bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome‐wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child–parent trios and a case–control design to identify novel rare variants
Authors: Sok Pagna , Sabo Aniko , Almli Lynn M. , Jenkins Mary M. , Nembhard Wendy N. , Agopian A. J. , Bamshad Michael J. , Blue Elizabeth E. , Brody Lawrence C. , Brown Austin L. , Browne Marilyn L. , Canfield Mark A. , Carmichael Suzan L. , Chong Jessica X. , Dugan‐Perez Shannon , Feldkamp Marcia L. , Finnell Richard H. , Gibbs Richard A. , Kay Denise M. , Lei Yunping , Meng Qingchang , Moore Cynthia A. , Mullikin James C. , Muzny Donna , Olshan Andrew F. , Pangilinan Faith , Reefhuis Jennita , Romitti Paul A. , Schraw Jeremy M. , Shaw Gary M. , Werler Martha M. , Harpavat Sanjiv , Lupo Philip J. ,   University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program, the National Birth Defects Prevention Study
Published: March 2023

AbstractThe etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein‐altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child–parent trios, one child–mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio‐based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case–control analysis using a sequence kernel‐based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex.
Chromosome 6p25 deletion syndrome: A case report and review of ophthalmic features
Authors: Le Hong , Jin Eva , Jewell Ann , Jackson‐Cook Colleen , Haskell Gloria T. , Couser Natario 
Published: March 2023

AbstractThe 6p25 deletion syndrome is a rare genetic disorder characterized by a wide spectrum of congenital anomalies. Ophthalmic abnormalities appear to be highly associated with the syndrome, although this relationship has not been well characterized to date. We conducted a systematic literature review to highlight the ocular features in patients with this deletion syndrome and describe a 7‐month‐old female who has a 6.07 MB 6p25.1p25.3 deletion and a 4.25 MB 17q25.3 duplication. Our patient presented with multiple congenital anomalies, including macrocephaly, frontal bossing, low set ears, tent‐shaped mouth, saddle nose, flat midface, and hearing impairment. Her ophthalmic features included proptosis, down‐slanting palpebral fissures, hypertelorism, nystagmus, bilateral posterior embryotoxon, and decentered and abnormally shaped pupils. A systematic review of the published cases with sufficient clinical eye descriptions included 63 cases with a confirmed 6p25 deletion. The most common eye findings observed were posterior embryotoxon, iris hypoplasia, corectopia, cornea opacity, and glaucoma.
Establishment of a non‐alcoholic fatty liver disease model by high fat diet in adult zebrafish
Authors: Li Xiang , Zhou Lei , Zheng Yuying , He Taiping , Guo Honghui , Li Jiangbin , Zhang Jingjing 
Published: March 2023

AbstractBackgroundNon‐alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in recent years, but the pathogenesis is not fully understood. Therefore, it is important to establish an effective animal model for studying NAFLD.MethodsAdult zebrafish were fed a normal diet or a high‐fat diet combined with egg yolk powder for 30 days. Body mass index (BMI) was measured to determine overall obesity. Serum lipids were measured using triglyceride (TG) and total cholesterol (TC) kits. Liver lipid deposition was detected by Oil Red O staining. Liver injury was assessed by measuring glutathione aminotransferase (AST) and glutamic acid aminotransferase (ALT) levels. Reactive oxygen species (ROS) and malondialdehyde (MDA) were used to evaluate oxidative damage. The level of inflammation was assessed by qRT‐PCR for pro‐inflammatory factors. H&E staining was used for pathological histology. Caspase‐3 immunofluorescence measured apoptosis. Physiological disruption was assessed via RNA‐seq analysis of genes at the transcriptional level and validated by qRT‐PCR.ResultsThe high‐fat diet led to significant obesity in zebrafish, with elevated BMI, hepatic TC, and TG. Severe lipid deposition in the liver was observed by ORO and H&E staining, accompanied by massive steatosis and ballooning. Serum AST and ALT levels were elevated, and significant liver damage was observed. The antioxidant system in the body was severely imbalanced. Hepatocytes showed massive apoptosis. RNA‐seq results indicated that several physiological processes, including endoplasmic reticulum stress, and glucolipid metabolism, were disrupted.ConclusionAdditional feeding of egg yolk powder to adult zebrafish for 30 consecutive days can mimic the pathology of human nonalcoholic fatty liver disease.
Direct Catalytic Asymmetric and Regiodivergent N1‐ and C3‐Allenylic Alkylation of Indoles
Authors: Zha Taochun , Rui Jiehui , Zhang Zhihan , Zhang Dongqiang , Yang Zhirong , Yu Peiyuan , Wang Yingcheng , Peng Fangzhi , Shao Zhihui 
Published: March 2023

