tbuckley/cabot-search huggingface dataset:
Tick-borne encephalitis in north-east Italy: a 14-year retrospective study, January 2000 to December 2013
Authors: Giovanni Rezza, Francesca Farchi, Patrizio Pezzotti, Maurizio Ruscio, Alessandra Lo Presti, Massimo Ciccozzi, Valeria Mondardini, Claudio Paternoster, Matteo Bassetti, Maria Merelli, Pier Giorgio Scotton, Roberto Luzzati, Josef Simeoni, Peter Mian, Rosanna Mel, Valter Carraro, Alessandra Zanin, Roberto Ferretto, Ermenegildo Francavilla
Journal: Eurosurveillance (2015)

Italy is considered at low incidence of tick-borne encephalitis (TBE), and the occurrence of human cases of TBE appears to be geographically restricted to the north east of the country. However, most information to date derives from case series, with no systematic data collection. To estimate incidence rates (IR) and spatial distribution of TBE cases, we conducted a retrospective study in north-eastern Italy. Data were collected through the infectious disease units and public health districts of three regions (Friuli Venezia Giulia, Trentino Alto Adige and Veneto) between 2000 and 2013. Overall, 367 cases were identified (IR: 0.38/100,000). The cases’ median age was 56 years and 257 (70%) were male. Central nervous system involvement was reported in 307 cases (84%). Annual fluctuations in case numbers occurred, with peaks in 2006 and in 2013, when 44 and 42 cases were respectively observed. A strong seasonality effect was noted, with the highest number of cases in July. In terms of geographical location, three main endemic foci with high TBE IR (&gt; 10/100,000) were identified in three provinces, namely Belluno (Veneto region), Udine (Friuli Venezia Giulia) and Trento (Trentino Alto-Adige). When investigating the whole study area in terms of altitude, the IR between 400 and 600 m was greater (2.41/100,000) than at other altitudes (p&lt; 0.01). In conclusion, the incidence of TBE in Italy is relatively low, even considering only the three known affected regions. However, three endemic foci at high risk were identified. In these areas, where the risk of TBEV infection is likely high, more active offer of TBE vaccination could be considered.
Abstract 4626: Genetic susceptibility to diffuse large B-cell lymphoma in a pooled study of three Eastern Asian populations
Authors: Nathaniel Rothman, Bryan A. Bassig, James R. Cerhan, Wing-Yan Au, Hee Nam Kim, Suleeporn Sangrajrang, Wei Hu, Jovic Tse, Sonja Berndt, Tongzhang Zheng, Heping Zhang, Pattarapong Pornsopone, Je-Jung Lee, Hyeoung-Joon Kim, Christine F. Skibola, Joseph Vijai, Laurie Burdette, Meredith Yeager, Paul Brennan, Min-Ho Shin, Raymond Liang, Stephen Chanock, Qing Lan
Journal: Cancer Research (2015)

Abstract Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide. Some epidemiologic data have indicated differences in DLBCL incidence rates and subtype distributions between Eastern Asian and Western countries. The first large-scale genome-wide association study (GWAS) of DLBCL with over 4000 cases conducted among individuals of European ancestry recently identified five independent SNPs that achieved genome-wide significance, and two SNPs that showed a suggestive association with DLBCL risk. In order to evaluate whether Eastern Asians and individuals of European ancestry share similar genetic risk factors for this disease, we attempted to replicate these GWAS findings in a pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea, and Thailand. Three of the five genome-wide significant SNPs from the DLBCL GWAS were significantly associated with DLBCL in our study population, including the top finding from the GWAS, EXOC2 rs116446171, which achieved genome-wide significance in our data (per allele OR = 2.04, 95% CI = 1.63-2.56; ptrend = 3.9 × 10-10). Additionally, we observed a significant association with PVT1 rs13255292 (per allele OR = 1.34, 95% CI = 1.19-1.52; ptrend = 2.1 × 10-6), which was the second strongest finding in the GWAS, and with HLA-B rs2523607 (per allele OR = 3.05, 95% CI = 1.32-7.05; ptrend = 0.009). Our study, which provides the first evaluation in Eastern Asians of SNPs definitively associated with DLBCL risk in individuals of European ancestry, indicates that at least some of the genetic factors associated with risk of DLBCL are similar between these populations. Citation Format: Nathaniel Rothman, Bryan A. Bassig, James R. Cerhan, Wing-Yan Au, Hee Nam Kim, Suleeporn Sangrajrang, Wei Hu, Jovic Tse, Sonja Berndt, Tongzhang Zheng, Heping Zhang, Pattarapong Pornsopone, Je-Jung Lee, Hyeoung-Joon Kim, Christine F. Skibola, Joseph Vijai, Laurie Burdette, Meredith Yeager, Paul Brennan, Min-Ho Shin, Raymond Liang, Stephen Chanock, Qing Lan. Genetic susceptibility to diffuse large B-cell lymphoma in a pooled study of three Eastern Asian populations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4626. doi:10.1158/1538-7445.AM2015-4626
Author response to Marrs<i>et al</i>., Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial: a critical appraisal
Authors: K. Anagnostou, A. Clark
Journal: British Journal of Dermatology (2015)

