tbuckley/cabot-search huggingface dataset:
Characterization of Wnt signaling pathway (WSP) aberrations in advanced prostate cancer.
Authors: Fady Ghali, Devin Patel, Christina Jamieson, J Kellogg Parsons, Rana R. McKay
Journal: Journal of Clinical Oncology (2020)

203 Background: Aberrations in Wnt signaling pathway (WSP) are implicated in disease progression and resistance of multiple malignancies including prostate cancer (PCa). We sought to characterize the clinical phenotype and molecular genotype of PCa patients with WSP alterations. Methods: Eligible patients included those with PCa having undergone clinical-grade next generation DNA sequencing of tumor derived from prostate or metastasis tissue. We identified patients with somatic activating mutations in CTNNB1 and RSPO2, or inactivating mutations in APC, RNF43, or ZNRF3. Patient and disease characteristics were collected. Clinical and outcome parameters were associated with WSP mutation status using STATA(V. 13.1, College Station, Texas). Results: A total of 169 patients were identified of whom 29 (18.1%) had a WSP activating mutation. Median age of the overall cohort was 64.85 (IQR 56.77, 70.36). 115 (68.0%) patients had Gleason 8-10 disease, 34 (20.1%) presented with de novo metastatic disease, 85 (50.3%) developed CRPC and 23 (13.6%) developed visceral metastases. Clinical characteristics were similar between biomarker groups. There was no association with the presence of a Wnt activating mutation and RB1, p53, pTEN, or BRCA1/2 alteration. Median time to CRPC was 39.42 (IQR 14.50 – 87.52) and 24.39 (IQR 14.99 – 46.03) months for no-WSP and WSP-aberrant respectively. Median 5-year OS was 83.7% (95% CI 73.0-90.4%) and 79.6% (95% CI 52.9 – 92.2%) months for no-WSP and WSP-aberrant respectively. Table evaluates biomarker status with time to CRPC development and overall survival (OS). Conclusions: We observe that somatic WSP activating mutations are present in 18.1% of patients with mPCa, consist with prior reports. Understanding the clinical significance of WSP alterations is critical to inform treatment strategies in patients with advanced disease.[Table: see text]
Metastatic renal cell carcinoma (mRCC) in young patients: A comprehensive genomic profiling (CGP) study.
Authors: Gennady Bratslavsky, Andrea Necchi, Petros Grivas, Oleg Shapiro, Joseph Jacob, Julia Andrea Elvin, Jo-Anne Vergilio, Keith Killian, Douglas I. Lin, Erik Williams, Shakti H. Ramkissoon, Eric Allan Severson, Amanda Hemmerich, Alexa Betzig Schrock, Jon Chung, Kimberly McGregor, Prasanth Reddy, Brian Michael Alexander, Natalie Danziger, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2020)

727 Background: We studied the genomic alterations (GA) in patients with mRCC under 40 years of age (&lt;40) and patients 40 years of age or older (&gt;40). Methods: 2,128 mRCC underwent hybrid-capture based CGP. Clear cell (ccRCC), papillary (pRCC), sarcomatoid (sRCC), NOS (nosRCC), chromophobe (chrRCC), medullary (medRCC) and collecting duct (cdRCC) were separately evaluated. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: Male preponderance in all subsets increased in the &gt;40 patients. The GA/tumor increased significantly in the &gt;40 cohorts except for in medRCC. The relatively low TMB was higher in all &gt;40 and MSI high status was infrequent in all groups. PD-L1 expression was generally low, the 44% high positive PD-L1 in sRCC was noteworthy. Significant differences in GA in &lt;40 vs &gt;40 RCC included increased PBRM1 and SETD2 GA in &gt;40 vs &lt;40 ccRCC; increased C DKN2A/B and TERT and decreased FH GA in &gt;40 vs &lt;40 pRCC; increased TP53, PTEN and TERT GA with decreased NF2 GA in &gt;40 vs &lt;40 sRCC; increased TP53, VHL and TERT in &gt;40 vs &lt;40 nosRCC. Changes in GA in &lt;40 vs &gt;40 chrRCC, medRCC and cdRCC were noted but insufficient cases prevented statistical evaluation. Conclusions: When evaluated by age, CGP of mRCC demonstrates significant differences in the genomic landscapes with &gt;40 cases featuring increasing male preponderance and higher GA/tumor, TMB and increases in TP53, CDKN2A/B and TERT GA. These findings may play important roles in the planning of future clinical trials designed to personalize the treatment of mRCC.[Table: see text]
Abstract 13086: What Is the Clinical Profile of ASCVD Patients With Elevated Baseline LDL-C? Insights From Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD): A Registry of High Cardiovascular Risk Patients in the United States
Authors: Christopher P Cannon, James A de Lemos, Robert S Rosenson, Christie M Ballantyne, Juan F Maya, Katherine E Mues, Yuyin Liu, Deepak L Bhatt, Mikhail N Kosiborod
Journal: Circulation (2018)

