tbuckley/cabot-search huggingface dataset:
M01 as a novel drug enhancer for specifically targeting the blood-brain barrier.
Authors: Olga Breitkreuz-Korff, Christian Tscheik, Giovanna Del Vecchio, Sophie Dithmer, Wolfgang Walther, Andrea Orthmann, Hartwig Wolburg, Reiner F. Haseloff, Leif Schröder, Ingolf E. Blasig, Lars Winkler
Journal: Journal of Controlled Release (2021)

Drug delivery to the brain is limited for most pharmaceuticals by the blood-brain barrier (BBB) where claudin-5 dominates the paraendothelial tightening. For circumventing the BBB, we identified the compound M01 as a claudin-5 interaction inhibitor. M01 causes transient permeabilisation of the BBB depending on the concentration of small molecules in different cell culture models within 3 to 48 h. In mice, brain uptake of fluorescein peaked within the first 3 h after M01 injection and normalised within 48 h. Compared to the cytostatic paclitaxel alone, M01 improved delivery of paclitaxel to mouse brain and reduced orthotopic glioblastoma growth. Results on interactions of M01 with claudin-5 were incorporated into a binding model which suggests association of its aromatic parts with highly conserved residues of the extracellular domain of claudin-5 and adjacent transmembrane segments. Our results indicate the following mode of action: M01 preferentially binds to the extracellular claudin-5 domain, which weakens trans-interactions between adhering cells. Further decrease in membranous claudin-5 levels due to internalization and transcriptional downregulation enables the paracellular passage of small molecules. In summary, the first small molecule is introduced here as a drug enhancer, which specifically permeabilises the BBB for a sufficient interval for allowing neuropharmaceuticals to enter the brain.
Atypical cause of bronchial cut-off sign
Authors: Brian Gaffney, Liam Chawke, Michaela Larkin, Gaith Qsous, David Healy, Michael P Keane, Aurélie Fabre, David J Murphy, Cormac McCarthy
Journal: Thorax (2021)

A 58-year-old woman with no prior medical history, presented with a 5-month history of productive cough, worsening breathlessness and weight loss of 5 kg despite three courses of oral antibiotic therapy. On examination she was afebrile, there was reduced air entry in the right lung base to auscultation and oxygen saturations on room air were 86%. Serum C reactive protein was elevated at 26.2 mg/L (range 0–5 mg/L) and white cell count was 9.6×109/L (3.5–11×109/L), and evidence of eosinophilia was 1.7×109/L (0–0.5×109/L). Chest radiograph showed complete collapse of the right middle and lower lobes and bronchial cut-off sign of the right main bronchus (figure 1A). CT of the chest demonstrated a large endobronchial obstructing lesion in the right main bronchus highly suspicious for an endobronchial tumour (figure 1B,C)



Figure 1 
(A) Chest radiograph demonstrating bronchial cut of sign …
Postnatal growth standards for preterm infants: the Preterm Postnatal Follow-up Study of the INTERGROWTH-21st Project
Authors: José Villar, Francesca Giuliani, Zulfiqar A. Bhutta, Enrico Bertino, Eric O. Ohuma, Leila Cheikh Ismail, Fernando C. Barros, Douglas G. Altman, Cesar Victora, Julia A. Noble, Michael G. Gravett, Manorama Purwar, Ruyan Pang, Ann Lambert, Aris T. Papageorghiou, Roseline Ochieng, Yasmin A. Jaffer, Stephen H. Kennedy
Journal: The Lancet (2015)
Interpreting the Results of Intention-to-Treat, Per-Protocol, and As-Treated Analyses of Clinical Trials
Authors: Valerie A. Smith, Cynthia J. Coffman, Michael G. Hudgens
Journal: JAMA (2021)

