tbuckley/cabot-search huggingface dataset:
Identification of the surgical indication line for the Denonvilliers’ fascia and its anatomy in patients with rectal cancer
Authors: Jianglong Huang, Jing Liu, Jiafeng Fang, Zongheng Zeng, Bo Wei, Tufeng Chen, Hongbo Wei
Journal: Cancer Communications (2020)

Abstract Background The high rate of urogenital dysfunction after traditional total mesorectal excision (TME) has caused doubts among scholars on the standard fashion of dissection. We have proposed the necessity to preserve the Denonvilliers’ fascia in patients with rectal cancer. However, how to accurately locate the Denonvilliers’ fascia is unclear. This study aimed to explore anatomical features of the Denonvilliers’ fascia by comparing autopsy findings and observations of surgical videos so as to propose a dissection method for the preservation of pelvic autonomic nerves during rectal cancer surgery. Methods Five adult male cadaver specimens were dissected, and surgical videos of 135 patients who underwent TME for mid‐low rectal cancer between January 2009 and February 2019 were reviewed to identify and compare the structure of the Denonvilliers’ fascia. Results The monolayer structure of the Denonvilliers’ fascia was observed in 5 male cadaver specimens, and it was located between the rectum, the bottom of the bladder, the seminal vesicles, the vas deferens, and the prostate. The Denonvilliers’ fascia was originated from the rectovesical pouch (or rectum‐uterus pouch), down to fuse caudally with the rectourethral muscle at the apex of the prostate, and fused to the lateral ligaments on both sides. The fascia was thinner on the midline with a thickness of 1.06 ± 0.10 mm. The crown shape of the Denonvilliers’ fascia was slightly triangular, with a height of approximately 5.42 ± 0.16 cm at midline. Nerves were more densely distributed in front of the Denonvilliers’ fascia than behind, especially on both sides of it. Under laparoscopic view, the Denonvilliers’ fascia was originated at the lowest point of the rectovesical pouch (or rectum‐uterus pouch), with a thickened white line which was a good mark for identifying the Denonvilliers’ fascia. Conclusion Identification of the surgical indication line for the Denonvilliers’ fascia could help us identify the Denonvilliers’ fascia, and it would improve our ability to protect the pelvic autonomic function of patients undergoing TME for rectal cancer.
Efficacy of Laser Facilitated Epicutaneous Immunotherapy with Dermatophagoides pteronyssinus Depigmented Extract in a Mouse Model of Allergy
Authors: Raquel Moya Lobo, Evgeniia Korotchenko, Sandra Scheiblhofer, David Calzada, Victor Iraola, Jeronimo Carnes, Richard Weiss
Journal: Journal of Allergy and Clinical Immunology (2020)
A new survey to measure how localized scleroderma affects children and adolescents
Authors: C.K. Zigler, K. Ardalan, S. Lane, K.L. Schollaert, K.S. Torok
Journal: British Journal of Dermatology (2020)

Localized scleroderma, also called morphoea, is a rare condition affecting about three in 100,000 people. It typically causes changes to the skin and underlying tissue, sometimes as deep as the muscle or bone. The authors, from the U.S.A., wanted to develop a survey that would let children and adolescents tell researchers and doctors about how localized scleroderma affects their daily life. The authors first identified a number of important ways localized scleroderma can affect children and adolescents. They then created survey questions asking about these problems. Next, the authors had children and adolescents with localized scleroderma fill out the survey to see if they could read and understand the questions and instructions. The authors also asked children if there were any questions missing from the survey. The authors found that overall the survey performed well. Children and adolescents aged 8-18 years could read the questions and understand the survey. Children and adolescents also suggested that three questions be added to the survey to make it more complete. The final version of the survey included questions about how a child's skin feels (e.g. if it hurts or itches), limitations in their daily activities, how they feel about their body, their relationships with friends and strangers, and finally how their medications make them feel. This survey, The Localized Scleroderma Quality of Life Instrument, is the first of its kind. Doctors and researchers can use it to better understand what life is like for children and adolescents with localized scleroderma. This is a summary of the study: A novel patient-reported outcome for paediatric localized scleroderma: a qualitative assessment of content validity
Nanopore metagenomic sequencing to investigate nosocomial transmission of human metapneumovirus from a unique genetic group among haematology patients in the United Kingdom
Authors: Yifei Xu, Kuiama Lewandowski, Katie Jeffery, Louise O. Downs, Dona Foster, Nicholas D. Sanderson, James Kavanagh, Ali Vaughan, Claudia Salvagno, Richard Vipond, Miles Carroll, Robert Danby, Timothy Peto, Derrick Crook, A. Sarah Walker, Philippa C. Matthews, Steven T. Pullan
Journal: Journal of Infection (2020)

