bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiota modulates COPD pathogenesis: role of anti-inflammatoryParabacteroides goldsteiniilipopolysaccharide
Authors: Lai Hsin-Chih , Lin Tzu-Lung , Chen Ting-Wen , Kuo Yu-Lun , Chang Chih-Jung , Wu Tsung-Ru , Shu Ching-Chung , Tsai Ying-Huang , Swift Simon , Lu Chia-Chen 
Published: March 2021

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacteriumParabacteroides goldsteiniiwas isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived fromP. goldsteiniiis anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.
Racial differences in management and outcomes of acute myocardial infarction during COVID-19 pandemic
Authors: Rashid Muhammad , Timmis Adam , Kinnaird Tim , Curzen Nick , Zaman Azfar , Shoaib Ahmad , Mohamed Mohamed O , de Belder Mark A , Deanfield John , Martin Glen Philip , Wu Jianhua , Gale Chris P , Mamas Mamas 
Published: March 2021

ObjectiveThere are concerns that healthcare and outcomes of black, Asian and minority ethnic (BAME) communities are disproportionately impacted by the COVID-19 pandemic. We investigated admission rates, treatment and mortality of BAME with acute myocardial infarction (AMI) during COVID-19.MethodsUsing multisource national healthcare records, patients hospitalised with AMI in England during 1 February–27 May 2020 were included in the COVID-19 group, whereas patients admitted during the same period in the previous three consecutive years were included in a pre-COVID-19 group. Multilevel hierarchical regression analyses were used to quantify the changes in-hospital and 7-day mortality in BAME compared with whites.ResultsOf 73 746 patients, higher proportions of BAME patients (16.7% vs 10.1%) were hospitalised with AMI during the COVID-19 period compared with pre-COVID-19. BAME patients admitted during the COVID-19 period were younger, male and likely to present with ST-elevation acute myocardial infarction. COVID-19 BAME group admitted with non-ST-elevation acute myocardial infarction less frequently received coronary angiography (86.1% vs 90.0%, p<0.001) and had a longer median delay to reperfusion (4.1 hours vs 3.7 hours, p<0.001) compared with whites. BAME had higher in-hospital (OR 1.68, 95% CI 1.27 to 2.28) and 7-day mortality (OR 1.81 95% CI 1.31 to 2.19) during COVID-19 compared with pre-COVID-19 period.ConclusionIn this multisource linked cohort study, compared with whites, BAME patients had proportionally higher hospitalisation rates with AMI, less frequently received guidelines indicated care and had higher early mortality during COVID-19 period compared with pre-COVID-19 period. There is a need to develop clinical pathways to achieve equity in the management of these vulnerable populations.
Association of state-level intoxicated driving laws with firearm homicide and suicide
Authors: Tessler Robert A , Haviland Miriam Joan , Bowen Andrew , Bowen Deidre , Rivara Frederick P , Rowhani-Rahbar Ali 
Published: March 2021

ObjectivesTo determine if an association exists between the number of driving under the influence (DUI) convictions required to activate federal firearms prohibitions and annual firearm homicide and suicide rates by state.MethodsEcological cross-sectional study of all US states from 2013 to 2017. We collected DUI law data from Thomson Reuters Westlaw database and firearm mortality data from the Centers for Disease Control and Prevention Vital Statistics programme.ResultsFive states had laws such that one or two DUI convictions could result in prohibitions to firearms access according to federal law. Four states had no legal framework that would restrict firearms access because of DUI convictions; the remaining states could activate federal restrictions at three or more DUI convictions. Firearm-specific homicide (victimisations) rates were 19% lower among women in states where federal restrictions of firearms access occurred after one or two DUI offences (incidence rate ratio (IRR) 0.81; 95% CI 0.64 to 1.01) and 18% lower in states with firearm prohibitions after three or more offences (IRR 0.82; 95% CI 0.71 to 0.95) compared with the states with no legal framework for prohibiting firearms after DUI convictions. There was no association between number of DUI activations and overall, or firearm-specific, suicide among the entire population (men and women) or among only women, or only men.ConclusionsDUI penalties that activate federal firearms prohibitions may be one pathway to reduce firearm homicide of female victims.
Releasing the brakes of tumor immunity with anti-PD-L1 and pushing its accelerator with L19–IL2 cures poorly immunogenic tumors when combined with radiotherapy
Authors: Olivo Pimentel Veronica , Marcus Damiënne , van der Wiel Alexander MA , Lieuwes Natasja G , Biemans Rianne , Lieverse Relinde IY , Neri Dario , Theys Jan , Yaromina Ala , Dubois Ludwig J , Lambin Philippe 
Published: March 2021

