tbuckley/cabot-search huggingface dataset:
Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial
Authors: Mark C Steinhoff, Joanne Katz, Janet A Englund, Subarna K Khatry, Laxman Shrestha, Jane Kuypers, Laveta Stewart, Luke C Mullany, Helen Y Chu, Steven C LeClerq, Naoko Kozuki, Monica McNeal, Adriana M Reedy, James M Tielsch
Journal: The Lancet Infectious Diseases (2017)
A homozygous missense mutation in <i>SLC25A16</i> associated with autosomal recessive isolated fingernail dysplasia in a Pakistani family
Authors: S. Khan, M. Ansar, A. K. Khan, K. Shah, N. Muhammad, S. Shahzad, D.A. Nickerson, M.J. Bamshad, R.L.P. Santos-Cortez, S.M. Leal, W. Ahmad
Journal: British Journal of Dermatology (2017)

Developmental nail disorders are heterogeneous group of genodermatosis, with nonsyndromic congenital nail disorder (NDNC) being a rare subgroup inherited in autosomal dominant or autosomal recessive pattern. These are classified into ten different types (NDNC1-10), which are described in OMIM.1 The genes described for isolated nail disorders include PLCD1 (MIM 602142), RSPO4 (MIM 610573), FZD6 (MIM 603409), COL7A1 (MIM 120120), HPGD (MIM 601688) and SLCO2A1 (MIM 601460). In Addition, two other loci for NDNC have been mapped on chromosome 17p13 and 17q25.1-17q25.3.1, 2

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Chronic myeloid leukemia incidence trends among Caucasians in the United States.
Authors: Rakesh Mandal, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2012)

e17005 Background: Information on trend of Chronic Myeloid Leukemia (CML) incidence rate is scant. This study was conducted to evaluate the time trends of CML incidence rates among Caucasians in the U.S. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program to extract annual age-adjusted incidence rates of CML from 1973-2008 for &lt;60yr and &gt;60yr age groups classified by gender. Trends of incidence rates were evaluated using the National Cancer Institute’s Joinpoint Regression Program (v 3.5.2). The maximum number of joinpoints used was 4. The annual percentage change (APC %) for the final selected joinpoint model for each cohort is shown in the table. Results: The annual age-adjusted CML incidence rates for 1973 vs. 2008 were 0.72/0.67, 5.67/4.47, 0.93/0.67, and 10.5/8.5 per 100,000 population for the 4 cohorts: women (&lt;60yr, &gt;60yr) and men (&lt;60yr, &gt;60yr), respectively. Among Caucasian women (&gt;60yr), the incidence rate decreased significantly from 5.58/100,000 in 2001 to 4.47/100,000 in 2008 (APC= -3.08, CI -5.8 to -0.3, p = 0.004). The incidence trend from 1973-2001 was stable for this cohort (APC=0.1, CI -0.3 to 0.5). The incidence trends among women &lt;60yr, men &lt;60yr, and men &gt;60yr were stable from 1973-2008. Conclusions: The annual age-adjusted incidence rates of chronic myeloid leukemia among older (&gt;60 year) Caucasian women has declined sharply from 2001-2008. The rate change is unexplained. It may help generate hypotheses regarding risk factors for CML. [Table: see text]
Influence of Direct Oral Anticoagulants on Rates of Oral Anticoagulation for Atrial Fibrillation
Authors: Lucas N. Marzec, Jingyan Wang, Nilay D. Shah, Paul S. Chan, Henry H. Ting, Kensey L. Gosch, Jonathan C. Hsu, Thomas M. Maddox
Journal: Journal of the American College of Cardiology (2017)
Trajectories of Depressive Symptoms Before Diagnosis of Dementia
Authors: Archana Singh-Manoux, Aline Dugravot, Agnes Fournier, Jessica Abell, Klaus Ebmeier, Mika Kivimäki, Séverine Sabia
Journal: JAMA Psychiatry (2017)

