tbuckley/cabot-search huggingface dataset:
Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial
Authors: Suzanne L. Topalian, Shailender Bhatia, Asim Amin, Ragini R. Kudchadkar, William H. Sharfman, Celeste Lebbé, Jean-Pierre Delord, Lara A. Dunn, Michi M. Shinohara, Rima Kulikauskas, Christine H. Chung, Uwe M. Martens, Robert L. Ferris, Julie E. Stein, Elizabeth L. Engle, Lot A. Devriese, Christopher D. Lao, Junchen Gu, Bin Li, Tian Chen, Adam Barrows, Andrea Horvath, Janis M. Taube, Paul Nghiem
Journal: Journal of Clinical Oncology (2020)

PURPOSE Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer commonly driven by the Merkel cell polyomavirus (MCPyV). The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunosuppressive pathway is often upregulated in MCC, and advanced metastatic MCC frequently responds to PD-1 blockade. We report what we believe to be the first trial of anti–PD-1 in the neoadjuvant setting for resectable MCC. METHODS In the phase I/II CheckMate 358 study of virus-associated cancer types, patients with resectable MCC received nivolumab 240 mg intravenously on days 1 and 15. Surgery was planned on day 29. Tumor regression was assessed radiographically and microscopically. Tumor MCPyV status, PD-L1 expression, and tumor mutational burden (TMB) were assessed in pretreatment tumor biopsies. RESULTS Thirty-nine patients with American Joint Committee on Cancer stage IIA-IV resectable MCC received ≥ 1 nivolumab dose. Three patients (7.7%) did not undergo surgery because of tumor progression (n = 1) or adverse events (n = 2). Any-grade treatment-related adverse events occurred in 18 patients (46.2%), and grade 3-4 events in 3 patients (7.7%), with no unexpected toxicities. Among 36 patients who underwent surgery, 17 (47.2%) achieved a pathologic complete response (pCR). Among 33 radiographically evaluable patients who underwent surgery, 18 (54.5%) had tumor reductions ≥ 30%. Responses were observed regardless of tumor MCPyV, PD-L1, or TMB status. At a median follow-up of 20.3 months, median recurrence-free survival (RFS) and overall survival were not reached. RFS significantly correlated with pCR and radiographic response at the time of surgery. No patient with a pCR had tumor relapse during observation. CONCLUSION Nivolumab administered approximately 4 weeks before surgery in MCC was generally tolerable and induced pCRs and radiographic tumor regressions in approximately one half of treated patients. These early markers of response significantly predicted improved RFS. Additional investigation of these promising findings is warranted.
The evidence landscape in precision medicine
Authors: Spencer Phillips Hey, Cory V. Gerlach, Garrett Dunlap, Vinay Prasad, Aaron S. Kesselheim
Journal: Science Translational Medicine (2020)

Precision medicine is beginning to make an impact on the treatment of different diseases, but there are still challenges that must be overcome, such as the complexity of interventions, the need for marker validation, and the level of evidence necessary to demonstrate effectiveness. In this Perspective, we describe how evidence landscapes can help to address these challenges.
A Man in His 80s With Dyspnea and a Malpositioned Pacemaker Lead
Authors: Anvesha Singh, Ian Loke, Jeffrey P. Khoo
Journal: JAMA Cardiology (2020)

This case report describes a lead entering the left atrium via the right upper pulmonary vein through a large sinus venosus atrial septal defect with a dilated right heart and substantial left-to-right shunt.
Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2
Authors: Guoshuai Cai, Yohan Bossé, Feifei Xiao, Farrah Kheradmand, Christopher I. Amos
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

