tbuckley/cabot-search huggingface dataset:
Abstract 182: Survival Outcome Analysis of Public Automated External Defibrillators in Taiwan
Authors: Hao Y Lin, Chih H Lin, Wen C Chiang, Chih W Yang, Ming J Hsieh, Kuo C Chang, Ying C Ko, Su M Wang, Szu W Hsu, Bin C Lee, Yao C Wang, Che H Tsai, Yu T Chung, Chan W Kuo, Chao W Chen, Jen T Sun, Yueh P Liu, Chung L Shih, Matthew H Ma
Journal: Circulation (2018)

Background: Public access defibrillation (PAD) increases survival in out-of-hospital cardiac arrest (OHCA) patients. However, native reports on PAD survival in Taiwan has not yet been described. Public automated external defibrillators (AED) installation at places with high incidence of cardiac arrests were required by law since 2013. A compulsory National AED Registry was set that registered all public AEDs. Incident reports and ECG tracings from those cardiac arrests were mandatory once public AEDs were use. Objective: We aimed to describe survival outcomes of PAD, including sustained return of spontaneous circulation (ROSC), survival to discharge, and Cerebral Performance Category (CPC). The effects of shockable rhythm and bystander CPR on survival along with survival of different public locations were analyzed. Method: Data was collected prospectively from July 2013 to August 2016 by PAD registry of Ministry of Health and Welfare, including incident reports and uploaded ECGs. Survival data were acquired from Taiwan Cardiac Arrests Registry and through contacting individual EMS systems. Outcomes were examined by locations, initial rhythms and bystander CPR. Results: A total of 344 AED utilization was recorded, in which 231 had complete ECG records. Overall shockable rate was 32.9 % (n=76), and bystander CPR rate was 69.3% (n=160). 152 cases had complete outcomes data. Sustain ROSC was 43.5% (69.6% in shockable group (n=46) and 70.3% in shockable plus B-CPR group (n=37)). Forty-two cases (29.4%) survived to discharge or transfer (mean age 53.5 (±21.9 year), male 78.6%). Most surviving patients had good neurological recovery. (CPC1:71.8%, n=28; CPC2:10.3%, n=4). For those with shockable rhythm and received B-CPR, survival to discharge (STD) were 56.8% and CPC1-2 54.1% . ROSC were highest among “Public Baths or Hot Spring Resorts” (60%), followed by “Traffic Hubs” (53.3%), “Schools/Large Gathering Venues” (47.6%), “Hotels” (46.7%), and “Others” (36.8%). Conclusions: Overall survival rates of PAD patients were three-fold compared to data from best performing EMS in Taiwan. PAD also doubled the survival for those with shockable rhythms. Policy facilitating PAD deployment and utilization have made a difference and should be continued and optimized.
School refusal.
Authors: B H Burne
Journal: BMJ (1972)

B.M.J. in press) inunosuppression has been managed on the basis of regular white cell counts with acute rejection episodes diagnosed on biochemical and clinical grounds.One patient has died, five nephrectomies have been performed, and the remaining 27 patients (82%) are alive and well at from three years to six months post- transplant.We feel from our research ex- perience that the rosette inhibition test is not sensitive or accurate enough as an index of "immune status" to be used as the basis of patient management in clinical renal transplantation.-Weare, etc.,
Integrative analysis of urine cell-free DNA for the detection of residual disease in localized bladder cancer patients.
Authors: Pradeep S. Chauhan, Alexander Shiang, Kevin Chen, Ramandeep Babbra, Wenjia Feng, Jeffrey J. Szymanski, Peter K. Harris, Casey Hatcher, Jessica Roussin, Franco Basarabescu, Lindsey Brunt, Lindsey R. Mayer, Ariel Borkowski, Lenon Maguire, Brian C. Baumann, Melissa Andrea Reimers, Eric H Kim, Vivek K Arora, Zachary L Smith, Aadel A Chaudhuri
Journal: Journal of Clinical Oncology (2022)

