tbuckley/cabot-search huggingface dataset:
Surveillance of OXA-244-producing Escherichia coli and epidemiologic investigation of cases, Denmark, January 2016 to August 2019
Authors: Anette M Hammerum, Lone Jannok Porsbo, Frank Hansen, Louise Roer, Hülya Kaya, Anna Henius, Karina Lauenborg Møller, Ulrik S Justesen, Lillian Søes, Bent L Røder, Philip K Thomsen, Mikala Wang, Turid Snekloth Søndergaard, Barbara Juliane Holzknecht, Claus Østergaard, Anne Kjerulf, Brian Kristensen, Henrik Hasman
Journal: Eurosurveillance (2020)

Background Carbapenemase-producing Escherichia coli are increasing worldwide. In recent years, an increase in OXA-244-producing E. coli isolates has been seen in the national surveillance of carbapenemase-producing organisms in Denmark. Aim Molecular characterisation and epidemiological investigation of OXA-244-producing E. coli isolates from January 2016 to August 2019. Methods For the epidemiological investigation, data from the Danish National Patient Registry and the Danish register of civil registration were used together with data from phone interviews with patients. Isolates were characterised by analysing whole genome sequences for resistance genes, MLST and core genome MLST (cgMLST). Results In total, 24 OXA-244-producing E. coli isolates were obtained from 23 patients. Among the 23 patients, 13 reported travelling before detection of the E. coli isolates, with seven having visited countries in Northern Africa. Fifteen isolates also carried an extended-spectrum beta-lactamase gene and one had a plasmid-encoded AmpC gene. The most common detected sequence type (ST) was ST38, followed by ST69, ST167, ST10, ST361 and ST3268. Three clonal clusters were detected by cgMLST, but none of these clusters seemed to reflect nosocomial transmission in Denmark. Conclusion Import of OXA-244 E. coli isolates from travelling abroad seems likely for the majority of cases. Community sources were also possible, as many of the patients had no history of hospitalisation and many of the E. coli isolates belonged to STs that are present in the community. It was not possible to point at a single country or a community source as risk factor for acquiring OXA-244-producing E. coli .
A Likelihood Approach for Uncovering Selective Sweep Signatures from Haplotype Data
Authors: Alexandre M Harris, Michael DeGiorgio
Journal: Molecular Biology and Evolution (2020)

Selective sweeps are frequent and varied signatures in the genomes of natural populations, and detecting them is consequently important in understanding mechanisms of adaptation by natural selection. Following a selective sweep, haplotypic diversity surrounding the site under selection decreases, and this deviation from the background pattern of variation can be applied to identify sweeps. Multiple methods exist to locate selective sweeps in the genome from haplotype data, but none leverages the power of a model-based approach to make their inference. Here, we propose a likelihood ratio test statistic T to probe whole-genome polymorphism data sets for selective sweep signatures. Our framework uses a simple but powerful model of haplotype frequency spectrum distortion to find sweeps and additionally make an inference on the number of presently sweeping haplotypes in a population. We found that the T statistic is suitable for detecting both hard and soft sweeps across a variety of demographic models, selection strengths, and ages of the beneficial allele. Accordingly, we applied the T statistic to variant calls from European and sub-Saharan African human populations, yielding primarily literature-supported candidates, including LCT, RSPH3, and ZNF211 in CEU, SYT1, RGS18, and NNT in YRI, and HLA genes in both populations. We also searched for sweep signatures in Drosophila melanogaster, finding expected candidates at Ace, Uhg1, and Pimet. Finally, we provide open-source software to compute the T statistic and the inferred number of presently sweeping haplotypes from whole-genome data.
Особенности иммунологического статуса и углеводного обмена на разных стадиях фиброза печени у больных хроническим гепатитом, ассоциированным с вирусом С
Authors: Yu.M. Stepanov, V.I. Didenko, I.S. Konenko, O.M. Tatarchuk, O.P. Petishko
Journal: GASTROENTEROLOGY (2020)

