tbuckley/cabot-search huggingface dataset:
Does vascular occlusion in liver resections predispose to recurrence of malignancy in the liver remnant due to ischemia/reperfusion injury? A comparative retrospective cohort study
Authors: Kassiani Theodoraki, Maria Papadoliopoulou, Zoe Petropoulou, Theodosios Theodosopoulos, Pantelis Vassiliu, Andreas Polydorou, Pantelis Xanthakos, George Fragulidis, Vassilios Smyrniotis, Nikolaos Arkadopoulos
Journal: International Journal of Surgery (2020)
Body Mass Index and Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer
Authors: Giuseppe Floris, François Richard, Anne-Sophie Hamy, Lynn Jongen, Hans Wildiers, Jan Ardui, Kevin Punie, Ann Smeets, Patrick Berteloot, Ignace Vergote, Diane De Croze, Didier Meseure, Anne Salomon, Marick Laé, Fabien Reyal, Elia Biganzoli, Patrick Neven, Christine Desmedt
Journal: JNCI Journal of the National Cancer Institute (2020)

High levels of stromal tumor-infiltrating lymphocytes (sTIL) are associated with increased pathological complete response (pCR) rate and longer survival after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Here, we evaluated the value of sTIL in predicting pCR and explored prognosis in TNBC patients treated with neoadjuvant chemotherapy according to body mass index (BMI).sTIL were scored centrally on pretreatment biopsies from 2 retrospective series of nonunderweight TNBC patients (n = 445). sTIL and BMI were considered as binary (sTIL: <30.0% vs ≥30.0%; BMI: lean vs overweight and obese) and continuous variables. Associations with pCR (ypT0/isN0) were assessed using logistic regression, and associations with event-free survival and overall survival were assessed using Cox regressions.236 (53.0%) patients were lean and 209 (47.0%) overweight and obese. pCR was achieved in 181 of 445 (41.7%) patients. Median sTIL was 11.0%, and 99 of 445 (22.2%) tumors had high sTIL. A statistically significant interaction between sTIL and BMI, considered as categorical or continuous variables, for predicting pCR was observed in the multivariable analysis (Pinteraction = .03 and .04, respectively). High sTIL were statistically significantly associated with pCR in lean (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.10 to 8.56; P < .001) but not in heavier patients (OR = 1.48, 95% CI = 0.75 to 2.91; P = .26) in the multivariable analysis. High sTIL were further associated with increased event-free survival in lean (hazard ratio [HR] = 0.22, 95% CI = 0.08 to 0.62; P = .004) but not in heavier patients (HR = 0.53, 95% CI = 0.26 to 1.08; P = .08). Similar results were obtained for overall survival.BMI is modifying the effect of sTIL on pCR and prognosis in TNBC patients treated with neoadjuvant chemotherapy.
Four interventions for pediatric femoral shaft fractures: Network meta-analysis of randomized trials
Authors: Zhao Chen, Dawei Han, Qingyu Wang, Lianghua Li
Journal: International Journal of Surgery (2020)