Background: Guidelines for the management of patients with atherosclerotic cardiovascular disease (ASCVD) recommend statin therapy. Target levels, or “goals of therapy,” for low-density lipoprotein...
Complex Evolution of Insect Insulin Receptors and Homologous Decoy Receptors, and Functional Significance of Their Multiplicity
Authors: Vlastimil Smýkal, Martin Pivarči, Jan Provazník, Olga Bazalová, Pavel Jedlička, Ondřej Lukšan, Aleš Horák, Hana Vaněčková, Vladimír Beneš, Ivan Fiala, Robert Hanus, David Doležel
Journal: Molecular Biology and Evolution (2020)

Abstract Evidence accumulates that the functional plasticity of insulin and insulin-like growth factor signaling in insects could spring, among others, from the multiplicity of insulin receptors (InRs). Their multiple variants may be implemented in the control of insect polyphenism, such as wing or caste polyphenism. Here, we present a comprehensive phylogenetic analysis of insect InR sequences in 118 species from 23 orders and investigate the role of three InRs identified in the linden bug, Pyrrhocoris apterus, in wing polymorphism control. We identified two gene clusters (Clusters I and II) resulting from an ancestral duplication in a late ancestor of winged insects, which remained conserved in most lineages, only in some of them being subject to further duplications or losses. One remarkable yet neglected feature of InR evolution is the loss of the tyrosine kinase catalytic domain, giving rise to decoys of InR in both clusters. Within the Cluster I, we confirmed the presence of the secreted decoy of insulin receptor in all studied Muscomorpha. More importantly, we described a new tyrosine kinase-less gene (DR2) in the Cluster II, conserved in apical Holometabola for ∼300 My. We differentially silenced the three P. apterus InRs and confirmed their participation in wing polymorphism control. We observed a pattern of Cluster I and Cluster II InRs impact on wing development, which differed from that postulated in planthoppers, suggesting an independent establishment of insulin/insulin-like growth factor signaling control over wing development, leading to idiosyncrasies in the co-option of multiple InRs in polyphenism control in different taxa.
Asialo GM1-positive liver-resident CD8 T cells that express CD44 and LFA-1 are essential for immune clearance of hepatitis B virus
Authors: Chi-Chang Sung, Jau-Hau Horng, Shih-Hong Siao, I-Tsu Chyuan, Hwei-Fang Tsai, Pei-Jer Chen, Ping-Ning Hsu
Journal: Cellular and Molecular Immunology (2020)
Neuropod Cells: The Emerging Biology of Gut-Brain Sensory Transduction
Authors: Melanie Maya Kaelberer, Laura E. Rupprecht, Winston W. Liu, Peter Weng, Diego V. Bohórquez
Journal: Annual Review of Neuroscience (2020)

