tbuckley/cabot-search huggingface dataset:
Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity
Authors: Eun-Young Lee, Hyun-Cheol Lee, Hyun-Kwan Kim, Song Yee Jang, Seong-Jun Park, Yong-Hoon Kim, Jong Hwan Kim, Jungwon Hwang, Jae-Hoon Kim, Tae-Hwan Kim, Abul Arif, Seon-Young Kim, Young-Ki Choi, Cheolju Lee, Chul-Ho Lee, Jae U Jung, Paul L Fox, Sunghoon Kim, Jong-Soo Lee, Myung Hee Kim
Journal: Nature Immunology (2016)
Exercise therapy is supplementary to arthroscopic surgery when surgery is indicated
Authors: Avinash Joshi
Journal: BMJ (2016)

Kise and colleagues conclude that exercise therapy is better than surgery for thigh muscle strength in patients with degenerative meniscal tears.1

Magnetic resonance imaging (MRI) was used to diagnose meniscal tears in all of their patients. This seems impractical with dwindling funding for hospitals …
Risk factors for second primary melanoma among Dutch patients with melanoma
Authors: M.S. Schuurman, A.C. de Waal, E.J.M. Thijs, M.M. van Rossum, L.A.L.M. Kiemeney, K.K.H. Aben
Journal: British Journal of Dermatology (2016)

Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified surveillance.To identify risk factors for a second primary cutaneous melanoma.Possible risk factors for a second primary melanoma were assessed in 1127 patients with cutaneous melanoma who were diagnosed between 2003 and 2011 and completed a baseline questionnaire. Additional data were extracted from the Netherlands Cancer Registry and medical files.Fifty-three patients were diagnosed with a second melanoma during a median follow-up time of 6·3 years. The 5-year cumulative risk was 3·7% and the conditional cumulative risk was 4·6% in years 5-10 after diagnosis. In multivariable analyses, the risk of a second melanoma increased with older age at diagnosis [hazard ratio (HR) 1·03 per year; 95% confidence interval (CI) 1·00-1·06], a high naevus density (HR 7·16, 95% CI 2·89-17·75) and working outside for > 10 years (HR 2·88, 95% CI 1·38-6·03). Patients with invasive melanoma (> 1 mm) had a decreased risk compared with patients with melanoma in situ (HR 0·35, 95% CI 0·13-0·93).Besides phenotypic characteristics, cumulative sun exposure seemed to increase the risk of a second melanoma. Patients with melanoma in situ may need to be offered follow-up, which is currently not advised. As the risk of a second melanoma did not decline in years 5-10 after diagnosis, a subgroup of patients may need a longer follow-up than is currently advised.
Association of Reports of Childhood Abuse and All-Cause Mortality Rates in Women
Authors: Edith Chen, Nicholas A. Turiano, Daniel K. Mroczek, Gregory E. Miller
Journal: JAMA Psychiatry (2016)

