tbuckley/cabot-search huggingface dataset:
GPs reject working from 8 am to 8 pm, seven days a week
Authors: Abi Rimmer
Journal: BMJ (2014)

GPs have agreed that they will not support the idea of working from 8 am to 8 pm, seven days a week.

Delegates at the BMA’s conference of local medical committees (LMCs) in York voted in favour of a motion that rejected the “concept of routine general practice care 8 to 8, seven days a week.” Delegates also voted in favour of part of the motion that commended general practice “for already …
Expanding the Scope of High-Value Practice Beyond Guideline-Based Care—Reply
Authors: Emmanuel Coronel, Vineet M. Arora, K. Gautham Reddy
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Overall and Central Obesity and Risk of Lung Cancer: A Pooled Analysis
Authors: Danxia Yu, Wei Zheng, Mattias Johansson, Qing Lan, Yikyung Park, Emily White, Charles E Matthews, Norie Sawada, Yu-Tang Gao, Kim Robien, Rashmi Sinha, Arnulf Langhammer, Rudolf Kaaks, Edward L Giovannucci, Linda M Liao, Yong-Bing Xiang, DeAnn Lazovich, Ulrike Peters, Xuehong Zhang, Bas Bueno-de-Mesquita, Walter C Willett, Shoichiro Tsugane, Yumie Takata, Stephanie A Smith-Warner, William Blot, Xiao-Ou Shu
Journal: JNCI Journal of the National Cancer Institute (2017)

The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored.
Associations between women's perceptions of gender relations and self-esteem and self-efficacy in a former conflict zone: baseline findings in South Kivu, DR Congo
Authors: Clea Sarnquist, Rasika Behl, Aisha Talib, Jonathan Altamirano, Barbara Jerome, Joseph Inungu, Yvonne Maldonado
Journal: The Lancet Global Health (2018)

BackgroundEastern DR Congo is recovering from decades of armed conflict in which violence against women (VAW) was widely used as a weapon of war. Even now, rates remain high: 34·5% and 47·5% of women in South Kivu report ever experiencing sexual or physical violence, respectively. However, there are few data on the impact of VAW on the health of women and their children.MethodsIn August 2016, we collected baseline data on demographic and health-related variables from mothers of children younger than 5 years in 843 households enrolled as part of a larger impact evaluation. Women's empowerment was measured using the previously validated Rosenberg's self-esteem scale (RSES), the generalised self-efficacy scale (GSES), and a gender relations scale originally developed by the Medical Research Council of South Africa. GSES and RSES scores were generated by averaging individual responses to questions; bivariate analyses of the scores with individual gender relations questions were conducted using χ2 tests.FindingsOf the 845 mothers interviewed, 325 (45·5%) had less than a primary education. The mean number of children younger than 18 years per household was four, with 66 (8%) of households having more than seven such children. Mean self-esteem score was 18·2 (SD 5·3) and mean self-efficacy score was 26·2 (SD 6·3), and internal reliability tests of the RSES and GSES scales yielded alphas of α=0·76 and α=0·89, respectively. Women with higher GSES or RSES scores were less likely to accept physical violence or sexual coercion than women with lower scores (p<0·05); however, perception of male authority and gender roles within the household did not vary by score.InterpretationThis population of women had lower self-esteem than for a generalised population in DR Congo (21·3), probably because of the prolonged conflict in eastern DR Congo. Furthermore, mean GSES was lower than that of another post-conflict setting (Iran, 30·2), as well as several higher-income countries (29–32).FundingAmerican Refugee Committee.
Patient-Customized Drug Combination Prediction and Testing for T-cell Prolymphocytic Leukemia Patients
Authors: Liye He, Jing Tang, Emma I. Andersson, Sanna Timonen, Steffen Koschmieder, Krister Wennerberg, Satu Mustjoki, Tero Aittokallio
Journal: Cancer Research (2018)