Актуальность. В статье рассматриваются вопросы взаимосвязей структурных изменений печени с показателями иммунологического статуса у больных с хроническим вирус­ным гепатитом С (ХГС). Цель: определить особенности изменений иммунологического статуса и углеводного обмена у больных ХГС в зависимости от стадии фиброза. Материалы и методы. Обследованы 94 пациента с хроническим гепатитом С, средний возраст которых составил (49,91 ± 11,23) года. Выполнили морфологическое исследование у 42 больных, сдвиговолновую эластографию печени (СВЭ) и оценку коэффициента затухания ультразвука. Для изучения ассоциа­ций иммунологического статуса и углеводного обмена со структурными изменениями печени всех больных разделили на группы: с умеренным (FI + FII) и выраженным фиброзом (FIII + FIV) по шкале METAVIR. Определяли субпопуляционный состав лимфоцитов, циркулирующих иммунных комплексов, проводили оценку иммунного статуса. Осуществили оценку инсулинорезистентности с помощью индекса HOMA-IR. Статистическую обработку полученных результатов проводили с помощью пакета прикладных программ Statistica 6.1 (серийный номер AGAR909 E415822FA). Результаты. У 73,4 % больных ХГС снижено относительное содержание СD3+-лимфоцитов. Медиана относительного содержания СD4+-лимфоцитов была ниже в 1,4 раза (р &lt; 0,05) по сравнению с контролем. У больных ХГС СD4+-клетки стимулируют продукцию антител В-лимфоцитами (r = 0,56, р &lt; 0,01) и активируют СD8+ Т-клетки (r = 0,59, р &lt; 0,01), специфические для вирусинфицированных клеток. Нарушение (снижение) индекса иммунорегуляции установлено у 79,8 % больных. Определены отрицательные корреляционные связи между содержанием Т-хелперов и СВЭ печени (r = –0,26, р &lt; 0,05). Определено увеличение содержания инсулина у больных ХГС с выраженным фиброзом относительно его уровня в группе контроля в 2,3 раза (р &lt; 0,05) и больных с умеренным фиброзом в 1,3 раза (р &lt; 0,05), установлена связь этого показателя с жесткостью печени по данным СВЭ (r = 0,43, р &lt; 0,05). Выявлена связь между уровнем ИЛ-6 и СВЭ печени (r = 0,68, р &lt; 0,01), степенью фиброза (по METAVIR) (r = 0,57, р &lt; 0,01). Отдельные иммунологические показатели (содержание В-лимфоцитов, Т-хелперов, TNF-α, ИЛ-6 и инсулина) могут быть использованы для разработки неинвазивной диагностики умеренного и выраженного фиброза печени у больных с ХГС. Выводы. У больных с ХГС прогрессирование фиброза печени сопровождается истощением клеточного звена иммунитета, повышением уровня провоспалительных цитокинов и нарушением углеводного обмена в зависимости от выраженности фиброзной трансформации.
Cyclosporine therapy during the COVID-19 pandemic
Authors: Lidia Rudnicka, Paulina Glowacka, Mohamad Goldust, Mariusz Sikora, Marta Sar-Pomian, Adriana Rakowska, Zbigniew Samochocki, Malgorzata Olszewska
Journal: Journal of the American Academy of Dermatology (2020)
Primary Neuroendocrine Tumor of the Ileostomy Stoma on 68Ga-DOTATATE PET/CT
Authors: Lei Yu, Alexander Braun, Neil J. Hansen, Ryan T. Downey, Craig M. Johnson
Journal: Clinical Nuclear Medicine (2020)

Abstract A 75-year-old man presented with bleeding ileostomy stoma 20 years after total colectomy and end ileostomy for chronic ulcerative colitis. On physical examination, the stoma was mass-like and firm with friable mucosa. Wedge biopsy of the ileostomy stoma revealed well-differentiated neuroendocrine tumor (intermediate grade). 68 Ga-DOTATATE PET/CT showed mass-like focal radiotracer uptake at the ileostomy site without radiotracer-avid lymphadenopathy or distant metastatic disease. No additional sites of neoplasm in the gastrointestinal tract were further identified by endoscopy. The diagnosis of isolated primary neuroendocrine tumor of the ileostomy stoma was confirmed, an extremely rare entity.
Peptide Receptor Radionuclide Therapy
Authors: Anna Yordanova
Journal: Clinical Nuclear Medicine (2020)

