tbuckley/cabot-search huggingface dataset:
Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia
Authors: Syed Haider, Alan McIntyre, Ruud G. P. M. van Stiphout, Laura M. Winchester, Simon Wigfield, Adrian L. Harris, Francesca M. Buffa
Journal: Genome biology (2016)

Altered metabolism is a hallmark of cancer. However, the role of genomic changes in metabolic genes driving the tumour metabolic shift remains to be elucidated. Here, we have investigated the genomic and transcriptomic changes underlying this shift across ten different cancer types. A systematic pan-cancer analysis of 6538 tumour/normal samples covering ten major cancer types identified a core metabolic signature of 44 genes that exhibit high frequency somatic copy number gains/amplifications (>20 % cases) associated with increased mRNA expression (ρ > 0.3, q < 10−3). Prognostic classifiers using these genes were confirmed in independent datasets for breast and kidney cancers. Interestingly, this signature is strongly associated with hypoxia, with nine out of ten cancer types showing increased expression and five out of ten cancer types showing increased gain/amplification of these genes in hypoxic tumours (P ≤ 0.01). Further validation in breast and colorectal cancer cell lines highlighted squalene epoxidase, an oxygen-requiring enzyme in cholesterol biosynthesis, as a driver of dysregulated metabolism and a key player in maintaining cell survival under hypoxia. This study reveals somatic genomic alterations underlying a pan-cancer metabolic shift and suggests genomic adaptation of these genes as a survival mechanism in hypoxic tumours.
Pretreatment urinary MHPG levels as predictors of antidepressant responses to alprazolam
Authors: J J Mooney, J O Cole, A F Schatzberg, B Gerson, J J Schildkraut
Journal: American Journal of Psychiatry (1985)

The authors present preliminary data showing that pretreatment levels of urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly higher in six depressed patients who responded to the antidepressant effects of alprazolam than in six depressed patients who showed no antidepressant response.
The Syk\Jak Inhibitor Cerdulatinib (PRT062070) Shows Promising Preclinical Activity in Chronic Lymphocytic Leukemia By Antagonising B Cell Receptor and Microenvironmental Signalling
Authors: Matthew D Blunt, Jack Parnell, Marta Larrayoz, Lindsay Smith, Rachel Dobson, Jonathan C Strefford, Freda K Stevenson, Francesco Forconi, Andrew J Davies, Peter W Johnson, Graham Packham, Greg P. Coffey, Mark S Cragg, Andrew J Steele
Journal: Blood (2015)
P-100 Phase IB study of sorafenib + evofosfamide in patients (pts) with advanced hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC): NCCTG N1153 (Alliance)
Authors: M. Borad, L. Renfro, N. Foster, P. Martin, S. Alberts, J. Hubbard, A. Silva, T. Halfdanarson, T. Byrne, C. Erlichman
Journal: Annals of Oncology (2016)
What can we salvage from care.data?
Authors: Fiona Godlee
Journal: BMJ (2016)

By now, if all had gone to plan, England would be reaping the early benefits of a national database of patients’ medical records spanning primary and secondary care. Patients would have the comfort of knowing that their records could soon be accessed wherever they were treated; the ability to monitor outcomes might already be suggesting better ways of doing things; and researchers might be starting to interrogate anonymised datasets to generate and test hypotheses.

But all did not go …
Overriding Patient Autonomy to Enhance It: Not the Role of a Consultation Team
Authors: John J. Paris, Robert L. Fogerty, Brian M. Cummings, M. Patrick Moore,
Journal: The American Journal of Bioethics (2016)

The target article “The Curious Case of the De-ICD” is a disturbing apologia pro vita sua, one that seemingly violates the long history of Anglo-Saxon legal norms on the rights of a competent patie...
The Relationship of the BRAFV600E Mutation and the Established Prognostic Factors in Papillary Thyroid Carcinomas
Authors: Bülent Kurt, Serap Yalçın, Engin Alagöz, Yıldırım Karslıoğlu, Nuri Yigit, Armağan Günal, M. Salih Deveci
Journal: Endocrine Pathology (2012)
Quality of Life in Patients With Advanced Cancer: Differential Association With Performance Status and Systemic Inflammatory Response
Authors: Barry J.A. Laird, Marie Fallon, Marianne J. Hjermstad, Sharon Tuck, Stein Kaasa, Pål Klepstad, Donald C. McMillan
Journal: Journal of Clinical Oncology (2016)

