bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absolute cardiovascular risk scores and medication use in rural India: a cross-sectional study
Authors: Birhanu Mulugeta Molla , Evans Roger G , Zengin Ayse , Riddell Michaela , Kalyanram Kartik , Kartik Kamakshi , Suresh Oduru , Thomas Nihal Jacob , Srikanth Velandai K , Thrift Amanda G 
Published: May 2022

ObjectivesWe compared the performance of laboratory-based cardiovascular risk prediction tools in a low-income and middle-income country setting, and estimated the use of antihypertensive and lipid-lowering medications in those deemed at high risk of a cardiovascular event.DesignA cross-sectional study.SettingThe study population comprised adult residents (aged ≥18 years) of the Rishi Valley region located in Chittoor District, south-western Andhra Pradesh, India.Participants7935 participants were surveyed between 2012 and 2015. We computed the 10-year cardiovascular risk and undertook pair-to-pair analyses between various risk tools used to predict a fatal or non-fatal cardiovascular event (Framingham Risk Score (FRS), World Health Organization Risk Score (WHO-RS) and Australian Risk Score (ARS)), or a fatal cardiovascular event (Systematic COronary Risk Evaluation (SCORE-high and SCORE-low)). Concordance was assessed by ordinary least-products (OLP) regression (for risk score) and quadratic weighted kappa (κw, for risk category).ResultsOf participants aged 35–74 years, 3.5% had prior cardiovascular disease. The relationships between risk scores were quasi-linear with good agreement between the FRS and ARS (OLP slope=0.96, κw=0.89). However, the WHO-RS underestimated cardiovascular risk compared with all other tools. Twenty per cent of participants had ≥20% risk of an event using the ARS; 5% greater than the FRS and nearly threefold greater than the WHO-RS. Similarly, 16% of participants had a risk score ≥5% using SCORE-high which was 6% greater than for SCORE-low. Overall, absolute cardiovascular risk increased with age and was greater in men than women. Only 9%–12% of those deemed ‘high risk’ were taking lipid-lowering or antihypertensive medication.ConclusionsCardiovascular risk prediction tools perform disparately in this setting of disadvantage. Few deemed at high risk were receiving the recommended treatment.
Protocol of mixed-methods assessment of demographic, epidemiological and clinical profile of decentralised patients with cancer at Nelson Mandela Academic Hospital and Rob Ferreira Hospital, South Africa
Authors: Chitha Wezile , Jafta Zukiswa , Mnyaka Onke R , Hongoro Danleen , Godlimpi Lizo , Swartbooi Buyiswa , Williams Natasha , Zungu Christopher , Buthi Lazola , Kuseni Sibulelo , Nasila John , Sibulawa Siyabonga , Giwu Olona , Mavimbela Awam , Essel Vivien , Mabunda Sikhumbuzo A 
Published: May 2022