559 Background: We previously developed a liquid biopsy assay to measure urine tumor DNA (utDNA) levels based on detection of single nucleotide variants (SNVs) in urine cell-free DNA (cfDNA). Nonsilent SNV detection in urine from muscle-invasive bladder cancer (MIBC) patients prior to radical cystectomy (RC) was associated with pathologic residual disease and worse progression-free survival (Chauhan et al., PLOS Medicine, 2021). Given the multiple types of genomic alterations present in bladder cancer (BC), here we developed a multi-omics approach for estimating utDNA levels without restricting our approach to SNVs. We performed ultra-low pass whole genome sequencing (ULP-WGS) based copy number analysis and urine Cancer Personalized Profiling by deep Sequencing (uCAPP-Seq) of urine cell-free DNA to predict pathologic complete response (pCR) in localized BC patients. Methods: We acquired urine preoperatively from 65 BC patients (69% muscle-invasive) on the day of standard-of-care RC, and after neoadjuvant chemotherapy in 48% of patients. We performed ULP-WGS of urine cfDNA from all 65 BC patients and 11 healthy adults. utDNA levels based on genome-wide copy number alterations (CNAs) in urine cfDNA was estimated using ichorCNA. In order to derive a SNV-based utDNA level as well, uCAPP-Seq was applied to urine cfDNA samples derived from 42 patients using a 145 kb panel of 49 consensus driver genes commonly mutated in MIBC. Results: In our cohort of 65 BC patients, 55% of patients achieved pCR ( n = 36) while 45% had residual disease detected in their surgical sample (no pCR; n = 29). Comparing ULP-WGS-derived utDNA levels between the groups, patients with no pCR had significantly higher CNA-derived tumor fractions in urine compared to patients with pCR (median 8.9% vs 1.8%, p = 0.01) and healthy adults ( n = 11) (median 8.9% vs 0%, p = 0.006). Further analysis with uCAPP-Seq in 42 patients revealed that nonsilent SNV-based utDNA detection correlated significantly with the absence of pCR ( p &lt; 0.001) with a sensitivity of 81% and specificity of 81%. Moreover, utDNA-positive patients exhibited significantly worse progression-free survival compared to utDNA-negative patients (HR = 7.4; 95% CI: 1.4–38.9; p = 0.02). Conclusions: Bladder cancer patients who did not attain a pCR at the time of RC had greater genome-wide copy number alterations and nonsilent single nucleotide variants in their urine cfDNA compared to patients with pCR. These results suggest that integrative multi-omics of urine derived from MIBC patients has potential real-world clinical impact for bladder-sparing approaches in select patients.
Five-year survival comparison of different treatment modalities for muscle invasive urothelial carcinoma, squamous cell carcinoma and adenocarcinoma of the bladder: An analysis of the National Cancer Database.
Authors: Carlos Rivera, Iktej Singh Jabbal, Marita Yaghi, Kevin Scott Landau, Nicolas Muruve, Diana Saravia, Tiffany L. George, Zeina A. Nahleh, Rafael Arteta-Bulos
Journal: Journal of Clinical Oncology (2022)

575 Background: Localized muscle invasive bladder cancer carries a significant recurrence and mortality rate. The purpose of this study was to compare 5-year overall survival (OS) of neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), RC alone, bladder preserving chemoradiotherapy (BPCRT) and radiation alone (RT) on selected histologies. Methods: We sampled the National Cancer Database (NCDB) for bladder cancer patients diagnosed with AJCC 7th Stage 2 and 3 for urothelial carcinoma (UC) including variant histologies, squamous cell carcinoma (SCC) and adenocarcinoma (AC) from 2004-2018 with definitive intent treatment. 5-year Kaplan-Meier survival plots were utilized to assess survival differences amongst treatment modalities and stratified by selected histologies. Multivariate cox regression models were used to compare hazard ratios and logistic regression analysis was performed for covariate analysis. A p-value &lt;0.05 was considered statistically significant. Results: A total of 20,629 patients met inclusion criteria. The average age was 69.51 + 11.02 years, 68% were male. UC represented 94.1% of selected histologies, followed by 4.6% SCC and 1.3% AC. For all combined histologies, 5-year OS for patients with NAC followed by RC was 58%, 48% for RC alone, 33% for BPCRT and 10% for RT alone. RC alone provided a longer OS in the SCC and AC groups, 48% and 47% respectively (p&lt;0.001). NAC followed by RC showed superior OS in the UC group (58%, p&lt;0.001), with OS decreasing to 43% in SCC and 44% in AC. BPCRT showed lower 5-year OS in all selected histologies when compared to NAC followed by RC and RC alone (33% in UC, 27% in SCC and 24% in AC group). In all selected histologies, RT showed the lowest 5-year OS (10% in UC, 8% in SCC and 17% in AC group; p&lt;0.001). Furthermore, covariables associated with lower 5-year survival were male sex (p&lt;0.001) and TNM Stage 3 (p&lt;0.001). Conclusions: NAC followed by RC showed improved 5-year OS for UC. The benefit of NAC was marginal for SCC and AC histology. RC is better than BPCRT for all histologies. RT alone showed inferior 5-year OS for all histologies.[Table: see text]
Role of the Lung in the Spread of Metastases
Journal: JAMA (1963)

