tbuckley/cabot-search huggingface dataset:
Effects of interleukin-17 inhibitors on hepatic fibrosis index in patients with psoriasis and metabolic dysfunction-associated fatty liver disease: Directed acyclic graphs
Authors: Saori Takamura, Yuichi Teraki, Eri Katayama, Takumi Kawaguchi, Machiko Kawaguchi, Dan Nakano, Tsubasa Tsutsumi, Sumiko Nagoshi, Takekuni Nakama, Takuji Torimura
Journal: Clinical and Molecular Hepatology (2022)

Keywords: Non-alcoholic fatty liver disease; Metabolic diseases; Psoriasis; Interleukin-17; Liver fibrosis
ADAM: A multicenter, non-interventional, prospective cohort study for determination of prevalence of homologous recombination repair genes mutations (HRRm) in metastatic castrate-resistant prostate cancer (mCRPC)—Interim analysis.
Authors: Boris Alexeev, Liudmila Lyubchenko, Marat Gordiev, Maxim Filipenko, Yulia Anzhiganova, Alexander Sultanbaev, Alexander Bystrov, Alexander Orlov, Galina Gopp, Evgeny Kopyltsov, Alexander Lykov, Vagif Atduev, Galina Alekseeva, Ovsep Mailyan, Vladislav Semenov, Olga Vedrova, Alexander Perevoschikov, Sergei Andreev, Logacheva Evgenia
Journal: Journal of Clinical Oncology (2022)

169 Background: The HRRm detection is used to prescribe PARP inhibitors in mCRPC patients. The frequency of HRR alterations has been investigated in several clinical studies, but the prevalence of HRRm in real clinical practice remains unclear. We conducted the first study to evaluate prevalence of HRRm in mCRPC patients in Russia. This interim analysis is aimed to provide HRRm rate in real practice in Russian population. Methods: Patients with mCRPC and available tumor tissue samples (FFPEs) were enrolled from October 2020 till May 2021. Samples were analyzed in 3 labs. Target enrichment using multiplex PCR and library preparation of genes involved in HRR (BRCA2, BRCA1, RAD54L, FANCL, BARD1, ATM, CHEK1, RAD51B, PALB2, RAD51D, CDK12, RAD51C, BRIP1, CHEK2) was performed using three different techniques: GeneReader NGS System (QIAGEN), KAPA HyperPlus and SeqCap EZ Choice (Roche) and in-house targeted NGS-panel. For last 2 sequencing was performed using MiSeq (Illumina). Results: In this interim analysis we included 331 mCRPC patients from 20 sites with median age 67 years, 86,7% caucasian. Family or personal history of oncological diseases had 66 (20%) of pts 300 FFPEs were analyzed by NGS, 31 (9%) were not valid (poor quality/not enough DNA). HRRm rate is 19,7% (59/300). Most frequently mutated genes ( &gt; 1%) listed in the table below. Other mutations (RAD51B, RAD51C, BARD1, FANCL, RAD51D, RAD54L) were detected in 1-2 cases per gene. Conclusions: This first systematic analysis of HRRm in Russian population of mCRPC patients showed general consistency with previously reported HRRm data (19,7% in our trial in comparison with 27.9% in PROfound trial). Lab approach using different techniques in real practice has to be established.[Table: see text]
Abstract 338: Impact of No-Flow Time on the Coagulopathy of Prolonged Cardiac Arrest
Authors: Pavel Hala, Matias Caceres, Aaron Prater, Jensyn VanZalen, Joshua Jung, Brendan M McCracken, Mohamad H Tiba, Cindy H Hsu, Jake Pitcher, Stephen Harvey, Katia Shpilband, Brandon C Cummings, Robert H Bartlett, Alvaro Rojas-Pena, Robert W Neumar
Journal: Circulation (2018)

