bluuebunny/crossref_metadata_2025_split huggingface dataset:
International modified Delphi study on malaria preventive behaviour: new themes, contexts and framework for future research onPlasmodium knowlesimalaria
Authors: Naserrudin Nurul Athirah , Hod Rozita , Saffree Jeffree Mohammad , Ahmed Kamruddin , Hassan Mohd Rohaizat 
Published: March 2023

IntroductionPlasmodium knowlesimalaria is a non-human simian malaria that threatens Southeast Asian rural communities. Studies indicate that non-compliant bednet usage, travelling into the forest and working as farmers and rubber tappers put communities at risk for infection. Despite guidelines, malaria incidence increases yearly and has become a public health concern. In addition to research gaps addressing factors that influence malaria prevention behaviour in these communities, there are no specific guidelines to facilitate strategies against the threat ofP. knowlesimalaria.MethodTo examine potential factors that influence malaria-prevention behaviour in communities exposed toP. knowlesimalaria, 12 malaria experts participated in a modified Delphi study; every participant maintained their anonymity throughout the study. Three Delphi rounds were conducted via different online platforms between 15 November 2021 and 26 February 2022, and consensus was achieved when 70% of the participants agreed on a particular point with a 4–5 median. The results from the open-ended questions were then subjected to thematic analysis, and the dataset generated by this study was analysed using a deductive and inductive approach.ResultsAfter a systematic, iterative process, knowledge and belief, social support, cognitive and environmental factors, past experience as a malaria patient, and the affordability and feasibility of a given intervention were critical contributors to malaria-prevention behaviour.ConclusionFuture research onP. knowlesimalaria could adapt this study’s findings for a more nuanced understanding of factors that influence malaria-prevention behaviour and improveP. knowlesimalaria programmes based on the expert consensus.
Estimating time and transportation costs associated with lung cancer screening and diagnostic lung procedures in Taiwan: a cross-sectional survey in a medical centre
Authors: Wu Chi-Hao , Ku Li-Jung Elizabeth , Lin Chien-Yu , Chung Ta-Jung , Liu Hui-Ju , Chao Ting-Hsing , Yang Szu-Chun 
Published: March 2023

ObjectivesEarlier research has evaluated the non-medical costs after lung cancer diagnosis. This study estimated the time costs and transportation costs associated with low-dose CT (LDCT) screening and diagnostic lung procedures in Taiwan.DesignCross-sectional study.SettingA tertiary referral medical centre.Participants and interventionsThe study participants were individuals aged 50–80 years who underwent LDCT screening or diagnostic lung procedures between 2021 and 2022. Participants completed a questionnaire including items on time spent on receiving care, time spent on travel and its cost and time taken off from work by the participant and any accompanying caregiver.Outcome measuresTime costs were valued using the age- and sex-specific average daily wage for employed participants/caregivers. Costs of informal healthcare sector consisted of time cost of the participant, transportation cost and time cost of the caregiver.ResultsA total of 209 participants who underwent LDCT screening (n=84) or non-surgical (n=12) or surgical (n=113) diagnostic lung procedures for the first time were enrolled. Considering the purchasing power parity, the average costs of informal healthcare sector were US$126.4 (95% CI 101.6 to 151.2), US$290.7 (95% CI 106.9 to 474.5) and US$749.8 (95% CI 567.3 to 932.4), respectively, for LDCT screening, non-surgical procedures and surgical procedures.ConclusionsThis study estimated time and transportation costs associated with LDCT screening and diagnostic lung procedures, which could be used for future analysis of cost-effectiveness of lung cancer screening in Taiwan.
Harnessing neuroplasticity to improve motor performance in infants with cerebral palsy: a study protocol for the GAME randomised controlled trial
Authors: Morgan Catherine , Badawi Nadia , Boyd Roslyn N , Spittle Alicia J , Dale Russell C , Kirby Adrienne , Hunt Rod W , Whittingham Koa , Pannek Kerstin , Morton Rachael L , Tarnow-Mordi William , Fahey Michael C , Walker Karen , Prelog Kristina , Elliott Catherine , Valentine Jane , Guzzetta Andrea , Olivey Shannon ,   the GAME study team, Novak Iona 
Published: March 2023

