bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel circulating microRNAs in advanced heart failure by next‐generation sequencing
Authors: Galluzzo Alessandro , Gallo Simona , Pardini Barbara , Birolo Giovanni , Fariselli Piero , Boretto Paolo , Vitacolonna Annapia , Peraldo‐Neia Caterina , Spilinga Martina , Volpe Alessandra , Celentani Dario , Pidello Stefano , Bonzano Alessandro , Matullo Giuseppe , Giustetto Carla , Bergerone Serena , Crepaldi Tiziana 
Published: May 2021

AbstractAimsRisk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF‐specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients.Methods and resultsWe performed a global miRNome analysis using next‐generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real‐time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty‐two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR‐210‐3p, miR‐22‐5p, miR‐22‐3p, miR‐21‐3p, miR‐339‐3p, and miR‐125a‐5p) significantly correlated with HF biomarkers, among which N‐terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR‐125a‐5p, miR‐10b‐5p, and miR‐9‐5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio‐HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82).ConclusionsThis discovery study has characterized, for the first time, the advanced chronic HF‐specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations.
Predictors and prognosis of right ventricular function in pulmonary hypertension due to heart failure with reduced ejection fraction
Authors: Schmeißer Alexander , Rauwolf Thomas , Groscheck Thomas , Fischbach Katharina , Kropf Siegfried , Luani Blerim , Tanev Ivan , Hansen Michael , Meißler Saskia , Schäfer Kerstin , Steendijk Paul , Braun‐Dullaeus Ruediger C. 
Published: May 2021

AbstractAimsFailure of right ventricular (RV) function worsens outcome in pulmonary hypertension (PH). The adaptation of RV contractility to afterload, the RV‐pulmonary artery (PA) coupling, is defined by the ratio of RV end‐systolic to PA elastances (Ees/Ea). Using pressure–volume loop (PV‐L) technique we aimed to identify an Ees/Ea cut‐off predictive for overall survival and to assess hemodynamic and morphologic conditions for adapted RV function in secondary PH due to heart failure with reduced ejection fraction (HFREF).Methods and resultsThis post hoc analysis is based on 112 patients of the prospective Magdeburger Resynchronization Responder Trial. All patients underwent right and left heart echocardiography and a baseline PV‐L and RV catheter measurement. A subgroup of patients (n = 50) without a pre‐implanted cardiac device underwent magnetic resonance imaging at baseline. The analysis revealed that 0.68 is an optimal Ees/Ea cut‐off (area under the curve: 0.697, P < 0.001) predictive for overall survival (median follow up = 4.7 years, Ees/Ea ≥ 0.68 vs. <0.68, log‐rank 8.9, P = 0.003). In patients with PH (n = 76, 68%) multivariate Cox regression demonstrated the independent prognostic value of RV‐Ees/Ea in PH patients (hazard ratio 0.2, P < 0.038). Patients without PH (n = 36, 32%) and those with PH but RV‐Ees/Ea ≥ 0.68 showed comparable RV‐Ees/Ea ratios (0.88 vs. 0.9, P = 0.39), RV size/function, and survival. In contrast, secondary PH with RV‐PA coupling ratio Ees/Ea < 0.68 corresponded extremely close to cut‐off values that define RV dilatation/remodelling (RV end‐diastolic volume >160 mL, RV‐mass/volume‐ratio ≤0.37 g/mL) and dysfunction (right ventricular ejection fraction <38%, tricuspid annular plane systolic excursion <16 mm, fractional area change <42%, and stroke‐volume/end‐systolic volume ratio <0.59) and is associated with a dramatically increased short and medium‐term all‐cause mortality. Independent predictors of prognostically unfavourable RV‐PA coupling (Ees/Ea < 0.68) in secondary PH were a pre‐existent dilated RV [end‐diastolic volume >171 mL, odds ratio (OR) 0.96, P = 0.021], high pulsatile load (PA compliance <2.3 mL/mmHg, OR 8.6, P = 0.003), and advanced systolic left heart failure (left ventricular ejection fraction <30%, OR 1.23, P = 0.028).ConclusionsThe RV‐PA coupling ratio Ees/Ea predicts overall survival in PH due to HFREF and is mainly affected by pulsatile load, RV remodelling, and left ventricular dysfunction. Prognostically favourable coupling (RV‐Ees/Ea ≥ 0.68) in PH was associated with preserved RV size/function and mid‐term survival, comparable with HFREF without PH.
Early follow‐up at outpatient care after discharge improves long‐term heart failure readmission rate and prognosis
Authors: Matsukawa Ryuichi , Masuda Seigo , Matsuura Hirohide , Nakashima Hiroka , Ikuta Hiroshi , Okabe Kousuke , Okahara Arihide , Kawai Shunsuke , Tokutome Masaki , Tobushi Tomoyuki , Mukai Yasushi 
Published: May 2021

