tbuckley/cabot-search huggingface dataset:
Lisa Jane Newton
Authors: Majid Kazmi
Journal: BMJ (2020)

Lisa Jane Newton was a much respected haematologist, who made a huge contribution to the population of south and west Yorkshire. Lisa and I did our A levels together and then went our separate ways to read medicine at university. She trained in Sheffield, having chosen that university above many others. She undertook an intercalated degree during her training a reflection of her academic ability and continuing desire to further her knowledge and push herself. She undertook general medical training in Sheffield, and, as fate would have it, we spent …
Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy
Authors: Francesco Mazzarotto, Upasana Tayal, Rachel J. Buchan, William Midwinter, Alicja Wilk, Nicola Whiffin, Risha Govind, Erica Mazaika, Antonio de Marvao, Timothy J.W. Dawes, Leanne E. Felkin, Mian Ahmad, Pantazis I. Theotokis, Elizabeth Edwards, Alexander Y. Ing, Kate L. Thomson, Laura L.H. Chan, David Sim, A. John Baksi, Antonis Pantazis, Angharad M. Roberts, Hugh Watkins, Birgit Funke, Declan P. O’Regan, Iacopo Olivotto, Paul J.R. Barton, Sanjay K. Prasad, Stuart A. Cook, James S. Ware, Roddy Walsh
Journal: Circulation (2020)

Dilated cardiomyopathy (DCM) is genetically heterogeneous, with >100 purported disease genes tested in clinical laboratories. However, many genes were originally identified based on candidate-gene studies that did not adequately account for background population variation. Here we define the frequency of rare variation in 2538 patients with DCM across protein-coding regions of 56 commonly tested genes and compare this to both 912 confirmed healthy controls and a reference population of 60 706 individuals to identify clinically interpretable genes robustly associated with dominant monogenic DCM.We used the TruSight Cardio sequencing panel to evaluate the burden of rare variants in 56 putative DCM genes in 1040 patients with DCM and 912 healthy volunteers processed with identical sequencing and bioinformatics pipelines. We further aggregated data from 1498 patients with DCM sequenced in diagnostic laboratories and the Exome Aggregation Consortium database for replication and meta-analysis.Truncating variants in TTN and DSP were associated with DCM in all comparisons. Variants in MYH7, LMNA, BAG3, TNNT2, TNNC1, PLN, ACTC1, NEXN, TPM1, and VCL were significantly enriched in specific patient subsets, with the last 2 genes potentially contributing primarily to early-onset forms of DCM. Overall, rare variants in these 12 genes potentially explained 17% of cases in the outpatient clinic cohort representing a broad range of adult patients with DCM and 26% of cases in the diagnostic referral cohort enriched in familial and early-onset DCM. Although the absence of a significant excess in other genes cannot preclude a limited role in disease, such genes have limited diagnostic value because novel variants will be uninterpretable and their diagnostic yield is minimal.In the largest sequenced DCM cohort yet described, we observe robust disease association with 12 genes, highlighting their importance in DCM and translating into high interpretability in diagnostic testing. The other genes analyzed here will need to be rigorously evaluated in ongoing curation efforts to determine their validity as Mendelian DCM genes but have limited value in diagnostic testing in DCM at present. This data will contribute to community gene curation efforts and will reduce erroneous and inconclusive findings in diagnostic testing.
Obesity surgery does not lead to long term alleviation of mental health problems in teens, study finds
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Adolescents who have bariatric surgery continue to experience mental health problems five years after surgery despite substantial weight loss, a study has found.1

The authors of a study published in the Lancet Child and Adolescent Health said that, while surgery can improve many aspects of health, their results suggested that alleviation of mental health problems “should not be expected.”

The research team, from Sweden, used records of psychiatric drug prescriptions and specialist care for mental health disorders in combination with self-reported data to assess the long term impact of weight loss surgery in 161 adolescents aged 13-18.

At five year follow-up, despite small improvements in self-esteem and moderate improvements in binge eating, adolescents who had had surgery did not see …
Performance comparison of a non-invasive P300-based BCI mouse to a head-mouse for people with SCI
Authors: Aviroop Dutt-Mazumder, Jane E. Huggins
Journal: Brain-Computer Interfaces (2020)

