bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing Self-harm in Adolescents. An individual participant data meta-analysis (RISA-IPD): systematic review protocol
Authors: Wright-Hughes Alexandra , Walwyn Rebecca , Wright Judy M , Farrin Amanda , Fonagy Peter , Ougrin Dennis , Stahl Daniel , Cottrell David 
Published: May 2021

IntroductionUp to 10% of adolescents report self-harm in the previous year. Non-fatal repetition is common (18% in 1 year), death from any cause shows a fourfold and suicide a 10-fold excess. Despite the scale of the problem, there is insufficient evidence for effective interventions for self-harm. Those who self-harm do so for a variety of different reasons. Different treatments may be more effective for subgroups of adolescents; however, little is known about which subgroups are appropriate for further study. This protocol outlines a systematic review and individual participant data meta-analysis (IPD-MA) to identify subgroups of adolescents for which therapeutic interventions for self-harm show some evidence of benefit.Methods and analysisA systematic literature search was conducted in August 2019 (including Cochrane Library, Embase, trial registers and other databases). An update search is planned. Study selection will identify randomised controlled trials examining interventions to reduce self-harm in adolescents who have self-harmed and presented to services. Identified research teams will be invited to contribute data and form a collaborative group. Two-stage IPD-MA will be used to evaluate effectiveness of different therapeutic interventions compared with any active or non-active control on repetition of self-harm, general psychopathology, depression, suicidal ideation, quality of life and death. Subgroup analyses will identify adolescent subgroups in whom different therapeutic interventions may be more effective. Meta-regression will explore moderating study and intervention effects. Sensitivity analyses will incorporate aggregate data from studies lacking IPD and test the robustness of results to methods for handling missing data, within-study clustering, non-adherence and study quality.Ethics and disseminationEthical approval is provided by the University of Leeds, Faculty of Medicine and Health Ethics Committee (18-098). Outcomes will inform research recommendations and will be disseminated internationally through the collaborative group, a service user advisory group, open-access peer-reviewed publication and conference presentations.PROSPERO registration numberCRD42019152119.
Trends in hospital admissions and mortality rates for asthma in Ecuador: a joinpoint regression analysis of data from 2000 to 2018
Authors: Cabrera Angelita , Rodriguez Alejandro , Romero-Sandoval Natalia , Barba Sergio , Cooper Philip J 
Published: April 2021

BackgroundAlthough asthma has emerged as an important public health problem over recent decades in Latin America, there are limited published data on national hospital admission and mortality rates for asthma from countries in the region.ObjectiveTo analyse trends in asthma hospitalisation and mortality rates in Ecuador over a 19-year period from 2000 to 2018.MethodsHospital discharge and death certificates listing asthma, as defined in the International Classification of Diseases 10th Revision codes (J45 and J46), were used to analyse time trends in rates of hospital admissions and mortality for asthma. The data were obtained from the Ecuadorian National Institute of Statistics and Census. Crude and age-standardised rates were estimated for the entire population. Additionally, specific rates by sex, age and region were estimated. We used joinpoint analysis to identify national trends.ResultDuring 2000–2018, a total of 58 250 hospitalisations and 1328 deaths due to asthma were identified. The average annual rates for hospitalisation and mortality attributed to asthma were estimated to be 21 (95% CI 19.3 to 22.8) and 5.2 (95% CI 4.4 to 6.0) per 100 000 population, respectively, over this period. Asthma hospital admissions decreased from 28 to 13.7 per 100 000 population between 2000 and 2018, and asthma mortality decreased from 0.8 to 0.3 per 100 000 population over the same period. Based on jointpoint analysis, two temporal trends were identified for hospital admissions. Between 2000 and 2011, hospital admissions decreased 0.8% per year and between 2011 and 2018 decreased 6.6% per year (p<0.05). On average, hospitalisation rates decreased 3.1% per year (p<0.05) over the entire study period. Mortality rate decreased 5.6% per year (p<0.05) over the 19-year period. Hospitalisation rates were higher among females, those aged 5 to 19 years and those living in the Coast region.ConclusionsOur analysis shows a temporal trend of reduction in rates of hospitalisations and deaths attributed to asthma between 2000 and 2018 in Ecuador, consistent with similar trends elsewhere in the Latin American region. Health registration systems in Latin America need to be improved to provide reliable data for future between and within country comparisons of trends in asthma hospitalisations and deaths.
Out-of-hospital cardiac arrest due to hanging: a retrospective analysis
Authors: Turner Jake , Brown Aidan , Boldy Rhiannon , Lumley-Holmes Jenny , Rosser Andy , James Alex 
Published: April 2021