Research has linked childhood abuse to a variety of adult psychiatric problems, but little is known about associations of child abuse with adult mortality.To test associations of retrospective reports of physical and emotional abuse in childhood with all-cause mortality rates in adulthood.National sample of 6285 adults (aged 25-74 years at baseline) from the survey of Midlife Development in the United States. Baseline psychosocial data were collected in 1995 and 1996, with follow-up mortality data collected through October 2015.Participants completed questionnaires at baseline about self-report of childhood emotional abuse, moderate physical abuse, and severe physical abuse. Mortality data during the next 20 years was tracked using the National Death Index.Of the 6285 participants included in the study sample, 2987 were men (48%) and 5581were white (91%), with a mean (SD) age of 46.9 (12.95) years. Women who reported childhood emotional abuse (hazard ratio [HR], 1.22; 95% CI, 1.01-1.49; P = .04), moderate physical abuse (HR, 1.30; 95% CI, 1.05-1.60; P = .02), or severe physical abuse (HR, 1.58; 95% CI, 1.20-2.08; P = .001) were at increased risk for all-cause mortality during the follow-up period. Reports of more types of childhood abuse were also associated with a greater risk of all-cause mortality in women (all vs none HR, 1.68; 95% CI, 1.24-2.30; P = .001; some vs none HR, 1.24; 95% CI, 1.01-1.52; P = .04). These effects could not be accounted for by childhood socioeconomic status, personality traits, or adult depression. No associations were observed in men.These results suggest that in addition to the established psychiatric consequences of abuse, women who report childhood abuse also remain vulnerable to premature mortality into adulthood. Thus, reported childhood abuse may have long-term ramifications for health and longevity in women.
Genomic Profiling In Fit, Elderly Patients Receiving Oral Fludarabine, Oral Cyclophosphamide and Intravenous Rituximab (ALLG CLL5 OFOCIR trial) As Initial Treatment Of Chronic Lymphocytic Leukemia (CLL)
Authors: Xavier Badoux, Giles Best, Sara Gabrielli, Miss Miss, Ying Zhu, Melanie Hayes, Bryone J Kuss, William Stevenson, Stephen P Mulligan
Journal: Blood (2013)
Predisposition to Myelodysplastic Syndrome with Deletion 5q Is Associated with TP53 Codon 72 Genotype
Authors: Kathy Rocha McGraw, Lan Min Zhang, Dana E. Rollison, Hui-Yi Lin, Bhupendra Rawal, Debbie Billingsley, Sandra E. Kurtin, Gisela Caceres, Justine Clark, Lubomir Sokol, P.K. Epling-Burnette, Kathryn Guinta, Jaroslaw P Maciejewski, Mar Mallo, Francesc Solé, Maria Jose Calasanz, Jose Cervera, Esperanzo Such, Teresa Gonzalez Martinez, Sandy Sung, Thomas J. Nevill, Aly Karsan, Alan F. List
Journal: Blood (2010)
Quantitative MRD Assessments Predict Progression Free Survival in CLL Patients Treated with Fludarabine and Cyclophosphamide with or without Rituximab – a Prospective Analysis in 471 Patients from the Randomized GCLLSG CLL8 Trial
Authors: Sebastian Boettcher, Kirsten Fischer, Stephan Stilgenbauer, Raymonde Busch, Günter Fingerle-Rowson, Anna-Maria Fink, Hartmut Döhner, Michael Hallek, Michael Kneba, Matthias Ritgen, on Behalf Of GCLLSG
Journal: Blood (2008)
NY-ESO-1 Single Edited T Cells to Treat Multiple Myeloma without Inducing GvHD
Authors: Sara Mastaglio, Pietro Genovese, Zulma Magnani, Elisa Landoni, Barbara Camisa, Giulia Schiroli, Elena Provasi, Angelo Lombardo, Andreas Reik, Nicoletta Cieri, Maurilio Ponzoni, Fabio Ciceri, Claudio Bordignon, Michael C. Holmes, Philip D Gregory, Luigi Naldini, Chiara Bonini
Journal: Blood (2014)
Health Care-Associated Infection (HAI) Rates Are More Pertinent Quality Indicators Than Nosocomial Infection (NI) Ones for Hematology Programs.
Authors: Sami Chehata, Chiraz Grira, Patrick Legrand, Cecile Pautas, Sebastien Maury, Mathieu Kuentz, Jean Carlet, Catherine Cordonnier
Journal: Blood (2005)
Management of Patients With Sickle Cell Disease
Authors: Simeon Pollack
Journal: JAMA (2015)

To the Editor The Special Communication reporting a summary of the National Heart, Lung, and Blood Institute expert panel report on the management of patients with sickle cell disease (SCD)1 distilled best practice recommendations from the extensive sickle cell anemia literature. However, the recommendation that chelation therapy should be standard for patients with SCD and iron overload failed to consider an important aspect of the problem.
Combined HRT may raise breast cancer risk, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Women taking combined hormone replacement therapy (HRT) are 2.7 times more likely to develop breast cancer than non-users, and the risk may increase with longer use, a study published in the British Journal of Cancer has found.1

The researchers, from the Institute of Cancer Research in London, said that previous studies may have substantially underestimated the risk of breast cancer from combined HRT, as they did not update information about a woman’s HRT use or analyse accurately to allow for her age at menopause.

The new research was part of the Breast Cancer Now Generations Study, which is following more than 100 000 women for 40 years to investigate the causes of breast cancer. The current …
The survival difference between gastric cancer patients from the United Kingdom and Japan after using weighted propensity score for adjustment of differing background factors.
Authors: Takaki Yoshikawa, Takanobu Yamada, Tsutomu Hayashi, Henry M Sue-Ling, Kiran Bonam, Masataka Taguri, Jeremy D. Hayden, Heike I. Grabsch
Journal: Journal of Clinical Oncology (2014)

