tbuckley/cabot-search huggingface dataset:
Accelerated barrier recovery and enhancement of the barrier integrity and properties by topical application of a pH 4 vs. a pH 5·8 water-in-oil emulsion in aged skin
Authors: I. Angelova-Fischer, T.W. Fischer, C. Abels, D. Zillikens
Journal: British Journal of Dermatology (2018)

Increased skin‐surface pH is an important host‐related factor for deteriorated barrier function in aged skin. We investigated whether restoration of skin pH through topical application of a water‐in‐oil emulsion with pH 4 improved the barrier homeostasis in aged skin, and compared the effects with an identical galenic formulation with pH 5·8. The effects of the test formulations on barrier recovery were investigated by repeated measurements of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone‐induced impairment of barrier function in aged skin. The long‐term effects of the pH 4 and pH 5·8 emulsions were analysed by investigation of the barrier integrity and cohesion, the skin‐surface pH and the skin roughness and scaliness before and after a 4‐week, controlled application of the formulations. The application of the pH 4 emulsion accelerated barrier recovery in aged skin: 3 h and 6 h after acetone‐induced barrier disruption the differences in the TEWL recovery between the pH 4 treated and acetone control fields were significant. Furthermore, long‐term application of the pH 4 formulation resulted in significantly decreased skin pH, enhanced barrier integrity and reduced skin‐surface roughness and scaliness. At the same time points, the pH 5·8 formulation exerted only minor effects on the barrier function parameters. Exogenous acidification through topical application of a water‐in‐oil emulsion with pH 4 leads to improvement of the skin barrier function and maintenance of the barrier homeostasis in aged skin.
Analysis of cluster randomised trials with an assessment of outcome at baseline
Authors: Richard Hooper, Andrew Forbes, Karla Hemming, Andrea Takeda, Lee Beresford
Journal: BMJ (2018)

In a cluster randomised clinical trial, all the participants who belong to the same cluster (eg, a local community, school, or general practice) are randomised to receive the same treatment. People from the same cluster tend to be more similar than those from different clusters, and the analysis must allow for this.<b><i></i></b>A common enhancement is to add an assessment of participants' outcomes in a baseline period—that is, before randomisation. Even if different participants are assessed at baseline and follow-up, the fact that they are sampled from the same cluster allows some control for cluster differences. But the analysis of cluster randomised trials is more complex than for individually randomised trials, and it is not obvious how best to adjust for baseline assessments. A variety of methods of analysis have been suggested: in this article, we describe different approaches and their flaws, and make recommendations.
Chemically defined and growth-factor-free culture system for the expansion and derivation of human pluripotent stem cells
Authors: Shin-ya Yasuda, Tatsuhiko Ikeda, Hosein Shahsavarani, Noriko Yoshida, Bhavana Nayer, Motoki Hino, Neha Vartak-Sharma, Hirofumi Suemori, Kouichi Hasegawa
Journal: Nature Biomedical Engineering (2018)
General practice doubles its QOF attainment
Authors: Caroline White
Journal: BMJ (2012)

Almost twice as many general practices achieved the maximum score on the GP reward and incentive scheme last year as did practices the previous year, new figures from the NHS Health and Social Care Information Centre show.

In 2011-12, 2.4% of practices—192 of a total of 8123—achieved the full 1000 points on the Quality and Outcomes Framework (QOF) scheme, which rewards GPs for the quality of care they give …
DNA damage and repair (DDR) gene variants and outcomes in localized and metastatic prostate cancer (mPC).
Authors: Brandon David Bernard, Kathryn P. Gray, Grace Shaw, Laura E MacConaill, Carolyn Evan, Anis Hamid, Atish Dipankar Choudhury, Christopher Sweeney
Journal: Journal of Clinical Oncology (2018)