This JAMA Guide to Statistics and Methods describes how intention-to-treat, per-protocol, and as-treated approaches to analysis differ with regard to the patient population and treatment assignments and their implications for interpretation of treatment effects in clinical trials.
Tandem peroral endoscopic myotomy (POEM) and transoral incisionless fundoplication: a strategy to reduce reflux after POEM
Authors: Nicholas A. Hoerter, Rebekah E. Dixon, Christopher J. DiMaio, Satish Nagula, David Greenwald, Nikhil A. Kumta
Journal: Endoscopy (2021)

Peroral endoscopic myotomy (POEM) is an effective treatment for achalasia, comparable to laparoscopic Heller myotomy (LHM) [1]. Gastroesophageal reflux disease (GERD) is a common adverse event, and POEM vs. LHM has higher abnormal acid exposure (39 % vs. 16.8 %) and esophagitis (29.4 % vs. 7.6 %) [2] [3]. Transoral incisionless fundoplication (TIF) is an endoscopic intervention for GERD that reduces acid exposure [4] [5].
Antibody response to SARS-CoV-2 among individuals with IBD diminishes over time: a serosurveillance cohort study
Authors: Gilaad G Kaplan, Christopher Ma, Carmen Charlton, Jamil N Kanji, Graham Tipples, Nastaran Sharifi, Michelle Herauf, Stephanie Coward, Richard J M Ingram, Lindsay Hracs, Eric I Benchimol, Remo Panaccione
Journal: Gut (2021)

We read with interest the highly impactful CLARITY IBD study that demonstrated a diminished serological response to SARS-CoV-2 in individuals with IBD receiving infliximab as compared with those receiving vedolizumab.1 We assessed the prevalence of antibodies to SARS-CoV-2 in patients with IBD and evaluated whether serological response to SARS-CoV-2 wanes over time following infection.

Individuals with IBD from Calgary, Canada, were recruited from October 2020 to April 2021 and stratified into two cohorts: (1) serosurveillance (n=279) defined as those who were not previously diagnosed with COVID-19; and (2) COVID-19 recovered (n=45), defined as those with a molecular-confirmed diagnosis of SARS-CoV-2 infection via PCR.

Serum was analysed using the Abbott Architect SARS-CoV-2 IgG antibody to the nucleocapsid protein. A positive antibody test was defined as an index signal/cut-off ≥1.4. The assay has been validated with 95% sensitivity and >99% specificity 12 days following symptom onset and correlates to neutralising antibodies.2

We assessed the proportion, with 95% CIs, of individuals with IBD who mounted an antibody response among those undergoing serosurveillance and following infection with SARS-CoV-2. In those diagnosed with COVID-19, we calculated the days from diagnosis to serological testing and developed a logistic regression model that assessed the effect of time from COVID-19 diagnosis to serology testing (before vs after 90 days) on nucleocapsid positive versus negative antibody; adjusted for age, sex and anti-tumour necrosis factor (TNF) usage.

The baseline characteristics of the two cohorts are summarised in table 1. Among the serosurveillance cohort, 1.08% (95% CI 0.22 to …
Large-scale prospective genome-wide association study of oxaliplatin in stage II/III colon cancer and neuropathy
Authors: M. Kanai, T. Kawaguchi, M. Kotaka, D. Manaka, J. Hasegawa, A. Takagane, Y. Munemoto, T. Kato, T. Eto, T. Touyama, T. Matsui, K. Shinozaki, S. Matsumoto, T. Mizushima, M. Mori, J. Sakamoto, A. Ohtsu, T. Yoshino, S. Saji, F. Matsuda
Journal: Annals of Oncology (2021)

