bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concordance between fasting plasma glucose and HbA1cin the diagnosis of diabetes in black South African adults: a cross-sectional study
Authors: Wade Alisha N , Crowther Nigel J , Abrahams-Gessel Shafika , Berkman Lisa , George Jaya A , Gómez-Olivé F Xavier , Manne-Goehler Jennifer , Salomon Joshua A , Wagner Ryan G , Gaziano Thomas A , Tollman Stephen M , Cappola Anne R 
Published: June 2021

ObjectivesWe investigated concordance between haemoglobin A1c (HbA1c)-defined diabetes and fasting plasma glucose (FPG)-defined diabetes in a black South African population with a high prevalence of obesity.DesignCross-sectional study.SettingRural South African population-based cohort.Participants765 black individuals aged 40–70 years and with no history of diabetes.Primary and secondary outcome measuresThe primary outcome measure was concordance between HbA1c-defined diabetes and FPG-defined diabetes. Secondary outcome measures were differences in anthropometric characteristics, fat distribution and insulin resistance (measured using Homoeostatic Model Assessment of Insulin Resistance (HOMA-IR)) between those with concordant and discordant HbA1c/FPG classifications and predictors of HbA1cvariance.ResultsThe prevalence of HbA1c-defined diabetes was four times the prevalence of FPG-defined diabetes (17.5% vs 4.2%). Classification was discordant in 15.7% of participants, with 111 individuals (14.5%) having HbA1c-only diabetes (kappa 0.23; 95% CI 0.14 to 0.31). Median body mass index, waist and hip circumference, waist-to-hip ratio, subcutaneous adipose tissue and HOMA-IR in participants with HbA1c-only diabetes were similar to those in participants who were normoglycaemic by both biomarkers and significantly lower than in participants with diabetes by both biomarkers (p<0.05). HOMA-IR and fat distribution explained additional HbA1cvariance beyond glucose and age only in women.ConclusionsConcordance was poor between HbA1cand FPG in diagnosis of diabetes in black South Africans, and participants with HbA1c-only diabetes phenotypically resembled normoglycaemic participants. Further work is necessary to determine which of these parameters better predicts diabetes-related morbidities in this population and whether a population-specific HbA1cthreshold is necessary.
A pragmatic health centre-based evaluation comparing the effectiveness of a PCV13 schedule change from 3+0 to 2+1 in a high pneumococcal carriage and disease burden setting in Malawi: a study protocol
Authors: Swarthout Todd D , Ibarz-Pavon Ana , Kawalazira Gift , Sinjani George , Chirombo James , Gori Andrea , Chalusa Peter , Bonomali Farouck , Nyirenda Roseline , Bulla Edwin , Brown Comfort , Msefula Jacquline , Banda Marjory , Kachala Jean , Mwansambo Charles , Henrion Marc YR , Gordon Stephen B , French Neil , Heyderman Robert S 
Published: June 2021

IntroductionStreptococcus pneumoniae(the pneumococcus) is commonly carried as a commensal bacterium in the nasopharynx but can cause life-threatening disease. Transmission occurs by human respiratory droplets and interruption of this process provides herd immunity. A 2017 WHO Consultation on Optimisation of pneumococcal conjugate vaccines (PCV) Impact highlighted a substantial research gap in investigating why the impact of PCV vaccines in low-income countries has been lower than expected. Malawi introduced the 13-valent PCV (PCV13) into the national Expanded Programme of Immunisations in 2011, using a 3+0 (3 primary +0 booster doses) schedule. With evidence of greater impact of a 2+1 (2 primary +1 booster dose) schedule in other settings, including South Africa, Malawi’s National Immunisations Technical Advisory Group is seeking evidence of adequate superiority of a 2+1 schedule to inform vaccine policy.MethodsA pragmatic health centre-based evaluation comparing impact of a PCV13 schedule change from 3+0 to 2+1 in Blantyre district, Malawi. Twenty government health centres will be randomly selected, with ten implementing a 2+1 and 10 to continue with the 3+0 schedule. Health centres implementing 3+0 will serve as the direct comparator in evaluating 2+1 providing superior direct and indirect protection against pneumococcal carriage. Pneumococcal carriage surveys will evaluate carriage prevalence among children 15–24 months, randomised at household level, and schoolgoers 5–10 years of age, randomly selected from school registers. Carriage surveys will be conducted 18 and 33 months following 2+1 implementation.AnalysisThe primary endpoint is powered to detect an effect size of 50% reduction in vaccine serotype (VT) carriage among vaccinated children 15–24 months old, expecting a 14% and 7% VT carriage prevalence in the 3+0 and 2+1 arms, respectively.Ethics and disseminationThe study has been approved by the Malawi College of Medicine Research Ethics Committee (COMREC; Ref: P05.19.2680), the University College London Research Ethics Committee (Ref: 8603.002) and the University of Liverpool Research Ethics Committee (Ref: 5439). The results from this study will be actively disseminated through manuscript publications and conference presentations.Trial registration numberNCT04078997.
Kobe project for the exploration of newer strategies to reduce the social burden of dementia: a study protocol of cohort and intervention studies
Authors: Nagai Yoji , Kojima Shinsuke , Kowa Hisatomo , Yamamoto Yasuji , Kajita Hiroyuki , Osaki Tohmi , Kakei Yasumasa , Kothari Kavita U , Kayano Ryoma 
Published: June 2021