Peptide receptor radionuclide therapy (PRRT) uses, as a therapeutic target, the overexpression of somatostatin receptors (SSTRs) in neuroendocrine tumours (NETs). The radiopharmaceutical contains generally a somatostatin analogue, which binds somatostatin receptors, and a linking molecule (chelator), which binds the radioisotope: most commonly Lutetium-177 or Yttrium-90.SSTR imaging must be performed in patients before starting PRRT to prove the SSTR-positive status of the tumour. Furthermore, [18F]F-FDG-PET may be useful to evaluate the metabolic activity of the tumour sites and can help to decide whether PRRT should be performed as a monotherapy or combined with more aggressive treatment. Required for the PRRT are good general condition, sufficient bone marrow function and renal function.PRRT is indicated as a palliative treatment in patients with non-resectable metastatic NET with good SSTR expression if there is progression of disease after first-line treatment. Even in this late stage of disease, the majority of patients achieve a stable disease (5–77%) or objective response (14–75%). PRRT has been shown to be especially effective in patients with slow-growing, G1–G2 (well- or moderately differentiated) gastroenteropancreatic neuroendocrine tumours.Common subacute adverse events after PPRT administration are fatigue, mild alopecia, hypo−/azoospermia, mild/moderate renal impairment and hematological abnormalities (11% severe haematotoxicity). Severe late toxicity such as myelodysplastic syndrome (2.35% of patients), acute leukaemia (1.1%) and nephrotoxicity (1.5%) is rare. Nephrotoxicity is more common in patients treated with Yttrium-90-labelled somatostatin analogues than with Lutetium-177 ones. Generally, PRRT is mostly well tolerated with rarely occurring severe adverse events.
Abstract 3898: Structure-based optimization of small molecule inhibitors of the protein-protein interaction between menin and mixed lineage leukemia (MLL)
Authors: Jonathan Pollock, Dmitry Borkin, Katarzyna Kempinska, Trupta Purohit, Xiaoqin Li, Bo Wen, Ting Zhao, Hongzhi Miao, Shirish Shukla, Miao He, Duxin Sun, Tomasz Cierpicki, Jolanta Grembecka
Journal: Cancer Research (2016)

Abstract Chromosomal translocations that affect the Mixed Lineage Leukemia (MLL) gene result in acute myeloid and lymphoid leukemias. Fusion of MLL with one of 60 different partner genes generates MLL fusion proteins which lead to enhanced cell proliferation, up-regulation of Hoxa9 and Meis1 genes and block hematopoietic differentiation, ultimately leading to acute leukemia. Importantly, the N-terminal region of MLL is retained in all MLL fusion proteins and represents the interaction site of menin, a critical oncogenic cofactor for MLL fusion proteins. As a result, inhibition of the menin-MLL interaction should abrogate the development and progression of MLL leukemia. Therefore, disruption of the menin-MLL interaction with small molecule inhibitors might represent a therapeutic strategy for patients harboring MLL-rearrangements. The development of potent small molecule inhibitors of protein-protein interactions with optimized drug-like properties represents a challenging task in the lead optimization process. Here, we employed structure-based design with extensive medicinal chemistry efforts to optimize the thienopyrimidine class of menin-MLL inhibitors represented by the MI-136 compound. Our efforts resulted in development of MI-538, which represents the most potent small molecule inhibitor of the menin-MLL interaction developed to date. MI-538, which binds to menin with a Kd of 6.5 nM demonstrated superior cellular activity in MLL-AF9 transformed leukemic cells with a GI50 = 83 nM. In a mouse xenograft model utilizing MV4:11 human MLL leukemia cells, treatment with MI-538 significantly reduced tumor growth. Overall, systematic exploration of substituents on MI-136 led to the identification of MI-538 with improved activity, selectivity, polarity and pharmacokinetic profile, making it suitable for in vivo studies. Interestingly, we found that simultaneous incorporation of multiple substituents optimized for each site on the cyanoindole ring of MI-136 does not always positively affect the activity or drug-like properties of these compounds. This study demonstrates challenges in optimizing inhibitors of protein-protein interaction for potential therapeutic applications. Citation Format: Jonathan Pollock, Dmitry Borkin, Katarzyna Kempinska, Trupta Purohit, Xiaoqin Li, Bo Wen, Ting Zhao, Hongzhi Miao, Shirish Shukla, Miao He, Duxin Sun, Tomasz Cierpicki, Jolanta Grembecka. Structure-based optimization of small molecule inhibitors of the protein-protein interaction between menin and mixed lineage leukemia (MLL). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3898.
Abstract 12356: Bayesian Analysis to Harmonize Discordant Coronary CT Angiography With Coronary CT Fractional Flow Reserve Results
Authors: Timothy F Christian, Simcha Pollack, Jane Cao
Journal: Circulation (2019)

Introduction: Derived from the same image, CT coronary angiography (CTA) for coronary stenosis and CT fractional flow reserve (CTFFR) can be discordant. Since neither technique is perfectly accurat...
Contact Tracing, Testing, and Control of COVID-19—Learning From Taiwan
Authors: Robert Steinbrook
Journal: JAMA Internal Medicine (2020)

