tbuckley/cabot-search huggingface dataset:
Slow Conduction and Reentry in the Ventricular Conducting System
Authors: ANDREW L. WIT, BRIAN F. HOFFMAN, PAUL F. CRANEFIELD
Journal: Circulation Research (1972)

Depression of excitability and responsiveness provoked by the action of high K + and epinephrine on short bundles of excised canine Purkinje fibers yields reentrant excitation. An impulse entering a depressed area undergoes marked slowing of conduction; the impulse then may continue forward while also returning through the pathway by which the initiating impulse entered the depressed area. The impulse may be delayed or blocked in either the forward or the retrograde direction. The reentrant excitation can occur in the absence of premature excitation. Various methods of depression of excitability produce return extrasystoles in Purkinje fibers. The common factor is very slow conduction which depends upon the abolition of the fast upstroke and the appearance of a low-voltage, slowly propagated action potential that is readily blocked.
Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial
Authors: Jonathan A Ledermann, Amit M Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Johanne I Weberpals, Andrew R Clamp, Giovanni Scambia, Alexandra Leary, Robert W Holloway, Margarita Amenedo Gancedo, Peter C Fong, Jeffrey C Goh, David M O'Malley, Deborah K Armstrong, Susana Banerjee, Jesus García-Donas, Elizabeth M Swisher, Terri Cameron, Lara Maloney, Sandra Goble, Robert L Coleman
Journal: The Lancet Oncology (2020)
Grounded procedures: A proximate mechanism for the psychology of cleansing and other physical actions
Authors: Spike W. S. Lee, Norbert Schwarz
Journal: Behavioral and Brain Sciences (2020)

Abstract Experimental work has revealed causal links between physical cleansing and various psychological variables. Empirically, how robust are they? Theoretically, how do they operate? Major prevailing accounts focus on morality or disgust, capturing a subset of cleansing effects, but cannot easily handle cleansing effects in non-moral, non-disgusting contexts. Building on grounded views on cognitive processes and known properties of mental procedures, we propose grounded procedures of separation as a proximate mechanism underlying cleansing effects. This account differs from prevailing accounts in terms of explanatory kind, interpretive parsimony, and predictive scope. Its unique and falsifiable predictions have received empirical support: Cleansing attenuates or eliminates otherwise observed influences of prior events (1) across domains and (2) across valences. (3) Cleansing manipulations produce stronger effects the more strongly they engage sensorimotor capacities. (4) Reversing the causal arrow, motivation for cleansing is triggered more readily by negative than positive entities. (5) Conceptually similar effects extend to other physical actions of separation. On the flipside, grounded procedures of connection are also observed. Together, separation and connection organize prior findings relevant to multiple perspectives (e.g., conceptual metaphor, sympathetic magic) and open up new questions. Their predictions are more generalizable than the specific mappings in conceptual metaphors, but more fine-grained than the broad assumptions of grounded cognition. This intermediate level of analysis sheds light on the interplay between mental and physical processes.
