tbuckley/cabot-search huggingface dataset:
Diffusion tensor tractography: Two methods comparative evaluation for gliomas presurgical workup
Authors: Sara Hassanein, Laura Mancini, Sotirios Bisdas, Gehan Seifeldein, Ehab Mansour Moussa, Samy Abdelaziz Khalil, Tarek Yousry
Journal: Neuro-Oncology (2018)

Glioma is the most common primary brain tumour, characterized by invasive growth along white matter (WM) fiber tracts. Tractography providesan importantanatomic guidance in the preoperative planning process, which aims at maximizing resection whilst minimising morbidity. This study aimed atdetermining the agreement between two different software packages for delineating corticospinal tract (CST), arcuate fasciculus (AF) and optic radiation (OR). Forty-six histopathologically proven gliomapatients subdivided into:groupA with tracts passing at the tumour margin; and groupB with tracts passing through tumour and/or in the peritumoural oedema. FSL and MRTrix software were used for tracking, in each patient,CST (hand, foot and lips component), AF and OR using the same regions of interest. Qualitative evaluation of the agreement between the two methods was performed by two experienced observers in consensus. The tracts identified: Were comparable for: CST-foot in 8(5) out of 11(8) cases in groupA (B); CST-hand in 6 out of 8 cases in groupB; Had less false positives in MRTrix for: CST-hand in 7 out of 11 cases in groupA; CST-lips in 5(6) out of 8(8) cases in groupA (B); AF in 4(8) out of 7(9) cases in groupA (B); Were more accurate in FSL for: OR in 6(6) out of 6(7) cases in groupA (B). The accuracy of the tracts is comparable for most fascicle identification, with the exception of MRTrix presenting less false positives for AF in groupB, CST-hand in groupA and CST-lips in groupsA and B; and FSL identifying more accurately the OR in both groups.
Locum GP shortage in Northern Ireland leaves out of hours services understaffed and rural partners unable to take leave, BMA says
Authors: Abi Rimmer
Journal: BMJ (2014)

A shortage of locum GPs in Northern Ireland has left out of hours services understaffed and rural GPs unable to take leave, the BMA’s General Practitioners Committee for Northern Ireland (NIGPC) has said.

Tom Black, the chairman of the NIGPC, said that GPs at the Northern Ireland local medical committees’ conference in Newcastle last weekend had voted against calls for the NIGPC to walk away from discussions with the government on out of hours services. 

Speaking after the conference he said that GPs at the conference were concerned about the provision of out of hours care. …
Kinase domain activation through gene rearrangement in multiple myeloma
Authors: Gareth J Morgan, Jie He, Ruslana Tytarenko, Purvi Patel, Owen W Stephens, Shan Zhong, Shayu Deshpande, Michael Bauer, Niels Weinhold, Carolina Schinke, Leo Rasche, Mark Bailey, Siraj Ali, Jeff Ross, Vincent A Miller, Phillip Stephens, Sharmilan Thanendrarajan, Maurizio Zangari, Frits van Rhee, Tariq Mughal, Faith E Davies, Brian A Walker
Journal: Leukemia (2018)

Chromosomal rearrangements that result in oncogenic kinase activation are present in many solid and hematological malignancies, but none have been reported in multiple myeloma (MM). Here we analyzed 1421 samples from 958 myeloma patients using a targeted assay and detected fusion genes in 1.5% of patients. These fusion genes were in-frame and the majority of them contained kinase domains from either receptor tyrosine kinases (ALK, ROS1, NTRK3, and FGFR1) or cytoplasmic kinases (BRAF, MAP3K14, and MAPK14), which would result in the activation of MEK/ERK, NF-κB, or inflammatory signaling pathways. Fusion genes were present in smoldering MM, newly diagnosed MM, and relapse patient samples indicating they are not solely late events. Most fusion genes were subclonal in nature, but one EML4-ALK fusion was clonal indicating it is a driver of disease pathogenesis. Samples with fusions of receptor tyrosine kinases were not found in conjunction with clonal Ras/Raf mutations indicating a parallel mechanism of MEK/ERK pathway activation. Fusion genes involving MAP3K14 (NIK), which regulates the NF-κB pathway, were detected as were t(14;17) rearrangements involving NIK in 2% of MM samples. Activation of kinases in myeloma through rearrangements presents an opportunity to use treatments existing in other cancers.
Ninety-five consultant posts are vacant in Northern Ireland
Authors: Helen Jaques
Journal: BMJ (2012)

A total of 95 consultant posts are vacant in Northern Ireland, around 6% of the overall number of posts available in the country.