BackgroundThere has been little research into the prehospital management of cardiac arrest following hanging despite it being among the most prevalent methods of suicide worldwide. The aim of this study was to report the characteristics, resuscitative treatment and outcomes of patients managed in the prehospital environment for cardiac arrest secondary to hanging and compare these with all-cause out-of-hospital cardiac arrest (OHCA).MethodsData from a UK ambulance service cardiac arrest registry were extracted for all cases in which treatment was provided for OHCA due to hanging between 1 January 2013 and 30 June 2018. Cases were linked to outcome data obtained from the Trauma Audit and Research Network. Comparison of the cohort was made to previously published data from a UK study of all-cause OHCA with 95% CIs calculated for the proportional difference between the studies in selected presentation and outcome variables.Results189 cases were identified. 95 patients were conveyed to hospital and four of these survived to discharge. 40 patients were conveyed despite absence of a spontaneous circulation and none of these patients survived. While only three patients were initially in a shockable rhythm, DC shocks were administered in 20 cases. There was one case of failed ventilation prompting front-of-neck access for oxygenation. By comparison with all-cause OHCA the proportion of patients with a spontaneous circulation at hospital handover was similar (27.0% vs 27.5%; 0.5% difference, 95% CI −5.9% to 6.8%, p=0.882) but survival to hospital discharge was significantly lower (2.2% vs 8.4%; 6.2% difference, 95% CI 4.1% to 8.3%, p=0.002).ConclusionClinical outcomes following OHCA due to hanging are poor, particularly when patients are transported while in cardiac arrest. Failure to ventilate was uncommon, and clinicians should be alert to the possibility of shockable rhythms developing during resuscitation.
Effectiveness of community interventions for protecting and promoting the mental health of working-age adults experiencing financial uncertainty: a systematic review
Authors: McGrath Michael , Duncan Fiona , Dotsikas Kate , Baskin Cleo , Crosby Liam , Gnani Shamini , Hunter Rachael Maree , Kaner Eileen , Kirkbride James Bowes , Lafortune Louise , Lee Caroline , Oliver Emily , Osborn David P , Walters Kate R , Dykxhoorn Jennifer 
Published: April 2021

BackgroundThe COVID-19 pandemic has created a period of global economic uncertainty. Financial strain, personal debt, recent job loss and housing insecurity are important risk factors for the mental health of working-age adults. Community interventions have the potential to attenuate the mental health impact of these stressors. We examined the effectiveness of community interventions for protecting and promoting the mental health of working-age adults in high-income countries during periods of financial insecurity.MethodsEight electronic databases were systematically screened for experimental and observational studies published since 2000 measuring the effectiveness of community interventions on mental health outcomes. We included any non-clinical intervention that aimed to address the financial, employment, food or housing insecurity of participants. A review protocol was registered on the PROSPERO database (CRD42019156364) and results are reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.ResultsFrom 2326 studies screened, 15 met our inclusion criteria. Five categories of community intervention were identified: advice services colocated in healthcare settings; link worker social prescribing; telephone debt advice; food insecurity interventions; and active labour market programmes. In general, the evidence for effective and cost-effective community interventions delivered to individuals experiencing financial insecurity was lacking. From the small number of studies without a high risk of bias, there was some evidence that financial insecurity and associated mental health problems were amenable to change and differences by subpopulations were observed.ConclusionThere is a need for well-controlled studies and trials to better understand effective ingredients and to identify those interventions warranting wider implementation.
Overlap of immunotherapy-related pneumonitis and COVID-19 pneumonia: diagnostic and vaccine considerations
Authors: Abid Muhammad Bilal 
Published: April 2021

