bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential impact of intervention strategies on COVID-19 transmission in Malawi: a mathematical modelling study
Authors: Mangal Tara , Whittaker Charlie , Nkhoma Dominic , Ng'ambi Wingston , Watson Oliver , Walker Patrick , Ghani Azra , Revill Paul , Colbourn Timothy , Phillips Andrew , Hallett Timothy , Mfutso-Bengo Joseph 
Published: July 2021

BackgroundCOVID-19 mitigation strategies have been challenging to implement in resource-limited settings due to the potential for widespread disruption to social and economic well-being. Here we predict the clinical severity of COVID-19 in Malawi, quantifying the potential impact of intervention strategies and increases in health system capacity.MethodsThe infection fatality ratios (IFR) were predicted by adjusting reported IFR for China, accounting for demography, the current prevalence of comorbidities and health system capacity. These estimates were input into an age-structured deterministic model, which simulated the epidemic trajectory with non-pharmaceutical interventions and increases in health system capacity.FindingsThe predicted population-level IFR in Malawi, adjusted for age and comorbidity prevalence, is lower than that estimated for China (0.26%, 95% uncertainty interval (UI) 0.12%–0.69%, compared with 0.60%, 95% CI 0.4% to 1.3% in China); however, the health system constraints increase the predicted IFR to 0.83%, 95% UI 0.49%–1.39%. The interventions implemented in January 2021 could potentially avert 54 400 deaths (95% UI 26 900–97 300) over the course of the epidemic compared with an unmitigated outbreak. Enhanced shielding of people aged ≥60 years could avert 40 200 further deaths (95% UI 25 300–69 700) and halve intensive care unit admissions at the peak of the outbreak. A novel therapeutic agent which reduces mortality by 0.65 and 0.8 for severe and critical cases, respectively, in combination with increasing hospital capacity, could reduce projected mortality to 2.5 deaths per 1000 population (95% UI 1.9–3.6).ConclusionWe find the interventions currently used in Malawi are unlikely to effectively prevent SARS-CoV-2 transmission but will have a significant impact on mortality. Increases in health system capacity and the introduction of novel therapeutics are likely to further reduce the projected numbers of deaths.
Relationship between osteonecrosis and antiphospholipid antibodies in patients with systemic lupus erythematosus: a systematic review protocol
Authors: Wei Qijiao , Zhou Meng , Liu Jianwen , Zhang Shengli , Gao Fei , Lin He , Chen Zhihan 
Published: July 2021

IntroductionOsteonecrosis (ON) is characterised by the destruction of the normal blood supply to the bone tissue. ON is the main cause of disability in patients with systemic lupus erythematosus (SLE). Studies have reported the existence of many risk factors for SLE complicated by ON, including the use of high-dose glucocorticoids and high disease activity. The correlation between antiphospholipid antibodies (aPLs) and ON in SLE has been controversial. We aim to conduct a systematic review of the literature related to SLE, aseptic ON and aPLs, to provide a reference for the clinical screening of high-risk patients and for early prevention.Methods and analysisThe following six databases will be searched: MEDLINE/PubMed, Embase, Web of Science, Chinese Biomedical Literature Database, Wan-Fang Database and China National Knowledge Infrastructure. The database searches will not be restricted by date. Case–control studies, cohort studies or observational studies that compare aPLs between SLE patients with and without ON will be considered eligible. Articles published in English and Chinese will be included. Two researchers will independently perform the processes of study selection, data extraction and study quality assessment. The Newcastle–Ottawa Quality Assessment Scale will be used to assess the quality of the retrieved studies. A meta-analysis will be performed after screening the studies. Data will be analysed using ORs for dichotomous data.Ethics and disseminationEthical approval is not required because this systematic review will use published data. The systematic review will be electronically disseminated through a peer-reviewed publication or conference presentations.PROSPERO registration numberCRD42020209637.
United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): a retrospective cohort study using linked routinely collected data, study protocol
Authors: Teece Lucy , Gray Laura J , Melbourne Carl , Orton Chris , Ford David V , Martin Christopher A , McAllister David , Khunti Kamlesh , Tobin Martin , John Catherine , Abrams Keith R , Pareek Manish 
Published: July 2021

IntroductionCOVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities.Methods and analysisThis study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes.Ethics and disseminationEthical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/).Trial registration numberISRCTN11811602.
Effects of high-load and low-load resistance training in patients with coronary artery disease: rationale and design of a randomised controlled clinical trial
Authors: Kambic Tim , Šarabon Nejc , Hadžić Vedran , Lainscak Mitja 
Published: July 2021

IntroductionResistance training (RT) combined with aerobic training (AT) enhances the effects of cardiac rehabilitation (CR) in patients with coronary artery disease (CAD). However, it remains to be investigated which type of RT (high loads (HLs) vs low loads (LLs)) is more efficacious in improving exercise performance, cardio-metabolic health and quality of life.Methods and analysisA randomised, controlled, clinical trial will enrol 20 patients with CAD into each of three study arms (total 60 patients): HL-RT (70%–80% of one repetition maximum (1-RM)) combined with AT; LL-RT (30%–40% of 1-RM) combined with AT and AT alone as standard care. Primary outcomes (maximal aerobic capacity, maximal leg isometric strength) will be assessed at baseline and after 36 training sessions. Other outcomes will include acute haemodynamic responses to LL-RT and HL-RT, body composition, physical performance, blood biomarkers (lipids, glucose metabolism, inflammation, growth factors), physical activity and quality of life. The intention-to-treat principle will be used to analyse the data.Ethics and disseminationThe study design and protocol have been approved by the National Medical Ethics Committee of Slovenia (registration number: 0120-573/2019/15). The study will be conducted in accordance with the Declaration of Helsinki. The results of the study will be published as peer-reviewed manuscripts and congress presentations, communicated with patients and the clinical community, and shared through posts on social media. The findings of the study will be disseminated among the national CR clinical community (CR centres, Slovenian association of coronary clubs) with active participation of the patients enrolled in the study. This study will expand our knowledge of RT in combination with AT in CR. We expect to find different effects of HL-RT versus LL-RT, with implications for RT strategies in rehabilitation of patients with CAD.Trial registration numberNCT04638764.
Early essential newborn care is associated with improved newborn outcomes following caesarean section births in a tertiary hospital in Da Nang, Vietnam: a pre/post-intervention study
Authors: Tran Hoang Thi , Murray John Charles Scott , Sobel Howard Lawrence , Mannava Priya , Huynh Le Thi , Nguyen Phuong Thi Thu , Giang Hoang Thi Nam , Le Tuyen Thi Mong , Hoang Tuan Anh , Nguyen Vinh Duc , Li Zhao , Pham Nga Thi Quynh 
Published: July 2021

BackgroundTo improve maternal and neonatal outcomes, Vietnam implemented early essential newborn care (EENC) using clinical coaching and quality improvement self-assessments in hospitals to introduce policy, practice and environmental changes. Da Nang Hospital for Women and Children began EENC with caesarean section births to inform development of national guidelines. This study compared newborn outcomes after caesarean sections pre/post-EENC introduction.MethodsMaternity records of all live in-born hospital caesarean births and separate case records of the subpopulation admitted to the neonatal intensive care unit (NICU) were reviewed pre-EENC (November 2013–October 2014) and post-EENC (November 2014–October 2015) implementation. NICU admissions and adverse outcomes on NICU admission were compared using descriptive statistics.FindingsA total of 16 927 newborns were delivered by caesarean section: 7928 (46.8%) pre-EENC and 8999 post-EENC (53.2%). Total NICU admissions decreased from 16.7% to 11.8% (relative risk 0.71; 95% CI 0.66 to 0.76) after introduction of EENC. Compared with the pre-EENC period, babies with hypothermia on admission to the NICU declined from 5.0% to 3.7% (relative risk 0.73; 95% CI 0.63 to 0.84) and cases of sepsis from 3.2% to 0.8% (relative risk 0.26; 95% CI 0.20 to 0.33) post-EENC implementation. While more than half of all newborns in the NICU were fed something other than breastmilk pre-EENC introduction, 85.8% were exclusively breast fed post-EENC (relative risk 1.86; 95% CI 1.75 to 1.98). Preterm newborns <2000 g receiving kangaroo mother care (KMC) increased from 50% to 67% (relative risk 1.33; 95% CI 1.12 to 1.59).ConclusionThe EENC quality improvement approach with caesarean section births was associated with reduced NICU admissions, admissions with hypothermia and sepsis, and increased rates of exclusive breast feeding and KMC in the NICU.
Substitutions of physical activity, sedentary behaviour and sleep: associations with mental health in middle-aged and elderly persons
Authors: Hofman Amy , Voortman Trudy , Ikram M. Arfan , Luik Annemarie I 
Published: July 2021