Belfast trust has 44 unfilled positions, 20 of which are at Royal Victoria Hospital, and the northern trust has six vacant posts. 

A further 12 vacancies are in the south eastern trust, with 10 …
Neuro-oncology family caregivers’ view on keeping track of care issues using eHealth systems: it’s a question of time
Authors: Florien Boele, Cornelia Van Uden-kraan, Karen Hilverda, Jason Weimer, Heidi Donovan, Jan Drappatz, Frank Lieberman, Irma Verdonck-de Leeuw, Paula Sherwood
Journal: Neuro-Oncology (2018)

Primary brain tumors (PBTs) are rare but have a great impact on both patient and family caregiver wellbeing. Supporting caregivers can help them to continue their caregiving activities to maintain the patients’ best possible level of quality of life. Efforts to improve PBT caregiver wellbeing should take into account country- or culture-specific differences in care issues and supportive care needs to serve larger caregiver groups. To explore PBT caregivers’ satisfaction with the current supportive care provision, as well as their thoughts on monitoring their care issues with both paper-based and digital instruments. Twelve PBT caregivers were interviewed in the United States. The semi-structured interviews were transcribed verbatim and analyzed by two coders independently. Data were combined with those collected in the Netherlands, following similar methodology (N=15). PBT caregivers utilize both formal and informal support services, but those who experience more care issues would prefer more support, particularly in the early disease phase. Keeping track of care issues was thought to provide more insight into unmet needs and help them find professional help, but it requires investment of time and takes discipline. Caregivers preferred a brief and easy-to-use ‘blended care’ instrument that combines digital monitoring with personal feedback. The present study shows that the preferences of family caregivers in neuro-oncology toward keeping track of care issues are likely not heavily influenced by country- or culture-specific differences. The development of any instrument thus has the potential to benefit a large group of family caregivers.
Systemic chemotherapy for gastric cancer with early recurrence after adjuvant S-1 monotherapy: A multicenter retrospective study.
Authors: Hiroko Hasegawa, Seiichiro Mitani, Takeru Wakatsuki, Hiroki Hara, Motohiro Hirao, Daisuke Takahari, Keisho Chin, Shigenori Kadowaki, Kei Muro
Journal: Journal of Clinical Oncology (2018)

154 Background: S-1 monotherapy is one of the standard adjuvant treatments for stage II or III gastric cancer patients (pts). Early recurrence after adjuvant therapy has a poor prognosis and the optimal regimen remains to be established. This study aimed to clarify the treatment outcomes of systemic chemotherapy and explore encouraging regimens for gastric cancer pts with early recurrence. Methods: We retrospectively reviewed gastric cancer pts at four institutions who underwent curative gastrectomy followed by adjuvant S-1 monotherapy and identified pts who developed recurrence during the adjuvant therapy or within 6 months after completion between 2005 and 2015. Other main eligibility criteria were Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2, adequate organ function and no massive ascites. The Cox proportional hazards model was used to evaluate the survival outcomes, adjusting for relevant factors. Results: A total of 112 pts were included. Pts characteristics were as follows: median age (range), 62 (29-83) years; male/female, 84/28; ECOG-PS 0/1/2, 39/63/10; diffuse/intestinal, 73/39; HER2 status positive/negative/unknown, 17/46/49; metastatic site liver/peritoneum, 32/44; and number of metastatic sites 1/≥2, 94/18. The taxane-based regimens were as follows: weekly paclitaxel (PTX) (38), nab-PTX (4), trastuzumab (Tmab) + PTX (4), S-1 + PTX (3), and the others (4). The platinum-based regimens were irinotecan + cisplatin (IP) (31), capecitabine + cisplatin (XP) (7), S-1 + cisplatin (5), Tmab + XP (4), and the others (2). For all pts, the median PFS and OS were 3.7 months (M) and 11.4 M, respectively. After excluding HER2-positive pts, there were no statistically significant differences between the taxane-based and platinum-based regimens in survival outcomes (median OS, 7.6 M vs. 12.2 M; adjusted HR = 0.93, 95% CI 0.58-1.49), nor between IP and the other platinum-based regimens (median OS, 11.8 M vs. 13.3 M; adjusted HR = 0.64, 95% CI 0.28-1.46). Multivariate analysis showed treatment regimen was not a prognostic factor. Conclusions: The regimens so far selected for gastric cancer with early recurrence resulted in similar, poor prognosis.
Authors’ reply to Ryan, Menzies-Gow and Alexander, and Littlejohns
Authors: Duncan Keeley, Noel Baxter
Journal: BMJ (2018)

