Takshan/R1 huggingface dataset:
Impact of red and processed meat and fibre intake on treatment outcomes among patients with chronic inflammatory diseases: protocol for a prospective cohort study of prognostic factors and personalised medicine.

INTRODUCTION: Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes. METHODS AND ANALYSIS: This prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14-16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics. ETHICS AND DISSEMINATION: The principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT03173144; Pre-results.
Risk communication: climate change as a human-health threat, a survey of public perceptions in Malta.

BACKGROUND: Scientific evidence shows that climate change is very likely the product of human behaviour and lifestyle. The effects of climate change on human health are diverse in nature and range from direct effects due to extreme weather events such as heat waves, floods and storms, to indirect effects such as those caused by water and food shortages. METHODS: A telephone survey was conducted between January and February 2009, on a stratified representative random sample of the Maltese population over the age of 18 years (N = 310,819). RESULTS: Five hundred and forty-three individuals successfully participated in the survey giving a response rate of 92.7%. The respondent sample was very similar to the target population by gender (P = 0.977), age (P = 0.767) and district (P = 0.812). The results of the study demonstrate a very strong relationship between the perception of climate change as a threat to health and well-being, support for climate change mitigation policy and a willingness to implement measures to address climate change. CONCLUSION: The findings of this study show that the perception that climate change may claim lives, cause disease, reduce the standard of living and worsen water shortages, may be the strongest driver behind support for climate change mitigation policy and a willingness to act. It is recommended that, in order to gain more public support, climate change campaigns and risk communication strategies should frame climate change as a threat to human health and general well-being.
Reframing climate change as a public health issue: an exploratory study of public reactions.

BACKGROUND: Climate change is taking a toll on human health, and some leaders in the public health community have urged their colleagues to give voice to its health implications. Previous research has shown that Americans are only dimly aware of the health implications of climate change, yet the literature on issue framing suggests that providing a novel frame--such as human health--may be potentially useful in enhancing public engagement. We conducted an exploratory study in the United States of people's reactions to a public health-framed short essay on climate change. METHODS: U.S. adult respondents (n = 70), stratified by six previously identified audience segments, read the essay and were asked to highlight in green or pink any portions of the essay they found "especially clear and helpful" or alternatively "especially confusing or unhelpful." Two dependent measures were created: a composite sentence-specific score based on reactions to all 18 sentences in the essay; and respondents' general reactions to the essay that were coded for valence (positive, neutral, or negative). We tested the hypothesis that five of the six audience segments would respond positively to the essay on both dependent measures. RESULTS: There was clear evidence that two of the five segments responded positively to the public health essay, and mixed evidence that two other responded positively. There was limited evidence that the fifth segment responded positively. Post-hoc analysis showed that five of the six segments responded more positively to information about the health benefits associated with mitigation-related policy actions than to information about the health risks of climate change. CONCLUSIONS: Presentations about climate change that encourage people to consider its human health relevance appear likely to provide many Americans with a useful and engaging new frame of reference. Information about the potential health benefits of specific mitigation-related policy actions appears to be particularly compelling. We believe that the public health community has an important perspective to share about climate change, a perspective that makes the problem more personally relevant, significant, and understandable to members of the public.
Clinical and electrophysiological impact of repetitive low-frequency transcranial magnetic stimulation on the sensory-motor network in patients with restless legs syndrome.

