tbuckley/cabot-search huggingface dataset:
Medicinal use of cannabis based products and cannabinoids
Authors: Tom P Freeman, Chandni Hindocha, Sebastian F Green, Michael A P Bloomfield
Journal: BMJ (2019)

What you need to know• Cannabis based products for medicinal use contain cannabinoids derived from the cannabis plant, including ∆ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of THC and CBD.Synthetic cannabinoids for medicinal use typically mimic the effects of specific cannabinoids such as THC• THC is the constituent of cannabis that causes the "high," whereas CBD is not intoxicating at typical doses.THC and CBD have contrasting mechanisms of action and therapeutic indications; THC carries a higher risk of adverse events compared with CBD• Rescheduling on 1 November 2018 permits some unlicensed cannabis based products to be prescribed for the first time in the UK, but only by doctors on the relevant Specialist Register of the General Medical Council• Indications for treatment, supported by evidence of low to moderate certainty, include chronic pain, some treatment resistant epilepsies, and nausea and vomiting caused by chemotherapy (table 2)• Non-medicinal CBD products are legal and widely available on the internet and from health food retailers, but they lack quality standards and should not be used for medicinal purposesUntil recently, cannabis and its derivatives were widely restricted under legislation which stated they had no medical value and carried a substantial risk of misuse.Policy is rapidly changing, and cannabis can now be prescribed for medicinal use in many countries, including the UK.This provides important new opportunities for treating patients although these need to be weighed up against potential risks.Several different medicinal products exist, with contrasting mechanisms of action, efficacy, and safety.Use of these products may increase as new evidence arises and policy changes occur.Here we review this emerging field.
Irinotecan plus S‐1 versus S‐1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open‐labeled phase 3 trial
Authors: Jing Huang, Binghe Xu, Ying Liu, Junxing Huang, Ping Lu, Yi Ba, Lin Wu, Yuxian Bai, Shu Zhang, Jifeng Feng, Ying Cheng, Jie Li, Lu Wen, Xianglin Yuan, Changwu Ma, Chunhong Hu, Qingxia Fan, Xi Wang
Journal: Cancer Communications (2019)

The benefit of systemic treatments in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established. We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum- or taxane-based chemotherapy. We conducted a prospective randomized, multicenter, open-label, phase 3 trial in 15 centers across China. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC, and were randomly assigned (ratio, 1:1) to receive either irinotecan plus S-1 (intravenous infusion of irinotecan [160 mg/m2] on day 1 and oral S-1 [80-120 mg] on days 1-10, repeated every 14 days) or oral S-1 monotherapy (80-120 mg/day on days 1-14, repeated every 21 days) using a central computerized minimization procedure. The primary endpoint was progression-free survival (PFS). Between December 23, 2014 and July 25, 2016, we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen (n = 61) or S-1 monotherapy (n = 62). After a median follow-up of 29.2 months (95% confidence interval [CI] 17.5-40.9 months), the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group (3.8 months [95% CI 2.9-4.3 months] vs. 1.7 months [95% CI 1.4-2.7 months], hazard ratio = 0.58, 95% CI 0.38-0.86, P = 0.006). The objective response rates were 24.6% in the irinotecan plus S-1 group and 9.7% in the S-1 monotherapy group (P = 0.002). The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia (16.4% vs. 0%), neutropenia (14.8% vs. 1.6%), and nausea (4.9% vs. 0%). No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups. The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC. Clinical Trial Registration NCT02319187. Registered on December 9, 2014.
Longitudinal Retinal Perfusion Status in Eyes with Diabetic Macular Edema Receiving Intravitreal Aflibercept or Laser in VISTA Study
Authors: Charles C. Wykoff, Chirag Shah, Dilsher Dhoot, Hanna Rodriguez Coleman, Desmond Thompson, Weiming Du, Keith Baker, Robert Vitti, Alyson J. Berliner, Carola Metzig, Namrata Saroj
Journal: Ophthalmology (2019)
c-Src is in the effector pathway linking uPAR and podocyte injury
Authors: Jeffrey B. Kopp, Jurgen Heymann
Journal: Journal of Clinical Investigation (2019)

