tbuckley/cabot-search huggingface dataset:
Abstract P329: Neighborhood Social Cohesion Partially Mediates the Association Between Seeing People Walk and Leisure-Time Walking in Latino Adults
Authors: Rosenda Murillo, Shreya Desai, Layton M Reesor, Daphne C Hernandez
Journal: Circulation (2019)

Introduction: Higher frequency of seeing others exercise is associated with higher leisure-time (LT) physical activity. However, few studies have examined the association between frequency of seeing people walk within sight of home and LT walking among Latino adults. Moreover, the extent to which neighborhood social cohesion mediates the relationship between seeing people walk and LT walking is unknown. We examined the association between frequency of seeing people walk and LT walking, and tested whether neighborhood social cohesion mediated this association. Hypothesis: We hypothesized that higher frequency of seeing people walk within sight of home would be associated with higher LT walking, and that neighborhood social cohesion would mediate this association. Methods: We used cross-sectional data from 4,756 NHIS 2015 Latino participants aged 18+ years. Logistic regression models were used to estimate the association between frequency of seeing people walk (every day, every 2-3 days, and once a week versus less than once a week) and LT walking level (high and medium versus low). Models were adjusted for age, sex, education, and acculturation proxies (based on nativity, years living in the US). Indirect effects were assessed using bootstrap methods outlined by Preacher and Hayes, to quantify the extent to which neighborhood social cohesion mediates the association of seeing people walk with LT walking. Results: In adjusted models, those seeing people walk every day, and about once per week were significantly more likely to engage in medium levels of LT walking, relative to low (Odds Ratio [OR]: 2.07; 95% Confidence Interval [CI]: 1.40, 3.06, and OR: 1.96; 95% CI: (1.15, 3.34), respectively). Individuals seeing people walk every day and every 2-3 days were more likely to engage in high levels of LT walking (OR: 2.79; 95% CI: 2.02, 3.85, and OR: 1.98; 95% CI: (1.28, 3.07), respectively). The direct effects of seeing people walk every day ( b= 0.06, CI [0.02, 0.11]), every 2-3 days ( b= 0.07, CI [0.00, 0.14]), and once a week ( b= 0.11, CI [0.03, 0.18]), on medium levels of LT walking were significant. The direct effects of seeing people walk every day ( b= 0.10, CI [0.06, 0.13]), and every 2-3 days ( b= 0.05, CI [0.00, 0.10]) on high levels of LT walking were significant. Indirect effects indicate that neighborhood social cohesion was only a significant mediator of the association between seeing people walk every day on medium levels of LT walking ( b =0.004, CI [0.00, 0.01]), accounting for 6% of the total effect of seeing people walk every day on LT walking ( b= 0.07, CI [0.01,0.14]). Conclusions: These findings suggest that higher neighborhood social cohesion may account for a portion of the contribution of frequency of seeing people walk within sight of home on LT walking among Latino adults. However, the mediation results suggest that other factors may be more pertinent.
