tbuckley/cabot-search huggingface dataset:
Second cancer risk 40 years after cure for Hodgkin lymphoma.
Authors: Michael Schaapveld, Berthe M Aleman, Anja M Eggermond, Cecile P Janus, Augustinus Krol, RWM Van Der Maazen, John M. M. Raemaekers, J. P. De Boer, Jose M Zijlstra, Gustaaf Willem Van Imhoff, Max L Beijert, Philip M. Poortmans, Marnix L. Lybeert, Ina Mulder, Otto Visser, Marieke J. Louwman, Cherita Sombroek, Pieternella Lugtenburg, Flora E. van Leeuwen
Journal: Journal of Clinical Oncology (2012)

8039 Background: During the last decades Hodgkin Lymphoma (HL) treatment changed towards less toxic chemotherapy schemes and smaller radiation fields. The impact of these changes on second cancer (SC) risk is still unknown. Methods: We calculated standardized incidence ratios (SIR), comparing SC risk after HL treatment with expected risk, based on cancer incidence in the general population, and compared SC risk between treatment modalities, accounting for competing events, in a large Dutch cohort comprising 3,390 5-years HL survivors, aged 15-51 years at HL treatment and diagnosed between 1965-2000. Results: The median follow-up was 18.2 years; 23% of the patients was followed ≥25 years. During follow-up 734 SCs and 92 third cancers (TC) occurred. The SIR for any SC was 4.5 (95% confidence interval (95%CI) 4.1-4.9). SC risk was still elevated after 35 years of follow-up (SIR 3.9; 95%CI 2.5-5.8) and cumulative incidence (CI) reached 47.1% (95%CI 43.6-50.5) at 40 years follow-up. For TCs the SIR was 5.5 (95%CI 4.4-6.9); the 20-year CI was 22.3% (95%CI 17.8-27.2). Risks of NHL and leukemia strongly decreased in more recent treatment periods (P-trend &lt;0.001). The CI of solid tumors (ST) between 5-19 years after HL treatment did not differ for patients treated between 1965-1979, 1980-1989 or 1990-2000 (P=0.21; 19-year CI 9.1%, 11.6% and 11.4%, respectively). Radiotherapy (RT) above the diaphragm increased risk of STs above the diaphragm (hazard ratio (HR) 2.4, P&lt;0.001), while subdiaphragmatic RT was associated with a 1.7-fold increased HR of a subdiaphragmatic ST (P=0.001). An incomplete mantle field was associated with significantly lower breast cancer (BC) risk (hazard ratio (HR) 0.4, 95%CI 0.2-0.8). A cumulative procarbazine dose &gt;4.2 g/m 2 yielded a 1.3-fold increased HR (95%CI 1.0-1.7) for non-breast STs and a 2-fold (95%CI 1.2-3.1) increased HR for gastrointestinal STs, but was associated with a strongly decreased BC risk (HR 0.3, 95%CI 0.2-0.6). Conclusions: SC risk after HL has decreased with treatment changes over the last decades, due to strongly decreasing risk of leukemia and NHL. Smaller radiation fields and procarbazine doses &gt;4.2 g/m 2 are associated with lower breast cancer risk, while high procarbazine doses increase risk of gastrointestinal STs.
Incidence of neonatal abstinence syndrome triples in US
Authors: Michael McCarthy
Journal: BMJ (2016)

The incidence of neonatal abstinence syndrome, primarily because of in utero exposure to opioids, increased by almost 300% from 1999 to 2013, rising from 1.5 to 6.0 cases per 1000 hospital births, researchers from the US Centers for Disease Control and Prevention (CDC) have found.1

The …
KRAS mutations as potential mechanism of crizotinib acquired resistance: a study on circulating tumor DNA.
Authors: Marzia Del Re, Paola Bordi, Valentina Citi, Stefania Crucitta, Eleonora Rofi, Iacopo Petrini, Marcello Tiseo, Romano Danesi
Journal: Journal of Clinical Oncology (2016)