IntroductionThis research project addresses the lack of screening tools for the early detection of high-risk individuals for long-term care, through four individual studies.Study 1 investigates the predictive ability of the ‘Kihon Check List’, study 2 the ‘Cognitive Function instrument’ and EuroQol-5 Dimension (EQ-5D) and study 3 the ‘Cognitive Function instrument’ and EQ-5D as well as the ‘Frail Kenshin’ health check-up, for incident long-term care certification over a follow-up period of up to 4 years. This is the first large prospective study to evaluate the predictive ability of these tools for the outcome measure long-term care certification. The last subsection of this project study four aims to explore a mixed methods intervention for delaying the need for long-term care. This section is purely exploratory, looking for clues for further studies.Methods and analysisBaseline data have been collected through local government programs, as well as through postal self-reported questionnaires. The primary outcome variable for all studies is long-term care certification data. Statistical analysis will be carried out using Kaplan-Meier, Multiple Cox regression as well as logistic regression.ConclusionThis project hopes to identify tools effective in predicting long-term care need. This will enable identification of citizens that are of higher risk for long-term care in the near future. This subset of high-risk individuals can in the future be addressed for extra support/intervention.Ethics and disseminationAll studies have been approved by respective institutional ethical committees and the WHO ethical committee ERC.0002899. In addition, all studies conform to the provisions of the Declaration of Helsinki and are conducted in accordance with Japan’s ‘Ethical Guidelines for Medical and Health Research Involving Human Subjects’. All findings will be disseminated at conferences and published in peer-reviewed journals.Trial registration numberUMIN000023283.
Surveillance testing for SARS-COV-2 infection in an asymptomatic athlete population: a prospective cohort study with 123 362 tests and 23 463 paired RT-PCR/antigen samples
Authors: Harmon Kimberly , de St Maurice Anabelle M , Brady Adam C , Swaminathan Sankar , Aukerman Doug F , Rueda Miguel A , Terrell Kim , Cohen Randall P , Gamradt Seth C , Henry Sunday D , Huston Lindsay M , McAllister David R , McCarty Kenneth M , Pass Anthony N , Paul Stephen R , Petron David J , Kliethermes Stephanie A 
Published: June 2021

ObjectiveTo assess the diagnostic accuracy of antigen compared with reverse transcriptase (RT)-PCR testing in an asymptomatic athlete screening programme and to monitor infection in college athletes.MethodsQuidel Sofia-2 SARS-CoV-2 Antigen Tests were performed daily before sports participation for football, basketball, wrestling and water polo from 29 September 2020 to 28 February 2021. Paired RT-PCR and antigen tests were performed at least once a week. Positive antigen tests were confirmed with RT-PCR.Results81 175 antigen and 42 187 RT-PCR tests were performed, including 23 462 weekly paired antigen/RT-PCR screening tests in 1931 athletes. One hundred and seventy-two athletes had a positive screening RT-PCR (0.4%), of which 83 (48%) occurred on paired testing days. The sensitivity of antigen tests varied with the frequency of RT-PCR testing and prevalence of COVID-19. The sensitivity of antigen testing was 35.7% (95% CI: 17% to 60%) and specificity 99.8% (95% CI: 99.7% to 99.9%) with once-a-week RT-PCR testing after adjusting for school prevalence. Daily antigen testing was similar to RT-PCR testing two to three times a week in identifying infection. Antigen testing identified infection before the next scheduled PCR on 89 occasions and resulted in 234 days where potentially infectious athletes were isolated before they would have been isolated with RT-PCR testing alone. Two athletic-related outbreaks occurred; 86% of total infections were community acquired.ConclusionAntigen testing has high specificity with a short turnaround time but is not as sensitive as RT-PCR. Daily antigen testing or RT-PCR testing two to three times a week is similar. There are benefits and drawbacks to each testing approach.
Experiences of fathers of children with a life-limiting condition: a systematic review and qualitative synthesis
Authors: Fisher Victoria , Fraser Lorna , Taylor Johanna 
Published: June 2021