4055 Background: Previous studies comparing survival between gastric cancer (GC) patients (pts) from the East and the West either used calibrated survival based on a Western nomogram, only considered a highly selected set of background factors in multivariate analyses or did not consider differences in background factors and prognostic factors at all . The present study aimed to first compare all available characteristics from GC pts from the UK and Japan and then compare the survival of the two cohorts after adjusting for all significantly different background factors using weighted propensity score. Methods: Data from 654 pts from the Kanagawa Cancer Center, Yokohama, Japan (KCCH) and 680 pts from the Leeds Teaching Hospital NHS Trust, Leeds, UK (LTHT) who had surgery for GC were analyzed. Patient characteristics, surgery, pathology, and outcome were compared. Prognostic factors for overall survival (OS) and cancer specific survival (CSS) were identified by univariate and multivariate analyses. After initial comparison of ‘unadjusted’ survival, survival was compared after adjusting for all significantly different background factors. Results: Significant differences between KCCH and LTHT pts were observed for age, gender, tumor location, type of gastrectomy, splenectomy, pancreatectomy, residual tumor (R), number of examined lymph nodes, and histological tumor type. Unadjusted stage-specific OS and CSS were significantly better in KCCH. Independent prognostic factors for unadjusted OS and CSS were age, tumor location, depth of invasion (T), nodal metastasis (N), and distant metastasis (M) in KCCH; and age, tumor location, splenectomy, T, N, M, R status and number of examined lymph nodes in LTHT. Even after adjusting for all background characteristics, survival remained better in KCCH in TNM stages I, II, and III for OS and TNM stages II and III for CSS. Conclusions: These results suggest that the differences in background factors between GC pts from UK and Japan cannot fully explain differences in survival. Further studies are needed to investigate whether survival differences are due to GC tumor biology and/or host specific factors.
PGAM5-mediated programmed necrosis of hepatocytes drives acute liver injury
Authors: Gui-Wei He, Claudia Günther, Andreas E Kremer, Veronika Thonn, Kerstin Amann, Christopher Poremba, Markus F Neurath, Stefan Wirtz, Christoph Becker
Journal: Gut (2016)

<h3>Objectives</h3> Autoimmune hepatitis (AIH) is a severe necroinflammatory liver disease associated with significant mortality. Although loss of hepatocytes is generally recognised as a key trigger of liver inflammation and liver failure, the regulation of hepatic cell death causing AIH remains poorly understood. The aim of this study was to identify molecular mechanisms that drive hepatocyte cell death in the pathogenesis of acute liver injury. <h3>Design</h3> Acute liver injury was modelled in mice by intravenous administration of concanavalin A (ConA). Liver injury was demonstrated by serum transaminases and histological assessment of liver sections. PGAM5-deficient mice (PGAM5−/−) were used to determine its role in experimental hepatitis. Mdivi-1 was used as an inhibitor of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Mitochondrial fission and the expression of PGAM5 were compared between liver biopsies derived from patients with AIH and control patients. <h3>Results</h3> PGAM5 was highly expressed in hepatocytes of patients with AIH and in mice with ConA-induced experimental hepatitis. Deficiency of PGAM5 protected mice from ConA-induced hepatocellular death and liver injury. PGAM5 regulated ConA-induced mitochondrial fission in hepatocytes. Administration of the Drp1-inhibitor Mdivi-1 blocked mitochondrial fission, diminished hepatocyte cell death and attenuated liver tissue damage induced by ConA. <h3>Conclusions</h3> Our data demonstrate for the first time that PGAM5 plays an indispensable role in the pathogenesis of ConA-induced liver injury. Downstream of PGAM5, Drp1-mediated mitochondrial fission is an obligatory step that drives the execution of hepatic necrosis and tissue damage. Our data highlight the PGAM5-Drp1 axis as a potential therapeutic target for acute immune-mediated liver injury.
Gastro-oesophageal reflux and idiopathic pulmonary fibrosis: in search of evidence
Authors: Wim Wuyts, Bruno Crestani
Journal: European Respiratory Journal (2016)

Gastro-oesophageal reflux (GOR) is a frequent comorbidity in many chronic respiratory conditions, particularly in idiopathic pulmonary fibrosis (IPF) [1]. However, the evidence that GOR contributes to the pathophysiology of IPF and that interventions aimed at controlling GOR may influence the evolution of lung fibrosis remains elusive. Despite that, the 2015 update of the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association clinical practice guidelines for IPF provides a conditional recommendation for antacid treatment as a possible treatment for IPF [2], albeit with very low confidence in estimates of effect because data on the efficacy of antacid therapy effect are limited. The same guidelines provide a conditional recommendation for pirfenidone and nintedanib treatment in patients with IPF based on the results of phase 3 randomised controlled trials [2]. We need evidence for anti-reflux therapy in IPF <http://ow.ly/zS9U302sOB7>
An Appraisal of Social Network Theory and Analysis as Applied to Public Health: Challenges and Opportunities
Authors: Thomas W. Valente, Stephanie R. Pitts
Journal: Annual Review of Public Health (2016)