304 Background: Moderate frequencies of DDR gene variants exist in mPC. Their prognostic role in localized and mPC is unclear. This study aims to characterize DDR variants in a cohort of hormone sensitive localized and mPC and assess for association with outcome. Methods: A retrospective cohort of men with PC and ≥ 2 follow up visits at DFCI and targeted next generation sequencing of prostate or metastatic tissue was identified. Biomarker (BM) positive was defined as pathogenic changes in the following DDR genes: ATM BAP1 BRCA1 BRCA2 BRIP1 CHEK2 MSH2 MSH6 PALB2 PMS2. For localized PC, outcome endpoints included event-free survival (EFS) (time from prostate biopsy to PSA relapse/metastasis/death), metastasis-free survival (MFS) (time to metastasis/death), time to castration resistance (CRPC), and death (OS); for mPC, outcome events included time from androgen deprivation start to CRPC and OS. BM status was descriptively summarized. Kaplan-Meier method and Cox regression model assessed associations of BM status with clinical outcomes. Results: Of the 237 men included, 16 (7%) were BM positive; 12 (6%) in 205 localized PC, 6 (14%) in 43 mPC. BM positive genes included 9 (4%) ATM, 6 (3%) BRCA2, and 2 (0.8%) CHEK2. In men with localized PC, EFS events occurred in 58% (7/12) BM positive vs 34% (66/193) BM negative at median follow up of 3.1 years; BM positive trended toward a shorter EFS (median 1.9 vs 5 years) than BM negative (HR 2.17, 95%CI 0.99-4.76). MFS events were observed in 17% (2/12) BM positive vs 7% (15/193) BM negative. CRPC events occurred in 17% (2/12) BM positive vs 6% (11/193) BM negative. In men with mPC, there were CRPC events in 100% (6/6) BM positive vs 67% (25/37) BM negative at median follow up of 3.3 years; BM positive trended toward a shorter time to CRPC (median 4 vs 8.8 months) compared to BM negative (HR 1.87, 95%CI 0.76-4.64). There was no association between BM status and OS. Conclusions: DDR variants appear infrequently in localized PC but may portend a shorter time to PSA relapse and metastasis. Similarly, DDR variants in mPC may be associated with a shorter time to CRPC. Low frequency of variants and short follow up limit these analyses. The prognostic value of DDR variants remains unclear and requires further research.
What is the difference between neuropathology and histopathology?
Authors: Carl Gray
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Dual role for inositol‐requiring enzyme 1α in promoting the development of hepatocellular carcinoma during diet‐induced obesity in mice
Authors: Ying Wu, Bo Shan, Jianli Dai, Zhixiong Xia, Jie Cai, Tianwei Chen, Songya Lv, Yuxiong Feng, Ling Zheng, Yan Wang, Jianfeng Liu, Jing Fang, Dong Xie, Liangyou Rui, Jianmiao Liu, Yong Liu
Journal: Hepatology (2018)

Obesity is associated with both endoplasmic reticulum (ER) stress and chronic metabolic inflammation. ER stress activates the unfolded protein response (UPR) and has been implicated in a variety of cancers, including hepatocellular carcinoma (HCC). It is unclear whether individual UPR pathways are mechanistically linked to HCC development, however. Here we report a dual role for inositol‐requiring enzyme 1α (IRE1α), the ER‐localized UPR signal transducer, in obesity‐promoted HCC development. We found that genetic ablation of IRE1α in hepatocytes not only markedly reduced the occurrence of diethylnitrosamine (DEN)‐induced HCC in liver‐specific IRE1α knockout (LKO) mice when fed a normal chow (NC) diet, but also protected against the acceleration of HCC progression during high‐fat diet (HFD) feeding. Irrespective of their adiposity states, LKO mice showed decreased hepatocyte proliferation and signal transducer and activator of transcription 3 (STAT3) activation, even in the face of increased hepatic apoptosis. Furthermore, IRE1α abrogation blunted obesity‐associated activation of hepatic inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ)‐nuclear factor kappa B (NF‐κB) pathway, leading to reduced production of the tumor‐promoting inflammatory cytokines tumor necrosis factor (TNF) and interleukin 6 (IL‐6). Importantly, higher IRE1α expression along with elevated STAT3 phosphorylation was also observed in the tumor tissues from human HCC patients, correlating with their poorer survival rate. Conclusion : IRE1α acts in a feed‐forward loop during obesity‐induced metabolic inflammation to promote HCC development through STAT3‐mediated hepatocyte proliferation. (H epatology 2018).
Many CESR and CEGPR decisions take longer than the statutory three months
Authors: Caroline White
Journal: BMJ (2012)

The General Medical Council is failing to meet its statutory three month target for certifying doctors who want to join the medical register through the equivalence routes, its own performance figures show.

