tbuckley/cabot-search huggingface dataset:
Football is medicine: it is time for patients to play!
Authors: Peter Krustrup, Birgitte R Krustrup
Journal: British Journal of Sports Medicine (2018)

In 2006, the recognised Nordic exercise physiologists Professors Pedersen and Saltin provided powerful evidence that exercise was an effective therapy in chronic disease—they emphasised exercise as a cornerstone in the prevention and non-pharmacological treatment of lifestyle diseases.1 Shortly after, American College of Sports Medicine (ACSM)’s president Dr Sallis delivered his well-documented and strong statement that ‘exercise is medicine and physicians need to prescribe it!’.2 These statements, and the research on which they are based, have influenced health authorities and governments around the globe to include exercise recommendations in the prevention and treatment of chronic diseases. Prominent worldwide exercise guidelines, including those from the WHO and ACSM, encourage sedentary individuals and patients to engage in exercise activities like brisk walking, jogging, cycling and fitness centre training. However, within physical activity guidelines, less emphasis has been placed on the health benefits of sporting activities.

In a 2012 Lancet review, it was concluded that ‘sport may contribute to the health of nations’.3 A subsequent meta-analysis published in 2015 concluded that, in terms of health effects of sport, ‘the best evidence was found for football and running’, and that ‘evidence for health benefits of other sport disciplines was either inconclusive or tenuous’.4 Since then, high-quality research has emphasised the preventive effects of several ball games for sedentary adults, and we report that the evidence for the health benefits of football (soccer) is even stronger.5–10 More than 150 peer-reviewed articles published …
The effectiveness of public health advertisements to promote health: a randomized-controlled trial on 794,000 participants
Authors: Elad Yom-Tov, Jinia Shembekar, Sarah Barclay, Peter Muennig
Journal: npj Digital Medicine (2018)

As public health advertisements move online, it becomes possible to run inexpensive randomized-controlled trials (RCTs) thereof. Here we report the results of an online RCT to improve food choices and integrate exercise into daily activities of internet users. People searching for pre-specified terms were randomized to receive one of several professionally developed campaign advertisements or the "status quo" (ads that would otherwise have been served). For 1-month pre-intervention and post-intervention, their searches for health-promoting goods or services were recorded. Our results show that 48% of people who were exposed to the ads made future searches for weight loss information, compared with 32% of those in the control group-a 50% increase. The advertisements varied in efficacy. However, the effectiveness of the advertisements may be greatly improved by targeting individuals based on their lifestyle preferences and/or sociodemographic characteristics, which together explain 49% of the variation in response to the ads. These results demonstrate that online advertisements hold promise as a mechanism for changing population health behaviors. They also provide researchers powerful ways to measure and improve the effectiveness of online public health interventions. Finally, we show that corporations that use these sophisticated tools to promote unhealthy products can potentially be outbid and outmaneuvered.
Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis Patients
Authors: Julie H. Ishida, Charles E. McCulloch, Michael A. Steinman, Barbara A. Grimes, Kirsten L. Johansen
Journal: Journal of the American Society of Nephrology (2018)

Background Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking. Methods From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (&gt;0–100, &gt;100–200, &gt;200–300, and &gt;300 mg) and pregabalin (&gt;0–100 and &gt;100 mg). Results In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%–41%) and fall (26%–30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively. Conclusions Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.
The frequency and impact of ROS1 rearrangement on clinical outcomes in GBM.
Authors: Miriam Dorta, Juan Manuel Sepúlveda, Aurelio Hernandez-Lain, Guillermo Velasco, Ray Manneh, Yolanda Ruano
Journal: Journal of Clinical Oncology (2014)

