bluuebunny/crossref_metadata_2025_split huggingface dataset:
A sandwich ELISA kit reveals marked elevation of titin N‐terminal fragment levels in the urine of mdx mice
Authors: Shirakawa Taku , Ikushima Ayumu , Maruyama Nobuhiro , Nambu Yoshinori , Awano Hiroyuki , Osawa Kayo , Nirasawa Kei , Negishi Yoichi , Nishio Hisahide , Fukushima Shoji , Matsuo Masafumi 
Published: February 2022

AbstractThe mdx mouse is a model of Duchenne muscular dystrophy (DMD), a fatal progressive muscle wasting disease caused by dystrophin deficiency, and is used most widely in preclinical studies. Mice with dystrophin deficiency, however, show milder muscle strength phenotypes than humans. In human, the introduction of a sandwich enzyme‐linked immunosorbent assay (ELISA) kit revealed a more than 700‐fold increase in titin N‐terminal fragment levels in the urine of pediatric patients with DMD. Notably, the urinary titin level declines with aging, reflecting progression of muscle wasting. In mouse, development of a highly sensitive ELISA kit has been awaited. Here, a sandwich ELISA kit to measure titin N‐terminal fragment levels in mouse urine was developed. The developed kit showed good linearity, recovery, and repeatability in measuring recombinant or natural mouse titin N‐terminal fragment levels. The titin N‐terminal fragment concentration in the urine of mdx mice was more than 500‐fold higher than that of normal mice. Urinary titin was further analyzed by extending the collection of urine samples to both young (3–11 weeks old) and aged (56–58 weeks old) mdx mice. The concentration in the young group was significantly higher than that in the aged group. It was concluded that muscle protein breakdown is active and persistent in mdx mice even though the muscle phenotype is mild. Our results provide an opportunity to develop DMD treatments that aim to alleviate muscle protein breakdown by monitoring urinary titin levels.
Leigh Syndrome: A Study of 209 Patients at the Beijing Children's Hospital
Authors: Stenton Sarah L. , Zou Ying , Cheng Hua , Liu Zhimei , Wang Junling , Shen Danmin , Jin Hong , Ding Changhong , Tang Xiaolu , Sun Suzhen , Han Hong , Ma Yanli , Zhang Weihua , Jin Ruifeng , Wang Hua , Sun Dan , Lv Jun Lan , Prokisch Holger , Fang Fang 
Published: January 2022

ObjectiveLeigh syndrome (LS) is a heterogeneous neurodegenerative disease and the most frequent pediatric manifestation of mitochondrial disease. In the largest patient collection to date, this study aimed to provide new insights into the clinical and genetic spectrum of LS, defect‐specific associations, and predictors of disease course and survival.MethodsClinical, metabolic, neuroimaging, onset, and survival data were collected from the medical records of 209 patients referred to the Beijing Children's Hospital with symmetrical basal ganglia and/or brainstem neuroimaging changes indicative of LS by 30 centers from the Chinese network of mitochondrial disease (mitoC‐NET) between January 2013 and July 2021 for exploratory analysis.ResultsPathogenic variants were identified in 52 genes, most frequently MT‐ATP6, SURF1, and PDHA1. Maternally inherited variants accounted for 42% (heteroplasmy level ≥90% in 64%). Phenotypes spanned 92 Human Phenotype Ontology terms. Elevated serum lactate (144/195), global developmental delay (142/209), and developmental regression (103/209) were most frequent. Discriminating neuroimaging and/or clinical features were identified for MT‐ATP6 (m.9176T>C), MT‐ND5, PDHA1, SUCLG1, and SURF1. Poorest survival was associated with MT‐ND5, MT‐ATP6 (m.8993T>C and m.9176T>C), SURF1, and ALDH5A1 (≤50% 3 year's survival), in contrast to milder defects with specific treatment (ECHS1 and SLC19A3, 100% 3 year's survival).InterpretationOur data define phenotype, onset, and survival of LS in a defect‐specific manner, identifying features discriminating between genetic defects and predictive of disease outcome. These findings are essential to early diagnosis, in optimizing family counseling, and to the design and monitoring of future clinical trials, the next frontier of LS research. ANN NEUROL 2022;91:466–482
Morphological variation of the brachial plexus in four phyllostomid bat species (Chiroptera, Phyllostomidae)
Authors: Toledo Karen Santos , Peracchi Adriano Lúcio , Nogueira Marcelo Rodrigues 
Published: February 2022