The role of urokinase-type plasminogen activator receptor (uPAR) in kidney physiology and pathology has attracted considerable attention. The protein uPAR has dual functions: as a key regulator of plasmin generation and a component of the innate immune system. In the current issue, Wei and colleagues describe a transgenic mouse expressing Plaur RNA in glomerular podocytes. The mice manifested podocyte injury, including c-Src phosphorylation, proteinuria, and focal segmental glomerulosclerosis (FSGS). Plaur-transgenic mice on a β3 integrin–deficient background were protected from podocyte injury. Renal biopsies from subjects with FSGS, but not those with other glomerular diseases, manifested increased c-Src phosphorylation in podocytes. These findings suggest a novel injury mechanism in FSGS, with possible implications for new treatment strategies.
Sequencing of the MHC region defines <i>HLA-DQA1</i> as the major genetic risk for seropositive rheumatoid arthritis in Han Chinese population
Authors: Jianping Guo, Tao Zhang, Hongzhi Cao, Xiaowei Li, Hao Liang, Mengru Liu, Yundong Zou, Yuanwei Zhang, Yuxuan Wang, Xiaolin Sun, Fanlei Hu, Yan Du, Xiaodong Mo, Xu Liu, Yue Yang, Huanjie Yang, Xinyu Wu, Xuewu Zhang, Huijue Jia, Hui Jiang, Yong Hou, Xin Liu, Yin Su, Mingrong Zhang, Huanming Yang, Jian Wang, Liangdan Sun, Liang Liu, Leonid Padyukov, Luhua Lai, Kazuhiko Yamamoto, Xuejun Zhang, Lars Klareskog, Xun Xu, Zhanguo Li
Journal: Annals of the Rheumatic Diseases (2019)

Objective The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen ( HLA)-DRB1 . However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC. Methods We first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case–control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants. Results HLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10 −36 , OR=2.29). DRβ1:37N had an independent protective effect (p=5.81×10 −16 , OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRβ1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility. Conclusions We provide the first evidence that HLA-DQα1:160D, instead of HLA-DRB1*0405 , is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.
Assessment of Parents’ Preferences for Incentives to Promote Engagement in Family-Based Childhood Obesity Treatment
Authors: Davene R. Wright, Brian E. Saelens, Angela Fontes, Tara A. Lavelle
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Family-based treatment (FBT) is recommended for childhood obesity, but even when sought, attrition is high. Extrinsic incentives, which have been effective for improving adult health, could improve FBT engagement. <h3>Objective</h3> To assess parents' preferences for FBT incentives. <h3>Design, Setting, and Participants</h3> Survey study of parents of children aged 6 to 17 years with obesity (body mass index in ≥95th percentile for age and sex). Parents' preferences for FBT incentive program attributes were assessed in a discrete choice experiment conducted using a nationally representative, web-based survey in March 2018. Attributes included (1) the monetary value of the incentive, (2) the payment structure, (3) the goal being incentivized, and (4) the person(s) being incentivized. A fractional factorial design was used to create a set of profiles representing hypothetical FBT incentives. Parents were presented with 10 pairs of profiles and asked which would most motivate them in FBT. Parents were also asked about preferences between a small, guaranteed incentive and a lottery for a large incentive. Analyses used a hierarchical Bayesian model and linear regressions. <h3>Main Outcomes and Measures</h3> Parents' preference for different incentive program attributes and levels. <h3>Results</h3> The nationally representative survey had a 41.4% eligibility rate (n = 339) and a 89.7% completion rate (n = 304). A total of 53.3% of respondents (weighted percentage) were non-Hispanic white, 42.6% had an annual household income less than $50 000, and 28.3% had a bachelor's degree. Parents preferred higher incentives, although they were willing to accept lower-value incentives if both the parent and the child (vs the child alone) were required to meet the goal (mean difference [MD], −$108; 95% CI, −$132 to −$84), if the incentive used a gain-framed vs loss-framed payment structure (MD, −$72; 95% CI, −$85 to −$59), and if physical activity goals were incentivized over weight loss (MD, −$63; 95% CI, −$82 to −$44) or dietary monitoring (MD, −$5; 95% CI, −$1 to $28). Only 20.6% of parents preferred a lottery over a guaranteed payment. Preferences did not vary among demographic or health subgroups. <h3>Conclusions and Relevance</h3> In this study, parent-stated preferences did not align with FBT best practices or behavioral economic theory. A randomized clinical trial could examine whether aligning incentives with preferences or best practices would maximize FBT engagement and behavior change.
Epidemiology of Second Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Relapsed Myelodysplastic Syndrome
Authors: Yoshimitsu Shimomura, Masahiko Hara, Takayoshi Tachibana, Kazuteru Ohashi, Yukiyasu Ozawa, Tetsuya Eto, Naoyuki Uchida, Takehiko Mori, Junya Kanda, Tatsuo Ichinohe, Yoshiko Atsuta, Takayuki Ishikawa, Ken Ishiyama
Journal: Blood (2018)
Abstract MP90: Identifying Risk Profiles for Sedentary Behavior in Youth Using Recursive Partitioning Based on Individual, Familial, and Neighborhood Environment Factors
Authors: Tracie A Barnett, Gisele Contreras, Andraea Van Hulst, Marie-Eve Mathieu, Melanie Henderson
Journal: Circulation (2016)