IntroductionCerebral palsy (CP) is the most common physical disability of childhood worldwide. Historically the diagnosis was made between 12 and 24 months, meaning data about effective early interventions to improve motor outcomes are scant. In high-income countries, two in three children will walk. This evaluator-blinded randomised controlled trial will investigate the efficacy of an early and sustained Goals–Activity–Motor Enrichment approach to improve motor and cognitive skills in infants with suspected or confirmed CP.Methods and analysisParticipants will be recruited from neonatal intensive care units and the community in Australia across four states. To be eligible for inclusion infants will be aged 3–6.5 months corrected for prematurity and have a diagnosis of CP or ‘high risk of CP’ according to the International Clinical Practice Guideline criteria. Eligible participants whose caregivers consent will be randomly allocated to receive usual care or weekly sessions at home from a GAME-trained study physiotherapist or occupational therapist, paired with a daily home programme, until age 2. The study requires 150 participants per group to detect a 0.5 SD difference in motor skills at 2 years of age, measured by the Peabody Developmental Motor Scales-2. Secondary outcomes include gross motor function, cognition, functional independence, social–emotional development and quality of life. A within-trial economic evaluation is also planned.Ethics and disseminationEthical approval was obtained from the Sydney Children’s Hospital Network Human Ethics Committee in April 2017 (ref number HREC/17/SCHN/37). Outcomes will be disseminated through peer-reviewed journal publications, presentations at international conferences and consumer websites.Trial registration numberACTRN12617000006347.
Rates of malignancies among patients with moderate to severe atopic dermatitis: a retrospective cohort study
Authors: Hedderson Monique M , Asgari Maryam M , Xu Fei , Quesenberry Charles P , Sridhar Sneha , Geier Jamie , Lemeshow Adina R 
Published: March 2023

ObjectivesPatients with atopic dermatitis (AD), also known as eczema, may be at an increased risk for malignancies compared with patients without AD; however, incidence rates (IRs) of malignancies in patients with moderate to severe AD are largely unknown. The objective of this study was to evaluate and compare IRs of malignancies in adults with moderate to severe AD (aged ≥18 years).DesignRetrospective cohort study using data from a Kaiser Permanente Northern California (KPNC) cohort. AD severity classification was adjudicated with medical chart review. Covariates and stratification variables included age, sex and smoking status.SettingData were obtained from the KPNC healthcare delivery system in northern California, USA. Cases of AD were defined by outpatient dermatologist-rendered codes and prescriptions of topical therapy or phototherapy (moderate) or systemic treatment (severe).ParticipantsKPNC health plan members with moderate or severe AD (2007–2018).Primary and secondary outcome measuresMalignancy IRs and 95% CIs per 1000 person-years were calculated.Results7050 KPNC health plan members with moderate and severe AD met eligibility criteria for inclusion. IRs (95% CI) were highest for non-melanoma skin cancer (NMSC) in patients with moderate and severe AD (4.6 (95% CI 3.9 to 5.5) and 5.9 (95% CI 3.8 to 9.2), respectively) and breast cancer (2.2 (95% CI 1.6 to 3.0) and 0.5 (95% CI 0.1 to 3.9), respectively). Except for breast cancer, which was only evaluated in women, malignancies were higher (with non-overlapping CIs) in patients with moderate and moderate to severe AD in men versus women for basal cell carcinoma and NMSC and in former versus never smokers for NMSC and squamous cell carcinoma.ConclusionsThis study estimated IRs of malignancies in patients with moderate and severe AD and provides valuable information for dermatology clinicians and ongoing clinical trials in these populations.
Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics (STARSHIP): protocol to study cerebral autoregulation in a prospective multicentre observational research database study
Authors: Agrawal Shruti , Placek Michal M , White Deborah , Daubney Esther , Cabeleira Manuel , Smielewski Peter , Czosnyka Marek , Young Adam , Watson Suzanna , Maw Anna , Hutchinson Peter John 
Published: March 2023

