tbuckley/cabot-search huggingface dataset:
Cortico–reticulo–spinal circuit reorganization enables functional recovery after severe spinal cord contusion
Authors: Leonie Asboth, Lucia Friedli, Janine Beauparlant, Cristina Martinez-Gonzalez, Selin Anil, Elodie Rey, Laetitia Baud, Galyna Pidpruzhnykova, Mark A. Anderson, Polina Shkorbatova, Laura Batti, Stephane Pagès, Julie Kreider, Bernard L. Schneider, Quentin Barraud, Gregoire Courtine
Journal: Nature Neuroscience (2018)
Current trends to comprehend lipid metabolism in diatoms
Authors: Nodumo Nokulunga Zulu, Krzysztof Zienkiewicz, Katharina Vollheyde, Ivo Feussner
Journal: Progress in Lipid Research (2018)

Diatoms are the most dominant phytoplankton species in oceans and they continue to receive a great deal of attention because of their significant contributions in ecosystems and the environment. Due to triacylglycerol (TAG) profiles that are abundant in medium-chain fatty acids, diatoms have emerged to be better feed stocks for biofuel production, in comparison to the commonly studied green microalgal species (chlorophytes). Importantly, diatoms are also known for their high levels of the essential ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are considered to be a promising alternative source of these components. The two most commonly exploited diatoms include Thalassiosira pseudonana and Phaeodactylum tricornutum. Although obvious similarities between diatoms and chlorophytes exist, there are some substantial differences in their lipid metabolism. This review provides an overview on lipid metabolism in diatoms, with P. tricornutum as the most explored model. Special emphasis is placed on the synthesis and incorporation of very long chain ω3 fatty acids into lipids. Furthermore, current approaches including genetic engineering and biotechnological methods aimed at improving and maximizing lipid production in P. tricornutum are also discussed.
Scrap national pay bargaining for public sector workers, says think tank
Authors: Caroline White
Journal: BMJ (2012)

National pay bargaining for public sector workers should be scrapped in favour of locally negotiated pay linked to performance, a report by an influential think tank has concluded.

Automatic annual pay increases and progression points should also be ditched, while incentives should be used to boost productivity, suggests Local Pay, Local Growth by Policy Exchange.1

This strategy would make public sector pay fairer for employees and the taxpayer, maximise local growth, and make the most of limited public finances, argues the think tank. Half of public sector spending goes on pay, …
Rheumatologic immune-related adverse events (irAE) in patients (pts) with genitourinary (GU) malignancies treated with immune checkpoint inhibitors (CPI).
Authors: Moshe Chaim Ornstein, Cassandra Calabrese, Laura S. Wood, Elizabeth Kirchner, Allison Janine Tyler, Pam Profusek, Kimberly D Allman, Apostolos Kontzias, Petros Grivas, Jorge A. Garcia, Leonard Calabrese, Brian I. Rini
Journal: Journal of Clinical Oncology (2018)

652 Background: Rheumatologic irAEs in pts treated with CPIs present a clinical challenge. We describe the clinical characteristics, treatment, and outcomes of rheumatologic irAEs in CPI-treated GU malignancy pts. Methods: Pts with GU malignancies who were treated with CPIs and developed grade ≥ 2 (per CTCAEv4) rheumatologic irAEs (i.e., arthralgias and myalgias) were retrospectively reviewed. Patient-, disease-, and rheumatologic-related data were collected and analyzed. Results: Twenty-three pts were identified; 19 (83%) had renal cell carcinoma (RCC) and 4 (17%) had urothelial carcinoma (UC). The majority (70%) were male; median age at diagnosis was 56 (range, 36-78). All RCC pts had clear cell histology and all had prior nephrectomy; 1 UC pt had prior cystectomy. Most RCC pts (58%) received antiangiogenic therapy prior to CPI treatment and 50% of UC pts received prior chemotherapy. CPI therapy included anti-PD-L1 (30%), anti-PD-1 (43%), and combined PD-1 / CTLA-4 antibodies (26%). Median time from CPI initiation to rheumatologic irAE was 5.1 months (range, 0.23 – 51.3). Most (74%) patients had 2-4 muscle or joint groups involved. CPI was held in in 20 (87%) pts who developed rheumatologic irAEs. Most (96%) pts were treated with prednisone. Median initial prednisone dose was 40mg/d (range, 10-90mg/d) and median duration of prednisone therapy was 43.6 weeks (range, 2.5–206). Treatment intensification with methotrexate (14%), infliximab (14%), tocilizumab (9%), and etanercept (9%) was required in some pts for rheumatologic symptom control. Of the patients whose CPI was held for rheumatologic irAEs, 30% restarted CPI therapy following symptoms improvement, 15% switched to a subsequent therapy, and 55% have an ongoing sustained response to therapy (median 9.1 months; range, 0.63 - 46.1) despite no subsequent anti-cancer therapy. Conclusions: Rheumatologic irAEs in CPI-treated GU malignancy pts vary in timing of presentation, severity, and treatment. Multidisciplinary teams that include a rheumatologist are critical for optimal pt management. Larger pt populations are needed to assess the predictive/prognostic impact of these irAEs on outcome.
ECHOCARDIOGRAPHIC LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN IN U.S. HISPANICS/LATINOS: HCHS/SOL ECHOCARDIOGRAPHIC STUDY OF LATINOS
Authors: Maria Octavia Rangel, Ana Soto, Robert Kaplan, Sonia Ponce, Mayank Kansal, Sanjiv Jayendra Shah, Jianwen Cai, Martin Bilsker, Barry E. Hurwitz, Min Pu, Carlos Rodriguez
Journal: Journal of the American College of Cardiology (2018)
Four years on from medical school: what have we learnt?
Authors: Ali Hassan, Tabassum Khandker, Clinton Vaughn, Yasmin Akram
Journal: BMJ (2013)

