tbuckley/cabot-search huggingface dataset:
Global elimination of viral hepatitis and hepatocellular carcinoma: opportunities and challenges
Authors: Chien-Jen Chen
Journal: Gut (2018)

The most common causes of hepatitis worldwide is a group of viruses known as hepatitis A, B, C, D and E virus. Most deaths from viral hepatitis are due to hepatitis B and hepatitis C. Globally, an estimated 257 million people were living with HBV and 71 million people were living with HCV, which caused 1.34 million deaths in 2015 comparable with deaths from tuberculosis and exceeding deaths from HIV.1 

Both liver cancer, mostly hepatocellular carcinoma (HCC), and cirrhosis are end-stage clinical outcomes of chronic hepatitis B (CHB) and chronic hepatitis C (CHC).2 HBV and HCV are the main causes of liver cancer worldwide, and liver cancer was the seventh commonly diagnosed cancer and the second common cause of cancer death as reported in GLOBOCAN 2012.3 There was a significant increase in global deaths from liver cancer and cirrhosis from 1990 to 2013 with a 60% increase for liver cancer and a 45% increase for cirrhosis. Such increases are mostly attributable to the increase in infection of HBV and HCV.4 

The incidence of liver cancer and the prevalence of HBV and HCV infection are high in the East, Southeast and Central Asia and the sub-Saharan Africa.1–4 However, the aetiological proportion of liver cancer varies in different countries and regions. HCV is more prevalent in patients with HCC in Japan, North America and Europe, and HBV is more prevalent in patients with HCC in Taiwan, Southeast Asia and China.1 2 Around 75% of global liver cancer cases are caused by chronic HBV and HCV infection,4 and control of viral hepatitis may thus significantly reduce the burden of HCC globally.

The causality of chronic HBV infection to induce HCC was reported in several cross-sectional case-control studies2 and first confirmed by the GECC cohort study in Taiwan,5 …
Neddylation is required for herpes simplex virus type I (HSV-1)-induced early phase interferon-beta production
Authors: Xueying Zhang, Zhenjie Ye, Yujun Pei, Guihua Qiu, Qingyang Wang, Yunlu Xu, Beifen Shen, Jiyan Zhang
Journal: Cellular and Molecular Immunology (2015)

Type I interferons such as interferon-beta (IFN-β) play essential roles in the host innate immune response to herpes simplex virus type I (HSV-1) infection. The transcription of type I interferon genes is controlled by nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF) family members including IRF3. NF-κB activation depends on the phosphorylation of inhibitor of κB (IκB), which triggers its ubiqitination and degradation. It has been reported that neddylation inhibition by a pharmacological agent MLN4924 potently suppresses lipopolysaccharide (LPS)-induced proinflammatory cytokine production with the accumulation of phosphorylated IκBα. However, the role of neddylation in type I interferon expression remains unknown. Here, we report that neddylation inhibition with MLN4924 or upon UBA3 deficiency led to accumulation of phosphorylated IκBα, impaired IκBα degradation, and impaired NF-κB nuclear translocation in the early phase of HSV-1 infection even though phosphorylation and nuclear translocation of IRF3 were not affected. The blockade of NF-κB nuclear translocation by neddylation inhibition becomes less efficient at the later time points of HSV-1 infection. Consequently, HSV-1-induced early phase IFN-β production significantly decreased upon MLN4924 treatment and UBA3 deficiency. NF-κB inhibitor JSH-23 mimicked the effects of neddylation inhibition in the early phase of HSV-1 infection. Moreover, the effects of neddylation inhibition on HSV-1-induced early phase IFN-β production diminished in the presence of NF-κB inhibitor JSH-23. Thus, neddylation contributes to HSV-1-induced early phase IFN-β production through, at least partially, promoting NF-κB activation.
Preventing hamstring injuries in football through enhanced exercise and RTP strategies
Authors: Nick van der Horst
Journal: British Journal of Sports Medicine (2018)

This thesis consisted of seven publications on the prevention of hamstring injuries in male football, targeting primary prevention and return-to-play (RTP) after hamstring injuries.

Hamstring injuries is the number 1 muscle injury in football, and injury rates have been increasing consistently over the last decade.1 Furthermore, hamstring injuries are notorious for their high recurrence rates, leading to prolonged rehabilitation, personal suffering for the player and decreased team performance.

