bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of SARS-CoV-2 infection among front-line healthcare workers in Northeast Brazil: a respondent-driven sampling approach
Authors: Albuquerque Maria de Fátima Pessoa Militão de , Souza Wayner Vieira de , Montarroyos Ulisses Ramos , Pereira Cresio Romeu , Braga Cynthia , Araújo Thalia Velho Barreto de , Ximenes Ricardo Arraes de Alencar , Miranda-Filho Demócrito de Barros , Szwarcwald Celia Landmann , Souza-Junior Paulo Roberto Borges de , Xavier Morgana Nascimento , Morais Clarice Neuenschwander Lins de , Albuquerque Gabriela Diniz Militao de , Bresani-Salvi Cristiane , Mariz Carolline Araújo , Siqueira-Filha Noemia Teixeira de , Galindo Jadson Mendonça , França-Neto Cláudio Luiz , Barbosa Jessyka Mary Vasconcelos , Veras Maria Amelia Sousa Mascena , Lima Luana Nepomuceno Gondim Costa , Cruz Luciane Nascimento , Kendall Carl , Kerr Ligia Regina Franco Sansigolo , Martelli Celina Maria Turchi 
Published: June 2022

ObjectivesWe assessed the prevalence of SARS-CoV-2 infection, personal protective equipment (PPE) shortages and occurrence of biological accidents among front-line healthcare workers (HCW).Design, setting and participantsUsing respondent-driven sampling, the study recruited distinct categories of HCW attending suspected or confirmed patients with COVID-19 from May 2020 to February 2021, in the Recife metropolitan area, Northeast Brazil.Outcome measuresThe criterion to assess SARS-CoV-2 infection among HCW was a positive self-reported PCR test.ResultsWe analysed 1525 HCW: 527 physicians, 471 registered nurses, 263 nursing assistants and 264 physical therapists. Women predominated in all categories (81.1%; 95% CI: 77.8% to 84.1%). Nurses were older with more comorbidities (hypertension and overweight/obesity) than the other staff. The overall prevalence of SARS-CoV-2 infection was 61.8% (95% CI: 55.7% to 67.5%) after adjustment for the cluster random effect, weighted by network, and the reference population size. Risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56; 95% CI: 1.42 to 4.61), not always using all recommended PPE while assisting patients with COVID-19 (OR adj: 2.15; 95% CI: 1.02 to 4.53) and reporting a splash of biological fluid/respiratory secretion in the eyes (OR adj: 3.37; 95% CI: 1.10 to 10.34).ConclusionsThis study shows the high frequency of SARS-CoV2 infection among HCW presumably due to workplace exposures. In our setting, nursing assistant comprised the most vulnerable category. Our findings highlight the need for improving healthcare facility environments, specific training and supervision to cope with public health emergencies.
Weight loss for overweight and obese patients with prostate cancer: a study protocol of a randomised trial comparing clinic-based versus Telehealth delivered EXercise and nutrition intervention (the TelEX trial)
Authors: Galvão Daniel A , Taaffe Dennis R , Hayne Dickon , Lopez Pedro , Lyons-Wall P , Tang Colin I , Chambers Suzanne K , Devine Amanda , Spry Nigel , Jeffery Emily , Kudiarasu Christine , Joseph David , Newton Robert U 
Published: June 2022

IntroductionObese men with prostate cancer have an increased risk of biochemical recurrence, metastatic disease and mortality. For those undergoing androgen deprivation therapy (ADT), substantial increases in fat mass are observed in the first year of treatment. Recently, we showed that a targeted supervised clinic-based exercise and nutrition intervention can result in a substantial reduction in fat mass with muscle mass preserved in ADT-treated patients. However, the intervention needs to be accessible to all patients and not just those who can access a supervised clinic-based programme. The purpose of this study was to evaluate the efficacy of telehealth delivered compared with supervised clinic-based delivered exercise and nutrition intervention in overweight/obese patients with prostate cancer.Methods and analysisA single-blinded, two-arm parallel group, non-inferiority randomised trial will be undertaken with 104 overweight/obese men with prostate cancer (body fat percentage ≥25%) randomly allocated in a ratio of 1:1 to a telehealth-delivered, virtually supervised exercise and nutrition programme or a clinic-based, face-to-face supervised exercise and nutrition programme. Exercise will consist of supervised resistance and aerobic exercise performed three times a week plus additional self-directed aerobic exercise performed 4 days/week for the first 6 months. Thereafter, for months 7–12, the programmes will be self-managed. The primary endpoint will be fat mass. Secondary endpoints include lean mass and abdominal aortic calcification, anthropometric measures and blood pressure assessment, objective measures of physical function and physical activity levels, patient-reported outcomes and blood markers. Measurements will be undertaken at baseline, 6 months (post intervention), and at 12 months of follow-up. Data will be analysed using intention-to-treat and per protocol approaches.Ethics and disseminationEthics approval has been obtained from the Edith Cowan University Human Research Ethics Committee (ID: 2021–02157-GALVAO). Outcomes from the study will be published in academic journals and presented in scientific and consumer meetings.Trial registration numberACTRN12621001312831.
Hypertension and retinal microvascular dysfunction (HyperVasc): protocol of a randomised controlled exercise trial in patients with hypertension
Authors: Streese Lukas , Gander Joséphine , Carrard Justin , Hauser Christoph , Hinrichs Timo , Schmidt-Trucksäss Arno , Gugleta Konstantin , Hanssen Henner 
Published: June 2022