BackgroundChildren with a life-limiting condition often require extensive and complex care, much of which is provided by their parents at home. There is a growing body of research that aims to understand the experiences of these parents, but the majority of this research is from mothers’ perspectives, meaning that fathers’ experiences are not well understood.ObjectivesTo identify and synthesise findings from existing qualitative studies that have explored the experiences of fathers of children with a life-limiting condition.MethodsA systematic review of qualitative research was conducted using thematic synthesis. Searches were conducted in MEDLINE, CINAHL, EMBASE, PsycINFO and Social Science Citation Index.ResultsFindings from 30 studies were included, representing the experiences of 576 fathers of children with a range of diagnoses including cancer, cystic fibrosis, genetic and neurological conditions. Themes detailed fathers’ experiences of uncertainty and shock around the time of their child’s diagnosis, their accounts of a ‘new normal’, difficulties in discussing their emotions, forming relationships with and seeking support from professionals and working fathers’ role conflicts. They discussed the life-changing nature of their child’s diagnosis, an event that affected all aspects of their lives from everyday activities, to their relationships, spirituality, values and ambitions.ConclusionsFathers experience many difficulties in response to their child’s diagnosis and ongoing treatment. Findings highlight the need for healthcare professionals to recognise individual family dynamics and the evolving role of the father. Fathers’ responses are not widely understood, and research that directly addresses their own well-being is warranted.
Sexually transmitted infection laboratory testing and education trends in US outpatient physician offices, 2009–2016
Authors: Zeidan Amina R , Strey Kelsey , Vargas Michelle N , Reveles Kelly R 
Published: June 2021

ObjectiveTo describe national rates of sexually transmitted infection (STI) testing and education overall and among patient subgroups in US outpatient physician offices from 2009 to 2016.DesignThis was a cross-sectional study of the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey from 2009 to 2016. Data weights were applied to extrapolate to national estimates.SettingData were collected from a systematic random sample of outpatient physician office visits throughout USA. Physician office types include free standing clinics, private or group setting practices, centres offering community and mental health services, family planning clinics and health maintenance organisations/other prepaid clinics.ParticipantsAll sampled patient visits were eligible for inclusion and were assessed for the provision of STI prevention education and STI testing for chlamydia, gonorrhoea, hepatitis, human papillomavirus (HPV) and HIV.ResultsOf 7.6 billion total visits, 123 million included an STI test. Hepatitis was the most commonly tested STI (9.12 per 1000), followed by chlamydia (6.67 per 1000), gonorrhoea (6.00 per 1000), HIV (5.40 per 1000) and HPV (5.03 per 1000). Testing rates for the three STIs measured for the entire 8-year period increased over time and peaked in 2015 compared with 2009: chlamydia (R2=0.36), HPV (R2=0.28) and HIV (R2=0.51). Testing was highest among women (21.93 per 1000), 15–24-year olds (46.04 per 1000), non-Hispanic blacks (37.33 per 1000) and those seen by obstetrics/gynaecology specialists (103.75 per 1000). STI prevention education was provided to 4.89 per 1000 patients and remained relatively unchanged from 2013 to 2016.ConclusionSTI testing in outpatient physician offices increased over the study period but varied by patient characteristics and site of care. Few patients received STI prevention education, highlighting a potential gap in resource utilisation in these settings.
STING activation normalizes the intraperitoneal vascular-immune microenvironment and suppresses peritoneal carcinomatosis of colon cancer
Authors: Lee Seung Joon , Yang Hannah , Kim Woo Ram , Lee Yu Seong , Lee Won Suk , Kong So Jung , Lee Hye Jin , Kim Jeong Hun , Cheon Jaekyung , Kang Beodeul , Chon Hong Jae , Kim Chan 
Published: June 2021