Quality of life is a key component of cancer care; however, the factors that determine quality of life are not well understood. The aim of this study was to examine the relationship between quality of life parameters, performance status (PS), and the systemic inflammatory response in patients with advanced cancer.An international biobank of patients with advanced cancer was analyzed. Quality of life was assessed at a single time point by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30). PS was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. Systemic inflammation was assessed by using the modified Glasgow Prognostic Score (mGPS), which combines C-reactive protein and albumin. The relationship between quality of life parameters, ECOG PS, and the mGPS was examined.Data were available for 2,520 patients, and the most common cancers were GI (585 patients [22.2%]) and pulmonary (443 patients [17.6%]). The median survival was 4.25 months (interquartile range, 1.36 to 12.9 months). Increasing mGPS (systemic inflammation) and deteriorating PS were associated with deterioration in quality-of-life parameters (P < .001). Increasing systemic inflammation was associated with deterioration in quality-of-life parameters independent of PS.Systemic inflammation was associated with quality-of-life parameters independent of PS in patients with advanced cancer. Further investigation of these relationships in longitudinal studies and investigations of possible effects of attenuating systemic inflammation are now warranted.
RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells
Authors: Ulrike Höckendorf, Monica Yabal, Tobias Herold, Enkhtsetseg Munkhbaatar, Stephanie Rott, Stefanie Jilg, Johanna Kauschinger, Giovanni Magnani, Florian Reisinger, Michael Heuser, Hans Kreipe, Karl Sotlar, Thomas Engleitner, Roland Rad, Wilko Weichert, Christian Peschel, Jürgen Ruland, Mathias Heikenwalder, Karsten Spiekermann, Julia Slotta-Huspenina, Olaf Groß, Philipp J. Jost
Journal: Cancer Cell (2016)
Novel Evidence That a Quiescent Murine Population of Bone Marrow (BM)-Residing, Developmentally Early, Very Small Sca-1+Lin–CD45– Cells Is Highly Responsive to Prolonged Bleeding by in Vivo Proliferation and Differentiation Into CD45+ Hematopoietic Stem/Progenitor Cells (HSPCs)
Authors: Mariusz Z Ratajczak, Kasia Mierzejewska, Janina Ratajczak, Magdalena Kucia
Journal: Blood (2012)
Continuous wound infiltration versus epidural analgesia after hepato-pancreato-biliary surgery (POP-UP): a randomised controlled, open-label, non-inferiority trial
Authors: Timothy H Mungroop, Denise P Veelo, Olivier R Busch, Susan van Dieren, Thomas M van Gulik, Tom M Karsten, Steve M de Castro, Marc B Godfried, Bram Thiel, Markus W Hollmann, Philipp Lirk, Marc G Besselink
Journal: The Lancet. Gastroenterology & hepatology (2016)
Psychiatric disturbances of aged patients in skilled nursing homes
Authors: R B Teeter, F K Garetz, W R Miller, W F Heiland
Journal: American Journal of Psychiatry (1976)

The authors found that 85% of 74 patients supported by Medicaid in two skilled nursing facilities had significant psychiatric disorders in addition to serious multiple medical illnesses. Almost two-thirds of the psychiatric disturbances had not been diagnosed. Although staff were more concerned with the psychosocial than the physical aspects of patients' problems in more than half of the cases, they often had difficulty recognizing the legitimacy of psychological complaints and relating to patients with psychological disturbances. Staff were not clear about the orders for psychotropic medications that were prescribed for more than half of the patients. The authors point out that more psychiatric consultation is needed to ensure appropriate and effective care for psychiatric patients in such facilities.
Targeting Androgen Receptor Aberrations in Castration-Resistant Prostate Cancer
Authors: Adam Sharp, Jonathan Welti, Julian Blagg, Johann S. de Bono
Journal: Clinical Cancer Research (2016)

Abstract Androgen receptor (AR) splice variants (SV) have been implicated in the development of metastatic castration-resistant prostate cancer and resistance to AR targeting therapies, including abiraterone and enzalutamide. Agents targeting AR-SV are urgently needed to test this hypothesis and further improve the outcome of patients suffering from this lethal disease. Clin Cancer Res; 22(17); 4280–2. ©2016 AACR. See related article by Yang et al., p. 4466
Evaluation d'une épidémie d'amibiase en Géorgie
Authors: P Kreidl, P Imnadze, L Baidoshvili, D Greco
Journal: Eurosurveillance (1999)