AbstractAimsIt has been reported that congestive heart failure (CHF) readmission has not decreased in the last decade. It is also reported that CHF readmission is likely to occur shortly after discharge. We investigated whether an early follow‐up at outpatient care within 2 weeks after discharge affects the long‐term readmission rate and prognosis.Methods and resultsWe reviewed consecutive 1002 patients admitted to our hospital due to CHF. Two‐hundred and fifty‐nine patients who died in‐hospital or were transferred to another hospital or readmitted within 2 weeks were excluded and 743 of discharged patients were analysed. We extracted contributing variables associated with heart failure (HF) readmission and the composite adverse outcome (all cause death or HF readmissions) by univariate and multivariate analysis. Multivariate analysis showed that the early follow‐up was independently associated with freedom from HF readmission and the composite outcome. We divided these patients into two groups, with/without early follow‐up and performed a propensity score‐matching analysis (n = 259 each). HF readmission during 2 year follow‐up was significantly less in the early follow‐up group [P = 0.02, hazard ratio (HR) = 0.647, 95% confidence interval (CI) = 0.447–0.935] as well as the composite outcome was less in the early follow‐up group (P = 0.01, HR = 0.643, 95% CI = 0.456–0.908). Medication adjustments were done in only 33.2% of the patients. Rates of HF readmissions were comparable regardless of whether or not medication adjustment was done at the early follow‐up (P = 0.505, HR = 1.208, 95% CI = 0.692–2.106).ConclusionsThe present study demonstrates that an early follow‐up approach after discharge in CHF patients may improve the long‐term prognosis. These results may not depend on medication adjustment but rather on modifying patient factors early after discharge.
Immobilized Ru‐Pincer Complexes for Continuous Gas‐Phase Low‐Temperature Methanol Reforming‐Improving the Activity by a Second Ru‐Complex and Variation of Hydroxide Additives
Authors: Schwarz Christian H. , Kraus Dominik , Alberico Elisabetta , Junge Henrik , Haumann Marco 
Published: May 2021

AbstractRu‐pincer complexes were immobilized as supported liquid phase (SLP) materials to allow the methanol reforming reaction as continuous gas phase process. Under reaction conditions, the liquid phase forms from the hydroxide coating. Several hydroxides were screened and CsOH showed highest activity compared to the standard KOH coating. The well‐known Ru‐pincer complex carbonylchlorohydrido [bis(2‐di‐i‐propylphosphinoethyl)amine]ruthenium(II) is limited in catalyzing the final step of the methanol reforming. Addition of a second complex, having a methylated backbone in the pincer‐ligand, could overcome these limitations. Significant enhancement of the overall catalytic activity was observed.
Patient reported outcome measures in trigeminal neuralgia – A systematic review of psychometric performance
Authors: Venda Nova Carolina , Zakrzewska Joanna M. , R. Baker Sarah , Ni Riordain Richeal 
Published: May 2021

AbstractBackgroundTrigeminal neuralgia (TN) is a rare condition for which there are multiple treatment options available. To date, there has been difficulty in comparing the outcomes of treatment due to the variety of patient‐reported outcome measures (PROMs) and their inadequate psychometric testing. The aim of this review was to assess the psychometric properties of PROMs used to date in TN and make recommendations for their use in future studies.MethodsFive electronic databases (MEDLINE, EMBASE, CINAHL Plus, PsycINFO, Health and Psychosocial Instruments) were searched for studies assessing the development of PROMs or their psychometric properties in TN studies. The records obtained were assessed independently by two reviewers for their methodological quality, following guidance from the Consensus‐based Standards for the selection of Health Measurement Instruments (COSMIN).ResultsSix studies were identified and information on five PROMs (Brief Pain Inventory Facial (BPI‐F), Visual Analogue Scale (VAS), Barrow Neurology Institute Pain Scale (BNI‐PS), Penn Facial Pain Scale‐Revised (Penn‐FPS‐R) and Trigeminal Neuralgia Quality of Life Score) were retrieved. The Penn‐FPS‐R demonstrated moderate quality evidence for sufficient content validity. The BPI‐F showed moderate evidence for sufficient internal consistency and structural validity but low evidence for inconsistent content validity. The Trigeminal Neuralgia Quality of Life score showed very low‐quality evidence for insufficient content validity, structure validity and responsiveness. No evidence was found on the assessment of any psychometric properties of the VAS and BNI‐PS in TN.ConclusionThere is limited evidence of the psychometric performance of patient‐reported outcomes for TN and recommendations for their inclusion in future studies cannot be made. The validation of PROMs in TN studies should be a priority in this field of research.SignificanceThis review highlights the knowledge gap in the field of psychometrics of patient reported outcomes measures in the field of TN. Given the unavailability of an objective outcome measure for pain or health related quality of life, psychometrically sound PROMs are essential for assessing medical and surgical treatment outcomes in TN.
The combustion behavior of epoxy‐based multifunctional electrolytes
Authors: Shirshova Natasha , Rogaume Thomas , Najmi Hussain , Poisson Marc 
Published: May 2021

