tbuckley/cabot-search huggingface dataset:
Abstract 17189: Reprogramming of Fibroblasts Into Cardiac Progenitor Cells Using Crispr Activation System
Authors: Lin Jiang, Jialiang Liang, Wei Huang, Christian Paul, Yigang Wang
Journal: Circulation (2018)

Background and Objective: CRISPR tools that allow for precise manipulation of individual loci have not been used in generation of i nduced c ardiac p rogenitor c ells ( iCPC s). This study was designed to determine the feasibility and effectiveness of reprogramming fibroblasts into iCPC using CRISPR activation (CRISPRa) system. Methods: Tail-tip fibroblasts (TTFs) were isolated from Nkx2-5 cardiac enhancer GFP reporter mice. A gRNA pool targeting 17 progenitor genes was synthesized and transduced with dCas9-VP64 lentivirus into TTFs ( Fig.1A ). The phenotype of iCPCs was then characterized by immunostaining and FACS of progenitor markers. Finally, the cardiac-lineage differentiation potential of iCPCs was determined by immunostaining and electrophysiological assay under defined induction mediums. Results: iCPCs with GFP expression were formed in TTFs after transduction of CRISPRa targeting Isl1 , Gata4 , Baf60c , Tbx5 and Nkx2-5 (Fig.1B), while GFP was not activated by control virus. Cardiac progenitor markers were activated in iCPCs as shown by immunostaining (Fig.1C). The generation efficiency of Flk1-postive iCPCs induced by CRISPRa was ~60% as showed by FACS. iCPCs can be differentiated into cardiomyocytes as identified by immunostaining of cardiac-specific markers (Fig.1D). The iCPC-derived cardiomyocytes displayed spontaneous beating and showed cardiac action potentials (Fig.1E). Conclusion: The CRISPRa system is an efficient and specific way to generate iCPCs, which could provide a novel source of cells for cardiac regenerative medicine.
Address in Surgery
Authors: E. Hamilton
Journal: BMJ (1887)

TISSUE RESISTANCE AND ANTISEPTICISM.TwE,NrY years have passed away since the place which I have the honour to occupy to-day was filled by one of the brightest ornaments of British surgery, Robert William Smith.They who had the pleasure to listen to the address which he then delivered-clear, logical, -and chastely eloquent-can appreciate the difficulty under which I labour; for what is there that I could hope either to think, or write, or speak, which could at all approach the learning, the sagacity, or eager search after scientific truth which adorned that gifted Irishman.The Patho- logical Society of Dublia, of which he was the mainstay and the very life, was unequalled by any similar society in the world.There we used to see, in the theatre adjacent to where we are now assembled, Crampton, Stokes, Corrigan, Graves, and Adams, crowning the labours of each week by careful study, each succeeding Saturday, of the various examples of disease and illustrations of pathology which had oecurred in the hospitals of Dublin, while the best and most intelligent of our students crowded the benches above, and hung with eager- ness on the words of wisdom which fell from these great men.The merging of this Society in the Academy of Medicine may have raised the standard of pathology as a science, but, with all respect, I beg to think that it has not maintained the zeal for pathological knowledge or extended the study of this most important branch of our training.
Address in Medicine
Authors: W. T. Gairdner
Journal: BMJ (1887)

Agi, looking back on the early meetings of the Association, we findhow beneficial were its effects on the subject of vaccination, on the medical relief of the poor, the registration of disease, and its advo.caty of a national organisation for the promotion of social science.If fime admitted, much might be said as to what has been done by the Collective Investigation of Disease so well calculated to settle many disputed pointP, and establish our knowledge of disease on a firm basis as well as upon many other subjects, but I must hurry to a close.In conclusion, I desire to defend our Association from a charge which has been brought against it, and others of a cognate character, and that is that we meet chiefly, if not altogether, for amusement and recreation.To this we may give an emphatic denial, for labour takes the first place, and then come recreation and social intercourse, the value of which, we are free to admit, we highly appreciate.Virchow, in his address at the last meeting of the Association of Naturalists and Physicians at Berlin, well observed, after pointing out that the greater part of the time at their disposal should be devoted to earnest work: "Aber nach der Arbeit ziemt es sich wohl der Erholung und dem froundschaftlichen Verkehr ihr Recht zu lassen."The original statutes of this Association, now sixty-four years old, laid it down that the chief object of the meetings was to make the members personally known to each other.No one proclaimed this with more force than Alexander von Humboldt in opening the meeting fifty-eight years since.He said: " Der Hauptz weck dieser Gesellschaft ist die personliche Annaherung derer welche dasselbe Feld der Wissenschaft bearbeiten."These are the words of the renowned author of the Cosmos.In conclusion, I beg to reiterate my thankful acknowledgments for the high honour which has been conferred upon me,
The effect of prior docetaxel (DOC) treatment on efficacy and safety of apalutamide (APA) plus androgen deprivation therapy (ADT) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) from TITAN.
Authors: Kim N. Chi, Axel S. Merseburger, Mustafa Ozguroglu, Simon Chowdhury, Anders Bjartell, Byung Chung, Andrea Juliana Pereira de Santana Gomes, Robert Given, Álvaro Juárez, Hirotsugu Uemura, Dingwei Ye, Lawrence Ivan Karsh, Benjamin Adam Gartrell, Sabine D. Brookman-May, Suneel Mundle, Sharon Anne McCarthy, Florence Lefresne, Oliver Brendan Rooney, Amitabha Bhaumik, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2022)

