bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I Trial of Berberine in Chinese with Ulcerative Colitis
Authors: Xu Li , Zhang Yujie , Xue Xianmin , Liu Jie , Li Zeng-Shan , Yang Guang-Yu , Song Ying , Pan Yan , Ma Yueyun , Hu Sijun , Wen Aidong , Jia Yanyan , Rodriguez Luz Maria , Tull Mary Beth , Benante Kelly , Khan Seema A. , Cao Ying , Jovanovic Borko , Richmond Ellen , Umar Asad , Bergan Raymond , Wu Kaichun 
Published: October 2019

Abstract
The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.
Визначення показань та протипоказань до симультанних оперативних втручань у пацієнтів з поєднанням ендокринної та іншої хірургічної патології
Authors: Zavgorodnii S. M. , Kubrak M. A. , Danyluk M. B. , Rylov A. I. , Yareshko N. O. 
Published: October 2019

Мета роботи: розробити показання та протипоказання до виконання симультанних оперативних втручань на прикладі пацієнтів з поєднаною патологією щитоподібної залози (ЩЗ) та жовчнокам’яною хворобою (ЖКХ) / поліпозом жовчного міхура, з використанням шкали функціонального стану P-POSSUM.
Матеріали і методи. За період з січня 2015 до вересня 2018 року обстежено та прооперовано 35 пацієнтів з поєднаною патологією щитоподібної залози та ЖКХ / поліпозом жовчного міхура. На доопераційному етапі, а також на першу добу післяопераційного періоду всім пацієнтам проводили оцінку функціонального стану за шкалою P-POSSUM.
Результати досліджень та їх обговорення. У 22 (62,9 %) пацієнтів, функціональний стан яких до втручання оцінювався за фізіологічною субшкалою (ФС) ≤ 17 балів, мали місце післяопераційні зміни стану здоров’я з різницею середніх 0,13 бала, Т (Z) = 1,21, р = 0,225. У всіх цих хворих складність оперативного втручання за хірургічною субшкалою (ХС) шкали P-POSSUM була оцінена ≤ 14 балів. У 13 (37,1 %) хворих, стан яких був оцінений в ˃ 17 балів за ФС, виявлені значущі зміни функціонального стану здоров’я до та після операції з різницею середніх 1,15 бала, Т (Z) = 2,67; р = 0,0077. Складність операцій у них коливалася від 14 до 16 балів за ХС.
Етапний підхід у хірургічному лікуванні хворих з обтураційною непрохідністю товстої кишки бластоматозного генезу
Authors: Ioffe O. Yu. , Stets M. M. , Perepadja V. M. , Antoniv V. R. , Tsiura Y. P. 
Published: October 2019

Мета роботи: поліпшити результати хірургічного лікування хворих з обтураційною непрохідністю товстої кишки бластоматозного генезу шляхом удосконалення алгоритму лікувально-діагностичної тактики.
Матеріали і методи. За період 2009–2018 рр. у хірургічній клініці КМКЛ № 3 проліковано 127 хворих з обтураційною непрохідністю товстої кишки пухлинного генезу, що складає 5,1 % (2485 пацієнтів) від загальної кількості хворих із невідкладною хірургічною допомогою. Жінки становили 66,2 % (84 хворі), чоловіки склали 33,8 % (43 пацієнти). Середній вік хворих становив (68,2±15,4) року. Етіологічно причинами обтурації просвіту кишечника в 10 (7,9 %) хворих була пухлина сліпої кишки, у 11 (8,7 %) – висхідної ободової кишки, у 5 (3,9 %) – печінкового згину ободової кишки, у 6 (4,7 %) – поперечноободової кишки, у 5 (3,9 %) – селезінкового згину ободової кишки, у 18 (14,2 %) – низхідної ободової кишки, у 32 пацієнтів (25,2 %) рівень перешкоди локалізувався у сигмоподібній кишці та у 30 (23,6 %) – на рівні прямої кишки. Крім цього, у 10 (7,9 %) пацієнтів непрохідність зумовили проростання пухлин матки, яєчників або сечового міхура в дистальні відділи товстої кишки.
Результати досліджень та їх обговорення. Представлено результати лікування 127 хворих з обтураційною непрохідністю товстої кишки пухлинного генезу, що проходили лікування в хірургічній клініці КМКЛ № 3 за період 2009 – 2018 рр. Розроблено лікувально-діагностичний алгоритм етапності надання хірургічної допомоги пацієнтам із даною патологією. Етапний підхід та використання малоінвазивних методик декомпресії кишечника у вигляді стентування, реканалізації та заведення зонда проксимальніше стенозу збільшило відсоток відтермінованих оперативних втручань (до 37,8 %) та зменшило летальність на 14 %.
Вплив різних моделей іммобілізаційного стресу на функціональні зміни в серці високо- і низькостійких до гострої гіпоксичної гіпоксії щурів різної статі
Authors: Denefil O. V. , Ordynskyi Iu. M. 
Published: October 2019