AbstractDespite the remarkable morphological modifications that occurred in the thoracic limbs of bats, information about the brachial plexus in this group is still scarce. The present study aimed to describe the origin, structure, and distribution of these peripheral nerves in four Phyllostomidae species. Both antimeres of six Artibeus lituratus, five Desmodus rotundus, seven Glossophaga soricina, and five Phyllostomus hastatus—all adult males from the Adriano Lúcio Peracchi Collection (UFRRJ)—were dissected. After complete exposure of the structure, we found that the brachial plexus of D. rotundus and P. hastatus is formed by the same roots (C5–T1), whereas the fourth cervical spinal nerve and the second thoracic spinal nerve are present in G. soricina (C4–T1) and A. lituratus (C5–T2), respectively. There was intraspecific variation and asymmetry in the origin of the structure and the combinations of nerve segments forming terminal branches. The distribution to the target muscles and patagium, however, was not subject to significant variation in our sample. Data presented here support the presence of two prevailing conditions in distribution of nerves to the bat muscles, and the innervation of the membranes seems to be explained by embryogenesis. Although the brachial plexus in phyllostomid bats is similar to that of other terrestrial Laurasiatheria, aspects identified in these bats, apparently unique to Chiroptera, may be related to anatomical changes in the thoracic limbs functionally linked to flight.
Pyrimidines: Molecular docking and inhibition studies on carbonic anhydrase and cholinesterases
Authors: Duran Hatice Esra 
Published: February 2022

AbstractAlzheimer's disease (AD) is a neurodegenerative disorder. The disease is characterized by dementia, memory impairment, cognitive impairment, and speech impairment. Cholinesterases (ChEs; AChE, acetylcholinesterase and BChE, butyrylcholinesterase) inhibitors and their benefits of cholinergic replacement in the treatment of AD have been researched and documented by scientists in various ways to date. Recent studies prove that human carbonic anhydrases (hCAs) are also one of the important targets in the treatment of AD. Therefore, the development of new agents that can simultaneously modulate the various mechanisms or targets involved in the AD pathway may be a powerful strategy to treat AD, the current disease. Considering these data, the effects of the pyrimidines (1–7) were investigated in this study for the discovery and development of multitargeted ChEs and hCAs inhibitors associated with AD. In addition, the molecular docking analysis of the 4‐amino‐2‐choloropyrimidine (2) was performed to understand the binding interactions on the active site of the enzyme. All compounds (1–7) showed satisfactory enzyme inhibitory potency in micromolar concentrations against AChE, BChE, hCAI, and hCAII with KI values ranging from 0.099 to 0.241 μM, from 1.324 to 3.418 μM, from 0.201 to 0.884 μM, from 1.867 to 3.913 μM, respectively. Due to their ChEs and hCAs inhibition, these compounds (1–7) may be considered as leads for investigations in neurodegenerative diseases. All these results revealed that the 4‐amino‐5,6‐dichloropyrimidine (7) (KI value of 0.201 ± 0.041 μM for hCA I), the 4‐amino‐6‐hydroxypyrimidine (4) (KI value of 1.867 ± 0.296 μM for hCA II), the 4‐amino‐5,6‐dichloropyrimidine (7) (KI value of 0.099 ± 0.008 μM for AChE), and the 4‐amino‐2‐chloropyrimidine (2) (KI value of 1.324 ± 0.273 μM for BChE) from the pyrimidines in this series were the most promising derivatives, as they exhibited a good multifunctional inhibition at all experimental levels and in the in silico validation against these enzymes, for the treatment of AD.
Pyrazolo[3,4‐d]pyrimidine derivatives as irreversible Bruton's tyrosine kinase inhibitors
Authors: Yeom Hyesu , Achary Raghavendra , Choi Yunha , Park Chi Hoon , Lee Joo‐Youn , Lee Heung Kyoung , Kim Pilho , Cho Sung Yun 
Published: February 2022

