tbuckley/cabot-search huggingface dataset:
Preliminary outcomes of a prospective observational study of combinatorial abiraterone acetate/enzalutamide (AA/Enz) and radical radiotherapy (RT) in nonmetastatic node-positive (N+M0) prostate cancer (PCa).
Authors: Mark Ting Le Tan, Wai Yee Woo, Jeffrey Tuan, Terence Wee Kiat Tan, Michael Lian Chek Wang, Eu Tiong Chua, Wen Shen Looi, Youquan Li, Wen Long Nei, Hai-Tao Wang, Anusha Chimmiri, Adelene Sim Yen Ling, Enya Hui Wen Ong, Li Yan Khor, Joe Poh Sheng Yeong, Chien sheng Tan, Kae-Jack Tay, Lui Shiong Lee, Ravindran Kanesvaran, Melvin Lee Kiang Chua
Journal: Journal of Clinical Oncology (2020)

227 Background: Treatment paradigm for N+M0 PCa has evolved, with the advent of multiple options for upfront AA/Enz or RT in combination with conventional hormonal therapy (HT). However, the optimal treatment protocol remains undefined. We therefore conducted a prospective observational study of combination AA/Enz+RT in N+M0 PCa patients. Methods: Patients with biopsy-proven adenocarcinoma of the prostate and N+M0 by imaging ( 68 Ga-PSMA-PET or whole body MRI) were included. Exclusion criteria were 1) ECOG ≥2; 2) severe comorbidities; 3) cardiac event of &lt;6 mo interval. Treatment protocol involved 18 mo of AA (1000 mg with 5 mg prednisolone once daily)/Enz (160 mg once daily)+HT (LHRH agonist/antagonist) in combination with RT to pelvis (54 Gy with simultaneous boost of 60-66 Gy in 27 fr) and prostate (78 Gy/39 fr); RT commenced 1-3 mo upon initiation of AA/Enz. Primary endpoint of this analysis was PSA of ≤0.1 ng/ml at 12 mo. Results: From Jun 2017-Sep 2019, 13 men were recruited; median follow-up duration was 14.0 mo (range 3.0-28.0 mo). Median age of the cohort was 67.0 y (IQR 61.0 – 69.0 y); 84.0% of men had GS8-10 disease, and median number of cN+ nodes was 2 (range 1-5 nodes). 11 received AA, and 2 received Enz. 53.8% (N = 7) and 69.2% (N = 9) of patients achieved a PSA nadir of ≤0.1 ng/ml at 6.0 and 12.0 mo, respectively; this contrasts against a propensity-matched cohort (N = 27) treated by HT+RT alone (33.3% and 51.9%, respectively). No biochemical recurrence was recorded at the time of analysis. 3 and 2 acute ≥G2 GU and GI toxicities were reported during RT. Late ≥G2 GU toxicities were observed in 2 men (G2 frequency). 2 patients experienced G2 fatigue and one with G2 transaminitis secondary to AA, with dose reduction. Germline genetic profiling with whole exome sequencing revealed two patients (15.4%) with BRCA2 frameshift mutations; interestingly, GU/GI RT toxicities were not observed in these patients. Conclusions: Our preliminary results suggest that combinatorial AA/Enz and high dose RT is tolerated and can induce a pronounced PSA response in low volume N+M0 PCa.
Erratum: Corrigenda: Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome
Authors: Lydia E Kuo, Joanna B Kitlinska, Jason U Tilan, Lijun Li, Stephen B Baker, Michael D Johnson, Edward W Lee, Mary Susan Burnett, Stanley T Fricke, Richard Kvetnansky, Herbert Herzog, Zofia Zukowska
Journal: Nature Medicine (2007)
Reply
Authors: Parag Goyal, Jerard Kneifati-Hayek, Alexi Archambault, Krisha Mehta, Emily B. Levitan, Ligong Chen, Ivan Diaz, James Hollenberg, Joseph T. Hanlon, Mark S. Lachs, Mathew S. Maurer, Monika M. Safford
Journal: JACC Heart Failure (2020)
Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus
Authors: Weicheng Liang, Zhijie Feng, Shitao Rao, Cuicui Xiao, Xingyang Xue, Zexiao Lin, Qi Zhang, Wei Qi
Journal: Gut (2020)

A series of pneumonia cases caused by 2019 novel coronavirus (2019-nCoV, also named COVID-19) are being reported globally. Based on recent publications,1–3 the most common symptoms in patients infected by 2019-nCoV were fever and cough. However, the incidence of other clinical features differs in different reports. To address this issue, we collected the data from three reports1–3 and compared the incidence accordingly. We found that the incidence of leucopenia, fever and diarrhoea in the three studies showed a statistically significant difference (table 1). Among these symptoms, diarrhoea displayed the smallest p-value (p=0.016), suggesting that the criteria for diagnosing diarrhoea may differ in different hospitals. Due to the different criteria, clinicians may underestimate the value of this symptom in clinical practice, and it may affect the preliminary diagnostic accuracy.