IntroductionStudying cerebral autoregulation, particularly PRx (Pressure Reactivity Index), is commonly employed in adult traumatic brain injury (TBI) and gives real-time information about intracranial pathophysiology, which can help in patient management. Experience in paediatric TBI (PTBI) is limited to single-centre studies despite disproportionately higher incidence of morbidity and mortality in PTBI than in adult TBI.ProjectWe describe the protocol to study cerebral autoregulation using PRx in PTBI. The project called Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics is a multicentre prospective ethics approved research database study from 10 centres across the UK. Recruitment started in July 2018 with financial support from local/national charities (Action Medical Research for Children, UK).Methods and analysisThe first phase of the project is powered to detect optimal thresholds of PRx associated with favourable outcome in PTBI by recruiting 135 patients (initial target of 3 years which has changed to 5 years due to delays related to COVID-19 pandemic) from 10 centres in the UK with outcome follow-up to 1-year postictus. The secondary objectives are to characterise patterns of optimal cerebral perfusion pressure in PTBI and compare the fluctuations in these measured parameters with outcome. The goal is to create a comprehensive research database of a basic set of high-resolution (full waveforms resolution) neuromonitoring data in PTBI for scientific use.Ethics and disseminationFavourable ethical approval has been provided by Health Research Authority, Southwest-Central Bristol Research Ethics Committee (Ref: 18/SW/0053). Results will be disseminated via publications in peer-reviewed medical journals and presentations at national and international conferences.Trial registration numberNCT05688462.
Germline genetic variants are associated with development of insulin-dependent diabetes in cancer patients treated with immune checkpoint inhibitors
Authors: Caulfield Jasmine I , Aizenbud Lilach , Perdigoto Ana Luisa , Meffre Eric , Jilaveanu Lucia , Michalek Dominika A , Rich Stephen S , Aizenbud Yariv , Adeniran Adebowale , Herold Kevan C , Austin Matthew R , Kluger Harriet 
Published: March 2023

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically improved survival in patients with cancer but are often accompanied by severe immune-related adverse events (irAEs), which can sometimes be irreversible. Insulin-dependent diabetes is a rare, but life-altering irAE. Our purpose was to determine whether recurrent somatic or germline mutations are observed in patients who develop insulin-dependent diabetes as an irAE.MethodsWe performed RNA and whole exome sequencing on tumors from 13 patients who developed diabetes due to ICI exposure (ICI-induced diabetes mellitus, ICI-DM) compared with control patients who did not develop diabetes.ResultsIn tumors from ICI-DM patients, we did not find differences in expression of conventional type 1 diabetes autoantigens, but we did observe significant overexpression of ORM1, PLG, and G6PC, all of which have been implicated in type 1 diabetes or are related to pancreas and islet cell function. Interestingly, we observed a missense mutation in NLRC5 in tumors of 9 of the 13 ICI-DM patients that was not observed in the control patients treated with the same drugs for the same cancers. Germline DNA from the ICI-DM patients was sequenced; allNLRC5mutations were germline. The prevalence ofNLRC5germline variants was significantly greater than the general population (p=5.98×10−6). Although NLRC5 is implicated in development of type 1 diabetes, germlineNLRC5mutations were not found in public databases from patients with type 1 diabetes, suggesting a different mechanism of insulin-dependent diabetes in immunotherapy-treated patients with cancer.ConclusionsValidation of theNLRC5mutation as a potential predictive biomarker is warranted, as it might improve patient selection for treatment regimens. Furthermore, this genetic alteration suggests potential mechanisms of islet cell destruction in the setting of checkpoint inhibitor therapy.
Core overestimation of CT perfusion in patients with cardiac insufficiency who had a stroke is mediated by impaired collaterals
Authors: He Guangchen , Wei Liming , Lu Haitao , Deng Jiangshan , Wang Feng , Zhu Yueqi 
Published: March 2023