e20526 Background: Crizotinib is an effective treatment for patients with ALK rearranged NSCLC but, unfortunately, patients progress with a median of 9-10 months. Resistance could be acquired through ALK point mutations, amplification or activation of alternative pathways i.e. KIT, EGFR and KRAS [1]. Second-generation TKIs demonstrated an enhanced activity in crizotinib-resistant patients that retain ALK addiction. However, rebiopsy represents a critical issue in lung cancer and analysis of circulating tumor DNA (cftDNA) has a promising role for the identification of resistance to treatment. Methods: Sixteen NSCLC patients with ALK rearrangement were enrolled after progression to ALK-TKI. Blood was collected at several time points during and after TKI treatment. CftDNA was extracted from plasma using QIAamp circulating nucleic acid kit (Qiagen) and ALK and KRAS codon 12 mutations were tested using the Digital Droplet PCR (ddPCR - BioRad). Results: All patients were stage IV adenocarcinoma; 15 patients received crizotinib and 1 ceritinib. ALK-TKIs were administered mainly as second-line, in 2 cases as first and in the remaining as third-line therapy. The best responses to treatment were 12 partial responses (PRs), 3 stable diseases (SDs) and 1 progressive disease (PD). The median PFS was 8 months. ALK point mutations alone were identified in 2 patients; one showed both p.L1196M and p.G1269A mutations. Six patients were carriers of a KRAS mutation at crizotinib PD, 2 of them presented both ALK and KRAS mutations. CftDNA was monitored during second generation ALK-TKI therapy and the amount of both ALK or KRAS mutations decreased along with tumor response. Interestingly, one additional extra-patient analysed before treatment with crizotinib was carrying the ALK p.F1174L mutation and showed primary refractoriness. Conclusions: KRAS and ALK mutations induce acquired resistance to TKIs targeting ALK rearrangement. The detection of KRAS mutation in circulating tumor DNA could represent a predictive marker of acquired resistance. Moreover, the quantification of mutant alleleS burden could be useful to monitor treatment response. 1. Katayama R, et al. Sci Transl Med. 2012 Feb;4(120):120ra17
Tracking the MDS Clone in Peripheral Blood (PB) Cells from Patients (pts) with Myelodysplastic Syndrome (MDS) Undergoing Azacitidine (AZAC)-Based Therapy.
Authors: Amanda Cozza, Lewis Silverman, Rosalie Odchimar-Reissig, Ilene Schulman, Svetlana Zinzar, Vesna Najfeld
Journal: Blood (2007)
Tissue-specific emergence of regulatory and intraepithelial T cells from a clonal T cell precursor
Authors: Angelina M. Bilate, Djenet Bousbaine, Luka Mesin, Marianna Agudelo, Justin Leube, Andreas Kratzert, Stephanie K. Dougan, Gabriel D. Victora, Hidde L. Ploegh
Journal: Science Immunology (2016)

Peripheral Foxp3+ regulatory T cells (pTregs) maintain immune homeostasis by controlling potentially harmful effector T cell responses toward dietary and microbial antigens. Although the identity of the T cell receptor (TCR) can impose commitment and functional specialization of T cells, less is known about how TCR identity governs pTreg development from conventional CD4+ T cells. To investigate the extent to which TCR identity dictates pTreg fate, we used somatic cell nuclear transfer to generate a transnuclear (TN) mouse carrying a monoclonal TCR from a pTreg (pTreg TN mice). We found that the pTreg TCR did not inevitably predispose T cells to become pTreg but instead allowed for differentiation of noninflammatory CD4+CD8αα+ intraepithelial lymphocytes (CD4IELs) in the small intestine. Only when we limited the number of T cell precursors that carried the TN pTreg TCR did we observe substantial pTreg development in the mesenteric lymph nodes and small intestine lamina propria of mixed bone marrow chimeras. Small clonal sizes and therefore decreased intraclonal competition were required for pTreg development. Despite bearing the same TCR, small intestine CD4IEL developed independently of precursor frequency. Both pTreg and CD4IEL development strictly depended on the resident microbiota. A single clonal CD4+ T cell precursor can thus give rise to two functionally distinct and anatomically segregated T cell subsets in a microbiota-dependent manner. Therefore, plasticity of the CD4 T cell compartment depends not only on the microbiota but also on specialized environmental cues provided by different tissues.
Hand eczema and steroid-refractory chronic hand eczema in general practice: prevalence and initial treatment
Authors: M.M. Crane, D.J. Webb, E. Watson, T. Cunliffe, J. English
Journal: British Journal of Dermatology (2016)