Abstract4,6‐Disubstituted pyrazolo[3,4‐d]pyrimidine derivatives were explored as irreversible Bruton's tyrosine kinase (BTK) inhibitors. The structure–activity relationship was established with over 20 derivatives synthesized to determine initial hit compounds, based on activities against BTK enzyme and TMD8 cells. It turned out that introducing 1‐acrylamido‐4‐aminopiperdine (1b) at the C4 position of pyrazolopyrimidine as in 5e, and 3‐acrylamido‐aniline (1j) as 4‐position substituent, such as in 9d, 10d, and 10e, delivered potent in vitro enzyme activities as well as TMD8 cell‐based cytotoxicities. Considering kinase selectivity profiles, 5e was selected for in vivo efficacy studies with a murine xenograft model using TMD8 cells, where 5e exhibited moderate tumor growth inhibition activities. Further optimization of 5e and 9d may lead to clinically useful compounds to overcome B‐cell‐mediated hematologic cancers.
Fibrous skeleton‐framed, flexible high‐energy‐density quasi‐solid‐state lithium metal batteries
Authors: Kim Seung‐Hyeok , Choe Ui‐Jin , Kim Nag‐Young , Lee Sang‐Young 
Published: January 2022

AbstractDespite the extensive investigation on solid‐state lithium‐metal batteries (SSLMBs), their application in flexible electronic devices has been plagued mainly by the physicochemical/mechanical instability of their electrode–electrolyte interfaces. Here, we present a fibrous skeleton‐framed, quasi‐solid‐state LMB (fs‐QSSLMB) as a new cell architecture concept to simultaneously achieve the high‐energy‐density, mechanical flexibility, and safety. The fs‐QSSLMB is fabricated by embedding poly(ethylene terephthalate) (PET) nonwovens, stainless‐steel meshes, and metal‐coated conductive PET nonwovens with a lithiophilic‐gradient morphology as customized fibrous skeletons into quasi‐solid‐state electrolytes (QSSEs), high‐capacity LiNi0.8Co0.1Mn0.1O2 (NCM811) cathodes, and Li metal anodes, respectively. The stepwise printing of the NCM811 cathode/QSSE/Li anode assembly and the subsequent one‐pot ultraviolet curing of the gel electrolyte precursors in the assembly enable the formation of seamless interfaces between the electrodes and QSSE, thereby ensuring the electrochemical sustainability and mechanical deformability of the fs‐QSSLMB. In addition, owing to its fibrous skeleton‐based structural uniqueness and seamless interfaces, the fs‐QSSLMB exhibits electrochemical reliability, mechanical flexibility, safety (i.e., electrochemically active after being vertically cut in half and exposed to flame), and high (cell‐based) gravimetric/volumetric energy densities (385 Wh kgcell−1/451 Wh Lcell−1).
Use of the Medtronic Microvascular Plug 7Q for transcatheter closure of large patent ductus arteriosus in infants weighing less than 2.5 kg
Authors: Nasef Mohamed Al , O'Sullivan Donnchadh , Ng Li Yen , Walsh Kevin P. , Oslizlok Paul , McCrossan Brian , Kenny Damien , Sathanandam Shyam 
Published: January 2022