Мета роботи: визначити вплив різних моделей іммобілізаційного стресу на зміни показників електрокардіограми (ЕКГ) у самців і самиць щурів з високою і низькою стійкістю до гіпоксії (ВГ, НГ).
Матеріали і методи. У дослід взяли 135 щурі. Тварин поділено на три групи – контрольну та дві дослідні (які зазнали іммобілізаційного стресу). Стрес моделювали 4 рази одногодинною м’якою іммобілізацією щурів спинкою донизу з інтервалом 24 години (стрес 1) і 72 години (стрес 2). Дослідження проводили через 24 години після останньої іммобілізації. У всіх піддослідних тварин під наркозом реєстрували ЕКГ.
Результати досліджень та їх обговорення. При аналізі показників ЕКГ у щурів спостерігали незначні зміни тривалості та амплітуди зубців та інтервалів. Так, при порівнянні груп контрольних ВГ і НГ самців достовірних показників на ЕКГ не виявлено. Аналогічно не було достовірної різниці між досліджуваними ЕКГ показниками у ВГ і НГ самиць. Стрес 1 призвів до зниження відхилення сегмента ST від ізолінії порівняно з контрольними значеннями у ВГ самців і у ВГ самиць. У НГ самиць зросла ЧСС, зменшилися тривалість інтервалу RR та показник QTc. У ВГ самців, порівняно з ВГ самицями, була менша амплітуда зубця R. Стрес 2, порівняно з контролем, у ВГ самців спричинив підвищення амплітуди зубця R. У ВГ самців, порівняно з НГ, спостерігали більше відхилення сегмента ST від ізолінії; у НГ самиць зросла ЧСС, зменшилися тривалість інтервалу RR, тривалість та амплітуда зубця Р, тривалість інтервалу QT та QTc. У ВГ самиць, порівняно з НГ, була більша тривалість інтервалу QT. Після стресу 2 встановили, що у ВГ самців, порівняно з самицями, були більшими амплітуда зубця R і відхилення сегмента ST від ізолінії. У НГ самців, порівняно з НГ самицями, була більшою тривалість інтервалу QT.
Characterizing Patient‐Centered Postoperative Recovery After Adult Cardiac Surgery: A Systematic Review
Authors: Mori Makoto , Angraal Suveen , Chaudhry Sarwat I. , Suter Lisa G. , Geirsson Arnar , Wallach Joshua D. , Krumholz Harlan M. 
Published: October 2019

Background
Improving postoperative recovery is important, with a national focus on postacute care, but the volume and quality of evidence in this area are not well characterized. We conducted a systematic review to characterize studies on postoperative recovery after adult cardiac surgery using patient‐reported outcome measures.

Methods and Results

From
MEDLINE
and Web of Science, studies were included if they prospectively assessed postoperative recovery on adult patients undergoing cardiac surgery using patient‐reported outcome measures. Six recovery domains were defined by prior literature: nociceptive symptoms, mental health, physical function, activities of daily living, sleep, and cognitive function. Of the 3432 studies, 105 articles met the inclusion criteria. The studies were small (median sample size, 119), and mostly conducted in single‐center settings (n=81; 77%). Study participants were predominantly men (71%) and white (88%). Coronary artery bypass graft was included in 93% (n=98). Studies commonly selected for elective cases (n=56; 53%) and patients with less comorbidity (n=67; 64%). Median follow‐up duration was 91 (interquartile range, 42–182) days. Studies most commonly assessed 1 domain (n=42; 40%). The studies also varied in the instruments used and differed in their reporting approach. Studies commonly excluded patients who died during the follow‐up period (n=48; 46%), and 45% (n=47) did not specify how those patients were analyzed.