BackgroundPhysical activity, sedentary behaviour and sleep are potential risk factors of mental health disorders, but previous studies have not considered the dependency between these activity domains. Therefore, we examined the associations of reallocations of time among older adults’ physical activity, sedentary behaviour and sleep with depressive and anxiety symptoms using compositional isotemporal substitution analyses.MethodsWe included 1943 participants (mean age 71 years, SD: 9; 52% women) from the population-based Rotterdam Study. Between 2011 and 2016, we collected accelerometer data (mean duration 5.8 days, SD: 0.4) on physical activity, sedentary behaviour and sleep and self-reported data on depressive symptoms and anxiety.ResultsA reallocation of 30 min more moderate-to-vigorous physical activity was associated with a −0.55 (95% CI −1.04 to −0.06) points lower depressive symptoms score when replacing sleep and a −0.59 (95% CI −1.06 to −0.12) points lower score when replacing sedentary behaviour, but not when replacing light physical activity (−0.70, 95% CI −1.63 to 0.24). No associations were found for anxiety.ConclusionReplacing sedentary behaviour or sleep with more moderate-to-vigorous physical activity was associated with less depressive symptoms, suggesting that mainly intensive types of physical activity are important for middle-aged and older adults in relation to depressive symptoms.
ATM/NEMO signaling modulates the expression of PD-L1 following docetaxel chemotherapy in prostate cancer
Authors: Wang Zongren , Zhang Xueling , Li Wuguo , Su Qiao , Huang Zhaoyang , Zhang Xinyao , Chen Haiqi , Mo Chengqiang , Huang Bin , Ou Wei , Chen Junxing , Zhao Guangyin , Chen Lingwu , Shao Lan 
Published: July 2021

BackgroundThe efficacy of docetaxel-based chemotherapy is limited by the development of drug resistance. Recent studies demonstrated the efficacy of anti-programmed death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immunotherapies in metastatic prostate cancer. The ataxia telangiectasia mutation (ATM) protein plays a crucial role in maintaining genome stability and function of mitosis. Here, we aimed to determine whether PD-1/PD-L1 signaling contributes to the resistance to DTX and to elucidate the mechanism underlying DTX-induced PD-L1 expression.MethodsIn this retrospective study, PD-L1 expression was analyzed in 33 tumor tissue samples from prostate cancer patients. Prostate cell lines were used to perform functional assays and examine underlying mechanisms in vitro. A fully mouse prostate cancer model and a humanized chimeric mouse bearing human prostate tumors and peripheral blood mononuclear cells were used for in vivo assays.ResultsWe have shown that DTX, a chemotherapeutic drug which causing microtubule interference, could significantly induce the expression of PD-L1 in prostate cancer cells. This effect is blocked by the inhibition of ATM, suggesting that it plays an essential role in PD-L1 expression upregulated by DTX. Mechanistic studies have shown that ATM activity in cancer cells enhances the stability of the NF-κB essential modulator (NEMO), which leading to an increase in the NF-κB activity and PD-L1 expression. Using the mouse model, it was further demonstrated that a combination of ATM and NEMO inhibitors along with DTX augmented the antitumor efficacy of chemotherapy, which are comparable to that of PD-L1 antibody.ConclusionsOur findings have revealed that a previously unrecognized ATM-NEMO signaling which induced by DTX is capable of suppressing tumor immunity by activating the expression of PD-L1, suggesting that the ATM-NEMO-NF-κB axis can be exploited to restore the immune balance and overcome cancer resistance triggered by DTX.Graphic Abstract: supplementary file 1
Antiviral antibody responses to systemic administration of an oncolytic RNA virus: the impact of standard concomitant anticancer chemotherapies
Authors: Roulstone Victoria , Mansfield David , Harris Robert J , Twigger Katie , White Christine , de Bono Johann , Spicer James , Karagiannis Sophia N , Vile Richard , Pandha Hardev , Melcher Alan , Harrington Kevin 
Published: July 2021