Background: Based on the hyperexcitability and disinhibition observed in patients with restless legs syndrome (RLS) following transcranial magnetic stimulation (TMS), we conducted a study with low-frequency repetitive TMS (rTMS) over the primary motor (M1) and somatosensory cortical areas (S1) in patients with RLS. Methods: A total of 13 right-handed patients and 10 age-matched controls were studied using clinical scales and TMS. Measurements included resting motor threshold (rMT), motor-evoked potentials (MEPs), cortical silent period (CSP), and central motor conduction time (CMCT). A single evening session of rTMS (1 Hz, 20 trains, 50 stimuli each) was administered over the left M1, left S1, and sham stimulation over M1 in a random order. Clinical and TMS measures were repeated after each stimulation modality. Results: Baseline CSP was shorter in patients than in controls and remained shorter in patients for both motor and somatosensory stimulation. The patients reported a subjective improvement of both initiating and maintaining sleep the night after the rTMS over S1. Patients exhibited a decrease in rMT after rTMS of S1 only, although the effect was smaller than in controls. MEP latency and CMCT changed only in controls after stimulation. Sham stimulation was without effect on the observed variables. Conclusions: rTMS on S1-M1 connectivity alleviated the sensory-motor complaints of RLS patients. The TMS indexes of excitation and inhibition indicate an intracortical and corticospinal imbalance, mainly involving gamma-aminobutyric acid (GABA)ergic and glutamatergic circuitries, as well as an impairment of the short-term mechanisms of cortical plasticity. The rTMS-induced activation of the dorsal striatum with the consequent increase of dopamine release may have contributed to the clinical and neurophysiological outcome.
Accuracy and Feasibility of an Android-Based Digital Assessment Tool for Post Stroke Visual Disorders-The StrokeVision App.

Background: Visual impairment affects up to 70% of stroke survivors. We designed an app (StrokeVision) to facilitate screening for common post stroke visual issues (acuity, visual fields, and visual inattention). We sought to describe the test time, feasibility, acceptability, and accuracy of our app-based digital visual assessments against (a) current methods used for bedside screening and (b) gold standard measures. Methods: Patients were prospectively recruited from acute stroke settings. Index tests were app-based assessments of fields and inattention performed by a trained researcher. We compared against usual clinical screening practice of visual fields to confrontation, including inattention assessment (simultaneous stimuli). We also compared app to gold standard assessments of formal kinetic perimetry (Goldman or Octopus Visual Field Assessment); and pencil and paper-based tests of inattention (Albert's, Star Cancelation, and Line Bisection). Results of inattention and field tests were adjudicated by a specialist Neuro-ophthalmologist. All assessors were masked to each other's results. Participants and assessors graded acceptability using a bespoke scale that ranged from 0 (completely unacceptable) to 10 (perfect acceptability). Results: Of 48 stroke survivors recruited, the complete battery of index and reference tests for fields was successfully completed in 45. Similar acceptability scores were observed for app-based [assessor median score 10 (IQR: 9-10); patient 9 (IQR: 8-10)] and traditional bedside testing [assessor 10 (IQR: 9-10); patient 10 (IQR: 9-10)]. Median test time was longer for app-based testing [combined time to completion of all digital tests 420 s (IQR: 390-588)] when compared with conventional bedside testing [70 s, (IQR: 40-70)], but shorter than gold standard testing [1,260 s, (IQR: 1005-1,620)]. Compared with gold standard assessments, usual screening practice demonstrated 79% sensitivity and 82% specificity for detection of a stroke-related field defect. This compares with 79% sensitivity and 88% specificity for StrokeVision digital assessment. Conclusion: StrokeVision shows promise as a screening tool for visual complications in the acute phase of stroke. The app is at least as good as usual screening and offers other functionality that may make it attractive for use in acute stroke. Clinical Trial Registration: https://ClinicalTrials.gov/ct2/show/NCT02539381.
The English National Cohort Study of Flooding and Health: the change in the prevalence of psychological morbidity at year two.