IntroductionHypertension is a global healthcare burden that affects the structure and function of the macrocirculation and microcirculation and induces disease-specific end-organ damage. Vascular biomarkers are essential to timely diagnose this end-organ damage to improve cardiovascular (CV) risk stratification and medical decision making. Exercise therapy is an effective means to improve vascular health and reduce overall CV risk. However, it is still not clear whether high-intensity interval training (HIIT) is recommendable for patients with hypertension to reduce blood pressure, increase cardiorespiratory fitness and ameliorate vascular health.Methods and analysisThe ‘Hypertension and retinal microvascular dysfunction’ trial will investigate macrovascular and microvascular impairments in hypertensive patients compared with healthy controls to investigate hypertension-induced end-organ damage by using gold-standard methods as well as newly developed unique retinal microvascular biomarkers. In addition, this trial will investigate the reversibility of retinal end-organ damage by assessing the effects of an 8-week supervised and walking based HIIT on blood pressure, cardiorespiratory fitness as well as macrovascular and microvascular health, compared with a control group following standard physical activity recommendations. Primary outcome will be the arteriolar-to-venular diameter ratio. Secondary outcomes will be arteriolar and venular diameters as well as the flicker-light-induced dilation. Further outcomes will be other retinal microvascular biomarkers, flow-mediated dilation of the brachial artery as well as blood pressure, cardiorespiratory fitness, microalbuminuria, hypertensive retinopathy and classical CV risk markers. Analysis of variance and analysis of covariance will be used to investigate group differences between healthy controls and hypertensive patients and training effects in hypertensive patients, respectively.Ethics and disseminationThe Ethics Committee of Northwestern and Central Switzerland approved this study (EKNZ-2021-00086). All participants will give informed consent.Trial registration numberNCT04763005.
I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations
Authors: Files Daniel Clark , Matthay Michael A , Calfee Carolyn S , Aggarwal Neil R , Asare Adam L , Beitler Jeremy R , Berger Paul A , Burnham Ellen L , Cimino George , Coleman Melissa H , Crippa Alessio , Discacciati Andrea , Gandotra Sheetal , Gibbs Kevin W , Henderson Paul T , Ittner Caroline A G , Jauregui Alejandra , Khan Kashif T , Koff Jonathan L , Lang Julie , LaRose Mary , Levitt Joe , Lu Ruixiao , McKeehan Jeffrey D , Meyer Nuala J , Russell Derek W , Thomas Karl W , Eklund Martin , Esserman Laura J , Liu Kathleen D 
Published: June 2022

IntroductionThe COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021.Methods and analysisThe ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes—time to recovery and mortality. The statistical design uses a Bayesian model with ‘stopping’ and ‘graduation’ criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing.Ethics and disseminationISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals.Trial registration numberNCT04488081.
Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial
Authors: Said Bibie , Nuwagira Edwin , Liyoyo Alphonce , Arinaitwe Rinah , Gitige Catherine , Mushagara Rhina , Buzaare Peter , Chongolo Anna , Jjunju Samuel , Twesigye Precious , Boulware David R , Conaway Mark , Null Megan , Thomas Tania A , Heysell Scott K , Moore Christopher C , Muzoora Conrad , Mpagama Stellah G 
Published: June 2022

IntroductionSub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda.Methods and analysisThis is a phase 3, multisite, open-label, randomised controlled clinical 2×2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58.Ethics and disseminationThis clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation.Trial registration numberClinicalTrials.gov (NCT04618198).
Parenteral nutrition in palliative care: single-centre observational study
Authors: Berbée Clara , Marx Jan Philipp , Voelker Maria Theresa , Schotte Dörte , Bercker Sven 
Published: June 2022