However, the regulator has said that it expects to reach decisions on 95% of all applications for the certificate of eligibility for specialist registration (CESR) and certificate of eligibility for general practice registration (CEGPR) within the three month timeframe by the end of the year.

Doctors who have not followed a GMC approved training programme and been awarded a certificate of completion of training (CCT) must have a CESR or CEGPR to be licensed to practise as a consultant or GP in the UK.

Responsibility for the certification and registration of specialists and GPs through these equivalence …
Volume reduction rate of the primary tumor as an objective clinical measure to evaluate efficacy of neoadjuvant chemotherapy for esophageal squamous cell carcinoma.
Authors: Shinsuke Nagasawa, Takashi Ogata, Kentaro Hara, Hiroaki Osakabe, Masato Nakazono, Yuta Kumazu, Tsutomu Hayashi, Takanobu Yamada, Yasushi Rino, Munetaka Masuda, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2018)

42 Background: Neoadjuvant chemotherapy (NAC) followed by surgery is a standard treatment for esophageal squamous cell carcinoma (ESCC) in Japan. Efficacy of NAC on the primary tumor is clinically evaluated during NAC and before surgery and is pathologically examined after surgery. Clinical evaluation of the primary tumor is sometimes difficult because primary tumor is nonmesurable lesion and is usually evaluated subjectively, while pathological finding is objective and a gold standard to evaluate efficacy of NAC. In the present study, we tried to evaluate clinicaly efficacy objectively by calcurating tumor volume by esophagography and concordance between volume reduction rate and pathological efficacy. Methods: This retrospective study examined 53 patients who fullfilled the following criteria; (1) thoracic ESCC, (2) underwent resection following NAC between January 2011 and February 2017, and (3) T2-3N0 before surgey. Clinically, volume of the primary tumor was calculated by multiplying length and thickness in the lateral view of esophagography. Pathological efficacy was examined by the proportion of the tumor disappearance of the primary tumor and was classified as Grade 0-1 when degeneration area was &lt; 2/3, Grade 2 when those area was &gt; 2/3 and &lt; 3/3, and Grade 3 when there was no residual tumor. Volume reduction rate calculrated by the difference of pre- and post-NAC was compared by stratifying pathological grade. Results: T2/T3 was 23/30, respectively. Regimen of neoadjuvant chemotherapy was 5-FU/CDDP in 50 patients,docetaxel/5-FU/CDDP in 1,and 5-FU/CDDP and Radiotherapy in 2. Overall volume reduction rate was 58.9% in median (range -127-100%). Pathological response (Grade 0-1/2/3) was 28/18/4, respectively. Median volume reduction rate (range) was 38.5% (-127-100%) in Grade 0-1, 72.2% (21.7-100%) in Grade 2, and 91.1% (75.5-100%) in Grade 3, which was significantly different (p &lt; 0.01). Conclusions: The volume reduction rate of the primary tumor was correlated with pathological efficacy, suggesting that volume reduction rate could be a objective measure to evaluate efficacy of neoadjuvant chemotherapy for ESCC.
Beware of Limb Lead Reversal—Reply
Authors: Maen D. Abou Ziki, Lynda E. Rosenfeld
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
PATTERNA: transcriptome-wide search for functional RNA elements via structural data signatures
Authors: Mirko Ledda, Sharon Aviran
Journal: Genome biology (2018)