We would like to thank Marrs et al. for their critical appraisal of our paper in The Lancet.1 We appreciate the authors’ comments regarding the quality of the STOP II trial conduct and reporting, and share their view that this study represents an important addition to the existing published studies on peanut oral immunotherapy (OIT). In response to their appraisal, we would like to take this opportunity to present our comments. The stated aim of our study was to assess desensitization to peanut for up to 6 months, not long‐term tolerance. Previous studies have shown that tolerance attainment at this early time point is rare, but tolerance attainment is not necessarily the aim of treatment. Our study showed that desensitization resulted in an improvement in quality of life, due to improvement in emotional, social and anxiety scores. Long‐term protection from accidental ingestion, and relaxation of avoidance practice may be achieved by continued desensitization, which seems a reasonable aim for treatment given the shortcomings of the current standard of care. This approach is in agreement with the stated purpose of the trial,1 and therefore does not compromise internal validity.
Palestinian doctors are barred from entering UK
Authors: A. Gulland
Journal: BMJ (2015)

Palestinian campaigners in the United Kingdom are considering legal action after three doctors were refused entry to attend a conference.

The three doctors (and a nurse and a psychologist) were due to attend a conference on trauma and resilience at Kingston University, southwest London, on 14 and 15 November but had their visa applications turned down by the Home Office.

The three family doctors are employed by the Palestinian Ministry of Health and have been named as Hasnaa Al Sourani, head of the department of non-communicable diseases, Amal Shaat, and Rula Al Helo.

The doctors were due to give papers at the conference, which is focusing on trauma …
Exercise level before pregnancy and engaging in high-impact sports reduce the risk of pelvic girdle pain: a population-based cohort study of 39 184 women
Authors: Katrine Mari Owe, Elisabeth K Bjelland, Britt Stuge, Nicola Orsini, Malin Eberhard-Gran, Siri Vangen
Journal: British Journal of Sports Medicine (2015)

Objective To examine whether an association exists between exercise levels pre-pregnancy and pelvic girdle pain in pregnancy. Pelvic girdle pain in pregnancy has been associated with physical inactivity, a risk factor for adverse pregnancy outcomes. Methods We used data from a population-based cohort study including 39 184 nulliparous women with a singleton pregnancy enrolled in the Norwegian Mother and Child Cohort study. Pre-pregnancy exercise frequency and types were assessed by questionnaire in pregnancy week 17. Pelvic girdle pain, defined as combined pain in the anterior pelvis and in the posterior pelvis bilaterally, was self-reported in pregnancy week 30. Multivariable Poisson regression estimated risks of pelvic girdle pain associated with pre-pregnancy exercise. We examined a dose–response association of prepregnancy exercise frequency using restricted cubic splines. A test for non-linearity was also conducted. Final models were adjusted for pre-pregnancy BMI, age, education, history of low back pain and history of depression. Results 4069 women (10.4%) reported pelvic girdle pain in pregnancy and the prevalence among women who were non-exercisers prepregnancy was 12.5%. There was a non-linear association for pre-pregnancy exercise and risk of pelvic girdle pain (test for non-linearity, p=0.003). Compared to non-exercisers, women exercising 3–5 times weekly pre-pregnancy had a 14% lower risk of developing pelvic girdle pain in pregnancy (aRR 0.86, 95% CI 0.77 to 0.96). Taking part in high-impact exercises such as running, jogging, orienteering, ballgames, netball games and high-impact aerobics were associated with less risk of pelvic girdle pain. Summary Women who exercise regularly and engage in high-impact exercises before the first pregnancy may have a reduced risk of pelvic girdle pain in pregnancy.
A rare cause of upper GI bleeding and wasting disease
Authors: Rene J van Erp, Bernd Schröppel, Thomas F Barth, Thomas Seufferlein, Stefan A Schmidt, Alexander Meining, Alexander Kleger
Journal: Gut (2015)