ObjectiveCachexia and nutritional problems play a major role in palliative care. Artificial nutrition such as parenteral nutrition is common but its role and indications in terminal patients remain controversial due to lack of data. Therefore, recommendations are vague. Benefits and risks of parenteral nutrition in palliative care as well as the clinical implementation of the guidelines have not been adequately studied yet.MethodsIn this single-centre observational study, 72 palliative care patients were followed for 1 month. Patients with and without parenteral nutrition were analysed regarding venous access complications, oedema, weight and health-related quality of life.Results93% of all patients showed reduced food intake. 34 (47%) patients received parenteral nutrition. Parenteral nutrition reduced energy deficit but was not associated with quality of life. Complications with the venous accesses for parenteral nutrition were frequent. A relevant proportion of patients with planned parenteral nutrition received no or only a few days of parenteral nutrition. Moreover, patients with parenteral nutrition showed more frequent and pronounced oedema.ConclusionThe benefit–risk balance of palliative parenteral nutrition in end-of-life treatment seems to be questionable. In view of the identified risks, parenteral nutrition in end-of-life care should be initiated with caution.
High-Temperature-Resistant Diverting Acid for Carbonate Formation Fracturing in Sichuan Basin: A Property Evaluation and Field Study
Authors: Zhao Zhiheng , Sun Chuan , Liu Yuzhou 
Published: June 2022

The targeted carbonate formation in Gao-Mo Block located in the middle of Sichuan Basin becomes deeper with the progress of development, and it mainly exhibits high temperature and strong heterogeneity. Higher requirements for temperature resistance performance and acidizing effect of diverting acid are put forward. In this work, the high-temperature-resistant diverting acid (HTRDA) was employed to evaluate the compatibility, temperature resistance, friction reduction, and acidizing effectiveness based on formation characteristics, and it was applied to demonstrate its reliability and adaptability in field. The following study results are obtained. The HTRDA has good compatibility and its peak viscosity could reach 31 mPa·s at the temperature of 170°C. Compared with the friction of water, the friction reduction rate of HTRDA can reach 67.8%. And the permeability change of core with low permeability could be increased by 53.5-61% after acidification. Furthermore, during the acid fracturing of Well M, the maximum diverting pressure of HTRDA gets to 10 MPa and the friction reduction rate is about 66.5% that is consistent with the experimental data. The test production of Well M is

35.64
×

10

4

m

3

/
d

and the acid fracturing obtain a great result.
Tumor Intrinsic PD-L1 Promotes DNA Repair in Distinct Cancers and Suppresses PARP Inhibitor–Induced Synthetic Lethality
Authors: Kornepati Anand V.R. , Boyd Jacob T. , Murray Clare E. , Saifetiarova Julia , de la Peña Avalos Bárbara , Rogers Cody M. , Bai Haiyan , Padron Alvaro S. , Liao Yiji , Ontiveros Carlos , Svatek Robert S. , Hromas Robert , Li Rong , Hu Yanfen , Conejo-Garcia Jose R. , Vadlamudi Ratna K. , Zhao Weixing , Dray Eloïse , Sung Patrick , Curiel Tyler J. 
Published: June 2022

Abstract

BRCA1-mediated homologous recombination is an important DNA repair mechanism that is the target of FDA-approved PARP inhibitors, yet details of BRCA1-mediated functions remain to be fully elucidated. Similarly, immune checkpoint molecules are targets of FDA-approved cancer immunotherapies, but the biological and mechanistic consequences of their application are incompletely understood. We show here that the immune checkpoint molecule PD-L1 regulates homologous recombination in cancer cells by promoting BRCA1 nuclear foci formation and DNA end resection. Genetic depletion of tumor PD-L1 reduced homologous recombination, increased nonhomologous end joining, and elicited synthetic lethality to PARP inhibitors olaparib and talazoparib in vitro in some, but not all, BRCA1 wild-type tumor cells. In vivo, genetic depletion of tumor PD-L1 rendered olaparib-resistant tumors sensitive to olaparib. In contrast, anti-PD-L1 immune checkpoint blockade neither enhanced olaparib synthetic lethality nor improved its efficacy in vitro or in wild-type mice. Tumor PD-L1 did not alter expression of BRCA1 or its cofactor BARD1 but instead coimmunoprecipitated with BARD1 and increased BRCA1 nuclear accumulation. Tumor PD-L1 depletion enhanced tumor CCL5 expression and TANK-binding kinase 1 activation in vitro, similar to known immune-potentiating effects of PARP inhibitors. Collectively, these data define immune-dependent and immune-independent effects of PARP inhibitor treatment and genetic tumor PD-L1 depletion. Moreover, they implicate a tumor cell–intrinsic, immune checkpoint–independent function of PD-L1 in cancer cell BRCA1-mediated DNA damage repair with translational potential, including as a treatment response biomarker.

