tbuckley/cabot-search huggingface dataset:
Tissue-resident T cell–derived cytokines eliminate herpes simplex virus-2–infected cells
Authors: Pavitra Roychoudhury, David A. Swan, Elizabeth Duke, Lawrence Corey, Jia Zhu, Veronica Davé, Laura Richert Spuhler, Jennifer M. Lund, Martin Prlic, Joshua T. Schiffer
Journal: Journal of Clinical Investigation (2020)

The mechanisms underlying rapid elimination of herpes simplex virus-2 (HSV-2) in the human genital tract despite low CD8+ and CD4+ tissue-resident T cell (Trm cell) density are unknown. We analyzed shedding episodes during chronic HSV-2 infection; viral clearance always predominated within 24 hours of detection even when viral load exceeded 1 × 107 HSV DNA copies, and surges in granzyme B and IFN-γ occurred within the early hours after reactivation and correlated with local viral load. We next developed an agent-based mathematical model of an HSV-2 genital ulcer to integrate mechanistic observations of Trm cells in in situ proliferation, trafficking, cytolytic effects, and cytokine alarm signaling from murine studies with viral kinetics, histopathology, and lesion size data from humans. A sufficiently high density of HSV-2–specific Trm cells predicted rapid elimination of infected cells, but our data suggest that such Trm cell densities are relatively uncommon in infected tissues. At lower, more commonly observed Trm cell densities, Trm cells must initiate a rapidly diffusing, polyfunctional cytokine response with activation of bystander T cells in order to eliminate a majority of infected cells and eradicate briskly spreading HSV-2 infection.
PROGRESSION OF VALVULAR CALCIFICATION IS ASSOCIATED WITH 10-YEAR CHANGE IN LEFT VENTRICULAR STRUCTURE AND INCIDENT HEART FAILURE: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Oluwaseun E. Fashanu, Sireesha Upadhrasta, Di Zhao, Matthew J. Budoff, Ambarish Pandey, Joao A.C. Lima, Erin Michos
Journal: Journal of the American College of Cardiology (2020)
ASSESSMENT OF LEFT ATRIAL FUNCTION AND THE ASSOCIATION WITH LEFT VENTRICULAR FUNCTION IN PAROXYSMAL ATRIAL FIBRILLATION: USING THREE DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY
Authors: Liwen Bao, Lei Cheng, Lilian Bao, Jun Shen, Shangzhi Hong, Guoqian Huang, Haiming Shi
Journal: Journal of the American College of Cardiology (2020)
Surgical management and perioperative morbidity of patients with primary borderline ovarian tumor (BOT).
Authors: Fabian Trillsch, Jan David Ruetzel, Uwe Herwig, Ulrike Doerste, Linn Lena Woelber, Donata Grimm, Matthias Choschzick, Fritz Jaenicke, Sven Mahner
Journal: Journal of Clinical Oncology (2013)

e16535 Background: Surgery is the central aspect of clinical management in patients with borderline ovarian tumors (BOT). As patients have excellent overall prognosis after successful surgery, perioperative morbidity is a critical point for decision regarding the primary surgical approach. Methods: Clinical and surgical parameters of patients undergoing surgery for primary BOT at two gynecologic cancer centers between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparoscopy vs. laparotomy). Results: A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Primary laparoscopy was often performed with diagnostic intention and resulted in complete surgical staging in only 9.1% with subsequent formal indication for re-staging procedures. In contrast, complete surgical staging was achieved in 47.5% at primary laparotomy (p &lt; 0.001). Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Conclusions: Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy should be considered as the preferred surgical approach for staging of patients with BOT if this appears feasible in preoperative evaluation.
A purified membrane protein from <i>Akkermansia muciniphila</i> or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8<sup>+</sup> T cells in mice
Authors: Lijuan Wang, Lei Tang, Yiming Feng, Suying Zhao, Mei Han, Chuan Zhang, Gehui Yuan, Jun Zhu, Shuyuan Cao, Qian Wu, Lei Li, Zhan Zhang
Journal: Gut (2020)

