tbuckley/cabot-search huggingface dataset:
Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes
Authors: Anick Bérard, Jin-Ping Zhao, Irene Shui, Susan Colilla
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Leflunomide is known to be embryotoxic and teratogenic in rodents. However, there is less evidence in humans. We quantified the risk of major congenital malformation (MCM), prematurity, low birth weight (LBW) and spontaneous abortion associated with leflunomide exposure during pregnancy in humans. Methods From a cohort of 289 688 pregnancies in Montreal, Quebec, Canada, from 1998 to 2015, first-trimester leflunomide exposure and other antirheumatic drug exposures were studied for their association with MCM and spontaneous abortions. Also second or third-trimester leflunomide exposures were examined for associations with prematurity and LBW. Logistic regression model-based generalised estimating equations were used. Results 51 pregnancies were exposed to leflunomide during the first trimester, and 21 during the second/third trimesters. Adjusting for potential confounders, use of leflunomide during the first trimester of pregnancy was not associated with the risk of MCM (adjusted OR (aOR) 0.97, 95% CI 0.81 to 1.16; 5 exposed cases). No association was found between second/third-trimester exposure to leflunomide and the risk of prematurity (aOR 4.03, 95% CI 0.91 to 17.85; 7 exposed cases) nor LBW (aOR 1.06, 95%CI 0.90 to 1.25; 8 exposed cases). Pregnancy exposure to leflunomide was also not associated with the risk of spontaneous abortion (aOR 1.09, 95% CI 0.90 to 1.32; 11 exposed cases). Conclusions Maternal exposure to leflunomide during pregnancy was not associated with statistically significant increased risk of MCMs, prematurity, LBW or spontaneous abortions. However, given that relatively few women were exposed to leflunomide during pregnancy in this cohort, caution remains warranted.
Abstract 14159: Twenty Four-Hour Urinary Potassium Excretion, but not Sodium Excretion, Was associated With All-Cause Mortality in a General Population - the 27.5-year Prospective Data From the Tanushimaru Study
Authors: Yume Nohara, Hisashi Adachi, Mika Enomoto, Ako Fukami, Maki Otsuka, Eita Kumagai, Sachiko Nakamura, Aya Obuchi, Shoko Kono, Nagisa Morikawa, Erika Nakao, Akiko Sakaue, Tomoko Tsuru, Yoshihiro Fukumoto
Journal: Circulation (2016)

Introduction:  Lower potassium consumption has been associated with hypertension and stroke. However, few studies have examined the relationship between urinary potassium and mortality, and most of them have been conducted by estimated 24-hour urinary potassium excretion from a morning urinary sample.   Hypothesis:  The hypothesis of the present study is to investigate the association between 24-hour urinary potassium excretion and mortality in a healthy Japanese population using 24-hour urine collection.   Methods:  The baseline study was conducted in 1978. A total of 1,291 participants (535 men, 756 women), aged 21 to 85 years, underwent health check-ups, which included blood chemistry measurements and the collection of 24-hour urine samples. Of the 1,291 participants who followed up for 27.5 years; the final follow-up rate was 95.8%. Cox’s proportional hazards models were used to assess the association between 24-hour urinary sodium or potassium excretion and all-cause mortality.   Results:  At baseline, the mean 24-hour urinary sodium excretion was 5.80±2.28 g/day, and the mean 24-hour urinary potassium excretion was 1.85±0.82 g/day. There were 631 deaths: 153 (27%) from cancer, 77 (14%) from cardiovascular disease, 65 (12%) from stroke, 89 (16%) from infection and 173 (31%) from other causes. In the Cox’s proportional hazard model after adjustments for age and sex, 24-hour urinary potassium excretion was inversely associated with all-cause mortality ( p =0.013). Even after adjustments for confounding factors, the significance of 24-hour urinary potassium excretion still remained (inversely;  p =0.0006). Then, we divided the baseline 24-hour urinary potassium excretion levels into quartiles. After adjustments for confounding factors, the hazard ratio of all-cause mortality in the highest quartile of 24-hour urinary potassium excretion (>2.30g/day) vs. the lowest quartile ( p =0.0015). However, no significant associations were found between 24-hour urinary sodium excretion and all-cause mortality.   Conclusion:  This is the first report demonstrating that in the general population, 24-hour urinary potassium excretion was associated with all-cause mortality, while sodium excretion was not.
Cell‐Based Drug Delivery and Use of Nano‐and Microcarriers for Cell Functionalization
Authors: Alexander S. Timin, Maxim M. Litvak, Dmitry A. Gorin, Elena N. Atochina‐Vasserman, Dmitriy N. Atochin, Gleb B. Sukhorukov
Journal: Advanced Healthcare Materials (2017)