Conclusions
Studies of postoperative patient‐reported outcome measures are low in volume, most often single site without external validation, varied in their approach to missing data, and narrow in the domains and diversity of patients. The evidence base for postoperative patient‐reported outcome measures needs to be strengthened.
Abstract 209: iPSC Derived Cardiomyocytes Reproduce Divergent Phenotypes Caused by a LQTS Type-1 Likely Pathogenic Mutation
Authors: Campos De Carvalho Antonio C , Santos Danubia S , Brunswick Tais H , Ferreira Raphaela P , Araujo Daiana S , Farjun Bruna , Leitão Isabela C , Dias Glauber M , Coutinho Jorge , Vaz Isadora M , Brogonovo Tamara , Cruz Fernando E , Carvalho Adriana B 
Published: October 2019

The purpose of this work was to investigate if iPSC derived cardiomyocytes would reproduce the divergent phenotypes observed in a proband and mother that carried the same likely-pathogenic variant in KCNQ1 gene.
A 15 years old proband had syncope and cardiac arrest while swimming being diagnosed with LQTS based on a 12 lead ECG. The mother’s ECG showed no abnormalities. Genomic DNA from blood of daughter and mother was extracted using standard procedures. All coding exons and flanking intronic sequences of KCNQ1 (NM_000218) genes were amplified by polymerase chain reaction. Direct sequencing was performed on a 3500XL Genetic Analyzer. Data was analyzed with Geneious software for identification of mutations. For iPSC generation CD71+ CD36+ erythroblasts were reprogrammed using CytoTune™-iPS 2.0 Sendai Reprogramming Kit on irradiated mouse embryonic fibroblast feeder layers. Differentiation into cardiomyocytes was accomplished using the protocol described by Lian et al. (2012). Electrophysiological recordings were obtained from cardiomyocytes after 30–45 days of differentiation. Cells were transferred to acrylic plates pretreated with Matrigel and kept in culture for 3 days before microelectrode action potential (AP) were registered.
The ECG recordings showed a corrected QT interval (QTc) of 516 ms for the daughter and 436 ms for the mother. Sequencing showed that both daughter and mother had a c.1763C>T mutation resulting in p.Ile588Thr substitution. iPSC generated from daughter, mother and an unrelated control displayed normal karyotype and expressed pluripotent genes, besides spontaneously differentiating into cells of the three germ layers. Differentiation into cardiomyocytes was ascertained by immunofluorescence and flow cytometry for troponin T. In all differentiations more than 70% of cells were cardiomyocytes. Action potentials recordings showed that ventricular cardiomyocytes from the daughter exhibited significantly longer action potential durations at 90% repolarization than the mother’s or the unrelated control’s cardiomyocytes.
Cardiomyocytes derived from iPS cells reproduced the clinical phenotypes exhibited by daughter and mother.
Abstract 298: Downregulation of Delta and Kappa Opioid Receptors in Post-heart Transplantation in Human and Rats
Authors: Gebrie Mebratu A , Rungatscher Alessio , Linardi Daniele , Andrioli Anna , Ahmed Sajeela , Ahmed Naseer , Ismail Mahmoud , Forni Alberto , Tessari Maddalena , San Biagio Livio , Soave Alessandro , Milani Elizabetta , Innamorati Giulio , Luciani Giovanni B , Faggian Giuseppe 
Published: October 2019

Over the past decade, multiple data regarding local opioid regulation of heart function have been demonstrated. However, opioid receptors (ORs) have not yet characterized in post-heart transplantation. Since a transplanted heart is devoid of innervations and autonomic innervations modulate ORs, we assessed the hypothesis that a possible down-regulation of k-OR and δ-OR in heart transplants.
Endomyocardial biopsies were collected in 15 male patients at 30 days of orthotopic heart transplantation and in 15 control male patients during aortic valve surgery in human. Another study performed in 20 heterotopic heart transplants (HHT) and 20 naïve hearts of Sprague-Dawley male rats. The mRNA transcript encoding the Oprd1 and Oprk1, KOR and DOR proteins, distribution, and cellular localization were identified using RT-qPCR, Western blot, IHC, and IF, respectively.
Transcripts of mRNA encoding the Oprd1 and Oprk1 were detected in hearts of human and rats. Expression of Oprd1 (p=0.036) and Oprk1 (p = 0.004) was significantly reduced in transplanted hearts. In Western blot analysis, KOR and DOR levels of expression were significantly lowered (p=0.03, KOR; p=0.01, DOR) in HHT compared to naïve hearts in rats. Immunohistochemistry analysis demonstrated a lighter labeling on the distribution of DOR and KOR in heart transplants` tissue in both rats and human. In both species, dual labeling myocardial isoforms (KOR and DOR) co-localized in cardiomyocytes of transplant and control hearts.
These findings suggest that the down-regulation of DOR and KOR receptors in hearts transplant of both human and rats might have a possible increased susceptibility to ischemia-reperfusion injury.
Abstract 373: Regulation of Hypoxia by Chromatin Reader Protein Kinase C Binding Protein 1 (PRKCBP1)
Authors: Schunke Kathryn J , Shohet Ralph V 
Published: October 2019

