tbuckley/cabot-search huggingface dataset:
Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study
Authors: Linda E.T. Vissers, Ivonne Sluijs, Yvonne T. van der Schouw, Nita G. Forouhi, Fumiaki Imamura, Stephen Burgess, Aurelio Barricarte, Heiner Boeing, Catalina Bonet, Maria-Dolores Chirlaque, Guy Fagherazzi, Paul W. Franks, Heinz Freisling, Marc J. Gunter, J. Ramón Quirós, Daniel B. Ibsen, Rudolf Kaaks, Timothy Key, Kay T. Khaw, Tilman Kühn, Olatz Mokoroa, Peter M. Nilsson, Kim Overvad, Valeria Pala, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Annemieke M.W. Spijkerman, Anne Tjonneland, Rosario Tumino, Miguel Rodríguez-Barranco, Olov Rolandsson, Elio Riboli, Stephen J. Sharp, Claudia Langenberg, Nicholas J. Wareham
Journal: Diabetes Care (2019)

OBJECTIVE To estimate the causal association between intake of dairy products and incident type 2 diabetes. RESEARCH DESIGN AND METHODS The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C&amp;gt;T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. RESULTS Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6–23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0–4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β −7.0 g/day, 95% CI −12.4 to −1.7 per additional LP allele), nonalcoholic beverages (β −18.0 g/day, 95% CI −34.4 to −1.6), and wine (β −4.8 g/day, 95% CI −9.1 to −0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratioper 15 g/day 0.99, 95% CI 0.93–1.05). CONCLUSIONS rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result.
Abstract B048: Androgen metabolism and incidence of prostate cancer in Nigeria
Authors: Solomon Rotimi, Chidiebere Ogo, Olubanke Ogunlana, Shalom Chinedu, Emeka Iweala
Journal: Cancer Research (2018)

Abstract The risk of prostate cancer among blacks, especially of Nigerian descent, is higher than other races. This could be attributed to biologic and genetic variability. The role of androgen metabolism in prognosis of prostate cancer has been delineated and reported. One of the enzymes involved in androgen metabolism is CYP3A4, which has not been studied in Nigerian men afflicted with prostate cancer. Racial differences in this functional gene may contribute to variations in incidence of prostate cancer across ethnic divides. Therefore, identifying a diagnostic and prognostic biomarker such as CYP3A4 polymorphism for prostate cancer in black men will improve the treatment and management of the disease. In this study, we investigated the genotypes of CYP3A4 of prostate cancer patients from Nigeria for possible correlation to the high incidence of the disease in Nigerian men. The results obtained showed a preponderance of the GG genotypes, which indicates a possible correlation between this genotype of CYP3A4 and higher risk of prostate cancer among Nigerian men. Citation Format: Solomon Rotimi, Chidiebere Ogo, Olubanke Ogunlana, Shalom Chinedu, Emeka Iweala. Androgen metabolism and incidence of prostate cancer in Nigeria [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B048.
Tryptophan Deprivation Promotes an Adaptive Response and Contributes to Bioenergetics in Multiple Myeloma
Authors: Alessandra Romano, Nunziatina Laura Parrinello, Katia Todoerti, Piera La Cava, Fabrizio Puglisi, Cesarina Giallongo, Daniele Tibullo, Giuseppina Camiolo, Giuseppe Sapienza, Vittorio Del Fabro, Concetta Conticello, Francesco Piazza, Marilena Carrino, Giuseppe A. Palumbo, Simone Cenci, Antonino Neri, Francesco Di Raimondo
Journal: Blood (2018)
NFκB transcription factor binding is altered at many Atopic Dermatitis disease loci
Authors: Amy Eapen, Sreeja Parameswaran, Carmy Forney, Daniel Miller, Omer Donmez, Katelyn Dunn, Mehak Chawla, Amber Sauder, Ellen Fjellman, Mario Pujato, Xiaoming Lu, Xiaoting Chen, David I. Bernstein, Matthew T. Weirauch, Leah Claire Nesbitt Kottyan
Journal: Journal of Allergy and Clinical Immunology (2019)
European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?
Authors: J. Nielsen, L.S. Vestergaard, L. Richter, D. Schmid, N. Bustos, T. Asikainen, R. Trebbien, G. Denissov, K. Innos, M.J. Virtanen, A. Fouillet, T. Lytras, K. Gkolfinopoulou, M. an der Heiden, L. Grabenhenrich, H. Uphoff, A. Paldy, J. Bobvos, L. Domegan, J. O'Donnell, M. Scortichini, A. de Martino, J. Mossong, K. England, J. Melillo, L. van Asten, M. MA de Lange, R. Tønnessen, R.A. White, S.P. da Silva, A.P. Rodrigues, A. Larrauri, C. Mazagatos, A. Farah, A.D. Carnahan, C. Junker, M. Sinnathamby, R.G. Pebody, N. Andrews, A. Reynolds, J. McMenamin, C.S. Brown, C. Adlhoch, P. Penttinen, K. Mølbak, T.G. Krause
Journal: Clinical Microbiology and Infection (2019)

Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe.Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures.Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths.The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.
The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: An exploratory subgroup analysis of JCOG1113.
Authors: Ikuhiro Yamada, Chigusa Morizane, Takuji Okusaka, Gakuto Ogawa, Yuya Sato, Makoto Ueno, Masafumi Ikeda, Kazuya Sugimori, Akira Fukutomi, Satoshi Shimizu, Nobumasa Mizuno, Hiroaki Yanagimoto, Keiji Sano, Kazutoshi Tobimatsu, Kei Yane, Shoji Nakamori, Naohiro Sata, Tomohiro Nishina, Hiroshi Ishii, Junji Furuse
Journal: Journal of Clinical Oncology (2019)

349 Background: JCOG1113 is a randomized phase III trial to confirm the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for advanced biliary tract cancer (BTC) in overall survival (OS). In the final analysis, GS demonstrated non-inferiority to GC in OS and was considered as a new option of standard of care for advanced BTC. However, there are few reports on the efficacy and safety of combination chemotherapy in elderly patients with advanced BTC. Therefore, this study aimed to explore the clinical outcomes of combination chemotherapy in elderly patients with advanced BTC. Methods: Among all enrolled patients in JCOG1113, ≥ 75 years old patients were included in this exploratory subgroup analysis. Cox regression analysis was performed to investigate the influence of age at baseline on OS and PFS. Clinically relevant adverse events (AEs) were defined as any of grade 2 or more fatigue, appetite loss, nausea, vomiting, oral mucositis, and diarrhea, and were compared using Fisher’s exact test. Results: Among all enrolled patients, 155 patients in GC and 139 patients in GS were included in &lt; 75 years old cohort and 20 patients in GC and 40 patients in GS were included in ≥ 75 years old cohort.The HR of ≥ 75 years old cohort to &lt; 75 years old cohort for OS was 0.96 (95% CI 0.71–1.30) in all enrolled patients. The HR of ≥ 75 years old cohort to &lt; 75 years old cohort for OS was 1.26 (95% CI 0.77–2.04) in GC, and 0.84 (95% CI 0.56–1.24) in GS. The HR of ≥ 75 years old cohort to &lt; 75 years old cohort for PFS was 1.01 (95% CI 0.63–1.61) in GC, and 0.78 (95% CI 0.54–1.12) in GS. Clinically relevant AEs were 36.1% in &lt; 75 years old cohort and 25.0% in ≥ 75 years old cohort in GC, and 29.5% in &lt; 75 years old cohort and 32.5% in ≥ 75 years old cohort in GS. Conclusions: The clinical outcomes of combination chemotherapy in elderly patients were comparable to non-elderly patients. Clinical trial information: 000010667.
Phase II Study of Stimulation of Healthy Sibling Donors with Single-Shot Pegfilgrastim - Update (EUDRACT Nr: 2005-004971-39)
Authors: Vladan Vucinic, Sabine Leiblein, Kristina Schakols, Claudia Nehring, Yvonne Remane, Madlen Jentzsch, Sebastian Schwind, Wolfram Pönisch, Runa Stiegler, Constanze Kliem, Michael Cross, Dietger Niederwieser
Journal: Blood (2018)
mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases
Authors: Giulietta Maruggi, Cuiling Zhang, Junwei Li, Jeffrey B. Ulmer, Dong Yu
Journal: Molecular Therapy (2019)

