tbuckley/cabot-search huggingface dataset:
Sex Disparity in Liver Transplant and Access to Living Donation
Authors: Ravikiran S. Karnam, Shiyi Chen, Wei Xu, Catherine Chen, Praniya Elangainesan, Anand Ghanekar, Ian McGilvray, Trevor Reichman, Blayne Sayed, Markus Selzner, Gonzalo Sapisochin, Zita Galvin, Gideon Hirschfield, Sumeet K. Asrani, Nazia Selzner, Mark Cattral, Leslie Lilly, Mamatha Bhat
Journal: JAMA Surgery (2021)

The Model for End-stage Liver Disease (MELD)-based organ allocation system has significantly decreased mortality on the transplant waiting list for patients with end-stage liver disease. However, women have remained at a disadvantage with respect to access to deceased donor liver transplant (DDLT) even after introduction of the MELD score for organ allocation.To determine whether availability of living donation in a transplant program can offset inequity in liver transplant (LT) allocation for women.This cohort study retrospectively analyzed adult patients listed for LT at the University Health Network in Toronto, Ontario, Canada. Patients included had a potential living donor (pLD) at the moment of listing. This study was performed from November 13, 2012, to May 31, 2019. A total of 1289 listed patients (830 men; 459 women) were analyzed during the study period.This study performed survival analysis and competing-risk analysis to delineate how access to livers from living donors was associated with events in women vs men on the transplant waiting list (LT, death, or dropout).Of 1289 included patients, 459 (35.6%) were women, and the mean (SD) age was 56.1 (10.0) years at assessment and listing. A total of 783 of 1289 listed patients underwent LT. Among those with no pLD at assessment, there was a higher median (range) Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score at listing (22 [6-50] vs 19 [6-50]; P < .001) and at LT (27 [6-49] vs 20 [6-52]; P < .001) in women receiving DDLT. Women were at a significant disadvantage without a pLD (hazard ratio [HR], 1.29; 95% CI, 1.04-1.60; P = .01); there was no difference in access to LT with availability of a pLD (HR, 0.93; 95% CI, 0.76,-1.14; P = .44). The instantaneous rate of receiving a transplant in men with a pLD was 1.39 times higher than men who did not have a pLD (HR, 1.39; 95% CI; P < .001) and the instantaneous rate of receiving a transplant in women with a pLD was 1.92 times higher than in women who did not (HR, 1.92; 95% CI, 1.51-2.44; P < .001). The HR was 1.38 times higher in women compared with men across the MELD-Na score strata (HR, 1.38; 95% CI, 1.03-1.84; P = .03) and 2.04 times higher when the MELD-Na score was less than 20 (HR, 2.04; 95% CI, 1.31-3.14; P = .001).These study findings suggest that women can overcome the complex problem of allocation inequity with access to livers from living donors. Women with access only to DDLT were much more unwell than men independent of liver disease at the time of listing, dropout, or LT. Therefore, the wider availability of living donation liver transplant would be helpful in addressing the sex disparity in access to LT in the current MELD-Na era.
NucHMM: a method for quantitative modeling of nucleosome organization identifying functional nucleosome states distinctly associated with splicing potentiality
Authors: Kun Fang, Tianbao Li, Yufei Huang, Victor X. Jin
Journal: Genome biology (2021)

We develop a novel computational method, NucHMM, to identify functional nucleosome states associated with cell type-specific combinatorial histone marks and nucleosome organization features such as phasing, spacing and positioning. We test it on publicly available MNase-seq and ChIP-seq data in MCF7, H1, and IMR90 cells and identify 11 distinct functional nucleosome states. We demonstrate these nucleosome states are distinctly associated with the splicing potentiality of skipping exons. This advances our understanding of the chromatin function at the nucleosome level and offers insights into the interplay between nucleosome organization and splicing processes.
Dissecting the precise nature of itch-evoked scratching
Authors: Nivanthika K. Wimalasena, George Milner, Ricardo Silva, Cliff Vuong, Zihe Zhang, Diana M. Bautista, Clifford J. Woolf
Journal: Neuron (2021)