The use of social network theory and analysis methods as applied to public health has expanded greatly in the past decade, yielding a significant academic literature that spans almost every conceivable health issue. This review identifies several important theoretical challenges that confront the field but also provides opportunities for new research. These challenges include (a) measuring network influences, (b) identifying appropriate influence mechanisms, (c) the impact of social media and computerized communications, (d) the role of networks in evaluating public health interventions, and (e) ethics. Next steps for the field are outlined and the need for funding is emphasized. Recently developed network analysis techniques, technological innovations in communication, and changes in theoretical perspectives to include a focus on social and environmental behavioral influences have created opportunities for new theory and ever broader application of social networks to public health topics.
A Christianson syndrome-linked deletion mutation (∆287ES288) in SLC9A6 disrupts recycling endosomal function and elicits neurodegeneration and cell death
Authors: Alina Ilie, Andy Y. L. Gao, Jonathan Reid, Annie Boucher, Cassandra McEwan, Hervé Barrière, Gergely L. Lukacs, R. Anne McKinney, John Orlowski
Journal: Molecular Neurodegeneration (2016)

Christianson Syndrome, a recently identified X-linked neurodevelopmental disorder, is caused by mutations in the human gene SLC9A6 encoding the recycling endosomal alkali cation/proton exchanger NHE6. The patients have pronounced limitations in cognitive ability, motor skills and adaptive behaviour. However, the mechanistic basis for this disorder is poorly understood as few of the more than 20 mutations identified thus far have been studied in detail. Here, we examined the molecular and cellular consequences of a 6 base-pair deletion of amino acids Glu287 and Ser288 (∆ES) in the predicted seventh transmembrane helix of human NHE6 expressed in established cell lines (CHO/AP-1, HeLa and neuroblastoma SH-SY5Y) and primary cultures of mouse hippocampal neurons by measuring levels of protein expression, stability, membrane trafficking, endosomal function and cell viability. In the cell lines, immunoblot analyses showed that the nascent mutant protein was properly synthesized and assembled as a homodimer, but its oligosaccharide maturation and half-life were markedly reduced compared to wild-type (WT) and correlated with enhanced ubiquitination leading to both proteasomal and lysosomal degradation. Despite this instability, a measurable fraction of the transporter was correctly sorted to the plasma membrane. However, the rates of clathrin-mediated endocytosis of the ∆ES mutant as well as uptake of companion vesicular cargo, such as the ligand-bound transferrin receptor, were significantly reduced and correlated with excessive endosomal acidification. Notably, ectopic expression of ∆ES but not WT induced apoptosis when examined in AP-1 cells. Similarly, in transfected primary cultures of mouse hippocampal neurons, membrane trafficking of the ∆ES mutant was impaired and elicited marked reductions in total dendritic length, area and arborization, and triggered apoptotic cell death. These results suggest that loss-of-function mutations in NHE6 disrupt recycling endosomal function and trafficking of cargo which ultimately leads to neuronal degeneration and cell death in Christianson Syndrome.
The utility of PET/CT in the treatment management of gastroesophageal cancer (GEC): Impact on staging and treatment decisions.
Authors: W. Shan, C. K. Kollmannsberger, D. Wilson, A. Briede, C. D. Blanke, H. J. Lim
Journal: Journal of Clinical Oncology (2010)

4138 Background: Accurate staging is important in GEC to determine which patients will benefit from curative resection and to spare patients from morbidity. We investigated the impact of PET/CT scan on staging and treatment plan in a tertiary academic center. Methods: We performed a retrospective chart review of 172 patients with GEC having had a PET/CT scan from June 2004 until March 2009 and extracted relevant data including demographics, tumor site, postoperative pathology, (neo)adjuvant treatments and staging via CT, PET/CT, and/or EUS. A prospective survey was sent to physicians ordering PET/CT about the impact in decision making at the time of scanning. Results: 172 patients were identified. Characteristics: M/F 77%/23%; median age of 66 years; tumor location and histology: 1.7% upper esophagus squamous cell carcinoma (SCC), 19.1% mid to lower esophagus SCC, 30.1% distal esophagus adenocarcinoma (adeno), 32.4% GE junction adeno, 15% gastric adeno, 1.7% undifferentiated. 13% were found to have metastatic disease on PET not identified on CT. 6% had metastatic disease found on CT not identified on PET. 5% had metastatic disease proven either by surgery or biopsy and not found on PET. 1 patient had metastatic disease on PET but was biopsy proven to not have metastatic disease. 17% of patients with N0 disease on PET were found to have node positive disease pathologically. 151 patients had surveys received. PET/CT resulted in a change in treatment intent 65.6% of the time, a change in treatment stage 64.2%, surgery or biopsy added or cancelled 66.7%, a change in systemic management 39.1% and radiation management 41.8%. Overall the sensitivity of PET scan for finding metastatic disease was 79% and specificity was 81%. 96.7% of surveys felt that PET/CT led to improved decision making and 87.4% led to a change in management. Conclusions: PET/CT is useful in staging of GEC. PET/CT also frequently changes decision making in this disease. No significant financial relationships to disclose.
Vitamin D insufficiency in the pediatric oncology population: defining who is at risk and the need for standardized screening
Authors: M. A. Helou, G. Massey, G. Francis, K. Godder, J. Laver
Journal: Journal of Clinical Oncology (2008)