Neuropsychiatric symptoms, depressive symptoms in particular, are common in patients with dementia but whether depressive symptoms in adulthood increases the risk for dementia remains the subject of debate.To characterize the trajectory of depressive symptoms over 28 years prior to dementia diagnosis to determine whether depressive symptoms carry risk for dementia.Up to 10 308 persons, aged 35 to 55 years, were recruited to the Whitehall II cohort study in 1985, with the end of follow-up in 2015. Data analysis for this study in a UK general community was conducted from October to December 2016.Depressive symptoms assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire.Incidence of dementia (n = 322) between 1985 and 2015.Of the 10 189 persons included in the study, 6838 were men (67%) and 3351 were women (33%). Those reporting depressive symptoms in 1985 (mean follow-up, 27 years) did not have significantly increased risk for dementia (hazard ratio [HR], 1.21; 95% CI, 0.95-1.54) in Cox regression adjusted for sociodemographic covariates, health behaviors, and chronic conditions. However, those with depressive symptoms in 2003 (mean follow-up, 11 years) had an increased risk (HR, 1.72; 95% CI, 1.21-2.44). Those with chronic/recurring depressive symptoms (≥2 of 3 occasions) in the early study phase (mean follow-up, 22 years) did not have excess risk (HR, 1.02; 95% CI, 0.72-1.44) but those with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did have higher risk for dementia (HR, 1.67; 95% CI, 1.11-2.49). Analysis of retrospective depressive trajectories over 28 years, using mixed models and a backward time scale, shows that in those with dementia, differences in depressive symptoms compared with those without dementia became apparent 11 years (difference, 0.61; 95% CI, 0.09-1.13; P = .02) before dementia diagnosis and became more than 9 times larger at the year of diagnosis (difference, 5.81; 95% CI, 4.81-6.81; P < .001).Depressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase the risk for dementia. Along with our analysis of depressive trajectories over 28 years, these results suggest that depressive symptoms are a prodromal feature of dementia or that the 2 share common causes. The findings do not support the hypothesis that depressive symptoms increase the risk for dementia.
2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy
Authors: Bernard J. Gersh, Barry J. Maron, Robert O. Bonow, Joseph A. Dearani, Michael A. Fifer, Mark S. Link, Srihari S. Naidu, Rick A. Nishimura, Steve R. Ommen, Harry Rakowski, Christine E. Seidman, Jeffrey A. Towbin, James E. Udelson, Clyde W. Yancy
Journal: Circulation (2011)
Disseminated Erythematous Crusted and Pustular Plaques on the Trunk
Authors: Enrique Rodríguez-Lomba, Pedro Vilas-Boas, Ricardo Suárez-Fernández
Journal: JAMA Dermatology (2017)

A woman with a history of several outbreaks of skin lesions limited to both axillae and groin presented with multiple annular erythematous plaques surrounded by a peripheral crusted and pustular collarette on her trunk. What is your diagnosis?
Intraductal papillary neoplasm of the bile duct: A rare liver tumor complicated by malignancy
Authors: Kentaro Tominaga, Kenya Kamimura, Akira Sakamaki, Shuji Terai
Journal: Hepatology (2017)

1Division of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata University, 1‐757, Aasahimachi‐DoriChuo‐KuNiigataJapan *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:Kenya Kamimura, M.D., Ph.D.Division of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata University1‐757 Asahimachi–doriChuo–ku, Niigata, Niigata, 9518510, JapanE‐mail: [email protected]Tel: +81‐(25)‐227‐2207 †These authors contributed equally to this work.
Using food insecurity in health prevention to promote consumer's embodied self-regulation
Authors: Olivia Petit, Charles Spence
Journal: Behavioral and Brain Sciences (2017)

Abstract Health messages designed to address obesity are typically focused on the long-term benefits of eating healthy food. However, according to the insurance hypothesis, obese people are food insecure, and this causes them to be overly concerned about short-term consumption. As such, it is necessary to rethink public health messaging and consider how to reduce short-term insecurity by eating healthy food.
High-throughput RNAi phenotypic screening for the identification of genes that modulate estrogen activity in human breast cancer cells
Authors: Angela Rojas, Irma Monzon, Gargi Basu, Spyro Mousses, David Azorsa
Journal: Cancer Research (2007)