SummaryMultifunctional or structural electrolytes are characterized by ionic conductivity high enough to be used in the electrochemical devices and mechanical performance suitable for the structural applications. Preliminary insights are provided into the combustion behavior of structural bi‐continuous electrolytes based on bisphenol A diglycidyl ether (DGEBA), synthesized using the techniques of reaction induced phase separation and emulsion templating. The effect of the composition of the structural electrolytes and external heat flux on the behavior of the formulations were studied using a cone calorimeter with gases formed during testing analyzed using FTIR. The composition of the formulations investigated was changed by varying the type and amount of the ion conductive part of the bi‐continuous electrolyte. Two ionic liquids, 1‐ethyl‐3‐methylimidazolium bis(fluorosulfonyl)imide (EMIM‐TFSI) and 1‐butyl‐3‐methylimidazolium tetrafluoroborate (BMIM‐BF4), as well as a deep eutectic solvent (DES) based on ethylene glycol and choline chloride, were used. The results obtained confirm that time to ignition, heat release rate (HRR), total mass loss, as well as the composition of the gases released during tests depend on the composition of the formulations. Addition of liquid electrolyte is found to reduce the time to ignition by up to 10% and the burning time by between 28% and 60% with the added benefit of reducing the HRR by at least 34%. Gaseous products such as CO2, CO, H2O, CH4, C2H2, N2O, NO, and HCN were detected for all formulations with the gases SO2, NH3, HCl, C2H4, and NH3 found to be for certain formulations only.
Pogostemon cablin extract as an anticancer agent on human acute myeloid leukemia
Authors: Chien Ju‐Huei , Huang Xiao‐Fan , Lai Wen‐Lin , Chang Kai‐Fu , Li Chia‐Yu , Chen Szu‐Yin , Wu Chun‐Yu , Li Kuan‐Ying , Tsai Nu‐Man 
Published: May 2021

AbstractPogostemon cablin has been indicated to treat many kinds of diseases and the progression of cancers, such as colorectal cancer. However, the effects of P. cablin extract (PPa extract) against acute myeloid leukemia have not been investigated. Thus, this study explored the anticancer potential of PPa extract and its mechanism in HL‐60 cells. The MTT assay results showed that PPa extract significantly inhibited the proliferation of HL‐60 cells in a dose‐dependent manner and affected cell morphology, causing cell shrinkage and the formation of debris. PPa extract blocked cell cycle progression at the G0/G1 phase in a dose‐ and time‐dependent manner and induced cell apoptosis, as shown by the observation of DNA fragments and apoptotic bodies. Furthermore, PPa extract caused the accumulation of a population of cells at G0/G1 phase via a reduction in p‐Rb, increasing p21 expression, and downregulating cell cycle regulator protein expression. Then, PPa extract was found to activate the extrinsic and intrinsic apoptosis pathways, leading to cell death. These data demonstrated that PPa extract exerted inhibitory activity and triggered cell apoptosis in HL‐60 cells and that PPa extract might be a chemopreventive agent for cancer therapy.
MLH1 epimutation is a rare mechanism for Lynch syndrome: A case report and review of the literature
Authors: Zyla Roman , Graham Tracy , Aronson Melyssa , Velsher Lea , Mrkonjic Miralem , Turashvili Gulisa 
Published: May 2021

