bluuebunny/crossref_metadata_2025_split huggingface dataset:
Air pollution and childhood respiratory consultations in primary care: a systematic review
Authors: Fonderson Mata Sabine , van Meel Evelien R , Bindels Patrick , Bohnen Arthur , Burdorf Alex , de Schepper Evelien 
Published: January 2024

BackgroundOutdoor air pollution is a known risk factor for respiratory morbidity worldwide. Compared with the adult population, there are fewer studies that analyse the association between short-term exposure to air pollution and respiratory morbidity in children in primary care.ObjectiveTo evaluate whether children in a primary care setting exposed to outdoor air pollutants during short-term intervals are at increased risk of respiratory diagnoses.MethodsA search in Medline, the Cochrane Library, Web of Science and Embase databases throughout March 2023. Percentage change or risk ratios with corresponding 95% CI for the association between air pollutants and respiratory diseases were retrieved from individual studies. Risk of bias assessment was conducted with the Newcastle–Ottawa Scale (NOS) for cohort or case–control studies and an adjusted NOS for time series studies.ResultsFrom 1366 studies, 14 were identified as meeting the inclusion criteria. Most studies had intermediate or high quality. A meta-analysis was not conducted due to heterogeneity in exposure and health outcome. Overall, studies on short-term exposure to air pollutants (carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and particulate matter ≤10 µm (PM10)) were associated with increased childhood respiratory consultations in primary care. In general, exposure to ozone was associated with a reduction in respiratory consultations.ConclusionsThe evidence suggests CO, SO2, NO2, PM10and PM2.5are risk factors for respiratory diseases in children in primary care in the short term. However, given the heterogeneity of the studies, interpretation of these findings must be done with caution.PROSPERO registration numberCRD42022259279.
Neurological development in children born moderately or late preterm: national cohort study
Authors: Mitha Ayoub , Chen Ruoqing , Razaz Neda , Johansson Stefan , Stephansson Olof , Altman Maria , Bolk Jenny 
Published: January 2024

AbstractObjectiveTo assess long term neurodevelopmental outcomes of children born at different gestational ages, particularly 32-33 weeks (moderately preterm) and 34-36 weeks (late preterm), compared with 39-40 weeks (full term).DesignNationwide cohort study.SettingSweden.Participants1 281 690 liveborn singleton children without congenital malformations born at 32+0to 41+6weeks between 1998 and 2012.Main outcome measuresThe primary outcomes of interest were motor, cognitive, epileptic, hearing, and visual impairments and a composite of any neurodevelopmental impairment, diagnosed up to age 16 years. Hazard ratios and 95% confidence intervals were estimated using Cox regression adjusted for parental and infant characteristics in the study population and in the subset of full siblings. Risk differences were also estimated to assess the absolute risk of neurodevelopmental impairment.ResultsDuring a median follow-up of 13.1 years (interquartile range 9.5-15.9 years), 75 311 (47.8 per 10 000 person years) liveborn singleton infants without congenital malformations had at least one diagnosis of any neurodevelopmental impairment: 5899 (3.6 per 10 000 person years) had motor impairment, 27 371 (17.0 per 10 000 person years) cognitive impairment, 11 870 (7.3 per 10 000 person years) epileptic impairment, 19 700 (12.2 per 10 000 person years) visual impairment, and 20 393 (12.6 per 10 000 person years) hearing impairment. Children born moderately or late preterm, compared with those born full term, showed higher risks for any impairment (hazard ratio 1.73 (95% confidence interval 1.60 to 1.87) and 1.30 (1.26 to 1.35); risk difference 4.75% (95% confidence interval 3.88% to 5.60%) and 2.03% (1.75% to 2.35%), respectively) as well as motor, cognitive, epileptic, visual, and hearing impairments. Risks for neurodevelopmental impairments appeared highest from 32 weeks (the earliest gestational age), gradually declined until 41 weeks, and were also higher at 37-38 weeks (early term) compared with 39-40 weeks. In the sibling comparison analysis (n=349 108), most associations remained stable except for gestational age and epileptic and hearing impairments, where no association was observed; for children born early term the risk was only higher for cognitive impairment compared with those born full term.ConclusionsThe findings of this study suggest that children born moderately or late preterm have higher risks of adverse neurodevelopmental outcomes. The risks should not be underestimated as these children comprise the largest proportion of children born preterm. The findings may help professionals and families achieve a better risk assessment and follow-up.
Adverse perinatal outcomes in gestational diabetes mellitus with and without SARS-CoV-2 infection during pregnancy: results from two nationwide registries in Germany
Authors: Liedtke Tatjana P , Weber Katharina S , Adamczewski Heinke , Weber Dietmar , Ramsauer Babett , Schaefer-Graf Ute M , Groten Tanja , Strathmann Eike A , Lieb Wolfgang , Rüdiger Mario , Pecks Ulrich , Kleinwechter Helmut J 
Published: January 2024