Abstract Cell functionalization with recently developed various nano‐ and microcarriers for therapeutics has significantly expanded the application of cell therapy and targeted drug delivery for the effective treatment of a number of diseases. The aim of this progress report is to review the most recent advances in cell‐based drug vehicles designed as biological transporter platforms for the targeted delivery of different drugs. For the design of cell‐based drug vehicles, different pathways of cell functionalization, such as covalent and noncovalent surface modifications, internalization of carriers are considered in greater detail together with approaches for cell visualization in vivo. In addition, several animal models for the study of cell‐assisted drug delivery are discussed. Finally, possible future developments and applications of cell‐assisted drug vehicles toward targeted transport of drugs to a designated location with no or minimal immune response and toxicity are addressed in light of new pathways in the field of nanomedicine.
Imaging-detected acute muscle injuries in athletes participating in the Rio de Janeiro 2016 Summer Olympic Games
Authors: Michel D Crema, Mohamed Jarraya, Lars Engebretsen, Frank W Roemer, Daichi Hayashi, Romulo Domingues, Abdalla Y Skaf, Ali Guermazi
Journal: British Journal of Sports Medicine (2017)

Acute muscle injuries in elite athletes are responsible for a large portion of time loss injuries.To describe the frequency, the anatomic distribution, and severity of imaging-detected acute muscle injuries among athletes who competed in the Rio de Janeiro 2016 Summer Olympics.We recorded all sports injuries reported by the National Olympic Committee medical teams and the Organising Committee medical staff during the 2016 Summer Olympics. Imaging of acute muscle injuries was performed at the IOC's polyclinic within the Olympic Village using ultrasound and 3.0 T and 1.5 T MRI scanners. The assessment of images was performed centrally by three musculoskeletal radiologists. The distribution of injuries by anatomic location and sports discipline and the severity of injuries were recorded.In total, 11 274 athletes from 207 teams were included. A total of 1101 injuries were reported. Central review of radiological images revealed 81 acute muscle injuries in 77 athletes (66% male, mean age: 25.4 years, range 18-38 years). Athletics (track and field) athletes were the most commonly affected (n=39, 48%), followed by football players (n=9, 11%). The majority of injuries affected muscles from lower limbs (n=68, 84%), with the hamstring being the most commonly involved. Most injuries were grade 2 injuries according to the Peetrons classification (n=44, 54%), and we found 18 injuries exhibiting intramuscular tendon involvement on MRI.Imaging-detected acute muscle injuries during the 2016 Summer Olympics affected mainly thigh muscles in athletics disciplines.
Abstract 18827: Critical Preoperative Factors and Specific Postoperative Adverse Events Drive Left Ventricular Assist Device Implant Hospitalization Costs.
Authors: Christine V Nikas, Jennifer O Larsen, Jeffrey J Teuteberg, Luigi G Lagazzi, Andrew D Althouse, Michael Sharbaugh, Michael A Shullo, Kathleen L Lockard, Elizabeth M Dunn, Nicole M Kunz, Robert L Kormos
Journal: Circulation (2016)