Guided by sight, scent, texture, and taste, animals ingest food. Once ingested, it is up to the gut to make sense of the food's nutritional value. Classic sensory systems rely on neuroepithelial circuits to convert stimuli into signals that guide behavior. However, sensation of the gut milieu was thought to be mediated only by the passive release of hormones until the discovery of synapses in enteroendocrine cells. These are gut sensory epithelial cells, and those that form synapses are referred to as neuropod cells. Neuropod cells provide the foundation for the gut to transduce sensory signals from the intestinal milieu to the brain through fast neurotransmission onto neurons, including those of the vagus nerve. These findings have sparked a new field of exploration in sensory neurobiology-that of gut-brain sensory transduction.
Tau Imaging in the 4-Repeat-Tauopathies Progressive Supranuclear Palsy and Corticobasal Syndrome
Authors: Nils Schröter, Ganna Blazhenets, Lars Frings, Christoph Barkhausen, Wolfgang H. Jost, Cornelius Weiller, Michel Rijntjes, Philipp T. Meyer
Journal: Clinical Nuclear Medicine (2020)

Background and Objectives To evaluate tau PET using 11 C-pyridinyl-butadienyl-benzothiazole 3 ( 11 C-PBB3) in the 4-repeat (4R)-tauopathies progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methods Retrospective analysis of 11 C-PBB3 PET in 2, 7, and 2 patients with CBS, PSP, and Alzheimer dementia (AD), respectively. Normalized 11 C-PBB3 uptake in clusters with significant hypometabolism on 18 F-FDG-PET and corresponding atlas-based volumes of interest was compared between diagnostic groups. Results In accordance with visually appreciable group differences, 11 C-PBB3 uptake was significantly higher in dorsolateral frontal and motor cortex in CBS patients and frontal and temporal cortices in AD patients as compared with PSP patients. Patients with PSP showed mildly but significantly higher uptake in midbrain compared with AD patients. Conclusions In line with known neuropathological changes, the spatial pattern and magnitude of 11 C-PBB3 tau binding differ between CBS, PSP, and AD, which may be of diagnostic utility. Thus, 11 C-PBB3 offers a promising lead structure for development of ligands for tau imaging, including 4R-tauopathies.
Molecular characterization of neuroendocrine bladder cancer.
Authors: Woonyoung Choi, Jean H. Hoffman-Censits, Megan Fong, Noah M. Hahn, Eva Comperat, David James McConkey
Journal: Journal of Clinical Oncology (2020)

561 Background: Neuroendocrine bladder cancer (NEBC) is a rare and aggressive variant that is associated with poor survival outcomes. Because NEBC is rare, the molecular features of NEBC remain poorly characterized. Therefore, we characterized NEBC at the molecular level to understand the underlying biology and identify novel therapeutic targets. Methods: Whole transcriptome RNAseq was performed on FFPE cores from 24 NEBCs and 51 conventional muscle-invasive bladder cancers (MIBCs) from Tenon Hospital in Paris. Results: Unsupervised cluster analysis of 75 tumors generated 2 distinct clusters that separated NEBCs from MIBCs. The NEBC tumors were strongly enriched with biomarkers for the characteristic of neuroendocrine or small cell malignancies, including DLL3, SOX2, and EZH2. In addition, E2F1 pathway is significantly enriched due to the impair of RB/p53 pathways. Further, the NEBCs were enriched with the TCGA’s neuronal differentiation genes that were associated with high response rates in patients treated in atezolizumab (anti-PDL1) within the context of the ImVigor 210 trial. Nevertheless, the NEBCs were characterized by suppressed immune pathway gene expression signatures, such as the Th1 pathway, effector T cell lymphocyte, and IFNg that are usually highly enriched in tumors that are sensitive to immune checkpoint blockade. Of candidate mechanisms, the suppressed TGFbpathway activity observed in the NEBCs was the most obvious explanation for sensitivity to checkpoint blockade. Conclusions: NEBCs are distinct from conventional MIBCs by gene expression signature. They are also characterized by overexpression of canonical neuroendocrine markers and inhibition of TGFb pathway activity.
Unmeasured Confounding in Observational Studies of Management of Cerebellar Intracranial Hemorrhage
Authors: Thomas A. van Essen, David K. Menon, Hester F. Lingsma
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
GP is struck off after he showed no insight into reasons for his suspension
Authors: Clare Dyer
Journal: BMJ (2020)

A GP who was suspended from the UK medical register in 2018 over his treatment of three patients has been struck off after missing two review hearings and failing to engage with the regulatory process.