Gut microbiota have been linked to inflammatory bowel disease (IBD) and colorectal cancer (CRC). Akkermansia muciniphila (A. muciniphila) is a gram-negative anaerobic bacterium that is selectively decreased in the faecal microbiota of patients with IBD, but its causative role and molecular mechanism in blunting colitis-associated colorectal cancer (CAC) remain inconclusive. This study investigates how A. muciniphila engages the immune response in CAC.Mice were given dextran sulfate sodium to induce colitis, followed by azoxymethane to establish CAC with or without pasteurised A. muciniphila or a specific outer membrane protein (Amuc_1100) treatment. Faeces from mice and patients with IBD or CRC were collected for 16S rRNA sequencing. The effects of A. muciniphila or Amuc_1100 on the immune response in acute colitis and CAC were investigated.A. muciniphila was significantly reduced in patients with IBD and mice with colitis or CAC. A. muciniphila or Amuc_1100 could improve colitis, with a reduction in infiltrating macrophages and CD8+ cytotoxic T lymphocytes (CTLs) in the colon. Their treatment also decreased CD16/32+ macrophages in the spleen and mesenteric lymph nodes (MLN) of colitis mice. Amuc_1100 elevated PD-1+ CTLs in the spleen. Moreover, A. muciniphila and Amuc_1100 blunted tumourigenesis by expanding CTLs in the colon and MLN. Remarkably, they activated CTLs in the MLN, as indicated by TNF-α induction and PD-1downregulation. Amuc_1100 could stimulate and activate CTLs from splenocytes in CT26 cell conditioned medium.These data indicate that pasteurised A. muciniphila or Amuc_1100 can blunt colitis and CAC through the modulation of CTLs.
Phase I study of ATN-224 in patients (pts) with advanced solid tumours
Authors: S. A. Lowndes, A. Adams, A. Timms, M. Middleton, C. Hayward, S. D. Reich, A. P. Mazar, A. L. Harris
Journal: Journal of Clinical Oncology (2006)

2065 Background: Copper chelation reduces the secretion of many angiogenic factors and reduces tumour growth and microvascular density in animal models. ATN-224 is a second generation analogue of ammonium tetrathiomolybdate, which reportedly can stabilise disease but was limited by the slow onset of copper depletion (50–60 days). Preclinical studies suggest ATN-224 may act primarily by superoxide dismutase 1 (SOD-1) inhibition. The aim of our phase I study was to reduce serum copper levels, as measured by ceruloplasmin (Cp), to 5–15 mg/dl (normal 16–60) in 14–21 days, to determine the pharmacokinetic profile, and to evaluate dose-limiting toxicities. Methods: Cohorts of pts were treated with escalating doses of ATN-224, twice daily, until copper depletion, followed by a titrated maintenance dose. Serum Cp was used as a surrogate marker of copper levels and was titrated to a target range of 5–15mg/dL (normal 16–60). Results: 18 pts have received 54 cycles of ATN-224. Tumours were breast (4), renal (2), melanoma (2), colon (2), and a variety of other types (1 each). Pts received ATN 224 loading doses in cohorts of 1 to 6 pts: 150 (1), 210 (2), 240 (1), 270 (6), 300 (5), and 330 mg/day (3). Mean age was 56 yrs (range 37–78) and PS 0–2. Mean baseline Cp was 39.6 (range 22–63 mg/dL). The maximum administered dose was 330 mg/day where grade 3 lethargy was observed in 3 pts. Of the 4 pts at the maximum tolerated dose of 300 mg/day who have currently completed the loading schedule, all 4 have achieved a reduction of Cp to within 10% of the target range within 21 days. Other toxicities at this dose level included sulphur burps (Gr 1), vomiting (Gr 2), neutropenia (Gr 2), and anaemia (Gr 3). Toxicities reduced in the second and subsequent cycles when doses were titrated downward to maintain Cp levels in target range. PK data indicate greater absorption of ATN 224 and more rapid reduction in Cp with concurrent administration of a proton pump inhibitor. Stable disease of &gt;6 months was observed in 4 pts. Conclusions: Oral ATN-224 is a well-tolerated therapy and at a loading dose of 300 mg/day leads to a reduction of serum Cp levels to 20% normal within 21 days. This will be the recommended starting dose level for phase II study. (Sponsored by Cancer Research UK; funded by Attenuon, LLC). [Table: see text]
PERFORMANCE OF ULTRA-HIGH RESOLUTION CT OF INSTENT RESTENOSIS OF BELOW 3.0MM CORONARY STENT
Authors: Masanori Taniwaki, Keiichi Onishi, Hirotaka Ezaki, Yoshio Maeno, Tomohisa Saitoh, Takayuki Miyake, Masami Sakurada
Journal: Journal of the American College of Cardiology (2020)
NO ROOM TO BREATHE: A CASE OF MASSIVE CARDIOMEGALY SECONDARY TO RHEUMATIC HEART DISEASE
Authors: Tarick Sheikh, Brian Holahan, Amogh Joshi, Lekha Racharla, Emilee Kurtz, Sara Godil, Paul Secheresiu, Sagar Vadhar
Journal: Journal of the American College of Cardiology (2020)
THE ABNORMAL DIASTOLIC FLOW IN THE PULMONARY ARTERY DOPPLER ON TRANSTHORACIC ECHOCARDIOGRAPHY (TTE)
Authors: Sangeeta Prabhakar Bhat, Madhava Rao, Najam Saqib, Muhammad Pir, Hamza Hafeez, Abdul Haseeb, Mirza Mujadil Ahmad, Sharath Rajagopalan, Pranjal Boruah
Journal: Journal of the American College of Cardiology (2020)
Concurrent chemoradiation therapy in cervical cancer: Prognostic factors, toxicity, and long-term survival in a center of reference for gynecologic cancer.
Authors: Marta Gil-Martin, Mivael Olivera, Beatriz Pardo, Cinta Bellobi, Valentín Navarro-Perez, Susanna Marin i Borras
Journal: Journal of Clinical Oncology (2013)