ABSTRACT The purpose of this study was to evaluate the feasibility of a novel non-invasive P300-based brain computer interface (BCI) mouse emulation device (MED), along with a commercial head-mouse among experienced head-mouse users with cervical spinal cord injury (SCI). The setting was a controlled experimental set-up. Feasibility was shown for the P300-BCI MED with an accuracy of 82%, response-time <149 seconds and lower response-time variability than head-mouse. There were improvements in response-time and error-distance in the P300-BCI MED from day 1 to day 2. However, the head-mouse performed better for all the outcome measures, i.e. higher accuracy, quicker response time, and lower error distance than P300-BCI MED. The P300-BCI MED was feasible, and participants expressed an interest in using it on a regular basis despite reporting that the head-mouse worked better. Thus, a P300-BCI MED is a promising alternative for those who require a MED, but further development would be desirable. Abbreviations BCI: Brain-computer interface; EEG: Electroencephalogram; P300: Event-related evoked potential occurring at 300 ms used to operate a BCI; SSVEP: Steady state visual evoked potential; MED: Mouse emulation device; FIM: FIM – FIM® instrument; NASA-TLX: National Aeronautics and Space Administration – Task Load Index
Germline cancer predisposition variants and pediatric glioma: a population-based study in California
Authors: Ivo S Muskens, Adam J de Smith, Chenan Zhang, Helen M Hansen, Libby Morimoto, Catherine Metayer, Xiaomei Ma, Kyle M Walsh, Joseph L Wiemels
Journal: Neuro-Oncology (2020)

Abstract Background Pediatric astrocytoma constitutes a majority of malignant pediatric brain tumors. Previous studies that investigated pediatric cancer predisposition have primarily been conducted in tertiary referral centers and focused on cancer predisposition genes. In this study, we investigated the contribution of rare germline variants to risk of malignant pediatric astrocytoma on a population level. Methods DNA samples were extracted from neonatal dried bloodspots from 280 pediatric astrocytoma patients (predominantly high grade) born and diagnosed in California and were subjected to whole-exome sequencing. Sequencing data were analyzed using agnostic exome-wide gene-burden testing and variant identification for putatively pathogenic variants in 175 a priori candidate cancer-predisposition genes. Results We identified 33 putatively pathogenic germline variants among 31 patients (11.1%) which were located in 24 genes largely involved in DNA repair and cell cycle control. Patients with pediatric glioblastoma were most likely to harbor putatively pathogenic germline variants (14.3%, N = 9/63). Five variants were located in tumor protein 53 (TP53), of which 4 were identified among patients with glioblastoma (6.3%, N = 4/63). The next most frequently mutated gene was neurofibromatosis 1 (NF1), in which putatively pathogenic variants were identified in 4 patients with astrocytoma not otherwise specified. Gene-burden testing also revealed that putatively pathogenic variants in TP53 were significantly associated with pediatric glioblastoma on an exome-wide level (odds ratio, 32.8, P = 8.04 × 10−7). Conclusion A considerable fraction of pediatric glioma patients, especially those of higher grade, harbor a putatively pathogenic variant in a cancer predisposition gene. Some of these variants may be clinically actionable or may warrant genetic counseling.
Partha Kar: What will the 2020s hold for diabetes care?
Authors: Partha Kar
Journal: BMJ (2020)

I’ve been reflecting on how much has changed in diabetes care over the past decade and what changes we may see over the next 10 years. The changes in the 2010s were nothing short of seismic, with fundamental shifts of treatment and approach towards tackling diabetes, irrespective of type.

Healthcare professionals have struggled to cope with some of the fast paced changes and the shifting evidence base, but the NHS itself has largely stayed ahead of the curve, although the National Institute for Health and Care Excellence has been criticised for not doing so. And people with diabetes have been even more nimble and aware, innovating themselves when necessary, such as with the DIY artificial pancreas system (APS).

Prevention of type 2 diabetes came to the fore …
A Rare Presentation of Melanoma as a Retroperitoneal Mass Seen on FDG PET
Authors: Yutang Yao, Wusong Liu, Zhuo Zuo, Zhuzhong Cheng
Journal: Clinical Nuclear Medicine (2020)

A 55-year-old woman presented with intermittent fatigue and abdominal pain. Ultrasound and CT scan showed a large heterogeneous mass in the retroperitoneum, suggestive of malignancy. F-FDG PET/CT was performed for staging. PET/CT images showed a hypermetabolic retroperitoneal mass. Endoscopy revealed a mass infiltrating the duodenum. Eventually, the mass was pathologically proved to be malignant melanoma. Further extensive clinical, radiological, and endoscopic investigations proved the retroperitoneum to be the primary site.
血管内皮過透過性は,クラークソン病(全身性毛細血管漏出症候群)の臨床症状を誘発する
Authors: Xie Zhihui, C Ghosh Chandra, Patel Roshni, Iwaki Shoko, Gaskins Donna, Nelson Celeste, Jones Nina, R Greipp Philip, M Parikh Samir, M Druey Kirk
Journal: Blood (2012)
Life-Course Cumulative Burden of Body Mass Index and Blood Pressure on Progression of Left Ventricular Mass and Geometry in Midlife
Authors: Yinkun Yan, Shengxu Li, Yajun Guo, Camilo Fernandez, Lydia Bazzano, Jiang He, Jie Mi, Wei Chen
Journal: Circulation Research (2020)