The clinically indistinguishable overlap between pneumonitis caused due to immune checkpoint inhibition (ICI) and pneumonia associated with COVID-19 has posed considerable challenges for patients with cancer and oncologists alike. The cancer community continues to face the challenges that lay at the complex immunological intersection of immune-based cancer therapy and immune dysregulation that results from COVID-19. Is there compounded immune dysregulation that could lead to poor outcomes? Could ICIs, in fact, ameliorate SARS-CoV-2-driven T-cell exhaustion?A little more is known about the kinetics of the viral replication in immunocompromised patients now as compared with earlier during the pandemic. Working knowledge of the diagnostic and therapeutic nuances of SARS-CoV-2 infection in patients with active cancers, issues related to viability and replication potential of the virus, unclear role of corticosteroids among those with diminished or dysfunctional effector T-cell repertoire, and the type of immunotherapy with differential risk of pneumonitis will inform decision making related to immunotherapy choices and decision for ICI continuation in the era of COVID-19.
SARS-CoV-2 serological assay and viral testing: a report of professional football setting
Authors: Hassanmirzaei Bahar , Haratian Zohreh , Ahmadzadeh Amiri Ali , Ahmadzadeh Amiri Amir , Moghadam Navid 
Published: April 2021

AbstractPurpose of the studyPCR is the current standard test for the diagnosis of SARS-CoV-2 infection. However, due to its limitations, serological testing is considered an alternative method for detecting SARS-CoV-2 exposure. In this study, we measured the level of SARS-CoV-2 IgM and IgG antibodies of male professional football players and compared the results with the standard PCR test to investigate the association between the two tests.Study designParticipants were male professional football players and team officials. Nasopharyngeal swabs and peripheral blood samples were collected for the PCR and serological tests, respectively. Also, previous records of COVID-19 testing and symptoms were gathered. Those with previous positive PCR tests who tested negative for the second time were considered to be recovered patients.ResultsOf the 1243 subjects, 222 (17.9%) were seropositive, while 29 (2.3%) tested positive for the SARS-CoV-2 PCR test. Sixty percent of symptomatic cases with a negative PCR were found to be seropositive. The mean level of IgM was significantly higher in PCR-positive and symptomatic subjects, whereas the recovered cases showed significantly higher levels of IgG.ConclusionOur study revealed an inconsistency of results between the two tests; therefore, although application of serological assays alone seems insufficient in diagnosing COVID-19 disease, the findings are beneficial in the comprehension and the management of the disease.
CLEC5A knockdown protects against cardiac dysfunction after myocardial infarction by suppressing macrophage polarization, NLRP3 inflammasome activation, and pyroptosis
Authors: Wang Xin , Hu Yu , Wang Yaguang , Shen Dapeng , Tao Guizhou 
Published: May 2021

Increasing evidence has shown that the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptotic cell death play vital roles in the pathophysiology of myocardial infarction (MI), a common cardiovascular disease characterized by cardiac dysfunction. C-type lectin member 5A (CLEC5A) has been reported to be strongly associated with activation of the NLRP3 inflammasome and pyroptosis. In this study, an in vivo MI model was established by ligation of the left anterior descending coronary artery in male C57BL/6 mice, and CLEC5A knockdown was further achieved by intra-myocardial injection of adenovirus delivering shRNA-CLEC5A. CLEC5A was found to be highly expressed in the left ventricle of MI mice, while CLEC5A knockdown alleviated cardiac dysfunction in MI mice. In addition, MI-induced classical activation of macrophages was significantly inhibited after CLEC5A silencing. Additionally, CLEC5A knockdown dramatically inhibited MI-triggered activation of NLRP3 inflammasome, pyroptosis, and NF-κB signaling in the left ventricle of mice. In vitro experiments further validated that CLEC5A knockdown suppressed M1 polarization in LPS/IFNγ-stimulated RAW264.7 cells and inhibited the polarized RAW264.7-induced activation of NLRP3 inflammasome/pyroptosis signaling in co-cultured cardiomyocytes. In conclusion, CLEC5A knockdown protects against MI-induced cardiac dysfunction by regulating macrophage polarization, NLRP3 inflammasome, and cell pyroptosis.
Teleparallel axions and cosmology
Authors: Hohmann Manuel , Pfeifer Christian 
Published: April 2021