PRKCBP1 (also known as RACK7 and Zmynd8) is a polyvalent chromatin reader known to cooperatively bind acetylated and methylated nucleosomes. Recently it has been shown to regulate transcription and cancer progression by coordinating histone methylation modifications affecting enhancer and promoter regions of genes. The role of PRKCBP1 in the cardiac myocardium is unexplored. Hypoxia-inducible factor 1α (HIF-1α) upregulation and stabilization is a common feature of both cancer and myocardial ischemia, promoting cellular functions such as proliferation, glucose metabolism and angiogenesis. Here we investigated the mechanism by which PRKCBP1 modulates the cardiac hypoxic response.
We hypothesize that PRKCBP1 inhibits the HIF-1 response in the hypoxic heart by reducing enhancer activity of HIF-1 target genes and altering availability of HIF-1 binding sites.

We have found that in transgenic mice with a mutation that increases HIF-induced expression of PRKCBP, the effect of induced oxygen-stable HIF is markedly diminished. These mice did not exhibit the typical HIF-1 over-expression phenotype of dilated vessels, increased heart size and reduced ventricular function. Semi-quantitative rtPCR analysis of mouse neonatal cardiomyocytes transfected with CMV-driven expression plasmids for PRKCBP1 and oxygen-stable HIF-1α showed striking reduction of multiple HIF-1 target genes such as PDK1 (45% reduction relative to Ehbp1) compared to the HIF-1α plasmid alone. RNAi mediated knockdown of PRKCBP1 removed this negative regulation (65% increase). Analysis of human PRKCBP1 and HIF-1α ChIP-seq data indicate that PRKCBP1 binds to the enhancer of 78% of HIF-1 regulated genes. ATAC-seq data suggest that PRKCBP1 affects genome-wide chromatin accessibility, with loci-specific modifications at numerous HIF-1 target genes, such as EGLN3. These data suggest that PRKCBP1 may be acting both by modulating enhancer activity
in cis
- to HIF-1 target genes and by preventing HIF-1 binding to hypoxia response elements of target genes.

We have discovered a new regulator of HIF-1 action that modifies the hypoxic response, likely through chromatin remodeling. This new form of regulation may modify the pathophysiology of ischemia and provide new targets for therapy.
Abstract 771: Identification of Pathological Pathways in Hypertrophic Cardiomyopathy via Single Nuclei RNA-Sequencing
Authors: Larson Amy , Bowditch Heather K , Rastegar Hassan , Chen Frederick , Rowin Ethan , Maron Marty , Huggins Gordon , Chin Michael T 
Published: October 2019

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease, is characterized by left ventricular hypertrophy, is often asymmetric, and is unexplained by secondary causes. The molecular and cellular basis of this asymmetric hypertrophy is unknown. HCM has been thought of as a disease of the sarcomere, with mutations in more than a dozen sarcomere-associated proteins correlated with HCM. These mutations, however, exhibit large phenotypic heterogeneity with little correlation between mutation and severity. Treatment of HCM is limited and thus, understanding what drives the disease at the molecular and cellular level could lead to novel treatment strategies.
Obstructive HCM is a severe form of the disease where the left ventricular outflow tract is obstructed. Patients with obstructive HCM often undergo septal myectomy surgery to remove the obstructive lesion. To understand the underlying mechanisms of obstructive HCM, we performed single nuclei RNA-sequencing on thousands of nuclei from 11 patients’ myectomy samples to determine the gene expression patterns in individual cells and identify the cell populations in those lesions. We used rejected donor hearts that do not exhibit any LV hypertrophy or have any major cardiovascular defects as control samples to compare the gene expression patterns in those cardiomyocytes to those in obstructive HCM lesions.
We performed principal component analysis and hierarchical clustering on the RNA expression counts to identify the different cell populations in each dataset, and looked for cell populations that were present across all HCM datasets. This analysis revealed distinct cardiomyocyte populations in obstructive lesions. Differential gene expression analysis among these clusters revealed a minority cardiomyocyte population in the obstructive lesions that exhibited a relatively normal gene expression pattern, while the majority cardiomyocyte cluster exhibited a shift in gene expression to genes involved in growth pathways. This abnormal cardiomyocyte population was absent in the control datasets. These findings imply that obstructive lesions seen in HCM may arise from abnormal growth of a subset of cardiomyocytes that could possibly be targeted by novel therapeutics.
Abstract 838: High Molecular Weight FGF2 Contributes to Pressure Overload Induced Systolic Dysfunction by a Mechanism Associated With Modulation of the NR1D1 Orphan Nuclear Receptor Expression
Authors: Koleini Navid , Nickel Barbara E , Nagalingam Raghu S , Landry Natalie M , Fandrich Robert R , Dixon Ian M , Czubryt Michael , Cattini Peter A , Kardami Elissavet 
Published: October 2019

