tbuckley/cabot-search huggingface dataset:
Vasoactive Intestinal Peptide in Checkpoint Inhibitor–Induced Pneumonitis
Authors: Björn C Frye, Frank Meiss, Dagmar von Bubnoff, Gernot Zissel, Joachim Müller-Quernheim
Journal: New England Journal of Medicine (2020)

Inhaled Vasoactive Intestinal Peptide for Checkpoint Inhibitor Pneumonitis A patient with severe autoimmune pneumonitis from immune checkpoint inhibitor therapy for metastatic melanoma had improved...
Baricitinib restrains the immune dysregulation in patients with severe COVID-19
Authors: Vincenzo Bronte, Stefano Ugel, Elisa Tinazzi, Antonio Vella, Francesco De Sanctis, Stefania Canè, Veronica Batani, Rosalinda Trovato, Alessandra Fiore, Varvara Petrova, Francesca Hofer, Roza Maria Barouni, Chiara Musiu, Simone Caligola, Laura Pinton, Lorena Torroni, Enrico Polati, Katia Donadello, Simonetta Friso, Francesca Pizzolo, Manuela Iezzi, Federica Facciotti, Pier Giuseppe Pelicci, Daniela Righetti, Paolo Bazzoni, Mariaelisa Rampudda, Andrea Comel, Walter Mosaner, Claudio Lunardi, Oliviero Olivieri
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Patients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK/STAT signaling pathways, which can be disabled by small molecules.
Incidence and prognosis of the takotsubo syndrome compared to acute myocardial infarction
Authors: B. Björn Redfors, S. Jha, S. Thorleifsson, O. Angeras, C. Dworeck, A. Ravn-Fischer, P. Petursson, G. Sarno, A. Lyon, Ole Fröbert, S. James, D. Erlinge, E. Omerovic
Journal: European Journal of Heart Failure (2019)
Association of Household Exposure to Primary Clostridioides difficile Infection With Secondary Infection in Family Members
Authors: Aaron C. Miller, Alberto M. Segre, Sriram V. Pemmaraju, Daniel K. Sewell, Philip M. Polgreen
Journal: JAMA Network Open (2020)

<h3>Importance</h3> <i>Clostridioides difficile</i>infection (CDI) is a common hospital-acquired infection. Whether family members are more likely to experience a CDI following CDI in another separate family member remains to be studied. <h3>Objective</h3> To determine the incidence of potential family transmission of CDI. <h3>Design, Setting, and Participants</h3> In this case-control study comparing the incidence of CDI among individuals with prior exposure to a family member with CDI to those without prior family exposure, individuals were binned into monthly enrollment strata based on exposure status (eg, family exposure) and confounding factors (eg, age, prior antibiotic use). Data were derived from population-based, longitudinal commercial insurance claims from the Truven Marketscan Commercial Claims and Encounters and Medicare Supplemental databases from 2001 to 2017. Households with at least 2 family members continuously enrolled for at least 1 month were eligible. CDI incidence was computed within each stratum. A regression model was used to compare incidence of CDI while controlling for possible confounding characteristics. <h3>Exposures</h3> Index CDI cases were identified using inpatient and outpatient diagnosis codes. Exposure risks 60 days prior to infection included CDI diagnosed in another family member, prior hospitalization, and antibiotic use. <h3>Main Outcomes and Measures</h3> The primary outcome was the incidence of CDI in a given monthly enrollment stratum. Separate analyses were considered for CDI diagnosed in outpatient or hospital settings. <h3>Results</h3> A total of 224 818 cases of CDI, representing 194 424 enrollees (55.9% female; mean [SD] age, 52.8 [22.2] years) occurred in families with at least 2 enrollees. Of these, 1074 CDI events (4.8%) occurred following CDI diagnosis in a separate family member. Prior family exposure was significantly associated with increased incidence of CDI, with an incidence rate ratio (IRR) of 12.47 (95% CI, 8.86-16.97); this prior family exposure represented the factor with the second highest IRR behind hospital exposure (IRR, 16.18 [95% CI, 15.31-17.10]). For community-onset CDI cases without prior hospitalization, the IRR for family exposure was 21.74 (95% CI, 15.12-30.01). Age (IRR, 9.90 [95% CI, 8.92-10.98] for ages ≥65 years compared with ages 0-17 years), antibiotic use (IRR, 3.73 [95% CI, 3.41-4.08] for low-risk and 14.26 [95% CI, 13.27-15.31] for high-risk antibiotics compared with no antibiotics), and female sex (IRR, 1.44 [95% CI, 1.36-1.53]) were also positively associated with incidence. <h3>Conclusions and Relevance</h3> This study found that individuals with family exposure may be at significantly greater risk for acquiring CDI, which highlights the importance of the shared environment in the transmission and acquisition of<i>C difficile</i>.
Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer
Authors: Javier Cortés, Véronique Diéras, Sylvie Lorenzen, Filippo Montemurro, Jorge Riera-Knorrenschild, Peter Thuss-Patience, Giacomo Allegrini, Michelino De Laurentiis, Caroline Lohrisch, Eva Oravcová, Jose M. Perez-Garcia, Francesco Ricci, Dina Sakaeva, Rosanne Serpanchy, Jozef Šufliarský, Maria Vidal, Natsumi Irahara, Christine Wohlfarth, Mounir Aout, Karen Gelmon
Journal: JAMA Oncology (2020)