IntroductionPregnancy is a known independent risk factor for a severe course of COVID-19. The relationship of SARS-CoV-2 infection and gestational diabetes mellitus (GDM) on neonatal outcomes is unclear. Our aim was to determine if SARS-CoV-2 infection represents an independent risk factor for adverse perinatal outcomes in pregnancy with GDM.Research design and methodsWe compared data from two German registries including pregnant women with GDM, established during the SARS-CoV-2 pandemic (COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS), a multicenter prospective observational study) and already existing before the pandemic (German registry of pregnant women with GDM; GestDiab). In total, 409 participants with GDM and SARS-CoV-2 infection and 4598 participants with GDM, registered 2018–2019, were eligible for analyses. The primary fetal and neonatal outcomes were defined as: (1) combined: admission to neonatal intensive care unit, stillbirth, and/or neonatal death, and (2) preterm birth before 37+0 weeks of gestation. Large and small for gestational age, maternal insulin therapy, birth weight>4500 g and cesarean delivery were considered as secondary outcomes.ResultsWomen with SARS-CoV-2 infection were younger (32 vs 33 years) and had a higher median body mass index (28 vs 27 kg/m²). In CRONOS, more neonates developed the primary outcome (adjusted OR (aOR) 1.48, 95% CI 1.11 to 1.97) and were born preterm (aOR 1.50, 95% CI 1.07 to 2.10). Fasting glucose was higher in women in CRONOS versus GestDiab (5.4 vs 5.3 mmol/L) considering each 0.1 mmol/L increase was independently associated with a 5% higher risk of preterm birth among women in CRONOS only (aOR 1.05, 95% CI 1.01 to 1.09).ConclusionsGDM with SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse fetal and neonatal outcomes as compared with GDM without SARS-CoV-2 infection.
Baseline characteristics of children in the International PANS Registry (IPR) Epidemiology Study
Authors: Masterson Erin E , Gavin Jessica M 
Published: January 2024

PurposeThe International PANS Registry (IPR) Epidemiology Study is a registry-based, longitudinal study. We designed this study to improve phenotyping and characterisation of children with paediatric acute-onset neuropsychiatric syndrome (PANS) and PANS-like features and facilitate multidisciplinary and translational health research. This cohort provides new opportunities to address unresolved research questions related to the broad spectrum of heterogenous PANS-like conditions.ParticipantsInclusion in the IPR Epidemiology Study remains open indefinitely via IPR enrolment online. Participants include children with PANS or who have PANS-like features and their healthy siblings. We collected cross-sectional survey data based on parent report, including details on phenotypic traits and characteristics that, to our knowledge, have not been previously collected for this patient population. We describe the baseline characteristics of cases and their healthy siblings here.Findings to dateThe IPR Epidemiology Study currently includes 1781 individuals (1179 cases, 602 siblings; from 1010 households). Many households include a sibling (n=390, 39%) and some include multiple cases (n=205, 20%). Mean enrolment age was 11.3±4.3 years for cases and 10.1±5.3 for siblings. Leading PANS-like features include anxiety (94%), emotional lability (92%) and obsessions (90%). Onsets were sudden and dramatic (27%), gradual with a subsequent sudden and dramatic episode (68%) or a gradual progression (5%). The mean age at early signs/symptom onset was 4 years and 7 years at sudden and dramatic increases, respectively. Infection/illness was the most common suspected symptom trigger (84%). Nearly all cases had been treated with antibiotics (88%) and/or non-steroidal anti-inflammatory drugs (79%). Parents reported immune-related conditions in cases (18%) and their nuclear, biological family (48%; 39% in biological mothers).Future plansFuture plans include increasing sample size, collecting longitudinal survey data, recruiting appropriate study controls and expanding the scope of the database, prioritising medical record data integration and creating a linked biorepository. Secondary data analyses will prioritise identifying subgroups by phenotypic traits, maternal health and disease characteristics.
Artificial intelligence-supported diabetic retinopathy screening in Tanzania: rationale and design of a randomised controlled trial
Authors: Cleland Charles R , Bascaran Covadonga , Makupa William , Shilio Bernadetha , Sandi Frank A , Philippin Heiko , Marques Ana Patricia , Egan Catherine , Tufail Adnan , Keane Pearse A , Denniston Alastair K , Macleod David , Burton Matthew J 
Published: January 2024