AbstractWe consider the most general teleparallel theory of gravity whose action is a linear combination of the five scalar invariants which are quadratic in the torsion tensor. Since two of these invariants possess odd parity, they naturally allow for a coupling to pseudo-scalar fields, thus yielding a Lagrangian which is even under parity transformations. In analogy to similar fields in gauge theories, we call these pseudo-scalar fields teleparallel axions. For the most general coupling of a single axion field, we derive the cosmological field equations. We find that for a family of cosmologically symmetric teleparallel geometries, which possess non-vanishing axial torsion, the axion coupling contributes to the cosmological dynamics in the early universe. Most remarkably, this contribution is also present when the axion is coupled to the teleparallel equivalent of general relativity, hence allowing for a canonical coupling of a pseudo-scalar to general relativity. For this case we schematically present the influence of the axion coupling on the fixed points in the cosmological dynamics understood as dynamical system. Finally, we display possible generalizations and similar extensions in other geometric frameworks to model gravity.
Petrogenesis and U–Pb zircon dating of the Chaitma Alkaline Complex from the southern margin of the Central Indian Tectonic Zone: geodynamic implications
Authors: Mahapatro Satya Narayana , Renjith M. L. , Martha Ranjit Kumar , Patel Rakesh Kumar , Upadhyay Dewashish , Sarma D. Srinivasa 
Published: May 2021

Abstract

In this study, we constrain the petrogenesis and U–Pb zircon age of a newly discovered alkaline complex, christened the Chaitma Alkaline Complex at the southern margin of the Central Indian Tectonic Zone in central India. The Chaitma Alkaline Complex comprises syenites and gabbros, emplaced coevally, and show features consistent with magma mixing. Geochemically, syenites are potassic–ultrapotassic (K
2
O/Na
2
O: 0.79–3.42), and contain high Ba (
c.
800–2700 ppm) and Sr (
c.
1400–3200 ppm). They show enrichment of the light rare earth elements (LREEs) relative to the heavy rare earth elements (HREEs) (La/Yb: 32–103) and do not display any Eu anomaly. Based on their geochemical signatures, such as low MgO (<0.87 wt%), Ni (8–16 ppm) and Cr (7–44 ppm) contents and prominent Zr–Hf negative anomaly, the syenites are inferred to have been derived by partial melting of a carbonated/metasomatized thickened lower crustal source. The coeval gabbros are undersaturated in silica (41–44 wt%), with relatively high total alkalis (Na
2
O + K
2
O: 3.7–5.1 wt%), Fe
2
O
3
(17–19 wt%), P
2
O
5
(3.1–4.9 wt%), Sr (1600–3400 ppm) and Ba (300–3500 ppm) contents. These have low MgO (<4.8 wt%), Ni (13–30 ppm) and Cr (18–84 ppm). Their chemistry is interpreted to be the result of interaction with the syenitic magma. These geochemical characters along with the high LREE/HREE ratio, negative trough in Nb–Ta, Zr–Hf, Ti, Sr and Rb, and positive spike of Pb in a multielement diagram, and enrichment of LILEs over HFSEs indicate their derivation from a metasomatized subduction-modified garnet–peridotite mantle source. Our study indicates that syenites and gabbros of the Chaitma Alkaline Complex were formed from genetically unrelated parental magmas derived from distinct sources. U–Pb dating of zircon yielded a magmatic emplacement age of 1626 ± 15 Ma for the syenites. The Chaitma Alkaline Complex was presumably formed during a short period of crustal extension in the midst of a protracted period of continent–continent collision and granulite-grade metamorphism (
c.
1.71–1.58 Ga) at the southern margin of the Central Indian Tectonic Zone.
New Players in the Regulation of DNA-PK Activity: Survivin Joins the Crowd
Authors: Iliakis George E. 
Published: May 2021