ERBB2 (HER2)-targeted therapy provides benefits in metastatic breast cancer (mBC) and gastric cancer, but additional treatments are needed to maximize efficacy and quality of life.
Abstract 14532: Serine Mutations in Hsp27 Abrogate Its Ability to Inhibit p53 Dependent Apoptosis and Doxorubicin-Induced Heart Failure in Mice
Authors: Ragu Kanagasabai, Krishanamurthy Karthikeyan, Jay L Zweier, Govindasamy Ilangovan
Journal: Circulation (2019)

Rationale: Small heat shock proteins (sHsps) protect the heart from chemotherapeutics-induced heart failure, by inhibition of p53-dependant apoptosis. However, mechanism of such protection has not ...
Lung Scintigraphy Imaging Features in a Young Patient With COVID-19
Authors: Christian Goetz, Thomas F. Fassbender, Philipp T. Meyer
Journal: Clinical Nuclear Medicine (2020)

A 31-year-old man developed diarrhea, fatigue, and intermittent fever for 2 weeks. The past few days he had experienced increasing dyspnea and dry cough. Ambulatory reverse transcriptase-polymerase chain reaction testing was positive for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Because of elevated D-dimer (1.5 mg/L), a lung scintigraphy (V/Q scan) was performed as SPECT/CT. Ventilation SPECT showed reduced ventilation with central nuclide deposition, whereas perfusion SPECT was inconspicuous, excluding pulmonary embolism. However, the low-dose CT revealed bilateral ground-glass opacities as previously described in COVID-19. This case highlights the procedure and findings of V/Q scanning (without embolism) in COVID-19.
Neoantigen prediction and computational perspectives towards clinical benefit: recommendations from the ESMO Precision Medicine Working Group
Authors: L. De Mattos-Arruda, M. Vazquez, F. Finotello, R. Lepore, E. Porta, J. Hundal, P. Amengual-Rigo, C.K.Y. Ng, A. Valencia, J. Carrillo, T.A. Chan, V. Guallar, N. McGranahan, J. Blanco, M. Griffith
Journal: Annals of Oncology (2020)
Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial
Authors: Federica Cappuccini, Richard Bryant, Emily Pollock, Lucy Carter, Clare Verrill, Julianne Hollidge, Ian Poulton, Megan Baker, Celia Mitton, Andrea Baines, Armin Meier, Guenter Schmidt, Richard Harrop, Andrew Protheroe, Ruth MacPherson, Steven Kennish, Susan Morgan, Selena Vigano, Pedro J Romero, Thomas Evans, James Catto, Freddie Hamdy, Adrian V S Hill, Irina Redchenko
Journal: Journal for ImmunoTherapy of Cancer (2020)

Prostate cancer (PCa) has been under investigation as a target for antigen-specific immunotherapies in metastatic disease settings for the last two decades leading to a licensure of the first therapeutic cancer vaccine, Sipuleucel-T, in 2010. However, neither Sipuleucel-T nor other experimental PCa vaccines that emerged later induce strong T-cell immunity.
Fall Prevention in Community-Dwelling Older Adults
Authors: Ben Kirk, Felipe Salech, Gustavo Duque
Journal: New England Journal of Medicine (2020)

