tbuckley/cabot-search huggingface dataset:
Thulium laser transurethral vaporesection of the prostate versus transurethral resection of the prostate for men with lower urinary tract symptoms or urinary retention (UNBLOCS): a randomised controlled trial
Authors: Hashim Hashim, Jo Worthington, Paul Abrams, Grace Young, Hilary Taylor, Sian M Noble, Sara T Brookes, Nikki Cotterill, Tobias Page, K Satchi Swami, J Athene Lane, Rupert Beck, Christopher Blake, Kim Davenport, Oliver Kayes, Jonathan Sullivan, Nicholas Cohen, Mathialagan Murugesan, Anthony Timoney, Lyndsey Johnson, Benita Adams, Angela Allan, Carol Brain, Fiona Hammonds, Joan Henderson, Paula Hilltout, Bernadette Kilbane, Leigh Morrison, Wendy Robson, Lorraine Wiseman, Vivian Zinyemba, Chris Metcalfe, Rafiyah Khan, Alan Uren, Aideen Ahern, Aida Moure Fernandez, Barbara Warnes, Tom Steuart-Feilding, Christopher Pawsey, Julie Plant, Mai Baquedano, David Carmichael
Journal: The Lancet (2020)

BackgroundTransurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction. Thulium laser transurethral vaporesection of the prostate (ThuVARP) is a technique with suggested advantages over TURP, including reduced complications and hospital stay. We aimed to investigate TURP versus ThuVARP in men with lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction.MethodsIn this randomised, blinded, parallel-group, pragmatic equivalence trial, men in seven UK hospitals with bothersome lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction were randomly assigned (1:1) at the point of surgery to receive ThuVARP or TURP. Patients were masked until follow-up completion. Centres used their usual TURP procedure (monopolar or bipolar). All trial surgeons underwent training on the ThuVARP technique. Co-primary outcomes were maximum urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS) at 12-months post-surgery. Equivalence was defined as a difference of 2·5 points or less for IPSS and 4 mL per s or less for Qmax. Analysis was done according to the intention-to-treat principle. The trial is registered with the ISRCTN Registry, ISRCTN00788389.FindingsBetween July 23, 2014, and Dec 30, 2016, 410 men were randomly assigned to ThuVARP or TURP, 205 per study group. TURP was superior for Qmax (mean 23·2 mL per s for TURP and 20·2 mL per s for ThuVARP; adjusted difference in means −3·12, 95% CI −5·79 to −0·45). Equivalence was shown for IPSS (mean 6·3 for TURP and 6·4 for ThuVARP; adjusted difference in means 0·28, −0·92 to 1·49). Mean hospital stay was 48 h in both study groups. 91 (45%) of 204 patients in the TURP group and 96 (47%) of 203 patients in the ThuVARP group had at least one complication.InterpretationTURP and ThuVARP were equivalent for urinary symptom improvement (IPSS) 12-months post-surgery, and TURP was superior for Qmax. Anticipated laser benefits for ThuVARP of reduced hospital stay and complications were not observed.FundingUK National Institute for Health Research Health Technology Assessment Programme.
Helen Salisbury: Is lifestyle a choice?
Authors: Helen Salisbury
Journal: BMJ (2020)

Doctors’ attention is currently focused on coronavirus, but previous agendas haven’t gone away, including the high prevalence of non-communicable diseases in wealthier parts of the world. A key driver of this burden—contributing to diabetes, cardiovascular pathology, arthritis, and cancer—is that so many people live unhealthy lives. All of us (excepting perhaps those with medicines to sell) would agree that avoiding, and sometimes even reversing, these illnesses through exercise, weight control, or avoidance of alcohol and tobacco would be better than treating the end results with drugs.