The thesis kicks off with a systematic review on the effect of general exercise programmes for the prevention of football injuries. The first study was a randomised controlled trial investigating …
Abstract 22: Cardiovascular Fat in Women at Midlife: Effects of Race, Overall Adiposity, and Central Adiposity. The SWAN Cardiovascular Fat Ancillary Study
Authors: Carrie L Hanley, Karen Matthews, Maria M Brooks, Imke Janssen, Matthew J Budoff, Akira Sekikawa, Suresh Mulukutla, Samar R El Khoudary
Journal: Circulation (2016)

Background: Racial differences exist in overall (BMI) and central adiposity (abdominal visceral fat (VAT)) measures. Recently, it has been shown that white men have higher volumes of cardiovascular fat (CF) that were found to be greater per increment increase in BMI when compared to black men. It is unknown whether similar racial differences exist in women. We assessed whether CF volumes vary by race and tested the effect modification of race on the associations between adiposity measures and CF among women at midlife, a time period marked with increased cardiovascular risk. Methods: Volumes of CF depots (epicardial fat (EAT), paracardial fat (PAT), total heart fat (TAT), and aortic perivascular fat (PVAT)), BMI, and VAT were examined among participants from the Study of Women’s Health Across the Nation (SWAN) Cardiovascular Fat Ancillary study. Linear regression was used for statistical analyses. All adiposity measures were log-transformed to achieve normality. Results: A total of 543 women (mean age: 50.9 ± 2.9 years; 34% postmenopausal) were included. Women were either white (62%) or black (38%). Significant racial differences existed in volumes of all CF depots with white women having higher volumes compared to black women, after adjusting for age, menopausal status, hypertension, diabetes, and alcohol consumption (all P-values &lt;0.05). These racial differences remained significant after further adjustment for BMI or VAT, with one exception of PAT after adjusting for VAT. Race significantly modified the associations between VAT and EAT (Interaction P-value=0.03) and between BMI and PAT (Interaction P-value=0.01), such that black women had more EAT than white women for every one-increment increase in VAT, while with every one-increment increase in BMI, white women had more PAT than black women. Race-stratified analyses confirmed the effect modification of race on the associations between VAT and EAT (effect size per 1 unit increase in VAT was higher in blacks (β (SE) = 0.62 (0.05) than in whites (β (SE) 0.51 (0.04)) and between BMI and PAT (effect size per 1 unit increase in BMI was higher in whites (β (SE) = 2.56 (0.18) than in blacks (β (SE) 1.92 (0.23)). Conclusions: Racial differences existed in CF volumes in midlife women similar to midlife men. Black women with greater central adiposity had higher EAT volumes than white women, while white women with greater overall adiposity had higher PAT volumes than black women. Future research should evaluate the impacts of these significant racial differences in explaining CVD risk disparity.
A Systematic Review and Meta-Analysis of Proportions of Thrombosis and Bleeding in Patients Receiving Venous Thromboembolism (VTE) Prophylaxis After Orthopedic Surgery (OS). An Update.
Authors: Alejandro Lazo-Langner, Jeff Hawell, Michael J. Kovacs, Philip S Wells, Dimitrios Scarvelis, Melissa Anne Forgie, Marc Rodger
Journal: Blood (2009)
Timing of Renal Support and Outcome of Septic Shock and Acute Respiratory Distress Syndrome. A <i>Post Hoc</i> Analysis of the AKIKI Randomized Clinical Trial
Authors: Stéphane Gaudry, David Hajage, Frédérique Schortgen, Laurent Martin-Lefevre, Charles Verney, Bertrand Pons, Eric Boulet, Alexandre Boyer, Guillaume Chevrel, Nicolas Lerolle, Dorothée Carpentier, Nicolas de Prost, Alexandre Lautrette, Anne Bretagnol, Julien Mayaux, Saad Nseir, Bruno Megarbane, Marina Thirion, Jean-Marie Forel, Julien Maizel, Hodane Yonis, Philippe Markowicz, Guillaume Thiery, Florence Tubach, Jean-Damien Ricard, Didier Dreyfuss
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The optimal strategy for initiation of renal replacement therapy (RRT) in patients with severe acute kidney injury in the context of septic shock and acute respiratory distress syndrome (ARDS) is unknown.To examine the effect of an early compared with a delayed RRT initiation strategy on 60-day mortality according to baseline sepsis status, ARDS status, and severity.Post hoc analysis of the AKIKI (Artificial Kidney Initiation in Kidney Injury) trial.Subgroups were defined according to baseline characteristics: sepsis status (Sepsis-3 definition), ARDS status (Berlin definition), Simplified Acute Physiology Score 3 (SAPS 3), and Sepsis-related Organ Failure Assessment (SOFA). Of 619 patients, 348 (56%) had septic shock and 207 (33%) had ARDS. We found no significant influence of the baseline sepsis status (P = 0.28), baseline ARDS status (P = 0.94), and baseline severity scores (P = 0.77 and P = 0.46 for SAPS 3 and SOFA, respectively) on the comparison of 60-day mortality according to RRT initiation strategy. A delayed RRT initiation strategy allowed 45% of patients with septic shock and 46% of patients with ARDS to escape RRT. Urine output was higher in the delayed group. Renal function recovery occurred earlier with the delayed RRT strategy in patients with septic shock or ARDS (P < 0.001 and P = 0.003, respectively). Time to successful extubation in patients with ARDS was not affected by RRT strategy (P = 0.43).Early RRT initiation strategy was not associated with any improvement of 60-day mortality in patients with severe acute kidney injury and septic shock or ARDS. Unnecessary and potentially risky procedures might often be avoided in these fragile populations. Clinical trial registered with www.clinicaltrials.gov (NCT 01932190).
Safety of cold snare polypectomy for duodenal adenomas in familial adenomatous polyposis: a prospective exploratory study
Authors: Kenta Hamada, Yoji Takeuchi, Hideki Ishikawa, Yasumasa Ezoe, Masamichi Arao, Sho Suzuki, Taro Iwatsubo, Minoru Kato, Yusuke Tonai, Satoki Shichijo, Yasushi Yamasaki, Noriko Matsuura, Hiroko Nakahira, Takashi Kanesaka, Sachiko Yamamoto, Tomofumi Akasaka, Noboru Hanaoka, Koji Higashino, Noriya Uedo, Ryu Ishihara, Hiroyuki Okada, Hiroyasu Iishi
Journal: Endoscopy (2018)