996  Breast cancer is the second leading cause of cancer related death among women in the United States. Of the diagnosed cases of breast cancer, the majority are estrogen receptor (ER) positive making the estrogen receptor a major target in breast cancer therapy. Although anti-estrogen therapy has proven successful in treating ER-positive breast cancer patients, acquired resistance of the tumor is known to occur. In order to develop a more effective anti-estrogen therapy, our goal is to identify genes involved in modulation of the response to estrogen signaling in breast cancer cells using an innovative functional genomics approach based on high-throughput RNA interference (HT-RNAi) analysis. Assays for HT-RNAi were developed to monitor estrogen dependent signaling utilizing the T47D-KBluc breast cancer cell line, which expresses luciferase under the control of the estrogen response element (ERE). This cell line was adapted for HT-RNAi by optimizing siRNA transfection conditions in a 384-well format. Dose response curves were generated in assay format to determine the EC50 for estrogen activity. The HT-RNAi assay involved the transfection of T47-KBluc cells with siRNA targeting 588 kinases and twenty-four hours later, treating the cells with an EC50 dose of estrogen. The assay readouts consisted of parallel measurements of both ERE reporter activity and proliferation. Genes that modulate the response to estrogen are further validated using functional assays examining the gene9s role in estrogen response. Furthermore, an assay for identifying modulators of the anti-estrogen activity of tamoxifen was developed utilizing the MCF-7 breast cancer cell line. This HT-RNAi assay measureed growth inhibition of MCF-7 cells transfected with siRNA targeting 588 kinases and treated with tamoxifen or vehicle. Modulators of tamoxifen response were also further validated. These approaches will rapidly and efficiently identify important genes involved in estrogen dependent growth of breast cancer cells including the identification of new drug targets.
Validation of prediction of distant recurrence (DR) by Prosigna (PAM50) in subgroups of a Danish Breast Cancer Cooperative Group (DBCG) cohort of node-positive (N1), hormone receptor positive (HR+), postmenopausal early breast cancer (EBC) patients allocated 5yr of endocrine therapy (ET).
Authors: Bent Ejlertsen, Maj-Britt Jensen, Jens Ole Eriksen, Torben Kibøll, Birgitte Bruun Rasmussen, Ann S. Knoop, Sean Ferree, Taryn Haffner, Carl Schaper, Anne-Vibeke Lænkholm
Journal: Journal of Clinical Oncology (2015)

513 Background: N1, HR+ EBC patients are routinely treated with both ET and chemotherapy (CT). Identification of N1 patients with good outcome who may be spared CT remains an elusive goal. In a combined analysis of 2 randomized trials, Prosigna (PAM50) risk of recurrence (ROR) score identified low risk N1 patients with outcome equivalent to N0 disease. We examined the ability of ROR to predict 10yr DR for patients with 1, 2 or 3+ nodes in a comprehensive nationwide cohort from Denmark to identify N1 women who may be spared overtreatment with CT. Methods: Using the population based DBCG database primary FFPE tumor blocks and follow-up data were collected from all Danish women diagnosed from 2000-2003 with HR+, postmenopausal, N1 EBC treated with ET alone (N = 1,480). PAM50 on the NanoString nCounter Analysis System categorized patients as Low, Intermediate, or High risk using pre-specified cutoffs varied by number of positive nodes. Multivariate analyses were performed to assess the ability of PAM50 to predict DR in patients with 1, 2, or 3+ nodes. Results: 1,466 (99%) passed PAM50 QC. Median follow-up was 9.25 years. Risk of 10yr DR based on the number of positive nodes and PAM50 is shown in the Table. Including ROR in a Fine and Gray’s multivariate proportional sub-hazards model improved outcome prediction for patients with 1, 2, and 3+ nodes (P < 0.0001, 0.0001, 0.008 respectively). Conclusions: Prosigna (PAM50) improves outcome prediction in N1 patients over standard variables. PAM50 can identify at least 37% of patients with 1 and 15% with 2 positive nodes who have an excellent prognosis and may be spared adjuvant CT in a real world setting. Nodes (N) DR risk by Risk Group % [95%CI] DR risk by Subtype % [95%CI] Low (N) Intermediate (N) High (N) Luminal A (N) Luminal B (N) 1+ Node (809) 3.6 [1.7-6.5] (298) 15 [10-21] (237) 21 [16-27] (274) 8.5 [5.9-12] (509) 18 [13-24] (248) 2+ Nodes (426) 4.6 [1.2-11] (65) 8.7 [4.4-15] (137) 21 [15-27] (224) 8.8 [5.4-13] (250) 20 [14-27] (142) 3+ Nodes (231) - 0 [NA] (26) 26 [20-33] (205) 9.4 [4.7-16] (124) 39 [26-51] (85)
Active Systemic Treatment of Pancreatic Cancer
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2017)

By 2020, pancreatic cancer is expected to be the second most common cause of cancer-related death, exceeded only by lung cancer. During her presentation at the NCCN 22nd Annual Conference, Dr. Margaret Tempero offered an update on the current state of systemic treatment of pancreatic cancer, focusing on resectable/borderline resectable, locally advanced, and metastatic disease.
Vitamin-D-Dependent Rickets Type II
Authors: Marion H. Brooks, Norman H. Bell, Leon Love, Paula H. Stern, Emilio Orfei, Sherry F. Queener, Alan J. Hamstra, Hector F. DeLuca
Journal: New England Journal of Medicine (1978)

Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman. The patient had normal serum 25-hydroxyvitamin D (14 ng per milliliter) and markedly elevated serum 1,25-dihydroxyvitamin D (137 pg per milliliter). Vitamin D3, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism. The results suggest that the disorder results from impaired end-organ response to 1,25-dihydroxyvitamin D. We propose that the entity be called vitamin-D-dependent rickets Type II.
Fixed second appointment improves breast screening attendance
Authors: Jacqui Wise
Journal: BMJ (2017)

Women who miss a breast screening appointment should be given a second appointment with a fixed date and time, researchers recommend in Lancet Oncology .1 Their study found that this approach was significantly more effective at improving poor attendance than supplying “open” invitations asking women to make an appointment by telephone.

In England, participation in breast cancer screening has decreased in the past 10 years, nearing the national minimum standard of 70%. Screening is particularly low in areas of social deprivation.

The …
May’s “tinkering” with social care funding fails to deliver “sustainable solution,” say experts
Authors: Matthew Limb
Journal: BMJ (2017)

The prime minister has signalled changes to social care funding while abandoning previous Tory commitments to cap the amount that people would have to pay themselves for care and scaling back some benefits for pensioners.

Launching the Conservatives’ general election manifesto in Halifax on 18 May (www.conservatives.com/manifesto), Theresa May said it was right that people should contribute to their care from savings and accumulated wealth if they could afford it, rather than expecting taxpayers to carry the cost on their behalf.

For the first time, homeowners’ property wealth would come under local councils’ means tests to gauge people’s entitlement to state funded support for social care in their own home.

Analysts said that under the proposal many more people would be likely to have to pay for services and that people with the greatest care needs would still be unable to limit potentially huge social care costs.

Currently, people can qualify …
PWE-059 Prevalence of gastro-esophageal reflux disease in individuals with irritable bowel syndrome: a systematic review and meta-analysis: Abstract PWE-059 Table 1
Authors: R M Lovell, A C Ford
Journal: Gut (2012)

<h3>Introduction</h3> Irritable bowel syndrome (IBS) and gastro-esophageal reflux disease (GERD) are common disorders in the general population, and there is thought to be a degree of overlap between the two. However, the strength of this association has not been examined systematically. We performed a systematic review and meta-analysis to estimate the prevalence of GERD in individuals with IBS. <h3>Methods</h3> MEDLINE, EMBASE, and EMBASE Classic were searched through October 2011 for cross-sectional surveys reporting the prevalence of IBS. A recursive search of the bibliographies of identified articles was also conducted. There were no language restrictions. Eligible studies were population-based, recruited ≥50 adult (≥15 years) subjects, and were required to define IBS via the Manning or Rome criteria, or according to a questionnaire. Eligibility assessment and data extraction were conducted independently in a double-blind fashion by two investigators, with any discrepancies resolved by consensus. Data were extracted and pooled, with a random effects model, to estimate prevalence of IBS in the population under study. The prevalence of GERD in individuals with and without IBS was compared using an OR, with a 95% CI. <h3>Results</h3> The search yielded 20 146 results, of which 390 studies appeared relevant and were retrieved for further assessment. There were 80 separate population-based studies that reported the prevalence of IBS according to the various criteria defined above. Of these, 13 studies, containing 49 939 participants, also reported the proportion of people who met criteria for GERD within the same population. The pooled prevalence of IBS in these 13 studies was 11.6% (95% CI 7.1% to 17.1%). The odds of GERD in individuals with IBS, compared with those without, was 4.17 (95% CI 2.85 to 6.09). Odds of GERD in individuals with IBS varied according to the criteria used to define IBS (see Abstract PWE-059 table 1). <h3>Conclusion</h3> The prevalence of GERD in individuals with IBS was fourfold that in those without. The degree of overlap varied according to the criteria used to define IBS, but remained significant in all cases. The strength of this association suggests common pathogenetic mechanisms. <h3>Competing interests</h3> None declared.
Proteomic analysis of JAK2V617F-induced changes identifies potential new combinatorial therapeutic approaches
Authors: S Pearson, A J K Williamson, R Blance, T C P Somervaille, S Taylor, N Azadbakht, A D Whetton, A Pierce
Journal: Leukemia (2017)