Ryan is sceptical about the role of the National Institute for Health and Care Excellence in producing guidelines, but judgments about the relative cost effectiveness of diagnostic approaches and treatments are important if we are to provide the best possible care with limited resources.12

We are encouraged that Menzies-Gow and Alexander3—and Baker in his remarks quoted in the accompanying news piece4—are in favour of a single collaborative and comprehensive UK guideline and hope that negotiations to achieve this will proceed swiftly.

We question Menzies-Gow and Alexander’s statement that “objective testing is shown to be cost effective in NICE’s primary care pilot …
Refocusing research ethics paradigms post Ebola: a narrative synthesis
Authors: Nicola Gailits, Elysée Nouvet
Journal: The Lancet Global Health (2018)

BackgroundThe 2014–15 west Africa Ebola outbreak presented a number of ethical challenges in terms of conducting research while managing the outbreak. As Ebola virus disease (EVD) rapidly spread throughout west African countries, intense bioethical debate centred around the ethics of using experimental treatments and how best to allocate these resources. We aimed to identify further ethical and practical challenges.MethodsWe did a narrative synthesis of scholarly literature emerging from research conducted during the west Africa Ebola outbreak. Articles from Jan 1, 2014, to Jan 1, 2017, were retrieved via MeSH and keyword searches of five indexes (Embase, JSTOR, PubMed, Philosopher's Index, and CINAHL). Keywords included "Ebola" with "trial" or "trials" or "ethics" or "ethical" or "study" or "studies." An initial 2062 articles were reduced to 427 articles after title and abstract screening. After full text screening, 145 articles were uploaded to Nvivo 11 for coding. Eligible articles were analysed inductively and deductively using a team-centred codebook and discussion.FindingsAlongside the central ethical dilemmas that emerged from bioethicist commentaries, a separate discussion could be heard: authors argued that the intense focus on short-term, individual bioethical dilemmas during the EVD outbreak detracted from big-picture inequalities: lack of health system and health capacity in Ebola-affected countries. These authors insisted on the moral imperative to rebalance unequal transnational power relations when doing research in the global South. More needed to be done to prevent exploitative research, differing standards of care, and false notions of minimal expertise in African researchers. They also highlighted the need to acknowledge the root historical and political causes of Ebola, such as neoliberal economic policies imposed on west African health infrastructure. In short, it was felt that to talk about ethics and Ebola without focusing on structural inequalities and neocolonial policies at the root of this public health disaster would be unethical.InterpretationDuring an outbreak of incredible proportion, the need to debate short-term, individual-focused bioethical dilemmas must be balanced with a long-term focus at the community and health-system level. Debates in global bioethics have a responsibility to keep uppermost in their analyses local bioethical paradigms and incorporate an understanding of global economic consequences on health infrastructure and trust building. To move forward, global health ethics needs to prioritise building trustworthy systems that embody solidarity and global justice.FundingR2HC: an ELRHA (Wellcome Trust/DFID/Save the Children) programme.
Abstract P1-08-04: Withdrawn
Authors: B Trabert, DC Bauer, LA Brinton, DS Buist, JA Cauley, CM Dallal, GL Gierach, RT Falk, TF Hue, JV Lacey, AZ LaCroix, JA Tice, X Xu
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Trabert B, Bauer DC, Brinton LA, Buist DS, Cauley JA, Dallal CM, Gierach GL, Falk RT, Hue TF, Lacey, Jr. JV, LaCroix AZ, Tice JA, Xu X. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-04.
Specialist registrar skills in general surgery
Authors: John O’Callaghan
Journal: BMJ (2011)

The specialist registrar skills in general surgery course is a four day programme run centrally by the Royal College of Surgeons of England that can be completed at a number of hospitals nationwide. Currently, dates are available in Liverpool (where I did the course) and Cardiff. The course gives a grounding in bowel anastomosis, vascular anastomosis, and the core principles of laparoscopic surgery.