In the last two decades, there has been growing interest in mRNA-based technology for the development of prophylactic vaccines against infectious diseases. Technological advancements in RNA biology, chemistry, stability, and delivery systems have accelerated the development of fully synthetic mRNA vaccines. Potent, long-lasting, and safe immune responses observed in animal models, as well as encouraging data from early human clinical trials, make mRNA-based vaccination an attractive alternative to conventional vaccine approaches. Thanks to these data, together with the potential for generic, low-cost manufacturing processes and the completely synthetic nature, the prospects for mRNA vaccines are very promising. In addition, mRNA vaccines have the potential to streamline vaccine discovery and development, and facilitate a rapid response to emerging infectious diseases. In this review, we overview the unique attributes of mRNA vaccine approaches, review the data of mRNA vaccines against infectious diseases, discuss the current challenges, and highlight perspectives about the future of this promising technology.
Impact of Omalizumab Treatment Withdrawal After 24 and 48 Weeks in Patients with Chronic Idiopathic Urticaria: Results From the XTEND-CIU Study
Authors: Allen P. Kaplan, Thomas Robert Murphy, Michael Holden, Ahmar Iqbal, Bongin Yoo, Jonathan A. Bernstein
Journal: Journal of Allergy and Clinical Immunology (2019)
Assessing Asthma Management Knowledge in Caregivers of Children with Moderate-to-Severe Asthma
Authors: Madeleine K. Kanaley, Kathy L. Boon, Jesse A. Blumenstock, Alexandria Bozen, Avneet S. Chadha, Pamela J. Newmark, Jolanta W. Szkodon, Kristin Kan, Deneen Vojta, Ruchi S. Gupta
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 16977: Characterization of Oxidative Stress Regulation of Endoplasmic Reticulum Stress Pathway in Cardiac Remodeling
Authors: Jie Wang, Ding Wang, Dominic Ng, Jessica Lee, Quan Cao, Peipei Ping
Journal: Circulation (2017)

Introduction: Emerging evidence implicates crosstalks between endoplasmic reticulum (ER) stress and oxidative stress in regulating pathogenesis of heart disease. At one arm, elevated ROS is reported to mediate reversible oxidation of the ER stress subproteome, altering their regulatory impact in cardiac remodeling; in conjunction, a cluster of ER stress proteins is found responsible to maintain homeostasis of the redox subproteome. However, three critical questions remain: (i) which of the ER stress proteins are targets of oxidative stress modification, (ii) what are the sites of their modification, and (iii) how is this process dynamically regulated. Methods: We have taken a targeted quantitative proteomics approach incorporating biotin-switch and isobaric labeling methods to determine proteome properties (expression, turnover, and PTM) of ER stress proteins in sham or ISO-challenged C57BL6/J mouse heart at 6 time points: Day 1, 3, 5, 7, 10, and 14. In parallel, functional evaluations (e.g., HW/BW) were ...
Multicenter open-label phase II trial to evaluate nivolumab and ipilimumab for second line therapy in elderly patients with advanced esophageal squamous cell cancer (RAMONA).
Authors: Nadja M Meindl-Beinker, Nicolai Hartel, Martin Maenz, Johannes Betge, Matthias Philip Ebert
Journal: Journal of Clinical Oncology (2019)