BackgroundOncolytic reovirus therapy for cancer induces a typical antiviral response to this RNA virus, including neutralizing antibodies. Concomitant treatment with cytotoxic chemotherapies has been hypothesized to improve the therapeutic potential of the virus. Chemotherapy side effects can include immunosuppression, which may slow the rate of the antiviral antibody response, as well as potentially make the patient more vulnerable to viral infection.MethodReovirus neutralizing antibody data were aggregated from separate phase I clinical trials of reovirus administered as a single agent or in combination with gemcitabine, docetaxel, carboplatin and paclitaxel doublet or cyclophosphamide. In addition, the kinetics of individual antibody isotypes were profiled in sera collected in these trials.ResultsThese data demonstrate preserved antiviral antibody responses, with only moderately reduced kinetics with some drugs, most notably gemcitabine. All patients ultimately produced an effective neutralizing antibody response.ConclusionPatients’ responses to infection by reovirus are largely unaffected by the concomitant drug treatments tested, providing confidence that RNA viral treatment or infection is compatible with standard of care treatments.
Predictive value of 3′-deoxy-3′-18F-fluorothymidine PET in the early response to anti-programmed death-1 therapy in patients with advanced non-small cell lung cancer
Authors: Sato Masayuki , Umeda Yukihiro , Tsujikawa Tetsuya , Mori Tetsuya , Morikawa Miwa , Anzai Masaki , Waseda Yuko , Kadowaki Maiko , Kiyono Yasushi , Okazawa Hidehiko , Ishizuka Tamotsu 
Published: July 2021

BackgroundAnti-programmed death-1 (anti-PD-1) therapy has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). However, it is difficult to evaluate the early response to anti-PD-1 therapy. We determined whether changes in 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) PET parameters before and soon after treatment initiation predicted the therapeutic effect of anti-PD-1 antibody.MethodsTwenty-six patients with advanced NSCLC treated with anti-PD-1 antibody were enrolled prospectively and underwent18F-FLT PET before and at 2 and 6 weeks after treatment initiation. Changes in maximal standardized uptake value (ΔSUVmax), proliferative tumor volume (ΔPTV) and total lesion proliferation (ΔTLP) of the lesions were calculated and evaluated for their associations with the clinical response to therapy.ResultsThe disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLP at 2 weeks, and decreased SUVmax, PTV, and TLP at 6 weeks, compared with those with PD, while three of eight (37.5%) patients who responded had increased TLP from baseline at 2 weeks (ie, pseudoprogression). Among the parameters that changed between baseline and 2 weeks, ΔPTV0-2 and ΔTLP0-2 had the highest accuracy (76.0%) to predict PD. Among the parameters that changed between baseline and 6 weeks, ΔSUVmax0-6, ΔPTV0-6 and ΔTLP0-6 had the highest accuracy (90.9%) to predict PD. ΔTLP0-2 (≥60%, HR 3.41, 95% CI 1.34–8.65, p=0.010) and ΔTLP0-6 (≥50%, HR 31.4, 95% CI 3.55 to 276.7, p=0.0019) were indicators of shorter progression-free survival.ConclusionsChanges in18F-FLT PET parameters may have value as an early predictive biomarker for the response to anti-PD-1 therapy in patients with NSCLC. However, it should be noted that pseudoprogression was observed in18F-FLT PET imaging at 2 weeks after treatment initiation.Trial registration numberjRCTs051180147.
Characteristics of cardiovascular autonomic dysfunction and association with quality of life in patients with systemic lupus erythematosus
Authors: Zinglersen Amanda Hempel , Iversen Katrine Kjær , Leffers Henrik Christian Bidstrup , Laugesen Esben , Fleischer Jesper , Jacobsen Søren 
Published: July 2021