Abstract Background Cold snare polypectomy (CSP) to remove multiple duodenal adenomas (MDAs) in patients with familial adenomatous polyposis (FAP) could be an effective and less invasive method than more extensive surgery. The aim of the present study was to determine the safety of this procedure. Methods This prospective exploratory study included 10 consecutive patients with FAP and MDAs who underwent CSP for as many as 50 duodenal adenomas. The primary outcome was the incidence of severe adverse events. Results 10 patients were enrolled and underwent 332 CSPs from June 2016 to January 2017. The median procedure time was 33 minutes (range 25 – 53), and the median number of polyps removed during a single session was 35 (range 10 – 50). Most of the removed polyps were ≤ 10 mm. None of the 10 patients experienced a severe adverse event. One patient developed arterial bleeding during the procedure, but it was easily managed using hemoclips. Conclusions CSP for MDAs in patients with FAP was safe. The long-term efficacy of this procedure should be investigated.
PD-1 Blockade with Pembrolizumab in Relapsed Low Grade Non-Hodgkin Lymphoma
Authors: Wei Ding, Betsy Laplant, Thomas E Witzig, Patrick B Johnston, Joseph P Colgan, Karen L Rech, Jose F. Leis, Andrew L Feldman, Rong He, Grzegorz S Nowakowski, Erik J Asmus, David J Inwards, Luis Porrata, Thomas M Habermann, Yi Lin, Gita Thanarajasingam, Nabila Nora Bennani, Craig B. Reeder, Donald Northfelt, Jeanne Palmer, Prashant Kapoor, David S Viswanatha, Stephen M Ansell
Journal: Blood (2017)
Abstract 06: Long-term Blood Pressure Variability Throughout Young Adulthood and Mid-life Cerebrovascular Structure and Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Yuichiro Yano, Norrina Allen, Guray Erus, Laura Colangelo, Deborah Levine, Stephen Sidney, R. Nick Bryan, Anthony Viera, Jared Reis, Daichi Shimbo, Pamela Schreiner, Hongyan Ning, Yacob Tedla, Kiang Liu, Philip Greenland, Donald Lloyd-Jones, Lenore Launer
Journal: Circulation (2016)

Introduction: In addition to average blood pressure (BP) values, BP variability has been suggested to be associated with lower cognitive function. It is unclear how long-term BP variability throughout young adulthood is associated with cerebrovascular structure (e.g., hippocampus) and function in midlife. Methods: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which recruited healthy young adults ages 18 to 30 years (mean age 25 years) in 1985-1986, we assessed average BP over visits and visit-to visit BP variability (average real variability [ARV], defined as the absolute differences of BP between successive BP measurements) during 25-year follow-up (8 visits). Normal brain volume, abnormal brain volume, brain integrity assessed by fractional anisotropy, and cerebral blood flow were calculated by 3-Tesla MRI at the Year 25 follow-up (n=557, 52.2 % women, and 34.5 % African Americans). Results: For the 557 participants, mean ARV of SBP was 7.8±3.1 mm Hg. Higher ARV of SBP was associated with lower normal total brain volume, gray matter, and hippocampus after adjustment for covariates including intracranial volume and average BP during follow-up (Table). Higher average SBP during follow-up was associated with higher abnormal brain volume and lower integrity in the whole brain and the white matter, and lower blood flow in the hippocampus. Conclusions: Long-term visit-to-visit BP variability for 25 years beginning in young adulthood was associated with midlife cerebrovascular structural and functional alterations, independent of average BP during follow-up. Focusing not only on BP values alone but also on visit-to-visit BPV may be important to identify younger adults who may be at risk for developing lower cognitive function later.
Abstract 18564: Ischemic Post-conditioning Enhances Induuction of Cardioprotective Heat Shock Protein 72 in Patients With Acute Myocardial Infarction
Authors: Toshiharu Takeuchi, Yuya Kitani, Akiho Minoshima, Naoyuki Hasebe
Journal: Circulation (2017)