Rationale: Data are limited regarding the influence of life-course cumulative burden of increased body mass index (BMI) and elevated blood pressure (BP) on the progression of left ventricular (LV) geometric remodeling in midlife. Objective: To investigate the dynamic changes in LV mass and LV geometry over 6.4 years during midlife and to examine whether the adverse progression of LV geometric remodeling is influenced by the cumulative burden of BMI and BP from childhood to adulthood. Methods and Results: The study consisted of 877 adults (604 whites and 273 blacks; 355 males; mean age=41.4 years at follow-up) who had 5 to 15 examinations of BMI and BP from childhood and 2 examinations of LV dimensions at baseline and follow-up 6.4 years apart during adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and systolic BP (SBP). After adjusting for age, race, sex, smoking, alcohol drinking, and baseline LV mass index, the annual increase rate of LV mass index was associated with all BMI measures (β=0.16–0.36, P &lt;0.05 for all), adult SBP (β=0.07, P =0.04), and total AUC of SBP (β=0.09, P =0.01) but not with childhood and incremental AUC values of SBP. All BMI and SBP measures (except childhood SBP) were significantly associated with increased risk of incident LV hypertrophy, with odds ratios of BMI (odds ratio=1.85–2.74, P &lt;0.05 for all) being significantly greater than those of SBP (odds ratio=1.09–1.34, P &lt;0.05 for all except childhood SBP). In addition, all BMI measures were significantly and positively associated with incident eccentric and concentric LV hypertrophy. Conclusions: Life-course cumulative burden of BMI and BP is associated with the development of LV hypertrophy in midlife, with BMI showing stronger associations than BP. Visual Overview: An online visual overview is available for this article.
Availability of anticancer biosimilars in 40 countries
Authors: Hui-Yao Huang, Da-Wei Wu, Fei Ma, Zhi-Lei Liu, Ju-Fang Shi, Xia Chen, Shu-Hang Wang, Hong Fang, Ying Bai, Yue Yu, Yuan Fang, Chao Sun, Qi Fan, Ying Wu, Rui-Hua Fan, Cai-Yun Zhou, Bao-Xia He, Min Dai, Ning Li, Bing-He Xu, Yan Sun, Jie He
Journal: The Lancet Oncology (2020)
KLF5 is an essential regulator of Myc expression
Authors: Peng Guo, Xue-yuan Dong, Kewen Zhao, Xiaodong Sun, Qunna Li, Jin-tang Dong
Journal: Cancer Research (2008)

66  KLF5 is a transcription factor that plays important roles in multiple physical and pathological processes including cell growth, cell cycle regulation and angiogenesis. KLF5 and MYC have similarities in distribution and functions in epithelial cells. Similar to MYC, expression of KLF5 strongly correlates with cell proliferation. In their physiological role, both KLF5 and MYC are broadly expressed during embryogenesis and in adult tissue compartments that possess high proliferative capacity, such as skin epidermis and gut. In addition, both of them up-regulate Cyclin D1 and suppress p15 in epithelial cells. Therefore, we investigated whether and how KLF5 regulates MYC expression. In the HaCaT immortalized epidermal epithelial cell line, we found that KLF5 knockdown reduced the expression of MYC at both RNA and protein levels, which was accompanied by reduced expression of MYC target genes hTERT and CDK4. To identify the binding site(s) of KLF5 on c-myc promoter, three different promoter activity reporter plasmids containing P1 and P2 c-myc promoters were transfected into HaCaT cells, and their activities were dramatically decreased by KLF5 knock down. Through CHIP assay, it was found that KLF5 binds to -108 to +54 bp of the c-myc promoter in vivo. To further identify the exact binding site of KLF5 in this region, TGF-β Inhibitory Element (TIE) GGCTTGGCGGG, which is essential for MYC expression and could be a potential KLF5 binding site as a GC rich element, was mutated to an AT-rich sequence in oligonucleotides or reporter plasmids. Through Oligo pull-down assay, we found that KLF5 bound to wildtype TIE, but the GGCT mutant abolished their interaction. This result suggests that KLF5 binds to GGCT in the TIE to regulate MYC expression. This was confirmed by luciferase activity assay in which the GGCT mutant significantly decreased c-myc promoter activity. Since KLF5 binds to TIE sequence, we further detected the effect of KLF5 on MYC expression in the presence of TGFβ. In HaCaT cells, KLF5 knockdown decreased the inhibitory effect of TGFβ on MYC expression. On the other hand, over-expression of KLF5 in PC3 and MDA-MB-231 tumor cells rescued the inhibition of MYC by TGFβ. These results indicate that deletion of KLF5 in prostate and breast cancers may impair the inhibition of MYC expression by TGFβ. Our findings suggest that KLF5 is an essential regulator of MYC expression in epithelial cells.
Abstract 277: Long-Term Daily Prophylactic Supplement With Melatonin as a Health Care Medicine Significantly Improved Survival and Neurological Outcome After Cardiac Arrest
Authors: Yanan Hu, Xuyan Zhao, Mingxin Jin, Ge Jiang, Xin Sui, Fei Han
Journal: Circulation (2019)