Entamoeba histolytica est un protozoaire qui sevit dans le monde entier et on estime que 12% de la population mondiale est infectee (1). La prevalence de l’infection varie de 1% dans les pays industrialises a 50-80% dans les pays tropicaux, ou la transmission des kystes d’E. histolytica par l’eau non traitee est frequente. L’ingestion d’aliments ou de boissons contamines par des kystes d’E. histolytica provenant de matieres fecales humaines et le contact direct de la bouche avec des matieres fecales sont les modes d’infections les plus frequents (2,3).
Big health data: the need to earn public trust
Authors: Tjeerd-Pieter van Staa, Ben Goldacre, Iain Buchan, Liam Smeeth
Journal: BMJ (2016)

Failures in implementation of data sharing projects have eroded public trust. In the wake of NHS England's decision to close down its care.data programme,<b> Tjeerd-Pieter van Staa and colleagues</b> examine how we can do better
Phase II clinical study of eribulin monotherapy in patients with metastatic breast cancer who presented well-defined taxane resistance.
Authors: Kenichi Inoue, Tsuyoshi Saito, Katsuhiko Okubo, Kei Kimizuka, Hirofumi Yamada, Takashi Sakurai, Kazuo Ishizuna, Reiji Hata, Toshio Kai, Masafumi Kurosumi
Journal: Journal of Clinical Oncology (2016)

e12517 Background: Eribulin is a nontaxane microtubule dynamics inhibitor, which has shown a survival benefit in patients (pts) with heavily-pretreated metastatic breast cancer (MBC). No clinical evidence on the efficacy and safety of eribulin has been obtained in pts with MBC who presented taxane resistance. The present Phase II, multicenter, single-arm, open-label study aimed to provide the evidence. Methods: Japanese pts, aged 33-74 years who had metastasis of taxane-resistant and histopathologically confirmed breast cancer, received eribulin mesylate 1.4 mg/m2 as a 2- to 5-min intravenous infusion on days 1 and 8 of each 21-day cycle. The primary endpoint was the clinical benefit rate (CBR) [complete response (CR), partial response (PR), and long-term stable disease (LSD) ≥ 24 weeks]. A woman with MBC who was already under chemotherapy was considered to present well-defined taxane resistance when falling under either of the following cases: 1) breast cancer recurred during taxane treatment or within 1 year after the last administration when undergoing neo- or adjuvant chemotherapy with taxane or 2) the tumor progressed (from CR/PR/SD to PD or PD) during taxane treatment. Results: A total of 51 pts underwent a median of 2 chemotherapy regimens (range, 0-7) after metastasis. The CBR was 39.2% (CR, 2.0%; PR, 23.5%, and LSD, 13.7%), and the rate of progressive disease was 49.0%. The median progression-free survival and the median overall survival were 3.6 months (95% CI: 2.6-4.6 months) and 11.7 months (95% CI: 9.2-14.2 months), respectively. The grade 3 adverse event were leukopenia (19.6%), neutropenia (17.6%), anemia (5.9%), and febrile neutropenia (7.8%). The incidences of grade 3 and 4 peripheral sensory neuropathy were 2.0% and 0%, respectively. Eribulin showed a clinically manageable tolerability profile through dose adjustments or symptomatic treatment. The median of cycles delivered was 4 (range, 1-42cycles). The median of relative dose intensity (RDI) was 85.6% (range, 31.0-101.3%). Conclusions: Eribulin was effective for and well tolerated by pts with MBC who had well-defined taxane resistance, thus providing a promising therapeutic option in the clinical settings. Clinical trial information: 000006965.
Progression-free survival (PFS) with maintenance treatment with bevacizumab (B) in patients with responding mCRC after first-line chemotherapy (CT) plus B.
Authors: Maria Agnese Fabbri, Fabrizio Nelli, Luca Moscetti, Enrico Cortesi, Teresa Gamucci, Isabella Sperduti, Daniela Franco, Ida Pavese, Roberta Grande, Daniele Alesini, Enzo Ruggeri
Journal: Journal of Clinical Oncology (2012)