View this table:

Table 1 
Intergroup comparison between three recent publications



Recent studies showed that the spike protein of 2019-nCoV shared the same cell entry receptor ACE2 as SARS-CoV.4 5 In terms of the pathological importance of ACE2 in modulating intestinal inflammation and diarrhoea,6 we examined the expression profiles of ACE2 in various human tissues and found that ACE2 was highly expressed in the human small intestine (online supplementary file 1). Intriguingly, the RNA level of ACE2 was quite low in lung tissues from healthy donors.### Supplementary data

[gutjnl-2020-320832supp001.pdf] 

Given that the distribution of ACE2 may determine the route of 2019-nCoV infection, we next evaluated the expression of ACE2 in different cell …
Nurse-Guided Internet-Delivered Cognitive Behavioral Therapy for Insomnia in General Practice: Results from a Pragmatic Randomized Clinical Trial
Authors: Tanja Van der Zweerde, Jaap Lancee, Pauline Slottje, Judith E. Bosmans, Eus J.W. Van Someren, Annemieke van Straten
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Guidelines recommend cognitive behavioral therapy for insomnia (CBT-I) as the first line of treatment for insomnia in general practice, but CBT-I is rarely available. Nurse-guided Internet-delivered CBT-I might be a solution to improve access to care. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; We aimed to determine the effectiveness of nurse-guided Internet-delivered CBT-I (I-CBT-I) on insomnia severity experienced by patients in general practice. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Nurse-guided I-CBT-I (“i-Sleep”) was compared to care-as-usual (and I-CBT-I after 6 months) in 15 participating general practices among 134 patients (≥18 years old) with clinical insomnia symptoms. Assessments took place at 8, 26 and 52 weeks. Primary outcome was self-reported insomnia severity (Insomnia Severity Index) at 8 weeks. Secondary outcomes were sleep diary indices, depression and anxiety symptoms (Hospital Anxiety and Depression Scale), fatigue, daytime consequences of insomnia, sleep medication and adverse events. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Two thirds of the 69 intervention patients (&lt;i&gt;n&lt;/i&gt; = 47; 68%) completed the whole intervention. At the posttest examination, there were large significant effects for insomnia severity (Cohen’s &lt;i&gt;d =&lt;/i&gt;1.66), several sleep diary variables (wake after sleep onset, number of awakenings, terminal wakefulness, sleep efficiency, sleep quality) and depression. At 26 weeks there were still significant effects on insomnia severity (&lt;i&gt;d&lt;/i&gt; = 1.02) and on total sleep time and sleep efficiency. No significant effects were observed for anxiety, fatigue, daily functioning or sleep medication. No adverse events were reported. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Nurse-guided I-CBT-I effectively reduces insomnia severity among general practice patients. I-CBT-I enables general practitioners to offer effective insomnia care in accordance with the clinical guidelines.
C1-esterase inhibitor treatment for antibody-mediated rejection after lung transplantation: two case reports
Authors: François Parquin, Elise Cuquemelle, Eve Camps, Jérôme Devaquet, Mathilde Phillips Houllbracq, Edouard Sage, Olivier Brugière, Morgan Le Guen, Elisabeth Longchampt, Stéphanie Malard, Clément Picard, Jean Luc Taupin, Antoine Roux
Journal: European Respiratory Journal (2020)

Antibody-mediated rejection (AMR) after lung transplantation (LTx) is associated with poor prognosis [1]. Recent International Society for Heart and Lung Transplantation recommendations propose a standardised classification of lung AMR [2]. Based on the number of features present, this classification describes three different degree of certainty for AMR diagnosis. However, in the absence of a true gold standard, the management of potential AMR are subject to quite a high degree of uncertainty. C1 esterase inhibitor could be efficient in complement dependent antibody mediated rejection in lung transplant patients <http://bit.ly/2Nsz6R4> We thank the patients who participated in this study and the staff members who cared for them.
Alzheimer’s Disease and Vascular Aging
Authors: Marta Cortes-Canteli, Costantino Iadecola
Journal: Journal of the American College of Cardiology (2020)