Taiwan is a country of about 24 million people, 81 miles off the coast of mainland China. As of late April 2020, Taiwan had about 330 confirmed cases of coronavirus disease 2019 (COVID-19) and 6 deaths. By comparison, the US had about 1 million confirmed cases of COVID-19, and 60 000 deaths.
Abstract 11813: Prognostic Relationship Between Coronary Artery Calcium Score, Perfusion Defects and Myocardial Flow Reserve in Patients With Suspected Coronary Artery Disease
Authors: Krishna K Patel, Poghni A Peri-Okonny, Femina S Patel, John Spertus, Brett Sperry, Paul Chan, A. Iain McGhie, Randall Thompson, Firas Al Badarin, Kevin F Kennedy, Timothy M Bateman
Journal: Circulation (2019)

Background: The relative prognostic importance of coronary vasomotor dysfunction (myocardial flow reserve (MFR)) and myocardial perfusion defects (sum rest score (SRS) and sum difference score (SDS...
Survival and glycemic control in patients with colorectal cancer and diabetes mellitus.
Authors: Nina J. Karlin, Shailja Amin, Patricia M. Verona, Heidi E. Kosiorek, Matthew Buras, Curtiss B. Cook
Journal: Journal of Clinical Oncology (2018)

e18755 Background: This study examined the impact of diabetes mellitus (DM) on survival in colorectal cancer patients, and the effect of colorectal cancer on glycemic control. Methods: Colorectal cancer patients (n = 85) from 2007 to 2015 were matched to colorectal cancer patients without DM (n = 85) according to age, gender, and year of cancer diagnosis. Overall survival (OS) was estimated with the Kaplan-Meier method and compared by Cox regression analysis. Mixed models compared hemoglobin A1c (HbA1c), CEA, and glucose over time. Results: Mean age of the entire cohort was 68 years, most (89%) were white, and 32% had stage III disease. No differences in age, race/ethnicity, tumor stage, or ECOG PS were detected between patients with and without DM, although DM patients had higher body mass index (p = 0.002). Among those with DM, the mean HbA1c during the year following cancer diagnosis was 6.8%. Mean glucose was significantly different between DM (144 mg/dL) and non-DM (108 mg/dL) patients (p < 0.001). Both groups had a decline in glucose value during the 1-year period following cancer diagnosis (p < 0.001). Five-year OS was 56% [95% CI: 42-68%] for DM patients versus 57% [95% CI: 43-69%] in non-DM patients (p = 0.62). There was a borderline significant difference in CEA between groups (p = 0.05) as well as significant time (p < 0.001) and interaction effects (p = 0.02). Conclusions: DM did not adversely impact survival in patients with colorectal cancer. Colorectal cancer did not affect glycemic control. There are differences between DM and non-DM with respect to CEA, and this requires further study.
PTH-054 Incidence of food in the upper gastrointestinal (GI) tract during endoscopy, factors involved and outcome
Authors: Munirih Shah, Muhammed Thoufeeq
Journal: Endoscopy (2018)

<h3>Introduction</h3> At the Northern General Hospital, patients are asked to fast for up to six hours prior to endoscopy. Despite this, some procedures are reported to be unsuccessful due to the presence of food. This service evaluation looks at the incidence of food reported, factors involved and its outcomes. <h3>Methods</h3> Retrospective analysis of 8756 patients who underwent elective gastroscopy from July 2016 to June 2017 at the Northern General Hospital. Data was obtained from databases, patient clinical files and procedure logs. <h3>Results</h3> Of the 8756 patients, 118 (1.3%) were noted to have food present during their endoscopy. A number of factors were looked at to see whether they correlated with the presence of food during endoscopy: time of day, age, and indication for endoscopy. Scopes were categorised into AM (8 am-1 pm), PM (1 pm-5 pm), evening (5 pm–8 pm) an out of hours (8 pm-midnight) according to the time they were carried out. The number of scopes reported to have food present were looked at across the different time frames and the results were as follows: AM: 56 (1.2%), PM 32 (1.0%), evening: 26 (2.7%), out of hours 5 (2.7%). The average age of patients reported to have food during their endoscopy was 59 (range 16–97) which matched an average of 59 (range 16–97) where there was no food reported. The number of scopes reported to have food present were looked at for each indication for endoscopy and the results were as follows: abnormal investigations (3.8%), vomiting (2.4%), reassessment (1.9%), GI bleed (1.5%), dysphagia (1.5%), dyspepsia (1.3%), anaemia (1.0%), weight loss (0.7%), tumour (0%), stent removal (0%). 53 (44.9%) of patients reported to have food present were re-scoped: 5 (9.4%) as emergencies and 48 (90.6%) as elective scopes. Of the elective re-scopes, 44 (91.7%) were reported to have no food present and 4 (8.3%) had food reported for a second time. Of the successful re-scopes 3 (6.8%) were given a different time slot, 21 (47.7%) were given further patient education in regards to starvation advice and 7 (15.9%) received both a different time slot and patient education. <h3>Conclusions</h3> From this service evaluation the following Conclusions can be drawn: evening scopes were noted to have a higher rate of presence of food, age did not influence presence of food and scopes which were carried out as a result of abnormal investigations had a higher prevalence of food reported. Re-scoping of patients noted to have food present resulted in successful outcomes as a result of allocation of a different time slot and patient education.
Dissecting RoomDigital“interactive”pathogenesisInteractive Case Study Companion to Robbins Pathologic Basis of Disease, 6th edition, CD-ROM, Vinay Kumar, Herbert K Hagler, System requirements: Windows 95, 98, NT, Macintosh, or UNIX, W B Saunders Company, Philadelphia (1999), $49·95, ISBN: 0-7216-8462-9
Authors: J Andrew Carlson
Journal: The Lancet (1999)
Microtubule-Associated Protein Mdp3 Promotes Breast Cancer Growth and Metastasis: Erratum
Authors: None Tala, Songbo Xie, Xiaodong Sun, Xiaoou Sun, Jie Ran, Linlin Zhang, Dengwen Li, Min Liu, Gang Bao, Jun Zhou
Journal: Theranostics (2020)

