tbuckley/cabot-search huggingface dataset:
The Anti-protease SPINK7 is a Checkpoint Regulator of Esophageal Epithelial Inflammatory Responses
Authors: Nurit P. Azouz, Mario Alberto Ynga-Durand, Julie M. Caldwell, Ayushi Jain, Mary Bedard, Mark Rochman, Demetria Michael, Melissa K. Mingler, Carmy Forney, Ting Wen, Jonathan Kuhl, Hua He, Jocelyn M. Biagini Myers, Vincent A. Mukkada, Philip E. Putnam, Gurjit K. Khurana Hershey, Leah C. Kottyan, Lisa J. Martin, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2018)
MSc in surgical science
Authors: Oliver Chan
Journal: BMJ (2010)

This is a postgraduate degree offered by University College London. It is intended for aspiring surgeons and aims to provide experience in scientific research before or during a surgical training programme. The course has the full approval of the royal colleges of surgery. Although not required, it is recommended that candidates have 24 months of clinical experience and part A of membership of the Royal College of Surgeons.

I took this course before starting my core surgical training rotation.

With the anticipated decrease in the number of higher surgical training numbers and the already highly competitive nature of all surgical specialties, I started this MSc during my foundation year 2 to improve my curriculum vitae and ultimately maximise my chances of securing a higher surgical training post. The research involved in attaining the degree also …
Linc00659, a long noncoding RNA, acts as novel oncogene in regulating cancer cell growth in colorectal cancer
Authors: Kuo-Wang Tsai, Yi-Hao Lo, Hsuan Liu, Chung-Yu Yeh, You-Zuo Chen, Chao-Wen Hsu, Wei-Shone Chen, Jui-Ho Wang
Journal: Molecular Cancer (2018)

Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death worldwide. In patients with CRC, metastasis is a crucial problem that leads to treatment failure and is the primary cause of the lethality of colon cancer. Long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in the development, cell growth, apoptosis, and metastasis of CRC.We investigated the transcriptome profiles of human lncRNAs in the primary tumor tissues and in the corresponding normal mucosa of two patients with CRC by using a microarray approach. The expression levels of lncRNAs were verified in colon cancer by real-time PCR. Using bioinformatics approach to illustrate putative biological function of Linc00659 in colon cancer. The effects of Linc00659 on cell growth, proliferation, cell cycle and apoptosis were studies by in vitro assays.Our data revealed that compared with adjacent normal tissues, 201 lncRNAs were deregulated (fold change ≥ 4 or ≤ 0.25) in CRC tissues. Among them, the expression levels of Linc00659 were significantly increased in colon cancer, and high expression levels were correlated with poor survival in patients with CRC. Bioinformatics analysis results indicated that Linc00659 was significantly coexpressed with cycle-related genes in CRC. Linc00659 expression knockdown could significantly suppress colon cancer cell growth by impairing cell cycle progression. In addition, our results showed that Linc00659 expression knockdown could accelerate cell apoptosis in colon cancer cells treated with chemotherapy drugs. Meanwhile, our results also demonstrated that silencing of Linc00659 expression leads to cell growth inhibition and induced apoptosis, possibly by suppressing PI3K-AKT signaling in colon cancer.Linc00659 is a novel oncogenic lncRNA involved in colon cancer cell growth by modulating the cell cycle. Our findings give an insight into lncRNA regulation and provide an application for colon cancer therapy.
Tory plan for seven day service is “empty pledge,” says BMA
Authors: Abi Rimmer
Journal: BMJ (2015)

The Conservative Party’s promise to offer seven day NHS services is an empty pledge, the BMA has said. 