The self-reported annual prevalence of hand eczema (HE) in adults is about 10%. Incidence and prevalence data for HE, chronic HE (CHE) and steroid-refractory CHE (SR-CHE) in physician-attended populations are lacking.To estimate the prevalences of HE, CHE and SR-CHE in a primary-care population using a cross-sectional design; and to estimate the incidence of each and describe initial therapy using a cohort approach.The population was all patients in the Clinical Practice Research Datalink for 2000-10, 2005-10 and 2010-11. HE was defined as any of 12 diagnoses (six specific to the hand, six for contact dermatitis). HE became CHE if any of these 12, or three additional diagnoses, occurred 90-365 days after the first HE, and if the patient was prescribed at least one course of potent topical steroids. A patient with CHE was classified as having SR-CHE if they were (i) referred to a dermatologist and/or (ii) prescribed phototherapy, systemic immunomodulators, oral corticosteroids, alitretinoin or acitretin.The 1-year adult prevalence of HE was 0·4%. The period prevalences of SR-CHE for 1, 5 and 10 years in adults were 0·008%, 0·036% and 0·072%, respectively; lifetime estimates were 0·071%, 0·080%, 0·098%. About one-half of cases of CHE were steroid refractory. All conditions were more common in female than in male patients. One-third of HE diagnoses were specific for the hand, the remainder were for contact dermatitis. The majority (62%) of newly diagnosed patients with HE were not prescribed treatment in the 12 months after diagnosis.Although the prevalence of HE could be 2-3 times higher than reported herein, the proportion of adults seeking medical care for HE is a fraction of those who self-report HE. SR-CHE is rare.
Dietary Sodium and Blood Pressure
Authors: Graham A. MacGregor
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The meta-analysis by Midgley et al<sup>1</sup>shows a slightly smaller decrease in blood pressure than that in previous analyses, which probably is due to different selection criteria. The authors also try to suggest that salt restriction is harmful and, in particular, cite a study by Alderman and colleagues.<sup>2</sup>Clearly, they have not read the article in detail or the correspondence that followed.<sup>3</sup>In this study, salt intake was assessed only after all subjects had been carefully instructed on how to restrict their salt intake to stimulate the renin-angiotensin system so that a renin/sodium profile could be derived. It has been consistently pointed out that it is only possible to distinguish low, normal, and high renin subgroups if patients are on a low sodium intake. Moreover, it is inappropriate to use this 24-hour urinary sodium after 5 days of sodium restriction as a guide to the patient's subsequent
Randomized Controlled Study of Metformin and Sitagliptin on Long-term Normoglycemia Remission in African American Patients With Hyperglycemic Crises
Authors: Priyathama Vellanki, Dawn D. Smiley, Darko Stefanovski, Isabel Anzola, Wenlan Duan, Megan Hudson, Limin Peng, Francisco J. Pasquel, Guillermo E. Umpierrez
Journal: Diabetes Care (2016)

OBJECTIVE After intensive insulin treatment, many obese African American patients with new-onset diabetic ketoacidosis (DKA) and severe hyperglycemia are able to achieve near-normoglycemia remission. The optimal treatment to prevent hyperglycemic relapses after remission is not known. RESEARCH DESIGN AND METHODS This prospective, 4-year, placebo-controlled study randomly assigned 48 African American subjects with DKA and severe hyperglycemia to metformin 1,000 mg daily (n = 17), sitagliptin 100 mg daily (n = 16), or placebo (n = 15) after normoglycemia remission. Hyperglycemic relapse was defined as fasting glucose &amp;gt;130 mg/dL (7.2 mmol/L) and HbA1c &amp;gt;7.0% (53 mmol/mol). Oral glucose tolerance tests were conducted at randomization and at 3 months and then every 6 months for a median of 331 days. Oral minimal model and incremental area under the curve for insulin (AUCi) were used to calculate insulin sensitivity (Si) and β-cell function, respectively. Disposition index (DI) was calculated as a product of Si and incremental AUCi. RESULTS Relapse-free survival was higher in sitagliptin and metformin (P = 0.015) compared with placebo, and mean time to relapse was significantly prolonged in the metformin and sitagliptin groups compared with the placebo group (480 vs. 305 days, P = 0.004). The probability of relapse was significantly lower for metformin (hazard ratio 0.28 [95% CI 0.10–0.81]) and sitagliptin (0.31 [0.10–0.98]) than for placebo. Subjects who remained in remission had a higher DI (P = 0.02) and incremental AUCi (P &amp;lt; 0.001) than those with hyperglycemia relapse without significant changes in Si. CONCLUSIONS This study shows that near-normoglycemia remission was similarly prolonged by treatment with sitagliptin and metformin. The prolongation of remission was due to improvement in β-cell function.
The Effect of Health Coverage on Use of Cesarean Section-Reply
Authors: Jennifer S. Haas
Journal: JAMA (1993)

