bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Palindrome Dual PPARγ‐GPR40 Agonists for Treating Type 2 Diabetes
Authors: Rodríguez‐Luévano Ana , Almanza‐Pérez Julio C. , Ortiz‐Andrade Rolffy , Lara‐González Samuel , Santillán Rosa , Navarrete‐Vázquez Gabriel , Giacoman‐Martínez Abraham , Lazzarini‐Lechuga Roberto C. , Bautista Elihú , Hidalgo‐Figueroa Sergio 
Published: September 2024

AbstractThis work describes a first attempt of palindromic design for dual compounds that act simultaneously on peroxisome proliferator‐activated receptor gamma (PPARγ) and G‐protein‐coupled receptor 40 (GPR40) for the treatment of type 2 diabetes. The compounds were synthesized by multi‐step chemical reactions and the relative mRNA expression levels of PPARγ, GPR40, and GLUT‐4 were measured in cultured C2 C12 muscle cells and RIN‐m5 f β‐pancreatic cells. In addition, insulin secretion and GLUT‐4 translocation were measured. Compound 2 displayed a moderate increase in the mRNA expression of PPARγ and GPR40. However, the translocation of the GLUT‐4 transporter was 400 % with a similar effect to pioglitazone. The in vivo effect of compound 2 was determined at 25 mg/kg single dose using a normoglycemic and non‐insulin dependent diabetes mellitus (NIDDM) rat models. Compound 2 showed basal plasma glucose in diabetic rats with feed intake, which is associated with the moderate release of insulin measured in cells. Surprisingly, the glucose does not decrease in normoglycemic rats. Compound 2 maintained significant interactions with the GPR40 and PPARγ receptors during molecular dynamics. Altogether, the results demonstrate that compound 2, with a palindromic design, simultaneously activates PPARγ and GPR40 receptors without inducing hypoglycemia.
Role of the Quantum Interactions in H2 Adsorption on Late Transition Metal Chelated Linkers of Covalent Organic Frameworks
Authors: Joshi Himani , Pakhira Srimanta 
Published: September 2024

AbstractTransition metal (Tm) chelation is an effective strategy to achieve optimal binding enthalpy (▵H) of H2‐adsorption in the linkers of covalent organic frameworks (COFs). The first principle‐based DFT method has been implemented to determine the H2 adsorption in nine organic linkers chelated with transition metal atoms from Cr to Zn. The obtained range of binding enthalpy for single H2 adsorbed on the pure and chelated complexes is −7 to −20 kJ/mol, which is required for onboard H2 storage. The Linker‐3 chelated with Ni (II) metal exhibits the most favorable binding enthalpy of approximately −18.72 kJ/mol for the single adsorbed H2 molecule, which falls within the physisorption range. Some of the complexes have shown the binding enthalpy range between physisorption and chemisorption, i. e., in that case, H2 binds via Kubas interactions. However, physisorption‐based complexes are preferable to others because physisorption is a reversible process with rapid kinetics. This study reveals that the dispersion, polarization, and electrostatic interactions mainly contribute to the binding enthalpy of H2 adsorption. Molecular surface potential analysis verifies the origin of induced dipole moment in the H2 molecule, which enhances the hydrogen adsorption in transition metal chelated COFs.
Enhanced active disturbance rejection speed controller for permanent magnet synchronous motors using virtual friction feedback technique
Authors: Dong Dingfeng , Huang Wenxin , Zhu Shanfeng , Bu Feifei 
Published: September 2024

AbstractActive disturbance rejection controller (ADRC) has been widely promoted in permanent magnet synchronous motor (PMSM) drives for its simple design and remarkable anti‐disturbance characteristics. To further improve the control performance, a variety of advanced ADRC schemes have been proposed in recent years. However, the majority of them focused on constructing more complicated extended state observers (ESOs) while ignoring the utilization of state feedback. Motivated by the above issue, this article proposes an enhanced virtual friction ADR speed controller (VFADRC). It is distinguished by the simpler structure compared with other ADRC schemes. Besides, the introduced zero in disturbance rejection function of VFADRC contributes to the preferable anti‐disturbance response. Moreover, the enhanced configuration of VFADRC proposed in the article further improves the speed dynamics and robustness to inertia variations. Both the theoretical analysis and experimental results validate the excellent performance of the proposed ADR controller.
Prediction factors and models for chronic kidney disease in type 2 diabetes mellitus: A review of the literature
Authors: Yang Yan , Yang Bixia , Wang Bin , Zhou Hua , Yang Min , Liu Bicheng 
Published: September 2024