Background:  Ischemic post-conditioning (iPoc) is known to reduce cardiac reperfusion injury in patients with acute myocardial infarction (AMI). Heat shock protein (HSP) 72 is an inducible cardioprotective factor in ischemia reperfusion events. However, the mechanism of cardioprotective effects of iPoc and its relation to HSP72 have not been fully clarified.   Methods:  The consecutive 96 AMI patients with single vessel occlusion, gained successful reperfusion, were recruited. 41 patients with iPoc (iPoc(+)) underwent four cycles of 60s inflation and 30s deflation of the angioplasty balloon. Both iPoC(+) and iPoC(-) groups were divided into two groups, with prodromal angina (PA(+)) and without (PA(-)). HSP 72 expression levels in white blood cells were measured by flow cytometry until 48 hours after reperfusion.   Results:  There were no significant differences in risk factors, time to reperfusion, collateral development, left ventricular ejection fraction, and area at risk among four groups. However, the peak CK-MB levels in PA(+) groups were significantly smaller than iPoC(-)PA(-) (iPoC(+)PA(+): 270±177 IU/l, iPoC(-)PA(+): 171±131 IU/l, iPoC(-)PA(-): 338±264 IU/l, p   Conclusions:  The iPoc procedure enhanced the levels of HSP72 expression in AMI, particularly in patients without prodromal angina.
Hypothyroidism Due to L-T4 Withdrawal Can Precipitate Optic Neuropathy in Patients with Moderate to Severe Graves' Ophthalmopathy: Report on Two Cases
Authors: Latrofa Francesco, Maria Antonietta Altea, Marino Michele, Menconi Francesca, Leo Marenza, Sisti Eleonora, Maria Antonietta Profilo, Lepri Paola, Nardi Marco, Vitti Paolo, Marcocci Claudio, Rocchi Roberto
Journal: Endocrine Reviews (2014)
Promoting Prevention Under the Affordable Care Act
Authors: Nadia Chait, Sherry Glied
Journal: Annual Review of Public Health (2018)

The Affordable Care Act (ACA) of 2010 placed a substantial emphasis on public health and prevention. Subsequent research on its effects reveals some notable successes and some missteps and offers important lessons for future legislators. The ACA's Prevention and Public Health Fund, intended to give public health budgetary flexibility, provided crucial funding for public health services during the Great Recession but proved highly vulnerable to subsequent budget cuts. Several programs that aimed to increase strategic thinking and planning around public health at the state level have proven to be more enduring, suggesting that the convening authority of the federal government can be a powerful tool for progress, especially when buttressed by some funding. Most important, by expanding insurance and mandating a minimum level of coverage, the ACA both increased access to clinical preventive services and freed up local public health budgets to engage in population health activities.
Tumor targeting aptamers identified by in vivo SELEX
Authors: Jing Mi, Yingmiao Liu, Zahid Rabbani, Zhongguang Yang, Bruce Sullenger, Bryan Clary
Journal: Cancer Research (2008)