The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach.A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored.No SNPs exceeded the genome-wide significance (P < 5.0 × 10-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs.Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.
A phosphorescent probe for in vivo imaging in the second near-infrared window
Authors: Baisong Chang, Daifeng Li, Ying Ren, Chunrong Qu, Xiaojing Shi, Ruiqi Liu, Hongguang Liu, Jie Tian, Zhenhua Hu, Taolei Sun, Zhen Cheng
Journal: Nature Biomedical Engineering (2021)
Thrombotic complications with SARS-CoV-2 infection in patients with cancer on high-risk therapies: Data from the COVID-19 and Cancer Consortium (CCC19).
Authors: Shuchi Gulati, Surbhi Shah, Amit Kulkarni, Aakash Desai, Julie Fu, Rebecca Zon, Vaibhav Kumar, Chih-Yuan Hsu, Clara Hwang, Deborah Blythe Doroshow, Imo Akpan, Jennifer Girard, Peter Paul Yu, Rana R. McKay, Ziad Bakouny, Jean Connors, Dimpy P. Shah, Jeremy Lyle Warner, Rachel Pam Greenerger Rosovsky, Petros Grivas
Journal: Journal of Clinical Oncology (2021)

e18788 Background: Patients (pts) with cancer have a high risk of venous thromboembolic (VTE) complications, further enhanced by anti-cancer treatments, specifically hormonal therapies, targeted therapies (VEGF inhibitors, other TKIs) and immune checkpoint inhibitors (ICIs). We hypothesized that high-risk therapies would predispose pts with cancer and COVID-19 to higher risk of VTE complications. Methods: CCC19 is the largest international registry (NCT04354701) recording outcomes of pts with cancer and COVID-19. The registry was queried for hospitalized pts who developed VTE and received systemic cancer treatment in the year prior to COVID-19. Incidence of VTE was analyzed as the primary endpoint; 30-day any cause mortality &amp; need for ICU admission at baseline were secondary endpoints in pts with and without VTE respectively. Pts were stratified by treatment type and time from last treatment dose: &lt;2 wk, 2-4 wk, 1-3 months (mos), 3-12 mos. Results: As of February 9th 2021, 4217 hospitalized pts with complications data were present in the registry. 1867 (44%) pts had received systemic anti-cancer therapy within the year prior to COVID-19 and were analyzed. There were a total of 186 (10%) VTE events. Of these, VTE incidence was 141 (10.5%) in pts with solid tumors and 57 (9%) in pts with hematologic malignancies. Overall 30-day mortality was 20% and 22% in pts with and without VTE respectively, while direct admission to ICU at presentation was seen in 17% and 10% of pts with and without VTE, respectively. Treatment timing and drug exposures are below (Table). Receipt of systemic anti-cancer treatment within 3 mos vs 3-12 mos was associated with increased rate of VTE, OR 2.44, 95% CI 1.18-5.84, p=0.011 (univariate Fisher test). Conclusions: We describe the incidence of VTE events in pts with cancer and COVID-19 with recent systemic cancer therapy. ICI and VEGFi were associated with numerically higher rates of VTE; other examined drugs and drug classes were not. Timing of therapy appears to modify risk of VTE. Although retrospective, with possible selection and confounding biases, our analysis suggests that factors other than anti-cancer drug exposures may drive VTE events in this population.[Table: see text]
Brisk bleeding after gastric lesion biopsy – possible needle tract seeding after endoscopic ultrasound-guided fine-needle biopsy of a pancreatic metastasis from renal cell carcinoma
Authors: Simone Freund, Tina Schaller, Claus Schöler, Helmut Messmann, Stefan K. Gölder
Journal: Endoscopy (2021)

A 62-year-old patient had undergone left-sided partial nephrectomy due to renal cell carcinoma. The postoperative tumor classification was pT1a, pNx, L0, V0, G2, R0.
Funding boost aims to expand England’s medical school places
Authors: Adrian O’Dowd
Journal: BMJ (2021)

Growing demand for medical school places is to be met with additional funding of as much as £10m (€11.8m; $13.8m) from the government as school A level results have reached a record high.

The government announced on 5 August that it would give medical and dental schools around England additional funding to expand courses for the coming academic year, to fulfil more offers for UK students who achieved the necessary grades.

Doctors’ representatives welcomed the news but said that this would equate to no more than an extra 250 medical school places and that they would like more solid guarantees of foundation places after graduation.

