bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in drug poisoning deaths, by sex, in Ireland: a repeated cross-sectional study from 2004 to 2017
Authors: Lynn Ena , Cousins Gráinne , Lyons Suzi , Bennett Kathleen E 
Published: September 2021

ObjectiveTo examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017.DesignRepeated cross-sectional study.SettingDrug poisoning deaths in Ireland.ParticipantsNational Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017.Outcome measuresThe primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004–2017), change points over time and average annual percentage changes (AAPCs) with 95% CI.ResultsIncreased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3).ConclusionDrugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.
Electrophysiological ventricular substrate of stroke: a prospective cohort study in the Atherosclerosis Risk in Communities (ARIC) study
Authors: Johnson John A , Haq Kazi T , Lutz Katherine J , Peters Kyle K , Paternostro Kevin A , Craig Natalie E , Stencel Nathan W L , Hawkinson Lila F , Khayyat-Kholghi Maedeh , Tereshchenko Larisa G 
Published: September 2021

ObjectivesThe goal of the study was to determine an association of cardiac ventricular substrate with thrombotic stroke (TS), cardioembolic stroke (ES) and intracerebral haemorrhage (ICH).DesignProspective cohort study.SettingThe Atherosclerosis Risk in Communities (ARIC) study in 1987–1989 enrolled adults (45–64 years), selected as a probability sample from four US communities (Minneapolis, Minnesota; Washington, Maryland; Forsyth, North Carolina; Jackson, Mississippi). Visit 2 was in 1990–1992, visit 3 in 1993–1995, visit 4 in 1996–1998 and visit 5 in 2011–2013.ParticipantsARIC participants with analysable ECGs and no history of stroke were included (n=14 479; age 54±6 y; 55% female; 24% black). Ventricular substrate was characterised by cardiac memory, spatial QRS-T angle (QRS-Ta), sum absolute QRST integral (SAIQRST), spatial ventricular gradient magnitude (SVGmag), premature ventricular contractions (PVCs) and tachycardia-dependent intermittent bundle branch block (TD-IBBB) on 12-lead ECG at visits 1–5.OutcomeAdjudicated TS included a first definite or probable thrombotic cerebral infarction, ES—a first definite or probable non-carotid cardioembolic brain infarction. Definite ICH was included if it was the only stroke event.ResultsOver a median 24.5 years follow-up, there were 899 TS, 400 ES and 120 ICH events. Cox proportional hazard risk models were adjusted for demographics, cardiovascular disease, risk factors, atrial fibrillation, atrial substrate and left ventricular hypertrophy. After adjustment, PVCs (HR 1.72; 95% CI 1.02 to 2.92), QRS-Ta (HR 1.15; 95% CI 1.03 to 1.28), SAIQRST (HR 1.20; 95% CI 1.07 to 1.34) and time-updated SVGmag (HR 1.19; 95% CI 1.08 to 1.32) associated with ES. Similarly, PVCs (HR 1.53; 95% CI 1.03 to 2.26), QRS-Ta (HR 1.08; 95% CI 1.01 to 1.16), SAIQRST (HR 1.07; 95% CI 1.01 to 1.14) and time-updated SVGmag (HR 1.11; 95% CI 1.04 to 1.19) associated with TS. TD-IBBB (HR 3.28; 95% CI 1.03 to 10.46) and time-updated SVGmag (HR 1.23; 95% CI 1.03 to 1.47) were associated with ICH.ConclusionsPVC burden (reflected by cardiac memory) is associated with ischaemic stroke. Transient cardiac memory (likely through TD-IBBB) precedes ICH.
Assessing the capacity of symptom scores to predict COVID-19 positivity in Nigeria: a national derivation and validation cohort study
Authors: Elimian Kelly Osezele , Aderinola Olaolu , Gibson Jack , Myles Puja , Ochu Chinwe Lucia , King Carina , Okwor Tochi , Gaudenzi Giulia , Olayinka Adebola , Zaiyad Habib Garba , Ohonsi Cornelius , Ebhodaghe Blessing , Dan-Nwafor Chioma , Nwachukwu William , Abdus-salam Ismail Adeshina , Akande Oluwatosin Wuraola , Falodun Olanrewaju , Arinze Chinedu , Ezeokafor Chidiebere , Jafiya Abubakar , Ojimba Anastacia , Aremu John Tunde , Joseph Emmanuel , Bowale Abimbola , Mutiu Bamidele , Saka Babatunde , Jinadu Arisekola , Hamza Khadeejah , Ibeh Christian , Bello Shaibu , Asuzu Michael , Mba Nwando , Oladejo John , Ilori Elsie , Alfvén Tobias , Igumbor Ehimario , Ihekweazu Chikwe 
Published: September 2021