2093 Background: The tirosine kinase (TK) receptor ROS1 is described in several preclinical analysis of glioblastoma (GBM) cells and its role in gliomagenesis has been reported as well. Since TK inhibitors has changed clinical response of ROS1 rearranged lung cancer, new therapeutic approach has emerged for GBM. However its rearrangement in GBM human tissue still has not been explored and it should be defined to check if those are relevant to assess ROS1 inhibitors in these neoplasms. We performed ROS1 FISH in human GBM tissue and correlates molecular alterations with overall survival (OS) and progression free survival (PFS) in a cohort of uniformly treated GBMs. Methods: Clinical history of 54 patients treated from GBM at Doce de Octubre Spanish Hospital, between 2008 and 2010, were reviewed. Only 33 patients had accessible data, tumor specimen, received treatment out of any other clinical trial and had an adequate follow-up. To better analyze the series of 33 cases, a tissue array paraffin platform was performed, and we disposed probes for ROS1 split. 30 samples from 33 from tissue array keeped enough quality to ROS1 microscope analysis. Results were sorted and pooled in non-mutated and mutated, including deletions and rearrangements in mutated group. Results: Mutations were found in 51,5% of samples. Deletion was the most common mutation (48,5%). Only 1 sample showed rearrangement (3%). 39,4% was not mutated, and 3 patients were not evaluable for ROS1 (9.1%). The median overall survival (OS) and progression-free survival (PFS) of the whole series (33 samples) was 19 months (CI 95 %: 13.66-24.34) and 8 months (95 % CI: 6.47 to 9.53), respectively. For ROS1 subgroup, median OS resulted in 19 versus 11 months for non-mutated and mutated cases, respectively, with statistical signification (p = 0.005). ROS1 median PFS was 9 versus 6 months for non-mutated and mutated respectively, also with statistical significance (p = 0.044). Conclusions: In our series of human GBM tissues treated uniformly, a high frequency of genetic splits is estimated, with just 3% of rearrangements. These findings have prognostic relevance by the relation resulted between ROS1 status and patients survival, being significantly worse for those with ROS1 rearrangements or deletions.
Trefoil factor 1 inhibits epithelial-mesenchymal transition of pancreatic intraepithelial neoplasm
Authors: Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo, Tomoki Ebata, Atsushi Enomoto, Masato Nagino
Journal: Journal of Clinical Investigation (2018)

The tumor-suppressive role of trefoil factor family (TFF) members in gastric carcinogenesis has been suggested, but their significance and mechanisms in other digestive diseases remain elusive. To clarify the role of TFF1 in pancreatic carcinogenesis, we performed IHC on human samples, transfected siRNA against TFF1 into pancreatic cancer cell lines, and employed mouse models in which PanIN development and loss of TFF1 occur simultaneously. In human samples, the expression of TFF1 was specifically observed in pancreatic intraepithelial neoplasm (PanIN), but was frequently lost in the invasive component of pancreatic ductal adenocarcinoma (PDAC). When the expression of TFF1 was suppressed in vitro, pancreatic cancer cell lines showed enhanced invasive ability and features of epithelial-mesenchymal transition (EMT), including upregulated Snail expression. TFF1 expression was also observed in PanIN lesions of Pdx-1 Cre; LSL-KRASG12D (KC) mice, a model of pancreatic cancer, and loss of TFF1 in these mice resulted in the expansion of PanIN lesions, an EMT phenotype in PanIN cells, and an accumulation of cancer-associated fibroblasts (CAFs), eventually resulting in the development of invasive adenocarcinoma. This study indicates that the acquisition of TFF1 expression is an early event in pancreatic carcinogenesis and that TFF1 might act as a tumor suppressor to prevent EMT and the invasive transformation of PanIN.
Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events
Authors: Heinz Läubli, Catharina Balmelli, Lukas Kaufmann, Michal Stanczak, Mohammedyaseen Syedbasha, Dominik Vogt, Astrid Hertig, Beat Müller, Oliver Gautschi, Frank Stenner, Alfred Zippelius, Adrian Egli, Sacha I. Rothschild
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined. <h3>Methods</h3> We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade. <h3>Results</h3> We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2&nbsp;months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). <h3>Conclusions</h3> Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population.
The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells
Authors: Jennifer K. Bando, Susan Gilfillan, Christina Song, Keely G. McDonald, Stanley C.-C. Huang, Rodney D. Newberry, Yasuhiro Kobayashi, David S.J. Allan, James R. Carlyle, Marina Cella, Marco Colonna
Journal: Immunity (2018)
Centralized analysis of phase II ECG dataset of resminostat, an orally available histone-deacetylase inhibitor (HDACi).
Authors: Bernhard Hauns, Henning Schulze-Bergkamen, Dirk Jaeger, Hans-Georg Kopp, Michael Bitzer, Babett Krauss, Stefan W. Henning, Bernd Hentsch, Wilhelm Haverkamp
Journal: Journal of Clinical Oncology (2014)