Publisher Correction: Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction
Authors: Sarah A. Dick, Jillian A. Macklin, Sara Nejat, Abdul Momen, Xavier Clemente-Casares, Marwan G. Althagafi, Jinmiao Chen, Crystal Kantores, Siyavash Hosseinzadeh, Laura Aronoff, Anthony Wong, Rysa Zaman, Iulia Barbu, Rickvinder Besla, Kory J. Lavine, Babak Razani, Florent Ginhoux, Mansoor Husain, Myron I. Cybulsky, Clinton S. Robbins, Slava Epelman
Journal: Nature Immunology (2019)
Changes in the Risk of Reaching Multiple Sclerosis Disability Milestones In Recent Decades
Authors: Omid Beiki, Paolo Frumento, Matteo Bottai, Ali Manouchehrinia, Jan Hillert
Journal: JAMA Neurology (2019)

Clinicians' experience and findings from recent natural history studies suggest that multiple sclerosis (MS) may now be running a more slowly progressing course than before.To investigate whether the risk of reaching MS disability milestones has changed over the last decade in Sweden.A nationwide population-based retrospective cohort study. By April 2017, 12 512 patients with available information on demographics, MS phenotype, and date of MS onset and diagnosis were registered in the Swedish MS Registry of which 7331 patients with at least 2 recorded Expanded Disability Status Scale scores (EDSS) and diagnosed between January 1995 and December 2010 were included. No further exclusion criteria were applied. Patients were followed up until December 2016 with a median duration follow-up of 8.5 (interquartile range, 4.7-13.8) years. Statistical analysis began in April 2017.Patients were followed up from MS onset date to the date of sustained EDSS 3.0, 4.0, and 6.0. To handle interval-censored observations, a Weibull model was fit, and the change in the risk of EDSS 3.0, 4.0, and 6.0 over calendar years was estimated and hazard ratios (HRs) with corresponding CIs were calculated.Of 7331 patients, 5196 (70.9%) were women, and the mean (SD) age at diagnosis was 38.3 (11.7) years. Adjusting for sex, number of clinic visits, diagnostic delay, and onset age, a 3% decrease per calendar year of diagnosis for the risk of sustained EDSS 3.0 (HR, 0.97; 95% CI, 0.96-0.97), a 6% decrease for the risk of EDSS 4.0 (HR, 0.94; 95% CI, 0.93-0.95), and a 7% decrease for the risk of EDSS 6.0 (HR, 0.93; 95% CI, 0.91-0.94) among patients with relapsing-onset MS was found. The trends were not significant for patients with progressive-onset MS (EDSS 3.0: HR, 1.01; 95% CI, 0.98-1.03; EDSS 4.0: HR, 1.00; 95% CI, 0.98-1.02; EDSS 6.0: HR, 1.00; 95% CI, 0.98-1.02).Risk of reaching major disability milestones has significantly decreased over the last decade in patients with relapsing-onset MS in Sweden. Several factors could potentially be responsible for this observation. However, given that no change was seen in disability accrual of patients with progressive-onset MS and the absence of efficacious treatment option in this group, increased use of more efficacious disease-modifying treatments could be a possible driver of this change.
Subgroup analysis from JAVELIN Renal 101: Outcomes for avelumab plus axitinib (A + Ax) versus sunitinib (S) in advanced renal cell carcinoma (aRCC).
Authors: Toni K. Choueiri, Robert J. Motzer, Matthew T. Campbell, Boris Y. Alekseev, Motohide Uemura, Christian K. Kollmannsberger, Gwenaelle Gravis, Georg A. Bjarnason, Howard Gurney, Jinsoo Chung, John B. A. G. Haanen, Brian I. Rini, James M. G. Larkin, Manuela Schmidinger, Franco Nole, Aleksander Chudnovsky, Bo Huang, Subramanian Hariharan, Alessandra di Pietro, Laurence Albiges
Journal: Journal of Clinical Oncology (2019)

544 Background: In the ongoing phase 3 JAVELIN Renal 101 trial, progression-free survival (PFS) was longer (median, 13.8 vs 8.4 mo; hazard ratio, 0.69; p=0.0001) and the objective response rate (ORR) was higher (51% vs 26%) with A + Ax vs S in patients with previously untreated aRCC. Here we report outcomes from an analysis of several prespecified subgroups. Methods: Patients were randomized 1:1 to receive A (10 mg/kg) IV every 2 weeks + Ax (5 mg) PO twice daily or S (50 mg) PO once daily for 4 wk (6-wk cycle). Primary and key secondary endpoints were PFS per independent review committee (IRC; RECIST v1.1) and OS in patients with PD-L1+ tumors (≥1% of immune cells) and in patients irrespective of PD-L1 expression; other secondary endpoints included OR per IRC (RECIST v1.1). Results: A total of 886 patients were randomized; 560 (63%) had PD-L1+ tumors. At data cut-off (Jun 2018), median follow-up was 12.0 vs 11.5 mo for A + Ax vs S groups. The table shows PFS and ORR by MSKCC and IMDC risk groups (F, favorable; I, intermediate; P, poor) and PD-L1 subgroup. Similar results for prognostic risk were seen in patients with PD-L1+ tumors. Outcome data (including PFS2) for additional clinical subgroups by baseline demographics and features will be presented. Clinical trial information: NCT02684006. Conclusions: A + Ax demonstrated PFS and OR benefit across all prognostic risk groups and PD-L1 subgroups vs S in aRCC.[Table: see text]