AbstractEndometrial carcinoma is one of the prototypical malignancies associated with Lynch syndrome, an inherited cancer syndrome most commonly caused by germline mutations in DNA mismatch repair (MMR) genes, although rare alternative mechanisms also exist. In this report, we describe a patient first diagnosed with colorectal cancer at age 33, then vulvar squamous cell carcinoma, facial sebaceous adenoma/sebaceoma, and finally endometrial carcinoma at age 52. All tumors were MLH1/PMS2‐deficient by immunohistochemistry, and MLH1 promoter methylation was identified in the endometrial cancer. Germline MLH1 testing was negative for pathogenic variants, but she was subsequently diagnosed with Lynch syndrome secondary to a germline monoallelic constitutional epimutation of the MLH1 promoter. Identification of patients displaying a Lynch syndrome phenotype but lacking germline MMR mutations is important to avoid delays in the diagnosis of Lynch syndrome as well as the initiation of appropriate cancer screening and genetic counseling.
Individual‐based morphological brain network organization and its association with autistic symptoms in young children with autism spectrum disorder
Authors: He Changchun , Cortes Jesus M. , Kang Xiaodong , Cao Jing , Chen Heng , Guo Xiaonan , Wang Ruishi , Kong Lingyin , Huang Xinyue , Xiao Jinming , Shan Xiaolong , Feng Rui , Chen Huafu , Duan Xujun 
Published: May 2021

AbstractIndividual‐based morphological brain networks built from T1‐weighted magnetic resonance imaging (MRI) reflect synchronous maturation intensities between anatomical regions at the individual level. Autism spectrum disorder (ASD) is a socio‐cognitive and neurodevelopmental disorder with high neuroanatomical heterogeneity, but the specific patterns of morphological networks in ASD remain largely unexplored at the individual level. In this study, individual‐based morphological networks were constructed by using high‐resolution structural MRI data from 40 young children with ASD (age range: 2–8 years) and 38 age‐, gender‐, and handedness‐matched typically developing children (TDC). Measurements were recorded as threefold. Results showed that compared with TDC, young children with ASD exhibited lower values of small‐worldness (i.e., σ) of individual‐level morphological brain networks, increased morphological connectivity in cortico‐striatum‐thalamic‐cortical (CSTC) circuitry, and decreased morphological connectivity in the cortico‐cortical network. In addition, morphological connectivity abnormalities can predict the severity of social communication deficits in young children with ASD, thus confirming an associational impact at the behavioral level. These findings suggest that the morphological brain network in the autistic developmental brain is inefficient in segregating and distributing information. The results also highlight the crucial role of abnormal morphological connectivity patterns in the socio‐cognitive deficits of ASD and support the possible use of the aberrant developmental patterns of morphological brain networks in revealing new clinically‐relevant biomarkers for ASD.
Hepatic Small Ubiquitin‐Related Modifier (SUMO)–Specific Protease 2 Controls Systemic Metabolism Through SUMOylation‐Dependent Regulation of Liver–Adipose Tissue Crosstalk
Authors: Liu Yang , Dou Xin , Zhou Wei‐yu , Ding Meng , Liu Ling , Du Ruo‐qi , Guo Liang , Qian Shu‐wen , Tang Yan , Yang Qi‐qi , Pan Dong‐ning , Li Xiao‐ying , Lu Yan , Cheng Jin‐ke , Tang Qi‐qun 
Published: May 2021

Background and Aims
NAFLD, characterized by aberrant triglyceride accumulation in liver, affects the metabolic remodeling of hepatic and nonhepatic tissues by secreting altered hepatokines. Small ubiquitin‐related modifier (SUMO)–specific protease 2 (SENP2) is responsible for de‐SUMOylation of target protein, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic metabolism remains unclear.

Approach and Results
We found that SENP2 was the most dramatically increased SENP in the fatty liver and that its level was modulated by fed/fasted conditions. To define the role of hepatic SENP2 in metabolic regulation, we generated liver‐specific SENP2 knockout (Senp2‐LKO) mice. Senp2‐LKO mice exhibited resistance to high‐fat diet–induced hepatic steatosis and obesity. RNA‐sequencing analysis showed that Senp2 deficiency up‐regulated genes involved in fatty acid oxidation and down‐regulated genes in lipogenesis in the liver. Additionally, ablation of hepatic SENP2 activated thermogenesis of adipose tissues. Improved energy homeostasis of both the liver and adipose tissues by SENP2 disruption prompted us to detect the hepatokines, with FGF21 identified as a key factor markedly elevated in Senp2‐LKO mice that maintained metabolic homeostasis. Loss of FGF21 obviously reversed the positive effects of SENP2 deficiency on metabolism. Mechanistically, by screening transcriptional factors of FGF21, peroxisome proliferator–activated receptor alpha (PPARα) was defined as the mediator for SENP2 and FGF21. SENP2 interacted with PPARα and deSUMOylated it, thereby promoting ubiquitylation and subsequent degradation of PPARα, which in turn inhibited FGF21 expression and fatty acid oxidation. Consistently, SENP2 overexpression in liver facilitated development of metabolic disorders.