e13526 Background: Resminostat (4SC-201) is an orally available pan-HDAC inhibitor that revealed substantial clinical activity and was well tolerated by patients with advanced malignancies when administered as single agent or in combination with anti-cancer compounds. Cardiac safety of resminostat was evaluated across patients of 3 clinical Phase II studies. Methods: Resminostat was administered in a dose range of 100 mg up to 800 mg once-daily in repeated 14-day cycles consisting of 5 consecutive treatment days followed by a 9-day rest period to 111 patients with advanced cancer (hepatocellular ca., Hodgkin lymphoma or colorectal ca.). Standard 12-lead rest ECGs were conducted frequently for determination of potential effects on QT interval prolongation. An intensive profile of >10 single ECGs was performed from Day 1 to 5 during Cycle 1, and less frequent in following cycles if no clinically relevant findings occurred. Subsequent to on-site clinical assessment, ECGs were analysed by a trained cardiologist. ECG parameters were measured in lead II across 3 consecutive beats using markers for the respective ECG intervals. In sum, 3792 ECGs from 108 evaluable patients were available for analysis. Results: QTc interval increased in a range from 0-10 ms during treatment days. A HR increase of 0-10 bpm was detected which was frequently accompanied with corresponding shortening of PR and QT intervals. HR correction with Fridericia’s formula did not reveal consistent QTc changes. Incidence of QTcF outliers was very small. The results suggest that resminostat does not affect the duration of myocardial repolarisation in a consistent manner. At daily doses ≥ 400 mg, unspecific flattening of the T-wave and slight depression of the ST-segment were frequently observed. However, in most cases such findings were already present at baseline. No severe arrhythmias were observed under treatment. Conclusions: Centralised analysis of Phase II ECG data did not reveal a consistent, drug-induced prolongation of the QTc interval. At doses levels ≥ 400 mg, unspecific changes in T-wave morphology and slight ST-segment depression were observed. Administration of resminostat was associated with moderate increases in HR.
Association of Food Allergy and Other Allergic Conditions With Autism Spectrum Disorder in Children
Authors: Guifeng Xu, Linda G. Snetselaar, Jin Jing, Buyun Liu, Lane Strathearn, Wei Bao
Journal: JAMA Network Open (2018)

IMPORTANCEThe prevalence of autism spectrum disorder (ASD) in US children has increased during the past decades.Immunologic dysfunction has recently emerged as a factor associated with ASD.Although children with ASD are more likely to have gastrointestinal disorders, little is known about the association between food allergy and ASD.OBJECTIVE To examine the association of food allergy and other allergic conditions with ASD in US children.DESIGN, SETTING, AND PARTICIPANTS This population-based, cross-sectional study used data from the National Health Interview Survey collected between 1997 and 2016.The data analysis was performed in 2018.All eligible children aged 3 to 17 years were included.Food allergy, respiratory allergy, and skin allergy were defined based on an affirmative response in the questionnaire by a parent or guardian.MAIN OUTCOMES AND MEASURES Reported ASD diagnosed by a physician or other health professional.RESULTS This analysis included 199 520 children (unweighted mean [SD] age, 10.21 [4.41] years; 102 690 boys [51.47%]; 55 476 Hispanic [27.80%], 97 200 non-Hispanic white [48.72%], 30 760 non-Hispanic black [15.42%], and 16 084 non-Hispanic other race [8.06%]).Among them, 8734(weighted prevalence, 4.31%) had food allergy, 24 555 (12.15%) had respiratory allergy, and 19 399 (9.91%) had skin allergy.A diagnosis of ASD was reported in 1868 children (0.95%).The weighted prevalence of reported food, respiratory, and skin allergies was higher in children with ASD (11.25%, 18.73%, and 16.81%, respectively) compared with children without ASD (4.25%, 12.08%, and 9.84%, respectively).In analyses adjusting for age, sex, race/ethnicity, family highest education level, family income level, geographical region, and mutual adjustment for other allergic conditions, the associations between allergic conditions and ASD remained significant.The odds ratio (OR) of ASD increased in association with food allergy (OR, 2.29; 95% CI, 1.87-2.81),respiratory allergy (OR, 1.28; 95% CI, 1.10-1.50),and skin allergy (OR, 1.50; 95% CI, 1.28-1.77)when comparing children with these conditions and those without. CONCLUSIONS AND RELEVANCEIn a nationally representative sample of US children, a significant and positive association of common allergic conditions, in particular food allergy, with ASD was found.Further investigation is warranted to elucidate the causality and underlying mechanisms.
CANKADO PRO-React: E-health solution with dynamic symptom questionnaires and automated recommendations for cancer patients.
Authors: Timo Schinkothe, Susan Praveen, Abhishek Lal, Baiju Rahman
Journal: Journal of Clinical Oncology (2018)