The number of available university places to study medicine is …
Associations Among Different Domains of Quality Among US Liver Transplant Programs
Authors: Craig S. Brown, Seth A. Waits, Michael J. Englesbe, Christopher J. Sonnenday, Kyle H. Sheetz
Journal: JAMA Network Open (2021)

<h3>Importance</h3> US liver transplant programs have traditionally been evaluated on 1-year patient and graft survival. However, there is concern that a narrow focus on recipient outcomes may not incentivize programs to improve in other ways that would benefit patients with end-stage liver disease. <h3>Objective</h3> To determine the correlation among different potential domains of quality for adult liver transplant programs. <h3>Design, Setting, and Participants</h3> This retrospective cohort study was conducted from 2014 to 2019 among adult liver transplant programs included in the United Network for Organ Sharing and Scientific Registry of Transplant Recipients program-specific reports. Liver transplant programs in the United States completing at least 10 liver transplants per year were included. Data were analyzed from March 2 to August 13, 2020. <h3>Main Outcomes and Measures</h3> The potential domains of quality examined included recipient outcomes (1-year graft and patient survival), aggressiveness (ie, marginal graft use, defined as the rate of use of donors with body mass index [calculated as weight in kilograms divided by height in meters squared] greater than 40, age older than 65 years, or deceased by cardiac death), and waiting list management (ie, waiting list mortality). The correlation among measures, aggregated at the center level, was evaluated using linear regression to control for mean Model for End Stage Liver Disease–Sodium score at organ allocation. The extent to which programs were able to achieve high quality across multiple domains was also evaluated. <h3>Results</h3> Among 114 transplant programs that performed a total of 44 554 transplants, the mean (SD) 1-year graft and patient survival was 90.3% (3.0%) with a total range of 75.9% to 96.6%. The mean (SD) waiting list mortality rate was 16.7 (6.1) deaths per 100 person-years, with a total range of 6.3 to 53.0 deaths per 100 person years. The mean (SD) marginal graft use rate was 15.8 (8.8) donors per 100 transplants, with a total range of 0 to 49.3 donors. There was no correlation between 1-year graft and patient survival and waiting list mortality (β = −0.053;<i>P</i> = .19) or marginal graft use (β = −0.007;<i>P</i> = .84) after correcting for mean allocation Model for End Stage Liver Disease–Sodium scores. There were 2 transplant programs (1.8%) that performed in the top quartile on all 3 measures, while 4 transplant programs (3.6%) performed in the bottom quartile on all 3 measures. <h3>Conclusions and Relevance</h3> This cohort study found that among US liver transplant programs, there were no correlations among 1-year recipient outcomes, measures of program aggressiveness, or waiting list management. These findings suggest that a program's performance in one domain may be independent and unrelated to its performance on others and that the understanding of factors contributing to these domains is incomplete.
Abstract 14400: Manipulating Myocardial Wnt Signalling For Post-Ischemic Myocardial Protection
Authors: Kylie M Venardos, David Williams, Duncan Horlock, Jason Peart, Sean L McGee, David M Kaye
Journal: Circulation (2011)

Myocardial injury due to ischemia-reperfusion (I-R) damage remains a major clinical challenge. Currently the pathogenesis of I-R injury continues to be debated and to date no clinically proven appr...
Diagnostic work‐up for severe aplastic anemia in children: Consensus of the <scp>North American Pediatric Aplastic Anemia Consortium</scp>
Authors: Kristin A. Shimano, Anupama Narla, Melissa J. Rose, Nicholas J. Gloude, Steven W. Allen, Katie Bergstrom, Larisa Broglie, Beth A. Carella, Paul Castillo, Jill L. O. de Jong, Yigal Dror, Amy E. Geddis, James N. Huang, Bonnie W. Lau, Catherine McGuinn, Taizo A. Nakano, Kathleen Overholt, Jennifer A. Rothman, Anjali Sharathkumar, Evan Shereck, Adrianna Vlachos, Timothy S. Olson, Alison A. Bertuch, Marcin W. Wlodarski, Akiko Shimamura, Jessica Boklan
Journal: American Journal of Hematology (2021)