Introduction:  The cost of LVAD’s and subsequent care results in unfavorable economic evaluations of cost-effectiveness. Cost estimates for LVAD implant hospitalization, however, have been based upon assumptions from CMS data using inpatient-billing codes. Specific hospital costs can be obtained through a detailed cost accounting system in order to determine the effects of pre-implant characteristics and adverse events (AE’s) occurring during implant hospitalization that drive costs.   Hypothesis:  We will identify a subset of pre-operative characteristics and subsequent AE’s that results in higher costs during implant hospitalization.   Methods:  80 patients received a rotary LVAD at a single institution (April 2013 to November 2015). Controllable cost obtained from a hospital cost management system was combined with patient demographics, pre-operative characteristics, AE’s and long-term follow-up data. The outcome variable was the cost of implant hospitalization, while the predictors were pre-operative characteristics and subsequent AE’s. Multivariable linear regression analysis was used to identify the strongest independent predictors of cost and to quantify the additional cost associated with pre-specified AE’s including infection, bleeding/tamponade, reoperation, respiratory events, renal failure, stroke, need for RVAD or RV failure, and arrhythmias.   Results:  The mean and median costs for LVAD implant hospitalization were: $219,866 +/- $67,203 and $194,728 (range: $129,733 - $464, 982) respectively. Adjusting for age, device type, emergent status, and intention-to-treat, strong pre-implant drivers of cost in multivariable analysis included pre-op ventilator ($125,348 additional cost; p   Conclusions:  Combined clinical and accurate cost data reveal critical drivers of total hospital costs.
Effects of 28-day <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> HN019 supplementation on colonic transit time and gastrointestinal symptoms in adults with functional constipation: A double-blind, randomized, placebo-controlled, and dose-ranging trial
Authors: Alvin Ibarra, Mathilde Latreille-Barbier, Yves Donazzolo, Xavier Pelletier, Arthur C. Ouwehand
Journal: Gut Microbes (2017)

Bifidobacterium animalis subsp. lactis HN019 (HN019) ameliorates chronic idiopathic constipation. Our aim was to determine the efficacy and safety of 28-day supplementation with 1 × 10
Abstract 16390: Impact of Revascularization of Chronic Total Occlusion in Patients With and Without Acute Myocardial Infarction
Authors: Parasuram Krishnamoorthy, Akshaya Gopalakrishnan, Jalaj Garg, Janani Rangaswami, Vikas Bhalla, Christian F Witzke, Sean Janzer, Dennis L Morris, Jon George
Journal: Circulation (2016)

Introduction: Percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) has been a major challenge due to technical difficulties with increased complication rates. Approximately 1...
Human Microbiomes Influence Cancer Therapy
Authors: Charlie Schmidt
Journal: JNCI Journal of the National Cancer Institute (2017)

Many factors influence how a cancer patient responds to treatment-among them, age, tumor stage, and other preexisting health conditions.What's increasingly apparent is that trillions of microbes in the body also determine how well cancer treatments will work.Initial evidence of how the microbiome affects cancer treatment came primarily from studies in mice.Now scientists are finding similar evidence in humans."We now know that the microbiome impacts directly on therapeutic outcomes in cancer," said Jeffrey Weber, M.D., a medical oncologist and director of New York University's Perlmutter Cancer Center."By intervening with therapies that alter microbial composition, we might be able to overcome resistance to treatment or even alter the potential for immune-related adverse events."These are early days in the field, and there's still a long way to go before the microbiome factors into clinical decisions."But these findings open our eyes to how the microbiome interferes with our best-laid plans for cancer precision medicine in ways we hadn't previously considered," said Todd Golub, M.D.,
La stratégie de la Communauté européenne contre la résistance antimicrobienne
Authors: S Bronzwaer, A Lönnroth, R Haigh
Journal: Eurosurveillance (2004)

En 2001, la Commission europeenne presentait une Strategie Communautaire contre la resistance  Au cours des annees precedentes, un nombre de plus en plus important de mesures isolees avaient ete mises en place pour faire face a ce probleme. La strategie definit par la Commission permet une approche communautaire globale concernant l'ensemble des secteurs concernes. Elle comprend quinze actions dans quatre secteurs cle : la surveillance, la prevention, la recherche et le developpement de produits, et la cooperation internationale. Les recommandations du Conseil relatives a une utilisation mesuree des antibiotiques en medecine humaine joue un role important dans cette strategie. Ce document fournit un ensemble detaille des actions de sante publique visant a contenir la resistance antimicrobienne. 
Cet article presente les onze points d'actions de la strategie directement liees a la medecine humaine, ainsi que les activites de la Communaute europeenne dans ce domaine. La resistance aux antibiotiques est une priorite dans le nouveau programme de sante publique ainsi que dans le programme de recherche de l'Union europeenne.
“Occipital Tunnel” Sign on FDG PET for Differentiating Dementias
Authors: David M. Sawyer, Phillip H. Kuo
Journal: Clinical Nuclear Medicine (2017)