Establishing a link between RNA structure and function remains a great challenge in RNA biology. The emergence of high-throughput structure profiling experiments is revolutionizing our ability to decipher structure, yet principled approaches for extracting information on structural elements directly from these data sets are lacking. We present PATTERNA, an unsupervised pattern recognition algorithm that rapidly mines RNA structure motifs from profiling data. We demonstrate that PATTERNA detects motifs with an accuracy comparable to commonly used thermodynamic models and highlight its utility in automating data-directed structure modeling from large data sets. PATTERNA is versatile and compatible with diverse profiling techniques and experimental conditions.
CESR=CCT, says chairman of Academy of Medical Royal Colleges
Authors: Helen Jaques
Journal: BMJ (2012)

Employers should view the certificate of eligibility for specialist registration (CESR) as identical to the Certificate of Completion of Training (CCT), the chairman of the Academy of Medical Royal Colleges has recommended. 

Speaking at the joint royal colleges’ conference for staff and associate specialist doctors last week, Neil Douglas said that colleges need to work to remove the “stigma” associated with the …
NHS should keep national pay framework for Agenda for Change staff, says health department
Authors: Helen Jaques
Journal: BMJ (2012)

The NHS should retain a national pay framework for staff on the Agenda for Change contract (most staff, but not doctors, dentists, and senior managers) rather than move to a completely decentralised local approach to determining salaries, the Department of Health has said.

However, employers should make better use of existing flexibilities …
The problems facing academic surgeons
Authors: Zain Khalpey
Journal: BMJ (2004)

It's fascinating how simple questions such as “Do you want to be an academic?” can sometimes land a trainee in a difficult position. “Not sure” is always the safest bet because aspiring to academia (or rather, admitting to aspiring to academia) at an early stage of your career carries the risk of being misinterpreted: you might be seen as an arrogant part timer, a failing clinician, an inadequately skilled surgeon, or someone looking for an alternative career.

The present cultural view of surgical academia is something of an oxymoron because it strays from the Arcadian role of a surgeon: one who knows nothing but does everything. The Oxford Dictionary defines an academic as “a teacher or scholar in a university or institute of higher learning,” conventionally with duties including teaching and research. When you add these definitions together, you end up with a person who operates, teaches, and does research.

Trainees may aspire to academia in order to reach the pinnacle of their …
RX‐3117, an oral hypomethylating agent to treat advanced solid tumors: Interim results from an ongoing phase 2a study in advanced urothelial cancer (aUC).
Authors: Meghan Salgia, Sumanta K. Pal, Vincent M. Chung, Scott T. Tagawa, Joel Picus, Hani M. Babiker, Sumati Gupta, Julie Poore, Christine Peterson, Ely Benaim
Journal: Journal of Clinical Oncology (2018)

501 Background: RX-3117 is an oral small molecule hypomethylating agent, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 shows efficacy in various xenograft models, including those of gemcitabine resistant bladder cancer. Preliminary data from Stage 2 of a Phase 2a clinical study of RX‐3117 as a single agent in subjects with aUC is described below. Methods: This Phase 2a study (2‐stage design, NCT02030067) evaluates the efficacy of RX‐3117 in eligible patients (aged ≥ 18 years) with refractory aUC. Primary objectives include safety and efficacy of the recommended Phase 2 dose and schedule identified in the Phase 1 portion of the study. Patients received 700 mg of oral RX‐3117 daily for either 3 weeks with 1 week off in each 4-week cycle or 4 continuous weeks. The primary endpoint is a ≥ 20% rate of progression free survival benefit (i.e., proportion of patients with stable disease for at least 4 months) and/or a 10% of evaluable patients with a partial response or better. Results: As of October 2017, 17 patients (12 males, 5 females) with aUC were treated with RX‐3117. The median age was 66 years, ECOG performance status was 0 to 1 and 53% received ≥ 3 prior therapies. Metastatic disease sites included lung, liver, lymph nodes, and mediastinum. Four patients achieved stable disease for 4 cycles of RX‐3117 treatment; one patient received treatment for 168 days and another patient for 301 days. One patient showed tumor shrinkage as measured by RECIST (‐15.5%) after 4 cycles of RX-3117; another patient showed a 19% tumor reduction after 1 cycle. The most frequent related adverse events were G1 diarrhea (13%), fatigue (13%), nausea (10%), G1/G2 anemia (10%), vomiting (10%) and G3 thrombocytopenia (10%). Conclusions: RX‐3117 is safe and well tolerable and shows preliminary evidence of anti-tumor activity. The study continues to enroll patients with aUC in Stage 2. Clinical trial information: NCT02030067.
RATES OF ANTICOAGULATION FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Sarah Gorgis, Elsheikh Abdelrahim, Dee Dee Wang, Janet Fredal Wyman, Gaetano Paone, Adam Greenbaum, Brad Kendall, William W. O’Neill, Marvin Eng
Journal: Journal of the American College of Cardiology (2018)
Impact of pre-existing diabetes mellitus on survival in stage I renal cell carcinoma.
Authors: Stephen Ryan, Ahmet Bindayi, Aaron Bloch, Ryan Nasseri, Zachary Hamilton, Kendrick Yim, Madhumitha Reddy, Fang Wan, Umberto Capitanio, Alessandro Larcher, Francesco Montorsi, Brian R. Lane, Sabrina L Noyes, Sumi Dey, Robert Uzzo, Shreyas Joshi, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2018)