Alzheimer's disease, the leading cause of dementia in the elderly, is a neurodegenerative condition characterized by accumulation of amyloid plaques and neurofibrillary tangles in the brain. However, age-related vascular changes accompany or even precede the development of Alzheimer's pathology, raising the possibility that they may have a pathogenic role. This review provides an appraisal of the alterations in cerebral and systemic vasculature, the heart, and hemostasis that occur in Alzheimer's disease and their relationships to cognitive impairment. Although the molecular pathogenesis of these alterations remains to be defined, amyloid-β is a likely contributor in the brain as in the heart. Collectively, the evidence suggests that vascular pathology is a likely pathogenic contributor to age-related dementia, including Alzheimer's disease, inextricably linked to disease onset and progression. Consequently, the contribution of vascular factors should be considered in preventive, diagnostic, and therapeutic approaches to address one of the major health challenges of our time.
An Evolutionary Insertion in the Mxra8 Receptor-Binding Site Confers Resistance to Alphavirus Infection and Pathogenesis
Authors: Arthur S. Kim, Ofer Zimmerman, Julie M. Fox, Christopher A. Nelson, Katherine Basore, Rong Zhang, Lorellin Durnell, Chandni Desai, Christopher Bullock, Sharon L. Deem, Jonas Oppenheimer, Beth Shapiro, Ting Wang, Sara Cherry, Carolyn B. Coyne, Scott A. Handley, Michael J. Landis, Daved H. Fremont, Michael S. Diamond
Journal: Cell Host & Microbe (2020)
Medical oncologists’ first-line treatment preferences in metastatic urothelial carcinoma.
Authors: Andrea B. Apolo, M. Janelle Cambron-Mellott, Kathleen Beusterien, Brian S. Seal, Martine C. Maculaitis, Andrew Bernstein, Megan Epperson, Mara Lisa Jeffress, Yunes Doleh
Journal: Journal of Clinical Oncology (2020)

449 Background: Immunotherapy and combination platinum chemotherapy are effective treatment options with different adverse events (AEs) for patients (pts) with metastatic urothelial carcinoma (mUC). This study quantified treatment preferences based on perceived benefit-risk trade-offs associated with first-line (1L) therapy among medical oncologists (MOs). Methods: MOs completed a cross-sectional online survey assessing treatment preferences for 3 pt groups: cisplatin (cis)-eligible (elig) PD-L1 high, cis-ineligible (inelig) PD-L1 high, and cis-inelig PD-L1 low. Three discrete choice experiments (DCEs) showed a series of tasks where MOs chose between 2 alternative treatment profiles varying on 7 attributes identified as important in qualitative research: overall survival (OS), overall response rate (ORR), all grades (G) neuropathy, G3/4 nausea/vomiting, colitis, pneumonitis, and neutropenia. Hierarchical Bayes models were used to estimate preference weights for each attribute. Results: A total of 210 MOs, averaging 16 years in practice (65% community [C], 35% academic [A]), participated. PD-L1 testing was available to most MOs, 87.5% (C) and 74.3% (A). In cis-elig PD-L1 high and cis-inelig -PD-L1 low pts, the order of relative importance was: OS, ORR, G3/4 nausea/vomiting, G3/4 neutropenia, G3/4 pneumonitis, all G neuropathy, and G3/4 colitis. In cis-inelig PD-L1 high pts, improved OS was most important but decreasing G3/4 nausea/vomiting was more important than improving ORR. In cis-elig PD-L1 high, cis-inelig PD-L1 high, and cis-inelig PD-L1 low pts, to accept increases in AEs, MOs require OS increases of 2.0, 3.0, and 2.5 months (G3/4 nausea/vomiting by 21%); 1.6, 1.8, and 2.0 months (G3/4 neutropenia by 23%); 0.9, 0.4, and 1.1 (G3/4 pneumonitis by 3%); and 0.9, 0.6, and 0.7 months (all G neuropathy by 5%), respectively. Conclusions: OS and ORR are key drivers for MOs in the choice of 1L therapy for pts with mUC. MO selection of therapy is governed by platinum eligibility, PD-L1 status, and a desire to limit AEs. Future 1L treatments for mUC pts need to provide a substantial OS benefit in exchange for a higher risk of AEs, especially in cis-inelig PD-L1 low pts, whom are perceived as having poor outcomes.
Natural History of Epitope-Specific IgD, IgG1, IgA, IgG4 and IgE Development in Peanut Allergic Children
Authors: Maria Suprun, Galina Grishina, Marc Witmer, Alice Henning, Peter Dawson, Scott Sicherer, Robert Wood, Stacie Jones, A. Wesley Burks, Donald Leung, Robert Getts, Mayte Suarez-Farinas, Hugh Sampson
Journal: Journal of Allergy and Clinical Immunology (2020)
Circulating tumor DNA (ctDNA) landscape in metastatic castrate-resistant prostate cancer patients with germline alterations.
Authors: Marcus W. Moses, Peter Steinwald, Ellen Jaeger, Whitley Hatton, Patrick Cotogno, Charlotte Manogue, Jodi Lyn Layton, Brian E. Lewis, Pedro C. Barata, A. Oliver Sartor, Elisa Marie Ledet
Journal: Journal of Clinical Oncology (2020)