Speaking at the Conservative Party’s spring forum last month, Prime Minister David Cameron said that a future Conservative government would create “a truly seven day NHS.” Cameron said that by 2020 he wanted all patients to be able to see …
RIP1–HAT1–SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer
Authors: Vincenzo Carafa, Angela Nebbioso, Francesca Cuomo, Dante Rotili, Gilda Cobellis, Paola Bontempo, Alfonso Baldi, Enrico P. Spugnini, Gennaro Citro, Angela Chambery, Rosita Russo, Menotti Ruvo, Paolo Ciana, Luca Maravigna, Jani Shaik, Enrico Radaelli, Pasquale De Antonellis, Domenico Tarantino, Adele Pirolli, Rino Ragno, Massimo Zollo, Hendrik G. Stunnenberg, Antonello Mai, Lucia Altucci
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes. Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models. Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3–SIRT1/2–HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8–mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene–induced mammary gland hyperproliferation in vivo. Conclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention. Clin Cancer Res; 24(12); 2886–900. ©2018 AACR.
PREDICTING HOSPITAL COST IN PATIENTS WITH HFPEF: A CONTEMPORARY ANALYSIS OF NATIONAL POPULATION-BASED COHORT STUDY
Authors: Chayakrit Krittanawong, Bing Yue, Mario Roberto Rodriguez Rivera, Saranapoom Klomjit, Xin Wei, Mariam Khandaker, Ritu Raj Singh, Eyal Herzog, Edgar Argulian
Journal: Journal of the American College of Cardiology (2018)
NON-INVASIVE ASSESSMENT OF ACUTE DYSPNEA USING LUNG DOPPLER SIGNALS
Authors: Muhammad Ashraf, Marton Tokodi, Hama Amin Ali, Chetan Virmani, Moe Alsumidaie, Lan Hu, George Sokos, Partho P. Sengupta
Journal: Journal of the American College of Cardiology (2018)
A Survey of Graph Cuts/Graph Search Based Medical Image Segmentation
Authors: Xinjian Chen, Lingjiao Pan
Journal: IEEE Reviews in Biomedical Engineering (2018)

Medical image segmentation is a fundamental and challenging problem for analyzing medical images. Among different existing medical image segmentation methods, graph-based approaches are relatively new and show good features in clinical applications. In the graph-based method, pixels or regions in the original image are interpreted into nodes in a graph. By considering Markov random field to model the contexture information of the image, the medical image segmentation problem can be transformed into a graph-based energy minimization problem. This problem can be solved by the use of minimum s-t cut/ maximum flow algorithm. This review is devoted to cut-based medical segmentation methods, including graph cuts and graph search for region and surface segmentation. Different varieties of cut-based methods, including graph-cuts-based methods, model integrated graph cuts methods, graph-search-based methods, and graph search/graph cuts based methods, are systematically reviewed. Graph cuts and graph search with deep learning technique are also discussed.
CASPIR trial: Using prostatic calculi as an alternative to fiducial markers for IGRT in for localized prostate cancer.
Authors: Angela G.M O'Neill, Raymond King, Sarah Osman, Suneil Jain, Alan R Hounsell, Joe M. O'Sullivan
Journal: Journal of Clinical Oncology (2018)

60 Background: Image guided Radiotherapy (IGRT) for prostate cancer (PCA) frequently employs surgically implanted fiducial markers (FMs). However, it is estimated that up to 35% of prostate radiotherapy patients have prostatic calculi (PC) visible on treatment cone beam CTs (CBCT). The purpose of this clinical trial is to directly compare FMs with PCs as an aid to prostate IGRT. Methods: We report data from a single institution prospective clinical trial investigating the feasibility of using prostate calcifications as natural FMs for IGRT. Patients planned for standard prostate radical EBRT +/- brachytherapy were eligible. Prior to CT planning, 3 gold fiducial markers are inserted into the prostate by the trans-perineal route under TRUS guidance. PCs visible within the PTV were contoured. Participants were aligned to FMs for EBRT using daily CBCT image guidance on a Varian TrueBeam linac. Off-line, a single experienced user analyses CBCTs using Image Registration in Eclipse (version 13.6). Random and systematic set-up errors are determined based on FMs, PCs (where present), prostate gland (PG) and bony landmarks (BL) and CTV-PTV margins derived for each data set. Results: 30 participants with PC have been recruited. Data from the first 19 patients (365 fractions), resulted in 2555 individual image registrations (7665 individual data points). The PTV margins required based on each reference structure are summarised in Table 1. The maximum difference between the CTV-PTV (PC) margin and CTV-PTV (FM) margin is 2.2mm in the X or L/R dimension. Margins required for FM, PG and PC in the Y and Z dimensions are comparable, with a maximum difference of 0.5mm between CTV-PTV (PC) and CTV-PTV (PG) . Conclusions: Preliminary results from this study demonstrate some evidence to support the use of PCs as an alternative to FMs for prostate IGRT. Future analysis will include location of PC according to the PIRADs schema and patient feedback in relation to FM implantation. Clinical trial information: NA. [Table: see text]
Pharmacokinetic (PK) subgroup results from the phase 2 pharmacodynamic and bioequivalence study of abiraterone acetate fine particle formulation (AAFP) in patients with metastatic castration-resistant prostate cancer (mCRPC): The STAAR study.
Authors: Curtis Dunshee, Cy Aaron Stein, Paul R. Nemeth, Bill Bosch, Jillian Chapas-Reed, Robert Dreicer
Journal: Journal of Clinical Oncology (2018)