declared the coronavirus disease (COVID-19) outbreak a pandemic.As of May 28, 2020, laboratories had confirmed 5,701,337 COVID-19 cases, and 357,668 deaths had been reported in 216 countries, areas, or territories (1).COVID-19 is caused by a new type of pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is phylogenetically similar to SARS-CoV, with approximately 80% identity between the genomes (2).SARS viruses affect the respiratory tract and cause an acute respiratory response through the same cell-entry receptor, ACE2 (angiotensin-converting enzyme 2), which is the only experimentally confirmed SARS-CoV-2 receptor.SARS-CoV-2 infection also uses activation of the spike proteins found on the surface of the virus for cellular entry.The best candidates for priming spike proteins are two host cell enzymes called Furin and TMPRSS2 (2).In the current severe global emergency, to enable effective prevention and care, it is imperative to identify potential risk factors, such as cigarette smoking, which is a substantial risk factor for various important bacterial and viral infections.Some of the results of this study were previously published in preprint form (medRxiv, https://www.medrxiv.org/content/10.1101/2020.02.05.20020107v3). MethodsWe evaluated a comprehensive set of transcriptomic data sets to investigate the associations of smoking with ACE2, FURIN, and TMPRSS2 gene expression in lung tissues.Two data sets were generated using normal lung tissues from patients with lung adenocarcinoma: a Caucasian RNA-sequencing (RNA-seq) data set from The Cancer Genome Atlas (n = 48) (3) and an Asian RNA-seq data set from the Gene Expression Omnibus (GSE40419, n = 74) (4).We included three polyethnic microarray data sets of gene expression in healthy small airway epithelium samples (GSE63127, n = 230 [5]; GSE19667, n = 116 [6]; and GSE5058, n = 24 [7]) and large airway epithelium samples (GSE7895, n = 104 [8]).In addition, we analyzed three microarray data sets of samples derived from healthy subjects and patients with chronic obstructive pulmonary disease (COPD), including small airway epithelium samples from current smokers (from GSE5058, n = 26 [7]),
Differential sympathetic response to lesion-induced chronic kidney disease in rabbits
Authors: Yusuke Sata, Sandra L. Burke, Anna M.D. Watson, Jay C. Jha, Cindy Gueguen, Nina Eikelis, Kyungjoon Lim, Kristy L. Jackson, Gavin W. Lambert, Karin A.M. Jandeleit-Dahm, Kate M. Denton, Murray D. Esler, Markus P. Schlaich, Geoffrey A. Head
Journal: Kidney International (2020)
Respirable Crystalline Silica Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Analysis of Case–Control Studies
Authors: Calvin Ge, Susan Peters, Ann Olsson, Lützen Portengen, Joachim Schüz, Josué Almansa, Thomas Behrens, Beate Pesch, Benjamin Kendzia, Wolfgang Ahrens, Vladimir Bencko, Simone Benhamou, Paolo Boffetta, Bas Bueno-de-Mesquita, Neil Caporaso, Dario Consonni, Paul Demers, Eleonóra Fabiánová, Guillermo Fernández-Tardón, John Field, Francesco Forastiere, Lenka Foretova, Pascal Guénel, Per Gustavsson, Vikki Ho, Vladimir Janout, Karl-Heinz Jöckel, Stefan Karrasch, Maria Teresa Landi, Jolanta Lissowska, Danièle Luce, Dana Mates, John McLaughlin, Franco Merletti, Dario Mirabelli, Nils Plato, Hermann Pohlabeln, Lorenzo Richiardi, Peter Rudnai, Jack Siemiatycki, Beata Świątkowska, Adonina Tardón, Heinz-Erich Wichmann, David Zaridze, Thomas Brüning, Kurt Straif, Hans Kromhout, Roel Vermeulen
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.
The L‐α‐Lysophosphatidylinositol/G Protein–Coupled Receptor 55 System Induces the Development of Nonalcoholic Steatosis and Steatohepatitis
Authors: Marcos F. Fondevila, Uxia Fernandez, Maria J. Gonzalez‐Rellan, Natalia Da Silva Lima, Xabier Buque, Agueda Gonzalez‐Rodriguez, Cristina Alonso, Marta Iruarrizaga‐Lejarreta, Teresa C. Delgado, Marta Varela‐Rey, Ana Senra, Vera Garcia‐Outeiral, Eva Novoa, Cristina Iglesias, Begoña Porteiro, Daniel Beiroa, Cintia Folgueira, Marta Tojo, Jorge L. Torres, Lourdes Hernández‐Cosido, Óscar Blanco, Juan Pablo Arab, Francisco Barrera, Diana Guallar, Miguel Fidalgo, Miguel López, Carlos Dieguez, Miguel Marcos, Maria L. Martinez‐Chantar, Marco Arrese, Carmelo Garcia‐Monzon, Jose M. Mato, Patricia Aspichueta, Ruben Nogueiras
Journal: Hepatology (2020)