IntroductionGlobally, diabetic retinopathy (DR) is a major cause of blindness. Sub-Saharan Africa is projected to see the largest proportionate increase in the number of people living with diabetes over the next two decades. Screening for DR is recommended to prevent sight loss; however, in many low and middle-income countries, because of a lack of specialist eye care staff, current screening services for DR are not optimal. The use of artificial intelligence (AI) for DR screening, which automates the grading of retinal photographs and provides a point-of-screening result, offers an innovative potential solution to improve DR screening in Tanzania.Methods and analysisWe will test the hypothesis that AI-supported DR screening increases the proportion of persons with true referable DR who attend the central ophthalmology clinic following referral after screening in a single-masked, parallel group, individually randomised controlled trial. Participants (2364) will be randomised (1:1 ratio) to either AI-supported or the standard of care DR screening pathway. Participants allocated to the AI-supported screening pathway will receive their result followed by point-of-screening counselling immediately after retinal image capture. Participants in the standard of care arm will receive their result and counselling by phone once the retinal images have been graded in the usual way (typically after 2–4 weeks). The primary outcome is the proportion of persons with true referable DR attending the central ophthalmology clinic within 8 weeks of screening. Secondary outcomes, by trial arm, include the proportion of persons attending the central ophthalmology clinic out of all those referred, sensitivity and specificity, number of false positive referrals, acceptability and fidelity of AI-supported screening.Ethics and disseminationThe London School of Hygiene & Tropical Medicine, Kilimanjaro Christian Medical Centre and Tanzanian National Institute of Medical Research ethics committees have approved the trial. The results will be submitted to peer-reviewed journals for publication.Trial registration numberISRCTN18317152.
Increased NAFLD risk in newly diagnosed patients with RA during the first 4 years of follow-up: a nationwide, population-based cohort study
Authors: Ho Wei-Li , Chen Hsin-Hua , Chen Po-Ku , Liao Tsai-Ling , Chang Shih-Hsin , Chen Yi-Ming , Lin Ching-Heng , Tang Kuo-Tung , Chen Der-Yuan 
Published: January 2024