<h3>In Reply.</h3> —We agree with Dr Waszak that cesarean sections are frequently performed for fetal indications. Although our article reports on the effect of coverage for uninsured pregnant women on maternal health status and the use of cesarean section, we had previously reported that expanded health coverage was not associated with improved rates of low birth weight or prematurity.<sup>1</sup> We recognize that our data do not permit us to examine the appropriateness of the observed increase in cesarean sections. Nevertheless, our article adds to a growing body of literature that suggests that insurance status may be a determinant of cesarean section use independent of clinical circumstance.<sup>2-4</sup>Further study will be needed to examine prospectively the appropriateness of cesarean section use. Prior studies on the impact of expanded health coverage for low-income pregnant woman have focused solely on infant health outcomes. Our study was intended to be an initial
Measuring the Stigma Surrounding Type 2 Diabetes: Development and Validation of the Type 2 Diabetes Stigma Assessment Scale (DSAS-2)
Authors: Jessica L. Browne, Adriana D. Ventura, Kylie Mosely, Jane Speight
Journal: Diabetes Care (2016)

OBJECTIVE To develop and validate a self-report measure of perceived and experienced stigma for use with adults with type 2 diabetes: the Type 2 Diabetes Stigma Assessment Scale (DSAS-2). RESEARCH DESIGN AND METHODS An item pool was drafted based on qualitative data from 25 adults with type 2 diabetes and content from other health-related stigma questionnaires. Thirteen adults with type 2 diabetes completed 57 draft diabetes stigma items and participated in cognitive debriefing interviews. Based on participant feedback, the pool was reduced to 48 items with a 5-point Likert scale (strongly disagree to strongly agree). A total of 1,064 adults with type 2 diabetes completed a survey including these 48 items and other validated measures. Data were subject to principal components analysis and Spearman ρ correlations. RESULTS The scale was reduced to 19 items, with an unforced three-factor solution indicative of three subscales: Treated Differently (6 items, α = 0.88), Blame and Judgment (7 items, α = 0.90), and Self-stigma (6 items, α = 0.90). A forced one-factor solution supported the calculation of a total score (α = 0.95). Satisfactory concurrent, convergent, and discriminant validity were demonstrated. CONCLUSIONS The 19-item DSAS-2 is a reliable and valid measure of type 2 diabetes stigma. A rigorous design and validation process has resulted in a relatively brief measure of perceived and experienced stigma in type 2 diabetes. The novel scale has satisfactory psychometric properties and is now available to facilitate much-needed research in this field.
Anti-acid treatment in patients with IPF: interpret results from post-hoc, subgroup, and exploratory analyses with great caution – Authors' reply
Authors: Michael Kreuter, Wim Wuyts, Elisabetta Renzoni, Dirk Koschel, Toby M Maher, Martin Kolb, Derek Weycker, Paolo Spagnolo, Klaus-Uwe Kirchgaessler, Felix J F Herth, Ulrich Costabel
Journal: The Lancet Respiratory Medicine (2016)
Redox Imaging Using Cardiac Myocyte-Specific Transgenic Biosensor Mice
Authors: Lija Swain, Andrea Kesemeyer, Stefanie Meyer-Roxlau, Christiane Vettel, Anke Zieseniss, Annemarie Güntsch, Aline Jatho, Andreas Becker, Maithily S. Nanadikar, Bruce Morgan, Sven Dennerlein, Ajay M. Shah, Ali El-Armouche, Viacheslav O. Nikolaev, Dörthe M. Katschinski
Journal: Circulation Research (2016)

Changes in redox potentials of cardiac myocytes are linked to several cardiovascular diseases. Redox alterations are currently mostly described qualitatively using chemical sensors, which however do not allow quantifying redox potentials, lack specificity, and the possibility to analyze subcellular domains. Recent advances to quantitatively describe defined redox changes include the application of genetically encoded redox biosensors.Establishment of mouse models, which allow the quantification of the glutathione redox potential (EGSH) in the cytoplasm and the mitochondrial matrix of isolated cardiac myocytes and in Langendorff-perfused hearts based on the use of the redox-sensitive green fluorescent protein 2, coupled to the glutaredoxin 1 (Grx1-roGFP2).We generated transgenic mice with cardiac myocyte-restricted expression of Grx1-roGFP2 targeted either to the mitochondrial matrix or to the cytoplasm. The response of the roGFP2 toward H2O2, diamide, and dithiothreitol was titrated and used to determine the EGSH in isolated cardiac myocytes and in Langendorff-perfused hearts. Distinct EGSH were observed in the cytoplasm and the mitochondrial matrix. Stimulation of the cardiac myocytes with isoprenaline, angiotensin II, or exposure to hypoxia/reoxygenation additionally underscored that these compartments responded independently. A compartment-specific response was also observed 3 to 14 days after myocardial infarction.We introduce redox biosensor mice as a new tool, which allows quantification of defined alterations of EGSH in the cytoplasm and the mitochondrial matrix in cardiac myocytes and can be exploited to answer questions in basic and translational cardiovascular research.
Brief Report: Peripheral Osteolysis in Adults Linked to <i>ASAH1</i> (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease
Authors: Luisa Bonafé, Ariana Kariminejad, Jia Li, Beryl Royer‐Bertrand, Virginie Garcia, Shokouholsadat Mahdavi, Bita Bozorgmehr, Ralph L. Lachman, Lauréane Mittaz‐Crettol, Belinda Campos‐Xavier, Sheela Nampoothiri, Sheila Unger, Carlo Rivolta, Thierry Levade, Andrea Superti‐Furga
Journal: Arthritis & Rheumatology (2016)