Background and Aims G protein–coupled receptor (GPR) 55 is a putative cannabinoid receptor, and l‐α‐lysophosphatidylinositol (LPI) is its only known endogenous ligand. Although GPR55 has been linked to energy homeostasis in different organs, its specific role in lipid metabolism in the liver and its contribution to the pathophysiology of nonalcoholic fatty liver disease (NAFLD) remains unknown. Approach and Results We measured (1) GPR55 expression in the liver of patients with NAFLD compared with individuals without obesity and without liver disease, as well as animal models with steatosis and nonalcoholic steatohepatitis (NASH), and (2) the effects of LPI and genetic disruption of GPR55 in mice, human hepatocytes, and human hepatic stellate cells. Notably, we found that circulating LPI and liver expression of GPR55 were up‐regulated in patients with NASH. LPI induced adenosine monophosphate–activated protein kinase activation of acetyl–coenzyme A carboxylase (ACC) and increased lipid content in human hepatocytes and in the liver of treated mice by inducing de novo lipogenesis and decreasing β‐oxidation. The inhibition of GPR55 and ACCα blocked the effects of LPI, and the in vivo knockdown of GPR55 was sufficient to improve liver damage in mice fed a high‐fat diet and in mice fed a methionine‐choline–deficient diet. Finally, LPI promoted the initiation of hepatic stellate cell activation by stimulating GPR55 and activation of ACC. Conclusions The LPI/GPR55 system plays a role in the development of NAFLD and NASH by activating ACC.
Efficient drug and gene delivery to liver fibrosis: rationale, recent advances, and perspectives
Authors: Somayeh Mahdinloo, Seyed Hossein Kiaie, Ala Amiri, Salar Hemmati, Hadi Valizadeh, Parvin Zakeri-Milani
Journal: Acta Pharmaceutica Sinica B (2020)

Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix, and no specific medical therapy is approved for that until now. Due to liver metabolic capacity for drugs, the fragility of drugs, and the presence of insurmountable physiological obstacles in the way of targeting, the development of efficient drug delivery systems for anti-fibrotics seems vital. We have explored articles with a different perspective on liver fibrosis over the two decades, then collected and summarized the information by providing corresponding in vitro and in vivo cases. We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals. Furthermore, the critical chemical and herbal anti-fibrotics, biological molecules such as micro-RNAs, siRNAs, and growth factors, which can affect cell division and differentiation, are mentioned. Likewise, drug and gene delivery and therapeutic systems on in vitro and in vivo models are summarized in the data tables. This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.
Assessment of SARS-CoV-2 Infection Prevalence in Homeless Shelters — Four U.S. Cities, March 27–April 15, 2020
Authors: Emily Mosites, Erin M. Parker, Kristie E. N. Clarke, Jessie M. Gaeta, Travis P. Baggett, Elizabeth Imbert, Madeline Sankaran, Ashley Scarborough, Karin Huster, Matt Hanson, Elysia Gonzales, Jody Rauch, Libby Page, Temet M. McMichael, Ryan Keating, Grace E. Marx, Tom Andrews, Kristine Schmit, Sapna Bamrah Morris, Nicole F. Dowling, Georgina Peacock, Ann Buff, Calla Jamison, Ruthanne Marcus, Carol Y. Rao, Julie L. Self, Farrell Tobolowsky, Samantha Williams, Meagan Kay, Naveena Bobba, Stephanie Cohen, Jonathan Fuchs, Trang Nguyen, Julie Stoltey
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In the United States, approximately 1.4 million persons access emergency shelter or transitional housing each year (1). These settings can pose risks for communicable disease spread. In late March and early April 2020, public health teams responded to clusters (two or more cases in the preceding 2 weeks) of coronavirus disease 2019 (COVID-19) in residents and staff members from five homeless shelters in Boston, Massachusetts (one shelter); San Francisco, California (one); and Seattle, Washington (three). The investigations were performed in coordination with academic partners, health care providers, and homeless service providers. Investigations included reverse transcription-polymerase chain reaction testing at commercial and public health laboratories for SARS-CoV-2, the virus that causes COVID-19, over approximately 1-2 weeks for residents and staff members at the five shelters. During the same period, the team in Seattle, Washington, also tested residents and staff members at 12 shelters where a single case in each had been identified. In Atlanta, Georgia, a team proactively tested residents and staff members at two shelters with no known COVID-19 cases in the preceding 2 weeks. In each city, the objective was to test all shelter residents and staff members at each assessed facility, irrespective of symptoms. Persons who tested positive were transported to hospitals or predesignated community isolation areas.
RAC2 Links B-Cell Receptor Signaling and Cell Adhesion in Mantle Cell Lymphoma
Authors: Weige Wang, Franzen Carrie, Madina Sukhanova, Venkataraman Girish, Ming Mei, Guo Ailin, Pin Lu, Dong Sheng, Gao Anhui, Xia Chunmei, Li Jia, Zhou Xiaoyan, Y Lynn Wang
Journal: Blood (2017)
OC-081 Retract-ligate-unroof-biopsy: a novel approach to the management of gastric submucosal lesions
Authors: H Smart, A Moore
Journal: Gut (2017)