Background: Being sedentary is an established risk factor for obesity and related cardiometabolic complications, independently of physical activity (PA) levels. We used recursive partitioning analysis (RPA) to identify unique combinations of individual, familial, and neighborhood factors that increased the likelihood of being very sedentary. Methods: Baseline data were collected in 2005-2008 for 512 Quebec youth (aged 8-10 years) with a history of parental obesity (QUALITY study). Sedentary behavior and PA were assessed by accelerometry (Actigraph). Children with ≥10h of valid wear time on at least 4 days were retained for analysis. Children were categorized as being very sedentary if they accumulated at least 300 minutes/day of ≤100 counts/min on average. Fifteen variables were submitted to the recursive partitioning process in order to identify sub-groups by likelihood of being very sedentary. MLR was used to estimate likelihood of being very sedentary across subgroups, controlling for the child’s age, sex, household income, and PA level. Indicator variables were used, retaining the lowest risk group as the reference. Results: Data were complete for 445/512 participants. Six variables were retained to construct the classification tree. A total of 7 subgroups were identified, with proportions very sedentary equal to 5%, 22%, 31%, 26%, 33%, 40%, and 77%, respectively. The 7 risk subgroups, in order of increasing likelihood of being very sedentary, comprised children who: (1) met MVPA guidelines (engaged in at least 60 min/day of MVPA), (2) did not meet MVPA guidelines, but resided in lower poverty areas, (3) did not meet MVPA guidelines, resided in higher poverty areas, but with a higher park area ratio; (4) did not meet MVPA guidelines, resided in higher poverty areas, had a lower park area ratio, but did not have an obese father; (5) did not meet MVPA guidelines, resided in higher poverty areas, had a lower park area ratio, had an obese father, but lived in more urban areas; (6) same as subgroup (5) but living in less urban areas and not exceeding 2 hours/day of screentime on weekends; and finally (7) same as subgroup (6) but exceeding 2 hours per day of screentime on weekends. In multivariable logistic regressions, compared to subgroup 1, groups 2 to 7 were significantly more likely to be very sedentary, after controlling for age, sex and household income. However, after further controlling for minutes of MVPA, only children in group 7 remained significantly more likely to be categorized as very sedentary (OR: 7.3, 95% CI: 1.3-45.1). Conclusion: The relationship between physical activity and sedentary behaviour is complex. Specific combinations of factors appear particularly conducive to engaging in excessive sedentary behaviour, with weekend screen time possibly being the most salient individual contributor.
Abstract 18198: The Spleen Regulates Apoptotic Cell Clearance, Tissue Neovascularization, and Wound Healing After Myocardial Infarction
Authors: Mohamed Ameen Mohamed Ismahil, Bindiya Patel, Shyam S Bansal, Tariq Hamid, Mehak Goel, Hai Zhong, Guihua Zhou, Amy M Michaud, Sumanth D Prabhu
Journal: Circulation (2015)