Given that this is so uncontroversial, I’m interested in the negative reactions …
Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis
Authors: Yao-Wen Cheng, Dana Alhaffar, Srishti Saha, Sahil Khanna, Matthew Bohm, Emmalee Phelps, Marwan Ghabril, Eric Orman, Sagi Sashidhar, Nicholas Rogers, Huiping Xu, Alexander Khoruts, Byron Vaughn, Dina Kao, Karen Wong, Giovanni Cammarota, Gianluca Ianiro, Tanvi Dhere, Colleen S. Kraft, Nirja Mehta, Michael H. Woodworth, Jessica R. Allegretti, Lotem Nativ, Jenna Marcus, Najwa El-Nachef, Monika Fischer
Journal: Clinical Gastroenterology and Hepatology (2020)
Detection of <i>TP53</i> Clonal Variants in Papanicolaou Test Samples Collected up to 6 Years Prior to High-Grade Serous Epithelial Ovarian Cancer Diagnosis
Authors: Lara Paracchini, Chiara Pesenti, Martina Delle Marchette, Luca Beltrame, Tommaso Bianchi, Tommaso Grassi, Alessandro Buda, Fabio Landoni, Lorenzo Ceppi, Cristina Bosetti, Mariachiara Paderno, Marco Adorni, Debora Vicini, Patrizia Perego, Biagio Eugenio Leone, Maurizio D’Incalci, Sergio Marchini, Robert Fruscio
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The low 5-year survival rate of women with high-grade serous epithelial ovarian cancer (HGS-EOC) is related to its late diagnosis; thus, improvement in diagnosis constitutes a crucial step to increase the curability of this disease. <h3>Objective</h3> To determine whether the presence of the clonal pathogenic<i>TP53</i>variant detected in matched primary tumor biopsies can be identified in DNA purified from Papanicolaou test samples collected from women with HGS-EOC years before the diagnosis. <h3>Design, Setting, and Participants</h3> This cohort study was conducted among a single-center cohort of women with histologically confirmed diagnosis of HGS-EOC recruited at San Gerardo Hospital, Monza, Italy, from October 15, 2015, to January 4, 2019. Serial dilutions of DNA derived from tumor samples and DNA extracted from healthy women’s Papanicolaou test samples were analyzed to define the sensitivity and specificity of droplet digital polymerase chain reaction assays designed to detect the<i>TP53</i>variants identified in tumors. All available brush-based Papanicolaou test slides performed up to 6 years before diagnosis were investigated at the Mario Negri Institute, Milano, Italy. Data were analyzed from October 2018 to December 2019. <h3>Main Outcomes and Measures</h3> The presence of tumor pathogenic<i>TP53</i>variants was assessed by the droplet digital polymerase chain reaction approach in DNA purified from Papanicolaou test samples obtained from the same patients before diagnosis during cervical cancer screenings. <h3>Results</h3> Among 17 included patients (median [interquartile range] age at diagnosis, 60 [53-69] years), Papanicolaou tests withdrawn before diagnosis presented tumor-matched<i>TP53</i>variants in 11 patients (64%). In 2 patients for whom longitudinal Papanicolaou tests were available, including 1 patient with Papanicolaou tests from 25 and 49 months before diagnosis and 1 patient with Papanicolaou tests from 27 and 68 months before diagnosis, the<i>TP53</i>clonal variant was detected at all time points. <h3>Conclusions and Relevance</h3> These findings suggest that noninvasive early molecular diagnosis of HGS-EOC is potentially achievable through detection of<i>TP53</i>clonal variants in the DNA purified from Papanicolaou tests performed during cervical cancer screening.
Audio Interview: A Covid-19–Related Syndrome in Children
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

A Covid-19–Related Syndrome in Children In this audio interview conducted on July 1, 2020, the editors discuss MIS-C, a multisystem inflammatory syndrome that can follow SARS-CoV-2 infection in chi...
Circulating tumour cells as a potential biomarker for lung cancer screening: a prospective cohort study
Authors: Charles-Hugo Marquette, Jacques Boutros, Jonathan Benzaquen, Marion Ferreira, Jean Pastre, Christophe Pison, Bernard Padovani, Faiza Bettayeb, Vincent Fallet, Nicolas Guibert, Damien Basille, Marius Ilie, Véronique Hofman, Paul Hofman, Charles-Hugo MARQUETTE, Jacques BOUTROS, Jonathan Benzaquen, Marion FERREIRA, Jean PASTRE, Christophe Pison, Bernard PADOVANI, Faiza BETTAYEB, Vincent FALLET, Nicolas GUIBERT, Damien BASILLE, Marius ILIE, Véronique HOFMAN, Paul HOFMAN, Dominique ISRAEL-BIET, François CHABOT, Anne GUILLAUMOT, Gaetan DESLEE, Jeanne-Marie PEROTIN, Sandra DURY, Hervé MAL, Armelle MARCEAU, Romain Kessler, Jean-Michel Vergnon, Carole Pelissier, Fabrice Di Palma, Antoine Cuvelier, Maxime PATOUT, Arnaud Bourdin, Anne Sophie GAMEZ, Claire ANDREJAK, Claire POULET, Géraldine FRANCOIS, Vincent Jounieaux, Nicolas Roche, Stéphane Jouneau, Graziella Brinchault, Philippe Bonniaud, Ayoub ZOUAK, Arnaud Scherpereel, Simon BALDACCI, Alexis CORTOT, Jean François Mornex, François Steenhouwer, Sylvie LEROY, Jean-Philippe BERTHET, Eric FONTAS, Julie BULSEI, Coralie CRUZEL, Johanna Pradelli, Maureen Fontaine, Charlotte MANIEL, Jennifer Griffonnet, Catherine BUTORI, Eric SELVA, Michel POUDENX, Bernard AguilanIu, Gilbert Ferretti, François Arbib, Amandine Briault, Anne-Claire Toffart, Raissa Dahalani, Marie Destors, Pascal Chanez, Laurent GREILLIER, Philippe ASTOUL, Fabrice BARLESI, Jean-Yves GAUBERT, Julien Mazières, Sylvain Marchand-Adam, Jacques Cadranel, Nouha CHAABANE, Armine IZADIFAR, Lise ROSENCHER, Anne-Marie RUPPERT, Thibault VIEIRA, Nathalie MATHIOT
Journal: The Lancet Respiratory Medicine (2020)
Dermatoscopic Evaluation of Central Centrifugal Cicatricial Alopecia Beyond the Vertex Scalp
Authors: Kayla Felix, Brianna De Souza, Nataly Portilla, Latrice Hogue, Christine S. Ahn, Omar Sangueza, Amy J. McMichael
Journal: JAMA Dermatology (2020)