A 74-year-old Turkish woman was admitted with loss of appetite, weight loss and progressive anaemia. Her medical history included rheumatoid arthritis, type 2 diabetes and end-stage renal disease with nephrotic syndrome diagnosed 2 years ago. Endoscopy of the upper GI tract revealed a distinct intramural gastric haematoma with diffuse, seeping haemorrhage and large gastric intraluminal blood clots (figure 1A, B; online supplementary films 1 and 2). The mucosa appeared partly necrotic, and the gastric wall showed a sponge-like consistence and marked vulnerability. An abdominal CT scan was performed.



Figure 1 
Endoscopic and radiological imaging. (A and B) Intraluminal view of the patient’s stomach during gastroscopy shows large blood clots and reveals a sponge-like consistence and marked vulnerability on biopsies. (C …
Charity urges drug firms to reduce price of pneumonia vaccine
Authors: A. Gulland
Journal: BMJ (2015)

The charity Medecins Sans Frontieres (MSF) has launched a global campaign urging drug companies GlaxoSmithKline (GSK) and Pfizer to reduce the price of the pneumonia vaccine for developing countries. The organisation launched its global petition on world pneumonia day, 12 November.

Earlier this year the charity published a report showing that the cost of fully immunising a child had increased 68 times between 2001 and 2014, while over the same period the number of vaccines in the full childhood vaccination schedule increased from six to …
A strategy for evaluation of new treatments in untreated patients: application to a clinical trial of AMSA for acute leukemia.
Authors: M J Keating, E A Gehan, T L Smith, E H Estey, R S Walters, H M Kantarjian, K B McCredie, E J Freireich
Journal: Journal of Clinical Oncology (1987)

This clinical trial (DT7995) was designed to evaluate amsacrine (AMSA) plus cytosine arabinoside (ara-C), vincristine, and prednisone (OAP) therapy in previously untreated patients with adult acute leukemia and to investigate a new strategy for assignment of patients to treatment using estimated probabilities of complete remission (PPR) based on six prognostic factors. In the first stage of the trial, patients with unfavorable prognosis (PPR less than .40) received AMSA-OAP for remission induction and patients with favorable prognosis (PPR greater than or equal to .40) received Adriamycin [Adria Laboratories, Columbus, OH] plus OAP (Ad-OAP). As AMSA-OAP was found to be promising in patients with unfavorable prognosis, it was administered to relatively more favorable patients (PPR less than .60) in the second stage of the trial and to all patients in the third stage. There were 242 patients entered into study; 134 received AMSA-OAP and 108 received Ad-OAP. Outcomes were compared with 242 paired patients who received Ad-OAP therapy from 1973 to 1977. The estimated complete remission rate in previously untreated adults with acute leukemia is 61% for patients receiving Ad-OAP (95% confidence interval, 59% to 64%). Overall, the survival experience for the 242 patients on DT7995 was significantly better than that in the control series (P = .03), but there was no strong statistical evidence (P = .10) that the 134 patients receiving AMSA-OAP had better survival than control patients receiving Ad-OAP, with a median of 32 v 21 weeks, respectively. It is concluded that AMSA-OAP is equivalent to Ad-OAP in the induction of complete remissions (estimated complete remission rate, 61%) and that assignment of patients to treatment based on predicted prognosis is an ethical and efficient strategy for the evaluation of new therapies in previously untreated patients with acute leukemia.
Characterization of a Novel Integrin Binding Protein, VPS33B, Which Is Important for Platelet Activation and In Vivo Thrombosis and Hemostasis
Authors: Binggang Xiang, Guoying Zhang, Shaojing Ye, Rui Zhang, Cai Huang, Jun Liu, Min Tao, Changgeng Ruan, Susan S. Smyth, Sidney W. Whiteheart, Zhenyu Li
Journal: Circulation (2015)