IntroductionCancer is the second leading cause of death globally. However, cancer care services are often concentrated in urban centres. Two of South Africa’s hospitals have decentralised cancer care delivery since February 2018 and August 2019, respectively. This study aims to describe the demographic, epidemiological and clinical profile of various cancers at Nelson Mandela Academic Hospital (NMAH) and Rob Ferreira Hospital (RFH), in South Africa’s Eastern Cape and Mpumalanga provinces, respectively.Methods and analysisThis study will be conducted in the Eastern Cape and Mpumalanga provinces. A mixed-methods study design will be undertaken to gain insight on the characteristics of randomly sampled patients who are treated for cancer at NMAH and RFH between 1 March 2018 and 28 February 2022. A validated, researcher-administered survey questionnaire will be used to assess demographic characteristics, and prevalence of different cancers among patients. Concurrently, a document review will be undertaken on patients with cancer using a patient registry to ascertain the duration of diagnosis, type of cancer(s), management plan and patient survival time. STATA V.17 will be used for data analysis. The Shapiro-Wilk test will be used to explore the distribution of numerical variables. The χ2or Fisher’s exact tests will be used depending on the value of the expected frequencies to compare categorical variables. Kaplan-Meier survival estimates will be used to determine the survival time. Hazard ratios will be used to determine the predictors of death. The level of statistical significance will be set at p value ≤0.05. The 95% CI will be used for the precision of estimates.Ethics and disseminationEthics approval was obtained from the Human Research Ethics Committees of the University of the Witwatersrand (M210211) and Walter Sisulu University, South Africa (Ref: 040/2020). Findings will be reported through peer-reviewed journal(s), presentations at conferences and at partner meetings.
Concurrent chemoradiation and brachytherapy alone or in combination with nelfinavir in locally advanced cervical cancer (NELCER): study protocol for a phase III trial
Authors: Chopra Supriya , Goda Jayant Sastri , Mittal Prachi , Mulani Jaahid , Pant Sidharth , Pai Venkatesh , Kannan Sadhna , Deodhar Kedar , Krishnamurthy Manjunath Nookala , Menon Santosh , Charnalia Mayuri , Shah Sneha , Rangarajan Venkatesh , Gota Vikram , Naidu Lavanya , Sawant Sheela , Thakkar Praffula , Popat Palak , Ghosh Jaya , Rath Sushmita , Gulia Seema , Engineer Reena , Mahantshetty Umesh , Gupta Sudeep 
Published: May 2022

IntroductionIn locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS).Methods and analysisRadiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years.Ethics and disseminationThe trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained.Trial registration numberThe trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).
Assessment of COVID-19 pandemic responses in African countries: thematic synthesis of WHO intra-action review reports
Authors: Talisuna Ambrose , Iwu Chinwe , Okeibunor J , Stephen Mary , Musa Emmanuel Onuche , Herring Belinda Louise , Ramadan Otim Patrick Cossy , Yota Daniel , Nanyunja Miriam , Mpairwe Allan , Banza Freddy Mutoka , Diallo Amadou Bailo , Wango Roland Kimbi , Massidi Christian , Njenge Hilary Kagume , Traore Martin , Oke Antonio , Bonkoungou Boukare , Mayigane Landry Ndriko , Conteh Ishata Nannie , Senait Fekadu , Chungong Stella , Impouma Benido , Ngoy Nsenga , Wiysonge Charles Shey , Yoti Zabulon , Gueye Abdou Salam 
Published: May 2022

ObjectivesWe conducted a review of intra-action review (IAR) reports of the national response to the COVID-19 pandemic in Africa. We highlight best practices and challenges and offer perspectives for the future.DesignA thematic analysis across 10 preparedness and response domains, namely, governance, leadership, and coordination; planning and monitoring; risk communication and community engagement; surveillance, rapid response, and case investigation; infection prevention and control; case management; screening and monitoring at points of entry; national laboratory system; logistics and supply chain management; and maintaining essential health services during the COVID-19 pandemic.SettingAll countries in the WHO African Region were eligible for inclusion in the study. National IAR reports submitted by March 2021 were analysed.ResultsWe retrieved IAR reports from 18 African countries. The COVID-19 pandemic response in African countries has relied on many existing response systems such as laboratory systems, surveillance systems for previous outbreaks of highly infectious diseases and a logistics management information system. These best practices were backed by strong political will. The key challenges included low public confidence in governments, inadequate adherence to infection prevention and control measures, shortages of personal protective equipment, inadequate laboratory capacity, inadequate contact tracing, poor supply chain and logistics management systems, and lack of training of key personnel at national and subnational levels.ConclusionThese findings suggest that African countries’ response to the COVID-19 pandemic was prompt and may have contributed to the lower cases and deaths in the region compared with countries in other regions. The IARs demonstrate that many technical areas still require immediate improvement to guide decisions in subsequent waves or future outbreaks.
Impact of aeroplane noise on mental and physical health: a quasi-experimental analysis
Authors: Wang Scarlett Sijia , Glied Sherry , Williams Sharifa , Will Brian , Muennig Peter Alexander 
Published: May 2022