Dermatoscopic Evaluation of Central Centrifugal Cicatricial Alopecia Beyond the Vertex ScalpCentral centrifugal cicatricial alopecia (CCCA) is a scarring alopecia commonly seen in African American individuals. 1It classically affects the vertex scalp, although 1 study 2 suggests that it may manifest as patchy hair loss beyond the vertex.In that study, the histopathologic, dermatoscopic, and clinical findings were crucial in diagnosis.However, another study 3 reported histopathologic changes in the vertex scalp consistent with CCCA even without clinically visible hair loss.Our study explored dermatoscopic and histopathologic findings in areas of the scalp without clinically active disease, specifically beyond the vertex scalp.We also assessed the reliability of dermatoscopy, which may serve as a less invasive diagnostic tool than biopsy, for the diagnosis of CCCA in the context of subclinical disease.
Glioma escape signature and clonal development under immune pressure
Authors: Cecile L. Maire, Malte Mohme, Michael Bockmayr, Krystian D. Fita, Kristoffer Riecken, Daniela Börnigen, Malik Alawi, Antonio Failla, Katharina Kolbe, Svenja Zapf, Mareike Holz, Katrin Neumann, Lasse Dührsen, Tobias Lange, Boris Fehse, Manfred Westphal, Katrin Lamszus
Journal: Journal of Clinical Investigation (2020)

Immunotherapeutic strategies are increasingly important in neuro-oncology, and the elucidation of escape mechanisms that lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing WT and Pd-1-/- mice survived significantly longer than immunodeficient Pfp-/- Rag2-/- mice. While tumors in Pfp-/- Rag2-/- mice were highly polyclonal, immunoedited tumors in WT and Pd-1-/- mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in WT mice were distinguished by an IFN-γ-mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even more strongly to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas.
CD38 deletion of human primary NK cells eliminates daratumumab-induced fratricide and boosts their effector activity
Authors: Meisam Naeimi Kararoudi, Yuya Nagai, Ezgi Elmas, Marcelo de Souza Fernandes Pereira, Syed Abbas Ali, Philip Hollingsworth Imus, Darren Wethington, Ivan Marques Borrello, Dean Anthony Lee, Gabriel Ghiaur
Journal: Blood (2020)

