1) and medium (G2) textural groups and were sampled weekly for 33 weeks per year during four years. Data analyses included descriptive statistics, time-series decomposition, and time autocorrelation function (ACF). Since results of these analyses showed a clear seasonal effect only for Mehlich-3 extracted phosphorus (PM3), soil phosphorus saturation index (SPS) for both G1 and G2 soils, and for pHW for G1 only, we recommend that the sampling calendar should be restricted to the first five weeks of spring (until the end of May) and to the entire fall period (starting in early September). Also, the temporal autocorrelation was four weeks on average. This implies that, for an initial year, whichever date is chosen for the sampling, the following annual sampling should be done within a four-week time window (i.e., two weeks before until two weeks after the initial sampling date). Time series are an important element to consider in selecting a representative sampling period for soil fertility indicators.
SOX10 Regulates Melanoma Immunogenicity through an IRF4–IRF1 Axis
Authors: Yokoyama Satoru , Takahashi Atsushi , Kikuchi Ryota , Nishibu Soshi , Lo Jennifer A. , Hejna Miroslav , Moon Wooyoung M. , Kato Shinichiro , Zhou Yue , Hodi F. Stephen , Song Jun S. , Sakurai Hiroaki , Fisher David E. , Hayakawa Yoshihiro 
Published: November 2021

Abstract

Loss-of-function mutations of JAK1/2 impair cancer cell responsiveness to IFNγ and immunogenicity. Therefore, an understanding of compensatory pathways to activate IFNγ signaling in cancer cells is clinically important for the success of immunotherapy. Here we demonstrate that the transcription factor SOX10 hinders immunogenicity of melanoma cells through the IRF4–IRF1 axis. Genetic and pharmacologic approaches revealed that SOX10 repressed IRF1 transcription via direct induction of a negative regulator, IRF4. The SOX10–IRF4–IRF1 axis regulated PD-L1 expression independently of JAK–STAT pathway activity, and suppression of SOX10 increased the efficacy of combination therapy with an anti-PD-1 antibody and histone deacetylase inhibitor against a clinically relevant melanoma model. Thus, the SOX10–IRF4–IRF1 axis serves as a potential target that can bypass JAK-STAT signaling to immunologically warm up melanoma with a "cold" tumor immune microenvironment.

Significance:
This study identifies a novel SOX10/IRF4 pathway that regulates noncanonical induction of IRF1 independent of the JAK–STAT pathway and can be targeted to improve the efficacy of anti-PD-1 therapy in melanoma.