612 Background: Maintenance treatment with B is considered an option for mCRC pts in responding pts after a first line CT + B, but few data are available on its real benefit on PFS. Methods: We collected data from a cohort of mCRC pts consecutively treated in five oncologic centers of Lazio. One-hundred-ninety-nine mCRC pts treated with first line CT + B achieving a response [partial (PR) or complete (CR)] or a stable disease (SD) were considered eligible, 117 pts had received B maintenance (BM) whereas 82 did not (noBM). The two groups were homogeneous for main characteristics. First-line therapy in the BM vs noBM group included FOLFIRI regimen (96 vs 59 pts), FOLFOX (18 vs 22 pts) and FUFA (3 vs 1 pts). K-ras status was analyzed in 115 pts with an higher percentage of wild-type (wt) in the BM group (65 vs 50 pts, p= 0.04). A CR or PR have been achieved in 65% of pts in the BM group and 61% of noBM group, while a SD was observed in 35% and 39% of pts respectively for the BM and noBM group. The median number of BM cycles administered was 7 (range 3-25). Effectiveness measures included the PFS duration. A multivariate Cox proportional hazard model was developed using stepwise regression (forward selection) Results: At a median follow-up of 18 months (1-109), the median PFS was 13 months (C.I.95%: 11-15) vs 8 months (C.I.95%: 7-10; p&lt;0.0001, and the 1-year PFS 53% vs 28% for BM and noBM respectively. Pts with CR/PR had a mPFS of 15 months (CI 95% 12-19) vs 10 months (CI 95% 10-12) p=0.004 and a 1-year PFS of 62.6% vs 33.7% for the BM vs noBM group respectively. No difference in the 1-year PFS was observed in pts showing SD to chemotherapy and bevacizumab. The mPFS in these patients was 12 (CI 95% 10-13) vs 8 months (CI 95% 7-10, p=0.11) for the BM and noBM group respectively. The multivariate analysis did not show any difference in PFS comparing age, sex, number and site of metastasis, ECOG PS and k ras status. A significant difference in PFS was observed for response to first-line CT (CR/PR vs SD, p=0.002) and for BM vs noBM (p=0.003). Conclusions: The maintenance strategy with B shows a longer PFS in pts responding to the first line chemotherapy + B whereas for pts who achieving an SD no difference was observed.
Phase III randomized study of ipilimumab (IPI) plus dacarbazine (DTIC) versus DTIC alone as first-line treatment in patients with unresectable stage III or IV melanoma.
Authors: J. D. Wolchok, L. Thomas, I. N. Bondarenko, S. O'Day, J. S. Weber, C. Garbe, S. Francis, R. A. Ibrahim, A. Hoos, C. Robert
Journal: Journal of Clinical Oncology (2011)

LBA5 The full, final text of this abstract will be available in Part II of the 2011 Annual Meeting Proceedings, distributed onsite at the Meeting on June 4, 2011, and as a supplement to the June 20, 2011, issue of Journal of Clinical Oncology.
Investigation of a staphylococcal food poisoning outbreak combining case–control, traditional typing and whole genome sequencing methods, Luxembourg, June 2014
Authors: Joël Mossong, Frédéric Decruyenaere, Gilbert Moris, Catherine Ragimbeau, Christophe M. Olinger, Sophia Johler, Monique Perrin, Patrick Hau, Pierre Weicherding
Journal: Eurosurveillance (2015)

In June 2014, a staphylococcal food poisoning outbreak occurred at an international equine sports event in Luxembourg requiring the hospitalisation of 31 persons. We conducted a microbiological investigation of patients and buffet items, a case–control study and a carriage study of catering staff. Isolates of Staphylococcus aureus from patients, food and catering staff were characterised and compared using traditional typing methods and whole genome sequencing. Genotypically identical strains (sequence type ST8, spa -type t024, MLVA-type 4698, enterotoxin A FRI100) were isolated in 10 patients, shiitake mushrooms, cured ham, and in three members of staff. The case–control study strongly suggested pasta salad with pesto as the vehicle of infection (p&lt;0.001), but this food item could not be tested, because there were no leftovers. Additional enterotoxigenic strains genetically unrelated to the outbreak strain were found in four members of staff. Non-enterotoxigenic strains with livestock-associated sequence type ST398 were isolated from three food items and two members of staff. The main cause of the outbreak is likely to have been not maintaining the cold chain after food preparation. Whole genome sequencing resulted in phylogenetic clustering which concurred with traditional typing while simultaneously characterising virulence and resistance traits.
Slow response contributed to scale of west African Ebola epidemic, CDC concludes
Authors: Michael McCarthy
Journal: BMJ (2016)

A slow initial response contributed to the scale of the 2014-16 outbreak of Ebola virus disease in west Africa that infected more than 28 000 people and killed more than 11 000, the US Centers for Disease Control and Prevention concluded in a new report detailing its early response to the situation.1

Writing in the report’s introduction, CDC director Tom Frieden noted that it was not well recognized how close the world came to a global catastrophe during the west African outbreak. He wrote, “If Ebola had not been rapidly contained in Lagos, Nigeria, a densely populated city with many international airline connections, the disease most likely would have spread to other parts of Nigeria, elsewhere in Africa, and possibly to other continents.”