Paco 2 ) and elevated ventilator driving pressure (defined as the difference between plateau pressure and positive end-expiratory pressure [PEEP]).The Paco 2 and pH did not differ in the two groups during the 7-day intervention.The PEEP was slightly higher in the liberal-oxygen group, but both the plateau and driving pressures were similar in the two groups.We calculated a surrogate of oxygen transport for the 7-day intervention period comprising the hemoglobin level, arterial oxygen saturation, and heart rate, and it did not differ in the two groups.Furthermore, we did not observe any signal of an increased lactate level or increased Sequential Organ Failure Assessment score during follow-up.Several studies that have investigated the relationship between oxygen delivery and oxygen consumption in critically ill patients or patients with sepsis 4 have not shown differences in outcomes.Oxygen delivery has to decrease to a level below 25% to reach the anaerobic threshold. 5Our findings do not provide any evidence that the hypothesis of acute cor pulmonale and low cardiac output could explain our results.
Pulmonary Aspergillosis in Patients with Suspected Ventilator-associated Pneumonia in UK ICUs
Authors: Laura Loughlin, Thomas P. Hellyer, P. Lewis White, Danny F. McAuley, Andrew Conway Morris, Raquel B. Posso, Malcolm D. Richardson, David W. Denning, A. John Simpson, Ronan McMullan
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale:Aspergillus infection in patients with suspected ventilator-associated pneumonia remains uncharacterized because of the absence of a disease definition and limited access to sensitive diagnostic tests.Objectives: To estimate the prevalence and outcomes of Aspergillus infection in adults with suspected ventilator-associated pneumonia.Methods: Two prospective UK studies recruited 360 critically ill adults with new or worsening alveolar shadowing on chest X-ray and clinical/hematological parameters supporting suspected ventilator-associated pneumonia. Stored serum and BAL fluid were available from 194 nonneutropenic patients and underwent mycological testing. Patients were categorized as having probable Aspergillus infection using a definition comprising clinical, radiological, and mycological criteria. Mycological criteria included positive histology or microscopy, positive BAL fluid culture, galactomannan optical index of 1 or more in BAL fluid or 0.5 or more in serum.Measurements and Main Results: Of 194 patients evaluated, 24 met the definition of probable Aspergillus infection, giving an estimated prevalence of 12.4% (95% confidence interval, 8.1-17.8). All 24 patients had positive galactomannan in serum (n = 4), BAL fluid (n = 16), or both (n = 4); three patients cultured Aspergillus sp. in BAL fluid. Patients with probable Aspergillus infection had a significantly longer median duration of critical care stay (25.5 vs. 15.5 d, P = 0.02). ICU mortality was numerically higher in this group, although this was not statistically significant (33.3% vs. 22.8%; P = 0.23).Conclusions: The estimated prevalence for probable Aspergillus infection in this geographically dispersed multicenter UK cohort indicates that this condition should be considered when investigating patients with suspected ventilator-associated pneumonia, including patient groups not previously recognized to be at high risk of aspergillosis.
Clinical trial of proton craniospinal irradiation for leptomeningeal metastases
Authors: T Jonathan Yang, Neil A Wijetunga, Josh Yamada, Suzanne Wolden, Michelle Mehallow, Debra A Goldman, Zhigang Zhang, Robert J Young, Mark G Kris, Helena A Yu, Andrew D Seidman, Igor T Gavrilovic, Andrew Lin, Bianca Santomasso, Christian Grommes, Anna F Piotrowski, Lauren Schaff, Jacqueline B Stone, Lisa M DeAngelis, Adrienne Boire, Elena Pentsova
Journal: Neuro-Oncology (2020)

Abstract Background Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. Methods We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). Results We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment–related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention. The median CNS PFS was 7 months (95% CI: 5–13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. Conclusion Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.
A comparison of epigenetic mitotic-like clocks for cancer risk prediction
Authors: Andrew E. Teschendorff
Journal: Genome Medicine (2020)