ObjectivesHistorically, departures at New York City’s LaGuardia airport flew over a large sports complex within a park. During the US Open tennis games, flights were diverted to fly over a heavily populated foreign-born neighbourhood for roughly 2 weeks out of the year so that the tennis match was not disturbed (the ‘TNNIS’ departure). In 2012, the use of the TNNIS departure became year-round to better optimise flight patterns around the metropolitan area.MethodsWe exploited exogenously induced spatial and temporal variation in flight patterns to examine difference-in-difference effects of this new exposure to aircraft noise on the health of individual residents in the community relative to individuals residing within a demographically similar community that was not impacted. We used individual-level Medicaid records, focusing on conditions associated with noise: sleep disturbance, psychological stress, mental illness, substance use, and cardiovascular disease.ResultsWe found that increased exposure to aeroplane noise was associated with a significant increase in insomnia across all age groups, but particularly in children ages 5–17 (OR=1.64, 95% CI=1.12 to 2.39). Cardiovascular disease increased significantly both among 18–44-year-old (OR=1.45, 95% CI=1.41 to 1.49) and 45–64-year-old Medicaid recipients (OR=1.15, 95% CI=1.07 to 1.25). Substance use and mental health-related emergency department visits also increased. For ages 5–17,rate ratio (RR) was 4.11 (95% CI=3.28 to 5.16); for ages 18–44, RR was 2.46 (95% CI=2.20 to 2.76); and for ages 45–64, RR was 1.48 (95% CI=1.31 to 1.67).ConclusionWe find that increased exposure to aeroplane noise was associated with an increase in diagnosis of cardiovascular disease, substance use/mental health emergencies and insomnia among local residents.
Optimising the treatment for uncomplicated acute appendicitis (OPTIMA trial): a protocol for a multicentre, randomised, double-blinded placebo-controlled study
Authors: Wu Jie , Jiang Haiyang , Li Shikuan , Wu Xiuwen , Wang Peige , Sawyer Robert , Ren Jianan 
Published: May 2022

IntroductionEmerging evidence has shown that an antibiotic first strategy is a viable treatment option for uncomplicated acute appendicitis (AA). Although there has recently been an interest and increase in the use of antibiotics as the primary strategy for treating uncomplicated AA, there is no consensus regarding the optimum antibiotic regimen. In particular, the long-term outcomes of different antibiotic regimens, such as the recurrence rate, still lack evidence. Given that the flora of the appendix is mainly anaerobic bacteria, we hypothesised that antianaerobe regimens could decrease the recurrence rate compared with those that did not include antianaerobic antibiotics.Methods and analysisThe OPTIMA(Optimising the treatment for uncomplicated acute appendicitis) trial is a multicentre, double-blinded placebo-controlled superiority randomised study aimed to evaluate the role of antianaerobic antibiotics in the resolution of uncomplicated AA. Patients (18–65 years) with uncomplicated AA (without gangrenous, perforated appendicitis, appendiceal abscess, or appendiceal fecaliths) are eligible for inclusion. The primary endpoint of this study is the success rate of the treatment, defined as the resolution of AA resulting in discharge from the hospital without surgical intervention and recurrent symptoms within one year. Secondary endpoints include mortality, postintervention complications, recurrent symptoms up to one year after treatment, hospital stay, sick leave, treatment cost, pain symptom scores and quality of life. Data are reported as the number of cases (%), median (range) and relative risk, which will be analysed using the Mann-Whitney U test or χ2 test, as appropriate. P-value<0.05 will be considered significant.Ethics and disseminationThe protocol has been approved by the Ethics Committee of Jinling Hospital on 13 November 2018 (2018NZKY-027-01). The trial findings will be published in peer-reviewed journals.Trial registration numberChiCTR1800018896.
Contribution of an extensive medication-based comorbidity index (Rx-Risk) in explaining the excess mortality after hip fracture in older Norwegians: a NOREPOS cohort study
Authors: Holvik Kristin , Hjellvik Vidar , Karlstad Øystein , Gunnes Nina , Hoff Mari , Tell Grethe S , Meyer Haakon E 
Published: May 2022