Human metapneumovirus (HMPV) infection causes a spectrum of respiratory tract disease, and may be a significant pathogen in the context of immunocompromise. Here, we report direct-from-sample metagenomic sequencing of HMPV using Oxford Nanopore Technology.We applied this sequencing approach to 25 respiratory samples that had been submitted to a clinical diagnostic laboratory in a UK teaching hospital. These samples represented 13 patients under the care of a haematology unit over a 20-day period in Spring 2019 (two sampled twice), and ten other patients elsewhere in the hospital between 2017-2019.We generated HMPV reads from 20/25 samples (sensitivity 80% compared to routine diagnostic testing) and retrieved complete HMPV genomes from 15/20 of these. Consensus sequences from Nanopore data were identical to those generated by Illumina, and represented HMPV genomes from two distinct sublineages, A2b and B2. Sequences from ten haematology patients formed a unique genetic group in the A2b sublineage, not previously reported in the UK. Among these, eight HMPV genomes formed a cluster (differing by ≤3 SNPs), likely to reflect nosocomial transmission, while two others were more distantly related and may represent independent introductions to the haematology unit.Nanopore metagenomic sequencing can be used to diagnose HMPV infection, although more work is required to optimise sensitivity. Improvements in the use of metagenomic sequencing, particularly for respiratory viruses, could contribute to antimicrobial stewardship. Generation of full genome sequences can be used to support or rule out nosocomial transmission, and contribute to improving infection prevention and control practices.
Perineural Invasion Reprograms the Immune Microenvironment through Cholinergic Signaling in Pancreatic Ductal Adenocarcinoma
Authors: Min-Wei Yang, Ling-Ye Tao, Yong-Sheng Jiang, Jian-Yu Yang, Yan-Miao Huo, De-Jun Liu, Jiao Li, Xue-Liang Fu, Ruizhe He, Chaoyi Lin, Wei Liu, Jun-Feng Zhang, Rong Hua, Qing Li, Shu-Heng Jiang, Li-Peng Hu, Guang-Ang Tian, Xiao-Xin Zhang, Ningning Niu, Ping Lu, Juanjuan Shi, Gary G. Xiao, Li-Wei Wang, Jing Xue, Zhi-Gang Zhang, Yong-Wei Sun
Journal: Cancer Research (2020)

Abstract Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed. Perineural invasion was associated with impaired immune responses characterized by decreased CD8+ T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe perineural invasion. Acetylcholine impaired the ability of PDAC cells to recruit CD8+ T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFNγ production by CD8+ T cells in a dose-dependent manner and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T-cell response in an orthotopic PDAC model. Conversely, blocking perineural invasion with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8+ T cells, an elevated Th1/Th2 ratio, and improved survival. In conclusion, perineural invasion–triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8+ T-cell infiltration and a reduced Th1/Th2 ratio. Significance: These findings provide a promising therapeutic strategy to modulate the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma with severe perineural invasion.
Tislelizumab plus cisplatin/carboplatin and gemcitabine versus placebo plus cisplatin/carboplatin and gemcitabine in Chinese patients with advanced urothelial carcinoma: A phase III trial in progress.
Authors: Feng BI, Han-Zhong Li, Shaoxing Zhu, Qing Zou, Jia Tang, Wei Zhang, Dingwei Ye
Journal: Journal of Clinical Oncology (2020)