Background— Integrins are heterodimeric (α/β) membrane proteins that play fundamental roles in many biological processes, for example, cell adhesion and spreading, which are important for platelet function and hemostasis. The molecular mechanism that regulates integrin activation is not completely understood. Methods and Results— Here, we show that VPS33B, a member of the Sec1/Munc18 family, binds directly to the integrin β subunit. Overexpression of VPS33B in Chinese hamster ovary cells potentiated αIIbβ3 outside-in signaling but not inside-out signaling. Platelets, from megakaryocyte- and platelet-specific VPS33B conditional knockout mice, had normal morphology, yet their spreading on fibrinogen was impaired and they failed to support clot retraction. Platelet aggregation and ATP secretion in response to low-dose agonists were reduced in the VPS33B knockout mice. αIIbβ3-mediated endocytosis of fibrinogen was also defective. Tail bleeding times and times to occlusion in an FeCl 3 -induced thrombosis model were prolonged in the VPS33B knockout mice. Furthermore, VPS33B acted upstream of the RhoA-ROCK-MLC and Rac1-dependent pathways that lead to clot retraction and cell spreading, respectively. Conclusions— Our work demonstrates that vesicular trafficking complexes, containing VPS33B, are a novel class of modifiers of integrin function. Our data also provide insights into the molecular mechanism and treatment of arthrogryposis, renal dysfunction, and cholestasis syndrome.
The death analysis of HIV-infected patients in the antituberculous hospital
Authors: Elvira Borodulina, Ekaterina Skvortsova, Elena Borodulina
Journal: European Respiratory Journal (2014)

One of the most common secondary diseases HIV-infected patients may have is the tuberculosis. Recently the issue whether the tuberculosis causes the death of HIV-infected patients has been raised a lot.

The goals: to estimate a situation according to the mortality level of patients in a tubercular hospital in a city with high diffusion of HIV.

Reference sources and methods: the death analysis of 437 patients in 2012 and 2013 (6 months) has been carried out in Samara tubercular hospital. Among them 297 people (66,4 %) are HIV-infected. 66,7 % of patients have died of AIDS with concurrent tuberculosis and 33,3% of them have died of tuberculosis combined with HIV-infection. In accordance with this the groups have been formed: 1st group - 198 patients, 2nd-99 patients.

Results: Among dead patients men prevail, in the first group the number of them comprises 120 (60,6 %), in the second group it is 72 (72,8 %). Patients died in the efficient age from 21 to 40 years: 1st group comprises 29± 3,2 (85 %), the second one - 35 ±4,6 (35 %). The HIV has been revealed before tuberculosis in 1st group in 85 % of all cases (thus patients have been infected more than 7 years ago), in the second one it happened in 64 %. In the second group where tuberculosis was a cause of death, at postmortem examination by a cause of death was disseminated tuberculosis in 49 (24,7 %) cases, miliary tuberculosis at 19 (9,6 %), a caseous pneumonia at 13 (6,6 %), a tubercular meningitis at 7 (3,5 %), cavitary disease at 11 (5,5 %). In the first group brain edema with foramen magnum herniation was a cause of death in 80 %.

Conclusion. 80% of HIV -infected patients with a tuberculosis had lethal outcomes because of the end-stage of a HIV - AIDS.
Changes in Sex and Ethnic Diversity in Dermatology Residents Over Multiple Decades
Authors: Gordon Bae, Mengting Qiu, Erin Reese, Vinod Nambudiri, Susan Huang
Journal: JAMA Dermatology (2015)

Increased ethnic diversity of physicians is associated with increased access to health care for underserved communities, better anticipation of patient needs, and acceleration of medical research. 1Similarly, sex concordance between physicians and patients can improve communication and patient satisfaction. 2Although sex and ethnic diversity of US physicians have both increased over the past several decades, not all clinical specialties have been impacted equally.To better characterize the dermatology field's evolution during this time period, we analyzed sex and ethnicity trends among dermatology residents and compared them with other specialties and medical school graduates over multiple decades.
Socioeconomic Disparities in Weight and Behavioral Outcomes Among American Indian and Alaska Native Participants of a Translational Lifestyle Intervention Project
Authors: Luohua Jiang, Haixiao Huang, Ann Johnson, Edward J. Dill, Janette Beals, Spero M. Manson, Yvette Roubideaux
Journal: Diabetes Care (2015)