Conclusions
Our finding demonstrated a key role of hepatic SENP2 in governing metabolic balance by regulating liver–adipose tissue crosstalk, linking the SUMOylation process to metabolic regulation.
Reduction of cycles of bendamustine plus rituximab therapy in the cases with good response for indolent B‐cell lymphomas
Authors: Takezaki Toshiaki , Nakazaki Kumi , Toyama Kazuhiro , Matsuda Kensuke , Kogure Yasunori , Chiba Akira , Nakamura Fumihiko , Honda Akira , Kurokawa Mineo 
Published: May 2021

AbstractBendamusutine plus rituximab (BR) regimen is one of the standard regimens for indolent B‐cell lymphomas, yet the possibility of reduction of cycles of BR therapy without compromising therapeutic effects is not still uncovered. We retrospectively surveyed 57 cases including 40 follicular lymphoma cases who underwent BR regimen in our institute. The overall response (OR) rate and complete response (CR) rate were 86.0% (95% confidential interval (CI), 74.2–93.7) and 54.4% (40.7–67.6), respectively. Five‐year overall survival (OS) and 5‐years progression‐free survival (PFS) were 76.8% and 45.7%, respectively. We then grouped the patients by the number of administered cycles of BR regimen. PFS was significantly longer in 41 cases of the later cessation group (cycle 4–6) than in 16 cases of the earlier cessation group (cycle 1–3) (p = 0.012, 5‐years PFS; 46.8% vs. 35.2%, respectively), and both of OR and CR rate of the former was better than the latter (OR rate; 95.1% vs. 62.5%, p < 0.01, CR rate; 61.4% vs. 31.3%, p = 0.04). Interestingly PFS of twenty‐one (36.8%) cases receiving just 4 cycles was longer than that of 20 cases who received five or 6 cycles (p < 0.01, 5‐years PFS; 71.8% vs. 23.2%, respectively). Focusing on the group of four cycles, the 12 case with CR revealed longer PFS than seven cases with partial response (PR), and median PFS was not reached in CR cases and 16.9 months in the PR cases (p < 0.01). These results suggest that four cycles at least should be administered if possible, and the outcome of the patients who discontinued BR after four cycles was not inferior to that of the cases who received five or six cycles. In conclusion, discontinuation after four cycles may be permissible in some cases with complete response to BR regimen.
Healthcare systems and Covid19: Lessons to be learnt from efficient countries
Authors: Ordu Muhammed , Kirli Akin Hediye , Demir Eren 
Published: May 2021

AbstractBackgroundThe novel coronavirus is rapidly spreading over the world and puts the health systems of countries under intense pressure. High hospitalization levels due to the pandemic outbreak have caused the intensive care units to work above capacity.PurposeA data envelopment analysis (DEA) based modelling approach was developed to evaluate the effectiveness of regions (i.e. city, country or clinical commissioning groups) against the pandemic outbreak. The objective is to enable related authorities better manage the struggle against the outbreak and put in place the emergency action plans immediately.Methodology/ApproachDEA method was used to measure the efficiency scores of countries. Super efficiency DEA method was also applied to countries based on the level of efficiencies they have achieved. Sixteen countries were selected that have been facing with Covid19 pandemic outbreak for at least 5 consecutive weeks after their 100th confirmed case.ResultsA total of 80 DEA models were developed, that is, 16 DEA models for each week. The percentage of efficient countries decreased dramatically over time, from 43.75% in the first week to 25% in the fifth week. Unlike most European countries, China and South Korea increased their effectiveness after first week of implementing all the necessary measures.ConclusionThis study sheds light into better understanding the effectiveness of policies adopted by countries and their management strategy in dealing with Covid19 pandemic. Our model will enable political leaders to identify inadequate policies as quickly as possible and learn from their peers for more effective decisions.