176 Background: AAFP, a novel formulation, showed therapeutic equivalence to originator abiraterone acetate (OAA) in the Phase 2 STAAR study (Stein et al. Urologic Oncol). A patient-subgroup analysis compared steady-state PK parameters between AAFP and OAA. Methods: This multicenter, open-label, active-controlled study enrolled men with progressive mCRPC treated 1:1 with 500 mg AAFP tablets QD + 4 mg methylprednisolone BID, or 1000 mg OAA tablets QD + 5 mg prednisone BID for 9 days. Study drug was taken 2 hours post morning meal. On day 9, plasma abiraterone blood samples were collected at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 24 hr time points. Results: PK samples were evaluable for 13 of 14 patients (n=5, AAFP; n=8, OAA). Mean age was 67.4 and 73.3 years, respectively. Twelve patients completed the 12-week study without clinical disease progression. One OAA patient died from MI in week 4. PK parameters (AUC, C max , C min ), were numerically lower but not statistically significantly different for those treated with AAFP vs OAA (Table). Conclusions: Clinical benefit in this subgroup of patients was consistent with the overall study results. High PK variability was observed in both groups. PK parameters were not statistically different between AAFP and OAA. 24-hour PK Parameters at Steady State Clinical trial information: NCT02737332. [Table: see text]
A comparison of doublet versus triplet chemotherapy regimens for esophagogastric adenocarcinoma (EGC): Is more always better?
Authors: Tiago Felismino, Ana Caroline Alves, Audrey Oliveira, Wilson Luiz da Costa, Felipe José Fernandez Coimbra, Victor Hugo Fonseca Jesus, Marcos Pedro Guedes Camandaroba, Celso Lopes Mello
Journal: Journal of Clinical Oncology (2018)

124 Background: Recent data showed that a taxane-containing triplet regimen (FLOT) was superior to an anthracycline-containing regimen (ECX/ECF). However, there is no comparison between more costly and toxic triplet (T) regimens versus doublets (D) in the perioperative setting (periCT) of EGC. Methods: A retrospective analysis of patients (pts) with newly diagnosed EGC was carried out at AC Camargo Cancer Center from 2007 to 2015. Pts received either a D with a fluopyrimidine and platin or T with addition of epirubicin or docetaxel. Variables used in the Cox model were age, site, TNM, Lauren subtype and periCT (T versus D). The selection between T and D was at physician's choice. Endpoints were Relapse Free Survival (RFS) and Overall Survival (OS). Results: A total of 128 pts were included. Median age was 59.5y (56.5y for T and 67y for D, respectively). Male/female ratio was 82/46. Sixty-six received T (DCF 26 pts, EOX 28, ECX 8, 4 others) and 62 received D (FOLFOX 47 pts, CF 13, 2 others). Primary site: gastric in 93 pts and 35 EGJ. Main clinical staging cT3 N = 81 (63.3%), cN+ 84 (65.4%). Lauren subtype: intestinal N = 48, diffuse N = 54. Regarding surgery: 114 pts were resected and median lymph nodes removed 30. Pathologic complete response was seen in N = 9 (14.5%) and N = 4 (6.1%) considering D and T regimens, respectively (p = 0.14). In multivariate analysis there was no advantage of T over D regarding RFS (HR = 1.65, 0.87 – 3.11, p = 0.12) or OS (HR = 1.29, 0.65 – 2.57, p = 0.45). The 3y RFS rate was 63.2% for D and 40.6% for T and the 3y OS was 69.4% for D and 56.1% for T. Conclusions: In our analysis outcomes of pts treated with T regimen was not superior to D. Our main T was DCF and D was FOLFOX. We consider that doublet regimens may still have a role in periCT in EGC and could be an option for frail or elderly pts. Future trials are needed to confirm our data.
Comparative Heterochromatin Profiling Reveals Conserved and Unique Epigenome Signatures Linked to Adaptation and Development of Malaria Parasites
Authors: Sabine A. Fraschka, Michael Filarsky, Regina Hoo, Igor Niederwieser, Xue Yan Yam, Nicolas M.B. Brancucci, Franziska Mohring, Annals T. Mushunje, Ximei Huang, Peter R. Christensen, Francois Nosten, Zbynek Bozdech, Bruce Russell, Robert W. Moon, Matthias Marti, Peter R. Preiser, Richárd Bártfai, Till S. Voss
Journal: Cell Host & Microbe (2018)