e16539 Background: Concurrent chemoradiation therapy has been the standard treatment in locally advanced cervical cancer since 1999, and our institution is a centre of reference for treatment of this pathology. Methods: In a homogeneous series of 288 patients treated between 1996 and December 2011, survival data, prognostic factors and toxicity of the treatment have been analyzed. The treatment includes external beam radiotherapy, concurrent weekly chemotherapy and brachytherapy. Results: Median age of the patients is 54 years old, and the FIGO classification for disease stages shows 14.6% IB2, 47.1% IIB, 24.4% III, and 7.8% IVA. Squamous cell carcinoma (77.4%) and adenocarcinoma (16.8%) are the most common histologies. After a median follow-up of 4.4 years, the 5-year overall survival rate is 80.2%. Classified by diagnostic stage, they are 85% in IB2, 76% in IIB, 70% in III, and 68% in IVA. The main location for recurrence is cervix (11.8%), and the most common site for distant disease is lung (4.8%). For patients with disease progression, 24.4% have local and distant recurrence. After local recurrence, radical surgery with pelvic exenteration was practised in 6 cases, 5 of them are still alive. In the multivariate analysis, the prognostic factors for overall survival that have been identified with a statistical significance, are HPV and HIV infection, high stages of disease and older patients. Performance status ≥1 and brachytherapy have only a significant value in the univariate analysis. The acute toxicity grade ≥3 was observed in 19.4% of patients (14.1% haematological). The most frequent low grade toxicity was 46.3% haematological, 40% of bowel-related toxicity, 38.9% of nausea and vomiting, and 8.1% of renal dysfunction. Chronic toxicity grade ≥3 has been only seen in 1.2% of patients (renal dysfunction), and in the low grades, it is a 6% of bowel-related toxicity and 1.4% of mild renal dysfunction. Conclusions: This long follow-up series shows a good overall survival rate with chemoradiation therapy in locally advanced stages of cervical cancer, with a low rate of acute and, especially, chronic toxicity, indicating a good quality of life for these patients.
Clinical experience of oxaliplatin-based regimen for patients with relapsed or refractory B-cell lymphoma: A Bangladesh perspective.
Authors: Ehteshamul Hoque
Journal: Journal of Clinical Oncology (2013)

e19501 Background: We performed a clinical study to evaluate the efficacy and toxicity of R-GemOx in the treatment of patients with relapsed or refractory B-cell lymphoma in Bangladeshi patient population. Methods: A total number of twenty (male 13, female 7, average age 60) patients with recurrent or refractory CD20 positive lymphoma, previously treated with CHOP of any performance status were eligible for inclusion. No primary and new cases were included. Treatment regimen consisting of rituximub 375 mg/m 2 , Gemcitabine 1000 mg/m 2 and oxaliplatin 100 mg/m 2 on day 1. Cycle was repeated every 3 weekly for six cycles. The patients were enrolled at our institution between December 2009 and December 2011. The primary endpoint was overall response rate and toxicity, assessed by Response Evaluation Criteria, secondary endpoints included both event free survival (EFS), and overall survival (OS). Results: A total of 20 patients were evaluable for efficacy and toxicity. The overall response rate was 75%. The EFS and OS under follow-up. No fatal toxicity was observed. Treatment was generally well tolerated. 13% patients complained about GIT upset (nausea, vomiting). Grade 3/4 neutropenia occurred in 8% of patients. Grade 2 neurotoxicity occurred in 5% of patients. No renal toxicity was observed. No other grade ¾ non hematological toxicity was observed. Conclusions: The combination of R-GemOx was effective in Bangladeshi patient population with Refractory B-cell lymphoma, with a predictable and manageable safety profile similar to that observed in Western patients.
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1
Authors: Neeltje van Doremalen, Trenton Bushmaker, Dylan H. Morris, Myndi G. Holbrook, Amandine Gamble, Brandi N. Williamson, Azaibi Tamin, Jennifer L. Harcourt, Natalie J. Thornburg, Susan I. Gerber, James O. Lloyd-Smith, Emmie de Wit, Vincent J. Munster
Journal: New England Journal of Medicine (2020)