The molecular pathways that drive cancer progression and treatment resistance are highly redundant and variable between individual patients with the same cancer type. To tackle this complex rewiring of pathway cross-talk, personalized combination treatments targeting multiple cancer growth and survival pathways are required. Here we implemented a computational-experimental drug combination prediction and testing (DCPT) platform for efficient in silico prioritization and ex vivo testing in patient-derived samples to identify customized synergistic combinations for individual cancer patients. DCPT used drug-target interaction networks to traverse the massive combinatorial search spaces among 218 compounds (a total of 23,653 pairwise combinations) and identified cancer-selective synergies by using differential single-compound sensitivity profiles between patient cells and healthy controls, hence reducing the likelihood of toxic combination effects. A polypharmacology-based machine learning modeling and network visualization made use of baseline genomic and molecular profiles to guide patient-specific combination testing and clinical translation phases. Using T-cell prolymphocytic leukemia (T-PLL) as a first case study, we show how the DCPT platform successfully predicted distinct synergistic combinations for each of the three T-PLL patients, each presenting with different resistance patterns and synergy mechanisms. In total, 10 of 24 (42%) of selective combination predictions were experimentally confirmed to show synergy in patient-derived samples ex vivo The identified selective synergies among approved drugs, including tacrolimus and temsirolimus combined with BCL-2 inhibitor venetoclax, may offer novel drug repurposing opportunities for treating T-PLL.Significance: An integrated use of functional drug screening combined with genomic and molecular profiling enables patient-customized prediction and testing of drug combination synergies for T-PLL patients. Cancer Res; 78(9); 2407-18. ©2018 AACR.
Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer’s Disease Models
Authors: C.Y. Daniel Lee, Anthony Daggett, Xiaofeng Gu, Lu-Lin Jiang, Peter Langfelder, Xiaoguang Li, Nan Wang, Yingjun Zhao, Chang Sin Park, Yonatan Cooper, Isabella Ferando, Istvan Mody, Giovanni Coppola, Huaxi Xu, X. William Yang
Journal: Neuron (2018)
Optimized RNP transfection for highly efficient CRISPR/Cas9-mediated gene knockout in primary T cells
Authors: Akiko Seki, Sascha Rutz
Journal: The Journal of Experimental Medicine (2018)

CRISPR (clustered, regularly interspaced, short palindromic repeats)/Cas9 (CRISPR-associated protein 9) has become the tool of choice for generating gene knockouts across a variety of species. The ability for efficient gene editing in primary T cells not only represents a valuable research tool to study gene function but also holds great promise for T cell–based immunotherapies, such as next-generation chimeric antigen receptor (CAR) T cells. Previous attempts to apply CRIPSR/Cas9 for gene editing in primary T cells have resulted in highly variable knockout efficiency and required T cell receptor (TCR) stimulation, thus largely precluding the study of genes involved in T cell activation or differentiation. Here, we describe an optimized approach for Cas9/RNP transfection of primary mouse and human T cells without TCR stimulation that results in near complete loss of target gene expression at the population level, mitigating the need for selection. We believe that this method will greatly extend the feasibly of target gene discovery and validation in primary T cells and simplify the gene editing process for next-generation immunotherapies.
DNA Nanotubes with Hydrophobic Environments: Toward New Platforms for Guest Encapsulation and Cellular Delivery
Authors: Janane F. Rahbani, Empar Vengut‐Climent, Pongphak Chidchob, Yasser Gidi, Tuan Trinh, Gonzalo Cosa, Hanadi F. Sleiman
Journal: Advanced Healthcare Materials (2018)

Abstract Natural systems combine different supramolecular interactions in a hierarchical manner to build structures. In contrast, DNA nanotechnology relies almost exclusively on DNA base pairing for structure generation. Introducing other supramolecular interactions can expand the structural and functional range of DNA assemblies, but this requires an understanding of the interplay between these interactions. Here, an economic strategy to build DNA nanotubes functionalized with lipid‐like polymers is reported. When these polymers are linked to the nanotube using a spacer, they fold inside to create a hydrophobic environment within the nanotube; the nanotube can encapsulate small molecules and conditionally release them when specific DNA strands are added, as monitored by single‐molecule fluorescence microscopy. When the polymers are directly linked to the nanostructure without spacers, they interact intermolecularly to form a network of DNA bundles. This morphological switch can be directly observed using a strand displacement strategy. The two association modes result in different cellular uptake behavior. Nanotubes with internal hydrophobic association show dye‐mediated mitochondrial colocalization inside cells; while the bundles disassemble into smaller polymer‐coated structures that reduce the extent of nonspecific cellular uptake. This approach uncovers parameters to direct the hierarchical assembly of DNA nanostructures, and produces promising materials for targeted drug delivery.
Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia
Authors: Jessica C. Petrov, Masayuki Wada, Kevin G. Pinz, Lulu E. Yan, Kevin H. Chen, Xiao Shuai, Hua Liu, Xi Chen, Lai-Han Leung, Huda Salman, Nabil Hagag, Fang Liu, Xun Jiang, Yupo Ma
Journal: Leukemia (2018)