Introduction: Prolonged cardiac arrest (CA) eligible for ECPR has pathologic features that are more pronounced than CA durations in which ROSC is typically achieved. One such feature is consumptive coagulopathy resulting in microvascular thrombosis and no-reflow. In this study we examined the impact of no-flow time on CA coagulopathy during prolong CPR in swine Hypothesis: No-flow time amplifies the coagulopathy of prolonged cardiac arrest. Methods: Animals were anesthetized and instrumented for hemodynamic monitoring. After 4 or 8 min of untreated ventricular fibrillation (groups CA-4 and CA-8, n=5/group), goal-directed CPR was initiated and continued for a total arrest time of 45 minutes. Viscoelastic properties of clot formation and fibrinolysis were measured by TEG in whole blood at baseline and at the end of resuscitation protocol. Rate of fibrin activation (Angle alpha), Maximum amplitude (MA), Time to MA (TMA), and reduction of clot after 30 min (CL30) were measured to describe coagulation status. Results: TEG showed reduction in clot strength after the CPR protocol. For groups CA-4 and CA-8, Alpha declined from 71(4) to 55(7) and from 68(5) to 51(9) deg, MA reduced from 75(2) to 58(7) and from 73(3) to 53(11) mm and TMA prolonged from 21(2) to 27(4) and from 20(4) to 25(2) min. CL30 increased from 95(2) to 97(2) and from 96(2) to 100(1) % (all p&lt;0.05). Clot lysis was more reduced in CA-8 (p&lt;0.05) but other parameters did not significantly vary between groups. Overall, platelets declined from 328(86) to 138(81) thousands/mm3 while hematocrit increased (all p&lt;0.01). Conclusion: In this clinically relevant model of prolonged CA with consumptive coagulopathy, the reduction of clot formation and clot strength after 45 minutes of CA and CPR was not significantly different with 4 and 8 min no-flow time. However, clot lysis was more reduced after 8-min no-flow. Further studies are needed to determine the impact of no-flow time on CA coagulopathy at the microvascular level.
FIVE YEAR SURVIVAL AFTER PERCUTANEOUS CORONARY INTERVENTION WITH DRUG ELUTING STENTS AND BARE METAL STENTS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION. A NEW JERSEY STATEWIDE DATABASE STUDY
Authors: Tudor Dumitru Vagaonescu, Abel E. Moreyra, Alan C. Wilson, Nora M. Cosgrove, John B. Kostis
Journal: Journal of the American College of Cardiology (2011)
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2019</i>
Journal: Diabetes Care (2018)

The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Royal malady.
Authors: A. F. Maclean
Journal: BMJ (1968)

The authors take issue with me that those who inherit porphyria variegata and avoid the drugs that can precipitate an acute attack of porphyria remain in good health except for increased sensitivity of the light-exposed skin.The evidence for this is that the forebears of porphyric families in South Africa in the seventeenth, eighteenth, and nineteenth cen- turies had just as large families as average- and the average family was large, usually 8 to 15 children-which is why the porphyrics increased in number pari passu with the descendants of the rest of the small nucleus of early South African Free Burghers.If they were having attacks of acute porphyria and died from the attacks before the advent of modern drugs their descendants would not have increased as rapidly as they did.Furthermore, here in the Eastern Cape there is not a doctor with a general practice of any size who has not among his patients men and women who have inherited porphyria variegata, and they can confirm that their porphyric patients do not have attacks of acute porphyria except after taking drugs, usually a barbiturate.In my last letter I ended on the kindly note that their claim was " not proven."This time I shall end more firmly by promis- ing to "eat my hat" (a paper one) if the authors can produce convincing evidence that they are right.-Iam, etc.,
Body weight regulation via MT1-MMP-mediated cleavage of GFRAL
Authors: Chi Fung Willis Chow, Xuanming Guo, Pallavi Asthana, Shuo Zhang, Sheung Kin Ken Wong, Samane Fallah, Sijia Che, Susma Gurung, Zening Wang, Ki Baek Lee, Xin Ge, Shiyang Yuan, Haoyu Xu, Jacque Pak Kan Ip, Zhixin Jiang, Lixiang Zhai, Jiayan Wu, Yijing Zhang, Arun Kumar Mahato, Mart Saarma, Cheng Yuan Lin, Hiu Yee Kwan, Tao Huang, Aiping Lyu, Zhongjun Zhou, Zhao-Xiang Bian, Hoi Leong Xavier Wong
Journal: Nature Metabolism (2022)
Characterization of aberrant alternative splicing landscape in patients with renal cell carcinoma (RCC).
Authors: Ameish Govindarajan, Apurva M. Hegde, Neal Shiv Chawla, Nazli Dizman, Zeynep Busra Zengin, Luis A Meza, Ramya Muddasani, Alex Chehrazi-Raffle, Jasnoor Malhotra, Daniela V. Castro, Sabrina Salgia, Cristiane Decat Bergerot, Nishita Tripathi, Nicolas Sayegh, Errol James Philip, Joann Hsu, Sara A. Byron, Patrick Pirrotte, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2022)