ObjectivesThis study aimed to develop and validate a symptom prediction tool for COVID-19 test positivity in Nigeria.DesignPredictive modelling study.SettingAll Nigeria States and the Federal Capital Territory.ParticipantsA cohort of 43 221 individuals within the national COVID-19 surveillance dataset from 27 February to 27 August 2020. Complete dataset was randomly split into two equal halves: derivation and validation datasets. Using the derivation dataset (n=21 477), backward multivariable logistic regression approach was used to identify symptoms positively associated with COVID-19 positivity (by real-time PCR) in children (≤17 years), adults (18–64 years) and elderly (≥65 years) patients separately.Outcome measuresWeighted statistical and clinical scores based on beta regression coefficients and clinicians’ judgements, respectively. Using the validation dataset (n=21 744), area under the receiver operating characteristic curve (AUROC) values were used to assess the predictive capacity of individual symptoms, unweighted score and the two weighted scores.ResultsOverall, 27.6% of children (4415/15 988), 34.6% of adults (9154/26 441) and 40.0% of elderly (317/792) that had been tested were positive for COVID-19. Best individual symptom predictor of COVID-19 positivity was loss of smell in children (AUROC 0.56, 95% CI 0.55 to 0.56), either fever or cough in adults (AUROC 0.57, 95% CI 0.56 to 0.58) and difficulty in breathing in the elderly (AUROC 0.53, 95% CI 0.48 to 0.58) patients. In children, adults and the elderly patients, all scoring approaches showed similar predictive performance.ConclusionsThe predictive capacity of various symptom scores for COVID-19 positivity was poor overall. However, the findings could serve as an advocacy tool for more investments in resources for capacity strengthening of molecular testing for COVID-19 in Nigeria.
Cross-sectional association between long working hours and endoscopic gastritis: the Kangbuk Samsung Health Study
Authors: Mun Eunchan , Lee Yesung , Lee Woncheol , Park Soyoung 
Published: September 2021

ObjectivesThis study aimed to determine the cross-sectional association between long working hours and gastritis diagnosed by endoscopy.DesignCross-sectional study.SettingLarge university hospitals in Seoul and Suwon, South Korea.ParticipantsWorkers in formal employment who underwent a comprehensive health examination at the Kangbuk Samsung Hospital Total Healthcare Centre clinics in Seoul and Suwon, South Korea, between January 2011 and December 2018. Of the 386 488 participants, 168 391 full-time day workers met the inclusion criteria and were included in the analysis.Primary outcome measureEndoscopic gastritis.ResultsThe participants were predominantly college graduates or above (88.9%), male (71.2%) and in their 30s (51.1%), and the median age was 36 (IQR 31–42). Approximately 93.2% of participants had positive endoscopic gastritis, and there was a significant association between working hours and positive findings of endoscopic gastritis. The multivariate fully adjusted prevalence ratio (PR) of endoscopic gastritis for participants working >55 hours per week compared with 35–40 hours per week was 1.011 (95% CI 1.007 to 1.015). Furthermore, endoscopic findings were classified into nine subtypes of gastritis, including superficial gastritis, erosive gastritis, atrophic gastritis, intestinal metaplasia and haemorrhagic gastritis increased with longer working hours (p for trends <0.05). Their PRs for participants working >55 hours per week compared with 35–40 hours per week were 1.019 (95% CI 1.012 to 1.026), 1.025 (95% CI 1.011 to 1.040), 1.017 (95% CI 1.008 to 1.027), 1.066 (95% CI 1.028 to 1.105) and 1.177 (95% CI 1.007 to 1.375), respectively.ConclusionsWorking over 55 hours per week was cross-sectionally associated with positive findings of endoscopic gastritis. The study findings indicated potentially increased risks of superficial gastritis, erosive gastritis, atrophic gastritis, intestinal metaplasia and haemorrhagic gastritis among workers with long working hours (>55 hours per week), supporting the need for further exploration via longitudinal studies.
Protocol for a multicentre, randomised, parallel-control, superiority trial comparing administration of clotting factor concentrates with a standard massive haemorrhage protocol in severely bleeding trauma patients: the FiiRST 2 trial (a 2020 EAST multicentre trial)
Authors: da Luz Luis Teodoro , Callum Jeannie , Beckett Andrew , Hucke Hans-Peter , Carroll Jo , Grewal Deep , Schwartz Bruce , Peng Henry , Engels Paul T , Parry Neil , Petrosoniak Andrew , Tien Homer , Nathens Avery B , Scales Damon , Karkouti Keyvan 
Published: September 2021