AbstractBackgroundThe sole Food and Drug Administration‐approved device for transcatheter closure of the patent arterial duct in premature infants is indicated for patent ductus arteriosus (PDAs) ≤ 4 mm in diameter. We report a two‐center experience with transcatheter closure of large PDAs (>4 mm) in infants weighing <2.5 kg using the Microvascular Plug 7Q (MVP‐7Q) device.MethodsThis is a retrospective review of departmental databases and medical charts to define patient cohort and report demographic, procedural, and follow‐up data.ResultsTwenty‐two patients (12 male) with a median gestational age and birthweight of 25.5 weeks (interquartile range [IQR] = 24–28) and 800 g (572–1075), respectively, underwent attempted PDA occlusion with the MVP‐7Q using a transvenous approach. The median age and weight at the time of PDA occlusion was 32 days (IQR = 24–28) and 1100 g (IQR = 960–1700), respectively. The median PDA length was 12 mm (IQR = 11–12.65). The median PDA diameters at the aortic and pulmonary ends were 5.1 (IQR = 4.9–5.5) and 4.8 mm (IQR = 4.6–5.3), respectively. Successful device occlusion was achieved in 20 patients (91%). There were two failed attempts: One due to inappropriate sizing, and the other secondary to left pulmonary artery stenosis. There were no procedural complications and no residual shunting on follow‐up.ConclusionsThe MVP‐7Q is safe and effective for transcatheter closure of large (>4 mm) PDAs in infants <2.5 kg. The lack of retention disks may help with avoiding impingement on surrounding vessels.
Sex differences in outcomes of transcatheter edge‐to‐edge repair with MitraClip: A meta‐analysis
Authors: Ya'Qoub Lina , Gad Mohamed , Faza Nadeen N. , Kunkel Katherine J. , Ya'acoub Rawan , Villablanca Pedro , Bagur Rodrigo , Alasnag Mirvat , Eng Marvin , Elgendy Islam Y. 
Published: January 2022

AbstractBackgroundTranscatheter edge‐to‐edge repair (TEER) with MitraClip improves outcomes among select patients with moderate–to‐severe and severe mitral regurgitation; however, data regarding sex‐specific differences in the outcomes among patients undergoing TEER are limited.MethodsAn electronic search of the PubMed, Embase, Central, and Web of Science databases for studies comparing sex differences in outcomes among patients undergoing TEER was performed. Summary estimates were primarily conducted using a random‐effects model.ResultsEleven studies with a total of 24,905 patients (45.6% women) were included. Women were older and had a lower prevalence of comorbidities, including diabetes, chronic kidney disease, and coronary artery disease. There was no difference in procedural success (odds ratio [OR]: 0.75, 95% confidence interval [CI]: 0.55–1.05) and short‐term mortality (i.e., up to 30 days) between women and men (OR: 1.16, 95% CI: 0.97–1.39). Women had a higher incidence of periprocedural bleeding and stroke (OR: 1.34, 95% CI: 1.15–1.56) and (OR: 1.57, 95% CI: 1.10–2.25), respectively. At a median follow‐up of 12 months, there was no difference in mortality (OR: 0.98, 95% CI: 0.89–1.09) and heart failure hospitalizations (OR: 1.07, 95% CI: 0.68–1.67). An analysis of adjusted long‐term mortality showed a lower incidence of mortality among women (hazards ratio: 0.77, 95% CI: 0.67–0.88).ConclusionsDespite a lower prevalence of baseline comorbidities, women undergoing TEER with MitraClip had higher unadjusted rates of periprocedural stroke and bleeding as compared with men. There was no difference in unadjusted procedural success, short‐term or long‐term mortality. However, women had lower adjusted mortality on long‐term follow‐up. Future high‐quality studies assessing sex differences in outcomes after TEER are needed to confirm these findings.
Validation of the V‐RESOLVE (Visual Estimation for Risk prEdiction of Side Branch OccLusion in Coronary Bifurcation interVEntion) score system in unprotected left main bifurcation
Authors: He Jining , Zhang Dong , Zhang Rui , Wang Haoyu , Wu Shaoyu , Feng Lei , Yin Dong , Xu Bo , Dou Kefei 
Published: January 2022