Fractures of the pediatric femoral shaft are uncommon, although serious injuries could lead to long-term disability, pain and an impaired quality of life. There are 4 main interventions: cast (C), plate fixation (PF), titanium elastic nail (TEN) and external fixation (EF). However, for pediatric patients under the age of 16, which intervention is the best choice remains a controversial topic. Therefore, a comprehensive network meta-analysis (NMA) is needed to summarize existing studies and to compare the safety and efficacy of the interventions for pediatric femoral shaft fractures. We searched through eight electronic databases (PubMed, Embase, Cochrane, Web of Science, CBM, CNKI, Wangfang, and VIP) for randomized controlled trials of femoral shaft fracture in pediatric patients, which were published until the end of March 2020. We performed a Bayesian NMA to integrate the adverse events and fracture union time of all interventions. Twenty-three randomized controlled trials with a total number of 1627 patients were included in our NMA. Among these patients, 386 patients underwent C, 524 patients underwent PF, 574 patients underwent TEN, and 143 patients underwent EF. In terms of adverse events, C had the lowest infection rates and TEN the second lowest infection rates. TEN also had the lowest anchylosis and malunion rates. In addition, TEN had a lower fracture union time than C, PF and EF. Notably, C showed the weakest effects on reducing malunion rates in pediatric patients. This current study indicated that TEN has potential superior clinical outcomes in pediatric femoral shaft fractures compared to C, PF and PF. However, high-quality large sample RCTs are still needed. I.
Long-Term Outcome and Prognosis Factors of Isolated Aortitis
Authors: Yasmina Ferfar, Sarah Morinet, Olivier Espitia, Christian Agard, Mathieu Vautier, Chloé Comarmond, Anne Claire Desbois, Fanny Domont, Pierre Jean Fouret, Alban Redheuil, Philippe Cluzel, Laurent Chiche, Fabien Koskas, Matthieu Resche-Rigon, Patrice Cacoub, Lucie Biard, David Saadoun
Journal: Circulation (2020)
Evaluating multiple living kidney donor candidates simultaneously is more cost-effective than sequentially
Authors: Steven Habbous, Lianne Barnieh, Scott Klarenbach, Braden Manns, Sisira Sarma, Mehmet A. Begen, Kenneth Litchfield, Krista L. Lentine, Sunita Singh, Amit X. Garg
Journal: Kidney International (2020)
Impaired Stress Myocardial Oxygenation and Not Perfusion Reserve is Associated With Arrhythmic Risk in Hypertrophic Cardiomyopathy: Insights From a Novel Oxygen Sensitive Cardiac Magnetic Resonance Approach
Authors: Betty Raman, Kenneth Chan, Rina Ariga, Masliza Mahmod, Moritz Hundertmark, Sanjay Sivalokanathan, Theodoros D Karamitsos, Joseph Selvanayagam, Aaron Hess, Elizabeth Tunnicliffe, Hugh Watkins, Stefan Neubauer
Journal: Circulation (2019)

In hypertrophic cardiomyopathy (HCM), myocardial ischemia may promote life-threatening ventricular arrhythmias. Blood oxygen level dependent cardiac magnetic resonance (BOLD CMR) detects blunted st...
Necrolytic Acral Erythema in Association With Hypothyroidism
Authors: Ashwin Singh Parihar, Garima Dabas, Dipankar De, Ashwani Sood, Abhiram G. A. Jois, Bishan Dass Radotra, Bhagwant Rai Mittal
Journal: JAMA Dermatology (2020)

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The DisEntangling Chronic Obstructive pulmonary Disease Exacerbations clinical trials NETwork (DECODE-NET): rationale and vision
Authors: Alexander G. Mathioudakis, Pradeesh Sivapalan, Alberto Papi, Jørgen Vestbo
Journal: European Respiratory Journal (2020)

<b>The DisEntangling Chronic Obstructive pulmonary Disease Exacerbations clinical trials NETwork: #DECODE_NET. Vision statement of an emerging, global network aiming to conduct collaborative clinical research on COPD exacerbation management @ERSpublications</b>https://bit.ly/36kISgp
Therapeutic potential of targeting MKK3-p38 axis with Capsaicin for Nasopharyngeal Carcinoma
Authors: Chengyao Chiang, Min Zhang, Dian Wang, Tian Xiao, Lizhi Zhu, Kai Chen, Junrong Huang, Jingying Huang, Jiang Zhu, Li Li, Cheng Chen, Yangchao Chen, Hongyi Hu, Wenqi Jiang, Yongdong Zou, Ting Wang, Duo Zheng
Journal: Theranostics (2020)