BackgroundAlthough the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we examined NAFLD risk in patients with RA and identified the potential risk factors.DesignRetrospective study.SettingTaiwan.Participants2281 newly diagnosed patients with RA and selected 91 240 individuals without RA to match with patients with RA (1:40) by age, gender, income status and urbanisation level of the residence.OutcomesIn this retrospective study using the 2000–2018 claim data from two-million representative Taiwanese population, we identified and compared the incidence rates (IRs) of NAFLD and alcoholic fatty liver disease (AFLD) between RA and non-RA groups. Using multivariable regression analyses, we estimated adjusted HR (aHR) of NAFLD development in patients with RA compared with individuals without RA, with 95% CIs.ResultsThe incidences of NALFD and AFLD were not significantly different between individuals with RA and without RA during the 17-year follow-up period. However, patients with RA had significantly increased NAFLD risk during the first 4 years after RA diagnosis, with IR ratio of 1.66 fold (95% CI 1.18 to 2.33, p<0.005), but the risk was reduced after the first 4 years. Multivariable regression analyses revealed that aHR was 2.77-fold greater in patients not receiving disease-modifying anti-rheumatic drugs therapy than in non-RA subjects (p<0.05). Old age, women, low-income status and obesity could significantly predict NAFLD development.ConclusionsWe demonstrated elevated risk of NAFLD in patients with RA during the first 4 years after RA diagnosis, and old age, women, low-income status and obesity were significant predictors of NAFLD.
Perceptions of family medicine among long-term patients of a family medicine clinic in Japan: a mixed-methods study
Authors: Sato Kotaro , Michinobu Ryoko , Kusaba Tesshu 
Published: January 2024

ObjectivesTo examine the perceptions of family medicine among patients attending a family medicine clinic for over 10 years in Japan and explore the unique characteristics of a family medicine which was developed in the local community in northern Japan.DesignExplanatory, sequential mixed-method design comprising a survey by questionnaires and semistructured interviews.SettingThe study was conducted at one of the oldest family medicine primary care clinics in Japan. We surveyed and interviewed participants from November 2019 to March 2020.Participants144 patients who have attended a family medicine clinic since April 2009 completed the questionnaires. Semistructured interviews with nine participants were conducted.ResultsAmong the respondents, 131 (91%) reported having attended a family medicine clinic. In terms of their perceptions of what ‘family physicians’ do, 42 (35%) stated ‘a doctor who treats various diseases with a general view’, 34 (29%) stated ‘a doctor who treats outpatients and visit patients’ houses’, and 15 (13%) stated ‘a doctor whom one can consult for anything and is familiar with one’s family and lifestyle’. The results of the qualitative analysis revealed two themes with regard to patients’ perceptions of family medicine: ‘seeing the whole person and referring suitably’ and ‘medical care at home’. Patients’ perceptions of family medicine identified in the quantitative study were strongly associated with the characteristics extracted from the qualitative study.ConclusionPatients attending the family medicine clinic had clear perceptions of what family physicians do. The two major perceptions of the characteristics of family medicine were identified as ‘seeing the whole person and referring suitably’ and ‘medical care at home’.
Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma
Authors: Zhang Feng , Liu Wenfeng , Meng Fansheng , Jiang Qiuyu , Tang Wenqing , Liu Zhiyong , Lin Xiahui , Xue Ruyi , Zhang Si , Dong Ling 
Published: January 2024

BackgroundHepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy.MethodsIntratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy.ResultsSingle-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7highmacrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models.ConclusionsMacrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC.
LRP11 promotes stem-like T cells via MAPK13-mediated TCF1 phosphorylation, enhancing anti-PD1 immunotherapy
Authors: Sun Lingjuan , Ma Zhibo , Zhao Xiangli , Tan Xiaosheng , Tu Yuhao , Wang Jingzeng , Chen Li , Chen Zhishui , Chen Gang , Lan Peixiang 
Published: January 2024