[This corrects the article DOI: 10.7150/thno.9727.].
ACC/AHA/SCAI 2014 Health Policy Statement on Structured Reporting for the Cardiac Catheterization Laboratory
Authors: Timothy A. Sanborn, James E. Tcheng, H. Vernon Anderson, Charles E. Chambers, Sharon L. Cheatham, Matthew V. DeCaro, Jeremy C. Durack, Allen D. Everett, John B. Gordon, William E. Hammond, Ziyad M. Hijazi, Vikram S. Kashyap, Merrill Knudtson, Michael J. Landzberg, Marco A. Martinez-Rios, Lisa A. Riggs, Kui Hian Sim, David J. Slotwiner, Harry Solomon, Wilson Y. Szeto, Bonnie H. Weiner, William S. Weintraub, John R. Windle
Journal: Journal of the American College of Cardiology (2014)
THU0570 A Pilot Evaluation of Arthritis Self-Management Program by Lay Leaders in Patients with Chronic Inflammatory Arthritis in Hong Kong
Authors: Y.Y. Leung, J. Kwan, P. Chan, L.S. Tam, E.K. Li, A. Kwok
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Healthcare system has been shifting towards a partnership model of care. <h3>Objectives</h3> To evaluate the 6-week community based lay-led Arthritis Self-Management Program (ASMP) among patients with chronic inflammatory arthritis in Hong Kong, and evaluate the effectiveness of "shared care collaboration" between hospital care and community organizations. <h3>Methods</h3> A total of 17 lay leaders with chronic inflammatory arthritis were trained. Patients with chronic inflammatory arthritis were recruited via newly established referral systems from hospital rheumatology centers to community. Participants were allocated to experimental group or a wait list control group. Evaluation questionnaires were completed before, after (6 week) and 3 months after ASMP. We performed analysis of covariance for significant difference in various outcomes after ASMP, all analysis adjusted for age, sex, marital status, education, employment, duration of illness and disability at baseline. <h3>Results</h3> A total of 88 female and 9 male participants with ankylosing spondylitis (6.2%), psoriatic arthritis (13.4%) and rheumatoid arthritis (80.4%) were recruited. Referrals were from hospital rheumatology centers, community organizations and patient self-help groups in 26.4%, 54.7%, and 12.6% respectively. The mean (SD) age and duration of illness were 52.0 (11.4) and 5.6 (7.3). A total of 65 and 32 participants completed evaluation in the experimental group and control group. At the end of 6 weeks, the experimental group had significantly less pain (p=0.049), used more cognitive methods to manage symptoms (p=0.01) and practiced more aerobic exercise (p=0.049) after adjustment of covariance. The experimental group had a trend of improvement in self-efficacy, fatigue, self-rated health status, health distress, role limitation, disability and health related quality of life. At 3 months, the frequencies of stretching and aerobic exercise were increased in the experimental group. <h3>Conclusions</h3> In this pilot study, the lay led ASMP conducted in community base showed positive beneficial effects on participants with chronic inflammatory arthritis. Significant improvement in pain, cognitive management and frequencies of exercise was observed. Shared care collaboration between physicians, community organizations and patient self-help group was demonstrated. <h3>Acknowledgements</h3> This project is supported by the Hong Kong Arthritis Foundation <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1647