Estimating neoplasia detection rate (NDR) in patients with Barrett’s oesophagus based on index endoscopy: a systematic review and meta-analysis
Authors: Sravanthi Parasa, Madhav Desai, Anusha Vittal, Viveksandeep T Chandrasekar, Asad Pervez, Kevin F Kennedy, Neil Gupta, Nicholas J Shaheen, Prateek Sharma
Journal: Gut (2019)

Background Biopsies are obtained to confirm intestinal metaplasia and rule out prevalent dysplasia and cancer when Barrett’s oesophagus (BE) is detected at index upper endoscopy (oesophagogastroduodenoscopy [EGD]). Aim The purpose of this systematic review was to obtain summary estimates of the prevalence of high-grade dysplasia (HGD) and oesophageal adenocarcinoma (EAC) associated with BE during index EGD for chronic GERD symptoms, defined as neoplasia detection rate (NDR) which could be used as a quality measure. Methods An extensive search was performed within PUBMED, EMBASE and the Cochrane Library databases to identify studies in which patients underwent index endoscopy for the evaluation of the presence of BE. Two reviewers independently evaluated both the study eligibility and methodological quality and data extraction. A random-effects model (REM) based on the binomial distribution was used to calculate the pooled effects of the prevalence of BE-associated dysplasia and EAC. Results For the calculation of dysplasia and EAC prevalence rates, a total of 11 studies with 10 632 patients met the inclusion criteria including 80.4% men with a mean age of 58.7 years and average BE length of 3.5 cm. The pooled prevalence of EAC, HGD and LGD was 3%(95% CI 2 to 5, 9 studies: 396/10 539 patients), 3%(95% CI 2 to 5 [REM], 9 studies: 388/10 539 patients) and 10%(95% CI 7 to 15 [REM], 10 studies: 907/8945 patients), respectively. For NDR, that is, the pooled prevalence of HGD/EAC was 7%(95% CI 4 to 10 [REM], 10 studies: 795/10 632 patients). Conclusion NDR is approximately 4% and could be used as a quality measure.
The prognostic value of FOXA1 expression in prostatectomy specimens for patients undergoing salvage radiation therapy.
Authors: Rafi Kabarriti, Hongying Huang, Nitin Ohri, Jidong Shan, Yinghui Song, Nima Tishbi, Shyamal Patel, Daniel Mark, Reza Ghavamian, Mark Schoenberg, Shalom Kalnicki, Chandan Guha, Madhur Garg
Journal: Journal of Clinical Oncology (2015)

e16129 Background: In this study, we evaluate the prognostic value of Forkhead box protein A1 (FOXA1), a pioneer transcription factor, Immunohistochemistry staining in a cohort of prostate cancer patients that have undergone salvage radiation therapy (SRT) after failing radical prostatectomy (RP). Methods: We reviewed an institutional database and identified all prostate cancer patients who were treated with SRT between the years 2004 and 2008 and had pathology slides available for IHC. Disease characteristics, treatment information, and clinical outcomes data were tabulated for each patient. Paraffin embedded prostatectomy tissue slides were stained with FOXA1 antibody using immunohistochemistry. The expression of FOXA1 in each sample were scored by a single GU pathologist and assigned a proportion score (PS) representing the number of positively stained tumor cells (0, none; 1, < 1/100; 2, 1/100 to 1/10; 3, 1/10 to 1/3; 4, 1/3; to 2/3; and 5, > 2/3), as well as an intensity score (IS) representing the average intensity of the positive tumor cells (0, none; 1, weak, 2, intermediate; and 3, strong). These two scores were combined to yield a total score (TS), which ranged from 0 to 8. Kaplan-meier curves were generated to depict actuarial rates of freedom from biochemical recurrence and freedom from distant metastasis for patients with low ( < 6) and high ( ≥ 7) TS. Comparisons were made using logrank testing. Results: Twenty-three patients met eligibility criteria for this analysis. TS was ≤ 6 in 7 patients, 7 in 8 patients, and 8 in 8 patients. With a median follow-up time of 85 months after SRT, 13 biochemical recurrences occurred, and 5 patients developed distant metastases. High TS was associated with inferior freedom from biochemical recurrence (5-year rates 31% v. 86%) and inferior freedom from distant metastasis (5-year rates 68% v. 100%), though these associations approached but did not reach statistical significance. Conclusions: FOXA1 expression levels on prostatectomy specimens may be a valuable prognostic factor for subsequent clinical outcomes. Future studies with a larger sample size should investigate the value of FOXA1 expression and how these results may be used to personalize therapy.