Itch is a discrete and irritating sensation tightly coupled to a drive to scratch. Acute scratching developed evolutionarily as an adaptive defense against skin irritants, pathogens, or parasites. In contrast, the itch-scratch cycle in chronic itch is harmful, inducing escalating itch and skin damage. Clinically and preclinically, scratching incidence is currently evaluated as a unidimensional motor parameter and believed to reflect itch severity. We propose that scratching, when appreciated as a complex, multidimensional motor behavior, will yield greater insight into the nature of itch and the organization of neural circuits driving repetitive motor patterns. We outline the limitations of standard measurements of scratching in rodent models and present new approaches to observe and quantify itch-evoked scratching. We argue that accurate quantitative measurements of scratching are critical for dissecting the molecular, cellular, and circuit mechanisms underlying itch and for preclinical development of therapeutic interventions for acute and chronic itch disorders.
Abstract 13143: Time Course and Outcomes of Major Bleeding Events According to Bleeding Site in Patients Receiving Anticoagulant Therapy for Venous Thromboembolism
Authors: Behnood Bikdeli, Fares Moustafa, José Antonio Nieto, Alfred I Lee, Nuria Ruíz-Giménez, Alicia Lorenzo, Sebastian M Schellong, Silvia Soler, Maria Del Valle Morales, Marijan Bosevski, Olga Gavín, Gregory Lip, Manuel Monreal
Journal: Circulation (2019)

Background: Bleeding is the most feared complication of anticoagulant therapy in patients with venous thromboembolism (VTE). Limited data exist about patient characteristics, time course and outcom...
DIFFERENTIAL DIAGNOSIS OF LIVER ADENOCARCINOMA BY GENE EXPRESSION FINGERPRINTING
Authors: Saiura Akio, Koga Rintaro, Shimoji Takashi, Katori Masamichi, Nagasaki Koichi, Noda Tetsuo, Yamamoto Junji, Yamamoto Toshiharu
Journal: Annals of Oncology (2011)
Systematic functional interrogation of human pseudogenes using CRISPRi
Authors: Ming Sun, Yunfei Wang, Caishang Zheng, Yanjun Wei, Jiakai Hou, Peng Zhang, Wei He, Xiangdong Lv, Yao Ding, Han Liang, Chung-Chau Hon, Xi Chen, Han Xu, Yiwen Chen
Journal: Genome biology (2021)

Abstract Background The human genome encodes over 14,000 pseudogenes that are evolutionary relics of protein-coding genes and commonly considered as nonfunctional. Emerging evidence suggests that some pseudogenes may exert important functions. However, to what extent human pseudogenes are functionally relevant remains unclear. There has been no large-scale characterization of pseudogene function because of technical challenges, including high sequence similarity between pseudogene and parent genes, and poor annotation of transcription start sites. Results To overcome these technical obstacles, we develop an integrated computational pipeline to design the first genome-wide library of CRISPR interference (CRISPRi) single-guide RNAs (sgRNAs) that target human pseudogene promoter-proximal regions. We perform the first pseudogene-focused CRISPRi screen in luminal A breast cancer cells and reveal approximately 70 pseudogenes that affect breast cancer cell fitness. Among the top hits, we identify a cancer-testis unitary pseudogene, MGAT4EP, that is predominantly localized in the nucleus and interacts with FOXA1, a key regulator in luminal A breast cancer. By enhancing the promoter binding of FOXA1, MGAT4EP upregulates the expression of oncogenic transcription factor FOXM1. Integrative analyses of multi-omic data from the Cancer Genome Atlas (TCGA) reveal many unitary pseudogenes whose expressions are significantly dysregulated and/or associated with overall/relapse-free survival of patients in diverse cancer types. Conclusions Our study represents the first large-scale study characterizing pseudogene function. Our findings suggest the importance of nuclear function of unitary pseudogenes and underscore their underappreciated roles in human diseases. The functional genomic resources developed here will greatly facilitate the study of human pseudogene function.
Local Recurrence and Disease-Free Survival After Transanal Total Mesorectal Excision: Results From the International TaTME Registry
Authors: Sapho X. Roodbeen, Marta Penna, Susan van Dieren, Brendan Moran, Paris Tekkis, Pieter J. Tanis, Roel Hompes, _ _
Journal: Journal of the National Comprehensive Cancer Network (2021)