The North American Pediatric Aplastic Anemia Consortium (NAPAAC) is a group of pediatric hematologist-oncologists, hematopathologists, and bone marrow transplant physicians from 46 institutions in North America with interest and expertise in aplastic anemia, inherited bone marrow failure syndromes, and myelodysplastic syndromes. The NAPAAC Bone Marrow Failure Diagnosis and Care Guidelines Working Group was established with the charge of harmonizing the approach to the diagnostic workup of aplastic anemia in an effort to standardize best practices in the field. This document outlines the rationale for initial evaluations in pediatric patients presenting with signs and symptoms concerning for severe aplastic anemia.
Abstract 15905: Silencing Prolyl Hydroxylase-1(phd-1) Induces Neovascularization, Reduces Ventricular Remodeling by Stabilization and Activation of Hif-1 Alpha, Nf-Kappab/Hspa12b in the Infarcted Myocardium: A Study With Phd-1 Knockout Mice
Authors: Mahesh Thirunavukkarasu, Babatunde Oriowo, Lijun Zhan, Gautam Maulik, Kotaro Takeda, Guo-Hua Fong, Juan A Sanchez, Nilanjana Maulik
Journal: Circulation (2011)

Hypoxia-inducible factor (HIF)-prolylhydroxylases (PHDs) are oxygen sensors that regulate the stability of HIF in an oxygen-dependent manner thus mediating cellular adaptive responses to changes in...
Heart Failure with Preserved Ejection Fraction: Mechanisms and Treatment Strategies
Authors: Kazunori Omote, Frederik H. Verbrugge, Barry A. Borlaug
Journal: Annual Review of Medicine (2021)

Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome.
Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial
Authors: Frederikus A Klok, Gerrit Toenges, Anna C Mavromanoli, Stefano Barco, Walter Ageno, Hélène Bouvaist, Marianne Brodmann, Claudio Cuccia, Francis Couturaud, Claudia Dellas, Konstantinos Dimopoulos, Daniel Duerschmied, Klaus Empen, Pompilio Faggiano, Emile Ferrari, Nazzareno Galiè, Marcello Galvani, Alexandre Ghuysen, George Giannakoulas, Menno V Huisman, David Jiménez, Matija Kozak, Irene Marthe Lang, Mareike Lankeit, Nicolas Meneveau, Thomas Münzel, Massimiliano Palazzini, Antoniu Octavian Petris, Giancarlo Piovaccari, Aldo Salvi, Sebastian Schellong, Kai-Helge Schmidt, Franck Verschuren, Irene Schmidtmann, Guy Meyer, Stavros V Konstantinides, Jaime Antonio, Abelaira Freire, Walter Ageno, Ibrahim Akin, Toni Anusic, Stefano Barco, Dorothea Becker, Laurent Bertoletti, Giuseppe Bettoni, Harald Binder, Marianne Brodmann, Hélène Bouvaist, Regina Carels, Claudio Cuccia, Francis Couturaud, Claudia Dellas, Giuseppe Di Pasquale, Konstantinos Dimopoulos, Daniel Dürschmied, Klaus Empen, Iolanda Enea, Pompilio Faggiano, Emile Ferrari, Joachim Ficker, Nazzareno Galiè, Marcello Galvani, Sabine Genth-Zotz, George Giannakoulas, Philippe Girard, Stanislav Gorbulev, Alexandre Ghuysen, Matthias Held, Lukas Hobohm, Menno V. Huisman, David Jiménez, Frederikus A. Klok, Stavros V. Konstantinides, Matija Kozak, Kai Kronfeld, Irene Marthe Lang, Mareike Lankeit, Walter Lehmacher, Concepcion Patricia Lopez Miguel, Nadine Martin, Anna Mavromanoli, Nicolas Meneveau, Guy Meyer, Thomas Münzel, Massimiliano Palazzini, Roman Pareznik, Antoniu Octavian Petris, Giancarlo Piovaccari, Kurt Quitzau, Irinel Raluca Parepa, Purificacion Ramirez Martin, Marc Righini, Aldo Salvi, Sebastian Schellong, Kai-Helge Schmidt, Irene Schmidtmann, Gerrit Toenges, Silviu Bogdan Todea, Adam Torbicki, Luca Valerio, Thomas Vanassche, Franck Verschuren, Luminita Animarie Vida-Simiti, Anamaria Wolf-Pütz
Journal: The Lancet Haematology (2021)
DA(A)術後慢性腎不全にDICを併発した吻合部偽性動脈瘤に対してBentall+半弓部大動脈置換術を行った1例
Authors: 渕上泰, 小出昌秋, 國井佳文, 梅原伸大, 渡邊一正
Journal: Circulation (2008)
Abstract 15645: Long Term Results of Patients With d-Transposition of the Great Arteries and Native Bicuspid Pulmonary Valves After the Arterial Switch Operation
Authors: Kathleen E Walsh, Denise A Hayes, Jan M Quaegebeur, Emile Bacha, Leonardo Liberman
Journal: Circulation (2013)