676 Background: AUA guidelines recommend consideration of nephron sparing surgery in patients with comorbidities that are likely to impact renal function, such as diabetes mellitus (DM). We compared the impact of partial nephrectomy (PN) and radical nephrectomy (RN) on overall survival (OS) in patients with pre-existing DM and Stage I Renal Cell Carcinoma (RCC). Methods: Multicenter retrospective analysis of surgically treated Stage I RCC from 2005-16 with or without DM. Primary outcome was OS analyzed by DM+ or DM- and surgical approach (PN or RN) for AJCC Stage I. Logistic (OR) and Cox (HR) regression were utilized for OS. Results: 2173 patients were analyzed (1223 RN, 1819 PN, 555 DM+, 2487 DM-) with mean follow-up of 49.1 months. Increasing Age (OR 1.028, p = .009), RN (OR 2.446, p = .001), and most recent eGFR &lt; 45 (OR 2.306 p = .002) remained significant on multivariate analysis for OS (Table 1). In the PN subgroup, DM+ or DM- was not associated with decreased OS (HR 1.48 p = 0.19). DM+ was associated with decreased OS in the RN subgroup (HR 1.97 p = 0.005). Conclusions: In Stage I RCC, DM and RN negatively impacted OS, while only RN remained significant on MVA. Subgroup analysis of PN showed that OS was similar in DM- and DM+ patients, but diagnosis of DM had a profound impact on OS in the RN group. This supports the guideline statements and offers evidence that urologists should prioritize nephron sparing surgery in patients with DM and Stage I Renal Cell Carcinoma.[Table: see text]
How health informatics will revolutionise medicine
Authors: Apul R Parikh, Mark Lloyd, Jon Simmons, Simon Withey, Peter E M Butler
Journal: BMJ (2006)

“What do you mean my notes have gone missing?” “The hospital must have a copy of my notes?” “I never received the clinic appointment letter.” Comments such as these are a common occurrence, and both patients and clinicians have lost faith in the organisational abilities of hospitals.

Health informatics is an emerging academic discipline that will have a fundamental role in healthcare delivery. It deals with the application of information and communication technologies to health care.1 The need for better information for health is one …
Once-weekly carfilzomib, pomalidomide, and low-dose dexamethasone for relapsed/refractory myeloma: a phase I/II study
Authors: Sara Bringhen, Roberto Mina, Anna Maria Cafro, Anna Marina Liberati, Stefano Spada, Angelo Belotti, Gianluca Gaidano, Francesca Patriarca, Rossella Troia, Renato Fanin, Lorenzo De Paoli, Giuseppe Rossi, Alessandra Lombardo, Paola Bertazzoni, Antonio Palumbo, Pieter Sonneveld, Mario Boccadoro
Journal: Leukemia (2018)