BackgroundPeritoneal carcinomatosis is a fatal clinical presentation of colon cancer, characterized by unresponsiveness to conventional anticancer therapies, including immune checkpoint inhibitors. Here, we elucidated the immune-evasion mechanisms during the peritoneal carcinomatosis of colon cancer and developed a novel immunotherapy by activating the stimulator of interferon genes (STING) pathway.MethodsWe generated a syngeneic peritoneal carcinomatosis model of colon cancer. Mice were intraperitoneally treated with either STING agonist (MIW815, also known as ADU-S100) or PD-1 blockade or both. The tumor microenvironment was comprehensively analyzed using multiplexed immunofluorescence imaging, flow cytometry, and NanoString immune profiling.ResultsIntraperitoneal colon cancer cells induce a massive influx of immunosuppressive M2-like macrophages, upregulate immune checkpoints, and impair effector T cell functions during peritoneal dissemination; these collectively create a highly angiogenic and immunosuppressive milieu that is resistant to anti-PD-1 monotherapy. Intraperitoneal administration of a STING agonist suppressed aberrant angiogenesis, increased pericyte coverage, and normalized tumor vessels, thereby facilitating the infiltration of activated CD8+ T cells into peritoneal tumor nodules. Moreover, STING activation reprogramed tumor-associated macrophages toward the M1 phenotype. STING activation converted immunologically cold peritoneal tumors into T-cell-inflamed tumors in a type-I interferon-dependent manner. Lastly, the STING agonist synergistically cooperated with PD-1 and/or COX2 blockade to further suppress the peritoneal dissemination of colon cancer, resulting in complete eradication of tumor and ascites, and inducing durable antitumor immunity.ConclusionsSTING activation can normalize the peritoneal vascular and immune microenvironment, providing a rationale for a novel combination therapeutic strategy for peritoneal carcinomatosis in colon cancer.
Biallelic truncating variants in ATP9A cause a novel neurodevelopmental disorder involving postnatal microcephaly and failure to thrive
Authors: Vogt Guido , Verheyen Sarah , Schwartzmann Sarina , Ehmke Nadja , Potratz Cornelia , Schwerin-Nagel Anette , Plecko Barbara , Holtgrewe Manuel , Seelow Dominik , Blatterer Jasmin , Speicher Michael R , Kornak Uwe , Horn Denise , Mundlos Stefan , Fischer-Zirnsak Björn , Boschann Felix 
Published: June 2021

BackgroundGenes implicated in the Golgi and endosomal trafficking machinery are crucial for brain development, and mutations in them are particularly associated with postnatal microcephaly (POM).MethodsExome sequencing was performed in three affected individuals from two unrelated consanguineous families presenting with delayed neurodevelopment, intellectual disability of variable degree, POM and failure to thrive. Patient-derived fibroblasts were tested for functional effects of the variants.ResultsWe detected homozygous truncating variants in ATP9A. While the variant in family A is predicted to result in an early premature termination codon, the variant in family B affects a canonical splice site. Both variants lead to a substantial reduction of ATP9A mRNA expression. It has been shown previously that ATP9A localises to early and recycling endosomes, whereas its depletion leads to altered gene expression of components from this compartment. Consistent with previous findings, we also observed overexpression of ARPC3 and SNX3, genes strongly interacting with ATP9A.ConclusionIn aggregate, our findings show that pathogenic variants in ATP9A cause a novel autosomal recessive neurodevelopmental disorder with POM. While the physiological function of endogenous ATP9A is still largely elusive, our results underline a crucial role of this gene in endosomal transport in brain tissue.
Mortality in hypotensive trauma patients requiring laparotomy is related to degree of hypotension and provides evidence for focused interventions
Authors: Davis James W , Dirks Rachel C , Jeffcoach David R , Kaups Krista L , Sue Lawrence P , Lilienstein Jordan T , Wolfe Mary M , Kwok Amy M 
Published: June 2021