Significance:
PD-L1 upregulates BRCA1-mediated homologous recombination, and PD-L1–deficient tumors exhibit BRCAness by manifesting synthetic lethality in response to PARP inhibitors, revealing an exploitable therapeutic vulnerability and a candidate treatment response biomarker.
See related commentary by Hanks, p. 2069
A Programmable In Vivo CRISPR Activation Model Elucidates the Oncogenic and Immunosuppressive Functions of MYC in Lung Adenocarcinoma
Authors: Thege Fredrik I. , Rupani Dhwani N. , Barathi Bhargavi Brahmendra , Manning Sara L. , Maitra Anirban , Rhim Andrew D. , Wörmann Sonja M. 
Published: June 2022

Conventional genetically engineered mouse models (GEMM) are time-consuming, laborious, and offer limited spatiotemporal control. Here, we describe the development of a streamlined platform for in vivo gene activation using CRISPR activation (CRISPRa) technology. Unlike conventional GEMMs, this model system allows for flexible, sustained, and timed activation of one or more target genes using single or pooled lentiviral guides. Myc and Yap1 were used as model oncogenes to demonstrate gene activation in primary pancreatic organoid cultures in vitro and enhanced tumorigenic potential in Myc-activated organoids when transplanted orthotopically in vivo. Implementation of this model as an autochthonous lung cancer model showed that transduction-mediated activation of Myc led to accelerated tumor progression and significantly reduced overall survival relative to nontargeted tumor controls. Furthermore, Myc activation led to the acquisition of an immune suppressive, “cold” tumor microenvironment. Cross-species validation of these results using publicly available RNA/DNA-seq datasets linked MYC to a previously described immunosuppressive molecular subtype in patient tumors, thus identifying a patient cohort that may benefit from combined MYC- and immune-targeted therapies. Overall, this work demonstrates how CRISPRa can be used for rapid functional validation of putative oncogenes and may allow for the identification and evaluation of potential metastatic and oncogenic drivers through competitive screening.

Significance:
A streamlined platform for programmable CRISPR gene activation enables rapid evaluation and functional validation of putative oncogenes in vivo.
Tracking control for planar nonminimum-phase bilinear control system with disturbance using backstepping
Authors: Mu`tamar Khozin , Naiborhu Janson , Saragih Roberd , Handayani Dewi 
Published: June 2022

This article <span>presents the design control of a tracking problem for a non-minimum phase bilinear control system containing disturbance. The bilinear control system is assumed to have a relative degree one and non-minimum phase, which means it has unstable internal dynamics. The disturbance exists only in state variables corresponding to the control function in external dynamics. The control design was carried out using the backstepping method, which was applied to the normal form of the bilinear control system. Internal dynamics will be stabilised using virtual control to overcome unstable internal dynamics. The last step will stabilise the external dynamics and disturbance using the original control function. The simulation results show that the proposed control method can rapidly drive the output to the given trajectory. Control performance varies depending on the control parameter setting. The higher the control parameter, the better the control performance, evaluated using integral absolute error.</span>
Enhancement of code division multiple access system performance using raptor codes
Authors: Farhan Ikhlas Mahmoud , Zaghar Dhafer R. , Abdullah Hadeel Nasrat 
Published: June 2022

Some kinds of communication systems work in very low signal-to-noise (LSNR) environments. For these systems to function reliably, <span>specific techniques and methodologies have to be used to mitigate the degrading effects of the channel. The channel coding method is the key element in most LSNR communication systems, but emphasizing the code division multiple access (CDMA) is a new transmission technique in these channels. To enhance the CDMA scheme's system capacity and reach unprecedented ranges of LSNR values in wireless sensor network. This paper suggests combining CDMA with certain types of channel coding algorithms, such as the raptor codes. The raptor channel encoding technique has improved the CDMA system's performance when using binary phase-shift keying (BPSK) modulation in additive white gaussian noise (AWGN) channels. It has achieved a low bit error rate in range of 10-7 at Eb/No value of (-3) dB and about 10-6 at shannon's limit. The Raptor-coded CDMA scheme works well for channel signal to noise ration (SNR) values of greater than -9 dB, showing an improvement of about 7 dB compared with turbo/convolutional channel coding methods used with the CDMA system bit error rate (BER) and throughput. On the other hand, it has been shown that the convolutional encoder presents the weakest performance compared to both the turbo and raptor codes.</span>