200 Background: Circulating tumor-DNA (ctDNA) in mCRPC patients (pts) provides a viable approach for examining the genetic landscape of prostate cancer. In this follow-up, we report ctDNA variants in germline tested mCRPC pts. Methods: ctDNA alterations in 73 genes were detected using Guardant360 (G360) assays. Alteration types assessed were missense, frameshift, insertions, splice variants, truncations, amplifications (amp), deletions, and other. Pts included in the analysis received germline genetic testing (Invitae Corporation, San Francisco, CA) and ctDNA assays at various treatment timepoints. Statistical analyses were performed using chi-square and fisher exact test with p-value &lt;0.05 for significance. Results: Germline and ctDNA testing was completed in 270 mCRPC pts. 13% (35/270) of pts had pathogenic germline alterations. Germline alterations detected were BRCA2 (43%, n=15), ATM (8.5%, n=3), CHEK2 (8.5%, n=3), and BRCA1 (6%, n=2). Of the 673 alterations detected in G360 assays, TP53 (25%, n=167) and AR (17%, n=117) were most commonly observed. ctDNA alteration breakdown for germline negative/positive pts is summarized in Tables A/B. Germline negative pts had more AR alterations compared to germline positive (p = 0.023). Also, germline negative pts presented with more amps (p &lt; 0.001) and germline positive pts with more frameshift alterations (p = 0.005). The association of ctDNA alteration to clinical outcomes in germline positive/negative pts was also assessed and is ongoing. Conclusions: Pts with germline positive alterations had few somatic AR alterations and higher frequency of deleterious mutation in comparison to their germline negative counterparts.[Table: see text][Table: see text]
Doublesex Mediates the Development of Sex-Specific Pheromone Organs in Bicyclus Butterflies via Multiple Mechanisms
Authors: Anupama Prakash, Antónia Monteiro
Journal: Molecular Biology and Evolution (2020)

Abstract The Bicyclus lineage of satyrid butterflies exhibits male-specific traits, the scent organs, used for chemical communication during courtship. These organs consist of tightly packed brush-like scales (hair-pencils) that rub against scent patches to disperse pheromones, but the evolution and molecular basis of these organ’s male-limited development remains unknown. Here, we examine the evolution of the number and location of the scent patches and hair-pencils within 53 species of Bicyclus butterflies, and the involvement of the sex determinant gene doublesex (dsx) in scent organ development in Bicyclus anynana using CRISPR/Cas9. We show that scent patches and hair-pencils arose via multiple, independent gains, in a correlated manner. Further, an initially nonsex-specific Dsx protein expression pattern in developing wing discs becomes male-specific and spatially refined to areas that develop the scent patches. Functional perturbations of dsx show that this gene activates patch development in males whereas hair-pencils develop in both sexes without Dsx input. Dsx in females is, instead, required to repress hair-pencils whereas Dsx in males regulates minor aspects of its development. These findings suggest that the patches and hair-pencils evolve as correlated composite organs presumably due to their functional integration. Divergence in the function of dsx isoforms occurred across the sexes, where the male isoform promotes patch development in males and the female isoform represses hair-pencil development in females, both leading to the development of male-limited traits. Furthermore, evolution in number of patches in males is due to the evolution of spatial regulation of dsx.
Abstract 13249: New Onset Peri-Operative Atrial Fibrillation After Coronary Artery Bypass Graft (CABG) Surgery
Authors: Alexander Crystal, Cassandra Freitas, Bing Yu, Peter Austin, Andrew C Ha, Douglas S Lee
Journal: Circulation (2018)

Introduction: Post-operative atrial fibrillation (POAF) is a well-known complication after coronary artery bypass (CABG) surgery, occurring in up to 40% of patients. However, anticoagulation of POA...
Revisiting Immunotherapy: A Focus on Prostate Cancer
Authors: Ha-Ram Cha, Joo Hyoung Lee, Selvarangan Ponnazhagan
Journal: Cancer Research (2020)