Officially the course is aimed at trainees in general surgery, from core training year 1 (CT1) to specialty training year 4 (ST4). At the session I attended candidates were mostly from ST3, with a few in CT2 and non-training registrar posts. To get the most out of the course I would recommend that core trainees wait until they are well into CT2. Those who have worked as registrars for more than …
Is expanded radiographic criteria for clinically positive lymph nodes associated with outcome in pathologically node positive prostate cancer?
Authors: Chad A. Reichard, Justin Gregg, Tharakeswara Bathala, Mary F. Achim, John W. Davis, Brian Francis Chapin
Journal: Journal of Clinical Oncology (2018)

126 Background: Patients with pN1 prostate cancer (PCa) have heterogeneous outcomes largely dependent on variables only known post-treatment. Traditionally, the size criteria for clinically positive pelvic adenopathy is axial diameter of 10mm. We employed expanded radiographic criteria (ERC) to evaluate for association with differences in outcome differences. Methods: 187 men treated with RP BPLND for PCa from 2001-2013 were identified as pN1. Imaging studies were re-reviewed by a single radiologist (TB) for nodes that were considered positive if they were 8mm or greater in size OR if they were 6mm or greater in size AND either rounded, asymmetrical OR heterogeneously enhancing. This yielded a group of 34 cN1 patients by ERC. Time to biochemical recurrence (BCR) was compared between cN0 and cN1 patients by K-M method. Cox proportional hazards modeling was used to determine association of baseline PSA, node status, adjuvant therapy, Gleason score, positive margins, and ECR with time to BCR and overall survival (OS). Results: Median age (61 v 59 p = 0.3), baseline PSA (8.7 v 11.1 p = 0.2), and positive margin rate (33% vs 32% p = 0.9) did not differ between cN0 and cN1 patients. Median number of positive LNs was higher in the cN1 group (2.7 v 1.8) p = 0.03. Median biochemical recurrence free survival did not differ between groups (3.3 vs 1.8 years p = 0.3) (Fig1). Only Gleason score was associated with shorter BCR free survival HR 1.3 (95%CI 1.0-1.62, p = 0.047). cN1 disease with expanded radiographic criteria did not predict BCR (HR 1.03, 95CI 0.62-171, p = 0.9) or ACM (HR 0.46, 95CI, 0.1-2.12, p = 0.3). Conclusions: Expanded radiographic criteria for clinically positive lymph nodes was not associated with BCR-free survival or OS in a group of pN1 PCa patients. Further study is required to determine if cN1 status based on expanded clinical criteria or more sensitive imaging methods is associated with outcome differences.
Rare Case of Intratracheal Metastasis Detected on 68Ga–Prostate-Specific Membrane Antigen PET/CT Scan in a Case of Thyroglobulin Elevated Negative Iodine Scan Syndrome
Authors: Arun Sasikumar, Ajith Joy, M. R. A. Pillai, Karuna Elza Oommen, R. Jayakumar
Journal: Clinical Nuclear Medicine (2018)

Abstract A 64-year-old woman underwent completion thyroidectomy with upper tracheal ring resection and right-sided neck dissection for papillary carcinoma of the thyroid infiltrating the trachea and was given 131 I radioiodine treatment. Three years later, she presented with hemoptysis. On evaluation, she had increased serum thyroglobulin and negative iodine scan (TENIS). 18 F-FDG PET/CT scan did not identify any site of disease. One year later, 68 Ga-PSMA scan done revealed a moderate focal tracer-avid intratracheal soft tissue; biopsy revealed it to be metastatic papillary carcinoma of the thyroid. This case kindles the possibility of using 68 Ga-PSMA PET/CT to reveal occult disease in cases of TENIS.
Editor’s Choice: Understanding others and oneself
Authors: Tom Moberly
Journal: BMJ (2015)

This week Deborah Kirkham describes some of the challenges facing doctors in training as they try to develop management and leadership skills (http://careers.bmj.com/careers/advice/view-article.html?id=20020642). Frequent job changes mean that trainee doctors do not have long enough in each role to develop positions as leaders or to acquire the followers required to fulfil the role of a leader. The lack of experience …
Editor’s Choice: Peer support
Authors: Abi Rimmer
Journal: BMJ (2015)

Doctors are often very good at supporting their patients but less good at supporting themselves and their colleagues. When you combine this with the pressures of working in an environment where patient expectations are rising and budgets are shrinking, it is unsurprising that some doctors feel abandoned by the system and that a few even quit medicine entirely.