ObjectivesPatients with hip fracture are typically characterised by extensive comorbidities and excess mortality. Methods that account for a wide range of comorbidities are needed when attempting to identify causal associations in registry-based studies. We aimed to study the association between the prescription-based Rx-Risk Comorbidity Index (abbreviated Rx-Risk) and mortality by history of hip fracture, and to quantify the contribution of Rx-Risk in explaining the excess mortality after hip fracture.SettingIn this prospective study, we used nationwide registry data from outpatient care. Rx-Risk was based on filled prescriptions recorded in the Norwegian Prescription Database. Medications were mapped to 46 comorbidity categories by Anatomical Therapeutic Chemical code. Information on hip fractures during 1994–2013 was available from the Norwegian Epidemiologic Osteoporosis Studies hip fracture database, and year of death was obtained from Statistics Norway. We estimated 1-year mortality risk (January through December 2014) according to Rx-Risk score based on dispensed prescriptions in 2013, history of hip fracture, age and sex using Poisson regression.ParticipantsAll individuals aged 65 years and older who were alive by the end of 2013 and had filled at least one prescription in an outpatient pharmacy in Norway in 2013 (n=735 968).ResultsMortality increased exponentially with increasing Rx-Risk scores, and it was highest in persons with a history of hip fracture across the major range of Rx-Risk scores. Age- and sex-adjusted mortality risk difference according to history of hip fracture (yes vs no) was 4.4 percentage points (7.8% vs 3.4%). Adjustment for Rx-Risk score further attenuated this risk difference to 3.3 percentage points.ConclusionsHistory of hip fracture and comorbidity assessed by Rx-Risk are independent risk factors for mortality in the community-dwelling older population in Norway. Comorbidity explained a quarter of the excess mortality in persons with a history of hip fracture.
Safety and feasibility study of non-invasive robot-assisted high-intensity focused ultrasound therapy for the treatment of atherosclerotic plaques in the femoral artery: protocol for a pilot study
Authors: Simons Michelle V , Groen Marijn H A , de Borst Gert J , Leiner Tim , Doevendans Pieter A F , Ebbini Emad , Slieker Fons J B , van Es René , Hazenberg Constantijn E V B 
Published: May 2022

IntroductionPeripheral arterial disease (PAD) is an atherosclerotic disease leading to stenosis and/or occlusion of the arterial circulation of the lower extremities. The currently available revascularisation methods have an acceptable initial success rate, but the long-term patency is limited, while surgical revascularisation is associated with a relatively high perioperative risk. This urges the need for development of less invasive and more effective treatment modalities. This protocol article describes a study investigating a new non-invasive technique that uses robot assisted high-intensity focused ultrasound (HIFU) to treat atherosclerosis in the femoral artery.Methods and analysisA pilot study is currently performed in 15 symptomatic patients with PAD with a significant stenosis in the common femoral and/or proximal superficial femoral artery. All patients will be treated with the dual-mode ultrasound array system to deliver imaging-guided HIFU to the atherosclerotic plaque. Safety and feasibility are the primary objectives assessed by the technical feasibility of this therapy and the 30-day major complication rate as primary endpoints. Secondary endpoints are angiographic and clinical success and quality of life.Ethics and disseminationEthical approval for this study was obtained in 2019 from the Medical Ethics Committee of the University Medical Center Utrecht, the Netherlands. Data will be presented at national and international conferences and published in a peer-reviewed journal.Trial registration numberNL7564.
Unemployment due to the SARS-CoV-2-pandemic among people with and without severe disabilities: a difference-in-differences analysis
Authors: Booke Frederike , Fauser David , Reims Nancy , Bethge Matthias 
Published: May 2022

