tbuckley/cabot-search huggingface dataset:
Effectiveness of adjuvant radiotherapy after radical cystectomy for locally advanced bladder cancer.
Authors: Benjamin Walker Fischer-Valuck, Jeff M. Michalski, John Paul Christodouleas, Eric Kim, Todd A. DeWees, Gerald L. Andriole, Vivek Arora, Ruben Carmona, Robert S. Figenshau, Robert L. Grubb, Thomas J. Guzzo, Eric Marshall Knoche, S. Bruce Malkowicz, Ronac Mamtani, Russell Kent Pachynski, Joel Picus, Sriram Venigalla, Bruce J. Roth, Hiram Alberto Gay, Brian Christopher Baumann
Journal: Journal of Clinical Oncology (2018)

484 Background: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemo and is associated with high morbidity/mortality. Adjuvant radiotherapy (adjRT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of adjRT would improve OS in LABC in a large multi-institutional cohort. Methods: We identified ≥pT3 pN0-3, M0 LABC pts in the NCDB diagnosed in 2004 – 2013 who underwent RC +/- adjRT. AdjRT cohort included pts treated to ≥40Gy to the pelvis within 1 yr of diagnosis. Propensity matching was performed to match RC pts who received adjRT vs. those who did not. OS was calculated using Kaplan-Meier. Factors significant on univariate analysis were entered into Cox proportional hazards regression model to identify predictors of OS. Results: 15,246 RC pts were identified, with 450 (3.0%) receiving adjRT. Median OS was 23.0 mo (95% CI, 22.4-23.6) for RC vs. 19.7 mo (95% CI, 17.7-21.7) for adjRT [Log-rank P = 0.002; Wilcoxon P = 0.862]. Propensity score matching on demographic, clinical, &amp; treatment variables yielded 742 pts (371 in each group). In the matched cohort, OS was 17.1 mo [95%CI, 14.5 - 19.6] for RC vs. 20.1 mo [95% CI, 17.8– 22.5] for adjRT [Log-rank P = 0.044]. On MVA in the matched cohort, factors predictive of OS were sex, pT stage, pN+ status, surgical margin status, number of nodes removed, adjRT, &amp; chemo (p &lt; 0.01 for all). On MVA of subgroups, adjRT was associated with significantly improved OS in pts with positive margins [HR 0.55 (95% CI, 0.43 – 0.71), P &lt; 0.001], pN+ disease [HR 0.62 (95% CI, 0.49 – 0.79), P &lt; 0.001], &amp; pT4 disease [HR 0.68 (95% CI, 0.55 – 0.85), P = 0.001]. In MVA of pts with urothelial carcinoma (N = 578), adjRT remained associated with improved OS in pts with positive margins [HR 0.57 (95% CI, 0.43 – 0.76), P &lt; 0.001], pN+ disease [HR 0.65 (95% CI, 0.50 – 0.86), P = 0.002], &amp; pT4 disease [HR 0.68 (95% CI, 0.54 – 0.85), P = 0.001]. Conclusions: In this observational study, adjRT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of adjRT in selected pts with LABC, regardless of histology. Prospective trials of adjRT are warranted.
Suppression of diabetes by accumulation of non–islet-specific CD8 <sup>+</sup> effector T cells in pancreatic islets
Authors: Gustaf Christoffersson, Grzegorz Chodaczek, Sowbarnika S. Ratliff, Ken Coppieters, Matthias G. von Herrath
Journal: Science Immunology (2018)

Non–antigen-specific CD8 + T cells act as local suppressors to limit autoimmunity and viral inflammation.
Lords ensure that commissioners and providers have duty to promote education under health bill
Authors: Ingrid Torjesen
Journal: BMJ (2012)

The NHS Commissioning Board and local clinical commissioning groups will have a duty to promote education and training under a government amendment to the Health and Social Care Bill that has been approved by the House of Lords.

Another amendment to the bill tabled by the crossbench peer Narendra Patel was also agreed. This will require commissioners to put a duty in their commissioning contracts to ensure that providers of services pay regard to education and training.