After myocardial infarction (MI), mononuclear phagocytes infiltrate the heart to orchestrate wound healing. The spleen is considered to be one reservoir for infiltrating immune cells. In chronic heart failure (HF), mononuclear splenocytes are pathologically activated and pro-inflammatory; however, their precise role in early post-MI healing is unclear. We hypothesized that the spleen is necessary for efficient tissue repair after MI, thereby limiting long-term pathological remodeling. Survival or sham splenectomy (Spx or nSpx) were performed in adult CD45.2 C57Bl/6 mice. One month later, Spx and nSpx control mice were subjected to left coronary ligation or sham operation (n=5-10/group), and post-MI remodeling was assessed at 24 h, 10 d, and 8 w. As compared with nSpx sham at 8 w, nSpx MI hearts exhibited significant (p &lt; 0.01): 1) LV dilatation (EDV 112 ± 20 vs 50 ± 6 μL), 2) systolic dysfunction (EF 39 ± 25 vs 63 ± 12%); and 3) hypertrophy (LV/tibia length 10.6 ± 0.7 vs 7.7 ± 0.3 mg/mm). In contrast, as compared with nSpx MI, Spx MI hearts exhibited significant worsening (p &lt; 0.05) of: 1) LV dilatation (EDV 163 ± 80 μL); 2) systolic dysfunction (EF 21 ± 10%); 3) hypertrophy (LV/tibia length 13.3 ± 0.8 mg/mm); 4) ~2-fold decrease in border zone (BZ) neovasculature by isolectin B4 staining; and 5) significantly reduced anti-inflammatory CD206+iNOS– BZ macrophages by immunostaining. Moreover, as compared with nSpx hearts 24 h post-MI, the infarct zone (IZ) of Spx MI hearts exhibited significant decreases in the subset of Tim4+ macrophages, which are primary mediators of apoptotic cell efferocytosis. Notably, Tim4+ macrophage levels in Spx MI hearts were restored upon adoptive transfer of mononuclear splenocytes from CD45.1 syngeneic mice 6 h post-MI. Lastly, at 10 d post-MI, as compared with nSpx, Spx MI hearts revealed reduced MMP9 activation, collagen deposition, and CD206+iNOS– macrophages in the IZ by immunostaining. Hence, we conclude that splenocytes regulate apoptotic cell clearance, tissue neovascularization, and wound healing after MI. Unlike chronic ischemic HF, where mononuclear splenocytes are pro-inflammatory and tissue-injurious, the cardiosplenic axis early after MI is necessary for wound repair and cardioprotective against adverse LV remodeling.
Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial
Authors: Charlotte K Boughton, Lia Bally, Franco Martignoni, Sara Hartnell, David Herzig, Andreas Vogt, Maria M Wertli, Malgorzata E Wilinska, Mark L Evans, Anthony P Coll, Christoph Stettler, Roman Hovorka
Journal: The Lancet Diabetes & Endocrinology (2019)