Objective To establish a diagnosis and provide counseling and treatment for 3 adult patients from one family presenting with peripheral osteolysis. Methods Following clinical and radiographic assessment, exome sequencing, targeted gene resequencing, and determination of enzyme activity in cultured fibroblasts were performed. Results The proband (age 40 years) had a history of episodic fever and pain in childhood that subsided around puberty. He and 2 of his older sisters (ages 58 and 60 years, respectively) showed adult‐onset progressive shortening of fingers and toes with redundancy of the overlying skin. Radiographs showed severe osteolysis of the distal radius and ulna, carpal bones, metacarpal bones, and phalanges. Sequencing of the known genes for recessively inherited osteolysis, MMP2 and MMP14 , failed to show pathogenic mutations. Exome sequencing revealed compound heterozygosity for mutations c.505T&gt;C (p.Trp169Arg) and c.760A&gt;G (p.Arg254Gly) in ASAH1 , the gene coding for acid ceramidase. Sanger sequencing confirmed correct segregation in the family, and enzyme activity in fibroblast cultures from the patients was reduced to ∼8% of that in controls, confirming a diagnosis of Farber's disease. Conclusion Our findings indicate that hypomorphic mutations in ASAH1 may result in an osteoarticular phenotype with a juvenile phase resembling rheumatoid arthritis that evolves to osteolysis as the final stage in the absence of neurologic signs. This observation delineates a novel type of recessively inherited peripheral osteolysis and illustrates the long‐term skeletal manifestations of acid ceramidase deficiency (Farber's disease) in what appear to be the oldest affected individuals known so far.
Food: a new form of personalised (gut microbiome) medicine for chronic diseases?
Authors: Tess Pallister, Tim D Spector
Journal: Journal of the Royal Society of Medicine (2016)

Filling in the knowledge gaps between what we eat and the diseases we develop may lie in our guts, literally. The human large intestine houses the largest reservoir of microorganisms in or on the human body. With a 100-fold greater gene count than humans, the gut microbiome has huge potential to place a large metabolic burden (or advantage) on its host. The number of diverse gut microbial species is diminished in nearly all modern chronic conditions studied. The 'Western diet', rich in animal protein, fats and artificial additives, and lacking in fibre, beneficial microbes, plant phytochemicals, vitamins and minerals, is thought to drive these conditions by encouraging gut dysbiosis. Evidence from recent dietary intervention studies suggest adopting a plant-based, minimally processed high-fibre diet may rapidly reverse the effects of meat-based diets on the gut microbiome. However, recent work has shown that individual diet responses may be complicated by host genetics and the wide variation in the gut microbiome. Now that we measure genes and microbes more accurately, we are embarking on an exciting era of using both food and microbes as potential therapies.
<i>ESR1</i>Mutations in Cell-Free DNA of Breast Cancer
Authors: Suzanne A. W. Fuqua, Yassine Rechoum, Guowei Gu
Journal: JAMA Oncology (2016)

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Circulating Tumor Cells in a Phase 3 Study of Docetaxel and Prednisone with or without Lenalidomide in Metastatic Castration-resistant Prostate Cancer
Authors: Nicholas J. Vogelzang, Karim Fizazi, John M. Burke, Ronald De Wit, Joaquim Bellmunt, Thomas E. Hutson, Edward Crane, William R. Berry, Kevin Doner, John D. Hainsworth, Pawel J. Wiechno, Kejian Liu, Michelle F. Waldman, Anita Gandhi, Debora Barton, Ulf Jungnelius, Abderrahim Fandi, Cora N. Sternberg, Daniel P. Petrylak
Journal: European Urology (2016)