Laszlo Szabo, who worked in the UK as a GP from 2005, was reported to the General Medical Council by NHS England after he failed to detect clear signs of gastrointestinal bleeding during an out-of-hours home visit to an elderly patient in 2014.

Szabo failed to carry out basic examinations such as blood pressure, temperature, and oxygen saturation, despite recording a “weak pulse” and “cold and clammy skin” in the patient’s notes.

Although she had diabetes, he failed to consider a diagnosis of diabetic ketoacidosis, circulatory shock, or gastrointestinal …
Overall survival (OS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) receiving bicalutamide (BIC) followed by enzalutamide (ENZA) or abiraterone (ABI).
Authors: Daniel J. George, Scott T. Tagawa, Stanislav Lechpammer, Dave Russell, Agnes Hong, Jack Mardekian, Ahong Huang, Li Wang, Nora Janjan, Krishnan Ramaswamy
Journal: Journal of Clinical Oncology (2020)

40 Background: The objective of this study was to evaluate real-world OS in men with chemotherapy-naïve mCRPC treated with first-line ENZA or ABI or sequencing to these agents after treatment with BIC ( &gt; 90 d). Methods: A retrospective analysis was performed using the Veterans Health Administration (VA) database. Men with mCRPC and ≥ 1 pharmacy claim for ABI or ENZA (1st claim date = index date) following surgical or medical castration and with no chemotherapy treatment 12 months pre-index date were identified from 01APR2014 to 31MAR2017. Men had continuous VA enrollment for ≥ 12 months pre- index date and were followed until death or study end. Cox proportional hazards regression models examined the impact of treatment on OS, and the impact of first using BIC ( &gt; 90 d) vs first-line use of ABI and ENZA on OS. Adjusted Kaplan-Meier analysis was conducted to graphically describe OS. Results: This study included 1229 ENZA- and 1945 ABI-treated men with mCRPC with mean ages of 74 and 73 y, respectively. Median follow‐up was 548 and 572 d, and median OS was 892 and 786 d, respectively. ENZA and ABI were first-line treatment in 1068 and 1628 men, but BIC ( &gt; 90 d) was first used before sequencing to ENZA or ABI in 161 and 317 men, respectively. Median duration of BIC treatment was similar in men subsequently treated with ENZA or ABI (251 v 246 d, respectively). Compared with first-line ABI, use of ABI following BIC led to shorter OS (hazard ratio [HR] = 1.30; 95% CI 1.11 -1.52). Compared with first-line ENZA, use of ENZA following BIC resulted in a nonsignificant effect on OS (HR = 0.92; 95% CI 0.72-1.19). In the Cox analysis, ENZA-treated men had longer OS compared with ABI-treated men (HR = 0.84; 95% CI 0.76-0.94). Conclusions: Use of BIC ( &gt; 90 d) before sequencing to ENZA did not negatively effect OS, however BIC before ABI impacted OS adversely in men with chemotherapy-naïve mCRPC. There are significant differences in OS favoring ENZA compared with ABI regardless of prior BIC. Real-world observational data are nonrandomized, and markers for disease severity/volume are not available in the claims database. Further research is required to confirm these findings.
二重微小染色体をもつ急性骨髄性白血病におけるC-myc癌遺伝子の増幅とN-RAS癌遺伝子点突然変異の点突然変異
Authors: Tanaka K, Takechi M, Nishimura S, Oguma N, Kamada N
Journal: Leukemia (1993)
Indocyanine Green Tracer-Guided Lymph Node Retrieval During Radical Dissection in Gastric Cancer Surgery
Authors: Marco G. Patti, Fernando A. Herbella
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
Acknowledge, in the curriculum, those who suffered for the advancement of medical science
Authors: Rageshri Dhairyawan
Journal: BMJ (2020)