AbstractObjectivesThis study aimed to assess the risk of side branch (SB) occlusion using the V‐RESOLVE (The Visual Estimation for Risk prEdiction of Side Branch OccLusion in Coronary Bifurcation interVEntion) score in unprotected left main (LM) bifurcation percutaneous coronary intervention (PCI).BackgroundThe V‐RESOLVE score is a validated score system, based on visual estimation of angiographic data, for prediction of the risk of SB occlusion after main vessel (MV) stenting in non‐LM bifurcation lesions. However, its predictive value for unprotected LM bifurcation lesions remains to be validated.MethodsFrom January 2014 to December 2016, 855 patients undergoing unprotected LM bifurcation PCI using a provisional strategy were included. Baseline and prestenting angiographic data were analyzed, and the V‐RESOLVE score was calculated. SB occlusion was defined as any decrease in thrombolysis in myocardial infarction (TIMI) flow grade or the absence of flow in the SB after MV stenting. The predictive performance of the V‐RESOLVE score was judged by discrimination, calibration, and clinical application.ResultsvSB occlusion occurred in 19 (2.2%) of 855 unprotected LM bifurcation PCI procedures using a provisional strategy. The V‐RESOLVE score for SB occlusion had brilliant discrimination (the area under the receiver operating characteristic curve = 0.80, 95% confidence interval [CI]: 0.77–0.84) and good calibration (Hosmer–Lemeshow: p = 0.154). Stratified by the V‐RESOLVE score, significantly higher rates of SB occlusion were observed in the high‐risk group (score: 12–43) compared with the nonhigh‐risk group (score: 0–11) (4.4% vs. 0.6%, p < 0.001).ConclusionsThe V‐RESOLVE score is a promising tool to predict the risk of SB occlusion and facilitate decision‐making for unprotected LM bifurcation PCI.
Improvement of cardiac function after coronary artery bypass grafting surgery reduces the risk of postoperative acute kidney injury
Authors: Xu Jiarui , Chen Xin , Xie Yeqing , Lin Jing , Jiang Wuhua , Yu Jiawei , Wang Yimei , Luo Zhe , Wang Chunsheng , Ding Xiaoqiang , Teng Jie , Shen Bo 
Published: January 2022

AbstractBackgroundPre‐existing renal dysfunction is an independent risk factor for cardiac surgery‐associated acute kidney injury (AKI). We aimed to investigate whether the improvement of postoperative cardiac function after coronary artery bypass grafting (CABG) surgery would affect the risk of AKI in patients with different levels of baseline renal function.MethodsData were collected from patients who underwent CABG surgery from January 2018 to April 2019. Patients were divided into normal (GFR ≥ 90 ml/min/1.73 m2), non‐CKD (60≤GFR < 90 ml/min/1.73 m2), and CKD (GFR < 60 ml/min/1.73 m2) groups. Improvement in cardiac function was defined as △LVEF (postoperative LVEF–preoperative LVEF) ≥ 10% preoperative LVEF. Patients were further divided into subgroups according to postoperative cardiac function improvement.ResultsA total of 1365 patients were enrolled, including 793 (58.1%) in the normal group, 476 (34.9%) in the non‐CKD group, and 96 (7.0%) in the CKD group. The AKI incidence in the normal, non‐CKD, and CKD groups was 22.2%, 28.4%, and 40.6%, respectively. Patients with improved cardiac function in the non‐CKD and CKD groups had significantly lower AKI incidence than those without improved cardiac function (22.8% vs. 36.9%, p = .002% and 32.8% vs. 54.3%, p = .037, respectively). For non‐CKD patients with improved cardiac function, the serum creatinine at discharge was significantly lower than its preoperative serum creatinine (0.8 ± 0.5 vs 1.2 ± 0.9 mg/dl, p = .002). Multivariate logistic regression analysis showed that the improvement in cardiac function could reduce the risk for postoperative AKI in non‐CKD patients but not in CKD patients.ConclusionsFor patients with renal dysfunction and mildly reduced eGFR (60≤GFR < 90 ml/min/1.73 m2), improved cardiac function after CABG surgery can reduce the serum creatinine level and reduce the risk for postoperative AKI.
Surrogate‐based Bayesian calibration of biomechanical models with isotropic material behavior
Authors: Römer Ulrich , Liu Jintian , Böl Markus 
Published: January 2022