ObjectivesCardiovascular autonomic neuropathy (CAN) may affect the clinical course of SLE leading to reduced quality of life. CAN is assessed by heart rate variability (HRV) measures and cardiovascular autonomic reflex tests (CARTs). In patients with SLE, we aimed to determine the characteristics of CAN and if CAN associates with health-related quality of life (HRQoL).MethodsPatients with SLE and healthy controls (HCs) were CAN tested with 5 min HRV and three CARTs to determine parameters reflecting parasympathetic and mixed sympathetic–parasympathetic function. Subjects were classified as having no, early or definitive CAN by having none, one or more than one abnormal CART, respectively. HRQoL as determined by the Short Form 12 (SF-12) was assessed in SLE.ResultsOf 111 patients with SLE, 92 answered the SF-12 and 54 were matched with 54 HCs for characterisation of CAN. Definitive CAN was present in 24.1% (95% CI 15% to 37%) patients with SLE and 1.9% (95% CI 0.3% to 9.8%) HCs (OR 16.8, 95% CI 2.1 to 133.8, p=0.008). The corresponding prevalences of any CAN were 53.7% (95% CI 41% to 66%) and 22.6% (95% CI 13% to 35%). SLE patients with definitive CAN showed signs of mixed sympathetic–parasympathetic dysfunction, whereas patients without CAN primarily presented with impaired parasympathetic activity. Signs of parasympathetic as well as sympathetic–parasympathetic dysfunction were associated with low physical SF-12 component score (all: β>0.211, p<0.05). The mental SF-12 component score was not associated with any CAN indices.ConclusionsCAN was a frequent finding in SLE and associated to self-report on impaired physical HRQoL. Even patients without CAN showed signs of impaired parasympathetic function compared with controls.
Leveraging in situ resources for lunar base construction
Authors: Ellery Alex 
Published: July 2021

We explore the limits of in situ resource utilization (ISRU) on the Moon to maximize living off the land by building lunar bases from in situ material. We adopt the philosophy of indigenous peoples who excelled in sustainability. We are interested in leveraging lunar resources to manufacture an entire lunar base in such a fashion that is fully sustainable and minimizes supplies required from Earth. A range of metals, ceramics and volatiles can be extracted from lunar minerals to support construction of a lunar base that include structure, piping and electrical distribution systems. To 3D print a lunar base, we must 3D print the load-bearing structure, electrical distribution system, water-based heating system, drinking water system, air system and orbital transport system from in situ resources. We also address the manufacture of the interior of the lunar base from local resources. The majority of systems constituting a lunar base can be manufactured from in situ resources.
Economic optimum plant density of irrigated early-maturity soybean in southern Alberta
Authors: Thai Tram T.N. , Le Roy Danny G. , Bandara Manjula S. , Thomas James E. , Larney Francis J. 
Published: July 2021

With soybean [Glycine max (L.) Merr.] seed cost increasing in Alberta, understanding economic optimum plant density (EOPD) could help growers save on input expenses. A study was conducted at two irrigated locations in southern Alberta (Bow Island and Lethbridge), in three growing seasons (2014–2016), using two maturity group (MG) 00 soybean genotypes, two row spacings (RS; narrow, 17.5 cm; wide, 35 cm), and three seeding densities (SD; 30, 50 and 80 seeds·m−2). Exponential plant density–yield relationships were used to estimate EOPD. The earlier MG 00.4 genotype compensated yield at lower plant density (39 vs. 43 plants·m−2) and emergence (74% vs. 80%) than the later MG 00.8 genotype. The EOPD gaps between environments, genotypes, and RS were minimal (from 1–3 plants·m−2), resulting in only 1.3%–2.0% differences in grain yield (37–56 kg·ha−1), and gross revenue at EOPD ($16–24·ha−1). The overall EOPD estimate was 46 plants·m−2, regardless of environment, genotype or RS. The study highlighted the difference between agronomic production and profit maximization in choosing an optimum plant density, and the need to establish a seeding density calculator for irrigated soybean in southern Alberta.