The oncologic safety of transanal total mesorectal excision (TaTME) for rectal cancer has recently been questioned, with high local recurrence (LR) rates reported in Dutch and Norwegian experiences. The objective of this study was to evaluate the oncologic safety of TaTME in a large cohort of patients with primary rectal cancer, primarily in terms of LR, disease-free survival (DFS), and overall survival (OS).This was a prospective international registry cohort study, including all patients who underwent TaTME for primary rectal adenocarcinoma from February 2010 through December 2018. The main endpoints were 2-year LR rate, pattern of LR, and independent risk factors for LR. Secondary endpoints included 2-year DFS and OS rates. Kaplan-Meier survival analysis was used to calculate actuarial LR, DFS, and OS rates.A total of 2,803 patients receiving primary TaTME were included, predominantly men (71%) with a median age of 65 years (interquartile ratio, 57-73 years). After a median follow-up of 24 months (interquartile ratio, 12-38 months), the 2-year LR rate was 4.8% (95% CI, 3.8%-5.8%) with a unifocal LR pattern in 99 of 103 patients (96%). Independent risk factors for LR were male sex, threatened resection margin on baseline MRI, pathologic stage III cancer, and a positive circumferential resection margin on final histopathology. The 2-year DFS and OS rates were 77% (95% CI, 75%-79%) and 92% (95% CI, 91%-93%), respectively.This largest TaTME cohort to date supports the oncologic safety of the TaTME technique for rectal cancer in patients treated in units that contributed to an international registry, with an acceptable 2-year LR rate and a predominantly unifocal LR pattern.
Two Decades of Cardiac Amyloidosis
Authors: Oscar Westin, Jawad H. Butt, Finn Gustafsson, Morten Schou, Morten Salomo, Lars Køber, Mathew Maurer, Emil L. Fosbøl
Journal: JACC CardioOncology (2021)

Cardiac amyloidosis (CA) has been associated with poor outcomes. Screening studies suggest that CA is overlooked-especially in the elderly. Recent advances in treatment have brought attention to the disease, but data on temporal changes in CA epidemiology are sparse.The aim of this work was to describe all patients with CA in Denmark, examining changes in patient characteristics from 1998 to 2017.All patients with any form of amyloidosis diagnosed from 1998 to 2017, as well as their comorbidities and pharmacotherapy, were identified in Danish nationwide registries. CA was defined as any diagnosis code for amyloidosis combined with a diagnosis code for heart failure, cardiomyopathy, or atrial fibrillation or a procedural code for pacemaker implantation, regardless of the order. The index date was defined as the date of meeting those criteria. Patients were divided into 5-year periods by index date. For comparison, we also included control subjects (1:4 ratio) from the general population.CA criteria were met by 619 patients. Comparing 1998-2002 vs 2013-2017, the median age at baseline increased from 67.4 years (interquartile range [IQR]: 53.9-75.2 years) to 72.3 years (IQR: 66.0-79.3 years). The frequency of male patients increased from 62.1% to 66.2%. The incidence of CA rose from 0.88 to 3.56 per 100,000 person-years in the Danish population aged ≥65 years, and the 2-year mortality decreased from 82.6% (IQR: 69.9%-90.5%) to 50.2% (IQR: 43.1%-56.9%). Compared with control subjects, the mortality among CA patients was significantly higher (log-rank test: P < 0.0001).CA, as defined in this study, was increasingly diagnosed on a national scale. The increasing frequency of male patients and median age suggest that wild-type transthyretin amyloidosis is driving this increase. Greater recognition of earlier, less advanced cases might explain decreasing mortality.
Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation
Authors: Qiubing Chen, Qian Li, Yuqi Liang, Menghang Zu, Nanxi Chen, Brandon S.B. Canup, Liyong Luo, Chenhui Wang, Liang Zeng, Bo Xiao
Journal: Acta Pharmaceutica Sinica B (2021)