IntroductionAcute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma.Methods and analysisThe factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study.Ethics and disseminationThe study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma.Trial registration numberNCT04534751, pre results.
Implementing person-centred outcome measures (PCOMs) into routine palliative care: A protocol for a mixed-methods process evaluation of The RESOLVE PCOM Implementation Strategy
Authors: Bradshaw Andy , Santarelli Martina , Khamis Assem M , Sartain Kathryn , Johnson Miriam , Boland Jason , Pearson Mark , Murtagh Fliss E M 
Published: September 2021

IntroductionPerson-centred outcome measures improve quality of care and patient outcomes but are used inconsistently in palliative care practice. To address this implementation gap, we developed the ‘RESOLVE Implementation Strategy’. This protocol describes a process evaluation to explore mechanisms through which this strategy does, or does not, support the implementation of outcome measures in routine palliative care practice.Methods and analysisMultistrand, mixed-methods process evaluation. Strand one will collect routine outcomes data (palliative Phase of Illness, Integrated Palliative care Outcomes Scale, Australia-modified Karnofsky Performance Status) to map the changes in use of outcome measures over 12 months (July 2021–July 2022). Strand two will collect survey data over the same 12-month period to explore how professionals’ understandings of, skills in using and ability to build organisational practices around, outcome measures change over time. Strand three will collect interview data to understand the mechanisms underpinning/affecting our implementation strategy. Thematic framework analysis and descriptive statistics will be used to analyse qualitative and quantitative data, respectively.Ethics and disseminationFor strand one, ethical approval has been obtained (Cambridge REC, REF: 20/EE/0188). For strands two and three, ethical approval has been obtained from Hull York Medical School ethics committee (2105). Tailored feedback of study findings will be provided to participating sites. Abstracts and papers will be submitted to national/international conferences and peer-reviewed journals. Lay and policy briefings and newsletters will be shared through patient and public involvement and project networks, plus via the project website.
Additive effects of variants of unknown significance in replication repair-associated DNA polymerase genes on mutational burden and prognosis across diverse cancers
Authors: Ying Jieer , Yang Lin , Yin Jiani C , Xia Guojie , Xing Minyan , Chen Xiaoxi , Pang Jiaohui , Wu Yong , Bao Hua , Wu Xue , Shao Yang , Zhu Lingjun , Cheng Xiangdong 
Published: September 2021

BackgroundDefects in replication repair-associated DNA polymerases often manifest an ultra-high tumor mutational burden (TMB), which is associated with higher probabilities of response to immunotherapies. The functional and clinical implications of different polymerase variants remain unclear.MethodsTargeted next-generation sequencing using a 425-cancer gene panel, which covers all exonic regions of three polymerase genes (POLE,POLD1, andPOLH), was conducted in a cohort of 12,266 patients across 16 different tumor types from January 2017 to January 2019. Prognostication ofPOLvariant-positive patients was performed using a cohort of 4679 patients from the The Cancer Genome Atlas (TCGA) datasets.ResultsThe overall prevalence of somatic and germline polymerase variants was 4.2% (95% CI 3.8% to 4.5%) and 0.7% (95% CI 0.5% to 0.8%), respectively, with highest frequencies in endometrial, urinary, prostate, and colorectal cancers (CRCs). While most germline polymerase variants showed no clear functional consequences, we identified a candidate p.T466A affecting the exonuclease domain of POLE, which might be underlying the early onset in a case with childhood CRC. Low frequencies of known hot-spot somatic mutations inPOLEwere detected and were associated with younger age, the male sex, and microsatellite stability. In both the panel and TCGA cohorts,POLEdrivers exhibited high frequencies of alterations in genes in the DNA damage and repair (DDR) pathways, includingBRCA2,ATM,MSH6, andATR. Variants of unknown significance (VUS) of different polymerase domains showed variable penetrance with those in the exonuclease domain ofPOLEandPOLD1displaying high TMB. VUS inPOLgenes exhibited an additive effect as carriers of multiple VUS had exponentially increased TMB and prolonged overall survival. Similar to cases with driver mutations, the TMB-highPOLVUS samples showed DDR pathway involvement and polymerase hypermutation signatures. Combinatorial analysis ofPOLand DDR pathway status further supported the potential additive effects ofPOLVUS and DDR pathway genes and revealed distinct prognostic subclasses that were independent of cancer type and TMB.ConclusionsOur results demonstrate the pathogenicity and additive prognostic value ofPOLVUS and DDR pathway gene alterations and suggest that genetic testing may be warranted in patients with diverse solid tumors.
Non-equilibrium phase separation in mixtures of catalytically active particles: size dispersity and screening effects
Authors: Ouazan-Reboul Vincent , Agudo-Canalejo Jaime , Golestanian Ramin 
Published: September 2021