BackgroundPoorly immunogenic tumors are hardly responsive to immunotherapies such as immune checkpoint blockade (ICB) and are, therefore, a therapeutic challenge. Combination with other immunotherapies and/or immunogenic therapies, such as radiotherapy (RT), could make these tumors more immune responsive. We have previously shown that the immunocytokine L19–IL2 combined with single-dose RT resulted in 75% tumor remission and a 20% curative abscopal effect in the T cell-inflamed C51 colon carcinoma model. This treatment schedule was associated with the upregulation of inhibitory immune checkpoint (IC) molecules on tumor-infiltrating T cells, leading to only tumor growth delay in the poorly immunogenic Lewis lung carcinoma (LLC) model.MethodsWe aimed to trigger curative therapeutic responses in three tumor models (LLC, C51 and CT26) by “pushing the accelerator” of tumor immunity with L19–IL2 and/or “releasing the brakes” with ICB, such as antibodies directed against cytotoxic T lymphocyte associated protein 4 (CTLA-4), programmed death 1 (PD-1) or its ligand (PD-L1), combined with single-dose RT (10 Gy or 5 Gy). Primary tumor endpoint was defined as time to reach four times the size of tumor volume at start of treatment (4T×SV). Multivariate analysis of 4T×SV was performed using the Cox proportional hazards model comparing each treatment group with controls. Causal involvement of T and natural killer (NK) cells in the anti-tumor effect was assessed by in vivo depletion of T, NK or both cell populations. Immune profiling was performed using flow cytometry on single cell suspensions from spleens, bone marrow, tumors and blood.ResultsCombining RT, anti-PD-L1 and L19–IL2 cured 38% of LLC tumors, which was both CD8+ T and NK cell dependent. LLC tumors were resistant to RT +anti-PD-L1 likely explained by the upregulation of other IC molecules and increased T regulatory cell tumor infiltration. RT+L19–IL2 outperformed RT+ICB in C51 tumors; effects were comparable in CT26 tumors. Triple combinations were not superior to RT+L19–IL2 in both these models.ConclusionsThis study demonstrated that combinatorial strategies rationally designed on biological effects can turn immunotherapy-resistant tumors into immunologically responsive tumors. This hypothesis is currently being tested in the international multicentric randomized phase 2 trial: ImmunoSABR (NCT03705403).
Circulating cytokines associated with clinical response to systemic therapy in metastatic renal cell carcinoma
Authors: Chehrazi-Raffle Alexander , Meza Luis , Alcantara Marice , Dizman Nazli , Bergerot Paulo , Salgia Nicholas , Hsu JoAnn , Ruel Nora , Salgia Sabrina , Malhotra Jasnoor , Karczewska Ewa , Kortylewski Marcin , Pal Sumanta 
Published: March 2021