BackgroundWe hypothesized that left ventricular systolic dysfunction (LVSD) would lead to an ischemic core overestimation in patients with acute ischemic stroke (AIS), and impaired collateral status might partly mediate this effect.ObjectiveA pixel-based analysis of CT perfusion (CTP) and follow-up CT was undertaken to investigate the optimum CTP thresholds for the ischemic core if overestimation was found.MethodsA total of 208 consecutive patients with AIS with large vessel occlusion in the anterior circulation, who received initial CTP evaluation and successful reperfusion, were retrospectively analyzed and divided into an LVSD (left ventricular ejection fraction (LVEF) ratio <50%; n=40) and a normal cardiac function (LVEF≥50%; n=168) group. Ischemic core overestimation was considered when the CTP-derived core was larger than the final infarct volume. We investigated the relationship between cardiac function, probability for core overestimation, and collateral scores using mediation analysis. A pixel-based analysis was undertaken to define the optimum CTP thresholds for ischemic core.ResultsLVSD was independently associated with impaired collaterals (aOR=4.28, 95% CI 2.01 to 9.80, P<0.001) and core overestimation (aOR=2.52, 95% CI 1.07 to 5.72, P=0.030). In mediation analysis, the total effect on core overestimation is composed of the direct effect of LVSD (+17%, P=0.034) and the mediated indirect effect of collateral status (+6%, P=0.020). Collaterals explained 26% of the effect of LVSD on core overestimation. Compared with relative cerebral blood flow (rCBF) thresholds of <35%, <30%, and <20%, a rCBF <25% cut-off point had the highest correlation (r=0.91) and best agreement (mean difference 3.2±7.3 mL) with the final infarct volume to determine the CTP-derived ischemic core in patients with LVSD.ConclusionsLVSD increased the possibility of ischemic core overestimation on baseline CTP, partly due to impaired collateral status, and a stricter rCBF threshold should be considered.
Cosmic expansion of the universe characterized by anisotropic viscous fluid cosmological models
Authors: Dixit Archana , Chawla Chanchal , Pradhan Anirudh 
Published: March 2023

In this paper, the cosmic expansion of the universe filled with viscous fluid has been discussed in Bianchi type-I space-time. To solve Einstein’s field equations, a time-varying deceleration parameter, ( q( t)) yields a time variable scale factor [Formula: see text], with " α" and " n" are positive constants. We also consider a time-varying gravitational constant ( G) via the formulation 8π G = G0 a m , where " G0" and " m" are positive constants. Further, based on the third constraint, two different viscous cosmological models, one by considering the perfect gas equation of state p = ωρ and the other by considering time-varying bulk viscosity coefficient ( ξ( t)), have been constructed. It is mentioned here that this particular choice of scale factor generates a class of accelerating models for n < 1, while for n > 1, the transition of the universe from early deceleration to current acceleration takes place. An important feature of the models is decreasing dark energy candidate, i.e., cosmological constant (Λ) with time, fine-tuning with the results from recent supernovae Ia observations. The various physical parameters involved in the models have been discussed analytically and graphically and are found in good agreement with recent observations. For the physical acceptability of both the models, energy conditions are shown graphically. The models are found to be physically acceptable, particularly in identifying the universe’s transition. We have discussed the statefinder and observed that all the trajectories indicate dark energy candidates as Chaplygin gas and quintessence for different constraints ( α, n). We have also calculated the cosmographic parameters such as jerk, lerk, and maxout to analyze the physical behavior of the DE models.
Arithmetic Chern–Simons theory with real places
Authors: Lee Jungin , Park Jeehoon 
Published: March 2023

The goal of this paper is two-fold: we generalize the arithmetic Chern–Simons theory over totally imaginary number fields studied in [H.-J. Chung, D. Kim, M. Kim, J. Park and H. Yoo, Arithmetic Chern–Simons theory II, preprint (2016), arXiv:1609.03012v3; M. Kim, Arithmetic Chern–Simons theory I, preprint (2015) arXiv:1510.05818v4] to arbitrary number fields (with real places) and provide new examples of non-trivial arithmetic Chern–Simons invariant with coefficient [Formula: see text] [Formula: see text] associated to a non-abelian gauge group. The main idea for the generalization is to use cohomology with compact support (see [17]) to deal with real places. Before the results of this paper, non-trivial examples were limited to some non-abelian gauge group with coefficient [Formula: see text] in [H.-J. Chung, D. Kim, M. Kim, J. Park and H. Yoo, Arithmetic Chern–Simons theory II, preprint (2016), arXiv:1609.03012v3] and the abelian cyclic gauge group with coefficient [Formula: see text] in [H.-J. Chung, D. Kim, M. Kim, J. Park and H. Yoo, Arithmetic Chern–Simons theory II, preprint (2016), arXiv:1609.03012v3]. Our non-trivial examples (with non-abelian gauge group and general coefficient [Formula: see text]) will be given by a simple twisting argument based on examples of [F. Bleher, T. Chinburg, R. Greenberg, M. Kakde, G. Pappas and M. Taylor, Cup products in the étale cohomology of number fields, New York J. Math. 24 (2018) 514–542].
IL18 at the Crossroads between Chronic Inflammation and T-cell Exhaustion in Pancreatic Cancer
Authors: Stromnes Ingunn M. 
Published: March 2023