Background: A native bicuspid pulmonary valve (BPV) that takes on the role of the neo-aortic valve after the arterial switch operation (ASO) could be a source of increased morbidity in patients wit...
Brain tumors
Authors: E. R. Laws, K. Thapar
Journal: CA A Cancer Journal for Clinicians (1993)

Brain tumors are a relatively common cancer in all age groups, and the incidence of both primary and metastatic brain tumors is increasing. Fortunately, dramatic advances in methods of diagnosis, surgical technique, and adjuvant therapy have all contributed to an improved outlook for patients with brain tumors. This article reviews the classification, symptoms, diagnosis, and treatment of brain tumors.
Abstract 10718: Novel Application of a Clinical Pathway Embedded in the Electronic Health Record to Improve Quality of Care in Patients Hospitalized With Acute Decompensated Heart Failure
Authors: Sunil E Saith, Tony Mathews, David Rhee, Amit Patel, Yu Guo, Jonathan S Austrian, Frank M Volpicelli, Stuart D Katz
Journal: Circulation (2018)

Introduction: Acute decompensated heart failure (ADHF) is the leading admission and readmission diagnosis to hospitals in the United States today. There are 6.5 million Americans with heart failure...
Propylene Glycol Monomethyl Ether
Journal: Environmental Health Perspectives (1997)

The aim of this study is to develope an analytical method for propylene glycol monomethy1 ether(PGME) and 1,2-propylene glycol(PG) in biological fluid by derivatization using benzoyl chloride using GC/FID/MSD. The detection limits of PGME and PG are 4.02ppm and 1.25ppm, respectively. Reproducibilities of derivatization of PGME and PG are 99.0±4.9 and 98.0±4.8 with 4.5%(n=5) of pooled coefficient variation(pooled CV) Benzoylation of PGME and PG are quantitatively performed by the reaction of 522nmol of PGME and 163umol of benzoyl chloride, and 527nmol of PG and 734umol of benzoyl chloride in a mixture of 1ml of 2M NaOH aqueous solution and 1ml of n-hexan. The reactions are completed within 30 minutes. The relative weight response of PG dibenzoate is 4.71 times higher than PGME benzoate by GC/FID. The formations of PGME benzoate and PG dibenzoate in spiked human urine and rat urine which were adrmnistered lml of PGME were confirmed by GC/FID/MSD. The relative weight response of PGME benzoate to PG dibenzoate of first-day rat urine is 3.01-5.50 times(weight ratio) higher, and 0.18-1.95 times higher at following day.