BMJ Careers has been following the progress of a cohort of doctors since their first day on the job. <b>Ali Hassan, Tabassum Khandker, Clinton Vaughn, </b>and<b> Yasmin Akram </b>reflect on their experiences of the four years since they left medical school
QT INTERVAL PROLONGATION IN AN INPATIENT POPULATION RECEIVING ANTIPSYCHOTICS
Authors: Erika Rincon, Carlos Alberto Miranda, Juan Carlos Rivas, Juliana Galindo, Luis Fernando Zambrano, Ana Maria Rivas, Sandra Milena Ramirez, Mauricio Hernandez, Pablo Perafan, Juan Esteban Gomez Mesa
Journal: Journal of the American College of Cardiology (2018)
Paediatric trainees withdrawn from training over supervision concerns
Authors: Matthew Limb
Journal: BMJ (2013)

An NHS trust has said it will halt training of junior doctors in paediatrics after concerns over lack of supervision. The trust has announced an urgent review of its children’s services.

Bedford Hospital NHS Trust said that an external independent review would take place after a decision by the local medical training body to withdraw the department’s most junior medical trainees.

Health Education East of England acted after trainee doctors raised concerns about inadequate levels of senior clinical supervision for trainee doctors in paediatrics. The situation was “recognised as an unacceptable potential risk to …
MRI increases detection of prostate cancers and reduces overdiagnosis, finds study
Authors: Susan Mayor
Journal: BMJ (2018)

Using magnetic resonance imaging (MRI) to guide targeted biopsies increased the detection of clinically significant cancer by 12% when compared with standard transrectal ultrasonography guided biopsy, in the first large randomised trial to compare these two approaches in men with suspected prostate cancer.1

MRI revealed no sign of prostate cancer in more than one in four men, avoiding the need for unnecessary biopsy or treatment.

“This is the first international multi-centre randomised trial to show the benefits of using MRI at the start of the prostate cancer diagnosis process,” said the lead author, Veeru Kasivisvanathan, from University College London, UK.

He added, “In men who need to have investigation for prostate cancer for …
Potential of SUSD2 as a predictor of recurrences after curative resection of gastric cancer.
Authors: Shinichi Umeda
Journal: Journal of Clinical Oncology (2018)