Abstract Background DNA methylation changes that accrue in the stem cell pool of an adult tissue in line with the cumulative number of cell divisions may contribute to the observed variation in cancer risk among tissues and individuals. Thus, the construction of epigenetic “mitotic” clocks that can measure the lifetime number of stem cell divisions is of paramount interest. Methods Building upon a dynamic model of DNA methylation gain in unmethylated CpG-rich regions, we here derive a novel mitotic clock (“epiTOC2”) that can directly estimate the cumulative number of stem cell divisions in a tissue. We compare epiTOC2 to a different mitotic model, based on hypomethylation at solo-WCGW sites (“HypoClock”), in terms of their ability to measure mitotic age of normal adult tissues and predict cancer risk. Results Using epiTOC2, we estimate the intrinsic stem cell division rate for different normal tissue types, demonstrating excellent agreement (Pearson correlation = 0.92, R 2 = 0.85, P = 3e−6) with those derived from experiment. In contrast, HypoClock’s estimates do not (Pearson correlation = 0.30, R 2 = 0.09, P = 0.29). We validate these results in independent datasets profiling normal adult tissue types. While both epiTOC2 and HypoClock correctly predict an increased mitotic rate in cancer, epiTOC2 is more robust and significantly better at discriminating preneoplastic lesions characterized by chronic inflammation, a major driver of tissue turnover and cancer risk. Our data suggest that DNA methylation loss at solo-WCGWs is significant only when cells are under high replicative stress and that epiTOC2 is a better mitotic age and cancer risk prediction model for normal adult tissues. Conclusions These results have profound implications for our understanding of epigenetic clocks and for developing cancer risk prediction or early detection assays. We propose that measurement of DNAm at the 163 epiTOC2 CpGs in adult pre-neoplastic lesions, and potentially in serum cell-free DNA, could provide the basis for building feasible pre-diagnostic or cancer risk assays. epiTOC2 is freely available from 10.5281/zenodo.2632938
Enhanced nose-to-brain delivery of tranilast using liquid crystal formulations
Authors: Gerard Lee See, Florencio Arce, Sabrina Dahlizar, Akie Okada, Muhammad Fikri Bin Mohd Fadli, Ichiro Hijikuro, Shoko Itakura, Masanori Katakura, Hiroaki Todo, Kenji Sugibayashi
Journal: Journal of Controlled Release (2020)
The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway
Authors: V. Kapil, R. S. Khambata, D. A. Jones, K. Rathod, C. Primus, G. Massimo, J. M. Fukuto, A. Ahluwalia
Journal: Pharmacological Reviews (2020)

In contrast to nitric oxide, which has well established and important roles in the regulation of blood flow and thrombosis, neurotransmission, the normal functioning of the genitourinary system, and the inflammation response and host defense, its oxidized metabolites nitrite and nitrate have, until recently, been considered to be relatively inactive. However, this view has been radically revised over the past decade and more. Much evidence has now accumulated demonstrating that nitrite serves as a storage form of nitric oxide, releasing nitric oxide preferentially under acidic and/or hypoxic conditions but also occurring under physiologic conditions: a phenomenon that is catalyzed by a number of distinct mammalian nitrite reductases. Importantly, preclinical studies demonstrate that reduction of nitrite to nitric oxide results in a number of beneficial effects, including vasodilatation of blood vessels and lowering of blood pressure, as well as cytoprotective effects that limit the extent of damage caused by an ischemia/reperfusion insult, with this latter issue having been translated more recently to the clinical setting. In addition, research has demonstrated that the other main metabolite of the oxidation of nitric oxide (i.e., nitrate) can also be sequentially reduced through processing in vivo to nitrite and then nitrite to nitric oxide to exert a range of beneficial effects—most notably lowering of blood pressure, a phenomenon that has also been confirmed recently to be an effective method for blood pressure lowering in patients with hypertension. This review will provide a detailed description of the pathways involved in the bioactivation of both nitrate and nitrite in vivo, their functional effects in preclinical models, and their mechanisms of action, as well as a discussion of translational exploration of this pathway in diverse disease states characterized by deficiencies in bioavailable nitric oxide. <h3>Significance Statement</h3> The past 15 years has seen a major revision in our understanding of the pathways for nitric oxide synthesis in the body with the discovery of the noncanonical pathway for nitric oxide generation known as the nitrate-nitrite-nitric oxide pathway. This review describes the molecular components of this pathway, its role in physiology, potential therapeutics of targeting this pathway, and their impact in experimental models, as well as the clinical translation (past and future) and potential side effects.
Validating new discoveries in sports medicine: we need FAIR play beyond p values
Authors: Chris Bleakley, James M Smoliga
Journal: British Journal of Sports Medicine (2020)

There is concern that a large proportion of scientific research is based on false-positive, non-replicable conclusions.1 As most experimental research in sports medicine is based on frequentist reasoning, p values have been at the centre of knowledge claims and new discoveries within this field. But many researchers and clinicians are unable to define or accurately interpret p values. Common misconceptions are that p values represent ‘the probability that the null hypothesis is true’ or ‘the probability that the hypothesis being tested is true’.2 In effect, p values only quantify the chances of getting the observed data (on the assumption that the null hypothesis is true) and therefore cannot exclusively inform clinical decision making. This editorial presents FAIR: a four-item approach to help validate new discovery in sports medicine.