386 Background: Aberrant alternative splicing (AS) events have been implicated in the initiation and progression of various cancers; however, the detailed nature of their role in RCC is yet to be fully elucidated. Our study aims to characterize AS events in RCC tumors using a novel AS pipeline (Bisbee). Methods: We retrospectively identified patients (pts) with RCC who had tumor-normal whole exome sequencing and tumor whole transcriptome sequencing (GEMExtra, Ashion Analytics) performed as part of their routine clinical care. AS events from RNA sequencing data were identified and further characterized as (1) alternative splice 3’ site (A3), (2) alternative splice 5’ site (A5), (3) exon skipping (ES), (4) intron retention (IR), and (5) mutually exclusive exons splice events (MUT). The Bisbee outlier analysis was performed against normal kidney tissues from the GTEx tissue library to further identify tumor-associated splice events. Outlier splice events were categorized as either non-coding/protein loss/silent, isoform switch, novel, or unknown. Results: Overall, 147 RCC pts (77% male) with RNA sequencing data were included in this analysis. Median age at diagnosis was 60 (range 31-94) and 97% of pts had metastatic RCC. The distribution of histology was 85% clear cell RCC followed by 11% papillary RCC. The AS analysis identified 25,928 outlier splice events. Approximately 60% of these were predicted to be protein-coding events, with the majority arising from IR and ES. These were followed by A3, A5, and MUT, in descending order of frequency. We also examined tumor-associated novel outlier events where 70% of analyzed RCC tumor samples noted 34 tumor-associated novel events were present, shared in most of the cohort and found an enrichment for IR events leading to frame disruptions. Data of splice variants will be presented at the meeting. Conclusions: In depth examination of this large cohort suggests that IR resulting from AS events occur frequently within RCC. Further efforts to investigate the association of AS events and clinical outcomes are underway.
Lectures on Diseases of Women and Children
Authors: C. H. F. Routh
Journal: BMJ (1862)

LET me now turn to the subject of endometritis.And here, in the onset, I would make two general remarks.First: the affection eminently resembles inflammation of other mucous membranes.These tissues -mucous membranes-more than any other mem- branes, appear to have the faculty, when diseased, of secreting morbid products of a very acrid cha-
Abstract 184: AED Application in Non-Shockable Out-of-Hospital Cardiac Arrest Does Not Reduce Survival
Authors: Ross A Pollack, Siobhan P Brown, Thomas Rea, Peter J Kudenchuk, Myron L Weisfeldt
Journal: Circulation (2018)

Introduction: It is well established that AEDs improve outcome in shockable out-of-hospital cardiac arrest (OHCA). An increasing proportion (now the majority) of OHCAs present with non-shockable rhythms. Survival from non-shockable OHCA depends on high-quality CPR in transit to definitive care. Studies of AED use in non-shockable in-hospital arrest (as opposed to OHCA) have shown reduced survival with AED application possibly due to CPR interruptions to apply pads and perform rhythm analysis. We sought to determine whether AED application in non-shockable public, witnessed OHCA has a significant association with survival to discharge. Methods: This is a retrospective analysis of OHCA from 2010-2015 at 10 Resuscitation Outcomes Consortium centers. All adult, public, witnessed non-shockable OHCAs were included. Non-shockable arrest was defined as no shock delivered by the AED or by review of defibrillator tracings (10%). The initial rhythm on EMS arrival was used to confirm the rhythm. The primary outcome was survival to hospital discharge with favorable neurological status (modified rankin score &lt;3). The OR was adjusted for the Utstein variables. Results: During the study period there were 1,597 non-shockable public, witnessed OHCA, 9.8% of which had an AED applied. The initial rhythm on EMS arrival was PEA or asystole in 86% of cases. Significantly more OHCA in the AED applied group had CPR performed. 6.5% of those without an AED applied survived with favorable neurologic status compared to 9% with an AED. After adjustment for the Utstein variables including bystander CPR, the aOR for survival with favorable neurologic outcome was 1.38 (95% CI:0.72-2.65). Conclusion: After adjusting for patient characteristics and bystander CPR, the application of an AED in non-shockable public witnessed OHCA had no significant association with survival or neurological outcome supporting the relative safety and potential benefit of AED application in non-shockable OHCA.
Abstract 17058: Generalizability of Outcomes From Cardiac Resynchronization Therapy Trials to African-Americans
Authors: Gilbert Essilfie, Sona Franklin, Lilian E Ahiable, John M Fontaine
Journal: Circulation (2018)