Induction Chemo-Immunotherapy with the Matrix Regimen in Patients with Newly Diagnosed PCNSL - a Multicenter Retrospective Analysis on Feasibility and Effectiveness in Routine Clinical Practice
Authors: Elisabeth Schorb, Chris P Fox, Benjamin Kasenda, Teresa Calimeri, Kim Linton, Jeffery Smith, Slavisa Ninkovic, Deborah Yallop, Hans-Guido Holl, Alberto Fabbri, Thomas E C Cummin, Gerald Illerhaus, Kate Cwynarski, Andrés J M Ferreri
Journal: Blood (2017)
Cholesterol metabolism in liver and gallbladder mucosa of patients with cholesterolosis*1
Authors: S SAHLIN
Journal: Hepatology (1995)

The objective of this study was to investigate possible pathogenetic factors for cholesterolosis. Liver tissue, gallbladder mucosa, and gallbladder bile were collected in patients with cholesterol gallstones (GS) (14 patients with and 14 patients without cholesterolosis) and gallstone-free (GSF) subjects (11 with and 21 without cholesterolosis) undergoing cholecystectomy. In cholesterolosis, the gallbladder mucosa was characterized by a fivefold increase in esterified cholesterol and normal content of free cholesterol. The hepatic levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, and acyl coenzyme A: acyltransferase activity, catalyzing the esterification of cholesterol, were similar in patients with and without cholesterolosis. Also in the gallbladder mucosa, the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was similar in patients with and without cholesterolosis. The acyl coenzyme A: acyltransferase activity of the gallbladder mucosa was increased in the GSF subjects with cholesterolosis. The nucleation time of gallbladder bile was shorter in the GSF subjects with cholesterolosis compared with the time of those without cholesterolosis. Occurrence of cholesterol crystals, lipid composition, and cholesterol saturation of gallbladder bile were not significantly influenced by the absence or presence of cholesterolosis. The study has confirmed that cholesterolosis is associated with a several-fold increased level of esterified cholesterol. The data suggest that patients with cholesterolosis have normal hepatic cholesterol formation and esterification. The local synthesis of cholesterol in the gallbladder mucosa seems to be normal. A positive correlation was obtained between the cholesterol saturation of bile and the content of esterified cholesterol in the gallbladder mucosa in the whole series of patients. However, because cholesterolosis may occur in both GSF subjects and patients with cholesterol GS with or without cholesterol-saturated bile, the uptake of cholesterol from the gallbladder bile may not be the only mechanism for the development of cholesterolosis.
A phase II study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin in advanced esophageal cancer.
Authors: J. Yoon, J. Hwang, W. Bae, H. Shim, T. Nam, K. Na, I. Chung
Journal: Journal of Clinical Oncology (2010)

e14549 Background: The optimal treatment of advanced esophageal cancer remains a controversial subject. To improve dysphagia, chemoradiotherapy (CRT) has been considered as a useful treatment for patients (pts) with unresectable esophageal cancer. This study was conducted to evaluate the clinical outcomes and safety of concurrent CRT with weekly docetaxel and cisplatin in advanced esophageal cancer. Methods: Patients with locally advanced or metastatic esophageal squamous cell carcinoma, who have adequate organ function were eligible. During CRT, docetaxel and cisplatin were given at a dose of 20 mg/m2 and 25 mg/m2, respectively at D1, D8, D15. The cycle of this treatment was 28 days. Two cycles of chemotherapy was done during radiotherapy. Radiotherapy was started at a dose of 200 cGy/day, up to a total of 5400 cGy. Results: Up to December 2009, 31 pts were enrolled. Among them 30 pts (97%) completed the planned CRT. The median age was 61 years (range: 45- 72); male/female = 29/2; ECOG performance status was 0/1/2 = 12/15/4; stage IIb/III/IVa/IVb = 3/16/3/9. Complete response was achieved in 7 pts (22.6%), partial response in 19 (61.3%), stable disease in 2 (6.5 %), progressive disease in 2 (6.5%) and 1 (3.2%) patient was not evaluable. Therefore, the overall response rate was 83.9% (95% CI, 70.9-96.8). The CRT related grade 3-4 hematologic toxicities were rarely observed: leucopenia (3.2%) and non-febrile neutropenia (3.2%) The most common non hematologic toxicity was esophagitis. Grade 3 or 4 of esophagitis has been developed in 5 pts (16.1%) and asthenia in 1 patient (3.2%). Improvement of dysphagia after CRT had been shown in 21 pts among 28 pts (67.7%) who had complained of dysphagia at the time of diagnosis. A clinically meaningful improvement in dysphagia was found after 27 days of the first treatment. At a mean follow-up of 16 months, the estimated 1-year progression-free survival rate and overall survival rate was 35.5% and 41.9% respectively. Conclusions: The concurrent CRT with weekly docetaxel and cisplatin was safe and well tolerated in pts with advanced esophageal cancer in the outpatient setting. This result indicated promising activity both in tumor control and in symptom control. No significant financial relationships to disclose.