AbstractDiabetes mellitus (DM) has become a major chronic disease seriously affecting human health. Type 2 diabetes mellitus (T2DM) accounts for about 90% of DM patients, which is the largest type. Approximately 25–35% of T2DM patients develop kidney disease, which not only impacts the survival rate and quality of life but also, to the family and society, are of great economic burden. Early identification of high‐risk T2DM patients with kidney disease is crucial for initiating targeted prevention and treatment measures in time to reduce or delay the occurrence and progression of diabetic kidney disease. Previous studies have identified a variety of clinical predictors for the progression of renal function in T2DM patients, including proteinuria, estimated glomerular filtration rate, blood glucose, blood pressure, serum uric acid, dyslipidemia, obesity, smoking, duration of DM, age, gender, race, family history of DM, and diabetic retinopathy. Clinical prediction models based on conventional clinical indicators are instrumental in evaluating the risk of kidney disease in T2DM patients, assisting in patient risk stratification. This article systematically reviews the clinical prediction factors and prediction models associated with the progression of renal function in T2DM patients, providing a comprehensive and current reference for improved clinical assessment of the risk of renal function progression.
PRP, Exosomes, and Stem Cells: An International Perspective
Authors: Singh Nupur , Brown Angela N. , Gold Michael H. 
Published: September 2024

ABSTRACTBackgroundRegenerative medicine is a novel, developing field centered on efforts to repurpose the body's own molecular makeup to target specific problems. Specifically, the use of stem cells, platelet‐rich plasma, and exosomes is rapidly expanding. Internationally, there remain different guidelines and a variety of medical uses, encouraging an exploration into the medical and cosmetic benefits offered.AimsThis study aims to investigate current literature on the international perspectives of PRP, stem cells, and exosomes to present a global review on how these are obtained and utilized.MethodsA literature search was conducted on PubMed reviewing PRP, exosomes, and stem cells, among other related topics, and their applications in medical, pharmacologic, and dermatologic fields. Research produced by various global regions was examined to identify similarities and differences.ResultsStem cells have been successfully implemented in the oncology and dermatology realms as a result of their plasticity and ability to quickly replicate and divide. Platelet‐rich plasma is of strong interest due to platelets' extracellular vesicles and their unmatched abilities. Exosomes are actively being studied in the fields of neurology and rheumatology, among others. International guidelines are reviewed based on regulations of these materials. Potential ethical barriers of isolation and source utilization are explored.ConclusionsThe perspectives and findings considered here stress the potential expanding uses of PRP, stem cells, and exosomes on a global scale. We highlight the need for further clinical studies and international collaboration among varying guidelines to best utilize these tools in the field of dermatology and medicine.
Enhanced Insulin Secretion Through Upregulation of Transcription Factors by Hydroalcoholic Extract of Securigera securidaca Seeds in Diabetic Animal Model
Authors: Hasani Maryam , Abbasi‐Oshaghi Ebrahim , Khomari Fatemeh , Kiani Bahar , Mirzaei Fatemeh , Alipourfard Iraj , Khodadadi Iraj , Tayebinia Heydar , Babaei Mohammad , Alizadeh‐Fanalou Shahin , Bahreini Elham 
Published: September 2024

ABSTRACTAimIn previous studies, the researchers observed an increase in insulin secretion in STZ‐treated diabetic rats following treatment with the hydroalcoholic extract of Securigera securidaca (HESS) seeds. This study focuses on the relationship between the antioxidant properties of HESS with changes in diabetic pancreatic tissue and the gene expression of factors that impact insulin secretion.MethodsIn this controlled experimental study, three varying doses of HESS were administered to three groups of diabetic rats induced by STZ. Oxidative stress indicators like total antioxidant capacity (TAC), total oxidant status (TOS) and malondialdehyde were assessed in both pancreatic and liver tissues. Pancreatic histology was studied post‐haematoxylin staining. Insulin and FGF21 levels in the blood were measured using the ELISA method. The expression of Nrf2 and FGF21 genes in the pancreas and liver, along with MafA and PDX‐1 genes in the pancreas, was quantified using real‐time PCR.ResultsThe administration of HESS in varying doses led to a dose‐dependent rise in blood insulin levels and a decrease in blood glucose levels and oxidative stress. By reducing oxidative stress, HESS treatment lowered the heightened levels of NRF2 and FGF21 in the liver and pancreas of diabetic rats, improving pancreatic tissue health. As oxidative stress decreased, the expression of MafA and PDX1 genes in the pancreas approached levels seen in healthy rats.ConclusionHESS elicits an increase in insulin secretion through the mitigation of oxidative stress and tissue damage, as well as the modulation of gene expression related to the insulin transcription factors PDX‐1 and MafA.
Myocardial viability assessment during Impella support with 18‐fluorodesoxyglucose PET imaging
Authors: Baldetti Luca , Busnardo Elena , Pazzanese Vittorio , Ricchetti Gianluca , Barone Giuseppe , Sacchi Stefania , Calvo Francesco , Gramegna Mario , Pieri Marina , Ingallina Giacomo , Camici Paolo Guido , Ajello Silvia , Scandroglio Anna Mara 
Published: September 2024