OBJECTIVE To investigate possible socioeconomic disparities in weight and behavioral outcomes among American Indian and Alaska Native (AI/AN) participants in a translational diabetes prevention project. RESEARCH DESIGN AND METHODS We analyzed data from the Special Diabetes Program for Indians Diabetes Prevention (SDPI-DP) Program, an evidence-based lifestyle intervention to prevent diabetes in 36 AI/AN grantee sites. A total of 2,553 participants started the 16-session Lifestyle Balance Curriculum between 1 January 2006 and 31 July 2008. Linear mixed models were used to evaluate the relationships of participant and staff socioeconomic characteristics with weight and behavioral outcomes at the end of the curriculum. RESULTS A strong, graded association existed between lower household income and less BMI reduction, which remained significant after adjusting for other socioeconomic characteristics. Compared with others, participants with annual income &amp;lt;$15,000 also had less improvement in physical activity and unhealthy food consumption in bivariate models, but the relationships were only marginally significant in multivariate regressions. Furthermore, grantee sites with fewer professionally prepared staff were less successful at improving participant BMI and healthy food consumption than the other sites. The strong association between income and BMI reduction was reduced by 20–30% in the models with changes in diet variables but was unrelated to changes in physical activity. CONCLUSIONS Significant socioeconomic disparities exist in weight outcomes of lifestyle intervention at both participant and site staff levels. Helping low-income participants choose more affordable healthy foods and increasing the proportion of professionally trained staff might be practical ways to maximize the effectiveness of lifestyle interventions implemented in “real-world” settings.
Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension
Authors: Abdul Q. Sheikh, Ashish Misra, Ivan O. Rosas, Ralf H. Adams, Daniel M. Greif
Journal: Science Translational Medicine (2015)

Excess and ectopic smooth muscle cells (SMCs) are central to cardiovascular disease pathogenesis, but underlying mechanisms are poorly defined. For instance, pulmonary hypertension (PH) or elevated pulmonary artery blood pressure is a devastating disease with distal extension of smooth muscle to normally unmuscularized pulmonary arterioles. We identify novel SMC progenitors that are located at the pulmonary arteriole muscular-unmuscular border and express both SMC markers and the undifferentiated mesenchyme marker platelet-derived growth factor receptor-β (PDGFR-β). We term these cells "primed" because in hypoxia-induced PH, they express the pluripotency factor Kruppel-like factor 4 (KLF4), and in each arteriole, one of them migrates distally, dedifferentiates, and clonally expands, giving rise to the distal SMCs. Furthermore, hypoxia-induced expression of the ligand PDGF-B regulates primed cell KLF4 expression, and enhanced PDGF-B and KLF4 levels are required for distal arteriole muscularization and PH. Finally, in PH patients, KLF4 is markedly up-regulated in pulmonary arteriole smooth muscle, especially in proliferating SMCs. In sum, we have identified a pool of SMC progenitors that are critical for the pathogenesis of PH, and perhaps other vascular disorders, and therapeutic strategies targeting this cell type promise to have profound implications.
Review of Ian Dowbiggin,<i>A Concise History of Euthanasia: Life, Death, God, and Medicine</i><sup>1</sup>and Neal Nicol and Harry Wylie,<i>Between the Dying and the Dead: Dr. Jack Kevorkian's Life and the Battle to Legalize Euthanasia</i><sup>2</sup>
Authors: Sandra Woien
Journal: The American Journal of Bioethics (2007)

Euthanasia and physician-assisted suicide raise a myriad of ethical issues. While these two books explore some of the cultural and historical controversies of euthanasia and physician-assisted suic...
Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma
Authors: Agrin Moeini, Daniela Sia, Nabeel Bardeesy, Vincenzo Mazzaferro, Josep M. Llovet
Journal: Clinical Cancer Research (2015)

Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous hepatobiliary neoplasm with poor prognosis and limited therapeutic options. The incidence of this neoplasm is growing globally. One third of iCCA tumors are amenable to surgical resection, but most cases are diagnosed at advanced stages with chemotherapy as the only established standard of practice. No molecular therapies are currently available for the treatment of this neoplasm. The poor understanding of the biology of iCCA and the lack of known oncogenic addiction loops has hindered the development of effective targeted therapies. Studies with sophisticated animal models defined IDH mutation as the first gatekeeper in the carcinogenic process and led to the discovery of striking alternative cellular origins. RNA- and exome-sequencing technologies revealed the presence of recurrent novel fusion events (FGFR2 and ROS1 fusions) and somatic mutations in metabolic (IDH1/2) and chromatin-remodeling genes (ARID1A, BAP1). These latest advancements along with known mutations in KRAS/BRAF/EGFR and 11q13 high-level amplification have contributed to a better understanding of the landscape of molecular alterations in iCCA. More than 100 clinical trials testing molecular therapies alone or in combination with chemotherapy including iCCA patients have not reported conclusive clinical benefits. Recent discoveries have shown that up to 70% of iCCA patients harbor potential actionable alterations that are amenable to therapeutic targeting in early clinical trials. Thus, the first biomarker-driven trials are currently underway.