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.
Secreted retrovirus-like GAG-domain-containing protein PEG10 is regulated by UBE3A and is involved in Angelman syndrome pathophysiology
Authors: Nikhil J. Pandya, Congwei Wang, Veronica Costa, Paul Lopatta, Sonja Meier, F. Isabella Zampeta, A. Mattijs Punt, Edwin Mientjes, Philip Grossen, Tania Distler, Manuel Tzouros, Yasmina Martí, Balazs Banfai, Christoph Patsch, Soren Rasmussen, Marius Hoener, Marco Berrera, Thomas Kremer, Tom Dunkley, Martin Ebeling, Ben Distel, Ype Elgersma, Ravi Jagasia
Journal: Cell Reports Medicine (2021)

Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of maternal UBE3A, a ubiquitin protein ligase E3A. Here, we study neurons derived from patients with AS and neurotypical individuals, and reciprocally modulate UBE3A using antisense oligonucleotides. Unbiased proteomics reveal proteins that are regulated by UBE3A in a disease-specific manner, including PEG10, a retrotransposon-derived GAG protein. PEG10 protein increase, but not RNA, is dependent on UBE3A and proteasome function. PEG10 binds to both RNA and ataxia-associated proteins (ATXN2 and ATXN10), localizes to stress granules, and is secreted in extracellular vesicles, modulating vesicle content. Rescue of AS patient-derived neurons by UBE3A reinstatement or PEG10 reduction reveals similarity in transcriptome changes. Overexpression of PEG10 during mouse brain development alters neuronal migration, suggesting that it can affect brain development. These findings imply that PEG10 is a secreted human UBE3A target involved in AS pathophysiology.
27430 Worldwide survey shows that atopic dermatitis is associated with a high disease burden in children
Authors: Stephan Weidinger, Eric L. Simpson, Jonathan I. Silverberg, Sébastien Barbarot, Ana B. Rossi, Lysel Brignoli, Grece Saba, Sébastien Auziere, Dimittri Delevry, Laurent Eckert, Puneet Mahajan
Journal: Journal of the American Academy of Dermatology (2021)
27368 Psoriasis Symptoms and Impacts Measure (P-SIM) responses from the BE VIVID bimekizumab in moderate to severe plaque psoriasis phase 3 trial
Authors: Richard B. Warren, Richard G. Langley, Akihiko Asahina, Matthias Augustin, Joseph F. Merola, Alice B. Gottlieb, Valerie Ciaravino, Christopher Cioffi, Luke Peterson, Mark Lebwohl
Journal: Journal of the American Academy of Dermatology (2021)
Reply to "Comment and response to the article "The clinical relevance of visualizing the peripheral retina"by Nicola Quinn, Lajos Csincsik, Erin Flynn, Christine A. Curcio, Szilard Kiss, SriniVas R. Sadda, Ruth Hogg, Tunde Peto & Imre Lengyel
Authors: Imre Lengyel, Christine Curcio
Journal: Progress in Retinal and Eye Research (2021)
26670 The contribution of itch and skin severity improvements to the Dermatology Life Quality Index in patients with atopic dermatitis in a baricitinib phase 3 study, BREEZE-AD5
Authors: Gil Yosipovitch, Kim Papp, Seth Forman, George Han, Jill Waibel, Maria Jose Rueda, Luna Sun, Yun-Fei Chen, Orin Goldblum, Evangeline Pierce, Jonathan Silverberg
Journal: Journal of the American Academy of Dermatology (2021)
Comparison of Midterm Outcomes Associated With Aspirin and Ticagrelor vs Aspirin Monotherapy After Coronary Artery Bypass Grafting for Acute Coronary Syndrome
Authors: Erik Björklund, Carl Johan Malm, Susanne J. Nielsen, Emma C. Hansson, Hans Tygesen, Birgitta S. Romlin, Andreas Martinsson, Elmir Omerovic, Aldina Pivodic, Anders Jeppsson
Journal: JAMA Network Open (2021)

Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak.To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy.This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020.Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only.Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up.A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P = .34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P = .29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P = .011). Sensitivity analyses confirmed the results.In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted.
Malignant Melanoma of Glans Penis: Findings on 18F FDG PET/CT.
Authors: Hemant Sachani, Sarthak Tripathy, Shamim Ahmed Shamim, Sameer Rastogi, Annie K Baa
Journal: Clinical Nuclear Medicine (2021)

ABSTRACT Melanomas usually arise in the sun exposed parts of the skin. Mucosal melanoma is a rare condition. Melanoma of glans penis is even a rarer phenomenon with less than 250 cases reported in literature so far. Here we present a case of a 55-year-old man diagnosed with melanoma of glans penis with findings on 18F FDG PET/CT scan done for metastatic workup. 18F-FDG PET/CT showed primary in the glans penis with metastases in the right supraclavicular, mediastinal, and abdominal lymph nodes.
Anti–SARS-CoV-2 spike protein S1 receptor-binding domain antibody after vaccination with inactivated whole-virus SARS-CoV-2 in end-stage kidney disease patients: an initial report
Authors: Sarinya Boongird, Piyatida Chuengsaman, Salinnart Phanprasert, Rungthiwa Kitpermkiat, Montira Assanatham, Arkom Nongnuch, Sasisopin Kiertiburanakul, Kumthorn Malathum, Angsana Phuphuakrat, Chavachol Setthaudom, Jackrapong Bruminhent
Journal: Kidney International (2021)
Sanat Kumar Panja
Authors: Ayan Panja
Journal: BMJ (2021)

Sanat Kumar Panja was born in Khardaha, a small village in the northern suburbs of Kolkata. Despite humble beginnings, he excelled academically at school and medical school taking a sweep of nine gold medals at Calcutta Medical College, where he was also the Junior Goodeve scholar and individual debating champion.

Like many Indian doctors, he and his wife came to the UK in 1972 to take their postgraduate exams. His gynaecology training started …
The Role of Dual Inhibition of EGFR and Vascular Endothelial Growth Factor (Receptor) in the Treatment of NSCLC With EGFR Mutation
Authors: Takashi Yamaoka, Young Hak Kim, Shigeaki Iwatsubo, Yoshihiro Nishimura, Yasuhiro Funada
Journal: Journal of Thoracic Oncology (2021)
Microglial activation and tau propagate jointly across Braak stages
Authors: Tharick A. Pascoal, Andrea L. Benedet, Nicholas J. Ashton, Min Su Kang, Joseph Therriault, Mira Chamoun, Melissa Savard, Firoza Z. Lussier, Cécile Tissot, Thomas K. Karikari, Julie Ottoy, Sulantha Mathotaarachchi, Jenna Stevenson, Gassan Massarweh, Michael Schöll, Mony J. de Leon, Jean-Paul Soucy, Paul Edison, Kaj Blennow, Henrik Zetterberg, Serge Gauthier, Pedro Rosa-Neto
Journal: Nature Medicine (2021)
27124 Impact of body mass index (BMI) on the efficacy and safety of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in patients with plaque psoriasis
Authors: Mark G. Lebwohl, James Q. Del Rosso, Javier Alonso-Llamazares, Mark Lattouf, Abby Jacobson
Journal: Journal of the American Academy of Dermatology (2021)
P19: Cutaneous manifestations of COVID‐19 in the UK: a registry of digital submissions from interdisciplinary healthcare professionals
Journal: British Journal of Dermatology (2021)

the need for a standardized care pathway to improve the early identification, prevention and treatment of infection in this patient group.As per NCCN recommendations this should include concurrent nasal and skin swabs, mupirocin ointment for nasal S. aureus carriage, routine herpes viral screening and the use of antiseptic techniques such as bleach baths, where appropriate.