Background: Capsaicin is an active compound found in plants of the Capsicum genus; it has a range of therapeutic benefits, including anti-tumor effects. Here we aimed to delineate the inhibitory effects of capsaicin on nasopharyngeal carcinoma (NPC). Methods: The anti-cancer effects of capsaicin were confirmed in NPC cell lines and xenograft mouse models, using CCK-8, clonogenic, wound-healing, transwell migration and invasion assays. Co-immunoprecipitation, western blotting and pull-down assays were used to determine the effects of capsaicin on the MKK3-p38 axis. Cell proliferation and EMT marker expression were monitored in MKK3 knockdown (KD) or over-expression NPC cell lines treated with or without capsaicin. Finally, immunohistochemistry was performed on NPC specimens from NPC patients (n = 132) and the clinical relevance was analyzed. Results: Capsaicin inhibited cell proliferation, mobility and promoted apoptosis in NPC cells. Then we found that capsaicin directly targets p38 for dephosphorylation. As such, MKK3-induced p38 activation was inhibited by capsaicin. Furthermore, we found that capsaicin-induced inhibition of cell motility was mediated by fucokinase. Xenograft models demonstrated the inhibitory effects of capsaicin treatment on NPC tumor growth in vivo, and analysis of clinical NPC samples confirmed that MKK3 phosphorylation was associated with NPC tumor growth and lymphoid node metastasis. Conclusions: The MKK3-p38 axis represents a potential therapeutic target for capsaicin. MKK3 phosphorylation might serve as a biomarker to identify NPC patients most likely to benefit from adjunctive capsaicin treatment.
ProstaTrend—A Multivariable Prognostic RNA Expression Score for Aggressive Prostate Cancer
Authors: Markus Kreuz, Dominik J. Otto, Susanne Fuessel, Conny Blumert, Catharina Bertram, Sophie Bartsch, Dennis Loeffler, Sven-Holger Puppel, Michael Rade, Tilo Buschmann, Sabina Christ, Kati Erdmann, Maik Friedrich, Michael Froehner, Michael H. Muders, Stephan Schreiber, Michael Specht, Marieta I. Toma, Fabio Benigni, Massimo Freschi, Giorgio Gandaglia, Alberto Briganti, Gustavo B. Baretton, Markus Loeffler, Jörg Hackermüller, Kristin Reiche, Manfred Wirth, Friedemann Horn
Journal: European Urology (2020)
Private Payer and Medicare Coverage for Circulating Tumor DNA Testing: A Historical Analysis of Coverage Policies From 2015 to 2019
Authors: Michael P. Douglas, Stacy W. Gray, Kathryn A. Phillips
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: Clinical adoption of the sequencing of circulating tumor DNA (ctDNA) for cancer has rapidly increased in recent years. This sequencing is used to select targeted therapy and monitor nonresponding or progressive tumors to identify mechanisms of therapeutic resistance. Our study objective was to review available coverage policies for cancer ctDNA–based testing panels to examine trends from 2015 to 2019. Methods: We analyzed publicly available private payer policies and Medicare national coverage determinations and local coverage determinations (LCDs) for ctDNA-based panel tests for cancer. We coded variables for each year representing policy existence, covered clinical scenario, and specific ctDNA test covered. Descriptive analyses were performed. Results: We found that 38% of private payer coverage policies provided coverage of ctDNA-based panel testing as of July 2019. Most private payer policy coverage was highly specific: 87% for non–small cell lung cancer, 47% for EGFR gene testing, and 79% for specific brand-name tests. There were 8 final, 2 draft, and 2 future effective final LCDs (February 3 and March 15, 2020) that covered non–FDA-approved ctDNA-based tests. The draft and future effective LCDs were the first policies to cover pan-cancer use. Conclusions: Coverage of ctDNA-based panel testing for cancer indications increased from 2015 to 2019. The trend in private payer and Medicare coverage is an increasing number of coverage policies, number of positive policies, and scope of coverage. We found that Medicare coverage policies are evolving to pan-cancer uses, signifying a significant shift in coverage frameworks. Given that genomic medicine is rapidly changing, payers and policymakers (eg, guideline developers) will need to continue to evolve policies to keep pace with emerging science and standards in clinical care.
Operative safety of curative gastrectomy after endoscopic submucosal dissection (ESD) for early gastric cancer - 1:2 propensity score matching analysis: A retrospective single-center study (cohort study)
Authors: Ki Bum Park, Chul Hyo Jeon, Ho Seok Seo, Yoon Ju Jung, Kyo Young Song, Cho Hyun Park, Han Hong Lee
Journal: International Journal of Surgery (2020)
A call to arms: helping family, friends and communities navigate the COVID-19 infodemic
Authors: Heidi J. Larson
Journal: Nature reviews. Immunology (2020)

With information on COVID-19 evolving daily, the public is confronted with a mix of partial information, conflicting information and sometimes outright misinformation. Who should they turn to for the truth? In the context of acute uncertainty, I discuss what scientists can do to help mitigate the misinformation about what we do know and give some context to help decision-making in the unfolding story of COVID-19. In this Comment, Heidi Larson discusses the COVID-19 'infodemic' and suggests the ways in which scientists can help to mitigate the spread of misinformation.
Analysis of Response Data for Assessing Treatment Effects in Comparative Clinical Studies
Authors: Bo Huang, Lu Tian, Zachary R. McCaw, Xiaodong Luo, Enayet Talukder, Mace Rothenberg, Wanling Xie, Toni K. Choueiri, Dae Hyun Kim, Lee-Jen Wei
Journal: Annals of Internal Medicine (2020)