Immune-related adverse events of checkpoint inhibitors
Authors: Manuel Ramos-Casals, Julie R. Brahmer, Margaret K. Callahan, Alejandra Flores-Chávez, Niamh Keegan, Munther A. Khamashta, Olivier Lambotte, Xavier Mariette, Aleix Prat, Maria E. Suárez-Almazor
Journal: Nature Reviews Disease Primers (2020)
ADTH-06 Microscopic residual lesion after apparent complete EMR of large lesions: evidence for mechanism of recurrence
Authors: Andrew Emmanuel, Shraddha Gulati, Monica Ortenzi, Margaret Burt, Bu Hayee, Amyn Haji
Journal: Endoscopy (2018)

<h3>Introduction</h3> Endoscopic mucosal resection (EMR) of large colorectal superficial neoplastic lesions (CSNL) is associated with significant recurrence and the risk of recurrence is significantly higher with piecemeal EMR (pEMR). The mechanism for recurrence has not been proven but has been postulated to occur as a result of microscopic areas of residual adenoma left between areas of sequential snare capture during pEMR. We aimed to determine the incidence of residual microadenoma in apparently normal mucosa left at the margin of the defect following EMR. <h3>Methods</h3> Following EMR/pEMR of 31 large CSNL, the base and margin of the resulting defect were examined with magnification chromoendoscopy and NBI/BLI to ensure complete resection. The apparently normal mucosa at the defect margin was then resected using the EndoRotor() device, removing and sampling the full extent of the defect margin. Areas of submucosal fibrosis or diathermy artefact at the base were also sampled if present. Data on the lesion characteristics, resection technique, number of pieces for pEMR, histopathology findings of the lesion and the mucosa at the margin were collected. <h3>Results</h3> Mean lesion size was 46.7 mm (range 32 mm-130 mm). Mucosa at the defect margin was sampled in all cases and 100% of the margin was achieved in 28 (90%). Final histopathology of resected lesions was adenoma in 27 (87%), serrated adenoma in 2 (6%) and adenocarcinoma in 2. Microscopic residual lesion was detected in the margin of apparently normal mucosa in 4 cases (13%). In 3 cases this was adenoma with low grade dysplasia and in one case a serrated lesion with no dysplasia was found in at the margin of a resected tubular adenoma. Microscopic residual lesion was detected in the base in 4 cases: 1 was microadenoma, 2 were serrated lesions without dysplasia in the base of resected adenomas and 1 was residual adenocarcinoma. There was no association with pEMR in &gt;3 pieces and residual microscopic lesion or pEMR ≤3 pieces (OR 0.89, 95% CI 0.16–4.8, p=0.89). There were no complications. <h3>Conclusions</h3> To our knowledge, this is the first series examining the findings after continuous sampling of the full circumferential margin of apparently normal mucosa left at the defect after EMR of large CSNL. Despite examination with magnification suggesting complete resection, microscopic residual lesion at the margin was present in 13%. This study provides evidence that microscopic residual lesion left after EMR underlies the pathophysiology of recurrence and lends support for techniques that continuously resect or ablate the circumferential margin of the defect to reduce recurrence.