AbstractFormal assessment of myocardial viability (MV) is challenging in acute myocardial infarction‐related cardiogenic shock (AMI‐CS) patients receiving Impella mechanical circulatory support, as the cardiac magnetic resonance gold standard technique is not feasible due to the metallic components of the device. 18‐fluorodesoxyglucose metabolic myocardial positron emission tomography (18FDG‐PET) may represent a valid and feasible alternative to obtain semi‐quantitative and objective evidence of MV during Impella support. We hereby report the first series of sequential AMI‐CS patients who received 18FDG‐PET scanning to assess MV during Impella support to demonstrate the safety and feasibility of this approach. In this cohort no adverse events occurred during 18FDG‐PET scans, and all images were of excellent quality. This study provides a pragmatic guidance on how to perform this imaging modality during Impella support and finally confirms the safety and feasibility of this advanced imaging method also in this vulnerable cohort of patients.
Correlation between coronary calcification and cardiac structure in non‐dialysis patients with chronic kidney disease
Authors: Rao Siyi , Weng Mengjie , Lian Ruoshan , Zhuo Yongjie , Lin Jiaqun , You Danyu , Cui Jiong , Chen Yi , Wan Jianxin 
Published: September 2024

AbstractAimsWe aim to explore the correlation between coronary artery calcification (CAC) score (CACS) and cardiac structure and function in chronic kidney disease (CKD) patients, create a clinical prediction model for severe CAC associated with cardiac ultrasound indexes.Methods and resultsThe study included 178 non‐dialysis CKD patients who underwent CACS testing and collected general information, serological indices, cardiac ultrasound findings and follow‐up on renal function, heart failure (HF) manifestations and re‐hospitalization. The mean age of participants in the study cohort was 67.4 years; 59% were male, and 66.9% of patients had varying degrees of comorbid CAC. CKD patients with CACS > 100 were older, predominantly male and had a higher proportion of smoking, diabetes and hypertension (P < 0.05) compared with those with CACS = 0 and 0 < CACS ≤ 100, and had higher brain natriuretic peptide, serum magnesium and fibrinogen levels were also higher (P < 0.05). CACS was positively correlated with left atrial inner diameter (LAD), left ventricular end‐diastolic inner diameter (LVDd), left ventricular volume at diastole (LVVd), output per beat (SV) and mitral orifice early diastolic blood flow velocity/early mitral annular diastolic myocardial motion velocity (E/e) (P < 0.05). We tested the associations between varying degrees of CAC and HF and heart valve calcification using multivariable‐adjusted regression models. The risk of HF in patients with severe CAC was about 1.95 times higher than that in patients without coronary calcification, and the risk of heart valve calcification was 2.46 times higher than that in patients without coronary calcification. Heart valve calcification and HF diagnosis, LAD and LVDd are essential in predicting severe CAC. During a mean follow‐up time of 18.26 ± 10.17 months, 65 (36.52%) patients had a composite renal endpoint event, of which 36 (20.22%) were admitted to renal replacement therapy. Patients with severe CAC had a higher risk of progression of renal function, re‐admission due to cardiovascular and renal events and more pronounced symptoms of HF (P < 0.05).ConclusionsThere is a correlation between CACS and cardiac structure and function in non‐dialysis CKD patients, which may mainly involve abnormalities in left ventricular structure and cardiac diastolic function. CAC may affect renal prognosis and quality of survival in CKD patients. Based on clinical information, HF, valvular calcification status and indicators related to left ventricular hypertrophy can identify people at risk for severe CAC.
Prevalence and characteristics of upfront diuretic resistance in acute heart failure: The P‐Value‐AHF study
Authors: Baumberger Julia , Dinges Sabine , Lupi Eleonora , Wolters Thomas , Stüssi‐Helbling Melina , Cippà Pietro E. , Bellasi Antonio , Huber Lars C. , Arrigo Mattia 
Published: September 2024