Generalizability of Outcomes from Cardiac Resynchronization Therapy Trials to African-Americans Introduction: Underrepresentation of African-Americans in clinical trials calls to question the generalizability of the observed results to this population. Methods: We studied 294 Caucasians and African-Americans and compared outcomes with those reported in major cardiac resynchronization therapy trials (CRT). Results from MIRACLE, COMPANION, CARE-HF, REVERSE, and MADIT-CRT were analyzed. Kaplan-Meier survival analysis and Cox proportional hazards regression were applied to our dataset. Results: We included 294 patients (45% African-Americans). In African-Americans the mean age was 65±12 compared with 70±13 for Caucasians, (p=0.0003). The median follow-up was 8.1± 6 years. Baseline characteristics were similar to landmark trials in age, ejection fraction, proportion with ischemic cardiomyopathy (ICM), diabetes mellitus and glomerular filtration rate (GFR). African-Americans had similar NYHA functional class as in MIRACLE, COMPANION, and CARE-HF. Survival in our patients was 7.6±0.3 years (95% CI 6.9-8.2). There was no difference in mortality between African-Americans (28%,) and Caucasians (37%, P=0.19) compared with that reported in MADIT-CRT (29 and 22%, respectively). Treatment with an aldosterone antagonist and a GFR greater than 60 were associated with lower mortality (P=0.04 and P=0.005, respectively). In African-Americans lack of treatment with an angiotensin converting-enzyme inhibitor (ACEI), GFR less than 60, and ischemic cardiomyopathy (ICM) were associated with increased mortality when compared with Caucasians (P=0.01, P=0.03, and P=0.04, respectively). In Caucasians, none of these variables were associated with increased mortality. Conclusions: Despite lack of specificity in details from the major trials, African-Americans had similar mortality outcomes as reported in the initial trials. These results support extrapolations of outcomes from landmark trials to African-Americans.
Comparison of prostate specific antigen testing in men aged 55 to 69 with and without a history of cancer.
Authors: Alon Lazarovich, Thenappan Chandrasekar, Oleg Shapiro, Joseph M Jacob, Alina Basnet, Gennady Bratslavsky, Hanan Goldberg
Journal: Journal of Clinical Oncology (2022)

230 Background: Prostate specific antigen (PSA) screening remains a controversial issue. However, most urological guidelines recommend PSA testing through a shared decision-making process with the patient. The rate of PSA screening in men with a history of cancer compared to men with no cancer history is not well known. We aimed to compare PSA testing in men aged 55-69 years with and without a history of cancer (excluding prostate cancer patients). Methods: Utilizing the National Health Interview Survey (NHIS) a retrospective cross-sectional study between the years 2015 and 2018 was carried out to analyze and compare PSA testing rates in men aged 55-69 years. Multivariable logistic regression model was implemented do demonstrate potential associations with PSA testing. Results: A total of 13,850 men aged 55-69 years included in the NHIS Survey were analyzed. 1519 (10.9%) men had a history of cancer (non-prostate). On multivariable analysis, men who were previously diagnosed with cancer had a higher rate of PSA testing compared to men with no history of cancer (OR: 1.88, 95% CI 1.39-2.54, p &lt; 0.001). Other factors associated with an increased likelihood of undergoing PSA testing included: age, homosexual orientation, and married men. In contrast, current smokers, American Indians and Alaskan Natives and Asians were less likely to undergo PSA testing. Conclusions: Our data suggest that men aged 55-69 with a history of cancer are more likely to undergo PSA testing than men with no cancer history.[Table: see text]
Abstract 298: Identification of LncRNA-miRNA-mRNA Network in Myocardium After Successful Resuscitation in a Rat Model of Prolonged Cardiac Arrest
Authors: Jingying Hou, Zhengfei Yang, Wanchun Tang
Journal: Circulation (2018)