89 Background: Addition of androgen receptor signaling inhibitors to ADT + DOC has been shown to improve clinical outcomes in pts with mCSPC. TITAN, a placebo-controlled phase 3 study, showed that APA + ADT improved overall survival (OS) and other clinical outcomes in mCSPC (Chi, J Clin Oncol 2021). This post hoc analysis of TITAN evaluated outcomes in pts who had received DOC prior to treatment with APA + ADT versus those who did not. Methods: In TITAN, 1052 pts were randomized 1:1 to APA (240 mg QD) or placebo added to ongoing ADT. We assessed radiographic progression-free survival (rPFS), OS, and time to prostate-specific antigen (PSA) progression in pts receiving DOC and ADT prior to adding APA vs those receiving only ADT plus APA. Outcomes by prior DOC were also assessed in pts with high- or low-volume disease at randomization (baseline [BL]) per adapted CHAARTED criteria, or those with matched BL characteristics. A Cox proportional hazards model was used to derive hazard ratios (HRs) and p values. rPFS was assessed using the first interim analysis cutoff (23 mo median follow-up); OS and time to PSA progression were assessed using the final analysis cutoff (44 mo median follow-up). Results: A total of 58/525 (11%) pts from the APA + ADT group had received DOC prior to randomization: 76% (n = 44) had high-volume disease, 62% (n = 36) had bone-only metastases, 16% (n = 9) had visceral metastases, and 59% (n = 34) had &gt; 10 bone lesions. In the overall APA-treated population and in the subset of pts with high-volume disease, OS, rPFS, and time to PSA progression were similar in those who received prior DOC and those who did not (Table). Pts with low-volume disease also had similar results, although the number of pts was small. Clinical outcomes in pts with matched BL characteristics (including PSA and time from initial diagnosis to randomization, among others) were similar regardless of prior use of DOC (Table). The safety profile of APA was not substantially different between pts with or without prior DOC. Limitations of this analysis include lack of data on tumor volume and other disease characteristics at the initiation of prior DOC treatment; interpretation was based on small number of pts with prior DOC (only 11% of TITAN pts), most notably in the rPFS analysis. Conclusions: Prior use of DOC in pts with mCSPC did not further improve clinical benefits of APA + ADT in TITAN. Clinical trial information: NCT02489318. [Table: see text]
Does presence of diabetes mellitus impact patient oncological outcomes in renal cell carcinoma: A multicenter analysis.
Authors: Ava Saidian, Arman Walia, Dattatraya Patil, Kazutaka Saito, Devin Patel, Mimi Vu Nguyen, Madison Chakoumakos, Fady Ghali, Rekha S Narasimhan, John M Perry, Margaret Meagher, Yosuke Yasuda, Yasuhisa Fujii, Viraj A. Master
Journal: Journal of Clinical Oncology (2022)

325 Background: Diabetes mellitus (DM) has been hypothesized to be a risk factor for development of renal cell carcinoma (RCC). We evaluated impact of DM on survival outcomes in RCC. Methods: We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC). The cohort was divided into three subgroups (patients with stage I vs. stage II vs. stage III RCC) for descriptive, survival and multivariable analysis of outcomes. Kaplan Meier Analysis (KMA) was used to compare diabetic and non-diabetic patients in the different stage subgroups to evaluate overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Cox Regression multivariable analysis (MVA) was used to elucidate independent risk factors for all-cause mortality (ACM). Results: 2,927 patients with stage I RCC (709-DM/ 2218 non-DM), 2,513 with stage II RCC (688 DM/1825 non-DM) and 460 with stage 3 RCC (355 DM/ 105 non-DM) were analyzed. MVA revealed DMII having no impact on CSM (p=0.118) or PFS (p=0.316) across all stages. MVA for ACM revealed age (HR 1.026, p&lt;0.001), male sex (HR=1.425, p&lt;0.001), hypertension (HR=1.693, p &lt;0.001) and tumor size (HR=1.064, p&lt;0.001) as independent risk factors. KMA identified increased ACM in stage I (p&lt;0.001) and stage III (p&lt;0.001) RCC patients with non-DM compared to diabetic patients. Conclusions: Our findings suggest that DM may have impact on survival of in RCC, but this impact is mostly driven by non-oncologic, as opposed to oncologic effects. Further investigation is requisite.
Long-term care.
Authors: M A Tudor, V Kendall
Journal: BMJ (1969)