BACKGROUND: The longer term impact of flooding on health is poorly understood. In 2015, following widespread flooding in the UK during winter 2013/14, Public Health England launched the English National Study of Flooding and Health. The study identified a higher prevalence of probable psychological morbidity one year after exposure to flooding. We now report findings after two years. METHODS: In year two (2016), a self-assessment questionnaire including flooding-related exposures and validated instruments to screen for probable anxiety, depression and post-traumatic stress disorder (PTSD) was sent to all participants who consented to further follow-up. Participants exposure status was categorised according to responses in year one; we assessed for exposure to new episodes of flooding and continuing flood-related problems in respondents homes. We calculated the prevalence and odds ratio for each outcome by exposure group relative to unaffected participants, adjusting for confounders. We used the McNemar test to assess change in outcomes between year one and year two. RESULTS: In year two, 1064 (70%) people responded. The prevalence of probable psychological morbidity remained elevated amongst flooded participants [n = 339] (depression 10.6%, anxiety 13.6%, PTSD 24.5%) and disrupted participants [n = 512] (depression 4.1%, anxiety 6.4%, PTSD 8.9%), although these rates were reduced compared to year one. A greater reduction in anxiety 7.6% (95% confidence interval [CI] 4.6-9.9) was seen than depression 3.8% (95% CI 1.5-6.1) and PTSD: 6.6% (95% CI 3.9-9.2). Exposure to flooding was associated with a higher odds of anxiety (adjusted odds ratio [aOR] 5.2 95%, 95% CI 1.7-16.3) and depression (aOR 8.7, 95% CI 1.9-39.8) but not PTSD. Exposure to disruption caused by flooding was not significantly associated with probable psychological morbidity. Persistent damage in the home as a consequence of the original flooding event was reported by 119 participants (14%). The odds of probable psychological morbidity amongst flooded participants who reported persistent damage, compared with those who were unaffected, were significantly higher than the same comparison amongst flooded participants who did not report persistent damage. CONCLUSIONS: This study shows a continuance of probable psychological morbidity at least two years following exposure to flooding. Commissioners and providers of health and social care services should be aware that the increased need in populations may be prolonged. Efforts to resolve persistent damage to homes may reduce the risk of probable psychological morbidity.
Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis.

BACKGROUND: The clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines. METHODS: We searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR)∗100. Narrative synthesis was undertaken where meta-analysis was not possible. RESULTS: We identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE=80%; 95% confidence interval [CI] 59-90%; unadjuvanted: VE=66%; 95% CI 47-78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14-82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18-64years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes. CONCLUSIONS: Adjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.
Restoring Th17/Treg balance via modulation of STAT3 and STAT5 activation contributes to the amelioration of chronic obstructive pulmonary disease by Bufei Yishen formula.

ETHNOPHARMACOLOGY RELEVANCE: Bufei Yishen formula (BYF), a Traditional Chinese Medicine (TCM), has been extensively applied in clinical treatment of chronic obstructive pulmonary disease (COPD) and provides an effective treatment strategy for the syndrome of lung-kidney qi deficiency in COPD patients. Here, we investigated its anti-COPD mechanism in COPD rats in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. METHODS: Rat model of cigarette smoke- and bacterial infection-induced COPD was established, and orally treated with BYF for 12 consecutive weeks. Then, the rats were sacrificed, their lung tissues were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were collected to evaluate the Th17 and Treg cells. RESULTS: Oral treatment of BYF markedly suppressed the disease progression and alleviated the pathological changes of COPD. It also decreased the bronchoalveolar lavage fluid (BALF) levels of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and Th17-related IL-17A, and induced a significant increase in Treg-related IL-10. Furthermore, BYF treatment obviously decreased the proportion of CD4+RORγt+ T (Th17) cell and increased the proportion of CD4+CD25+Foxp3+ T (Treg) cell, leading to restore the Th17/Treg balance. BYF treated groups also decreased RORγt and increased Foxp3 expression in the spleens and MLNs. BYF further inhibited the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and boosted the phosphorylation of STAT5, that were critical transcription factors for TH17 and Treg differentiation. CONCLUSION: these results demonstrated that BYF exerted its anti-COPD efficacy by restoring Th17/Treg balance via reciprocally modulating the activities of STAT3 and STAT5 in COPD rats, which may help to elucidate the underlying immunomodulatory mode of BYF on COPD treatment.
Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND: Approximately 15-20% of ulcerative colitis patients and 20-40% of those with Crohn's disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action. AIMS: This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action. METHODS: We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy. RESULTS: Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn's disease. CONCLUSIONS: These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.
The top 2,000 cited articles in critical care medicine: a bibliometric analysis.