Re-examining an old trend: The association of human papillomavirus and bladder cancer.
Authors: Lael Suzanne Reinstatler, Kevin Shee, Kristian D. Stensland, Lawrence Dagrosa, John D. Seigne, Einar F. Sverrisson
Journal: Journal of Clinical Oncology (2019)

362 Background: The Human Papilloma Virus (HPV) is a recognized carcinogenic factor. Previous studies have shown a possible association between HPV and bladder cancer, however HPV serology has not been reported. In this study, we assessed the correlation between bladder cancer and HPV positive serology. Methods: Using NHANES, a large nationally-representative population-based survey, we gathered clinical and demographic data on all patients with a diagnosis of bladder cancer over from 2007-2010 and analyzed their HPV serology status. We assessed the effects of positive serologic results for HPV18, HPV16, HPV11, and HPV6 on the rates of bladder cancer diagnosis. Results: Over the four-year period there was a weighted population of 155,650,000 Americans. The prevalence of HPV positive serology was as follows: HPV18–5.5%, HPV16–13.2%, HPV11–6.4%, HPV6–17.4%. There were 443,948 bladder cancer cases. Among cases there was a higher prevalence of male gender (80% vs. 53%, p = 0.0056), Caucasian race (93% vs. 66%, p = 0.001), and HPV6 positive serology (18.1% vs. 17.6%, p = 0.0005). There was no difference among the other three HPV types. On logistic regression controlling for race, gender, and smoking status, increasing body weight (OR 1.01, p &lt; 0.0001) and HPV6 positivity (OR 1.9, p &lt; 0.0001) were associated with increased odds of bladder cancer diagnosis while HPV11 positivity (OR 0.23, p &lt; 0.0001) was associated with a decreased odds of bladder cancer diagnosis. Conclusions: Prior research has shown that there is a relationship between HPV and bladder cancer, but this relationship has previously been incompletely defined. In this large, nationally representative database, we describe a significant association of HPV6 positive serology with a diagnosis of bladder cancer. This finding is striking and might affect future investigation into the pathophysiologic basis of this relationship.