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
Impact of PD-L1 expression on conventional urothelial bladder carcinoma (UBC) genomic alteration (GA) profile.
Authors: Petros Grivas, Andrea Necchi, Philippe E. Spiess, Gennady Bratslavsky, Joseph M Jacob, Oleksandr Kravtsov, Richard S.P. Huang, Vamsi Parini, Brennan Decker, Douglas I. Lin, Dean C. Pavlick, Natalie Danziger, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2022)

563 Background: Immunohistochemistry (IHC) to determine PD-L1 expression level has been proposed a companion assay related to the approval of immune checkpoint inhibitors in UBC. We hypothesized that the GA profiles would differ between UBC featuring high vs negative PD-L1 expression. Methods: 102 cases of advanced UBC with known PD-L1 expression underwent hybrid-capture based comprehensive genomic profiling to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Tumor cell (TC) PD-L1 expression was determined by IHC (Dako 22C3). Only PD-L1 high (H) (≥50% TC expression) and negative (N) (0% TC expression) cases were included with PD-L1 Low (1-49% TC expression) cases excluded from this study. Results: Overall, only 2 (8.3%) of the 24 PD-L1H UBC featured CD274 ( PD-L1) amplification (mean 19 copies) and none of 78 PD-L1N had CD274 amp (P =.05). The gender, age was similar in the groups. When compared with the PD-L1H UBC cases, FGFR3 GA were significantly more frequent in the UBC PD-L1N cases (p =.02). Currently “untargetable” GA that were more frequent in the PD-L1H UBC, but did not reach statistical significance, included TP53, TERT and RB1. MTAP loss, a potential target for PRMT5 and MTA2 inhibitors, were 3X more frequent in the PD-L1N UBC. ERBB2 amplification and ERBB3 and PIK3CA short variant (SV) GA were more frequent in the PD-L1N UBC with differences not reaching significance. Other ICPI-associated potential biomarkers, including MSI status, TMB level and GA in PBRM1, STK11 and MDM2 were not significantly different in the groups. For UBC cases where a mutational signature could be determined, 10/12 (83%) of PD-L1H and 21/29 (72%) of PD-L1N UBC featured APOBEC signature; 2 PD-L1N featured MMR signature and 6 PD-L1N UBC featured no dominant signature. Conclusions: PD-L1H and PD-L1N subtypes of UBC differ in their genomic profiles:PD-L1N UBC features greater frequencies of potentially “targetable” GA, including FGFR3, ERBB2, ERBB3 and PIK3CA. PD-L1 IHC may thus not only play a role in the selection of ICPI for advanced UBC but also in designing trials that may combine ICPI with targeted therapies. Limitations include small sample size, possible selection bias and lack of clinical annotation.[Table: see text]
Prognostic value and therapeutic implications of an integrative molecular subtype and immune content classifier in localized muscle-invasive bladder cancer.
Authors: Mark Farha, Brittney Cotta, Randy Vince, Srinivas Nallandhighal, Samuel D. Kaffenberger, Philip Palmbos, Ajjai Shivaram Alva, Todd Matthew Morgan, Ganesh S. Palapattu, Simpa Salami, Aaron M. Udager
Journal: Journal of Clinical Oncology (2022)