Lord Patel …
Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial
Authors: N. Franklin Adkinson, William E. Strauss, Iain C. Macdougall, Kristine E. Bernard, Michael Auerbach, Robert F. Kaper, Glenn M. Chertow, Julie S. Krop
Journal: American Journal of Hematology (2018)

Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double-blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate-to-severe HSRs, including anaphylaxis, or moderate-to-severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate-to-severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least-squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.
Biomarkers of carcinogenesis and tumour growth in patients with cutaneous melanoma and obstructive sleep apnoea
Authors: Fernando Santamaria-Martos, Ivan Benítez, Cristina Girón, Ferran Barbé, Miguel-Angel Martínez-García, Luis Hernández, Josep M. Montserrat, Eduardo Nagore, Antonio Martorell, Francisco Campos-Rodriguez, Jaime Corral, Valentin Cabriada, Jorge Abad, Olga Mediano, Maria F. Troncoso, Irene Cano-Pumarega, Ana Maria Fortuna Gutierrez, Trinidad Diaz-Cambriles, Maria Somoza-Gonzalez, Isaac Almendros, Ramon Farre, David Gozal, Manuel Sánchez-de-la-Torre
Journal: European Respiratory Journal (2018)

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and the levels of carcinogenesis- and tumour growth-related biomarkers in patients with cutaneous melanoma. This multicentre observational study included patients who were newly diagnosed with melanoma. The patients were classified as non-OSA (apnoea–hypopnoea index (AHI) 0–5 events·h −1 ), mild OSA (AHI 5–15 events·h −1 ) and moderate–severe OSA (AHI &gt;15 events·h −1 ). ELISAs were performed to analyse the serum levels of hypoxia- and tumour adhesion-related biomarkers (vascular endothelial growth factor (VEGF), interleukin (IL)-8, intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)-1) and markers of tumour aggressiveness (S100 calcium-binding protein B (S100B) and melanoma inhibitory activity (MIA)). A logistic model adjusted for age, sex and body mass index was fitted to each biomarker, and the AHI served as the dependent variable. 360 patients were included (52.2% male, median (interquartile range) age 55.5 (43.8–68.0) years and AHI 8.55 (2.8–19.5) events·h −1 ). The levels of VEGF, IL-8, ICAM-1, S100B and MIA were not related to the severity of OSA. The levels of VCAM-1 were higher in patients with OSA than those without OSA (mild OSA: odds ratio (OR) 2.07, p=0.021; moderate–severe OSA: OR 2.35, p=0.013). In patients with cutaneous melanoma, OSA was associated with elevated circulating levels of VCAM-1 that could indicate the contribution of OSA in tumorigenesis via integrin-based adhesion.
Before I blew my first two pay cheques on a mountain bike
Authors: Andrew Morritt
Journal: BMJ (2004)

1.  That as a preregistration house officer, I would not have any time to ride the bike. Unlike medical school, where I had lots of spare time, I was now a professional and had responsibilities. I would have to turn up to work every day and could leave only when I had finished all my jobs. I would spend evenings …
Bayesian belief updating after a replication experiment
Authors: Alex O. Holcombe, Samuel J. Gershman
Journal: Behavioral and Brain Sciences (2018)

Abstract Zwaan et al. and others discuss the importance of the inevitable differences between a replication experiment and the corresponding original experiment. But these discussions are not informed by a principled, quantitative framework for taking differences into account. Bayesian confirmation theory provides such a framework. It will not entirely solve the problem, but it will lead to new insights.
Identification and Validation of Stromal Immunotype Predict Survival and Benefit from Adjuvant Chemotherapy in Patients with Muscle-Invasive Bladder Cancer
Authors: Hangcheng Fu, Yu Zhu, Yiwei Wang, Zheng Liu, Junyu Zhang, Huyang Xie, Qiang Fu, Bo Dai, Dingwei Ye, Jiejie Xu
Journal: Clinical Cancer Research (2018)