AbstractAimsDiuretic resistance (i.e., insufficient diuretic and natriuretic response to an appropriate dose of intravenously administered loop diuretic) is a major cause of insufficient decongestion in acute heart failure (AHF). Early assessment of diuretic and natriuretic response already after the first administration of loop diuretic is currently recommended, but few data exist on the prevalence and characteristics of upfront diuretic resistance in AHF. The aim of this sub‐study of the P‐Value‐AHF randomized clinical trial was to investigate the prevalence and characteristics of upfront diuretic resistance in patients presenting with AHF in the emergency department (ED).MethodsConsecutive patients presenting with a clinical diagnosis of AHF, ≥1 sign of congestion, and NT‐proBNP >1000 ng/L between February and June 2024 were prospectively screened. Loop diuretics were administered per protocol: 40 mg furosemide i.v. in diuretic‐naïve patients and those on oral torasemide <40 mg, 80 mg furosemide i.v. in patients on oral torasemide ≥40 mg daily. Urine output was measured over the following 2 h and in patients with urine volume <300 mL, urine sodium concentration was additionally measured in a spot sample. Upfront diuretic resistance was defined as urine volume <300 mL in 2 h and urine sodium concentration <70 mmol/L.ResultsFrom a total of 127 screened AHF patients presenting to the ED, 17 subjects were excluded after denial of informed consent and 17 could not be treated according to the protocol due to one or more exclusion criteria. Of the remaining 93 per‐protocol‐treated patients, 91 showed an adequate diuretic response either in terms of urine volume or urine sodium concentration. Only two of 93 patients (2.2%) met the criteria of upfront diuretic resistance. In a post‐hoc analysis, patients with diuretic resistance had higher prevalence of chronic kidney or liver diseases, markedly lower blood pressure and heart rate, markedly higher serum creatinine and potassium levels, and lower serum sodium. Notably, clinical signs of congestion, circulating NT‐proBNP, and left‐ventricular ejection fraction were similar in both groups.ConclusionsUpfront diuretic resistance in an unselected population of AHF patients presenting to the ED affects only a minority of patients. These data highlight the importance of a standardized, protocolized approach to decongestive treatment in AHF, which includes the rapid administration of loop diuretics in an adequate dose. Pre‐existing chronic kidney disease and high creatinine levels were more prevalent in patients with diuretic resistance.
Real world experience in effect of torsemide vs. furosemide after discharge in patients with HFpEF
Authors: Li Xiao , Si Jinping , Liu Ying , Xu Danyan 
Published: September 2024

AbstractAimsFew studies have focused on the effect of torsemide versus furosemide after discharge on prognosis in patients with heart failure with preserved ejection fraction (HFpEF). This single‐centre retrospective real‐world study was conducted to evaluate the effect of torsemide versus furosemide after discharge on all‐cause mortality and rehospitalization for heart failure in patients with HFpEF.MethodsConsecutive patients who were diagnosis with HFpEF after discharge between January 2015 and April 2018 at the First Affiliated Hospital of Dalian Medical University and who had been treated with torsemide or furosemide were included in this study. The primary outcome was all‐cause mortality. The second outcome was rehospitalization for heart failure.ResultsA total of 445 patients (mean age 68.56 ± 8.07, female 55%) were divided into the torsemide group (N = 258) or furosemide group (N = 187) based on the treatment course at discharge from the hospital. During a mean follow‐up of 87.67 ± 11.15 months, death occurred in 68 of 258 patients (26.36%) in the torsemide group and 60 of 187 patients (30.09%) in the furosemide group [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.57–1.15, P = 0.239]. Rehospitalization for heart failure occurred in 111 of 258 patients (43.02%) in the torsemide groups and 110 of 187 patients (58.82%) in the furosemide group (HR 0.64, 95% CI 0.49–0.85, P = 0.002).ConclusionsCompared with furosemide, torsemide did not significantly reduce all‐cause mortality, but there was association between torsemide and reduced rehospitalization for heart failure in patients with HFpEF.
Development and validation of a machine learning‐based approach to identify high‐risk diabetic cardiomyopathy phenotype
Authors: Segar Matthew W. , Usman Muhammad Shariq , Patel Kershaw V. , Khan Muhammad Shahzeb , Butler Javed , Manjunath Lakshman , Lam Carolyn S.P. , Verma Subodh , Willett DuWayne , Kao David , Januzzi James L. , Pandey Ambarish 
Published: September 2024