Abstract Multiple myeloma (MM) is a plasma cell neoplasm that commonly expresses CD38. Daratumumab (DARA), a human monoclonal antibody targeting CD38, has significantly improved the outcome of patients with relapsed or refractory MM, but the response is transient in most cases. Putative mechanisms of suboptimal efficacy of DARA include downregulation of CD38 expression and overexpression of complement inhibitory proteins on MM target cells as well as DARA-induced depletion of CD38high natural killer (NK) cells resulting in crippled antibody-dependent cellular cytotoxicity (ADCC). Here, we tested whether maintaining NK cell function during DARA therapy could maximize DARA-mediated ADCC against MM cells and deepen the response. We used the CRISPR/Cas9 system to delete CD38 (CD38KO) in ex vivo expanded peripheral blood NK cells. These CD38KO NK cells were completely resistant to DARA-induced fratricide, showed superior persistence in immune-deficient mice pretreated with DARA, and enhanced ADCC activity against CD38-expressing MM cell lines and primary MM cells. In addition, transcriptomic and cellular metabolic analysis demonstrated that CD38KO NK cells have unique metabolic reprogramming with higher mitochondrial respiratory capacity. Finally, we evaluated the impact of exposure to all-trans retinoic acid (ATRA) on wild-type NK and CD38KO NK cell function and highlighted potential benefits and drawbacks of combining ATRA with DARA in patients with MM. Taken together, these findings provide proof of concept that adoptive immunotherapy using ex vivo expanded CD38KO NK cells has the potential to boost DARA activity in MM.
Evidence-Based and Patient-Centered Decisions Regarding Bariatric Surgery—Reply
Authors: Anita P. Courcoulas, R. Yates Coley, David Arterburn
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Multi-Agent Chemotherapy Overcomes Steroid Resistance Conferred by a BIM Deletion Polymorphism in Pediatric Acute Lymphoblastic Leukemia (ALL)
Authors: Sheila X.X. Soh, Joshua Y.S. Lim, John W.J. Huang, Shirley K.Y. Kham, Allen E.J. Yeoh, S. Tiong Ong
Journal: Blood (2013)
Outcome of primary mediastinal large B-cell lymphoma using R-CHOP: impact of a PET-adapted approach
Authors: Anna R. Hayden, Petter Tonseth, Derrick G. Lee, Diego Villa, Alina S. Gerrie, David W. Scott, Ciara L. Freeman, Graham W. Slack, Pedro Farinha, Brian Skinnider, Paul R. Yenson, Francois Benard, Andrea Lo, Tom Pickles, Donald Wilson, Joseph M. Connors, Laurie H. Sehn, Kerry J. Savage
Journal: Blood (2020)
SOAT1 promotes mevalonate pathway dependency in pancreatic cancer
Authors: Tobiloba E. Oni, Giulia Biffi, Lindsey A. Baker, Yuan Hao, Claudia Tonelli, Tim D.D. Somerville, Astrid Deschênes, Pascal Belleau, Chang-il Hwang, Francisco J. Sánchez-Rivera, Hilary Cox, Erin Brosnan, Abhishek Doshi, Rebecca P. Lumia, Kimia Khaledi, Youngkyu Park, Lloyd C. Trotman, Scott W. Lowe, Alexander Krasnitz, Christopher R. Vakoc, David A. Tuveson
Journal: The Journal of Experimental Medicine (2020)

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. Altered metabolism is a cancer vulnerability, and several metabolic pathways have been shown to promote PDAC. However, the changes in cholesterol metabolism and their role during PDAC progression remain largely unknown. Here we used organoid and mouse models to determine the drivers of altered cholesterol metabolism in PDAC and the consequences of its disruption on tumor progression. We identified sterol O-acyltransferase 1 (SOAT1) as a key player in sustaining the mevalonate pathway by converting cholesterol to inert cholesterol esters, thereby preventing the negative feedback elicited by unesterified cholesterol. Genetic targeting of Soat1 impairs cell proliferation in vitro and tumor progression in vivo and reveals a mevalonate pathway dependency in p53 mutant PDAC cells that have undergone p53 loss of heterozygosity (LOH). In contrast, pancreatic organoids lacking p53 mutation and p53 LOH are insensitive to SOAT1 loss, indicating a potential therapeutic window for inhibiting SOAT1 in PDAC.
Cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma: an open-label, single-centre, phase 2 trial
Authors: Andrea B Apolo, Rosa Nadal, Yusuke Tomita, Nicole N Davarpanah, Lisa M Cordes, Seth M Steinberg, Liang Cao, Howard L Parnes, Rene Costello, Maria J Merino, Les R Folio, Liza Lindenberg, Mark Raffeld, Jeffrey Lin, Min-Jung Lee, Sunmin Lee, Sylvia V Alarcon, Akira Yuno, Nancy A Dawson, Kimaada Allette, Arpita Roy, Dinuka De Silva, Molly M Lee, Tristan M Sissung, William D Figg, Piyush K Agarwal, John J Wright, Yangmin M Ning, James L Gulley, William L Dahut, Donald P Bottaro, Jane B Trepel
Journal: The Lancet Oncology (2020)
Football facing a future with global warming: perspectives for players health and performance
Authors: Lars Nybo, Andreas D Flouris, Sebastien Racinais, Magni Mohr
Journal: British Journal of Sports Medicine (2020)

Escalating environmental temperatures are expected to influence performance and planning of several future football events, for example, FIFA World Cups, regular league and continental cup matches and climate projections for Tokyo (Olympic Games postponed to August 2021) implies that athletes are facing high heat exposure in the next Olympic football tournament. Prompted by global warming, but also with current conditions and historic heat-events in mind, it is relevant to consider the consequences for football play and players health. Heat stress has detrimental effects on endurance performances and sudden or extreme exposure is a major health concern.1 2 Moreover, heat stress could, in some situations, create an unsportsmanlike competitive advantage for the home team3 and fair play may require special planning and precaution procedures.