530 Background: Localized muscle-invasive bladder cancer (MIBC) exhibits heterogeneous molecular features and outcomes, with a 5-year mortality rate of approximately 30%. Immune checkpoint blockade (ICB) has the potential to improve oncological outcomes but molecular tools are needed to identify those most likely to benefit. Here, we integrate transcriptomically derived tumor immune microenvironment (TIME) data with molecular subtypes to create a novel integrative classifier with prognostic and therapeutic implications. Methods: RNAseq data from patients with localized muscle-invasive bladder cancer (MIBC) from the Cancer Genome Atlas BLCA (TCGA-BLCA) project was utilized (n = 187). CIBERSORT was used for immune cell deconvolution, and unsupervised hierarchical clustering divided the cohort based on similar immune profiles. Consensus molecular clustering information for the cohort was obtained from Kamoun et al. Overall survival (OS) of each cluster were analyzed. The tumor immune dysfunction and exclusion (TIDE) tool, which uses a genomic signature validated on immunotherapy treated melanoma patients to model tumor immune evasion, was then used to predict response to ICB. Results: In the TCGA-BLCA cohort, there were two distinct clusters enriched with macrophages, CL1-M0 Hi (n = 18) and CL5-M2 Hi (n = 35). Compared to the rest of the cohort, these two macrophage enriched clusters combined exhibited a decreased OS (33.1 mo vs. NR, p = 0.01). TIDE tool predicted ICB response was lowest in CL1 (6/18, 33%; p = 0.09), CL5 (12/35, 34%; p = 0.02), and the Ba/Sq molecular cluster (16/57, 28%; p = 1.3x10 -5 ). Patients designated as CL1 or CL5 by immune clustering and Ba/Sq by molecular consensus were combined into a subgroup (n = 20). Compared to the rest of the cohort, this Ba/Sq_Macrophage Hi subgroup had a higher body mass index (31.0 vs. 25.8 BMI, p = 0.0004), more whites (95% vs. 64%, p = 0.03), and had a higher stage (80% Stage III/IV vs. 20% Stage I/II, p = 0.05). The Ba/Sq_Macrophage Hi cluster demonstrated higher PD-L1 expression (mean Z score 0.15 vs. -0.09; p = 0.008), there was a higher degree of T cell exclusion (mean Z score 0.16 vs. -0.06; p = 0.003) and cancer-associated fibroblasts (mean Z score 0.03 vs. -0.02; p = 3.4x10 -5 ). Overall, the predicted response to ICB by TIDE in the Ba/Sq_Macrophage Hi was lower (OR 0.15, 0.03-0.55 p = 0.002) and OS was significantly shorter (median 16.7 mos vs. 54.9 mo, p = 0.04). Conclusions: We demonstrated the prognostic significance of the Basal/Squamous subtype with macrophage enrichment in patients with localized MIBC. Pending further prospective validation, this sub-population may be less amenable to ICB treatment.
TRASTUZUMAB CARDIOTOXICITY IN EARLY STAGE HER2 POSITIVE BREAST CANCER PATIENTS IN MEXICO
Authors: María Betania Carrillo Cázares, Juan Betuel Ivey Miranda, Rocío Grajales Álvarez, Alicia Gutiérrez Mata, Montserrat Carrillo Estrada
Journal: JACC CardioOncology (2022)
The role of RNA-binding proteins in the processing of mRNAs produced by carcinogenic papillomaviruses
Authors: Naoko Kajitani, Stefan Schwartz
Journal: Seminars in Cancer Biology (2022)

Human papillomaviruses (HPV) are epitheliotropic DNA tumor viruses that are prevalent in the human population. A subset of the HPVs termed high-risk HPVs (HR-HPVs) are causative agents of anogenital cancers and head-and-neck cancers. Cancer is the result of persistent high-risk HPV infections that have not been cleared by the immune system of the host. These infections are characterized by dysregulated HPV gene expression, in particular constitutive high expression of the HPV E6 and E7 oncogenes and absence of the highly immunogenic viral L1 and L2 capsid proteins. HPVs make extensive use of alternative mRNA splicing to express its genes and are therefore highly dependent on cellular RNA-binding proteins for proper gene expression. Levels of RNA-binding proteins are altered in HPV-containing premalignant cervical lesions and in cervical cancer. Here we review our current knowledge of RNA-binding proteins that control HPV gene expression. We focus on RNA-binding proteins that control expression of the E6 and E7 oncogenes since they initiate and drive development of cancer and on the immunogenic L1 and L2 proteins as there silencing may contribute to immune evasion during carcinogenesis. Furthermore, cellular RNA-binding proteins are essential for HPV gene expression and as such may be targets for therapy to HPV infections and HPV-driven cancers.
Glucose Toxicity
Authors: Lciano Rossetti, Andrea Giaccari, Ralph A DeFronzo
Journal: Diabetes Care (1990)

Glucose toxicity is a well-established entity that has been shown in animal models of diabetes to contribute to development of insulin resistance and impaired insulin secretion. In type II (non-insulin-dependent) diabetes in humans, a considerable body of evidence has accumulated indicating that a chronic physiological increment in the plasma glucose concentration leads to progressive impairment in insulin secretion and may contribute to insulin resistance as well. The precise biochemical mechanism(s) responsible for the hyperglycemia-induced defect in insulin secretion remains to be defined but may be related to a defect in phosphoinositide metabolism. In animal models of diabetes, development of insulin resistance is related to downregulation of the glucose-transport system, and a similar phenomenon is also likely to occur in humans. In addition, hyperglycemia in humans may lead to a defect in glycogen synthesis. In this respect, humans may be different from rats. In type I (insulin-dependent) diabetic patients who are poorly controlled, insulin resistance is a characteristic feature and can be ameliorated by tight glycemic control, suggesting that hyperglycemia is responsible for the insulin resistance. Evidence also has accumulated to implicate glucose toxicity in the functional impairment in insulin secretion that occurs during the initial presentation of patients with type I diabetes, and this may explain the honeymoon period so commonly observed after the institution of insulin therapy.
Intractable Pain
Authors: E. B. Strauss
Journal: BMJ (1949)