ObjectivesUnemployment reduces health and impairs participation in important areas of life, especially for people with severe disabilities, who tend to have a longer duration of unemployment and are less likely to find new employment than their counterparts without such constraints. Our analysis examines the increase in unemployment due to the SARS-CoV-2 pandemic among people with and without severe disabilities in Germany.MethodsMonthly cross-sectional data on unemployment for 2019 and 2020 were provided by the Federal Employment Agency. We used a difference-in-differences model to estimate the increase in unemployment attributable to the pandemic. The months April to December 2020 represented the months of exposure to the pandemic. Incidence rate ratios (IRRs) are reported.ResultsThe increase in unemployment among people with severe disabilities due to the pandemic is 11.2% (IRR 1.112; 95% CI 1.107 to 1.117). People with severe disabilities receiving unemployment benefits due to unemployment lasting less than a year (Social Code III: short-term unemployment) and women have been most affected. Among people without severe disabilities, unemployment has increased by 24.8% due to the pandemic (IRR 1.248; 95% CI 1.246 to 1.249), while people receiving unemployment benefits according to social code III and men have been most affected. Both groups show a varying increase in unemployment depending on the region of residency.ConclusionsThe findings show a particularly significant increase in unemployment among people without severe disabilities. People with severe disabilities might be less impacted due to the special legal protection against their dismissal. The clear regional differences in the increase in unemployment suggest a strong influence of regional economics.
Workings of science
Authors: Delic Kemal A. , Riley Jeff A. 
Published: May 2022

While most people are not familiar with the details of how artificial intelligence (AI) works, the term itself is becoming more familiar to the non-scientific community, to the point that it ("AI") has almost become part of the regular vernacular of the ordinary person. AI has been with us for a long time-from first beginnings in ancient times in the form of automatons and other devices mimicking humans or other animals, through the middle of the last century when the term "artificial intelligence was actually coined, to the present times where it (the label rather than the actual technology) is entering the psyche of the general public.
This article explores the notion that the technology we call artificial intelligence is not yet ripe, but is establishing itself as a science in its own right, and that by 2156-the 200 year anniversary of the coining of the term-the technology should be in a position to deliver on its promises.
Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma
Authors: Zhang Bo , Peng Hui , Zhou Mi , Bao Lei , Wang Chenliang , Cai Feng , Zhang Hongxia , Wang Jennifer E. , Niu Yanling , Chen Yan , Wang Yijie , Hatanpaa Kimmo J. , Copland John A. , DeBerardinis Ralph J. , Wang Yingfei , Luo Weibo 
Published: May 2022

Abstract

Branched-chain amino acid transaminase 1 (BCAT1) is upregulated selectively in human isocitrate dehydrogenase (IDH) wildtype (WT) but not mutant glioblastoma multiforme (GBM) and promotes IDHWT GBM growth. Through a metabolic synthetic lethal screen, we report here that α-ketoglutarate (AKG) kills IDHWT GBM cells when BCAT1 protein is lost, which is reversed by reexpression of BCAT1 or supplementation with branched-chain α-ketoacids (BCKA), downstream metabolic products of BCAT1. In patient-derived IDHWT GBM tumors in vitro and in vivo, cotreatment of BCAT1 inhibitor gabapentin and AKG resulted in synthetic lethality. However, AKG failed to evoke a synthetic lethal effect with loss of BCAT2, BCKDHA, or GPT2 in IDHWT GBM cells. Mechanistically, loss of BCAT1 increased the NAD+/NADH ratio but impaired oxidative phosphorylation, mTORC1 activity, and nucleotide biosynthesis. These metabolic alterations were synergistically augmented by AKG treatment, thereby causing mitochondrial dysfunction and depletion of cellular building blocks, including ATP, nucleotides, and proteins. Partial restoration of ATP, nucleotides, proteins, and mTORC1 activity by BCKA supplementation prevented IDHWT GBM cell death conferred by the combination of BCAT1 loss and AKG. These findings define a targetable metabolic vulnerability in the most common subset of GBM that is currently incurable.

Significance:
Metabolic synthetic lethal screening in IDHWT glioblastoma defines a vulnerability to ΑΚG following BCAT1 loss, uncovering a therapeutic strategy to improve glioblastoma treatment.
See related commentary by Meurs and Nagrath, p. 2354