PET using FDG is a critical tool for evaluation of dementias, with characteristic patterns of hypometabolism suggesting specific diagnoses. Hypometabolism in the occipital region is recognized as an important finding associated with dementia with Lewy bodies and posterior cortical atrophy. We describe here the novel "occipital tunnel" sign, which results from relative sparing of FDG uptake in the medial occipital (primary visual) cortex compared with more severe loss in the surrounding lateral occipital (visual association) cortex. This sign is useful for recognizing the occipital findings of dementia with Lewy bodies and posterior cortical atrophy, especially when viewing sagittal projections.
Factors involved in cancer metastasis: a better understanding to “seed and soil” hypothesis
Authors: Qiang Liu, Hongfei Zhang, Xiaoli Jiang, Caiyun Qian, Zhuoqi Liu, Daya Luo
Journal: Molecular Cancer (2017)

Metastasis has intrigued researchers for more than 100 years. Despite the development of technologies and therapeutic strategies, metastasis is still the major cause of cancer-related death until today. The famous "seed and soil" hypothesis is widely cited and accepted, and it still provides significant instructions in cancer research until today. To our knowledge, there are few reviews that comprehensively and correlatively focus on both the seed and soil factors involved in cancer metastasis; moreover, despite the fact that increasingly underlying mechanisms and concepts have been defined recently, previous perspectives are appealing but may be limited. Hence, we reviewed factors involved in cancer metastasis, including both seed and soil factors. By integrating new concepts with the classic hypothesis, we aim to provide a comprehensive understanding of the "seed and soil" hypothesis and to conceptualize the framework for understanding factors involved in cancer metastasis. Based on a dynamic overview of this field, we also discuss potential implications for future research and clinical therapeutic strategies.
Using Fully-Immersive Simulation With Structured Debrief to Improve Non-Technical Skills in the Emergency Scenario
Authors: A. Ramjeeawon, A. Sharrock, A. Morbi, C. Pettengell, G. Martin, C. Riga, R.O. Smith, N.C. Patel, A.J. Tulloch, M.A. Eusman, H.Y. Choo, C. Bicknell
Journal: International Journal of Surgery (2017)
T Cells Expressing Checkpoint Receptor TIGIT Are Enriched in Follicular Lymphoma Tumors and Characterized by Reversible Suppression of T-cell Receptor Signaling
Authors: Sarah E. Josefsson, Kanutte Huse, Arne Kolstad, Klaus Beiske, Daniela Pende, Chloé B. Steen, Else Marit Inderberg, Ole Christian Lingjærde, Bjørn Østenstad, Erlend B. Smeland, Ronald Levy, Jonathan M. Irish, June H. Myklebust
Journal: Clinical Cancer Research (2017)