AbstractHerein we report a Pd‐catalyzed asymmetric allenylic alkylation strategy for the direct functionalization of 1H‐indoles by employing P‐chiral BIBOP‐type ligands. The regioselectivity (N1/C3) of this process can be switched efficiently. Using Cs2CO3 at elevated temperatures in MeCN, N1‐alkylated indoles bearing axial chirality with a stereocenter non‐adjacent (β) to the nitrogen are produced in good yields with high enantioselectivity and complete N1‐regioselectivity regardless of the electronic properties and substitution patterns of diverse indoles. Using K2CO3 at room temperature in CH2Cl2, chiral C3‐alkylated indoles can also be obtained. Notably, we introduce a new class of tri‐substituted allenylic electrophiles that proceeded through different pathways from di‐substituted allenylic electrophiles.
Light‐driven Orderly Assembly of Ir‐atomic Chains to Integrate a Dynamic Reaction Pathway for Acidic Oxygen Evolution
Authors: Xu Zuozheng , Zhou Liqi , Zhou Gang , Wu Shuyi , Wang Peifang , Li Hao , Huang Peilin , Liu Lizhe 
Published: March 2023

AbstractThis work suggests an intriguing light‐driven atomic assembly proposal to orderly configure the distribution of reactive sites to optimize the spin‐entropy‐related orbital interaction and charge transfer from electrocatalysts to intermediates. Herein, the introduced fluorine (F) atoms acting as photo‐corrosion centres in MnO1.9F0.1 effectively soften the bonding interaction of Mn−O bonds in the IrCl3 solution. Therefore, partial Mn atoms can be successively replaced to form orderly atomic‐hybridized catalysts with a spin‐related low entropy due to the coexistence of Ir‐atomic chains and clusters. The time‐related elemental analysis demonstrates that the dynamic dissolution/redeposition of Ir clusters in acidic oxygen evolution leads to a reintegration of the reaction pathway to seek the switchable rate‐limiting step with a lower activation energy.
Heptagon‐Containing Nanographene Embedded into [10]Cycloparaphenylene
Authors: Mora‐Fuentes Juan P. , Codesal Marcos D. , Reale Marco , Cruz Carlos M. , Jiménez Vicente G. , Sciortino Alice , Cannas Marco , Messina Fabrizio , Blanco Victor , Campaña Araceli G. 
Published: March 2023

AbstractWe report the synthesis and characterization of a novel type of nanohoop, consisting of a cycloparaphenylene derivative incorporating a curved heptagon‐containing π‐extended polycyclic aromatic hydrocarbon (PAH) unit. We demonstrate that this new macrocycle behaves as a supramolecular receptor of curved π‐systems such as fullerenes C60 and C70, with remarkably large binding constants (ca. 107 M−1), as estimated by fluorescence measurements. Nanosecond and femtosecond spectroscopic analysis show that these host‐guest complexes are capable of quasi‐instantaneous charge separation upon photoexcitation, due to the ultrafast charge transfer from the macrocycle to the complexed fullerene. These results demonstrate saddle‐shaped PAHs with dibenzocycloheptatrienone motifs as structural components for new macrocycles displaying molecular receptor abilities and versatile photochemical responses with promising electron‐donor properties in host‐guest complexes.
Effect of TESPT on viscoelastic and mechanical properties with the morphology of SSBR/BR hybrid nanocomposites
Authors: Barghamadi Mohammad , Karrabi Mohammad , Ghoreishy Mir Hamid Reza , Naderi Ghasem 
Published: March 2023

AbstractIn this study, the various properties of hybrid nanocomposite based on solution styrene butadiene rubber (SSBR)/butadiene rubber (BR) have been investigated. For this purpose, SSBR/BR rubber blend with nano‐silica and carbon black (CB) in constant filler content (60 phr) with and without Bis (triethoxysilylpropyl) tetrasulfide (TESPT) silane coupling agent was fabricated. The various properties, including curing behavior, morphology, dynamic–mechanical, and dissipation characteristics, were studied. For this objective, rheometry, field emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), tensile test, and Dynamic mechanical thermal analysis (DMTA) were used. The results of rheometry illustrated that the addition of nano‐silica increased the optimum cure time (t90) and declined the cure rate index (CRI). However, the addition of surface‐modified silica improved the t90 and CRI. Replacing nano‐silica with CB also reduced the scorch and optimum cure time. TEM and SEM micrographs showed the good dispersion state of nano‐silica in the SSBR/BR/nano‐silica/TESPT matrix. According to the mechanical test data, including tensile, hardness, and abrasion, the addition of hybrid filler containing 40 phr modified nano‐silica and 20 phr CB improved properties. The results of DMTA illustrated the appropriate compatibility between blend phases, also an increase in the glass transition temperature (Tg) and storage modulus (E′) for the samples containing higher amounts of CB. Considering the importance of the damping factor at temperatures of −20, 0, and 60°C, which is related to ice grip, wet grip, and rolling resistance, respectively, the TSi40CB20 sample showed the essential properties of the magic triangle better than other samples. Dissipative properties also revealed that by increasing the filler content and replacing nano‐silica with CB, the dissipation of the compound increases significantly. According to the results, the optimum amount of nano‐silica and CB in the SSBR/BR/TESPT was 40 and 20 phr, respectively.
Novel benzimidazole‐linked (thio)barbiturates as non‐hydroxamate HDAC6 inhibitors targeting leukemia: Design, synthesis, and structure–activity relationship
Authors: Mansour Reda El‐Sayed , Abdulwahab Hanan Gaber , El‐Sehrawi Hend M. 
Published: March 2023