Aerosol and Surface Stability of SARS-CoV-2 In this research letter, investigators report on the stability of SARS-CoV-2 and SARS-CoV-1 under experimental conditions. The viability of the two virus...
HIS BUNDLE PACING - A NEW SOLUTION FOR CARDIOMYOPATHY?
Authors: Sangeeta Prabhakar Bhat, Wilson Young, Najam Saqib, Muhammad Pir, Sharath Rajagopalan, Hamza Hafeez, Abdul Haseeb, Mirza Mujadil Ahmad, Pranjal Boruah
Journal: Journal of the American College of Cardiology (2020)
HEART TRANSPLANT SURVIVAL AT 8600 FEET ABOVE SEA LEVEL AN EXPERIENCE IN BOGOTÁ COLOMBIA
Authors: Ramón Medina, Juan Vasquez, Marietta Luz Juan-Guardela, Oscar Mauricio Pérez, Marisol Carreño, Juan Gallo, Monica Lopez Pareja, Jhon Rámirez, Jaime Camacho, Juan Umaña, Hector Medina, Maria Rodriguez Gonzalez
Journal: Journal of the American College of Cardiology (2020)
Covid-19 and community mitigation strategies in a pandemic
Authors: Shahul H Ebrahim, Qanta A Ahmed, Ernesto Gozzer, Patricia Schlagenhauf, Ziad A Memish
Journal: BMJ (2020)

The covid-19 pandemic that was declared on 11 March 2020 has affected countries on all continents.1 Reported case numbers are certainly underestimates given the shortages or unavailability of test kits in many countries, a virus with a basic reproductive value (R) of 2.2, and evidence of viral shedding from asymptomatic infected people.1234 In addition to suspending travel and efforts to reduce crowds, countries are taking unprecedented measures, including wartime strategies to enhance production of medical supplies in the US, the use of the national guard to restrict movement of people, and suspension of exports of medical products from certain countries (Saudi Arabia, India).5678 Our challenge is to make the best use of available tools through systematic implementation by communities and countries to mitigate the exponential spread of covid-19.

No specific drugs or vaccines are available, and health systems are overburdened everywhere. We have to rely on targeted, non-coercive, community interventions with sufficient transparency and public engagement and trust, and implement them urgently (box 1).91011 Such measures may help delay the exponential spread of the outbreak until drugs become available. Transparency and trust are …
Prevention of dementia in an ageing world: Evidence and biological rationale
Authors: Giulia Grande, Chengxuan Qiu, Laura Fratiglioni
Journal: Ageing Research Reviews (2020)

As the population ages, the number of people with dementia is expected to increase in the coming decades, with consequences at the societal and individual levels. In this narrative review, we provide a summary of the scientific evidence concerning dementia prevention, with a focus on the following three strategies: 1) Targeting the body to protect the brain, including prevention and treatment of cardiovascular morbidity; 2) Compensatory interventions to counteract brain ageing, including education and life-long engagement in cognitively and socially stimulating activities; and 3) Lifespan health promotion, such as a physically active lifestyle, smoking cessation, and a healthy and balanced diet. Next, we consider the biological mechanisms by which these strategies may act by taking into account the main pathways implicated in the development and progression of dementia: neurodegeneration, brain resilience, vascular damage, neuroinflammation, and oxidative stress. Based on the current evidence, and in line with the declining trends of dementia incidence in high-income countries, we conclude that timely multidomain preventive actions are promising strategies to reduce the dementia epidemic worldwide. There is still a considerable gap between the epidemiological evidence and its underlying biological mechanisms. Filling this gap will be crucial to move forward in dementia prevention worldwide.
ASSESSMENT OF SEVERITY OF AORTIC STENOSIS (AS) IS CHALLENGING IN THE SETTING OF LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION DUE TO THE HIGH VELOCITY IN LVOT
Authors: Manik Veer, Mahmoud Elsayed, Robert Biederman, Vinh Nguyen, Saad Tabbara, Victor Farah
Journal: Journal of the American College of Cardiology (2020)
Enterococcus in Graft-versus-Host Disease
Authors: Wendy S. Garrett
Journal: New England Journal of Medicine (2020)