Abstract
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a large protein kinase and a member of the PI3K-related family of protein kinases that also includes ATM and ATR. DNA-PKcs is a unique evolutionary endowment of higher eukaryotes, as it is absent in lower eukaryotes. It is central to the processing of DNA double-strand breaks by classical nonhomologous end-joining, where through interaction with the Ku70/Ku80 heterodimer it generates the DNA-PK holoenzyme. DNA-PK coordinates and regulates the joining of DNA ends through essential structural contributions and by direct phosphorylation of key repair factors, including itself. Recent structural studies advance our understanding of the functions of this giant enzyme and reveal functional complexity and sophistication compatible with a broad spectrum of activities. Along these lines, the observations reported in the article by Güllülü and colleagues in this issue of Cancer Research reveal intriguing new facets in the regulation of DNA-PKcs and open horizons for further exciting research. Güllülü and colleagues found that in addition to known modes of regulation, DNA-PKcs is also regulated by a direct interaction with survivin. The observations expand the functional and regulatory spectrum of this intriguing kinase and suggest contributions to DNA damage response that remain to be characterized. They formed the foundations for the development of drugs disrupting this interaction, thereby potentially sensitizing tumor cells to radiation.
See related article by Güllülü et al., p. 2304
Emerging Roles for AKT Isoform Preference in Cancer Progression Pathways
Authors: Degan Seamus E. , Gelman Irwin H. 
Published: April 2021

Abstract
The phosphoinositol-3 kinase (PI3K)–AKT pathway is one of the most mutated in human cancers, predominantly associated with the loss of the signaling antagonist, PTEN, and to lesser extents, with gain-of-function mutations in PIK3CA (encoding PI3K-p110α) and AKT1. In addition, most oncogenic driver pathways activate PI3K/AKT signaling. Nonetheless, drugs targeting PI3K or AKT have fared poorly against solid tumors in clinical trials as monotherapies, yet some have shown efficacy when combined with inhibitors of other oncogenic drivers, such as receptor tyrosine kinases or nuclear hormone receptors. There is growing evidence that AKT isoforms, AKT1, AKT2, and AKT3, have different, often distinct roles in either promoting or suppressing specific parameters of oncogenic progression, yet few if any isoform-preferred substrates have been characterized. This review will describe recent data showing that the differential activation of AKT isoforms is mediated by complex interplays between PTEN, PI3K isoforms and upstream tyrosine kinases, and that the efficacy of PI3K/AKT inhibitors will likely depend on the successful targeting of specific AKT isoforms and their preferred pathways.
Imaging of T-cell Responses in the Context of Cancer Immunotherapy
Authors: Xiao Zebin , Puré Ellen 
Published: May 2021

AbstractImmunotherapy, which promotes the induction of cytotoxic T lymphocytes and enhances their infiltration into and function within tumors, is a rapidly expanding and evolving approach to treating cancer. However, many of the critical denominators for inducing effective anticancer immune responses remain unknown. Efforts are underway to develop comprehensive ex vivo assessments of the immune landscape of patients prior to and during response to immunotherapy. An important complementary approach to these efforts involves the development of noninvasive imaging approaches to detect immune targets, assess delivery of immune-based therapeutics, and evaluate responses to immunotherapy. Herein, we review the merits and limitations of various noninvasive imaging modalities (MRI, PET, and single-photon emission tomography) and discuss candidate targets for cellular and molecular imaging for visualization of T-cell responses at various stages along the cancer–immunity cycle in the context of immunotherapy. We also discuss the potential use of these imaging strategies in monitoring treatment responses and predicting prognosis for patients treated with immunotherapy.