15 Background: Gastric cancer (GC) is the third common leading cause of cancer-related death worldwide with a high recurrence rate. Development of sensitive biomarkers to predict recurrences is needed to improve patient management. Methods: We conducted a recurrence pattern-specific transcriptome analysis of 57751 molecules for screening of candidate molecules specific for hematogenous metastasis with stageⅢ GC patients who underwent curative resection followed by S-1 adjuvant. Subsequently, mRNA expression analysis, PCR array analysis and siRNA-mediated knockdown experiments were performed using GG cell lines. Expression levels in primary GC tissues from 154 patients with resectable GC were determined and correlated to clinicopathological factors. Results: We identified 21 candidate molecules overexpressed significantly specifically in the hepatic recurrence group and decided to focus on Sushi domain containing 2 (SUSD2). PCR array analysis revealed that SUSD2 expression levels are positively correlated with Frizzled-7 , Cadherin 2 and ZEB1. Functional analysis revealed that knockdown of SUSD2 significantly reduced the proliferation, migration and invasion abilities of GC cells. Patients with high SUSD2 expression had a significantly higher prevalence of hematogenous recurrences and were more likely to experience shorter disease-free and overall survival, particularly in stage III patients. Conclusions: SUSD2 may serve as predictor of recurrences after curative resection of GC.
REDUCTION OF RADIATION EXPOSURE, FLUOROSCOPY TIME AND CONTRAST MEDIA USE IN CRYOBALLOON ABLATIONS BY IMPLEMENTATION OF ICE AND OTHER RADIOPROTECTIVE MEASURES: FLASH IN THE PAN OR ONGOING EFFECT IN DAILY CLINICAL ROUTINE?
Authors: Vanessa Rubesch-Kütemeyer, Stephan Molatta, Britta Körber, Dieter Horstkotte, Klaus Gutleben, Georg Nölker
Journal: Journal of the American College of Cardiology (2018)
A phase 1b/2 study evaluating activity and tolerability of the BTK inhibitor ibrutinib in combination with ofatumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases.
Authors: Samantha Mary Jaglowski, Jeffrey Alan Jones, Joseph M. Flynn, Leslie A. Andritsos, Kami J. Maddocks, Jennifer Ann Woyach, Kristie A. Blum, Michael R. Grever, Susan Michelle Geyer, Nyla A. Heerema, Gerard Lozanski, Mona Stefanos, Nathan Hall, Veena Nagar, Brian Munneke, Jamie-Sue West, Jutta Neuenburg, Danelle Frances James, Amy J. Johnson, John C. Byrd
Journal: Journal of Clinical Oncology (2014)

7009 Background: Ibrutinib (Ib), an oral covalent BTK inhibitor, has significant activity in relapsed/refractory (R/R) CLL. Adding ofatumumab (O), an anti-CD20 antibody, to chemotherapy in CLL can improve response and progression free survival (PFS). Here, Ib was given with O in 3 different administration sequences. Methods: Patients (pts) with R/R CLL/SLL, PLL or Richter’s transformation (RT) after ≥2 prior therapies including a purine analog were treated with 420 mg Ib daily and 300/2000 mg O (8 x weekly/then 4 x monthly) in 28-day cycles until progressive disease (PD). Group (G) 1 had 1 cycle of Ib monotherapy, then O was added. G2 started O on Day (D) 1/Cycle (C) 1 and Ib on D2/C1. G3 had 2 cycles of O monotherapy, then Ib was added on D1/C3. Results: 71 pts (27, 20, 24 in G1, 2, 3) were enrolled. Median age was 64 y; 61% had Rai stage III/IV; 65 pts had CLL, 1 SLL, 2 PLL and 3 RT; 75% had lymph nodes ≥5 cm; 44% had del(17p); 31% had del(11q). The most frequent AEs were diarrhea (68%), infusion-related reaction (IRR, 45%), peripheral sensory neuropathy (42%) and stomatitis (37%). In all, 61% had ≥1 AE ≥grade (g) 3; most common g 3-4 AE was neutropenia in 17%. 39% had SAEs including: 1 pt in G2 with ≥g 3 IRR; 6 pts with AEs leading to Ib discontinuation; 9 pts died within 30 days of last dose and 2 within f/u period. Overall response rate in CLL/SLL was 100% in G1, 79% in G2, and 71% in G3. 2 additional pts achieved a partial response with lymphocytosis. 4 pts in G3 progressed before starting Ib. At study end, 52/58 responders (90%) remained progression-free with f/u of 16, 12 and 11 months for G1, 2 and 3, respectively. Three RT pts had disease control followed by PD on Day 471, 168, and 137. At 12 months, PFS was 89%, 85%, and 90% in G1, 2 and 3, respectively; 76% continued on Ib in a long-term extension study; 2 pts had a transplant. Conclusions: Ib combined with O is well tolerated and highly active (83% ORR) in pts with R/R CLL/SLL in all 3 dosing sequences investigated. Because of these compelling results, randomized trials evaluating anti-CD20 antibodies in combination with Ib with a PFS endpoint are ongoing. Clinical trial information: NCT01217749.
Government seeks to remove “perverse” pay protection for consultants who lose clinical excellence awards
Authors: Helen Jaques
Journal: BMJ (2013)

The government is seeking to remove an “anomalous” feature of the clinical excellence award scheme that allows consultants who are unsuccessful in renewing their award to effectively continue to receive payment for the award.