The 106 page report appeared as a supplement in the 8 July issue of CDC’s …
Survival trends in young patients with Waldenstrom macroglobulinemia (WM).
Authors: Nishanth Vallumsetla, Jonas Paludo, Morie Gertz, Stephen Maxted Ansell, Ronald S. Go, Vincent Rajkumar, Robert A. Kyle, Francis Buadi, Angela Dispenzieri, Martha Lacy, David Dingli, Suzanne R. Hayman, Nelson Leung, Shaji Kumar, Prashant Kapoor
Journal: Journal of Clinical Oncology (2015)

8596 Background: Data in young patients (pts) with WM are sparse and the few available studies utilizing SEER database have yielded inconsistent results, possibly overestimating survival, in part related to inclusion of asymptomatic pts. Herein, we investigate trends in overall survival (OS), including the Rituximab era, in a cohort of young symptomatic WM pts, seen at Mayo Clinic over 5 decades. Methods: Of 1181 pts with WM seen consecutively between 1960 and 2013, 127 (11%) were ≤ 50 years (y) at diagnosis, and 123 of those received therapy. Pts were categorized into 3 equal year groups based on the timing of initiation of therapy: Group 1 (1960-77), Group 2 (1978-95) and Group 3 (1996-2013), and their OS was analyzed using the Kaplan Meier method. We also compared their outcomes with a cohort of pts, ≥ 65 y and matched (1:1) by the timing of diagnosis. Results: Follow-up from initiation of therapy was similar in the 2 cohorts (median: 10.8 y in young vs 10.4 y in control arm). The median OS from initial therapy was 15 y (95% CI 13-18) for the young compared to 7.3 y (CI 5-8) for the control arm. In the young pts, 92% of deaths with known causes were WM related compared to 59% in control arm (p = 0.0004). While there was no significant OS difference observed with the use of Rituximab-based initial therapy in the young [median 11.4 y (CI 6–NR*) versus 15.6 y (CI 13-21) for all other therapies; p = 0.13], the control arm showed superior OS for pts who received Rituximab based initial therapy [median 9.1 y (CI 7-NR) vs 5.8 y (CI 5-8) for other therapies; p = 0.03]. Among young pts, there was no OS improvement from initial therapy across the 3 groups (p = 0.47) while the OS trends for the controls showed improvement across the 3 groups (p = 0.002; Table). Conclusions: Survival of young pts with WM remains unchanged over the past 5 decades. In contrast to the patients aged ≥ 65,Rituximab use did not translate to improved survival in young pts. Parameter Young Pts Control Median Age (Range) 44 y (30-50) 73 y (65-85) OS in years (95% CI); Group 1 12.7 (5-16); n=13 4.7 (2-7); n=14 Group 2 16 (12-22); n=45 5.3 (4-10); n=43 Group 3 14.8 (10-NR*); n=65 8.3 (6-11); n=66 Initial Therapy (%) Rituximab-based 34 33 Chlorambucil-based 38 52 Nucleoside analogue-based 16 6 Other agents 15 11 *Not Reached
Patterns of psychiatric consultation in a Chinese general hospital
Authors: C Zuo, L Yang, C C Chu
Journal: American Journal of Psychiatry (1985)

The authors conducted a study of psychiatric consultation in a Chinese general hospital. Seventy-five inpatients (0.74% of the patients in the hospital) were referred by different services over a 1-year period. Internal medicine referred the most patients, and organic brain syndromes were the most common diagnoses. Depression was not a frequent diagnosis, but neurasthenia was a fairly common one. None of the referred patients had a diagnosis of alcoholism, drug abuse, or personality disorder. The authors compare these data with those of Western studies and discuss the possible factors influencing psychiatric consultation in China.
Case 3-1963
Journal: New England Journal of Medicine (1963)

Presentation of Case A fifty-six-year-old retired truck driver entered the hospital because of dyspnea and pain in the abdomen. The patient had been in good health until five years previously, when dyspnea on exertion began to occur occasionally. Shortly after the onset of these episodes he was thrown from his vehicle in an automobile accident and trapped under a rear wheel, which rested on his chest. He sustained multiple rib fractures, an acromioclavicular separation and multiple contusions, but did not lose consciousness. During convalescence the dyspnea on exertion increased in severity, and inspiratory and expiratory wheezes appeared. The vital capacity . . .