Acute myeloid leukemia (AML) bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CD123 expression comprise a rare population that also plays an important role in disease progression and relapse. Here, we report on the robust anti-tumor activity of a compound CAR (cCAR) T-cell possessing discrete scFv domains targeting two different AML antigens, CD123, and CD33, simultaneously. We determined that the resulting cCAR T-cells possessed consistent, potent, and directed cytotoxicity against each target antigen population. Using four leukemia mouse models, we found superior in vivo survival after cCAR treatment. We also designed an alemtuzumab safety-switch that allowed for rapid cCAR therapy termination in vivo. These findings indicate that targeting both CD123 and CD33 on AML cells may be an effective strategy for eliminating both AML bulk disease and LSCs, and potentially prevent relapse due to antigen escape or LSC persistence.
A third of doctors report bullying or harassment by managers
Authors: Helen Jaques
Journal: BMJ (2013)

A third (33%) of doctors and dental staff in England have experienced harassment, bullying, or abuse from managers in the past 12 months, the 2012 NHS staff survey shows. Only 30% of doctors and dental staff experiencing such an incident reported it. 

Overall, 23% of NHS staff reported bullying at the hands of managers over the past 12 months. 

Of NHS staff who said they had experienced harassment, bullying, or abuse at work, 44% said that they …
EU rule changes could restrict sharing of patient information and limit medical research
Authors: Abi Rimmer
Journal: BMJ (2013)

Proposed changes to the European Union’s rules on data protection could restrict the sharing of patient data, the Royal College of Physicians and the NHS Confederation have warned.

The organisations said that the change in legislation could also have a negative effect on health research in the UK.

Last month the European Parliament’s committee for civil liberties, justice, and home affairs agreed its position on proposed Europe-wide regulations on data protection. The vote marked a key step …
Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis
Authors: Chun-Yuan Chen, Shan-Shan Rao, Lu Ren, Xiong-Ke Hu, Yi-Juan Tan, Yin Hu, Juan Luo, Yi-Wei Liu, Hao Yin, Jie Huang, Jia Cao, Zhen-Xing Wang, Zheng-Zhao Liu, Hao-Ming Liu, Si-Yuan Tang, Ran Xu, Hui Xie
Journal: Theranostics (2018)

Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism. Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses. USC-Exos were isolated from the conditioned media of USCs and identified by transmission electron microscopy and flow cytometry. A series of functional assays in vitro were performed to assess the effects of USC-Exos on the activities of wound healing-related cells. Protein profiles in USC-Exos and USCs were examined to screen the candidate molecules that mediate USC-Exos function. The effects of USC-Exos on wound healing in streptozotocin-induced diabetic mice were tested by measuring wound closure rates, histological and immunofluorescence analyses. Meanwhile, the role of the candidate protein in USC-Exos-induced regulation of angiogenic activities of endothelial cells and diabetic wound healing was assessed. Results: USCs were positive for CD29, CD44, CD73 and CD90, but negative for CD34 and CD45. USCs were able to differentiate into osteoblasts, adipocytes and chondrocytes. USC-Exos exhibited a cup- or sphere-shaped morphology with a mean diameter of 51.57 ± 2.93 nm and positive for CD63 and TSG101. USC-Exos could augment the functional properties of wound healing-related cells including the angiogenic activities of endothelial cells. USC-Exos were enriched in the proteins that are involved in regulation of wound healing-related biological processes. Particularly, a pro-angiogenic protein called deleted in malignant brain tumors 1 (DMBT1) was highly expressed in USC-Exos. Further functional assays showed that DMBT1 protein was required for USC-Exos-induced promotion of angiogenic responses of cultured endothelial cells, as well as angiogenesis and wound healing in diabetic mice. Conclusion: Our findings suggest that USC-Exos may represent a promising strategy for diabetic soft tissue wound healing by promoting angiogenesis via transferring DMBT1 protein.
PROLONGED PAUSES IN CARDIOPULMONARY RESUSCITATION ARE ASSOCIATED WITH POOR SURVIVAL DURING IN-HOSPITAL CARDIAC ARREST
Authors: John Birchak, Owais Abdul-Kafi, Trinh Pham, Maya Viner, Maria Nehmer, Birju Rao, Amer Ardati, Dustin Fraidenburg
Journal: Journal of the American College of Cardiology (2018)
Low back pain: a call for action
Authors: Rachelle Buchbinder, Maurits van Tulder, Birgitta Öberg, Lucíola Menezes Costa, Anthony Woolf, Mark Schoene, Peter Croft, Rachelle Buchbinder, Jan Hartvigsen, Dan Cherkin, Nadine E Foster, Chris G Maher, Martin Underwood, Maurits van Tulder, Johannes R Anema, Roger Chou, Stephen P Cohen, Lucíola Menezes Costa, Peter Croft, Manuela Ferreira, Paulo H Ferreira, Julie M Fritz, Stéphane Genevay, Douglas P Gross, Mark J Hancock, Damian Hoy, Jaro Karppinen, Bart W Koes, Alice Kongsted, Quinette Louw, Birgitta Öberg, Wilco C Peul, Glenn Pransky, Mark Schoene, Joachim Sieper, Rob J Smeets, Judith A Turner, Anthony Woolf
Journal: The Lancet (2018)
IV阶段一对一随机对照试验就治疗面部或头皮光化性角化病比较了巨大戟醇甲基丁烯酸酯0.015%凝胶与双氯芬酸钠3%凝胶
Authors: E. Stockfleth, C.A. Harwood, C. Serra-Guillén, T. Larsson, M.L. Østerdal, T. Skov
Journal: British Journal of Dermatology (2018)

这项在德国、西班牙和英国开展的研究比较了两种凝胶疗法对治疗面部或头皮光化性角化病(AK)的有效性。AK是指皮肤表面出现小型、穗状、有鳞片或类似砂纸状的晒伤区域。有很小的比例会发展成皮肤鳞状细胞癌。当整个头皮等大面积区域受到多处AK影响时,建议在皮肤表面擦拭膏药或凝胶。研究人员在502名患者中比较了巨大戟醇甲基丁烯酸酯0.015%凝胶(IngMeb)和双氯芬酸钠3%凝胶(DS),这些患者大部分是男性且几乎都是白皮肤。IngMeb每天擦一次,连续擦三天,而DS则每天擦两次,连续擦90天(一般建议用量)。使用IngMeb的患者在第八周时如果有新增或剩余的AK,则可进行第二个三天周期,这意味着,此群体中有一半以上的患者使用了两次IngMeb。在第17周(DS疗程完成约4周后,IngMeb第二疗程(如使用)完成9周后,以及IngMeb第一(或唯一)疗程完成17周后)观察治疗区域时发现,IngMeb群体中完全清除AK的患者人数几乎是DS群体的两倍。在IngMeb群体中,即便AK并未完全消失,但更多的AK已部分清除,并且AK总数也显著下降。副作用也相当温和或适中,最常见的是擦拭凝胶的区域出现红斑。
Indoor Tanning, Sunless Tanning, and Sun-Protection Behaviors Among Sexual Minority Men
Authors: Yi Gao, Sarah T. Arron, Eleni Linos, Ingrid Polcari, Matthew D. Mansh
Journal: JAMA Dermatology (2018)