At present, consultants in receipt of national clinical excellence awards are required to renew their award once every five years. If they are unsuccessful at demonstrating that they meet the necessary criteria, their awards are withdrawn. But these individuals subsequently receive salary protection so that their pay is frozen until their basic pay catches up to this “mark time” value. 

The government estimates that it spent around £1.4m …
Assessment of risk factors for sexually transmitted infections in high-risk communities in Santo Domingo and La Romana, Dominican Republic
Authors: Catherine Nicholas, Leidy Soriano, Daira Berroa Nuñez, Samantha Stonbraker, Mina Halpern, Silvia Amesty
Journal: The Lancet Global Health (2018)

BackgroundThis study assesses the prevalence of sexually transmitted infections and risk factors among key populations living in La Romana and Santo Domingo, Dominican Republic: pregnant adolescents, men who have sex with men, trans women, sugar cane field (batey) residents, transactional sex workers, and people living with HIV. This work is based on a preliminary analysis of batey data collected in La Romana.MethodsIn 2017, 203 participants, aged 18–60 years, were recruited from eight bateys systematically selected using time-location sampling. Informed consent was obtained, and a 40 min questionnaire was administered. Blood, urine, Papanicolaou samples, and oral/anal swabs were used to test for HIV, syphilis, hepatitis B virus (HBV), hepatitis C virus (HCV), gonorrhoea, chlamydia, Trichomonas vaginalis, Ureaplasma spp, and Mycoplasma genitalium, and Papanicolaou (cervical) samples were collected. Participants with positive results received free treatment, when available, follow-up and education.FindingsOf 203 participants, 131 (65%) were women and 161 (79%) were Spanish-speaking. One (<1%) participant tested HIV-positive, 32 (16%) participants were chlamydia-positive, and 18 (9%) participants were anal chlamydia positive. 27 (13%) participants were positive for T vaginalis, and 60 (30%) participants were positive for Ureaplasma spp. 116 (88%) of 132 women underwent Papanicolaou testing. 21 (18%) women had abnormal Papanicolaou results, and 36 (31%) women were positive for human papillomavirus (HPV); of those, 25% of women had HPV16, 8% of women had HPV18/45, and 67% of women had indeterminate high-risk type. 19 (9%) participants were HBV positive. Two bateys were disproportionately affected: nine (33%) of 27 participants in Batey 1 and eight (32%) of 25 participants in Batey 2.InterpretationThe prevalence of HBV infection was disproportionately higher than those found in Central and Latin America. In response, Clínica de Familia La Romana and the Dominican Ministry of Health established an HBV vaccination and prevention programme for affected bateys, and this is underway. In terms of HIV, the prevalence was lower (<1% vs 3%) when compared to that previously reported in bateys. Targeted HIV prevention programmes conducted by Clínica de Familia La Romana and others might have helped curb HIV infection. The prevalence of high-risk HPV and other sexually transmitted infections in this study needs to be further explored. Overall, these results highlight the need for more research, for targeted prevention initiatives, and improved access to testing and treatment for sexually transmitted infections.FundingDavid E Rogers Fellowship, NY Academy of Medicine Bioreference Laboratories.
Prognostic value of circulating tumor cells in non-small cell lung cancer.
Authors: Sofia Agelaki, Oraianthi Fiste, Dimitra Grapsa, Eleni Politaki, Ioannis Stoupis, Dimitrios Mavroudis, Konstantinos N. Syrigos
Journal: Journal of Clinical Oncology (2017)