Heterochromatin-dependent gene silencing is central to the adaptation and survival of Plasmodium falciparum malaria parasites, allowing clonally variant gene expression during blood infection in humans. By assessing genome-wide heterochromatin protein 1 (HP1) occupancy, we present a comprehensive analysis of heterochromatin landscapes across different Plasmodium species, strains, and life cycle stages. Common targets of epigenetic silencing include fast-evolving multi-gene families encoding surface antigens and a small set of conserved HP1-associated genes with regulatory potential. Many P. falciparum heterochromatic genes are marked in a strain-specific manner, increasing the parasite's adaptive capacity. Whereas heterochromatin is strictly maintained during mitotic proliferation of asexual blood stage parasites, substantial heterochromatin reorganization occurs in differentiating gametocytes and appears crucial for the activation of key gametocyte-specific genes and adaptation of erythrocyte remodeling machinery. Collectively, these findings provide a catalog of heterochromatic genes and reveal conserved and specialized features of epigenetic control across the genus Plasmodium.
CHARACTERISTICS AND CLINICAL OUTCOMES IN PATIENTS WITH PRIOR CHEST RADIATION UNDERGOING TAVR: OBSERVATIONS FROM THE PARTNER 2 TRIAL AND REGISTRIES
Authors: Bibhu D. Mohanty, Megan Coylewright, Yangbo Liu, Shawn X. Li, Michael Fradley, Maria Alu, Michael J. Mack, Samir Kapadia, Susheel K. Kodali, Vinod H. Thourani, Raj Makkar, Martin B. Leon, David Malenka
Journal: Journal of the American College of Cardiology (2018)
Plasmacytoid urothelial carcinoma: A clinicopathological study.
Authors: Neda Hashemi-Sadraei, Carmen M Perrino, M. Francesca Monn, Elhaam Bandali, Liang Cheng, Muhammad Idrees, Richard Bihrle, Michael O. Koch, John Eble, Chia-Sui Kao, Costantine Albany, Roberto Pili, David A. Grignon, Hristos Z. Kaimakliotis
Journal: Journal of Clinical Oncology (2018)