Abstract Purpose: This study aims to construct the stromal immunotype, which could improve the prediction of postsurgical survival and adjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC). Experimental Design: A total of 118 patients with MIBC from Shanghai Cancer Center, 140 patients with MIBC from Zhongshan Hospital, and 287 patients with MIBC from TCGA cohort were included in the study. Immune cell infiltration was evaluated by IHC staining or CIBERSORT method. Five immune features were selected out of 22 immune features to construct immunotypes based on the LASSO Cox regression model. Results: Using the LASSO model, we classified patients with MIBC into stromal immunotype A subgroup (CTLhighNKhighTreglowMacrophagelowMClow) and stromal immunotype B subgroup (CTLlowNKlowTreghighMacrophagehighMChigh). Significant differences were found between immunotype A and immunotype B in the combined cohort with 5-year overall survival (OS, 76.0% vs. 44.0%; P &amp;lt; 0.001) and 5-year disease-free survival (DFS, 62.8% vs. 48.3%; P &amp;lt; 0.001). Stromal immunotype was revealed to be an independent prognostic indicator in multivariate analysis in all cohorts separately. Either OS or DFS was not improved by adjuvant chemotherapy (ACT) in pT2 stage patients or pT3+pT4 patients, but further analysis revealed that OS and disease-free was significantly improved by ACT in pT3+pT4 patients (P = 0.016 and P = 0.006, respectively). Finally, stromal immunotype A showed higher immune checkpoint molecules (PD-L1, PD-1, and CTLA-4) expression. Conclusions: The stromal immunotypes could effectively predict survival and recurrence of MIBC. Furthermore, the immunotypes might be a practical predictive tool to identify pT3+pT4 patients who would benefit from ACT. Clin Cancer Res; 24(13); 3069–78. ©2018 AACR.
Wearable Wireless Tyrosinase Bandage and Microneedle Sensors: Toward Melanoma Screening
Authors: Bianca Ciui, Aida Martin, Rupesh K. Mishra, Barbara Brunetti, Tatsuo Nakagawa, Thomas J. Dawkins, Mengjia Lyu, Cecilia Cristea, Robert Sandulescu, Joseph Wang
Journal: Advanced Healthcare Materials (2018)

Wearable bendable bandage-based sensor and a minimally invasive microneedle biosensor are described toward rapid screening of skin melanoma. These wearable electrochemical sensors are capable of detecting the presence of the tyrosinase (TYR) enzyme cancer biomarker in the presence of its catechol substrate, immobilized on the transducer surface. In the presence of the surface TYR biomarker, the immobilized catechol is rapidly converted to benzoquinone that is detected amperometrically, with a current signal proportional to the TYR level. The flexible epidermal bandage sensor relies on printing stress-enduring inks which display good resiliency against mechanical deformations, whereas the hollow microneedle device is filled with catechol-coated carbon paste for assessing tissue TYR levels. The bandage sensor can thus be used directly on the skin whereas microneedle device can reach melanoma tissues under the skin. Both wearable sensors are interfaced to an ultralight flexible electronic board, which transmits data wirelessly to a mobile device. The analytical performance of the resulting bandage and microneedle sensing systems are evaluated using TYR-containing agarose phantom gel and porcine skin. The new integrated conformal portable sensing platforms hold considerable promise for decentralized melanoma screening, and can be extended to the screening of other key biomarkers in skin moles.
Reduction of hyaluronan and increased expression of HYBID (alias CEMIP and KIAA1199) correlate with clinical symptoms in photoaged skin
Authors: H. Yoshida, A. Nagaoka, A. Komiya, M. Aoki, S. Nakamura, T. Morikawa, R. Ohtsuki, T. Sayo, Y. Okada, Y. Takahashi
Journal: British Journal of Dermatology (2018)

Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID (hyaluronan binding protein involved in hyaluronan depolymerization, alias CEMIP and KIAA1199) and the HA synthases HAS1 and HAS2. However, photoageing‐dependent changes in HA and their molecular mechanisms, and the relationship between HA metabolism and clinical symptoms in photoaged skin remain elusive. We examined the amount, size and tissue distribution of HA and expression levels of HYBID, HAS1 and HAS2 in photoaged skin, and analysed their relationship with the degree of photoageing. Photoageing‐dependent changes of HA were investigated by studying skin biopsies isolated from photoprotected and photoexposed areas of the same donors, and the relationships between HA and photoageing symptoms such as skin wrinkling and sagging were examined. Skin biopsy specimens showed that the amount and size of HA are decreased in photoexposed skin compared with photoprotected skin, and this was accompanied by increased expression of HYBID and decreased expression of HAS1 and HAS2. Histologically, HA staining in the papillary dermis was decreased in photoexposed skin, showing reverse correlation with HYBID expression. HYBID expression in the photoexposed skin directly correlated with skin roughness and sagging parameters, and the reduced HA staining in the papillary dermis in the photoexposed skin positively correlated with these symptoms. These data demonstrate that imbalance between HYBID‐mediated HA degradation and HAS‐mediated HA synthesis may contribute to enhanced HA catabolism in photoaged skin, and suggest that HYBID‐mediated HA reduction in the papillary dermis is related to skin wrinkling and sagging of photoaged skin.
GMC to pilot an induction programme for doctors new to UK practice
Authors: Sally Carter
Journal: BMJ (2012)

The GMC plans to pilot an induction programme for overseas doctors and for UK medical graduates who are starting foundation year 1 to introduce them to the ethical and practical issues involved in medical practice in the UK.