In comparative studies, treatment effect is often assessed using a binary outcome that indicates response to the therapy. Commonly used summary measures for response include the cumulative and current response rates at a specific time point. The current response rate is sometimes called the probability of being in response (PBIR), which regards a patient as a responder only if they have achieved and remain in response at present. The methods used in practice for estimating these rates, however, may not be appropriate. Moreover, whereas an effective treatment is expected to achieve a rapid and sustained response, the response at a fixed time point does not provide information about the duration of response (DOR). As an alternative, a curve constructed from the current response rates over the entire study period may be considered, which can be used for visualizing how rapidly patients responded to therapy and how long responses were sustained. The area under the PBIR curve is the mean DOR. This connection between response and DOR makes this curve attractive for assessing the treatment effect. In contrast to the conventional method for analyzing the DOR data, which uses responders only, the above procedure includes all patients in the study. Although discussed extensively in the statistical literature, estimation of the current response rate curve has garnered little attention in the medical literature. This article illustrates how to construct and analyze such a curve using data from a recent study for treating renal cell carcinoma. Clinical trialists are encouraged to consider this robust and clinically interpretable procedure as an additional tool for evaluating treatment effects in clinical studies.
Abstract A44: A CRISPRi screen to identify combination therapies for improved treatment of ovarian cancer
Authors: Erika D. Handly, Yi Wen Kong, Christian J. Braun, Jesse C. Patterson, Michael B. Yaffe
Journal: Clinical Cancer Research (2020)

Abstract Ovarian cancer is the fifth leading cause of cancer death for women in the United States, with only modest improvements in patient survival in the past few decades. Standard-of-care treatment is surgical debulking followed by a combination of platinum and taxane agents, but relapse and resistance frequently occur. In order to identify genes that cause sensitivity or resistance in tumor cells treated with platinum chemotherapeutics, I performed a CRISPRi-based screen that combined decreased gene expression of over 19,000 genes with the platinum drugs cisplatin and oxaliplatin. Genes whose knockdown caused sensitivity to the chemotherapeutics were identified through a multiobjective optimization approach to account for knockdown efficiencies and variances in sequencing depth. To filter the noise in the genome-wide screen and more confidently identify “hits,” a smaller pooled screen of one hundred targets was designed. Genes identified in this focused pooled screen as being important to platinum response in cells will be validated using approaches such as cell viability assays. The molecular mechanisms underlying the function of one or two of these genes in the chemotherapy response will be investigated in further detail. Thus, the project has the potential to define new molecular mechanisms by which tumors resist killing by chemotherapy and provide new therapeutic targets for front-line clinical standard-of-care combination chemotherapy regimes in the treatment of ovarian cancer. Citation Format: Erika D. Handly, Yi Wen Kong, Christian J. Braun, Jesse C. Patterson, Michael B. Yaffe. A CRISPRi screen to identify combination therapies for improved treatment of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A44.
PD1 gene polymorphism is associated with a poor prognosis in hepatocellular carcinoma following liver resection, cohort study
Authors: Masateru Yamamoto, Tsuyoshi Kobayashi, Hiroaki Mashima, Daiki Miki, Shintaro Kuroda, Michinori Hamaoka, Hiroshi Aikata, Kazuaki Chayama, Hideki Ohdan
Journal: International Journal of Surgery (2020)
CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas
Authors: Margery Gang, Nancy D. Marin, Pamela Wong, Carly C. Neal, Lynne Marsala, Mark Foster, Timothy Schappe, Wei Meng, Jennifer Tran, Maximilian Schaettler, Marco Davila, Feng Gao, Amanda F. Cashen, Nancy L. Bartlett, Neha Mehta-Shah, Brad S. Kahl, Miriam Y. Kim, Matthew L. Cooper, John F. DiPersio, Melissa M. Berrien-Elliott, Todd A. Fehniger
Journal: Blood (2020)
Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis
Authors: Dorothy A Machalek, Yusha Tao, Hannah Shilling, Jørgen S Jensen, Magnus Unemo, Gerald Murray, Eric P F Chow, Nicola Low, Suzanne M Garland, Lenka A Vodstrcil, Christopher K Fairley, Jane S Hocking, Lei Zhang, Catriona S Bradshaw
Journal: The Lancet Infectious Diseases (2020)
The stability of autistic traits in transgender adults following cross-sex hormone treatment
Authors: Anna Nobili, Cris Glazebrook, Walter Pierre Bouman, Simon Baron-Cohen, Jon Arcelus
Journal: International Journal of Transgender Health (2020)