Ecosystem Function and Services of Aquatic Predators in the Anthropocene
Authors: Neil Hammerschlag, Oswald J. Schmitz, Alexander S. Flecker, Kevin D. Lafferty, Andrew Sih, Trisha B. Atwood, Austin J. Gallagher, Duncan J. Irschick, Rachel Skubel, Steven J. Cooke
Journal: Trends in Ecology & Evolution (2019)
Genome-Wide RNAi Screen Identifies PMPCB as a Therapeutic Vulnerability in EpCAM+ Hepatocellular Carcinoma
Authors: Atsushi Takai, Hien Dang, Naoki Oishi, Subreen Khatib, Sean P. Martin, Dana A. Dominguez, Ji Luo, Rachel Bagni, Xiaolin Wu, Katie Powell, Qing-Hai Ye, Hu-Liang Jia, Lun-Xiu Qin, Jinqiu Chen, Gary A. Mitchell, Xiaoling Luo, Snorri S. Thorgeirsson, Xin Wei Wang
Journal: Cancer Research (2019)

Hepatocellular carcinoma (HCC) is a genetically heterogeneous disease for which a dominant actionable molecular driver has not been identified. Patients with the stem cell-like EpCAM+AFP+ HCC subtype have poor prognosis. Here, we performed a genome-wide RNAi screen to identify genes with a synthetic lethal interaction with EpCAM as a potential therapeutic target for the EpCAM+AFP+ HCC subtype. We identified 26 candidate genes linked to EpCAM/Wnt/β-catenin signaling and HCC cell growth. We further characterized the top candidate PMPCB, which plays a role in mitochondrial protein processing, as a bona fide target for EpCAM+ HCC. PMPCB blockage suppressed EpCAM expression and Wnt/β-catenin signaling via mitochondria-related reactive oxygen species production and FOXO activities, resulting in apoptosis and tumor suppression. These results indicate that a synthetic lethality screen is a viable strategy to identify actionable drivers of HCC and identify PMPCB as a therapeutically vulnerable gene in EpCAM+ HCC subpopulations. SIGNIFICANCE: This study identifies PMPCB as critical to mitochondrial homeostasis and a synthetic lethal candidate that selectively kills highly resistant EpCAM+ HCC tumors by inactivating the Wnt/β-catenin signaling pathway.
Effects of zolpidem on sleep parameters in patients with cirrhosis and sleep disturbances: A randomized, placebo-controlled trial
Authors: Manoj Kumar Sharma, Sumeet Kainth, Sachin Kumar, Ankit Bhardwaj, Hemant Kumar Agarwal, Rakhi Maiwall, Kapil Dev Jamwal, Saggere Muralikrishna Shasthry, Ankur Jindal, Ashok Choudhary, Lovkesh Anand, Rajender Mal Dhamija, Guresh Kumar, Barjesh Chander Sharma, Shiv Kumar Sarin
Journal: Clinical and Molecular Hepatology (2019)

The aim of this study was to study the efficacy and safety of zolpidem for sleep disturbances in patients with cirrhosis.Fifty-two Child-Turcotte-Pugh (CTP) class A or B cirrhotics with Pittsburgh Sleep Quality Index >5 were randomized to either zolpidem 5 mg daily (n=26) or placebo (n=26) for 4 weeks.The therapy of 4 weeks was completed by 23 patients receiving zolpidem (3 stopped treatment due to excessive daytime drowsiness) and 24 receiving placebo (2 refused to continue the study). In the zolpidem group, after 4 weeks of therapy, there was significant increase in total sleep time (TST) and sleep efficiency compared to baseline and improvement in polysomnographic parameters of sleep initiation and maintenance (i.e., decrease in sleep latency time, decrease in wake time, and decreases in number of arousals and periodic limbs movements per hour of sleep), without any significant change in sleep architecture.Four weeks of 5 mg daily zolpidem in CTP class A or B cirrhosis patients with insomnia led to significant increases in TST and sleep efficiency and improvement in polysomnographic parameters of sleep initiation and maintenance without any significant change in sleep architecture.