482 Background: Plasmacytoid urothelial carcinoma (PUC) is a rare variant histology with poor prognosis. We report clinical outcomes on patients with PUC. Methods: We retrospectively reviewed treatments and outcomes in patients with PUC seen at our institution from 1996 through 2016. The Kaplan-Meier method was used to calculate overall survival. Results: A total of 69 patients with a median age of 68 years were identified. Five patients presented with metastatic disease, whereas 64 were diagnosed with clinically localized PUC. Fifty-seven patients underwent radical cystectomy and the remainder elected for bladder preservation approaches. At time of cystectomy, 6 patients were found to have pathologically organ-confined disease (≤pT2 N0), and 51 had non-organ-confined disease (pT3,T4 or N+), 2 of which were noted to have diffuse peritoneal carcinomatosis. Twenty-eight patients had positive surgical margins, most of which had extensive infiltrative disease not amenable to complete excision. Of the 14 patients who received neoadjuvant cisplatin-based chemotherapy, 10 (71.4%) patients had lymph node involvement and 12 (85.7%) had pT3/4 disease at cystectomy. Only one patient had a pathologic complete response with pT0N0. Thirteen patients received adjuvant chemotherapy, 2 of which received neoadjuvant chemotherapy as well. Two patients received immunotherapy, with only a short-lived response. Median survival for all patients with PUC from time of initial diagnosis was 17.7 months (mo), and 14.0 mo from time of cystectomy for patients undergoing radical cystectomy. Patients with desmoplastic morphology tended to have the worst clinical outcomes (median survival 10.1 mo), whereas classic and pleomorphic subtypes had better survival (median survival 18.6 and 30.4 mo, respectively) (p = 0.083). Conclusions: PUC is an aggressive variant with overall poor outcomes. There appeared to be three morphologic subtypes of plasmacytoid disease; classic, desmoplastic and pleomorphic, with potentially distinct survival outcomes. Chemotherapy, whether in the neoadjuvant or adjuvant setting, or immunotherapy, appeared to have little effect on this cohort. Molecular markers/genomic analysis may provide insight to novel therapeutic approaches.
Outcomes of male patients with germ cell tumors and bone metastases: A mono-institutional retrospective study.
Authors: Guillaume Moriceau, Helen Jane Boyle, Nathalie Bonnin, Christophe Sajous, Patrice Peyrat, Pascal Pommier, Michel Rivoire, Aude Flechon
Journal: Journal of Clinical Oncology (2018)

570 Background: Bone metastases (BM) are considered as intermediate or poor prognosis according to the international classification of Germ Cell Tumors (GCT). The present study compares the outcomes between patients with bone disease at initial diagnosis and bone disease at relapse and between seminoma and non-seminoma GCT. Methods: We investigated retrospectively all male-patients presenting GCT with BM at initial diagnosis or at relapse, between 2005 and 2015, in a single institution. Results: Thirty-nine patients were included. Median age was 36 (from 20 to 67). Nineteen patients presented with BM at initial diagnosis (49%) and 20 patients presented BM at relapse (51%). Histologically, 13 patients (33%) presented a seminoma and 26 patients (67%) a non-seminoma GCT. Twenty-four patients (62%) had multiples bone metastatic sites. Vertebra was the most frequent location (70%). Bone surgery was performed for five patients with seminoma (38%) and four patients with non-seminoma GCT (15%). Median overall survival (OS) was 130.9 months for the 19 patients with BM at initial diagnosis and 15.2 months for the 20 patient with BM at relapse HR 5.3 95%CI[1.75;16.06], p &lt; 0.001. Median progression free survival (PFS) was 120.10 months for patients with BM at initial diagnosis and 9.21 months for patients with BM at relapse, HR 3.02 95%CI[1.16;7.83], p &lt; 0.0016. Survivals are longer for patients with seminoma than patients with non-seminoma GCT. Median PFS was 9.41 months for the 13 patient with non-seminoma GCT and not achieved for the 26 patients with seminoma, HR 0.15, 95%CI [0.003;0.65], p 0.001 . Median OS was 18.7 months for the 13 patient with non-seminoma GCT and not achieved for the 26 patients with seminoma, HR 0.16 95% CI [0.004;0.7], p 0.002. Conclusions: BM of GCT are associated with a worse prognosis especially for non-seminoma subtype and/or when BM arise at relapse. This data highlights the importance of the first line therapeutic strategy as the corner stone of treatment for patients with GCT.
Cardiac surgical unit advanced life support course
Authors: Khalid Mujahid
Journal: BMJ (2011)

The cardiac surgical unit advanced life support (CALS) course was developed to meet the need for a protocol in arrest and peri-arrest situations specific to cardiothoracic patients in the intensive care unit. Basic life support, advanced life support, and advanced trauma life support courses have enabled members of intensive care teams to adopt recognisable roles in a well rehearsed and ordered way, and the same can now be extended to help patients who undergo arrest after cardiac surgery. This course fills an important gap by addressing the unique circumstances of postoperative cardiac patients.

Any healthcare professional working in a cardiothoracic intensive care unit.

November 2010 as a core trainee year 1 in cardiothoracic surgery. This was just after the guidelines had been ratified by the European Association of Cardiothoracic Surgery and the European Resuscitation Council.

In my second week on the cardiothoracic intensive care unit, I realised that I was out of my depth on one occasion, when a patient became …