Therapeutic interventions to harness the immune system against tumor cells have provided mixed results in the past for several solid tumors and hematologic malignancies. However, immunotherapy has advanced considerably over the last decade and is becoming an integral combination for treating patients with advanced solid tumors. In particular, prostate cancer immunotherapy has shown modest efficacy for patients in the past. With several key discoveries on immune mechanisms and advanced molecular diagnostic platforms recently, immunotherapy is re-emerging as a viable option for prostate cancer, especially castration-resistant prostate cancer (CRPC), to stimulate antitumor immunity. Combination of patient-tailored immunotherapy and immune checkpoint blockers with conventional cytotoxic agents and androgen receptor-targeted therapies should move the field forward. With a recent adaptation that the application of immune checkpoint inhibitors has been successful in the treatment of more than a dozen solid tumors, including melanoma, lymphoma, liver, cervical, gastrointestinal, and breast cancers, it is a timely endeavor to harness immunotherapy for prostate cancer. Here, we provide an account on the progression of immunotherapy with new discoveries and precision approaches for tumors, in particular CRPC, from mechanistic standpoint to emerging limitations and future directions.
Increasing Capacity and Improving Quality in Substance Use Disorder Training—Reply
Authors: Megana Dwarakanath
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Role of metastases-directed therapy (MDT) in the management of solitary metastatic prostate cancer.
Authors: Mohamed E. Ahmed, Masaya Jimbo, Rimki Haloi, Jack R. Andrews, Giovanni Motterle, Vidhu B. Joshi, Ayse T. Kendi, Brad J. Stish, Sean Sunghun Park, Jeffrey Karnes, Eugene D. Kwon
Journal: Journal of Clinical Oncology (2020)

143 Background: Systemic treatment in the management of metastatic prostate cancer is inevitable. However, there is a growing interest in metastases-directed therapy (MDT). We sought to investigate the efficacy of MDT in treating patients with solitary metastatic prostate cancer and hence, delaying initiation of systemic treatment (i.e., Androgen deprivation therapy or chemotherapy). Methods: We retrospectively identified 61 patients treated with targeted therapy in the form of surgery (n = 30), stereotactic body radiation therapy (SBRT) (n = 25), or cryotherapy (n = 7) for their solitary metastases prostate cancer. Complete response was defined by achieving a PSA value of ≤0.2 ng/ml plus resolution of the solitary metastatic lesion on C-11 choline PET choline scan, while incomplete response was defined by a residual PSA of &gt; 0.2 ng/ml and/or radiographic evidence of disease following metastases-targeted therapy. Results: Mean (±SD) age was 68.4 (±7.8) yrs., median (IQR) primary Gleason Score was 7 (7-9) and median (IQR) pre-MDT PSA was 2 (1.3-3.8) ng/ml. Median (IQR) time from primary treatment of the prostate to MDT was 5.1 (2.7-10.1) years. None of the patients were on hormone therapy at the time of presentation with solitary metastases prostate cancer. 30 patients had bone metastases, 29 patients had lymph node metastases, 1 patient had soft tissue metastasis (pelvic metastatic mass), and another patient had visceral metastasis (to the lung). 42% of the patients (n = 26) achieved complete response to targeted therapy. Median time to initiation of 2nd line systemic treatment following MDT was 17.8 months for the complete responders versus 9.3 months for incomplete responders. 11% of the patients (n = 7) did not require 2nd line therapy after their MDT for a mean (±SD) time of 56.9 (±22.5) months. Conclusions: The use of targeted therapy in the management of patients with solitary metastatic disease or low-volume metastatic disease can provide comparable outcomes to those of systemic treatment. Further studies are warranted.
Functions and clinical significance of circular RNAs in glioma
Authors: Jikui Sun, Banban Li, Chang Shu, Quanfeng Ma, Jinhuan Wang
Journal: Molecular Cancer (2020)

Abstract CircRNAs are a class of single-stranded RNA molecules with a covalently closed loop structure and have been characterized by high stability, abundance, conservation, and display tissue/developmental stage-specific expression, furthermore, based on the abundance in distinct body fluids or exosomes, circRNAs present novel biomarkers and targets for the diagnosis and prognosis of cancers. Recently, the regulatory mechanisms of biogenesis and molecular functions, including miRNAs and RBPs sponge, translation as well as transcriptional and splicing regulation, have been gradually uncovered, although various aspects remained to be elucidated in combination with deep-sequence and bioinformatics. Accumulating studies have indicated that circRNAs are more enriched in neuronal tissues partly due to the abundance of specific genes promoting circularization, suggesting dysregulation of circRNAs is closely related to diseases of the nervous system, including glioma. In this review, we elaborate on the biogenesis, functions, databases as well as novel advances especially involved in the molecular pathways, highlight its great value as diagnostic or therapeutic targets in glioma.