TPS174 Background: Advanced esophageal squamous cell cancer (ESCC) is frequently diagnosed in elderly patients (pts) and impact of 2nd line chemotherapy is poorly defined. In line with recent data demonstrating effectiveness of checkpoint inhibitors Nivolumab (Nivo) and Ipilimumab (Ipi) in squamous cell carcinoma pts, combined Nivo/Ipi therapy will be assessed as 2nd line therapy of advanced ESCC in elderly pts. Methods: RAMONA is a multicenter open-label phase II trial (NCT03416244). Eligibility and geriatric status of the pts will be assessed by the G8 screening tool and the Deficit Accumulation Frailty Index (DAFI). Upon safety assessment after a three cycle run-in phase of Nivo (240 mg Q2W), eligible pts will be escalated to Nivo (240 mg Q2W)/Ipi (1 mg/kg Q6W) combination therapy. The other pts will remain on Nivo only. The primary objective of this trial is to demonstrate a significant survival benefit of the Nivo/Ipi combination therapy in advanced ESCC compared to historical data of standard chemotherapy regimens. Primary endpoint is overall survival (OS); secondary endpoints are tumor response, PFS, safety and quality of life (QoL). The trial has a 90% Power to detect a hazard ratio of 0.68 at a one-side significance level of alpha = 0.05 under the assumption of exponential survival. This corresponds to an increase of the 1-year OS rate by a margin of 13% compared to historical controls for standard chemotherapy (i.e. 30% vs 17%). Subjects are accrued for a period of 12 month. Follow-up continues for 24 month after the last subject is added. Including a sample size increase to compensate for uninformative drop-outs a total of n = 75 subjects will be recruited. The primary endpoint will be assessed using a one-sample log-rank test. A particular study objective is the evaluation of the tolerability of Nivo as single agent and in combination with Ipi in terms of QoL. Therefore time to QoL deterioration will be determined. 18 pts have been enrolled by mid of September 2018. RAMONA also includes translational research to identify predictive biomarkers, establish organoid cultures from tumor tissues and assess the utility of microbiome analyses for response prediction. Clinical trial information: NCT03416244.
A phase II study of M6620 and irinotecan in TP53 mutant gastric and gastroesophageal junction (GEJ) adenocarcinoma patients (pts) [NCT03641313].
Authors: Satya Das, Jennifer Whisenant, Austin Doyle, Carmen Joseph Allegra, Jordan Berlin
Journal: Journal of Clinical Oncology (2019)

TPS175 Background: Progressive metastatic or unresectable gastric/GEJ adenocarcinoma pts carry dismal prognoses with a significant need for novel systemic therapies. One avenue for drug development in this disease is targeting salvage DNA repair pathways. TP53, a central gene to DNA damage repair (DDR), is mutated in 50% of gastric/GEJ cancer pts. Pre-clinical models from multiple cancer types demonstrate that cancer cells with TP53 mutations rely on the ataxia telangiectasia and Rad-3 related protein kinase (ATR) axis as a primary pathway of salvage DDR in the face of cytotoxic stress. The ATR pathway is typically triggered by single strand DNA breaks such as those generated by topoisomerase I inhibitors. Irinotecan is already known to be active in later line gastric/GEJ pts, thus, there appears to be an opportunity to combine the agent with the ATR inhibitor M6620 in TP53 mutant pts with the disease. Methods: Our trial is a single arm phase II study of M6620 plus irinotecan in progressive gastric/GEJ adenocarcinoma pts. Only pts with TP53 mutations in exon 2 and exons 4-11, as determined by next-generation sequencing from archived tissue, will be eligible. Pts will receive 180 mg/m^2 of irinotecan immediately followed by M6620 every 2 weeks; the M6620 dose will be determined based on the recommended phase 2 dose from the ongoing phase I trial. CT scans will be repeated every 2 months to assess response. The primary endpoint of the study is overall response rate (ORR), with a pre-specified target of 35%. Correlative studies will be performed on fresh tumor tissue from the first 9 pts, obtained by biopsies on day 1 of cycle 1 post-irinotecan and day 2 of cycle 2, to assess dynamic changes in the biomarkers Y-H2AX, KAP1 p-Ser 824, and p-ATR. Our study employs a Simon’s two-stage design (α = 0.1, power = 0.8) where an initial analysis will be performed after 9 pts are enrolled. If &lt; 2 pts demonstrate objective response, the trial will stop for futility. If &gt; 2 pts demonstrate response, the study will enroll 14 more pts. If ≥ 6 pts experience an objective response, the trial will achieve its efficacy threshold. Accrual will be ensuing in the near future. Clinical trial information: NCT03641313.
Association of Geography and Access to Health Care Providers With Long‐Term Prescription Opioid Use in Medicare Patients With Severe Osteoarthritis: A Cohort Study
Authors: Rishi J. Desai, Yinzhu Jin, Patricia D. Franklin, Yvonne C. Lee, Brian T. Bateman, Joyce Lii, Daniel H. Solomon, Jeffrey N. Katz, Seoyoung C. Kim
Journal: Arthritis & Rheumatology (2019)