BackgroundTumor-infiltrating T cells enter an exhausted or dysfunctional state, which limits antitumor immunity. Among exhausted T cells, a subset of cells with features of progenitor or stem-like cells has been identified as TCF1+CD8+T cells that respond to immunotherapy. In contrast to the finding that TCF1 controls epigenetic and transcriptional reprogramming in tumor-infiltrating stem-like T cells, little is known about the regulation of TCF1. Emerging data show that elevated body mass index is associated with outcomes of immunotherapy. However, the mechanism has not been clarified.MethodsWe investigated the proliferation of splenic lymphocytes or CD8+T cells induced by CD3/CD28 stimulation in vitro. We evaluated the effects of low-density lipoprotein (LDL) and LRP11 inhibitors, as well as MAPK13 inhibitors. Additionally, we used shRNA technology to validate the roles of LRP11 and MAPK13. In an in vivo setting, we employed male C57BL/6J injected with B16 cells or MC38 cells to build a tumor model to assess the effects of LDL and LRP11 inhibitors, LRP11 activators, MAPK13 inhibitors on tumor growth. Flow cytometry was used to measure cell proportions and activation status. Molecular interactions and TCF1 status were examined using Western blotting. Moreover, we employed RNA sequencing to investigate the effects of LDL stimulation and MAPK13 inhibition in CD8+T cells.ResultsBy using a tumor-bearing mouse model, we found that LDL-induced tumor-infiltrating TCF1+PD1+CD8+T cells. Using a cell-based chimeric receptor screening system, we showed that LRP11 interacted with LDL and activated TCF1. LRP11 activation enhanced TCF1+PD1+CD8+T-cell-mediated antitumor immunity, consistent with LRP11 blocking impaired T-cell function. Mechanistically, LRP11 activation induces MAPK13 activation. Then, MAPK13 phosphorylates TCF1, leading to increase of stem-like T cells.ConclusionsLRP11-MAPK13-TCF1 enhanced antitumor immunity and induced tumor-infiltrating stem-like T cells.
Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer
Authors: Gu Chuanjia , Wang Xue , Wang Kaiyu , Xie Fangfang , Chen Luonan , Ji Hongbin , Sun Jiayuan 
Published: January 2024

BackgroundCryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated the local and systemic immunological effects of cryoablation and the potential of combining cryoablation with programmed cell death protein 1 (PD-1) blockade to boost immunotherapy efficacy in NSCLC.MethodsWe first investigated systemic immunological effects induced by cryoablation in patients with early-stage NSCLC. Subsequently, we explored cryoablation-induced antitumor immunity and the underlying biological mechanisms using KP (KrasG12D/+,Tp53−/−) mutant lung cancer cell allograft mouse models. Moreover, the synergistic efficacy of cryoablation and PD-1 blockade was explored in both mouse models and patients with unresectable NSCLC.ResultsWe found that cryoablation significantly increased circulating CD8+T cell subpopulations and proinflammatory cytokines in patients with early-stage NSCLC. In lung cancer cell allograft mouse models, we demonstrated that cryoablation resulted in abscopal growth inhibition of contralateral, non-ablated tumors. Integrated analysis of bulk, single-cell RNA and T cell receptor (TCR) sequencing data revealed that cryoablation reprogrammed the intratumoral immune microenvironment and increased CD8+T cell infiltration with higher effector signature, interferon (IFN) response, and cytolytic activity. Mechanistically, cryoablation promoted antitumor effect through the STING-dependent type I IFN signaling pathway, and type I IFN signaling blockade attenuated this antitumor effect. We also found that the combination of PD-1 blockade with cryoablation further inhibited tumor growth compared with either treatment alone in an allograft mouse model. Moreover, the combination therapy induced notable tumor suppression and CD8+T cell infiltration in patients with unresectable NSCLC.ConclusionsOur results provide mechanistic insights into how cryoablation triggers the antitumor immune effect in lung cancer, thereby potentiating programmed cell death ligand 1 (PD-L1)/PD-1 blockade efficacy in the clinical treatment of NSCLC.
Developing predictions for pion fragmentation functions
Authors: Xing H.-Y. , Yao Z.-Q. , Li B.-L. , Binosi D. , Cui Z.-F. , Roberts C. D. 
Published: January 2024

AbstractExploiting crossing symmetry, the hadron scale pion valence quark distribution function is used to predict the kindred elementary valence quark fragmentation function (FF). This function defines the kernel of a quark jet fragmentation equation, which is solved to obtain the full pion FFs. After evolution to a scale typical of FF fits to data, the results for quark FFs are seen to compare favourably with such fits. However, the gluon FF is markedly different. Notably, although FF evolution equations do not themselves guarantee momentum conservation, inclusion of a gluon FF which, for four quark flavours, distributes roughly 11% of the total light-front momentum fraction, is sufficient to restore momentum conservation under evolution. Overall, significant uncertainty is attached to FFs determined via fits to data; hence, the features of the predictions described herein could potentially provide useful guidance for future such studies.