Background: The bibliometric analysis has been performed on several topics in critical care medicine (CCM) focusing on top 100 cited articles, but the analysis on CCM literature as a whole is missing. The present study aimed to perform a complete bibliometric analysis in the field of CCM. Methods: An electronic search of the Scopus database was performed on Feb 13, 2018. The search strategy involved core terms related to CCM. The top 2,000 most cited articles in the field of CCM were included in the analysis. Descriptive statistics on these top-cited articles, country distributions, and journals are reported. Individual author's productivity was assessed with the Lotka's law. Co-occurrence of keywords was visualized with the Fruchterman-Reingold layout. The Walktrap algorithm was employed for clustering analysis. Results: A total of 2,000 documents were included in the analysis with median citations of 386 times [interquartile range (IQR): 308-562 times]. The most cited article was the original paper that described the Acute Physiology and Chronic Health Evaluation (APACHE) II score. The included articles were published in 411 journals. The median number of documents published in one journal was 1, and the mean number was 4.9, indicating a skewed distribution. The maximum number of publications was 217 in CCM. Author's productivity profile was significantly different from the Lotka's law (P=0.001), with n and C values of 2.8 and 0.52, respectively. Fruchterman-Reingold network plot showed that studies involving human subject were the most common literature type. Sepsis was a major research topic that co-occurred with keywords such as disease severity, nonhuman, risk assessment and practice guideline. Conclusions: The study performed bibliometric analyses of 2,000 top-cited articles in CCM. The most cited article was the one which developed the APACHE II score. Author's productivity was significantly different from the Lotka's law.
Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.

BACKGROUND: Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, the anti-tumorigenic effect and clinical benefit are only transient, and tumors are prone to treatment resistance and relapse. To elucidate mechanistic insights into drug resistance, we have established an in vitro cellular model of MAPK inhibitor resistance in malignant melanoma. METHODS: The cellular model evolved in response to clinical dosage of the BRAF inhibitor, vemurafenib, PLX4032. We conducted transcriptomic expression profiling using RNA-Seq and RT-qPCR arrays. Pathways of melanogenesis, MAPK signaling, cell cycle, and metabolism were significantly enriched among the set of differentially expressed genes of vemurafenib-resistant cells vs control. The underlying mechanism of treatment resistance and pathway rewiring was uncovered to be based on non-genomic adaptation and validated in two distinct melanoma models, SK-MEL-28 and A375. Both cell lines have activating BRAF mutations and display metastatic potential. RESULTS: Downregulation of dual specific phosphatases, tumor suppressors, and negative MAPK regulators reengages mitogenic signaling. Upregulation of growth factors, cytokines, and cognate receptors triggers signaling pathways circumventing BRAF blockage. Further, changes in amino acid and one-carbon metabolism support cellular proliferation despite MAPK inhibitor treatment. In addition, treatment-resistant cells upregulate pigmentation and melanogenesis, pathways which partially overlap with MAPK signaling. Upstream regulator analysis discovered significant perturbation in oncogenic forkhead box and hypoxia inducible factor family transcription factors. CONCLUSIONS: The established cellular models offer mechanistic insight into cellular changes and therapeutic targets under inhibitor resistance in malignant melanoma. At a systems biology level, the MAPK pathway undergoes major rewiring while acquiring inhibitor resistance. The outcome of this transcriptional plasticity is selection for a set of transcriptional master regulators, which circumvent upstream targeted kinases and provide alternative routes of mitogenic activation. A fine-woven network of redundant signals maintains similar effector genes allowing for tumor cell survival and malignant progression in therapy-resistant cancer.