False-positive risk (FPR) is ‘the probability of observing a statistically significant p-value and declaring that an effect is real, when it is not’.2 Crucially, a study’s FPR can be high, even when the corresponding p values are low. In a systematic audit of high-quality randomised controlled trials (RCTs) in sports physiotherapy, 18% of ‘statistically significant’ findings had a …
Author Correction: A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors
Authors: Michal Slyper, Caroline B. M. Porter, Orr Ashenberg, Julia Waldman, Eugene Drokhlyansky, Isaac Wakiro, Christopher Smillie, Gabriela Smith-Rosario, Jingyi Wu, Danielle Dionne, Sébastien Vigneau, Judit Jané-Valbuena, Timothy L. Tickle, Sara Napolitano, Mei-Ju Su, Anand G. Patel, Asa Karlstrom, Simon Gritsch, Masashi Nomura, Avinash Waghray, Satyen H. Gohil, Alexander M. Tsankov, Livnat Jerby-Arnon, Ofir Cohen, Johanna Klughammer, Yanay Rosen, Joshua Gould, Lan Nguyen, Matan Hofree, Peter J. Tramontozzi, Bo Li, Catherine J. Wu, Benjamin Izar, Rizwan Haq, F. Stephen Hodi, Charles H. Yoon, Aaron N. Hata, Suzanne J. Baker, Mario L. Suvà, Raphael Bueno, Elizabeth H. Stover, Michael R. Clay, Michael A. Dyer, Natalie B. Collins, Ursula A. Matulonis, Nikhil Wagle, Bruce E. Johnson, Asaf Rotem, Orit Rozenblatt-Rosen, Aviv Regev
Journal: Nature Medicine (2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Reply to Matsushita et al.
Authors: Martin Dahan, Anne Guyot, Aurelie Charissoux, Marion Schaefer, Romain Legros, Mathieu Pioche, Jérémie Jacques
Journal: Endoscopy (2020)

See also:Unroofing technique: effective “incomplete” endoscopic resection of large esophageal lymphangiomasEndoscopy 2020; 52(07): 621-621DOI: 10.1055/a-1157-8888
Serial Laboratory Testing for SARS-CoV-2 Infection Among Incarcerated and Detained Persons in a Correctional and Detention Facility — Louisiana, April–May 2020
Authors: Henry Njuguna, Megan Wallace, Sean Simonson, Farrell A. Tobolowsky, Allison E. James, Keith Bordelon, Rena Fukunaga, Jeremy A. W. Gold, Jonathan Wortham, Theresa Sokol, Danielle Haydel, Ha Tran, Kaylee Kim, Kiva A. Fisher, Mariel Marlow, Jacqueline E. Tate, Reena H. Doshi, Kathryn G. Curran
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

These two authors contributed equally.† COVID-19-related signs and symptoms include subjective fever, cough, shortness of breath, chills, muscle aches, headache, sore throat, loss of taste, or loss of smell.https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms
16235 An investigation of prevalence, risk factors, and health services utilization for onychomycosis in South Korea fishing villages
Authors: Gyeong Je Cho, Seong Min Hong, Jong Uk Kim, Woo Jung Jin, So Hee Park, In Ho Park, Jung Eun Seol, Jeong Ho Kim, Jong Soo Choi, Hyojin Kim
Journal: Journal of the American Academy of Dermatology (2020)
Kleptomania: a report of 20 cases
Authors: S L McElroy, H G Pope, J I Hudson, P E Keck, K L White
Journal: American Journal of Psychiatry (1991)

The authors' objective was to provide phenomenologic, family history, and treatment response data on a group of rigorously diagnosed patients with kleptomania.Twenty consecutive inpatients and outpatients met DSM-III-R criteria for current kleptomania or a past history of kleptomania. These patients were given structured diagnostic interviews, and their family histories of psychiatric disorders were assessed blindly. The patients' responses to psychosocial and biological treatments were also assessed.All of the kleptomanic patients had lifetime diagnoses of major mood disorders, 16 had lifetime diagnoses of anxiety disorders, and 12 had lifetime diagnoses of eating disorders. A high morbid risk of major mood disorders (0.31) was found in their first-degree relatives. Ten of 18 patients receiving thymoleptic medications reported reduction or remission of their stealing behavior.Kleptomania may be related to major mood disorder and perhaps may represent another form of "affective spectrum disorder."