Objective To evaluate the variation in long‐term opioid use in osteoarthritis ( OA ) patients according to geography and health care access. Methods We designed an observational cohort study among OA patients undergoing total joint replacement ( TJR ) in the Medicare program (2010 through 2014). The independent variables of interest were the state of residence and health care access, which was quantified at the primary care service area ( PCSA ) level as categories of number of practicing primary care providers ( PCP s) and categories of rheumatologists per 1,000 Medicare beneficiaries. The percentage of OA patients taking long‐term opioids (≥90 days in the 360‐day period immediately preceding TJR ) within each PCSA was the outcome variable in a multilevel, generalized linear regression model, adjusting for case‐mix at the PCSA level and for policies, including rigor of prescription drug monitoring programs and legalized medical marijuana, at the state level. Results A total of 358,121 patients with advanced OA, with a mean age of 74 years, were included from 4,080 PCSA s. The unadjusted mean percentage of long‐term opioid users varied widely across states, ranging from 8.9% (Minnesota) to 26.4% (Alabama), and this variation persisted in the adjusted models. Access to PCP s was only modestly associated with rates of long‐term opioid use between PCSA s with highest (&gt;8.6) versus lowest (&lt;3.6) concentration of PCPs (adjusted mean difference 1.4% [95% confidence interval 0.8%, 2.0%]), while access to rheumatologists was not associated with long‐term opioid use. Conclusion We note a substantial statewide variation in rates of long‐term treatment with opioids in OA , which is not fully explained by the differences in access to health care providers, varying case‐mix, or state‐level policies.
Lack of public health resources leaves us all vulnerable
Authors: Woody Caan
Journal: BMJ (2019)

Mass casualty events demand shared experience across the spectrum of public health skills.1 The BMA’s London regional council chair, Gary Marlowe, has warned of London’s specialist microbiology shortage,2 but the last coherent planning across London’s public health workforce was in 1992.3 Now the security minister warns: “Significant outbreaks of disease are among the highest impact risks faced by any society—threatening lives and causing disruption …
T‐cell responses against 4‐ <i>tert</i> ‐butylphenol‐exposed pigmented cells in a patient with occupational vitiligo
Authors: C. Vrijman, K.J. Willemsen, E.P.M. Tjin, A. Kammeyer, J.G. Boorn, J.P.W. Veen, F.H.W. Jungbauer, S.H. Kardaun, R.M. Luiten
Journal: British Journal of Dermatology (2019)

T-cell responses against 4-tert-butylphenolexposed pigmented cells in a patient with occupational vitiligo
Abstract 19059: Utility of A Wristband Device as a Portable Screening Tool for Obstructive Sleep Apnea
Authors: Benjamin A Steinberg, Melike Yuceege, Murad Mutlu, Mehmet H Korkmaz, Reinier A van Mourik, Onur Dur, Mihail Chelu, Nassir Marrouche
Journal: Circulation (2017)

Introduction: Obstructive sleep apnea (OSA) is highly prevalent in patients with cardiovascular disease (CVD), and is associated with increased mortality if left untreated. Health wearable devices capable of tracking physiologic parameters, trends, and patterns could provide convenient, early screening for OSA. This study is designed to assess (1) the accuracy of nocturnal biometric measurements collected by an investigational wrist-worn device, and (2) its utility as a portable screening device for detection of apnea. Methods: Thirty patients with suspected OSA were recruited for polysomnography (PSG) studies and asked to wear a photoplethsmography (PPG) device (Wavelet Health, Mt. View, CA) on their wrist. Multiple physiologic parameters from the ground truth PSG device were compared to those recorded by wristbands, and included heart rate (HR), heart rate variability (HRV), oxygen saturation (SpO2) and respiration rate (RR). Results: Comparison of HR, HRV, SpO2 and RR between PSG and wristband indicate...