Purpose: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing coinhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets.Experimental Design: Surface expression of 9 coinhibitory receptors governing T-cell function was characterized in T-cell subsets from FL lymph node tumors and from healthy donor tonsils and peripheral blood samples, using high-dimensional flow cytometry. The results were integrated with T-cell receptor (TCR)-induced signaling and cytokine production. Expression of T-cell immunoglobulin and ITIM domain (TIGIT) ligands was detected by immunohistochemistry.Results: TIGIT was a frequently expressed coinhibitory receptor in FL, expressed by the majority of CD8 T effector memory cells, which commonly coexpressed exhaustion markers such as PD-1 and CD244. CD8 FL T cells demonstrated highly reduced TCR-induced phosphorylation (p) of ERK and reduced production of IFNγ, while TCR proximal signaling (p-CD3ζ, p-SLP76) was not affected. The TIGIT ligands CD112 and CD155 were expressed by follicular dendritic cells in the tumor microenvironment. Dysfunctional TCR signaling correlated with TIGIT expression in FL CD8 T cells and could be fully restored upon in vitro culture. The costimulatory receptor CD226 was downregulated in TIGIT+ compared with TIGIT- CD8 FL T cells, further skewing the balance toward immunosuppression.Conclusions: TIGIT blockade is a relevant strategy for improved immunotherapy in FL. A deeper understanding of the interplay between coinhibitory receptors and key T-cell signaling events can further assist in engineering immunotherapeutic regimens to improve clinical outcomes of cancer patients. Clin Cancer Res; 24(4); 870-81. ©2017 AACR.
Investigating the roles of the p63 isoforms in tumor suppression and metastasis using mouse models
Authors: Xiaohua Su, Min Soon Cho, Wei Zhang, Elsa Flores
Journal: Cancer Research (2007)

2532    p53  is mutated in many human cancers; yet, the role of  p63  in tumor suppression remains controversial. In many human tumors, p63 is overexpressed, while in others it is lost indicating that it may be an oncogene and/or a tumor suppressor gene. Many isoforms of  p63  exist including a TA isoform that has transactivation activity and a ΔN isoform, which lacks transactivation activity and has dominant negative activities against p53 and TAp63. The lack of antibodies that distinguish between the TA and ΔN isoforms may account for the differences of expression seen in different human tumors, which have been assayed primarily by immunohistochemistry. We have recently shown using mouse models lacking all isoforms of  p63  that it is a suppressor of tumorigenesis and metastasis.  p53+/-;p63+/-  and  p63+/-;p73+/-  mice exhibited higher tumor burden and metastasis than  p53+/-  mice. Additionally, using cells from tumors of these mice, we found genes previously shown to play a role in metastasis to be differentially expressed in mice mutant for  p63.  Finally, using these tumor cells in Boyden chamber assays, cells mutant for  p63  exhibited increased motility and invasion compared to  p53  mutant cells. While these studies indicate that  p63  suppresses tumorigenesis and metastasis, it does not differentiate the individual contributions of the TA and ΔN isoforms of  p63  in these processes. We hypothesize that  TAp63  is a tumor suppressor gene while  Δ  Np63  is an oncogene. To test this hypothesis  in vivo , we have generated  TAp63  conditional knockout mice. Using primary mouse keratinocytes from these mice, we found that cells deficient for  TAp63  exhibited a profound increase in proliferation compared to wild-type keratinocytes. Furthermore, keratinocytes deficient for  TAp63  express keratin 5, a marker for the basal layer of the epithelium, but did not express keratin 10, a marker of epithelial differentiation, after the induction of differentiation. Additionally, day 18.5 embryos that lack  TAp63  had an expanded basal layer and defects in the spinous and granular layers of the epithelium. Taken together, these data indicate that loss of  TAp63  increases proliferation and inhibits the differentiation of epithelial cells. These data support a role for  TAp63  as a tumor suppressor gene. To further understand the roles of the TA and ΔN isoforms of  p63  in tumor suppression and metastasis, we are currently generating a  Δ  Np63  conditional knockout mouse. These studies will shed much needed light on the activities of the TA and ΔN isoforms of  p63  in cancer.
Improving Birth Outcomes in Low- and Middle-Income Countries
Authors: Robert L. Goldenberg, Elizabeth M. McClure
Journal: New England Journal of Medicine (2017)

Pregnancy outcomes in low- and many middle-income countries are far worse than those in high-income countries. Maternal mortality may be up to 100 times as great in the highest mortality regions as in the lowest mortality regions, and neonatal mortality and the rate of stillbirths are 10 to 20 times as great.1 Most of the adverse outcomes occur during labor and delivery or soon thereafter. Many experts have suggested that increasing the proportion of deliveries that take place in medical facilities would reduce mortality in low- and middle-income countries to near the level in high-income countries. Yet, despite a shift . . .