TPS588 Background: Platinum-based chemotherapy is standard first-line treatment for patients with advanced urothelial carcinoma (UC). Checkpoint inhibitors (ie, anti-PD-1 antibodies) are first-line treatment options for cisplatin-ineligible patients. Combining anti-PD-1 treatment with chemotherapy may have synergistic effects and has demonstrated antitumor activity in a variety of tumor types. Tislelizumab, an investigational monoclonal antibody with high affinity and specificity for PD-1, was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports showed tislelizumab, as a single agent or combined with chemotherapy, was generally well tolerated and had antitumor activity in patients with advanced UC. Methods: This phase 3, randomized, double-blind, placebo-controlled study (NCT03967977) will compare the efficacy and safety/tolerability of tislelizumab vs placebo, both in combination with cisplatin/carboplatin and gemcitabine. Adult Chinese patients (n≈420) with histologically confirmed, inoperable, locally advanced/metastatic UC who are eligible for (but have not received) systemic anticancer therapy for advanced UC, therapies targeting PD-1/L1, or other antibody/drug targeting T-cell costimulation or checkpoint pathways, will be randomized 1:1 to receive tislelizumab (200 mg Q3W) or placebo (Q3W) plus gemcitabine (1000 mg/m 2 administered on Day 1 and 8 of each 3-week cycle) and cisplatin (70 mg/m 2 ) or carboplatin (AUC 4.5) administered on Day 1 or 2 of each 3-week cycle. Patients must provide a fresh biopsy or archival tissue for central assessment of PD-L1 expression. Overall survival (OS) is the primary endpoint. Investigator-assessed overall response rate (RECIST v1.1), duration of response, progression-free survival, and OS rates at Year 1 and 2 are secondary endpoints. Safety/tolerability, assessed by monitoring incidence and severity of adverse events, and health-related quality-of-life measures will also be evaluated. Clinical trial information: NCT03967977.
Circulating tumor DNA-targeted sequencing to reveal germline and somatic alterations that can guide decision-making in metastatic castration-resistant prostate cancer.
Authors: Baijun Dong, Liancheng Fan, Bin Yang, Wei Chen, Yonghong Li, Kaijie Wu, Fengbo Zhang, Lei Li, Xudong Yao, Wei Xue
Journal: Journal of Clinical Oncology (2020)

173 Background: The genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) is dynamic with the application of multiple treatments. The circulating tumor DNA(ctDNA), which reveals germline and somatic alterations, provides a mini-invasive tool for monitoring tumor evolution. Methods: We performed an exploratory analysis of 299 ctDNA samples from 8 centers through application of multiple-gene deep targeted sequencing. Results: The most common recurrent genomic alterations were in AR(34.7%), TP53(18.9%), CDK12(15.4%), BRCA2(13.3%), and the majority of these clinically actionable gene alterations were identified in somatic level(CDK12 100% in somatic). The results showed the frequency of AR amplification and TP53 defect significantly increased in post-second and later line treatment group compared with treatment-naive group. AR amplification and TP53 or RB1 defect were associated with resistance to abiraterone or docetaxel. CDK12 was more frequently altered in our cohort than those in previous reports which mainly focused on Caucasian population. The patients with CDK12 defect showed rapid resistance to abiraterone and limited efficacy of PARPi. However, these patients seemed to benefit from chemotherapy, espeacially platnium-based chemotherapy. Conclusions: This multi-institutional real-world study explored the genomic landscape and captured the significant diversity of mCRPC at different treatment stages by liquid biopsy. These findings established genomic drivers associated with resistance to multiple treatments (including PARPi and platinum-based chemotherapy) in mCRPC. Hence, ctDNA targeted sequencing can help guide clinical decision making in mCRPC throughout the whole treatment process. CDK12 might be able to be a novel predictive biomarker to guide treatment selection in mCRPC.
The omentum, a niche for premetastatic ovarian cancer
Authors: Xiaojing Ma
Journal: The Journal of Experimental Medicine (2020)

The work by Etzerodt et al. in this issue of JEM (https://doi.org/10.1084/jem.20191869) identifies a distinct omentum-resident macrophage population of embryonic origin and demonstrates that these cells provide a niche for ovarian cancer metastasis and cancer stemness. This research opens up for many questions and therapeutic prospects.
Peanut oral immunotherapy induces gastrointestinal eosinophilia in a longitudinal randomized controlled trial
Authors: Benjamin Wright, Nielsen Fernandez-Becker, Neeraja Kambham, Natasha Purington, Shu Cao, Dana Tupa, Wenming Zhang, Matthew Rank, Hirohito Kita, David Katzka, Kelly Shim, Bryan Bunning, Alfred Doyle, Elizabeth Jacobsen, Scott Boyd, Monali Manohar Manohar, Stephen Galli, Kari Nadeau, Sharon Chinthrajah
Journal: Journal of Allergy and Clinical Immunology (2020)
Using the Electronic Health Record and a School-based Education Program to Increase Asthma Management Plan Creation
Authors: Nicholas Antos, Santiago Encalada, Robert Rohloff, Adam Traner, Nicole Fortuna, Steven Proper, Priya Dokken, Jessica Jansky, Ian Reineking, Brittany Farrell, Mark Meuer
Journal: Journal of Allergy and Clinical Immunology (2020)
Trends in management and outcomes in patients with upper tract urothelial carcinoma following radical nephrouretectomy at Memorial Sloan Kettering Cancer Center.
Authors: Nathan Colin Wong, Melissa Assel, Andrew Tracey, Ricardo Alvim, Nima Almassi, Nirmish Singla, Timothy Nguyen Clinton, Gregory Thomas Chesnut, Daniel D. Sjoberg, Dean F. Bajorin, Jonathan Coleman
Journal: Journal of Clinical Oncology (2020)