Glucose management is challenging in patients who require nutritional support in hospital. We aimed to assess whether fully closed-loop insulin delivery would improve glycaemic control compared with conventional subcutaneous insulin therapy in inpatients receiving enteral or parenteral nutrition or both.
Self-facilitated ROS-responsive nanoassembly of heterotypic dimer for synergistic chemo-photodynamic therapy
Authors: Cong Luo, Bingjun Sun, Chen Wang, Xuanbo Zhang, Yao Chen, Qin Chen, Han Yu, Hanqing Zhao, Mengchi Sun, Zhenbao Li, Haotian Zhang, Qiming Kan, Yongjun Wang, Zhonggui He, Jin Sun
Journal: Journal of Controlled Release (2019)
Features of cutaneous acute graft‐versus‐host disease by reflectance confocal microscopy
Authors: I. Saknite, M. Gill, C. Alessi‐Fox, M. Byrne, M. Jagasia, S. Gonzalez, M. Ardigo, E.R. Tkaczyk
Journal: British Journal of Dermatology (2019)

Confident diagnosis of acute cutaneous graft-versus-host disease (aGVHD) is often challenging due to nonspecific clinical appearance and histopathology. 1,2Biopsies from different locations on the same patient frequently differ in grade, while normal-appearing skin may show aGVHD features. 3Serial biopsies of a single lesion are not possible.Lacking ability for informed site selection, timing, and serial noninvasive microscopic monitoring, some clinicians advocate empiric treatment in lieu of skin biopsies. 4In vivo reflectance confocal microscopy (RCM), of proven value in many skin diseases, 5 might offer these missing insights and has been considered for aGVHD. 6A description of RCM features in patients is the next essential step towards evaluating possible clinical utility.To create a consensus understanding and initial description of the features of aGVHD visible by RCM, we convened a panel of experts (SG, MA, MG, ET, CF), including an RCMtrained dermatopathologist (MG).We retrospectively reviewed all upper chest RCM cases from the Vanderbilt transplant program with clinical diagnosis of aGVHD rendered by a
Abstract 30: Are Man-made Pollutants Originating From China, Central Asia One Of The Windborne Mystery Infections Of Kawasaki Disease Carried Across The Pacific?
Authors: Deniz Yeter, Richard Deth, Ho-Chang Kuo
Journal: Circulation (2015)

Kawasaki disease (KD) is an acute febrile illness predominately affecting children (75-80%) that is classified as an autoimmune vasculitis of small- to medium-sized arteries. KD is generally self-limited, although serious cardiac lesions develop in 25-30% of cases. Despite over four decades of extensive international investigation, no cause of KD has been confirmed. Significantly higher rates of concurrent viral infections were recently observed in patients during acute KD, while another study found significantly greater risk of early hospitalization for bacterial infections before KD onset. Several recent large investigations appear to confirm that patients are significantly more likely to develop asthma or common allergies such as acute rhinitis and atopic dermatitis both before and after KD. Seasonal shifts in large-scale wind currents originating from heavily polluted regions in China and Central Asia are significantly associated with the occurrence of KD cases in Japan, Hawaii, and San Diego. Recently, it appears these authors discovered that marked candida pollution from the soil of heavy agricultural and industrial areas in Northeastern China is significantly associated with the occurrence of KD in Japan. There is extensive precedent for trans-ocean wind transport of industrial pollutants, including across the Pacific. China now accounts for more than 50% of the world’s total anthropogenic emissions and is responsible for 20-29% of total air pollution in the United States, particularly as a result of its rapid industrialization and heavy reliance upon coal-fired power plants. Significantly higher consumption of seafood contaminated with methylmercury, PCBs, and dioxins may account for the disproportionate rates of KD in East Asian populations. In Japan, the appearance of KD during the 1950s and 1960s coincides with outbreaks of Minamata disease during this same period, which resulted from an unprecedented increase in mercury pollution and the contamination of seafood. Lastly, industrialization and subsequent pre- and postnatal exposure to various irritants are significantly associated with the development of asthma and common allergies during early childhood, which suggests a potential common link to KD that deserves scrutiny.