Recent research has shown that a high percentage of treatment-seeking transgender adults who were assigned female at birth (AFAB) reported scores above the clinical cutoff for autistic traits. It is unclear whether those scores reflect a stable trait or may be inflated by the high levels of anxiety typically associated with transgender people attending clinical services.
Abstract NT-108: TARGETING BROMODOMAIN PROTEINS AS A THERAPEUTIC STRATEGY FOR CLEAR CELL CARCINOMA OF THE OVARY
Authors: Shogo Shigeta, Reid Shaw, Russell Moser, Kay Gurley, Goldie Lui, Carla Grandori, Christopher Kemp
Journal: Clinical Cancer Research (2019)

Abstract Background and Objectives: Clear cell carcinoma of the ovary (OCCC) is more resistant to platinum-based chemotherapy than high-grade serous ovarian cancer (HGSOC). Also, the indication for PARP inhibitors seems to be limited in OCCC because of the lower frequency of homologous recombination deficiency. As genomic background significantly differs among subtypes, therapeutic strategies should be optimized in response to each subtype or unique gene alterations. This study was designed to find novel therapeutic targets for OCCC by utilizing siRNA screens and unique patient-derived ovarian cancer cells that phenocopy original tumors. Materials and Methods: Novel patient-derived ovarian cancer cells were established and kindly provided by Dr. Tan Ince at University of Miami. Genomic alterations of these cells were determined by DNA sequencing. siRNA screens targeting 2,172 unique genes were performed with ARID1A-mutated OCCC cell line OCI C5x, and high-grade serous ovarian cancer cell line OCI P5x. Genes inhibition of which significantly suppressed cell proliferation were selected as hits for each subtype independently. The difference of cell viability between OCI C5x and P5x was also compared, and subtype-specific hits were additionally determined. Hits were applied to Gene Ontology (GO) enrichment analysis to comprehend the gene set enrichment. Several prioritized targets for OCCC were validated with additional RNAi experiments and small molecule inhibitors. Results: 114 and 108 genes were selected as hits specific to OCI C5x and OCI P5x, respectively. GO enrichment analysis revealed OCCC is potentially more vulnerable to epigenetic interventions than HOGSC. The following inspection revealed bromodomain-containing proteins were enriched in the hits for OCI C5x. Among these, we highlighted bromodomain and extra-terminal domain (BET) family proteins BRD2 and BRD3. Subsequent RNAi experiments validated BRD2 and BRD3 are highly potent therapeutic targets for OCCC. Conclusions: siRNA screening results suggest different approaches are required according to subtypes for the targeted therapy of ovarian cancer. We propose that epigenetic intervention such as BET protein inhibition as a potential therapeutic option for OCCC, 50-60% of which harbor ARID1A mutation. Citation Format: Shogo Shigeta, Reid Shaw, Russell Moser, Kay Gurley, Goldie Lui, Carla Grandori, Christopher Kemp. TARGETING BROMODOMAIN PROTEINS AS A THERAPEUTIC STRATEGY FOR CLEAR CELL CARCINOMA OF THE OVARY [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-108.
COVID-19 in paediatric rheumatology patients treated with b/tsDMARDs: a cross-sectional patient survey study
Authors: Muserref Kasap Cuceoglu, Ezgi Deniz Batu, Yelda Bilginer, Seza Özen
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article by Salvarani et al comparing the COVID-19 infection susceptibility and severity between the patients treated with biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) and all residents in the Reggio Emilia area.1 In their cohort of 1195 patients treated with b/tsDMARDs, there were nine confirmed COVID-19 cases. None of these COVID-19 cases were ≤45 years of age while only two out of 25 patients who were tested for COVID-19 were ≤45 years. They did not observe a different susceptibility or severity of COVID-19 in patients treated with these drugs.1 

Biologic/targeted synthetic DMARDs often target pathways of the immune system and this may result in a tendency for infections.2 Serious infections have been reported in both children and adults treated with these drugs.3 However, the data about infection rate and severity in children on b/ts DMARDs are limited. Consistent …