4744  Background: Aptamers are single-stranded nucleic acids that can directly inhibit a protein’s function by their high affinity binding and specificity to that targeted protein. Systematic evolution of ligands by exponential enrichment (SELEX) is an iterative selection procedure used to identify oligonucleotides (aptamer) with desired protein or complex targets, such as cells, in vitro. Given the current limitations of regional and systemic treatments of most solid organ malignancies, we seek to develop tumor-targeting agents through a novel in vivo application of SELEX. Methods: SELEX procedure was performed on intrahepatic colon carcinoma-bearing mice by using single-stranded and chemically modified RNA library. To monitor the enrichment of library at various rounds, every two rounds of PCR products starting from round 6 to 14 were cloned and sequenced. We isolated two main families from round 14 by comparing their closely shared sequence, and further characterized their binding affinity and specificity for targeted tumor tissue. Results: (1) In tissue localization experiments, cryostat tissue sections were prepared from tumor-bearing mice and stained with fluorescent-labeled aptamer. High density of fluorescent is mainly localized in the tumor tissue stained with labeled aptamer isolated from round 14, whereas normal tissue including liver, lung, spleen, brain and kidney demonstrated only background autoflourescence. Staining was also absent in tumor tissue exposed to a labeled pool of early round SELEX (control aptamer). (2) In binding affinity assays, membrane protein was extracted from fresh tissue of tumor-bearing mice and incubated with 32P-labeled aptamer in a range of protein concentrations. The fraction of bound RNA was quantified and corrected for nonspecific background binding. After 14 rounds of selection, aptamer displayed significantly increased binding with 50% compare to early round of selection pool with 15%. (3) To further characterize the binding specificity, electrophorectic mobility shift assay was performed on the membrane protein extracted from tumor or liver tissue. In tumor tissue, a single, sharp band was noted with the round 14 RNA probes; in contrast, no binding was noted with the probe derived from early round of selection. In addition, 50× excess unlabeled round 14 probes could compete with labeled probes for binding. No specific binding was found on liver tissue using either labeled or unlabeled round 14 probe or probe derived from early round of selection. Conclusion: These data confirm that SELEX can be successfully used to identify aptamers that bind specifically to complex targets in vivo. We will screen for the aptamer targeted proteins using spectrometry and further characterize their functions in oncogenesis.
Abstract 11414: Comparison of the Cardiovascular and Bleeding Risks in Patients With Acute Myocardial Infarction Newly Treated With Ticagrelor versus Clopidogrel in East Asia: A Nationwide Propensity-matched Cohort Study in Taiwan
Authors: Cheng-Han Lee, Yi-Heng Li, Ching-Lan Cheng, Yea-Huei Kao Yang, Ting-Hsing Chao
Journal: Circulation (2016)

Background: The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor improved clinical outcomes in patients (pts) with acute coronary syndrome compared with clopidogrel. There were few real world data on the efficacy and safety of ticagrelor in East Asians in whom bleeding is a major concern with potent antithrombotic drugs. Methods: We conducted a nationwide population-based cohort study by using 2012 to 2014 Taiwan National Health Insurance Research Database. The 18-month clinical outcomes in pts with acute myocardial infarction (MI) treated with ticagrelor vs. clopidogrel were compared. Overall, we identified 27,339 acute MI pts (mean age 62.2 years, 71% male) who survived 30 days after the acute MI attack and took dual antiplatelet agents. Cohorts of ticagrelor and clopidogrel were 1:8 matched based on propensity score. The primary efficacy endpoints were all-cause death, recurrent MI or ischemic stroke. The safety endpoints consisted of major gastrointestinal (GI) bleeding and intracerebral hemorrhage (ICH). Results: In unmatched cohorts, ticagrelor-treated pts (n = 2,844) were younger with fewer comorbidities than clopidogrel-treated pts (n = 24,495). The 18-month primary efficacy endpoint rate was lower in ticagrelor group (10.1 vs. 18.3%, p &lt; 0.001). In ticagrelor group, the risks of ICH (0.3%) and ICH + GI bleeding (2.9%) were similar to the data reported in the PLATO trial (ICH 0.3% and non-CABG related TIMI major bleeding 2.8%). After propensity matching, we obtained 2,389 ticagrelor users and 19,112 clopidogrel users in the cohort. After adjusting for clinical characteristics, the 18-month primary efficacy endpoint rate was 21% lower in ticagrelor than in clopidogrel group (10.5 vs. 16.0%, adjusted HR, 0.79; 95% CI, 0.68-0.93). The composite safety endpoint rate was not different between ticagrelor and clopidogrel group (3.2 vs. 4.1%, adjusted HR, 1.01; 95% CI, 0.74-1.37). Subgroup analyses show consistent benefits of ticagrelor in old pts (≥ 75 years) and in pts with diabetes, heart failure or previous MI. Conclusions: In the real world acute MI Taiwanese pts, ticagrelor offered better cardiovascular protection than clopidogrel without increasing the major bleeding risk.
P2.01-013 HA-Liposome Nanocarrier Containing CD44 siRNA as a Targeted Chemotherapy to CD44 Related Chemoresistant Non-Small Cell Lung Cancer
Authors: Hyun Koo Kim, Yu Hua Quan, Ji-Young Lim, Byeong Hyeon Choi, Ji-Ho Park, Young Ho Choi
Journal: Journal of Thoracic Oncology (2017)