This week Rachel Bayliss (http://bit.ly/1DMbE8V) calls …
Integrated metabolomic and transcriptomic analyses revealed the distribution of saponins in Panax notoginseng
Authors: Guangfei Wei, Linlin Dong, Juan Yang, Lianjuan Zhang, Jiang Xu, Feng Yang, Ruiyang Cheng, Ran Xu, Shilin Chen
Journal: Acta Pharmaceutica Sinica B (2018)

Panax notoginseng is famous for its important therapeutic effects. Saponins are bioactive compounds found in different parts and developmental stages of P. notoginseng plants. Thus, it is urgently to study saponins distribution in different parts and growth ages of P. notoginseng plants. In this study, potential biomarkers were found, and their chemical characteristic differences were revealed through metabolomic analysis. High-performance liquid chromatography data indicated the higher content of saponins (i.e., Rg1, Re, Rd, and Rb1) in the underground parts than that in the aerial parts. 20(S)-Protopanaxadiol saponins were mainly distributed in the aerial parts. Additionally, the total saponin content in the 3-year-old P. notoginseng plant (188.0 mg/g) was 1.4-fold higher than that in 2-year-old plant (130.5 mg/g). The transcriptomic analysis indicated the tissue-specific transcription expression of genes, namely, PnFPS, PnSS, PnSE1, PnSE2, and PnDS, which encoded critical synthases in saponin biosyntheses. These genes showed similar expression patterns among the parts of P. notoginseng plants. The expression levels of these genes in the flowers and leaves were 5.2fold higher than that in the roots and fibrils. These results suggested that saponins might be actively synthesized in the aerial parts and transformed to the underground parts. This study provides insights into the chemical and genetic characteristics of P. notoginseng to facilitate the synthesis of its secondary metabolites and a scientific basis for appropriate collection and rational use of this plant.
Psychiatry trainees’ teaching skills course
Authors: Susil G Stephen
Journal: BMJ (2011)

The teaching skills course for psychiatry trainees run by the Royal College of Psychiatrists Scottish Division’s undergraduate student teaching and recruitment group is designed to provide its participants with the knowledge, skills, and practical techniques they need to become more proficient and enthusiastic teachers. They also learn strategies that will equip them to design and deliver academic lectures and small group teaching sessions.

It is for psychiatry trainees at any level of training, but an ideal participant would be a post-membership higher specialist trainee in the first or second year (specialty training year 4 or 5). At this level the trainee is relatively …
Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML
Authors: Andreas T. Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L. Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S. Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina Wikström, Pontus Blomberg, Björn Engelbrekt Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Journal: Clinical Cancer Research (2018)

Purpose: To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients.Experimental Design: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL2-activated haploidentical NK cells.Results: NK-cell infusions were well-tolerated, with only transient adverse events observed in the 16 patients. Six patients achieved objective responses with complete remission (CR), marrow CR, or partial remission (PR). Five patients proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). Three patients are still free from disease >3 years after treatment. All evaluable patients with objective responses (5/5 evaluable) had detectable donor NK cells at days 7/14 following infusion and displayed reduction of tumor cell clones, some of which carried poor prognosis mutations. Residual lin-CD34+CD123+CD45RA+ blast cells in responders had increased total HLA class I and HLA-E expression. Responding patients displayed less pronounced activation of CD8+ T cells and lower levels of inflammatory cytokines following NK-cell infusion. Intriguingly, despite omission of systemic IL2, all patients displayed increased frequencies of activated Ki-67+CD127-FoxP3+CD25hiCD4+ Treg cells of recipient origin following NK-cell therapy.Conclusions: Overall, this study suggests that high-risk MDS is responsive to NK-cell therapy and supports the use of haploidentical NK-cell infusions as a bridge to HSCT in refractory patients. Objective clinical responses and reduction of high-risk clones were associated with detectable donor-derived NK cells, immunoediting of residual blast cells, and less pronounced host immune activation. Clin Cancer Res; 24(8); 1834-44. ©2018 AACR.
The current role of MRI in differentiating multiple sclerosis from its imaging mimics
Authors: Ruth Geraldes, Olga Ciccarelli, Frederik Barkhof, Nicola De Stefano, Christian Enzinger, Massimo Filippi, Monika Hofer, Friedemann Paul, Paolo Preziosa, Alex Rovira, Gabriele C. DeLuca, Ludwig Kappos, Tarek Yousry, Franz Fazekas, Jette Frederiksen, Claudio Gasperini, Jaume Sastre-Garriga, Nikos Evangelou, Jacqueline Palace
Journal: Nature Reviews Neurology (2018)