AbstractBased on the well‐established pharmacophoric features required for histone deacetylase (HDAC) inhibition, novel easy‐to‐prepare benzimidazole‐linked (thio)barbiturate derivatives were designed and synthesized as HDAC6 inhibitors. The proposed structures of the title compounds were confirmed based on their spectral data and elemental analyses. The newly synthesized compounds were screened in vitro against HDAC6. All tested compounds showed potent HDAC6 inhibition at the nanomolar level. Several compounds displayed a remarkable HDAC6 inhibitory activity (IC50 = 48.85–75.62 nM), superior to that of the reference drug suberoylanilide hydroxamic acid (SAHA; IC50 = 91.73 nM). The most potent derivatives were further assessed for their in vitro anticancer activity against two human leukemia cell lines. Thiobarbiturate 3e was two times more potent than SAHA against the tested cells. The detailed structure–activity relationship was also described. Furthermore, molecular docking simulation revealed the ability of the title compounds to chelate the catalytic Zn+2 ion located within the binding pocket of HDAC6. In silico evaluation of physicochemical properties indicated that the target compounds are promising candidates in terms of pharmacokinetic aspects.
Gymnemic acid‐conjugated gelatin scaffold for enhanced bone regeneration: A novel insight to tissue engineering
Authors: Joy Shilpa , Thomas Nebu George 
Published: March 2023

AbstractBone tissue engineering deals with the design of bone scaffolds. The selection of porous scaffold for osteoblast attachment and suppression of microbial infections are the major challenges that were addressed by designing gelatin scaffolds conjugated with gymnemic acid. Gelatin scaffold was prepared by loading gymnemic acid and morphological characterization, porosity, water absorption behavior, and biocompatibility of the scaffold were studied. The scaffold was introduced to the rat calvarial bone defect (BD) and analyzed the serum C reactive protein, alkaline phosphatase activity, and histology for 1 month to study the reconstruction. Adult Sprague–Dawley rats were used as sham operated control, animal with BD, and animal with BD which was implanted with scaffold (BDMB). The scanning electron micrograph revealed porous nature of scaffold. There was no significant difference in water absorption ability of scaffold. The C reactive protein was not observed in the serum collected on the 5th day postsurgery, supported the biocompatibility. The alkaline phosphatase activity in BDMB was increased when compared with BD on 15th and 20th day and then decreased. New bone tissue formation was detected with hematoxylin–eosin staining. The scaffold is effective in enhancing bone regeneration, which will have therapeutic significance in orthopedics and dentistry.
N6‐ Methyladenosine defines a new checkpoint in γδ T cell development
Authors: Zhao Jiachen , Ding Chenbo , Li Hua‐Bing 
Published: March 2023

AbstractT cells, which are derived from hematopoietic stem cells (HSCs), are the most important components of adaptive immune system. Based on the expression of αβ and γδ receptors, T cells are mainly divided into αβ and γδ T cells. In the thymus, they share common progenitor cells, while undergoing a series of well‐characterized and different developmental processes. N6‐Methyladenosine (m6A), one of the most abundant modifications in mRNAs, plays critical roles in cell development and maintenance of function. Recently, we have demonstrated that the depletion of m6A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells through the regulation of Jag1/Notch2 signaling, but not αβ T cells, indicating a checkpoint role of ALKBH5 and m6A modification in the early development of γδ T cells. Based on previous studies, many key pathway molecules, which exert dominant roles in γδ T cell fate determination, have been identified as the targets regulated by m6A modification. In this review, we mainly summarize the potential regulation between m6A modification and these key signaling molecules in the γδ T cell lineage commitment, to provide new perspectives in the checkpoint of γδ T cell development.
Shell engineering in soft alginate‐based capsules for culturing liver spheroids
Authors: Peng Xuan , Janićijević Željko , Lemm Sandy , Laube Markus , Pietzsch Jens , Bachmann Michael , Baraban Larysa 
Published: March 2023