Understanding the Early Evolutionary Stages of a Tandem Drosophilamelanogaster-Specific Gene Family: A Structural and Functional Population Study
Authors: Bryan D Clifton, Jamie Jimenez, Ashlyn Kimura, Zeinab Chahine, Pablo Librado, Alejandro Sánchez-Gracia, Mashya Abbassi, Francisco Carranza, Carolus Chan, Marcella Marchetti, Wanting Zhang, Mijuan Shi, Christine Vu, Shudan Yeh, Laura Fanti, Xiao-Qin Xia, Julio Rozas, José M Ranz
Journal: Molecular Biology and Evolution (2020)

Abstract Gene families underlie genetic innovation and phenotypic diversification. However, our understanding of the early genomic and functional evolution of tandemly arranged gene families remains incomplete as paralog sequence similarity hinders their accurate characterization. The Drosophila melanogaster-specific gene family Sdic is tandemly repeated and impacts sperm competition. We scrutinized Sdic in 20 geographically diverse populations using reference-quality genome assemblies, read-depth methodologies, and qPCR, finding that ∼90% of the individuals harbor 3–7 copies as well as evidence of population differentiation. In strains with reliable gene annotations, copy number variation (CNV) and differential transposable element insertions distinguish one structurally distinct version of the Sdic region per strain. All 31 annotated copies featured protein-coding potential and, based on the protein variant encoded, were categorized into 13 paratypes differing in their 3′ ends, with 3–5 paratypes coexisting in any strain examined. Despite widespread gene conversion, the only copy present in all strains has functionally diverged at both coding and regulatory levels under positive selection. Contrary to artificial tandem duplications of the Sdic region that resulted in increased male expression, CNV in cosmopolitan strains did not correlate with expression levels, likely as a result of differential genome modifier composition. Duplicating the region did not enhance sperm competitiveness, suggesting a fitness cost at high expression levels or a plateau effect. Beyond facilitating a minimally optimal expression level, Sdic CNV acts as a catalyst of protein and regulatory diversity, showcasing a possible evolutionary path recently formed tandem multigene families can follow toward long-term consolidation in eukaryotic genomes.
OP0104 Knee Joint Distraction Compared with High Tibial Osteotomy: A Randomized Controlled Trial
Authors: J.-T. van der Woude, R.J. van Heerwaarden, S. Spruijt, K. Wiegant, P.M. van Roermund, D.B. Saris, S.C. Mastbergen, F.P. Lafeber
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Knee joint distraction (KJD) results in clinical improvement and cartilage repair in young, active patients with knee OA. Another knee preserving treatment, in medial compartment knee osteoarthritis, is a high tibial osteotomy (HTO), which has good mid-term and longer follow-up results. However, no comparative data on efficacy is available. A RCT was set out and determined whether there was a clinical relevant difference in functional outcome after 1-year between KJD and HTO. <h3>Methods</h3> 69 patients with medial osteoarthritis were included and randomized to KJD (23 patients) or HTO (46 patients). A WOMAC questionnaire (100 being the best) was assessed at baseline (BL) and 12 months. EQ-5D index score was used to assess improvement in the quality of life (1 being the best). Joint space width (JSW) of the medial compartment was determined on standardized semi-flexed x-rays at BL and 1-year. <h3>Results</h3> 45 patients received HTO (mean age at surgery 49.4±1.0, mean BMI 27.2±0.5 kg/m<sup>2</sup> and mean Kellgren &amp; Lawrence grade 2.5±0.1). 22 patients received KJD (mean age at surgery 51.2±1.1, mean BMI 27.5±0.7, mean Kellgren and Lawrence grade 2.3±0.2). Total WOMAC scores demonstrated significant clinical improvement in both groups. The KJD group increased from 57±17 points at BL to 76±17 points at 1-year (p&lt;0.001). Similarly, the HTO group had a score of 52±16 points at BL, which increased to 81±16 points (p&lt;0.001). Parallel results were seen for the VAS and the quality of life (table 2). None of the parameters showed a statistical significant difference between the two groups at 1-year (p=0.318, p=0.170 and p=0.787 resp.). Both the minimum and mean JSW showed a steeper increase in the KJD-group (table 2). <h3>Conclusions</h3> Six weeks of KJD does not lead to a clinical relevant difference in outcome compared with HTO after 1-year. Importantly both KJD and HTO lead to substantial newly formed cartilage-like tissue with superiority of KJD. Thus KJD is an alternative option in patients less suitable for HTO. <h3>Disclosure of Interest</h3> None declared