Introduction: Prophylactic pharmacotherapy for health care in reducing death after cardiac arrest (CA) is an elusive and less explored strategy. Melatonin, a natural health product contributing to sleep, was elevated upon arousal from torpor in hibernating mammals, which increased survival after blood return and reduced reperfusion injury. In this study, we sought to find the effects of long-term daily prophylactic supplement with melatonin as a health care medicine on the victim of CA. Methods: SD rats, 240-340 g, were used in this study. Sham, CA, and melatonin + CA (Mel + CA) groups were included. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 mins asphyxia and followed by manual CPR. The endpoint was 24 h after resuscitation. Neurological outcome was assessed. Hippocampal mitochondrial integrity, dynamics and function were observed. Results: Survival in the Mel + CA group was significantly higher than in the CA group (78% vs. 44%, P = 0.036). NDS was better in the Mel + CA group than the CA group ( P &lt; 0.001). Neurons of CA1 were less damaged in the Mel + CA group than in the CA group (Figure). The mitochondria integrity in the CA group was severely damaged compared with the Mel + CA group. Sirt3 was highly expressed in the Mel + CA group than in the CA group ( P &lt; 0.05). Ac-CypD was lower in the Mel + CA group than in the CA group ( P &lt; 0.05). Drp1 was lower in the Mel + CA group than in the CA group ( P &lt; 0.05). LC3 was highly expressed in the Mel + CA group than in the CA group ( P &lt; 0.05). ΔΨm, mitochondria respiratory rate, and respiratory control rate were higher in the Mel + CA group than in the CA group ( P &lt; 0.05). ROS production was lower in the Mel + CA group ( P &lt; 0.05). Cleaved caspase-3 and caspase-9 were lower in the Mel + CA group ( P &lt; 0.05). Conclusions: Long-term daily prophylactic supplement with melatonin as a health care medicine significantly improved survival, neurological outcome and neuronal mitochondrial function after cardiac arrest.
テトラヒドロフランジオール類(THF-ジオール),ロイコトキシンジオール類(LTX-ジオール)とラットにおける内分泌撹乱
Authors: M Markaverich Barry, Alejandro Mary, Thompson Trellis, Mani Shaila, Reyna Andrea, Portillo Wendy, Sharp John, Turk John, R Crowley Jan
Journal: Environmental Health Perspectives (2007)
超高齢者における頚動脈エコー(CE)所見の検討 動脈硬化の自然歴に迫れるか? | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 山内優美, 岡本勝, 青木智宏, 高見徹, 平岡裕
Journal: Circulation (2002)
THE PPAR gamma AGONIST PIOGLITAZONE UPREGULATES EAAT2 EXPRESSION IN HUMAN GLIOBLASTOMA CELLS
Authors: Jared Ching, Stephanie Amiridis, Andrew Bjorksten, Thomas Zheng, Stanley Stylli, Andrew Morokoff, Terence O'Brien, Andrew H Kaye
Journal: Neuro-Oncology (2014)
Four Faces of Fair Subject Selection
Authors: Douglas MacKay, Katherine Witte Saylor
Journal: The American Journal of Bioethics (2020)

Although the principle of fair subject selection is a widely recognized requirement of ethical clinical research, it often yields conflicting imperatives, thus raising major ethical dilemmas regarding participant selection. In this paper, we diagnose the source of this problem, arguing that the principle of fair subject selection is best understood as a bundle of four distinct sub-principles, each with normative force and each yielding distinct imperatives: (1) fair inclusion; (2) fair burden sharing; (3) fair opportunity; and (4) fair distribution of third-party risks. We first map out these distinct sub-principles, and then identify the ways in which they yield conflicting imperatives for the design of inclusion and exclusion criteria, and the recruitment of participants. We then offer guidance for how decision makers should navigate these conflicting imperatives to ensure that participants are selected fairly.
Effectiveness of an e-health tennis-specific injury prevention programme: randomised controlled trial in adult recreational tennis players
Authors: Haiko Ivo Maria Franciscus Lodewijk Pas, Babette M Pluim, Ozgur Kilic, Evert Verhagen, Vincent Gouttebarge, Rebecca Holman, Maarten H Moen, Gino M Kerkhoffs, Johannes L Tol
Journal: British Journal of Sports Medicine (2020)