Introduction: Previous studies have indicated that lncRNA participates in regional myocardial ischemia-reperfusion injury (IRI). However, the lncRNA-miRNA-mRNA crosstalk in the global myocardial IRI, which is implicated in the pathophysiology of post-resuscitation myocardial dysfunction (PRMD), has still not been explored. Hypothesis: To identify lncRNA-miRNA-mRNA regulatory network in myocardium after successful resuscitation in a rat model of prolonged cardiac arrest. Methods: Six male Sprague Dawley rats were randomized into sham control and ventricular fibrillation (VF)-CPR groups, with three rats in each group. VF was induced and untreated for 8 minutes. Defibrillation was attempted after 8 minutes of CPR. Heart tissue was obtained at 6 hours after resuscitation and lncRNA, miRNA and mRNA expression profiles were examined by using high-throughput sequencing. LncRNA-miRNA-mRNA interaction network was predicted and constructed. Results: Numbers of differentially expressed (DE) lncRNA, miRNA and mRNA were detected (Fig 1A). LncRNAs co-located or co-expressed target mRNAs and DE mRNAs were revealed (Fig 1B). The intersection of DE mRNAs with targeted mRNA of DE miRNAs was made (Fig 1C). A total of 129 feed forward loops were predicted as lncRNA-associated ceRNA networks,with 126 lncRNA (up)-miRNA (down)-mRNA (up) and 3 lncRNA (down)-miRNA (up)-mRNA (down) (Fig 2). Conclusions: LncRNA-miRNA-mRNAs network was predicted and constructed in myocardium after successful resuscitation in a rat model of prolonged cardiac arrest. Further exploration into the specific functional roles of the ceRNA regulatory network will be conducive for the treatment of PRMD.
Abstract 17344: Efficient Purification of Human iPSC-Derived Cardiomyocytes in a Large Scale Using a Synthetic microRNA Switch and Magnetic-Activated Cell Sorting
Authors: Takeshi Hatani, Kazuhisa Chonabayashi, Yoshihiko Fujita, Takeshi Kimura, Hirohide Saito, Yoshinori Yoshida
Journal: Circulation (2018)

Background: Although studies have demonstrated the feasibility of in vivo cardiac transplantation of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) using large animals, it requires large quantities of purified PSC-CMs. Moreover, genetic modification and contamination of non-CMs are inappropriate for clinical application. Using antibodies on the surface of the transplanted cells is one of the useful methods, but can be immunogenic and cause local inflammation or graft failure. We have shown the synthetic mRNAs encoding a fluorescent protein tagged with sequences targeted by microRNAs (miRNAs) expressed in specific cell types can efficiently detect and purify the particular cell populations. Using a miRNA switch and magnetic-activated cell sorting (MACS), we evaluated the efficiency of purification of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in a large scale. Methods: We used CD4 as a selection marker for MACS and miR-208a as a specific mRNA of CMs. We synthesized CD4 mRNA and transfected it into differentiated cells from iPSCs to confirm CD4 expressing on the surface of the transfected cells. We also synthesized a miRNA switch encoding CD4 tagged with sequences targeted by miR-208a (CD4-208a switch) and transfected it into differentiated cells to demonstrate transfected non-CMs expressing CD4 and transfected CMs non-expressing CD4. Finally, we transfected the CD4-208a switch and puromycin resistance mRNA simultaneously, and purified iPSC-CMs by eliminating CD4+ cells using MACS and untransfected cells using puromycin. Purified cells were transplanted into NOG mouse hearts with myocardial infarction by direct injections into the myocardium. Results: After transfecting CD4 mRNA into differentiated cells from iPSCs, 78±5% expressed CD4 on the surface. We also confirmed that the CD4-208a switch separated CMs and non-CMs. Using MACS and puromycin selection, we purified iPS-CMs 69±5% to 97±2% assessed by troponin T. Purified cells were also engrafted as CMs in mouse hearts. Conclusions: We demonstrated that CD4-208a switch purifies iPSC-CMs efficiently in a large scale. Synthetic microRNA switches can apply for many studies of stem cell-based cell replacement therapy for clinical application.
Human Protein‐Based Porous Scaffolds as Platforms for Xeno‐Free 3D Cell Culture
Authors: Sara C. Santos, Catarina A. Custódio, João F. Mano
Journal: Advanced Healthcare Materials (2022)

Extracellular matrix and protein-based biomaterials emerge as attractive sources to produce scaffolds due to their great properties regarding biocompatibility and bioactivity. In addition, there are concerns regarding the use of animal-derived supplements in cell culture not only due to the risk of transmission of xenogeneic contaminants and antigens but also due to ethical issues associated with collection methods. Herein, a novel human protein-derived porous scaffold produced from platelet lysates (PL) as platform for xeno-free 3D cell culture has been proposed. Human PL are chemically modified with methacryloyl groups (PLMA) to make them photocrosslinkable and used as precursor material to produce PLMA-based sponges. The herein reported human-based sponges have highly tunable morphology and mechanical properties, with an internal porous structure and Young's modulus dependent on the concentration of the polymer. Human adipose-derived stem cells (hASCs) are cultured on top of PLMA sponges to validate their use for 3D cell culture in xeno-free conditions. After 14 days hASCs remained viable, and results show that cells are able to proliferate during time even in the absence of animal-derived supplementation. This study reveals for the first time that such scaffolds can be promising platforms for culture of human cells avoiding the use of any animal-derived supplement.