The induction programme, which will be piloted by the end of the year, will be free and voluntary. It is not intended to identify concerns in new doctors, and completion of the programme will not be a condition of licensing.

Niall Dickson, chief executive of the GMC, said, “We believe there is a role for us …
Funding for doctors’ training could be transferred to other groups, HEE says
Authors: Matthew Limb
Journal: BMJ (2014)

Funds currently spent on doctors’ training could be transferred to non-medical roles, a Health Education England (HEE) official has indicated.

Wendy Reid, HEE’s director of education and quality, said that the organisation’s £5bn budget would have to be used more “creatively” and “flexibly,” rather than sums being earmarked for different groups of healthcare staff, such as doctors and nurses. 

“Those silos of money aren’t something we’re wedded to; we want to produce the right …
Phase I study of the safety and biological activity of intraperitoneal IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer administered in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed ovarian cancer.
Authors: Premal H. Thaker, Charles A. Leath, William Hampton Bradley, Kathleen N. Moore, Nicholas Borys, Khursheed Anwer, Ronald David Alvarez
Journal: Journal of Clinical Oncology (2016)

TPS5605 Background: This phase 1 study (NCT02480374) evaluates the use of weekly intraperitoneal GEN-1, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer in combination with dose-dense weekly taxane and carboplatinum (T/C) every three weeks in newly diagnosed epithelial ovarian, fallopian tube or primary peritoneal (EOC) cancer patients undergoing neoadjuvant therapy (NAC). Previous phase I study in platinum-sensitive EOC patients (n = 13) with escalating GEN-1 doses to 24 mg/m2 in combination T/C had an anti-tumor response of 17% complete response, 33% partial response and 42% stable disease (Anwer K. Gynecol Oncol. 2013 Oct;131(1):169-73). The primary objective of this study is to evaluate the tolerability and safety of GEN-1 with NAC in order to proceed with a phase 2 study. Secondary objectives are progression-free survival, pathological complete response, and response by CA-125. Translational research objectives include measuring levels of IL-12, IFN-γ, TNF-α, IL-10, TGF-β, and VEGF, determining the density of a wide range of immune activating and immune suppressing cells, and a comprehensive mRNA transcript panel for gene expression profile in the peritoneal cavity. Methods: Patient eligibility criteria: Females age > 18 years with newly diagnosed epithelial EOC not amenable to primary cytoreduction. Patients must not be on chronic steroids and have adequate renal, bone marrow, hepatic and neurologic functions. This protocol is a standard 3+3 design with a planned sample size up to 30 patients. Patients will receive GEN-1 at escalating dose levels from 36 mg/m2, 47 mg/m2, 61 mg/m2, 79 mg/m2, to 103 mg/m2 weekly for 8 treatments with concurrent T/C. After interval debulking patients do not receive further GEN-1 but continue on T/C. Patients are assessed for dose limiting toxicities and have tumor samples at time of diagnostic laparoscopy and interval debulking. After completion of therapy, patients are followed for every 3 months 2 years. As of January 31, 2016, 2 patients have completed dose level 1 and study enrollment continues. Clinical trial information: NCT02480374.
SERUM CYSTATIN C-ADIPONECTIN COMPLEX LEVELS PREDICT THE PROGNOSIS OF MALE PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Tetsuro Matsuoka, Hiroyasu Yamamoto, Akane Matsuomoto, Natsumi Matsuo, Yukika Mizukami, Kenji Fukuda, Yasunaka Makino, Shinji Kihara
Journal: Journal of the American College of Cardiology (2018)
FIRST RESPONDER HEART DISEASE RISK REDUCTION, INSULIN RESISTANCE, AND A PERSONALIZED LIFESTYLE MANAGEMENT PROGRAM
Authors: H. Robert Superko, Rosalynn Gill, Megan M. McCarthy, Jack Kepra, Debanjali Ghosh, Briana Jones, Joi A. Gleason, Paul T. Williams, Michael L. Dansinger
Journal: Journal of the American College of Cardiology (2018)
Public health must remain a training specialty, says BMA
Authors: Abi Rimmer
Journal: BMJ (2015)

Public health must continue as a specialty in the wake of planned changes to medical training, the BMA has said. 

Delegates at the BMA’s annual conference of public health medicine in London on Monday 27 April voted in favour of a motion that “insists public health must remain a specialty.” 