Introduction  Gastric submucosal lesions (SML) are challenging in terms of diagnosis and treatment. Mucosal biopsy is uniformly negative; endoscopic ultrasound (EUS) and cross-sectional imaging rarely provide a diagnosis. Whilst EUS aspiration biopsy can provide diagnostic information it doesn’t treat the SML. Endoscopic resection of gastric SML risks perforation; larger SML may require surgical resection. We report the use of a novel technique for the endoscopic management of gastric SML.  Method  The retract-ligate-unroof-biopsy (RLUB) technique is illustrated in the accompanying video. RLUB was only performed after thorough assessment of the SML by endoscopy and EUS. A twin-channel therapeutic endoscope (Olympus 2 T240 or 2TQ260M) was used for the procedure which was performed under deep sedation with propofol. The SML was identified and punctured with a tissue anchor device (OTSC Anchor, Ovesco Endoscopy). This allowed the SML to be retracted enabling a Polyloop (HX-400U-30, Olympus), inserted down the other channel of the endoscope, to be placed over the SML to provide ligation. A diathermy knife (DualKnife, Olympus) was then used to incise the ligated SML, enabling deep biopsy to be undertaken with large capacity forceps (Radial Jaw 4 with needle, Boston Scientific). Following tissue acquisition a further Polyloop was placed over the SML in order to optimise ischaemic necrosis. Repeat endoscopic assessment was undertaken after 3 months.  Results  Six patients (4 men) were treated by RLUB. Their mean age was 51.2 (range 24–73) years. They opted for RLUB rather than continued endoscopic observation or surgery. The median size of the SML on EUS was 23 (range 10–40) mm. All patients had a technically successful procedure in terms of ligation and biopsy. No significant adverse events (bleeding or perforation) occurred. In 1 patient insufficient tissue was obtained for histological assessment. Of the remainder, 2 had gastrointestinal stromal tumours (GIST) and 1 each had lipoma, adenomyoma and ectopic pancreas. Follow up endoscopy at 3 months showed complete resolution of the SML in 5 patients (including the patient with inadequate histology). The remaining patient’s SML took a further 6 months to resolve by ischaemic necrosis after repeat looping.  Conclusion  RLUB is a safe and effective technique for managing gastric SML in selected patients whom decline continued endoscopic follow up in favour of histological diagnosis and endoscopic treatment. In this small patient group no significant adverse events occurred, histological diagnosis was made in 83% and all SML resolved, usually within 3 months. RLUB deserves more widespread consideration.  Reference  . Binmoeller KF, Shah JN, Bhat YM, Kane SD. Retract-ligate-unroof-biopsy: a novel approach to the diagnosis and therapy of large non-pedunculated stromal tumours. Gastrointestinal Endoscopy 2013;77(5):803–808.  Disclosure of Interest  None Declared
Multidisciplinary and Holistic Models of Care for Patients With Dermatologic Disease and Psychosocial Comorbidity
Authors: Arsh Patel, Mohammad Jafferany
Journal: JAMA Dermatology (2020)