10023 Background: Survivors of childhood cancer are at increased risk for osteoporosis. Contributing factors include direct effects of chemotherapy and radiation therapy on bone, secondary hormone deficiencies, and chronic illness. However, vitamin D insufficiency could be a major risk factor during and after cancer therapy. Vitamin D insufficiency is common in healthy school aged children (median 25-hydroxy vitamin D [25(OH)D] = 28 ng/mL, 55% <30 ng/mL, 5% < 10 ng/mL.) Based on this data, we hypothesize that vitamin D insufficiency would be common among children with cancer. If vitamin D insufficiency is prevalent, correction may contribute to better bone health and immune responses in children with cancer. Methods: We determined the serum levels of 25(OH)D, PTH, calcium, and phosphorus for 40 children with leukemia or lymphoma currently on therapy (group 1), 34 children with leukemia or lymphoma off therapy (group 2), 16 children with solid tumors currently on therapy (group 3), and 10 children with solid tumors off therapy (group 4.) Prevalence of 25(OH)D insufficiency ( <32 ng/mL) and severe deficiency (<10 ng/mL) was compared by Chi square test to the healthy reference population (established by Weng, et al.) Results: For the majority of patients, calcium and phosphorus levels were within normal limits. Conclusions: Vitamin D insufficiency was very common in all groups, especially in children with solid tumors on therapy (Group 3.) 25(OH)D levels did improve off therapy, but for Group 2, still remained significantly less than normal reference population (p=0.0001.) The data suggests that vitamin D status should be determined for all children at diagnosis of malignancy with a strong recommendation to consider vitamin D supplementation during treatment and follow up. Group 25(OH)D mean and range [Reference Range 32–100 ng/mL] Insufficient % Severely Deficient % p value (compared to healthy children) Group 1 n=40 22.2 (<7–63.1) 80% 18% 0.0001 Group 2 n=34 25.2 (<7–61.4) 61% 18% 0.0001 Group 3 n=16 15.2 (<7- 35.3) 94% 44% 0.0001 Group 4 n=10 29.32 (9.8–58.8) 60% 10% 0.0622 Normal (Weng et al) n=382 - 55% 5% - No significant financial relationships to disclose.
Anencephalic Infants as Organ Donors
Authors: Melissa Ferguson
Journal: JAMA (1995)

To the Editor.  —The statement by the AMA Council on Ethical and Judicial Affairs 1 endorsing the qualified use of anencephalic neonates highlights the continuing dilemma of the national organ shortage. Other articles, such as those on mandated choice, 2 also address this crisis. However, the solutions set forth would provide minimal, if any, impact on the number of organs available for transplant.  Using anencephalic neonates for organ donors represents an ethically stimulating debate, but not a practical solution to the organ crisis. Whether or not surgeons use anencephalic infants as organ donors would only minimally impact the total number of pediatric donors available. For instance, the Medical Task Force on Anencephaly estimated that each year fewer than 100 infants in the United States would qualify as organ donors. 3 According to another estimate, fewer than 10 patients each year would benefit from the use of anencephalic infants as donors.
LATE EFFECTS IN Hodgkin's POPULATION Treated BETWEEN 1980-2005 IN A SINGLE INSTITUTION.
Authors: Guido Gini, Patrizia Caraffa, Massimo Offidani, Silvia Trappolini, Caterina Bocci, Andrea Stronati, Laura Corvatta, Claudia Polloni, Silvia Gentili, Agnese Savini, Mauro Montanari, Debora Capelli, Antonella Poloni, Attilio Olivieri, Pietro Leoni
Journal: Blood (2009)