Abstract 230: Humoral Immune Response Against <i>Trypanosoma</i> c <i>ruzi</i> Infection Using Plasmid DNA Immunotherapy in the Experimental Canine Model of Chagas Disease
Authors: Silvia C Carrillo-Sanchez, Mariana Martinez-Cruz, Olivia Rodriguez-Morales, Minerva Arce-Fonseca
Journal: Circulation Research (2016)

Chagas disease or American trypanosomiasis is a parasitic chronic infectious disease that is one of the major causes of heart disease in Latin America. However, this disease is now present in non-endemic regions such as Canada, the United States of America, Europe and is one of the most important emerging health problems. The World Health Organization reported recently that approximately 8 million people are infected worldwide. The pBCSP and pBCSSP4 plasmids were evaluated as DNA-antigens to promote the generation of antibodies against Trypanosoma cruzi as an option of immunotherapy in a canine model to protect against Chagas disease. We worked with 30 dogs, which were divided into 5 experimental groups, dogs from four of these groups were infected with 3,500 parasites / kg body weight (H8 strain) and at 15 days post infection were treated thrice at 2-week intervals with 500 micrograms of pBCSP and pBCSSP4 plasmids, separately and combined; dogs from control groups were treated with cloning empty vector and saline solution. Specific IgG antibodies detection by ELISA showed that the plasmid-DNA treatment generated a response of increased total IgG significantly with respect to the status preimmune. A significant increase of IgG after the two last doses was generated by the pBCSP plasmid treatment, whereas that the pBCSSP4 plasmid treatment induced a significant IgG rise only after the third dose of the immunotherapy. The combination of both plasmids showed an increase similar to that induced by the infection alone. An unpolarized Th1 or Th2 response after immunotherapy or infection was observed by a similar IgG1 or IgG2 antibodies detection, respectively. This shows that therapy with DNA recombinant plasmids generates a specific humoral immune response against T. cruzi in dogs with experimental Chagas disease.
Inhibition of Sirt-1 Alleviates Acute and Chronic Graft-Versus-Host-Disease While Preserving Graft-Versus-Leukemia Effect
Authors: Anusara Daenthanasanmak, Supinya Iamsawat, Hung D Nguyen, Shikhar Mehrotra, Xue-Zhong Yu
Journal: Blood (2017)
Serial ctDNA tracking reveals clonal evolution dynamics in advanced urothelial carcinoma (UC).
Authors: Dario Martin Villamar, Kristin Sedgwick Price, Rebecca Nagy, Scott T. Tagawa, Ana M. Molina, David M. Nanus, Petros Grivas, Guru Sonpavde, Nicholas J. Vogelzang, Bishoy Morris Faltas
Journal: Journal of Clinical Oncology (2019)

401 Background: UC is characterized by extensive genomic heterogeneity. Access to genomic DNA from all metastatic lesions is infeasible. Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) may recapitulate heterogeneity and offer an opportunity for continuous tracking of tumor evolution. Methods: We analyzed a cohort of advanced UC patients with serial (2 time points) ctDNA NGS using Guardant360. Restaging scans were examined to determine the relationship between ctDNA dynamics and radiologic progression. We performed whole exome sequencing (WES) of a subset of the corresponding tumors to define patterns of genomic heterogeneity. Results: NGS was performed on 214 individual ctDNA samples from 78 advanced UC patients (61 M, 17 F). A minimum of 2 serial ctDNA tests per patient (range 2-8) were collected over an average 21.5 (2-108) weeks between samples. Molecular alterations (MAs) were identified in 188 (88%) of samples with a mean of 4.3 alterations (1-31) per sample. 184 (85%) samples harbored SNVs, 30 (14%) harbored indels and 36 CNVs (17%). Most commonly mutated genes were TP53 (18%), ARID1A, NF1 (4.5% each ), EGFR (3.5%), FGFR3 (3.4%), ERBB2 and PIK3CA (3.4% each ). The most frequently amplified genes were ERRB2 and CCNE1. Serial analysis of maximum variant allele frequency (mVAF) revealed a mean 7.5-fold change between 1 st and 2 nd and a 6-fold change between 2 nd and 3 rd ctDNA samples. Interestingly, the mean rate of mVAF fold change/week was stable between serial testing time points (0.35, 0.32 p = 0.7). We observed that patients with higher initial mVAF ( &gt; 3%) experienced a significantly larger mean fold decrease compared to patients with initial mVAF below this threshold (p = 0.008). In patients with available restaging scans timed with ctDNA testing, all patients with radiologic progression exhibited increasing mVAF (mean: 8-fold). Interestingly, ctDNA identified several clinically-significant somatic MAs not present on matching tumor WES including PIK3CA (T727R, M1043I), TP53 (Q331*, P190L), RB1 (R556*, Q257*), APC (D2527H), and BRCA2 (P2804S).WES is ongoing in more patients. Conclusions: ctDNA sequencing enables dynamic monitoring of therapy-driven clonal evolution patterns of advanced UC.