Psychocutaneous disease affects an underrecognized patient population facing misdiagnosis and a reduced quality of life due to knowledge gaps and insufficient awareness. Clinicians worldwide serve as pioneers in offering specialized care for affected patients through the development of combined clinics. Results yield a framework needed to expand availability and ultimately improve patient outcomes.To report key findings generated from an in-depth analysis of available literature, highlight the importance and benefits of providing multidisciplinary care, and provide structural evidence of existing liaison clinics for more widespread future application.To identify data from inception to November 12, 2019, a search was conducted in PubMed and Google Scholar using the following search strategy: psychodermatology clinic OR psychodermatology liaison OR psychodermatology combined OR psychocutaneous clinic OR psychocutaneous liaison OR psychocutaneous combined OR psychiatry dermatology combined OR psychiatry dermatology clinic. Studies were excluded if they were single-patient case reports; if information regarding the number of patients, clinic setup, and presenting conditions was not provided; and if the reports were published in a language other than English.A total of 932 studies were screened, and 23 were retained after removal of duplicates and application of inclusion criteria. The combined clinics, varying in structure, design, and setting, provided collective data from 1677 patients in 12 countries worldwide. Results indicate that patients experience barriers in gaining access to care and clinicians lack appropriate knowledge and resources for proper diagnosis and treatment. The implementation of combined clinics provides a cost-reducing avenue in the management of dermatologic disease and psychosocial comorbidity by limiting inaccurate diagnoses, ineffective treatments, unnecessary referrals, and "doctor shopping." Increased patient satisfaction or improved patient outcomes after the use of holistic treatment with pharmacologic and nonpharmacologic therapies was reported by 20 included studies (87%).Examined data from the included clinics illuminate the increased need and demand for specialized care. The ability to provide high-quality integrative patient care, potential utility in medical education, and findings of reduced health care expenditures reflect the need for health care leaders to expand specialized care as key for moving forward. Practical clinic models consist of a well-informed dermatologist for identification of psychocutaneous disease, referral if needed, and treatment based on the physician's individual comfort level. Involvement of multiple specialists, including psychiatrists, psychologists, and residents and preferably within teaching institutions, in consultations and management-related discussions is recommended.
Maternal perinatal depressive symptoms and offspring psychotic experiences at 18 years of age: a longitudinal study
Authors: Ramya Srinivasan, Rebecca M Pearson, Sonia Johnson, Gemma Lewis, Glyn Lewis
Journal: The Lancet Psychiatry (2020)

BackgroundEvidence exists that maternal depression in the perinatal period has an adverse effect on a range of early childhood outcomes and increases the risk of offspring depression during adolescence. However, the association between maternal depression during the perinatal period and offspring psychotic experiences has not been investigated. We aimed to investigate whether there is an association between maternal antenatal or postnatal depression and offspring psychotic experiences at 18 years of age.MethodsThis longitudinal study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort, which recruited 14 541 pregnant women with an estimated delivery date between April 1, 1991, and Dec 31, 1992. Perinatal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS); offspring psychotic experiences at 18 years of age were measured using the Psychosis-Like Symptom Interview. Offspring of mothers with complete data on maternal perinatal depression measures, and complete data on outcome (psychotic experiences) and confounding variables were included in the main analysis. For the main analysis, we used logistic regression to examine the associations between maternal depression (antenatal and postnatal) and offspring psychotic experiences at the age of 18 years. We used biprobit regression to model the association between maternal antenatal depression and the two offspring outcomes (psychotic experiences and depression) at 18 years of age jointly.Findings3067 offspring for whom data were available on maternal perinatal depression and offspring psychotic experiences aged 18 years were included in analyses. Maternal antenatal depressive symptoms were associated with offspring psychotic experiences at 18 years of age, with an unadjusted odds ratio (OR) of 1·38 (95% CI 1·18–1·61, p=0·0001) and after adjustment for confounders, an OR of 1·26 (1·06–1·49, p=0·0074). Maternal antenatal depressive symptoms were associated with both offspring psychotic experiences at the age of 18 years (n=2830, OR for a 5-point increase in EPDS score: 1·32 [95% CI 1·16–1·51], p<0·0001) and offspring depression at 18 years (OR for a 5-point increase in EPDS score: 1·18 [1·03–1·34], p=0·016). From joint modelling, there was no evidence that the association between maternal antenatal depression and offspring psychotic experiences differed in strength compared with offspring depression (p=0·19).InterpretationThe offspring of mothers who experience depression in the perinatal period are more likely to report psychotic experiences at 18 years of age. If the association is found to be causal, it would strengthen the case for identifying and treating maternal depression during and after pregnancy.FundingUK Medical Research Council and the Wellcome Trust.