e20520 Background: Quantitative analysis of circulating tumor cells (CTCs) is increasingly investigated as a novel predictor of prognosis in non-small cell lung cancer (NSCLC). The primary aim of this study was to further investigate the prognostic value of CTCs enumeration in patients with advanced NSCLC. Methods: The medical records of patients with chemotherapy-naïve, advanced NSCLC and at least one available measurement of CTCs were retrospectively reviewed. The presence of CTCs was evaluated using the CellSearch system. A cut-off point of 2 CTCs ( &lt; 2 vs ≥2 ) was used to discriminate between negative and positive samples, respectively. The detection of CTCs was correlated with the clinicopathological features of patients and outcome. Results: Our study population comprised a total of 43 patients (mean age 67.1±9.9 years; male/female ratio: 39/4). Eight out of 43 patients (18.6%) harbored CTCs. No significant associations were found between treatment response and baseline count of circulating tumor cells (CTCs) (p = 0.067). Positive CTC count was associated with the presence of five or more metastatic sites (p = 0.018). Neither PFS nor OS were found to differ significantly between CTC-positive and CTC-negative cases (log-rank p = 0.079 and 0.549, respectively). The presence of five or more metastatic sites and worse PS were recognized as independent predictors of reduced PFS [HR = 2.9, p = 0.042 and HR = 2.7, p = 0.035, respectively], and reduced OS [HR = 7.8, p = 0.003 and HR = 16.9, p &lt; 0.001, respectively]. Conclusions:CTCs were detected in a relatively small percentage of our patient population and their presence was associated with increased metastatic burden. In contrast, we failed to observe any significant associations between baseline CTC count and the prognostic variables evaluated. Our results support the suggested role of CTCs in the metastatic dissemination of cancer and underline the need for more efficient methods of CTCs detection.
IDH1R132, IDH2R140 and IDH2R172 in AML: different genetic landscapes correlate with outcome and may influence targeted treatment strategies
Authors: Manja Meggendorfer, Luca Vincenzo Cappelli, Wencke Walter, Claudia Haferlach, Wolfgang Kern, Brunangelo Falini, Torsten Haferlach
Journal: Leukemia (2018)
THE ASSOCIATION BETWEEN CONTRAST DOSE AND RENAL FUNCTION IN TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Fergie Ramos Tuarez, Abdulah Alrifai, Edwin Grajeda, Mohamad Kabach, Jesus Pino, Pradeep Dayanand, Swethika Sundaravel, Eduardo Venegas, Lawrence Lovitz, Mark Rothenberg, Cristiano Faber, Roberto Cubeddu, Marcos Nores
Journal: Journal of the American College of Cardiology (2018)
Influence of aggressive-variant prostate cancer (AVPC) features on outcome of metastatic hormone-sensitive prostate cancer (mHSPC) treated by chemohormonal therapy (CHT).
Authors: Kim Koczka, James Vanhie, Andrea Ibrahim, Nedal Bukhari, M. Neil Reaume, Sandeep R. Sehdev, Kylea R. Potvin, Lori Sax, D. Scott Ernst, Michael M. Vickers, Christina M. Canil, Eric Winquist, Michael Ong
Journal: Journal of Clinical Oncology (2018)

193 Background: Outcomes of patients (pts) undergoing CHT for mHSPC are heterogeneous, with some rapidly developing castration-resistance (CRPC). While AVPC ("anaplastic") features are described in CRPC, less is known in the mHSPC setting. In this multi-institutional cohort, we explored pre-treatment factors associated with poor outcome. Methods: De-novo mHSPC pts treated with CHT from June 2014 to July 2017 at The Ottawa Hospital Cancer Centre (TOHCC) and London Regional Cancer Centre (LRCC) were retrospectively identified. AVPC features (defined below) were collected and cumulatively scored (0, 1, or 2+), along with baseline, treatment and outcome data. Statistical comparisons utilized Cox regression analysis and Kaplan-Meier method for association with CRPC and survival. Results: 92 pts (58 TOHCC, 34 LRCC) met inclusion for study; 83 (90%) had "high-volume" disease (≥4 bone lesions; or ≥1 visceral metastasis), 69/73 (95%) prostate biopsies scored Gleason 8-10, and 55 (60%) had AVPC features: &gt;5 cm nodal/pelvic mass (28), visceral metastases (21), lytic bone metastases (16), elevated LDH (12), low PSA (4), or neuroendocrine differentiation (2). Pre-docetaxel PSA fall of &lt;50, 50-75, 75-90, and ≥90% baseline occurred in 12, 13, 19, and 56% respectively. Docetaxel was initiated a median of 66 days after androgen-deprivation, with 82% completing 5 or 6 cycles. 9 pts (10%) progressed during docetaxel, and 31 pts (34%) developed CRPC &lt; 12 months. Median time to CRPC was 18.4, 14.0, and 11.0 months for 0, 1, and 2+ AVPC features (log rank p=0.009). CRPC was also associated with pre-docetaxel PSA fall &lt;75% (p&lt;0.001) and high alkaline phosphatase (p=0.016). At 18 months median follow-up, 16/55 (29%) with AVPC features have died versus 1/37 (3%) without (log rank p=0.001). In multivariable analysis, AVPC features and pre-docetaxel PSA fall were independently (p&lt;0.05) associated with survival. Conclusions: In our study, mHSPC pts with AVPC features and suboptimal (&lt;75%) pre-docetaxel PSA decline had poor prognosis. These features should be validated in larger cohorts to potentially identify mHSPC pts suitable for further study in clinical trials.