469 Background: Although there have been changes in the treatment paradigm of patients with upper tract urothelial carcinoma (UTUC) over the past 2 decades, there is limited data on the particular management strategies and associated outcomes. We evaluated surgical trends, perioperative management, and oncologic outcomes of patients who underwent radical nephroureterectomy (RNU) for UTUC at Memorial Sloan Kettering Cancer Center over a 24-year period. Methods: Between 1995 and 2018, we identified 760 patients with UTUC who underwent RNU. 15 had multiple RNU and we kept only the first procedure for analysis. Generalized additive models were fitted to examine the association between date of surgery and continuous while generalized additive models with a logit link were used to estimate categorical variables. As surgical approach was defined using three different categories (open, laparoscopic and robotic) a generalized additive multinomial model was used. Generalized additive cox proportional hazards models were used to estimate the association between surgery date and estimate 2-year cancer-specific survival. Results: The use of pre-operative diagnostic endoscopic biopsies also increased from 12% to 72% which coincides with an increased proportion high grade disease on final pathology from 55% to 91%. The rate of open RNU declined from 100% to 54% with a coinciding rise in the utilization of minimally invasive approaches. Laparoscopy peaked in 2008 and then was subsequently replaced by the robotic approach. Mean lymph node yield increased over the study interval with more retroperitoneal lymph node dissections performed. Utilization of neoadjuvant chemotherapy also increased over time with a current rate of 31%, coinciding with an increase in pT0 rate from only 2% to 9%.The 2-year cancer specific survival probability has improved from 76% to 87% over the study period. Conclusions: Several changes in treatment patterns for patients with UTUC over the past 2 decades appear to correspond with an improvement of oncologic outcomes. How these changes directly relate to each other requires further investigation.
Real-world experience with mechlorethamine gel in patients with mycosis fungoides-cutaneous lymphoma: Preliminary findings from a prospective observational study
Authors: Ellen J. Kim, Larisa Geskin, Joan Guitart, Christiane Querfeld, Michael Girardi, Amy Musiek, David R. Mink, Michael J. Williams, James T. Angello, William L. Bailey
Journal: Journal of the American Academy of Dermatology (2020)
Timing of Infant Dietary Peanut Introduction and Peanut Allergy at 5 years in the CHILD Study
Authors: Elinor Simons, Edmond Chan, Thomas Eiwegger, Kyla Hildebrand, Julia Upton, Rishma Chooniedass, Ciriaco Piccirillo, Yi Zhang, Theo Moraes, Stuart Turvey, Piush Mandhane, Malcolm Sears, Padmaja Subbarao, Meghan Azad, Allan Becker
Journal: Journal of Allergy and Clinical Immunology (2020)
Prognostic value of hypoxia gene expression in bladder cancer patients.
Authors: Hyun Chang, Seung-Hyun Lee, Taeryool Koo, Moon Ho Kim, Soo-Yoon Sung
Journal: Journal of Clinical Oncology (2020)