FAILURE OF AUREOMYCIN IN EXPERIMENTAL MELlOIDOSIS RDITsRNH 411 of observation.The dosages, which varied from 1 to 4 mg., are shown in Table II.The time to death was recorded, and each animal was submitted to post-mortem examination.rABLE II.-Treatment with Aureomycin of Experimizenital Melioidosis inl Guinea-pigs Days to Death Infecting Dose Treated of Pf. whitmori Untreated Daily Dosage of Aureomycin 1 mg. 2 mg. 4 mg.
Abstract 17079: MYBPC3 Truncation Mutations Cause Contractile Dysregulation in iPSC-Derived Cardiomyocytes
Authors: Adam S Helms, Vi Tang, Jonathan Hernandez, Mick Wauchope, Akul Arora, Sabrina Friedline, Michael Previs, Sharlene Day
Journal: Circulation (2018)

The mechanism of MYBPC3 (encoding cardiac myosin binding protein C, MyBP-C) truncation mutations, the most common genetic cause of hypertrophic cardiomyopathy, has been incompletely resolved. We hypothesized that truncating MYBPC3 mutations cause myofibrillar protein assembly defects and/or contractile dysfunction. Methods and Results: Control iPSCs were CRISPR/Cas9-edited to create cell lines with homozygous (homCT) and heterozygous (hetCT) C-terminal MYBPC3 truncation mutations and heterozygous MYBPC3 promoter knock-out (hetPROM). HetCT was further edited to add an N-terminal flag tag (FhetCT). Purified cardiomyocytes were assayed at day ~25. RNAseq showed a 50% reduction in MYBPC3 mRNA in hetCT (p&lt;0.01). Full ablation of MyBP-C was demonstrated in homCT but MyBP-C content was not reduced in hetCT or hetPROM by quantitative mass spectrometry. Immunofluorescence and co-IP of FhetCT showed no truncated MyBP-C. Sarcomere assembly, quantified by aligned myofilament number after replating onto 7:1 rectangular micropatterns, did not differ between lines; homCT (23±3), hetCT (23±3), hetPROM (22±3 myofilaments), control (22±3), p=NS. Quantitative mass spectrometry demonstrated that the stoichiometry of other major thick and thin filament proteins was not altered (all p=NS). Maximum force was reduced in homCT (866±366 uN, p&lt;0.001) and hetCT (1213±545 uN, p=0.03) vs controls (1509±441 uN), and not significantly different for hetPROM (1238±360 uN, p=0.07), when measured in single micropatterned iPSC-CMs on 8.7 kPa hydrogels by traction force microscopy. Time to peak contraction was shorter in homCT (0.27 s, p=0.02) vs control (0.42 sec), but not in hetCT (0.46 s) and hetPROM (0.49 s). Contractile deceleration time was reduced only in homCT (0.12 s vs 0.25 s, p=0.002). Conclusions: Heterozygous MYBPC3 truncation mutations result in haploinsufficent mRNA with steady state compensation of MYBP3 protein and no MYBPC3 truncated peptide. Even complete ablation of MyBP-C loss does not alter the overall stoichiometry of other sarcomeric thick and thin filament proteins. MyBP-C ablation and heterozygous truncating mutations impair maximal contractile force, strongly implicating contractile dysregulation as the primary mechanism of MYBPC3-HCM.
Wrong Place, Wrong Name
Journal: JAMA (1964)

edema, and hemorrhages were frequently found.These lesions were either primary (caused by forceful resuscitation), or more often, secondary to cerebral lesions (particularly hemorrhages), or due to defects in maturation of the central nervous system.Aspiration of the amniotic fluid was fre¬ quently observed, but it was not of a severe degree.Pul¬ monary hyaline membrane formations were rare.The authors suggest a possible relation between the occurrence of hyaline membrane and the intensive oxygénation of pre¬ mature infants.Inflammatory or infectious lesions were either isolated or in association with ventilatory disturb- Abdominal Epilepsy in Children.