BackgroundCirculating cytokines and angiogenic factors have been associated with clinical outcomes in patients with metastatic renal cell carcinoma (RCC) receiving systemic therapy. However, none have yet examined cytokine concentrations in parallel cohorts receiving either immunotherapy or targeted therapy.MethodsIn this prospective correlative study, we enrolled 56 patients who were planned for treatment with either a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) or immune checkpoint inhibitor (ICI). Eligibility requirements permitted any RCC histologic subtype, International Metastatic Renal Cell Carcinoma risk classification, and line of therapy. Immunologic profile was assessed at baseline and after 1 month on treatment using a Human Cytokine 30-plex protein assay (Invitrogen). Clinical benefit was defined as complete response, partial response, or stable disease ≥6 months per RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria.ResultsClinical benefit was similar between VEGF-TKI and ICI arms (65% vs 54%). Patients with clinical benefit from VEGF-TKIs had lower pretreatment levels of interleukin-6 (IL-6) (p=0.02), IL-1RA (p=0.03), and granulocyte colony-stimulating factor (CSF) (p=0.02). At 1 month, patients with clinical benefit from ICIs had higher levels of interferon-γ (IFN-γ) (p=0.04) and IL-12 (p=0.03). Among patients on VEGF-TKIs, those with clinical benefit had lower 1 month IL-13 (p=0.02) and granulocyte macrophage CSF (p=0.01) as well as higher 1 month VEGF (p=0.04) compared with patients with no clinical benefit.ConclusionFor patients receiving VEGF-TKI or ICI therapy, distinct plasma cytokines were associated with clinical benefit. Our findings support additional investigation into plasma cytokines as biomarkers in metastatic RCC.
Early factors associated with later conversion to multiple sclerosis in patients presenting with isolated myelitis
Authors: Murphy Olwen C. , Mukharesh Loulwah , Salazar-Camelo Andrea , Pardo Carlos A. , Newsome Scott D. 
Published: March 2021

ObjectiveTo identify early clinical and paraclinical factors that may help predict later conversion to multiple sclerosis (MS) in patients presenting with isolated myelitis (ie, ‘transverse myelitis’ without clinical or radiological evidence of inflammation/demyelination elsewhere in the central nervous system).MethodsIn this retrospective cohort study, we included patients with isolated myelitis who were followed clinically and radiologically at our specialised myelopathy clinic. We excluded patients with MS at the onset, aquaporin-4-IgG seropositivity, myelin oligodendrocyte glycoprotein-IgG seropositivity or other identified aetiology. Logistic regression was used to identify factors predictive of conversion to MS (defined by the 2017 McDonald criteria).ResultsWe included 100 patients, followed for a median of 4.3 years. Conversion to MS occurred in 25 of 77 patients (32%) with short-segment myelitis (longest lesion spanning <3 vertebral segments on MRI) as compared with 0 of 23 patients (0%) with longitudinally extensive myelitis (p=0.002). Among patients with short-segment myelitis, factors identified as highly predictive of conversion to MS using multivariate logistic regression included cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCB) (OR (OR) 9.2, 95% CI 2.1 to 41.0, p=0.004), younger age (OR 1.1 for each year younger, 95% CI 1.0 to 1.1, p=0.04) and longer follow-up (OR 1.3 for each year longer, 95% CI 1.0 to 1.6, p=0.04). Conversion to MS occurred at a median of 2.8 years after myelitis onset.ConclusionsShort-segment MRI cord lesion(s), CSF-restricted OCB, younger age and longer follow-up are all factors predictive of conversion to MS in patients presenting with isolated myelitis.
Post-traumatic epilepsy in adults: a nationwide register-based study
Authors: Karlander Markus , Ljungqvist Johan , Zelano Johan 
Published: March 2021

ObjectiveTraumatic brain injury (TBI) is a leading cause of epilepsy. Our aim was to characterise the risk of epilepsy in adults after hospitalisation for TBI.MethodsRegister-based cohort study. All individuals aged 18–100 with a first hospitalisation for TBI in the comprehensive national patient register in Sweden between 2000 and 2010 (n=111 947) and three controls per exposed (n=325 881), matched on age and sex were included. Exposed individuals were categorised according to TBI severity. Kaplan-Meier curves were used to estimate the risk of epilepsy and Cox regression to estimate the hazard in univariate or multivariate regression.ResultsThe 10-year risk of epilepsy was 12.9% (95% CI 11.7% to 14.1%) for focal cerebral injuries, 8.1% (95% CI 7.5% to 8.7%) for diffuse cerebral injuries, 7.3% (95% CI 6.9% to 7.7%) for extracerebral injuries, 2.8% (95% CI 2.4% to 3.2%) for skull fractures and 2.6% (95% CI 2.4% to 2.8%) for mild TBI. The risk of epilepsy after any TBI was 4.0% (95% CI 3.8% to 4.2%). The corresponding 10-year risk for controls was 0.9% (95% CI 0.9% to 0.9%). The HR increased with a more severe injury, from 3.0 (95% CI 2.8 to 3.2) for mild injury to 16.0 (95% CI 14.5 to 17.5) for focal cerebral injury. Multivariable analyses identified central nervous system (CNS) comorbidities as risk factors, but TBI remained significant also after adjustment for these. Other identified risk factors were male sex, age, mechanical ventilation and seizure during index hospitalisation.ConclusionThe risk of post-traumatic epilepsy is considerable, also with adjustments for CNS comorbidities.
How junior doctors perceive personalised yoga and group exercise in the management of occupational and traumatic stressors
Authors: Taylor Jennifer , Stratton Elizabeth , McLean Loyola , Richards Bethan , Glozier Nicholas 
Published: March 2021