AB0745 Rate of serious infections in behcet’s disease patients receiving biologic therapies: A prospective observational study
Authors: C. Ferrari, R. Talarico, C. Stagnaro, A. d’Ascanio, L. Bazzichi, S. Bombardieri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Behçet's disease (BD) is a multisystemic, chronic relapsing inflammatory disease classified among the vasculitis. Literature data show growing data reporting effectiveness of TNF-alpha blockers in inducing remission for sight- and life-threatening involvement in BD. Tumor necrosis factor (TNF) plays an important role in host defense and tumor growth control, therefore, anti-TNF antibody therapies may increase the risk of serious infections. <h3>Objectives</h3> the primary objective of the study was to assess the rate of serious infections associated with the use of biologic therapy (infliximab, adalimumab) in patients with BD; the secondary aims were: to quantify the latency period between the beginning of biologic therapy and the onset of infection and to study any potential correlation among clinical-epidemiological data and frequency of infections. <h3>Methods</h3> twenty-five patients (M/F:14/10; mean age 38,5 years, min-max 25:52; mean age at disease onset: 25 years; mean disease duration 13,4 years) were prospective evaluated. The rate of serious infections was expressed in terms of incidence rate ratio (IRR). The latency period between the beginning of biologic therapy and the onset of infection was evaluated both in terms of weeks and number of infusions received. <h3>Results</h3> The patients received infliximab at the dose of 3-5 mg/kg at week 0, 2, 4 and then every 8 weeks.; moreover after a minimum period of 44 weeks and maximum of 96 weeks, 3 patients was switched for loss of efficacy to adalimumab, at the dose of 40 mg every 2 weeks. During the follow-up, we found 3 cases of serious infections (12%): one case of pneumonia, one of myopericarditis and a mononucleosis, all cases receiving infliximab therapy. The incidence rate ratio (IRR) was 4.3/1000 person-months (95% CI 1-12). Moreover, the latency period between the beginning of therapy and the onset of each infection was 192, 428 and 168 weeks respectively, with the following number of infusions: 26, 55 and 23. Any correlations was found among clinical and epidemiological features and frequency of infections. <h3>Conclusions</h3> These findings show that overall, rate of serious infections in Behcet's disease patients receiving biologic therapies is not so different from the rate of serious infections reported in rheumatoid arthritis. However, in order to balance benefits and risks, it is desirable that results from long-term observational studies and clinical trials may allow the scientific community to reach the target of a suspension schedule of biologic therapies. <h3>Disclosure of Interest</h3> None Declared
Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19
Authors: Harmony R. Reynolds, Samrachana Adhikari, Claudia Pulgarin, Andrea B. Troxel, Eduardo Iturrate, Stephen B. Johnson, Anaïs Hausvater, Jonathan D. Newman, Jeffrey S. Berger, Sripal Bangalore, Stuart D. Katz, Glenn I. Fishman, Dennis Kunichoff, Yu Chen, Gbenga Ogedegbe, Judith S. Hochman
Journal: New England Journal of Medicine (2020)

There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference.Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.
Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case–control–control study
Authors: M. Bartoletti, M. Rinaldi, Z. Pasquini, L. Scudeller, S. Piano, D.R. Giacobbe, A.E. Maraolo, L. Bussini, F. Del Puente, S. Incicco, P. Angeli, M. Giannella, M. Baldassarre, P. Caraceni, C. Campoli, M.C. Morelli, M. Cricca, S. Ambretti, I. Gentile, M. Bassetti, P. Viale
Journal: Clinical Microbiology and Infection (2020)
Ambulatory treatment of low-risk pulmonary embolism in fragile patients: a subgroup analysis of the multinational Home Treatment of Pulmonary Embolism (HoT-PE) Trial
Authors: Lukas Hobohm, Toni Anušić, Stavros V. Konstantinides, Stefano Barco
Journal: European Respiratory Journal (2020)

<b>Early discharge and home treatment of acute pulmonary embolism in fragile patients appears to be feasible and acceptably safe. Caution is warranted due to the higher risk of major bleeding among fragile patients.</b>https://bit.ly/2YtStiU