7 Background: It is proven that the online documentation and transmission of symptoms can prolong the overall survival of cancer patients. Recent studies have shown that this advantage exists both in conventional chemotherapy and in oral therapy.Current implementations require a healthcare professional who monitors the data online. In most centers, such kind of human resources is not available except in clinical trials. It was therefore the goal of this project to develop an eHealth procedure, in which no permanent online observation is necessary. Methods: PRO-React, a symptom-based automated feedback or advice feature is integrated into the eHealth platform CANKADO. In the online settings, physician activates medication plans for his patients, documents drug-taking and sets reminders for the patient of future intake times. PRO-React assists the patients daily in global health documentation and dynamic symptom questionnaires. A built-in automated analysis brings forth suitable recommendations for patients like discuss with the physician, visit the physician immediately, visit directly or go to ER. The patient reported outcomes are shared in real-time with the physicians. Results: Trials are ongoing. Interim analysis is planed for January 2018. Results will be presented at the conference. Conclusions: PRO-React helps in the dynamic recognition of events with minimal daily documentation from the patients as well as assist in reacting to the needs of the patients. It also circumvents the need of a mediator group like nurses and thereby increase compliance and improve the doctor-patient-relationship leading to decreased mortality and higher patient satisfaction. PRO-React is available for routine care but also included into several multi-center trials.
Abstract 16784: Incidence of Cerebral Infarction is Relatively Low in Japanses Patients With Severe Carotid Sclerosis
Authors: Takanobu Tomaru, Takumi Matsubara, Erika Matsubara
Journal: Circulation (2015)

There have been few reports on prognosis of severe carotid sclerosis(SCS) in association with other cardiovascular disease(CVD).Then we evaluated new development or recurrence of cerebral infarction(CI) (Methods) Severe carotid sclerosis was diagnosed by carotid ultrasonography, and plaque score(PS) was calculated by summation of max thickness of each plaque. The 468 patients with severe carotid sclerosis(SCS: PS &gt;10)were studied and compared those with 262 patients with mild carotid sclerosis(MCS: PS 5). Patients with significant carotid stenosis (’50% in diameter)were excluded. We evaluated hypertension, diabetes mellitus, dyslipidemia and smoking history as risk factors for arteriosclerosis. (Results) In patients with SCS, mean age was 74.7±9.2(mean±SD), and mean PS was13.8. Cerebral infarction(CI) was observed in 114 patients(24.3%). Cardiovascular disease including peripheral artery disease was observed in 158(33.8 %), and coronary artery disease(CAD) only was observed in 124 (26.4 %). In patients with MCS, mean age was 69.5±8.6, and mean PS was 3.82. CI was observed in 28 patients(10.69%)(P 0.0001 vs SCS)Cardiovascular disease was observed in 26 patients(9.92%),and coronary artery disease(CAD) only was observed in 20(7.63%)(P 0001 vs SCS) . In 3 year follow up, CI developed in 13 (2.78%) out of 468 with SCS, and in 4(1.53%) out of 262 patients with MCS. Antiplatelet therapy had been done in 48% of patients with SCS and in 12% of MCS. There was no difference in percentage of antiplatelet therapy between patients with new CI and those without. All patients who developed CI had other cardiovascular disease. Mean number of RF was 2.7±1.0 in patients who developed CI and 2.5±0.9 in those who did not. Conclusions. Incidence of CAD or CI was greater in patients with SCS than in those with MCS. At 3 year follow up of patients with CS, CI did develop more commonly in patients with SCS than in those with MCS, but the difference was not significant. When patient has not severe carotid stenosis, risk of new development or recurrence of CI is very low in Japanese patients with SCS. Presence of poly vascular lesions may be major risk for CI.
Accurate authentication of Dendrobium officinale and its closely related species by comparative analysis of complete plastomes
Authors: Shuying Zhu, Zhitao Niu, Qingyun Xue, Hui Wang, Xuezhu Xie, Xiaoyu Ding
Journal: Acta Pharmaceutica Sinica B (2018)

Owing to its great medicinal and ornamental values, Dendrobium officinale is frequently adulterated with other Dendrobium species on the market. Unfortunately, the utilization of the common DNA markers ITS, ITS2, and matK+rbcL is unable to distinguish D. officinale from 5 closely related species of it (D. tosaense, D. shixingense, D. flexicaule, D. scoriarum and D. aduncum). Here, we compared 63 Dendrobium plastomes comprising 40 newly sequenced plastomes of the 6 species and 23 previously published plastomes. The plastomes of D. officinale and its closely related species were shown to have conserved genome structure and gene content. Comparative analyses revealed that small single copy region contained higher variation than large single copy and inverted repeat regions, which was mainly attributed to the loss/retention of ndh genes. Furthermore, the intraspecific sequence variability among different Dendrobium species was shown to be diversified, which necessitates a cautious evaluation of genetic markers specific for different Dendrobium species. By evaluating the maximum likelihood trees inferred from different datasets, we found that the complete plastome sequence dataset had the highest discriminatory power for D. officinale and its closely related species, indicating that complete plastome sequences can be used to accurately authenticate Dendrobium species.