Indoor Tanning, Sunless Tanning, and Sun-Protection Behaviors Among Sexual Minority Men Sexual minority men (SMM), including gay and bisexual men, report increased rates of skin cancer and indoor tanning, whereas sexual minority women report decreased rates of skin cancer and indoor tanning. 1 Indoor tanning has been associated with other risky behaviors, including decreased use of protective clothing and shade when outdoors. 2,3However, no data exist on these other skin cancer risk behaviors among SMM.This study assesses the impact of sexual orientation on indoor tanning, sunless tanning, and sun-protection behaviors among men.
Prevalence and clinical significance of respiratory viruses and bacteria detected in tuberculosis patients compared to household contact controls in Tanzania: a cohort study
Authors: F. Mhimbira, H. Hiza, E. Mbuba, J. Hella, L. Kamwela, M. Sasamalo, M. Ticlla, K. Said, G. Mhalu, M. Chiryamkubi, C. Schindler, K. Reither, S. Gagneux, L. Fenner
Journal: Clinical Microbiology and Infection (2018)
Monoclonal Antibodies for Emerging Infectious Diseases — Borrowing from History
Authors: Hilary D. Marston, Catharine I. Paules, Anthony S. Fauci
Journal: New England Journal of Medicine (2018)

Interview with Dr. Anthony Fauci on the use of monoclonal antibodies in the context of emerging infectious diseases. (09:25)Download Research advances could facilitate use of monoclonal antibodies for emerging infectious diseases — in treatment of infected individuals, targeted prophylaxis to protect high-risk individuals, and targeted prophylaxis to interrupt transmission in average-risk populations.
Impending workforce gaps could pose crisis for NHS, warns King’s Fund
Authors: Gareth Iacobucci
Journal: BMJ (2013)

The NHS will face a workforce crisis unless urgent action is taken to tackle impending staff shortages and shift the deployment of training resources, the health think tank the King’s Fund has warned.

A report by the fund has said that the current NHS workforce was ill equipped to meet the future challenges of an ageing population with more complex needs. The report warned of a mismatch between the supply and skills of different parts of the workforce and the needs of people using the service.1

The paper argued that the impending shortages of GPs …
Comparison of model-based dose escalation design with rule-based design of phase I oncology trials
Authors: A. Shimomura, T. Ebata, T. Koyama, S. Iwasa, S. Kondo, S. Kitano, K. Yonemori, Y. Fujiwara, T. Shimizu, N. Yamamoto
Journal: Annals of Oncology (2018)
The PACE trial: International randomised study of laparoscopic prostatectomy vs. stereotactic body radiotherapy (SBRT) and standard radiotherapy vs. SBRT for early stage organ-confined prostate cancer.
Authors: Kirsty Morrison, Alison Tree, Vincent Khoo, Nicholas John Van As
Journal: Journal of Clinical Oncology (2018)

TPS153 Background: The development of Stereotactic Body Radiotherapy (SBRT) has provided a further treatment option for early stage prostate cancer. In addition to the benefits of an overall treatment time reduction, profound hypofractionation could result in therapeutic gain given the radiobiology of prostate cancer. Evidence suggests SBRT to be safe and effective; however randomised data is lacking comparing outcomes with standard treatment options. Aim: To assess whether SBRT offers therapeutic benefit in comparison to prostatectomy or standard radiotherapy. Methods: The PACE trial is an international multicentre phase III trial, comprising two parallel randomisation processes. Within PACE A, potential surgical candidates are randomised between radical prostatectomy and SBRT (36.25 Gy in 5 fractions). In PACE B, randomisation is between standard radiotherapy (78Gy in 39 fractions or 62Gy in 20 fractions) and SBRT (36.35Gy in 5 fractions). SBRT can be delivered using Cyberknife or gantry based techniques. Patients with low or intermediate risk prostate cancer are eligible for the trial, and are treated without the use androgen deprivation therapy. Follow up is for a period of 10 years. The aim is to recruit 234 patients to PACE A (117 in each arm) and 858 patients to PACE B (429 patients in each arm). Primary Objectives: PACE A: To determine whether there is improved quality of life after SBRT compared with surgery at 2 years post treatment, using EPIC score to measure urinary incontinence and bowel bother. PACE B: to determine whether SBRT is non-inferior to surgery in terms of freedom from biochemical/clinical failure at 5 years from randomisation. Progress: PACE A has been slower to recruit than anticipated due to the difficulties of a surgery versus radiotherapy randomisation. However, it is expected to reach target accrual, having recruited 57 patients from 3 centres. In contrast, PACE B is recruiting exceptionally well, open in 40 centres, and as of October 2017 recruited 762 patients. Accrual target is expected to be reached by the end of 2017. Clinical trial information: NCT01584258.