548 Background: The prognostic value of hypoxia in bladder cancer remains unknown. We aimed to evaluate the potential role of hypoxia gene signature as prognostic factors in bladder cancer patients. Methods: We investigated the hypoxia gene signature and clinicopathologic features of The Cancer Genome Atlas (TCGA) bladder urothelial carcinoma (n = 408) using the Kaplan-Meier survival curves and multivariate Cox regression analyses. The clinicopathologic data and the processed data of hypoxia gene signature were obtained from TCGA Bladder urothelial carcinoma database. Results: Hypoxia gene signature score was significantly associated with overall survival (OS) and progression-free survival (PFS). Higher score resulted in shorter OS and PFS in Kaplan-Meier survival curves with Log-rank test ( P &lt; 0.01 and P &lt;0.05, respectively). In multivariate analysis containing clinical prognostic variables, higher hypoxia gene signature score predicted poor OS (adjusted HR= 1.58, 95% CI 1.15 - 2.19; P &lt;0.01). Conclusions: Hypoxia gene signature was an independent prognostic factor in bladder cancer. Prospective studies are needed to evaluate the prognostic role of hypoxia in bladder cancer patients.
Effects of Colesevelam on Bowel Symptoms, Biomarkers, and Colonic Mucosal Gene Expression in Patients With Bile Acid Diarrhea in a Randomized Trial
Authors: Priya Vijayvargiya, Michael Camilleri, Paula Carlson, Asha Nair, Sara Linker Nord, Michael Ryks, Deborah Rhoten, Duane Burton, Irene Busciglio, Alan Lueke, W. Scott Harmsen, Leslie J. Donato
Journal: Clinical Gastroenterology and Hepatology (2020)
Abstract 198: Public Perceptions on Why Women Receive Less Bystander CPR Than Men in Out of Hospital Cardiac Arrest
Authors: Sarah M Perman, Shelby K Shelton, Christopher Knoepke, Kathryn Rappaprt, Daniel D Matlock, Kathleen Adelgais, Edward P Havranek, Stacie L Daugherty
Journal: Circulation (2018)

Introduction: Women who suffer an out of hospital cardiac arrest have been observed to receive less bystander cardiopulmonary resuscitation (CPR) than men. Potential reasons for why women receive less bystander CPR than men are largely unknown. Methods: Mechanical Turk (MTurk), Amazon’s crowdsourcing platform, was used to pilot a national survey asking participants why they believe women receive less bystander CPR than men. Eligible participants were adults (18 years or over) located in the US. Participants were reimbursed $1 for their participation. To ensure adequate knowledge on the subject, survey responses were excluded if they incorrectly defined CPR. Participant demographics as well as familiarity with CPR were queried. Participants were asked to answer the following free-text question “Do you have any ideas on why women may be less likely to receive CPR than men when they collapse in public?” Descriptive statistics were used to define the cohort. The free text response was coded using thematic analysis and major themes were identified via classical content analysis. Results: Within 55 minutes of deploying the pilot survey, 54 individuals responded. All respondents answered the knowledge question correctly, and none were excluded. Mean age was 36.9 ±9.6 years and 38.9% were female. Participants were geographically distributed as follows: 13% West, 13% Southwest, 16.7% Midwest, 27.8% Southeast, 29.6% Northeast. Predominant themes identified for why women might receive less bystander CPR than men are identified in Table 1. Within this cohort, 27.8% were trained in CPR, and only 5.6% of respondents had actually performed CPR on a person. Conclusions: In this pilot survey, public perceptions identified social norms regarding fear of inappropriate touching and hurting women as significant contributors to reasons for why women receive less bystander CPR than men. Additional work using a larger national sample to confirm and expand on these findings is ongoing.
Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial
Authors: Håvard Ove Skjerven, Eva Maria Rehbinder, Riyas Vettukattil, Marissa LeBlanc, Berit Granum, Guttorm Haugen, Gunilla Hedlin, Linn Landrø, Benjamin J Marsland, Knut Rudi, Kathrine Dønvold Sjøborg, Cilla Söderhäll, Anne Cathrine Staff, Kai-Håkon Carlsen, Anna Asarnoj, Karen Eline Stensby Bains, Oda C Lødrup Carlsen, Kim M Advocaat Endre, Peder Annæus Granlund, Johanne Uthus Hermansen, Hrefna Katrín Gudmundsdóttir, Katarina Hilde, Geir Håland, Ina Kreyberg, Inge Christoffer Olsen, Caroline-Aleksi Olsson Mägi, Live Solveig Nordhagen, Carina Madelen Saunders, Ingebjørg Skrindo, Sandra G Tedner, Magdalena R Værnesbranden, Johanna Wiik, Christine Monceyron Jonassen, Björn Nordlund, Karin C Lødrup Carlsen
Journal: The Lancet (2020)