As a genitourinary physician I was taught about the Tuskegee syphilis experiment during my training, where it was acknowledged that much of what we know about syphilis was obtained unethically.1 It is now taught more widely as part of research ethics training. Much less known, however, are the Guatemalan syphilis experiments, carried out by the US government on soldiers, sex …
Determination of Parkinson Disease Laterality After Deep Brain Stimulation Using 123I FP-CIT SPECT
Authors: Hye Ran Park, Seunggyun Ha, Dong Soo Lee, Hyung-Jun Im, Sun Ha Paek
Journal: Clinical Nuclear Medicine (2020)

Introduction Symptom laterality is one of the main characteristics of Parkinson disease (PD) and reported to be associated with motor and nonmotor symptom severity and prognosis. This study aimed to evaluate the changes of laterality after deep brain stimulation (DBS) and the association between dopamine transporter SPECT using 123 I FP-CIT (DAT SPECT) and symptom laterality in PD before and after DBS. Methods Nineteen patients with PD who received bilateral subthalamic nucleus DBS were enrolled. The clinical scores including Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr were evaluated at baseline, 6 months, and 1 year after DBS. Also, the patients underwent DAT SPECT before and 6 months and 1 year after DBS. Symptom and DAT laterality indices were determined based on the UPDRS part 3 and DAT SPECT, respectively. The association between DAT and symptom laterality was assessed at baseline and 6 months and 1 year after DBS. Results At baseline, 11, 6, and 2 among 19 patients had left-side–dominant, right-side–dominant, and symmetric motor symptom, respectively. Among 19 patients, there were 10 patients who showed changed symptom laterality within 1 year after DBS. The agreement between symptom laterality and DAT laterality was good to excellent at baseline and 6 months and 1 year after DBS (weighted κ = 0.742, 0.736, and 0.813). Furthermore, symptom and DAT laterality indices showed significant correlation at baseline ( r = 0.542, P = 0.02), 6 months ( r = 0.579, P = 0.01), and 1 year after DBS ( r = 0.689, P = 0.02). Symptom laterality could be determined by DAT laterality index with areas under curve of 0.833 ( P = 0.045), 0.982 ( P &lt; 0.001), and 1.000 ( P &lt; 0.001) at baseline and 6 and 12 months after DBS, respectively. Conclusions The symptom laterality could be altered after DBS and was well correlated with laterality evaluated by DAT SPECT. An objective evaluation of laterality using DAT SPECT would be helpful for the management of patients with PD especially for adjusting the DBS programming for fine balancing of the asymmetric symptom after DBS. The large-scale study is warranted for validation of this result.
Lipopolysaccharide Responsive Beige-Like Anchor (LRBA) Protein Deficiency in a 12-year-old Female with Failure To Thrive Liburd, K., Chang, C. Division of Pediatric Immunology and Allergy. Joe DiMaggio Children’s Hospital, Hollywood, FL.
Authors: Kyndra Liburd, Christopher Chang
Journal: Journal of Allergy and Clinical Immunology (2020)
When entomology meets gastroenterology
Authors: Grigoriy E Gurvits, Rashelle Tsyrlin
Journal: Gut (2020)

A middle age man with coronary artery disease requiring recent percutaneous angioplasty with drug eluding stent was seen for evaluation of new onset iron deficiency anaemia. His medical history was remarkable for peptic ulcer disease as young adult requiring Billroth II resection. His current medications included aspirin 81 mg daily and prasugrel 10 mg daily. Laboratory analysis was notable for haemoglobin of 124 g/L, iron saturation of 5% and ferritin of 8 ng/mL. …