p. 432) was an excellent testimony to the efficacy of D.C. defibrillation in terminating ventricular fibrillation, it raises an important point.The values for arterial Pco2 quoted show that the patient was adequately " titrated " with, presumably, bicarbonate solutions, but the values quoted for arterial Pco2 are: 107 mm.Hg, 97 mm.Hg, and 107 mm.Hg, respectively.A high Pco2 is known to alter the automaticity of pacemaker cells, and above a value of about 70 mm.Hg may be associated with the production of ectopic beats,' especi- ally in an already abnormal myocardium.A high Pco2 will also cause the release of endo- genous catecholamines,2 which have a similar electrophysiological effect as well as changing the refractory periods and increasing the rate of discharge of pacemaker cells.'Could it be possible that, in the presence of the myocardial infarction, the episodes of ventricular fibrillation were related to the respiratory failure ?Were this the case then surely the appropriate therapy lies in the avoidance of high oxygen-enriched mixtures for the patient to breathe, and, should the hypercapnia persist at unacceptable levels, the institution of mechanical ventilation.-I am, etc.,
Association of Maternal Antidepressant Prescription During Pregnancy and Danish School-aged Children’s Standardized Test Scores—Reply
Authors: Jakob Christensen, Betina Trabjerg, Julie Werenberg Dreier
Journal: JAMA (2022)

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
Letter Indomethacin, prostaglandins, and dysmenorrhoea.
Authors: S Shafar, A Theodossiadis, L Steen
Journal: BMJ (1975)

Dear Fellow Psychiatrists, I understand that it was your intervention that helped me so quickly (and comparatively pain- lessly) to leave the U.S.S.R., where the righttohold one's own beliefs is being constantly violated.Life in the Soviet Union has taught me that the authorities in my country are extremely sensitive to the public opinion of the Western powers.I saw that help was especially effective
Mortality in Persons With Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder
Authors: Ferrán Catalá-López, Brian Hutton, Matthew J. Page, Jane A. Driver, Manuel Ridao, Adolfo Alonso-Arroyo, Alfonso Valencia, Diego Macías Saint-Gerons, Rafael Tabarés-Seisdedos
Journal: JAMA Pediatrics (2022)

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are childhood-onset disorders that may persist into adulthood. Several studies have suggested that they may be associated with an increased risk of mortality; however, the results are inconsistent.To assess the risk of mortality among persons with ASD or ADHD and their first-degree relatives.A search of MEDLINE, Embase, Scopus, Web of Science, and PsycINFO (published from inception to April 1, 2021) was supplemented by searching reference lists of the retrieved articles.Cohort and case-control studies that reported mortality rate ratios (RRs) in persons with ASD or ADHD and/or their first-degree relatives compared with the general population or those without ASD/ADHD were included.Screening, data extraction, and quality assessment were performed by at least 2 researchers independently. A random-effects model was used to meta-analyze individual studies and assessed heterogeneity (I2).All-cause mortality in association with ASD or ADHD. Secondary outcome was cause-specific mortality.Twenty-seven studies were included, with a total of 642 260 individuals. All-cause mortality was found to be higher for persons with ASD (154 238 participants; 12 studies; RR, 2.37; 95% CI, 1.97-2.85; I2, 89%; moderate confidence) and persons with ADHD (396 488 participants; 8 studies; RR, 2.13; 95% CI, 1.13-4.02; I2, 98%; low confidence) than for the general population. Among persons with ASD, deaths from natural causes (4 studies; RR, 3.80; 95% CI, 2.06-7.01; I2, 96%; low confidence) and deaths from unnatural causes were increased (6 studies; RR, 2.50; 95% CI, 1.49-4.18; I2, 95%; low confidence). Among persons with ADHD, deaths from natural causes were not significantly increased (4 studies; RR, 1.62; 95% CI, 0.89-2.96; I2, 88%; low confidence), but deaths from unnatural causes were higher than expected (10 studies; RR, 2.81; 95% CI, 1.73-4.55; I2, 92%; low confidence).This systematic review and meta-analysis found that ASD and ADHD are associated with a significantly increased risk of mortality. Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups. The substantial heterogeneity between studies should be explored further.
Abstract 217: Cooling Beneficially Impacts Cardiac Performance on Arrest Survivors Undergoing Targeted Temperature Management
Authors: Kevin Chen, Aldo L Schenone, Bashaer Gheyath, Nyal Borges, Abhijit Duggal, Zoran Popovic, Venu Menon
Journal: Circulation (2018)