AbstractThis work introduces a computational methodology to calibrate material models in biomechanical applications under uncertainty. We adopt a Bayesian approach, which estimates the probability distributions of hyperelastic material parameters, based on force‐strain measurements. We approximate the parametric biomechanical model by combining a reduced order representation of the force response with a Polynomial Chaos expansion. The surrogate model allows to employ sampling‐intensive Markov chain Monte Carlo methods and provides an efficient way to estimate (generalized) Sobol coefficients. We use a Sobol sensitivity analysis to assess the influence of material parameters and present an iterative procedure to quantify the accuracy of the surrogate model as additional uncertainty during Bayesian updating. The methodology is illustrated with three cases, tensile experiments on heat‐induced whey protein gel, indentation experiments for oocytes and a manufactured example. Real experimental data are used for the calibration.
Quantitative measurement of IgG to SARS‐CoV‐2 antigens using monoclonal antibody‐based enzyme‐linked immunosorbent assays
Authors: Sander Ingrid , Kespohl Sabine , Zahradnik Eva , Göcke Philipp , Hosbach Ingolf , Herrmann Burkhard L , Brüning Thomas , Raulf Monika 
Published: January 2022

AbstractObjectiveStandardised quantitative analysis of the humoral immune response to SARS‐CoV‐2 antigens may be useful for estimating the extent and duration of immunity. The aim was to develop enzyme‐linked immunosorbent assays (ELISAs) for the quantification of human IgG antibodies against SARS‐CoV‐2 antigens.MethodsEnzyme‐linked immunosorbent assays were developed based on monoclonal antibodies against human IgG and recombinant SARS‐CoV‐2 antigens (Spike‐S1 and Nucleocapsid). The WHO 67/086 immunoglobulin and WHO 20/136 SARS‐CoV‐2 references were used for standardisation. Sera of a study group of COVID‐19‐positive subjects (n = 144), pre‐pandemic controls (n = 135) and individuals vaccinated with BioNTech–Pfizer BNT162b2 vaccine (n = 48) were analysed. The study group sera were also tested using EuroImmun SARS‐CoV‐2‐ELISAs and a quantitative S1‐specific fluorescence enzyme immunoassay (FEIA) from Thermo Fisher.ResultsThe ELISA results were repeatable and traceable to international units because of their parallelism to both WHO references. In the study group, median anti‐S1‐IgG concentrations were 102 BAU mL−1, compared to 100 and 1457 BAU mL−1 in the vaccination group after first and second vaccination, respectively. The ELISAs achieved an area under the curve (AUC) of 0.965 (S1) and 0.955 (Nucleocapsid) in receiver operating characteristic (ROC) analysis, and a specificity of 1 (S1) and 0.963 (Nucleocapsid) and sensitivity of 0.903 (S1) and 0.833 (Nucleocapsid) at the maximum Youden index. In comparison, the commercial assays (S1‐FEIA, S1 and Nucleocapsid ELISA EuroImmun) achieved sensitivities of 0.764, 0.875 and 0.882 in the study group, respectively.ConclusionsThe quantitative ELISAs to measure IgG binding to SARS‐CoV‐2 antigens have good analytical and clinical performance characteristics and units traceable to international standards.