AbstractChronic inflammation and immune evasion are hallmarks of cancer. Cancer promotes T-cell differentiation toward an exhausted, or dysfunctional state, which contributes to immune evasion. In this issue, Lutz and colleagues show that the proinflammatory cytokine IL18 correlates with poor patient prognosis and promotes CD8+ T-cell exhaustion in pancreatic cancer by enhancing IL2R signaling. This link between proinflammatory cytokines and T-cell exhaustion elucidates consequences of modulating cytokine signaling during cancer immunotherapy.See related article by Lutz et al. p. 421 (1) .
Adverse Outcomes Associated With Interleukin-6 in Patients Recently Hospitalized for Heart Failure With Preserved Ejection Fraction
Authors: Mooney Leanne , Jackson Colette E. , Adamson Carly , McConnachie Alex , Welsh Paul , Myles Rachel C. , McMurray John J.V. , Jhund Pardeep S. , Petrie Mark C. , Lang Ninian N. 
Published: March 2023

Background:
Inflammation may play a role in the pathophysiology of heart failure with preserved ejection fraction. We examined whether circulating levels of interleukin-6 identify patients at greater risk of adverse outcomes following hospitalization with heart failure with preserved ejection fraction.

Methods:
We assessed relationships between interleukin-6 (IL-6) tertiles (T1-3) and all-cause death, cardiovascular death, and subsequent heart failure hospitalization (sHFH) in 286 patients recently hospitalized with heart failure with preserved ejection fraction. Associations between IL (interleukin)-6 and outcomes were examined in a Cox-regression model adjusted for risk factors including BNP (B-type natriuretic peptide). Biomarkers including hsCRP (high-sensitivity C-reactive protein) were assessed.

Results:

The range of IL-6 (pg/mL) in each tertile was T1 (0.71–4.16), T2 (4.20–7.84), and T3 (7.9–236.32). Compared with T1, patients in the highest IL-6 tertile were more commonly male (56% versus 35%) and had higher creatinine (117±45 versus 101±36 μmol/L), hsCRP (11.6 [4.9–26.6]mg/L versus 2.3[1.1–4.2] mg/L). In univariable analysis, rates of all-cause death, cardiovascular death, and sHFH were higher in T3 versus T1. All-cause and cardiovascular death rates remained higher in T3 versus T1 after adjustment (
P
<0.001). One log unit increase in IL-6 was associated with higher risk of all-cause death (hazard ratio, 1.46 [1.17–1.81]), cardiovascular death (hazard ratio, 1.40 [1.10–1.77]), and sHFH (hazard ratio, 1.24 [1.01–1.51]) after adjustment. One log unit increase in hsCRP was associated with a higher risk of cardiovascular death and all-cause death before and after adjustment for other factors but was not associated with risk of sHFH before or after adjustment.

Conclusions:
In patients recently hospitalized with heart failure with preserved ejection fraction, IL-6 is an independent predictor of all-cause mortality, cardiovascular death, and sHFH after adjustment for risk factors including BNP. These findings are of particular relevance in the context of current anti–IL-6 drug development.
A parcellation scheme of mouse isocortex based on reversals in connectivity gradients
Authors: Guyonnet-Hencke Timothé , Reimann Michael W. 
Published: March 2023

Abstract
The brain is composed of several anatomically clearly separated structures. This parcellation is often extended into the isocortex, based on anatomical, physiological, or functional differences. Here, we derive a parcellation scheme based purely on the spatial structure of long-range synaptic connections within the cortex. To that end, we analyzed a publicly available dataset of average mouse brain connectivity, and split the isocortex into disjunct regions. Instead of clustering connectivity based on modularity, our scheme is inspired by methods that split sensory cortices into subregions where gradients of neuronal response properties, such as the location of the receptive field, reverse. We calculated comparable gradients from voxelized brain connectivity data and automatically detected reversals in them. This approach better respects the known presence of functional gradients within brain regions than clustering-based approaches. Placing borders at the reversals resulted in a parcellation into 41 subregions that differs significantly from an established scheme in nonrandom ways, but is comparable in terms of the modularity of connectivity between regions. It reveals unexpected trends of connectivity, such as a tripartite split of somatomotor regions along an anterior to posterior gradient. The method can be readily adapted to other organisms and data sources, such as human functional connectivity.