Background Despite reported injury rates of up to 3 per 1000 hours exposure, there are no evidence-based prevention programmes in tennis. Purpose To evaluate the effectiveness of an e-health prevention programme for reducing tennis injury prevalence. Study design Two-arm, researcher-blinded randomised controlled trial. Methods Adult tennis players of all playing levels were randomised in an unsupervised programme lasting 12 weeks (TennisReady group or control group). The primary outcome was the overall injury prevalence over a 16-week period, measured at 2 weekly intervals with the Oslo Sports and Trauma Research Centre questionnaire. Estimates for the primary outcome and associated 95% CIs were obtained using generalised estimating equation models. Secondary outcome scores included prevalence of substantial injuries, overall incidence, adherence and time-loss injuries. Results A total of 579 (83%) (TennisReady n=286, control n=293) participants were included in the primary analysis. The mean injury prevalence was 37% (95% CI 33% to 42%) in the TennisReady vs 38% (95% CI 34% to 42%) in the control group (adjusted p-value 0.93). The prevalence of substantial injuries was 11% (95% CI 9% to 14%) in the TennisReady vs 12% (95% CI 9% to 15%) in the control group (p value of 0.79). Analysis of the secondary outcome scores showed no difference between groups. The mean prevalence rates between high (8%) and low (92%) adherent groups were 32% (95% CI 23% to 44%) and 37% (95% CI 33% to 42%), respectively (p value 0.36). Conclusion Providing an unsupervised e-health tennis-specific exercise programme did not reduce the injury rates and should not be implemented. Trial registration number NTR6443.
Is Nonalcoholic Fatty Liver Disease Not a Risk Factor for Cardiovascular Disease: Not Yet Time for a Change of Heart
Authors: Jacqueline B. Henson, Michael Roden, Giovanni Targher, Kathleen E. Corey
Journal: Hepatology (2020)

Henson, Jacqueline B. M.D.; Roden, Michael M.D.; Targher, Giovanni M.D.; Corey, Kathleen E. M.D.Editor(s): Corey, Kathleen E.7; Malhi, Harmeet8 Author Information
What’s hot that the other lot got
Authors: Alice Davies
Journal: Thorax (2020)

Prognosis and treatment options for small cell lung cancer (SCLC) remain poor and it is yet to see the benefits in prognosis conferred by immunotherapy in non-SCLC. CASPIAN was a randomised, open-label, phase III trial assessing the efficacy and safety of durvalumab (a monoclonal antibody that blocks PD-L1), with or without tremelimumab (a monoclonal antibody against CTLA-4) in combination with chemotherapy with platinum–etoposide, for the first-line treatment of patients with extensive stage SCLC (ES-SCLC). A total of 805 treatment-naive patients across 20 sites were randomly assigned into each cohort 1:1:1. Paz-Ares et al ( Lancet 2019:doi10.1016/S0140-6736(19)32222-6) report the interim survival analysis of the durvalumab plus platinum–etoposide versus platinum–etoposide groups. The addition of durvalumab was associated with a significant improvement versus chemotherapy alone in clinical outcomes including overall survival, with a HR of 0.73 (95% CI 0.59 to 0.91; p=0·0047); median overall survival was also prolonged at 13.0 (95% CI 11.5 to 14.8) months versus 10.3 (95% CI 9.3 to 11.2) months. Similar adverse events profiles were reported in both groups. These results align with those reported …
Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials
Authors: Frits van Rhee, Corey Casper, Peter M Voorhees, Luis E Fayad, Damilola Gibson, Karan Kanhai, Razelle Kurzrock
Journal: The Lancet Haematology (2020)
残存腫瘍の大きさ及びIGCCCGリスク分類法は,胚細胞腫瘍と残存腫瘍切除を有する患者において,追加の血管手術の要否を予測する:ドイツの精巣癌研究群の複数センターでの分析
Authors: Winter Christian, Bingoel Cigdem, Albers Peter, Pfister David, Heidenreich Axel, Busch Jonas, Ranft Ulrich, Schrader Mark, Dieckmann Klaus-Peter
Journal: European Urology (2012)