AimsAbnormalities in specific echocardiographic parameters and cardiac biomarkers have been reported among individuals with diabetes. However, a comprehensive characterization of diabetic cardiomyopathy (DbCM), a subclinical stage of myocardial abnormalities that precede the development of clinical heart failure (HF), is lacking. In this study, we developed and validated a machine learning‐based clustering approach to identify the high‐risk DbCM phenotype based on echocardiographic and cardiac biomarker parameters.Methods and resultsAmong individuals with diabetes from the Atherosclerosis Risk in Communities (ARIC) cohort who were free of cardiovascular disease and other potential aetiologies of cardiomyopathy (training, n = 1199), unsupervised hierarchical clustering was performed using echocardiographic parameters and cardiac biomarkers of neurohormonal stress and chronic myocardial injury (total 25 variables). The high‐risk DbCM phenotype was identified based on the incidence of HF on follow‐up. A deep neural network (DeepNN) classifier was developed to predict DbCM in the ARIC training cohort and validated in an external community‐based cohort (Cardiovascular Health Study [CHS]; n = 802) and an electronic health record (EHR) cohort (n = 5071). Clustering identified three phenogroups in the derivation cohort. Phenogroup‐3 (n = 324, 27% of the cohort) had significantly higher 5‐year HF incidence than other phenogroups (12.1% vs. 4.6% [phenogroup 2] vs. 3.1% [phenogroup 1]) and was identified as the high‐risk DbCM phenotype. The key echocardiographic predictors of high‐risk DbCM phenotype were higher NT‐proBNP levels, increased left ventricular mass and left atrial size, and worse diastolic function. In the CHS and University of Texas (UT) Southwestern EHR validation cohorts, the DeepNN classifier identified 16% and 29% of participants with DbCM, respectively. Participants with (vs. without) high‐risk DbCM phenotype in the external validation cohorts had a significantly higher incidence of HF (hazard ratio [95% confidence interval] 1.61 [1.18–2.19] in CHS and 1.34 [1.08–1.65] in the UT Southwestern EHR cohort).ConclusionMachine learning‐based techniques may identify 16% to 29% of individuals with diabetes as having a high‐risk DbCM phenotype who may benefit from more aggressive implementation of HF preventive strategies.
Trispyrazolyl Borate Iron Thiolate Complexes and the Dependence of their O2‐Reactivity on the Reaction Space
Authors: Weißer Kilian , Cula Beatrice , Limberg Christian 
Published: September 2024

AbstractThe work presented here investigates whether the TpMesFe+ moiety, which had been previously found to mediate the dioxygenation of cysteine and cysteamine, can do the same with simple thiols, which are not functionalized by an amine group. Accordingly, the complexes TpMesFeSR (R=Ph, iPr) were synthesized and after full characterization exposed to O2. They were found to react unselectively to yield sulfinates, disulfides, and thiosulfones as products. The sulfinate complex TpMesFeO2S‐p‐Tol was prepared independently and found to be air‐stable, suggesting that the additional products are not formed via overoxidation or subsequent reactions of coordinated sulfinate product. To investigate whether the larger reaction space, opened up due to the missing amine donor is responsible, a Tp‐ligand functionalized by a pyridyl donor was employed. A corresponding Tp‐iron(II) chlorido complex was prepared and converted through salt metathesis reactions into the respective thiolate analogues, which were fully characterized and structurally authenticated. However, subsequent O2 reactivity studies did not show an improved selectivity. The reason may lie in a more open reaction pocket in combination with an electronic situation which is less ideal than in case of TpMesFe(cysteamine).
CuI/CuII Chiral Homoleptic Complexes: Study of Self‐Recognition and Self‐Discrimination
Authors: Dussart Caitlyn , Bonnefont Antoine , Bellemin‐Laponnaz Stéphane 
Published: September 2024

AbstractThe formation of ML2 homoleptic copper(I) and copper(II) complexes from bidentate chiral ligands with C2 symmetry, comprising three types of substituents (namely benzyl, indanyl and phenyl groups), was investigated. The formation of homochiral or heterochiral complexes can be influenced by the nature of the substituents and the geometry induced by the oxidation state of the metal. All the complexes were isolated and characterized, in particular in the solid state by X‐ray diffraction studies. In solution, cyclic voltammetry was used to study ligand association and discrimination induced by the CuI/CuII transition.