Speaking ahead of the motion, Lucy-Jane Davis, chair of the BMA’s public health medicine registrars subcommittee, said that the Shape of Training review had failed to …
Nucleosome-inspired nanocarrier obtains encapsulation efficiency enhancement and side effects reduction in chemotherapy by using fullerenol assembled with doxorubicin
Authors: Jinglong Tang, Ruirui Zhang, Mengyu Guo, Leihou Shao, Ying Liu, Yuliang Zhao, Suojiang Zhang, Yan Wu, Chunying Chen
Journal: Biomaterials (2018)
Clinical and laboratory predictors of Lassa fever outcome in a dedicated treatment facility in Nigeria: a retrospective, observational cohort study
Authors: Peter Okokhere, Andres Colubri, Chukwuemeka Azubike, Christopher Iruolagbe, Omoregie Osazuwa, Shervin Tabrizi, Elizabeth Chin, Sara Asad, Ehi Ediale, Mojeed Rafiu, Donatus Adomeh, Ikponmwosa Odia, Rebecca Atafo, Chris Aire, Sylvanus Okogbenin, Meike Pahlman, Beate Becker-Ziaja, Danny Asogun, Terrence Fradet, Ben Fry, Stephen F Schaffner, Christian Happi, George Akpede, Stephan Günther, Pardis C Sabeti
Journal: The Lancet Infectious Diseases (2018)
A PHASE III, RANDOMIZED, DOUBLE-BLIND, MULTICENTER, PLACEBO-CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF NEUCARDIN™ IN PATIENTS WITH CHRONIC HEART FAILURE
Authors: Runlin Gao, Jian Zhang, Heping Liu, Lina Wang, Xiaohua Pang, Lu Fu, Fanbo Meng, Mingdong Zhou
Journal: Journal of the American College of Cardiology (2018)
THE REDUCTION OF LEFT VENTRICULAR MASS IS SMALLER IN PATIENTS WITH LOW PRESSURE GRADIENT SEVERE AORTIC STENOSIS AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Nobuyuki Enzan, Ken-Ichi Hiasa, Shunji Hayashidani, Oi Keiji, Takeshi Arita, Hiromichi Sonoda, Akira Shiose, Tsutsui Hiroyuki
Journal: Journal of the American College of Cardiology (2018)
Outcome of ABO-incompatible adult living-donor liver transplantation for patients with hepatocellular carcinoma
Authors: Young-In Yoon, Gi-Won Song, Sung-Gyu Lee, Shin Hwang, Ki-Hun Kim, Seok-Hwan Kim, Woo-Hyoung Kang, Hwui-Dong Cho, Eun-Kyoung Jwa, Jae-Hyun Kwon, Eun-Young Tak, Varvara A. Kirchner
Journal: Journal of Hepatology (2018)
TRENDS IN TRANSCATHETER AND SURGICAL REPAIR OF SECUNDUM ATRIAL SEPTAL DEFECT: INSIGHTS FROM A NATIONAL DATABASE
Authors: Arka Chatterjee, Manyoo Agarwal, Nirmanmoh Bhatia, Neal J. Miller, Anderson S. Marshall, Massoud Leesar, Marc Cribbs, Mark Law
Journal: Journal of the American College of Cardiology (2018)
Endoscopic sleeve gastroplasty of the remnant stomach in Roux-en-Y gastric bypass: a novel approach to a gastrogastric fistula with weight regain
Authors: Allison Schulman, Mustafa Huseini, Christopher Thompson
Journal: Endoscopy (2018)

A gastrogastric fistula is a channel that develops between the gastric pouch and gastric remnant following a Roux-en-Y gastric bypass (RYGB). The management includes symptom control, high dose acid suppression, and consideration of closure techniques for those with persistent symptoms. While endoscopic approaches are less invasive than surgical repair, less than one-third of fistulas remain closed. Here, we demonstrate a novel approach whereby we performed endoscopic sleeve gastroplasty (ESG) of the remnant stomach through the gastrogastric fistula, followed by reduction in volume of the gastric pouch ([Video 1]).
Snapchat is not for sharing
Authors: Sohini Patel, Susan Bewley, Nathan Hodson
Journal: BMJ (2016)

<i>Photo messaging app Snapchat is one of the most popular ways to share images online. But doctors who use it at work may be breaking patient confidentiality, say</i><b><i>Sohini Patel</i></b><i>and</i><b><i>Susan Bewley</i></b>