AbstractObjectivesJunior doctors are exposed to occupational and traumatic stressors, some of which are inherent to medicine. This can result in burnout, mental ill-health and suicide. Within a crossover pilot study comparing personalised, trauma-informed yoga to group-format exercise, qualitative interviews were conducted to understand the experience of junior doctors and whether such interventions were perceived to help manage these stressors.MethodsTwenty-one doctors, 76% female, were order-randomised to consecutive 8-week yoga and exercise programmes. Fifty-two interviews were recorded before and after each programme.ResultsMany participants reported being time poor, sleep-affected, frequently stressed and occasionally in physical pain/distress. Major stressor themes were workplace incivility, death/human suffering and shift work with minimal support. Both interventions were acceptable for different reasons. Personalised yoga offered a therapeutic alliance, time to check-in and reduced anxiety/rumination. Group exercise provided energy and social connection. One participant found yoga beneficial following an acute workplace trauma: ‘It was really eye opening how much I felt my body just needed to detox … I wouldn't have gone to a group fitness the next day … I just wanted to relax and breathe …We still had a big debrief which was great … (but) I almost felt like … I dealt with it physically and emotionally before going into it (P20).’ConclusionJunior doctors found both interventions useful for stress management adjunctive to other organisational programmes though for different and complementary reasons, possibly related to delivery mode. Personalised, trauma-informed yoga provided a confidential therapeutic alliance whereas group exercise offered social connection.
Radiation safety and knowledge: an international survey of 708 interventional pain physicians
Authors: Provenzano David Anthony , Florentino Samuel Ambrose , Kilgore Jason S , De Andres Jose , Sitzman B Todd , Brancolini Scott , Lamer Tim J , Buvanendran Asokumar , Carrino John A , Deer Timothy R , Narouze Samer 
Published: March 2021

IntroductionInterventional pain procedures have increased in complexity, often requiring longer radiation exposure times and subsequently higher doses. The practicing physician requires an in-depth knowledge and evidence-based knowledge of radiation safety to limit the health risks to themselves, patients and healthcare staff. The objective of this study was to examine current radiation safety practices and knowledge among interventional pain physicians and compare them to evidence-based recommendations.Materials and methodsA 49-question survey was developed based on an extensive review of national and international guidelines on radiation safety. The survey was web-based and distributed through the following professional organizations: Association of Pain Program Directors, American Academy of Pain Medicine, American Society of Regional Anesthesia and Pain Medicine, European Society of Regional Anesthesia and Pain Therapy, International Neuromodulation Society, and North American Neuromodulation Society. Responses to radiation safety practices and knowledge questions were evaluated and compared with evidence-based recommendations. An exploratory data analysis examined associations with radiation safety training/education, geographical location, practice type, self-perceived understanding, and fellowship experience.ResultsOf 708 responding physicians, 93% reported concern over the health effects of radiation, while only 63% had ever received radiation safety training/education. Overall, ≥80% physician compliance with evidence-based radiation safety practice recommendations was demonstrated for only 2/15 survey questions. Physician knowledge of radiation safety principles was low, with 0/10 survey questions having correct response rates ≥80%.ConclusionWe have identified deficiencies in the implementation of evidence-based practices and knowledge gaps in radiation safety. Further education and training are warranted for both fellowship training and postgraduate medical practice. The substantial gaps identified should be addressed to better protect physicians, staff and patients from unnecessary exposure to ionizing radiation during interventional pain procedures.
Estimation of treatment and prognostic factors of pneumocystis pneumonia in patients with connective tissue diseases
Authors: Ishikawa Yuichi , Nakano Kazuhisa , Tokutsu Kei , Miyata Hiroko , Fujino Yoshihisa , Matsuda Shinya , Tanaka Yoshiya 
Published: March 2021