Abstract
Biomolecular condensates in cells are often rich in catalytically active enzymes. This is particularly true in the case of the large enzymatic complexes known as metabolons, which contain different enzymes that participate in the same catalytic pathway. One possible explanation for this self-organization is the combination of the catalytic activity of the enzymes and a chemotactic response to gradients of their substrate, which leads to a substrate-mediated effective interaction between enzymes. These interactions constitute a purely non-equilibrium effect and show exotic features such as non-reciprocity. Here, we analytically study a model describing the phase separation of a mixture of such catalytically active particles. We show that a Michaelis–Menten-like dependence of the particles’ activities manifests itself as a screening of the interactions, and that a mixture of two differently sized active species can exhibit phase separation with transient oscillations. We also derive a rich stability phase diagram for a mixture of two species with both concentration-dependent activity and size dispersity. This work highlights the variety of possible phase separation behaviours in mixtures of chemically active particles, which provides an alternative pathway to the passive interactions more commonly associated with phase separation in cells. Our results highlight non-equilibrium organizing principles that can be important for biologically relevant liquid-liquid phase separation.

Graphic abstract
Henry Cavendish and the effect of gravity on propagation of light: a postscript
Authors: Lotze Karl-Heinz , Simionato Silvia 
Published: September 2021

AbstractThis paper is devoted to two hitherto unpublished original documents by Henry Cavendish (1731–1810) which provide insight into his calculations of the deflection of light by isolated celestial bodies. Together with a transcription of these documents, we comment on their contents in the present-day language of physics. Moreover, we compare them with a paper by Johann Georg von Soldner (1776–1833) on the same subject.
After-Action Review for AI (AAR/AI)
Authors: Dodge Jonathan , Khanna Roli , Irvine Jed , Lam Kin-ho , Mai Theresa , Lin Zhengxian , Kiddle Nicholas , Newman Evan , Anderson Andrew , Raja Sai , Matthews Caleb , Perdriau Christopher , Burnett Margaret , Fern Alan 
Published: September 2021

Explainable AI is growing in importance as AI pervades modern society, but few have studied how explainable AI can directly support people trying to
assess
an AI agent. Without a rigorous process, people may approach assessment in ad hoc ways—leading to the possibility of wide variations in assessment of the same agent due only to variations in their processes. AAR, or After-Action Review, is a method some military organizations use to assess human agents, and it has been validated in many domains. Drawing upon this strategy, we derived an After-Action Review for AI (AAR/AI), to organize ways people assess reinforcement learning agents in a sequential decision-making environment. We then investigated what AAR/AI brought to human assessors in two qualitative studies. The first investigated AAR/AI to gather formative information, and the second built upon the results, and also varied the type of explanation (model-free vs. model-based) used in the AAR/AI process. Among the results were the following: (1) participants reporting that AAR/AI helped to
organize their thoughts
and
think logically
about the agent, (2) AAR/AI encouraged participants to reason about the agent from a
wide range of perspectives
, and (3) participants were able to leverage AAR/AI with the model-based explanations to
falsify
the agent’s predictions.
CBIR Using Features Derived by Deep Learning
Authors: Maji Subhadip , Bose Smarajit 
Published: September 2021

In a Content-based Image Retrieval (CBIR) System, the task is to retrieve similar images from a large database given a query image. The usual procedure is to extract some useful features from the query image and retrieve images that have a similar set of features. For this purpose, a suitable similarity measure is chosen, and images with high similarity scores are retrieved. Naturally, the choice of these features play a very important role in the success of this system, and high-level features are required to reduce the “semantic gap.”
In this article, we propose to use features derived from pre-trained network models from a deep-learning convolution network trained for a large image classification problem. This approach appears to produce vastly superior results for a variety of databases, and it outperforms many contemporary CBIR systems. We analyse the retrieval time of the method and also propose a pre-clustering of the database based on the above-mentioned features, which yields comparable results in a much shorter time in most of the cases.