BackgroundMortality in hypotensive patients requiring laparotomy is reported to be 46% and essentially unchanged in 20 years. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been incorporated into resuscitation protocols in an attempt to decrease mortality, but REBOA can have significant complications and its use in this patient group has not been validated. This study sought to determine the mortality rate for hypotensive patients requiring laparotomy and to evaluate the mortality risk related to the degree of hypotension. Additionally, this study sought to determine if there was a presenting systolic blood pressure (SBP) that was associated with a sharp increase in mortality to target the appropriate patient group most likely to benefit from focused interventions such as REBOA.MethodsThe trauma registry at a level I trauma center was reviewed for patients undergoing emergent laparotomy from January 2007 to June 2020. Data included demographics, mechanism of injury, physiological data, Injury Severity Score, blood products transfused, and outcomes. Group comparisons were based on initial SBP (0 to 50 mm Hg, 60 to 69 mm Hg, 70 to 79 mm Hg, 80 to 89 mm Hg, and ≥90 mm Hg).ResultsDuring the study period, 52 016 trauma patients were treated and 1174 required laparotomy within 90 min of arrival; 424 had an initial SBP of <90 mm Hg. The overall mortality rate was 18%, but mortality increased as SBP decreased (≥90=9%, 80 to 89=20%, 70 to 79=21%, 60 to 69=48%, 0 to 59=66%). Mortality increased sharply with SBP of <70 mm Hg.DiscussionMortality rate increases with worsening hypotension and increases sharply with an SBP of <70 mm Hg. Further study on focused interventions such as REBOA should target this patient group.Level of evidenceTherapeutic/care management, level III.
On the ocean beach—why elliptic pebbles do not become spherical
Authors: Winzer Klaus , Hegerfeldt Gerhard C. 
Published: June 2021

AbstractAmong pebbles strewn across a sandy ocean beach, one can find relatively many with a nearly perfect elliptical (ellipsoidal) shape, and one wonders how this shape was attained and whether, during abrasion, the pebbles would remain elliptical or eventually become spherical. Mainly the latter question was addressed in a previous publication which identified frictional sliding and rotation of an elliptic pebble as main abrasion processes in the surf waves. In particular, it was predicted that the ellipticity $$\varepsilon = \left\{ {1 - b^{2} /a^{2} } \right\}^{1/2}$$

ε
=

1
-

b
2

/

a
2

1
/
2

(a > b, principal ellipse axes) converges to a common equilibrium value for elliptic-like pebbles. Unfortunately, the derivation was based on an invalid force expression and a dimensionally unsuitable curvature. In this paper, not only force and curvature but also the contact duration with the sand surface during rotations is taken into account by fairly simple physical arguments, and it is shown that elliptic pebbles neither approach the same ellipticity and nor become more spherical nor more disk-like but rather that the ellipticity $$\varepsilon$$
ε
increases.
Survival Outcomes of Nonsmall Cell Lung Cancer Patients Treated with Afatinib Who Are Affected by Early Adverse Events
Authors: Logan Jessica M. , Brooks Doug A. , Rowland Andrew , Sorich Michael J. , Hopkins Ashley M. 
Published: June 2021

Introduction. Afatinib is a first-line treatment option for patients with an advanced nonsmall cell lung cancer (NSCLC) expressing an epidermal growth factor receptor (EGFR) activating mutation. This study aimed to evaluate the association between early adverse events induced by afatinib and overall survival (OS) and progression free survival (PFS) in patients with advanced NSCLC. Methods. The study was a pooled post hoc analysis of the randomized trials LUX-Lung 3 and LUX-Lung 6 which evaluated afatinib versus pemetrexed-cisplatin or gemcitabine-cisplatin, respectively. Cox proportional hazard analysis was used to assess the impact of adverse events occurring within the first 28 days of afatinib therapy on the PFS and OS outcomes in treatment-naïve advanced NSCLC patients harbouring an EGFR activating mutation. Results. There were 468 patients who initiated first-line afatinib therapy within LUX-Lung 3 and LUX-Lung 6. A significant association between early rash and improved OS (hazard ratio (HR 95% CI); grade 1 = 0.74 [0.56–0.97]; grade 2+ = 0.64 [0.46–0.89]) (

P

= 0.018) was observed, although no significant association with PFS was present (

P

= 0.732). A significant association was identified between early diarrhoea and improved PFS (grade 1 = 0.83 [0.62–1.12]; grade 2+ = 0.62 [0.44–0.88]) (

P

= 0. 015), although no significant association with OS was present (

P

= 0.605). No associations between early stomatitis or paronychia and OS or PFS were identified. Conclusion. Rash occurring early after the initiation of afatinib was significantly associated with improved OS, an indicator that rash may be a surrogate of patients likely to achieve long-term survival. Consideration of using rash as a dose adjustment target may be warranted for future prospective trials aiming to optimise outcomes with afatinib therapy.