ObjectivesTo investigate short-term prognosis and prognostic factors for connective tissue disease-associated pneumocystis pneumonia (CTD-PCP) using the Japanese nationwide diagnosis procedure combination (DPC) inpatient database.MethodsThe present retrospective cohort study from April 2014 to March 2016 included data of patients with CTD-PCP extracted from the DPC database using the 10threvision of International Classification of Diseases and Injuries codes.ResultsIn 15 901 766 cases registered from 1329 hospitals, 333 of 67 890 patients who were admitted with PCP were diagnosed with CTD-PCP and included in the study. The median age was 71.0 years, and 214 (64.3%), 80 (24.0%), and 29 (8.7%) patients received sulfamethoxazole/trimethoprim (ST) monotherapy and pentamidine-containing and atovaquone-containing therapy, respectively. There were 114 (34.2%) in-hospital deaths, and the 30-day and 60-day in-hospital survival rates after PCP treatment initiation were 66.0% and 53.7%, respectively. Older age (HR 1.06, 95% CI 1.03 to 1.08) and concomitant interstitial lung disease (ILD) (HR 1.65, 95% CI 1.12 to 2.42) were poor prognostic factors. Patients who completed PCP treatment with ST monotherapy had a significantly higher survival rate than those treated with those not treated with ST monotherapy (p=0.015; log-rank test). Pentamidine versus atovaquone as second-line therapy was significantly higher with atovaquone (p=0.012; log-rank test).ConclusionOlder age and concomitant ILD were poor prognostic factors for CTD-PCP. ST was a reasonable first-line therapy in patients with CTD-PCP, and patients with inadequate response to ST treated with atovaquone tended to have a better prognosis than those treated with pentamidine.
'Menthol-Plus’: a major category of cigarette found among ‘concept’ descriptor cigarettes from Mexico
Authors: Pankow James F , Luo Wentai , McWhirter Kevin J , Gillette Samantha , Cohen Joanna E 
Published: March 2021

BackgroundTobacco companies are offering cigarettes with ‘concept’ descriptor names that suggest sensation and/or flavour properties (eg, Marlboro ‘Velvet Fusion’). Little has been known about the identities and levels of flavour chemicals in such cigarettes.MethodsThirty-three filter cigarette variants from 27 packs (including two sampler packs with four variations each) from Canada and Mexico were analysed (rod + filter) for 177 flavour chemicals plus triacetin, a filter plasticiser and possible flavourant. Five brands of US mentholated filter cigarettes were also analysed.ResultsTwenty-seven of the 33 cigarettes (all were Mexican variants) were categorised as ‘menthol-plus’: significant menthol (3.0–11.9 mg/cigarette), plus varying amounts (0.32–3.4 mg/cigarette) of total other flavour chemicals (TOFCs) (excludes triacetin). For 10 of the 27, TOFCs >1.0 mg/cigarette. For 7 of the 27, the TOFCs profile was categorised as containing total fruit flavour compounds (TFFCs) >1.0 mg/cigarette. One Mexican variant was categorised as ‘menthol-only’ (TOFCs ≤0.15 mg/cigarette). All menthol-plus and menthol-only cigarettes contained one or two optional-crush capsules in their filters (crushed prior to analysis). All five Canadian brand variants were ‘non-flavoured’. All five US brand variants were ‘menthol-only’.ConclusionsAll but one of the ‘concept’ descriptor cigarettes from Mexico were ‘menthol-plus’. While the Canadian cigarettes complied with Canada’s flavour chemical ban, concept descriptors on the packs may increase appeal. Given the scale of the problem posed by menthol alone, health officials seeking to decrease the appeal of smoked tobacco should examine the extent to which ‘concept descriptor’ cigarettes using ‘menthol-plus’ flavour profiling together with artful descriptors are furthering the problem of smoked tobacco.