Introduction: Targeted temperature management (TTM) is a widely accepted neuroprotective strategy in the management of comatose cardiac arrest (CA) survivors. The beneficial impact of TTM on cardiac performance in this population remains debatable. Hypothesis: Mild cooling enhances cardiac performance in arrest survivors undergoing TTM. Methods: We reviewed prospectively collected data on all CA survivors undergoing TTM at our CICU between Jan15 and Jun17. Enrollment was restricted to cases with invasive hemodynamics (iHDs) available at TTM initiation, every 8 hrs at target temperature (32-34°C) and at rewarming completion (&gt;36°C), unless precluded by mortality. Those with cooling initiated before admission and temperature of &lt;36°C prior to iHDs were excluded. iHDs included temperature (Temp), heart rate (HR), mean blood pressure (MAP), right atrial pressure (RAP), pulmonary wedge pressure (PCWP), systemic vascular resistance (SVR) and Fick Cardiac Index (CI). Left and right ventricular stroke work indices were calculated (LVSWI &amp; RVSWI).We also assessed changes induced by cooling, and overall improvements in cardiac performance and iHDs over time at completion of rewarming controlling for temp change using longitudinal data analysis. Results: 46 arrest survivors with average age of 61 years, 65% male, 83% out-hospital arrest with a shockable rhythm (74%) were evaluated. HR decreased with cooling (p&lt;0.001), to return to baseline after rewarming (p=0.6). MAP, SVR and PCWP decreased by cooling (p&lt;0.001 for all), with sustained improvement after rewarming (p &lt;0.001 for all). LVSWI increased with cooling (p&lt;0.001), with return to baseline after rewarming (p=0.6). Similar findings were encountered with RAP and RVSWI. Conclusion: Mild cooling during TTM improves cardiac performance indices. At TTM completion, there is a sustained decrease in filling pressures without a change in LVSWI indicative of improved contractile performance during cooling.
Opothérapie endocrinienne: Les bases physiologiques, les syndromes, la posologie de l'opothérapie.
Journal: JAMA (1933)

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
Abstract 158: Pediatric In-Hospital Cardiac Arrest Associated With Pulmonary Hypertension: A Common Pathophysiology
Authors: Ryan W Morgan, Alexis A Topjian, Yan Wang, Natalie J Atkin, Todd J Kilbaugh, Francis X McGowan, Robert A Berg, Laura Mercer-Rosa, Robert M Sutton, Adam S Himebauch
Journal: Circulation (2018)

Introduction: In laboratory studies, pulmonary hypertension (PH) during CPR worsens outcomes but can be ameliorated with inhaled nitric oxide (iNO). The prevalence of pre-arrest PH among children with IHCA and its impact on outcomes are not well described. Hypothesis: We hypothesized that among children with IHCA, pre-arrest PH would be common and associated with worse survival to discharge. Methods: Retrospective single-center cohort study of consecutive pediatric ICU patients (1/1/2006 - 12/31/2017) with an echocardiogram in the 48 hours preceding IHCA, excluding those with cyanotic congenital heart disease. Echocardiograms were analyzed by a cardiologist blinded to other patient data. PH was defined as abnormal septal position and/or peak tricuspid regurgitant velocity &gt; 2.8 m/sec. Patient and arrest characteristics and treatments were compared between subjects with and without PH using non-parametric tests. Logistic regression evaluated the association between PH and outcome, adjusting a priori for age and initial arrest rhythm, as well as for candidate variables associated with survival (p&lt;0.10). Results: Of 284 IHCA subjects, 57 (20%) had an evaluable echocardiogram. PH was present in 20/57 (35%); 9/20 (45%) had no prior clinical history of PH. Children with PH had worse RV systolic function as measured by median fractional area change (32% vs. 45%; p=0.005), RV global longitudinal strain (-15% vs. -21.1%; p=0.046), and tricuspid annular plane systolic excursion z-score (-4.50 vs. -3.53; p=0.17). Children with PH had more RV dilation (median RV:LV end-diastolic area ratio 0.90 vs. 0.52; p=0.005) and similar rates of qualitative LV dysfunction (45% vs. 59%, p=0.40). Children with PH were more likely to receive iNO [16/20 (80%) vs. 12/37 (32%); p&lt;0.001] and isoproterenol [9/20 (45%) vs. 1/37 (3%); p&lt;0.001] during CPR. There were no differences in other IHCA characteristics. On multivariable analysis, PH was not associated with ROSC [14/20 (70%) vs. 24/37 (65%); adjOR 1.30 (0.25 - 6.69); p=0.77] or survival to hospital discharge [8/20 (40%) vs. 10/37 (27%); adjOR 1.17 (0.22 - 6.44); p=0.85]. Conclusions: PH was present in 35% of children with IHCA. In a cohort with a high frequency of treatment with iNO during CPR, PH was not associated with survival.