Abstract In excess of 90% of patients with polycythaemia vera (PV) express a mutated form of Janus kinase 2 (JAK2), JAK2V617F. Such aberrant proteins offer great potential for the treatment of these diseases; however, inhibitors to JAK2 have had limited success in the clinic in terms of curing the disease. To understand the effects of this oncogene in haematopoietic cells with the aim of improving treatment strategies, we undertook a systematic evaluation of the effects of JAK2V617F expression using proteomics. The effects of JAK2V617F on over 5000 proteins and 2000 nuclear phosphopeptide sites were relatively quantified using either SILAC or eight-channel iTRAQ mass spectrometry. Pathway analysis of the proteins identified as changing indicated disruption to the p53 and MYC signalling pathways. These changes were confirmed using orthogonal approaches. The insight gained from this proteomic analysis led to the formation of hypothesis-driven analysis on inhibitor-mediated effects on primary cells from patients with a JAK2V617F mutation. Simultaneous inhibition of MYC and upregulation of p53 led to the preferential extinction of JAK2V617F-positive CD34+ cells, illustrating a potential therapeutic benefit from combined targeting of p53 and MYC.
DUSP22 and TP63 rearrangements predict outcome of ALK-negative anaplastic large cell lymphoma: a Danish cohort study
Authors: Martin Bjerregård Pedersen, Stephen Jacques Hamilton-Dutoit, Knud Bendix, Rhett P. Ketterling, Patrick P. Bedroske, Ivy M. Luoma, Christopher A. Sattler, Rebecca L. Boddicker, N. Nora Bennani, Peter Nørgaard, Michael Boe Møller, Torben Steiniche, Francesco d’Amore, Andrew L. Feldman
Journal: Blood (2017)
CHEMICAL STUDIES IN HOST-VIRUS INTERACTIONS
Authors: Seymour S. Cohen, Rachel Arbogast
Journal: The Journal of Experimental Medicine (1950)

A method has been described for following purine and pyrimidine synthesis in intact cells by measuring the ultraviolet absorption of a bacterial suspension. It has been shown that in cells infected with active virus, the rate of increase of ultraviolet absorption at 2600 A corresponded to that of DNA, although preceding DNA synthesis slightly. The amount of separation of the curves in time was determined by the multiplicity of infection. Under conditions of mutual reactivation of ultraviolet-irradiated virus, DNA synthesis was inhibited but not the increase in ultraviolet absorption. Thus a continuing purine and pyrimidine synthesis was indicated by the increase in this function. When an intact virus particle could be found within these bacteria, however, DNA synthesis began at the rate characteristic of normal infections. Certain peculiarities of lysis in this system were noted. The significance of these observations for various genetic theories has been discussed. It would appear that Luria's hypothesis of independent gene pool synthesis has probably been disproven. It has also been shown that the lesion produced by irradiation of a virus particle with ultraviolet light probably occurs in the DNA of the particle. The validity of these conclusions will depend on a knowledge of the relation of virus protein synthesis to DNA synthesis in this system.
Microcarriers with Synthetic Hydrogel Surfaces for Stem Cell Expansion
Authors: Andrew D. Dias, Jonathan M. Elicson, William L. Murphy
Journal: Advanced Healthcare Materials (2017)

Microcarriers are scalable support surfaces for cell growth that enable high levels of expansion, and are particularly relevant for expansion of human mesenchymal stem cells (hMSCs). The goal of this study is to develop a poly(ethylene glycol) (PEG)‐based microcarrier coating for hMSC expansion. Commercially available microcarriers do not offer customizability of microcarrier surface properties, including elastic modulus and surface cell adhesion ligands. The lab has previously demonstrated that tuning these material properties on PEG‐based hydrogels can modulate important cellular growth characteristics, such as cell attachment and expansion, which are important in microcarrier‐based culture. Eosin‐Y is adsorbed to polystyrene microcarriers and used as a photoinitiator for thiol‐ene polymerization under visible light. Resultant PEG coatings are over 100 µm thick and localized to microcarrier surfaces. This thickness is relevant for cells to react to mechanical properties of the hydrogel coating, and coated microcarriers support hMSC attachment and expansion. hMSC expansion is highly favorable on coated microcarriers in serum‐free media, with doubling times under 25 h in the growth phase, and retained osteogenic and adipogenic differentiation capacity after culture on microcarriers. These microcarriers with defined, synthetic coatings enable tailorable surfaces for cell expansion that may be suitable for a variety of biomanufacturing applications.