A major cause of poor outcome after allogeneic hematopoietic-cell transplantation is graft-versus-host disease. A recent study indicates that a patient's gut microbiota affect susceptibility to this disease and implicates the dietary sugar lactose as an instigator.
Natriuretic Peptides as Inclusion Criteria in Clinical Trials
Authors: Nasrien E. Ibrahim, John C. Burnett, Javed Butler, Alexander Camacho, G. Michael Felker, Mona Fiuzat, Christopher O’Connor, Scott D. Solomon, Muthiah Vaduganathan, Michael R. Zile, James L. Januzzi
Journal: JACC Heart Failure (2020)
LONG-TERM RISK OF HEART FAILURE IN WOMEN WITH HYPERTENSIVE DISORDERS OF PREGNANCY
Authors: Michael Honigberg, Hilde Kristin Refvik Riise, Anne Kjersti Daltveit, Grethe Seppola Tell, Gerhard Sulo, Jannicke Igland, Kari Klungsøyr, Nandita Scott, Pradeep Natarajan, Janet Rich-Edwards
Journal: Journal of the American College of Cardiology (2020)
Meeting the Educational Needs of an Increasingly Diverse Surgical Workforce—Reply
Authors: Patrick T. Dolan, Julie A. Sosa, Heather L. Yeo
Journal: JAMA Surgery (2020)

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Sentinel node biopsy in melanoma patients: The role of day surgery and local anaesthetic approach for quality-of-life and effective cost reduction.
Authors: Fabio Ricci, Erminio Saralli, Loreto Giovanni Capuano, Maurizio Dorkin, Mario Valleriani, Anna Maria D'Achille, Veronica Di Emma, Luigi Greco, Assunta Violante, Luca Filippi, Maurilio Natali, Alberto Pacchiarotti, Alessandro Annetta
Journal: Journal of Clinical Oncology (2012)

e19002 Background: Sentinel node biopsy (SNB) is used in the management of melanoma patients without nodal metastases. Methods: From January 1, 1998 to December 31, 2011 we performed 182 SNBs at St. M. Goretti Hospital. Patients presented a primary melanoma, Breslow thickness equal to or higher than 1 mm, lower than 1 mm with regression and/or ulceration, and/or IV-V Clark level, and/or mitotic rate ≥ 1/mm 2 , according to the 7th edition melanoma staging system. All patients underwent pre-operative lymphoscintigraphy with intradermal injection of 50-70 MBq 99 mTc colloidal albumina particles, 50-80 nm size range, in 0.1-0.2 ml saline solution. We never used blue dye. All patients underwent surgical treatment 4-12 h. later. We performed SNB in day-surgery (DS) under local anaesthesia (LA). Surgery incision was 3-4 cm. This study was approved by an ethics committee, discussed with all patients and informed consent was obtained. Purpose of the study is to investigate the validity of this approach for quality of life and cost reduction. Results: 165 patients underwent SNB, 64 (38.7%) in the inguinal region, 83 (50.3%) in axilla, 1 (0.6%) in the popliteal region, 4 (2.4%) patients showed inguinal bilateral sentinel lymph-node (SLN), 6 (3.6%) axillary bilateral SLN, 4 (2.4%) axillary and 3 (1.8%) inguinal double SLN. The SLN identification rate was 100%. After surgery we distributed a questionnaire to the patients about the acceptability of this approach. In 32 patients SLN was positive. In these patients we performed radical lymphoadenectomy, 12 (37.5%) inguinal and 20 (62.5%) axillary. Conclusions: The results achieved are extremely accurate. This procedure is safe, well accepted by patients (98%), reported better quality of life. The oncological results are absolutely reliable. As regards hospital logistics, operations in DS and LA can be easily managed, leading to a significant cost reduction, 42.15% less expensive than the same operation performed under general anaesthesia.
HIGH BLEEDING RISK AFTER PERCUTANEOUS CORONARY INTERVENTION: IMPACT OF RACE/ETHNICITY
Authors: Rishi Chandiramani, Roxana Mehran, Davide Cao, Ridhima Goel, Anastasios Roumeliotis, Johny Nicolas, Moritz Blum, Samantha Sartori, Huazhen Chen, Rashi Bedekar, Srinivas Kesanakurthy, Jason Kovacic, Joseph Sweeny, Prakash Krishnan, Nitin Barman, Usman Baber, George D. Dangas, Samin K. Sharma, Annapoorna Subhash Kini
Journal: Journal of the American College of Cardiology (2020)