Scientific football research with control and hot matches completed with standardised set-up1 as well as retrospective analyses of the 2014 FIFA World Cup2 reveal a characteristic change in game activity pattern including a marked reduction in high-intensity running. However, the overall fatigue development is not affected and peak sprinting speeds appear slightly higher when playing in the heat. The majority of sprint efforts in a game last 1–3 s4 and may benefit …
A Model Using Clinical and Endoscopic Characteristics Identifies Patients at Risk for Eosinophilic Esophagitis According to Updated Diagnostic Guidelines
Authors: Cary C Cotton, Renee Betancourt, Cara Randall, Irina Perjar, Christine Bookhout, John T Woosley, Nicholas J Shaheen, Evan S Dellon
Journal: Clinical Gastroenterology and Hepatology (2020)
A Phase II Trial of Tipifarnib for Patients with Previously Treated, Metastatic Urothelial Carcinoma Harboring<i>HRAS</i>Mutations
Authors: Hye Won Lee, Jason K. Sa, Antonio Gualberto, Catherine Scholz, Hyun Hwan Sung, Byong Chang Jeong, Han Yong Choi, Ghee Young Kwon, Se Hoon Park
Journal: Clinical Cancer Research (2020)

Abstract Purpose: To assess the antitumor activity and safety of tipifarnib, a highly potent and selective farnesyltransferase inhibitor, we performed a phase II clinical trial in patients with advanced and refractory urothelial carcinoma harboring missense HRAS mutations. Patients and Methods: A total of 245 adult patients with previously treated, advanced urothelial carcinoma entered the molecular screening program including HRAS. Those with missense HRAS mutations or STK11:rs2075606 received oral tipifarnib 900 mg twice daily on days 1–7 and 15–21 of 28-day treatment cycles. The primary endpoint was progression-free survival at 6 months (PFS6). Results: We identified 16 (7%) missense HRAS mutations (G13R, 7; Q61R, 4; G12S, 3; G12C, 2) and 104 (46%) STK11:rs2075606 carriers. In 21 patients enrolled in the study, 14 and 7 patients had missense HRAS mutations and STK11:rs2075606, respectively. The most frequently observed adverse events included fatigue (86%) and hematologic toxicities. With a median follow-up of 28 months, 4 patients (19%) reached PFS6: 3 had missense HRAS mutations and one patient, enrolled as an STK11 carrier, had HRAS frameshift insertions at H27fs and H28fs rendering a nonsense HRAS mutation. The overall response rate by intent-to-treat analysis was 24% (4 missense and one nonsense frameshift HRAS mutation); no response was observed in patients with urothelial carcinoma with wild-type HRAS tumors. Five responses were observed in 12 evaluable patients of 15 with tumors carrying HRAS mutations. Conclusions: Oral tipifarnib resulted in a manageable safety profile and encouraging antitumor efficacy against treatment-refractory urothelial carcinoma containing HRAS mutations.
Detecting Signatures of Positive Selection against a Backdrop of Compensatory Processes
Authors: Peter B Chi, Westin M Kosater, David A Liberles
Journal: Molecular Biology and Evolution (2020)

There are known limitations in methods of detecting positive selection. Common methods do not enable differentiation between positive selection and compensatory covariation, a major limitation. Further, the traditional method of calculating the ratio of nonsynonymous to synonymous substitutions (dN/dS) does not take into account the 3D structure of biomacromolecules nor differences between amino acids. It also does not account for saturation of synonymous mutations (dS) over long evolutionary time that renders codon-based methods ineffective for older divergences. This work aims to address these shortcomings for detecting positive selection through the development of a statistical model that examines clusters of substitutions in clusters of variable radii. Additionally, it uses a parametric bootstrapping approach to differentiate positive selection from compensatory processes. A previously reported case of positive selection in the leptin protein of primates was reexamined using this methodology.
Is a “Cytokine Storm” Relevant to COVID-19?
Authors: Pratik Sinha, Michael A. Matthay, Carolyn S. Calfee
Journal: JAMA Internal Medicine (2020)

Matthijs Kox, PhD; Nicole J. B. Waalders, BSc; Emma J. Kooistra, BSc; Jelle Gerretsen, BSc; Peter Pickkers, MD, PhD