Fibroblast growth factor 2 (FGF2) is implicated in normal cardiac development as well as cardiac pathophysiology; however, FGF2 exist as multiple high and low molecular weight isoforms. While endogenous low molecular weight FGF2 (Lo-FGF2) is cardioprotective during chronic stress, the more prevalent endogenous high molecular weight FGF2 (Hi-FGF2) is proposed to promote maladaptive cardiac remodeling. We have investigated the hypothesis that genetic elimination of Hi-FGF attenuates cardiac dysfunction in mice that have been subjected to pressure overload by transverse aortic constriction (TAC).
Two groups of male C57BL/6mice were compared: (1) Wild type (WT) mice, expressing Hi- and Lo-FGF2 (FGF[WT] mice); and (2) Hi-FGF2 knock-out mice, expressing only Lo-FGF2 (FGF[Lo] mice). Echocardiographic assessment of heart function and dimensions was done at baseline and then 4 and 8 weeks after TAC or sham surgery. FGF[WT] mice displayed a decline in systolic function compared to their corresponding sham animals at 4- and 8-weeks post-TAC, which was absent in the FGF[Lo] mice. Relative levels of B-type natriuretic peptide, a marker of cardiac pathology severity, were elevated in FGF[WT] but not FGF[Lo] mice compared to shams. Increased accumulation of the pro-cell death protein BCL2/adenovirus E1B 19 kDa protein-interacting protein-3 was more pronounced in the FGF(WT) compared to FGF(Lo) mice, post TAC. Microarray analysis of the whole transcriptome of hearts in FGF2[WT] and FGF2[Lo] mice indicated the pathway linked to circadian rhythm as a candidate for the most significant differentially regulated. Specifically, upregulation of the circadian rhythm master regulator, Nuclear Receptor Subfamily 1 Group D Member 1 (NR1D1), was validated by qPCR and protein immunoblotting in FGF[Lo] mice versus downregulation of NR1D1in FGF[WT] mice post-TAC, when compared to their sham operated littermates.
Taken together these studies suggest that expression of Hi-FGF2 contributes to cardiac systolic dysfunction in left ventricular pressure overloaded WT mice by downregulation of Nr1D1, post-TAC.
Abstract 930: Aerobic Dose Intensity and the Human Exercise Plasma Proteome
Authors: Guseh James S , Churchill Timothy W , Yeri Ashish , Lo Claire , Brown Marcel , Rosenzweig Anthony , Baggish Aaron 
Published: October 2019

Aerobic exercise confers myriad benefits to human health but the mechanism by which it does so remain incompletely understood. We hypothesize that exercise works in part through circulating protein signaling. Healthy adult men (n, 12) participated in treadmill running sessions at both low (6 mph) and high intensity (maximal effort). We used pre- and post-exercise plasma and a high-throughput aptamer-based assay (SomaScan) to examine the acute impact of exercise on the plasma proteome.
Acute aerobic exercise consistently alters the resting plasma proteome in an intensity-dependent fashion. Of 1,305 proteins assayed 184 (14%) and 598 (46%) change at low and high intensity respectively (FDR p < 0.05). 159 protein species (12%) are common to both intensities. Gene ontology analysis revealed enrichment of pathways associated with leukocyte chemotaxis and chylomicron metabolism at low intensity and Wnt signaling, neuronal axonogenesis, and nitric oxide metabolism pathways at high intensity. We used human sequencing data from the GTEX Consortium (Broad, Cambridge MA) to computationally infer the sources of increasing proteins and found major contributions from the cardiovascular, gastrointestinal, and nervous systems. We identified 43 cis-SNPs that approximate the upregulated proteomic response to acute exercise and used Mendelian randomization to infer a causal relationship between the exercise proteome and decreased muscle wasting in a UK Biobank cohort.
Although guidelines present low and high intensity exercise as equivalent alternatives for health, these data suggest that distinct exercise intensities might offer common and distinct exercise benefits.