AbstractFunctional interaction between cancer cells and the surrounding microenvironment is still not sufficiently understood, which motivates the tremendous interest for the development of numerous in vitro tumor models. Diverse parameters, for example, transport of nutrients and metabolites, availability of space in the confinement, etc. make an impact on the size, shape, and metabolism of the tumoroids. We demonstrate the fluidics‐based low‐cost methodology to reproducibly generate the alginate and alginate‐chitosan microcapsules and apply it to grow human hepatoma (HepG2) spheroids of different dimensions and geometries. Focusing specifically on the composition and thickness of the hydrogel shell, permeability of the microcapsules was selectively tuned. The diffusion of the selected benchmark molecules through the shell has been systematically investigated using both, experiments and simulations, which is essential to ensure efficient mass transfer and/or filtering of the biochemical species. Metabolic activity of spheroids in microcapsules was confirmed by tracking the turnover of testosterone to androstenedione with chromatography studies in a metabolic assay. Depending on available space, phenotypically different 3D cell assemblies have been observed inside the capsules, varying in the tightness of cell aggregations and their shapes. Conclusively, we believe that our system with the facile tuning of the shell thickness and permeability, represents a promising platform for studying the formation of cancer spheroids and their functional interaction with the surrounding microenvironment.
Experimental and Computational Fluid Dynamics‐Based Simulation of Oil‐in‐Water Emulsion Flow through a Pipeline
Authors: Vegad Girish D. , Jana Arun Kumar 
Published: March 2023

AbstractDue to its high viscosity, heavy crude oil (HCO) is often transported through pipelines as concentrated oil‐in‐water emulsion. Here, emulsions were prepared with different concentrations of polyoxyethylene (5) sorbitan monooleate to study their flow characteristics through a horizontal pipeline. Laminar flow of HCO and an emulsion with 75 % (v/v) HCO and 25 % (v/v) water was simulated by using Ansys Fluent 2019 R3 to study the effect of temperature, volumetric flow rate, and surfactant concentration on pressure drop, dynamic viscosity, hydrodynamic entrance length, flow behavior index, consistency index, and pumping power requirement. Laminar flow of the emulsion was simulated by using a two‐phase mixture flow model considering the emulsion as a pseudo‐homogeneous mixture, while the flow of HCO was simulated as viscous laminar flow. Flow behavior index and consistency index were predicted from experimental viscosity data and used to predict pressure drop and, hence, the pumping power requirement.
Extraktion von Zellstoff aus Nicht‐Holzpflanzen und Vergleich mit Holzpflanzen
Authors: Lexa Anna , Sängerlaub Sven , Zollner-Croll Helga 
Published: March 2023

AbstractEin Trend in der Zellstoff‐ und Papierindustrie ist die Nutzung von Nicht‐Holzpflanzen, z. B. von Einjahrespflanzen und Gräsern. Sie sollen Bäume als Rohstoffquelle für Zellstoff substituieren. Da sich die Zusammensetzung und die Fasereigenschaften unterscheiden, müssen diese bewertet werden. In dieser Machbarkeitsstudie wurden Zellstoff aus Hopfen, Hanf und Miscanthus extrahiert, die Ausbeuten und die Fasereigenschaften untersucht und mit verfügbaren Daten für Zellstoff aus Kiefern‐ und Fichtenholz (Northern Bleached Softwood Kraft) verglichen. Es zeigten sich sehr hohe Ausbeuten von bis zu 86,6 Ma.‐% für den Natural‐Pulping‐Aufschluss sowie eine niedrige Kappa‐Zahl von 3,5 für Miscanthus. Demnach wurde fast das gesamte Lignin entfernt. Damit bestätigt sich die hohe chemische Wirksamkeit der Aufschlüsse sowie das große Potenzial von Einjahrespflanzen und Gräsern.
Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG‐ALL‐2015: A multicenter study
Authors: Zhang Honghong , Wan Yang , Wang Hongsheng , Cai Jiaoyang , Yu Jie , Hu Shaoyan , Fang Yongjun , Gao Ju , Jiang Hua , Yang Minghua , Liang Changda , Jin Runming , Tian Xin , Ju Xiuli , Hu Qun , Jiang Hui , Li Zhifan , Wang Ningling , Sun Lirong , Leung Alex W. K. , Wu Xuedong , Qian Xiaowen , Qian Maoxiang , Li Chi‐kong , Yang Jun , Tang Jingyan , Zhu Xiaofan , Shen Shuhong , Zhang Li , Pui Ching‐Hon , Zhai Xiaowen 
Published: March 2023

AbstractBackgroundContemporary risk‐directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome.MethodsThe authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL‐2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate‐risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation.ResultsThe overall 5‐year event‐free survival was 84.4% (95% confidence interval [CI], 80.6–88.3) and 5‐year overall survival 88.9% (95% CI, 85.5–92.4). Independent factors associated with lower 5‐year event‐free survival were male sex (80.4%, [95% CI, 74.8–86.4] vs. 88.9%, [95% CI, 84.1–93.9] in female, p = .03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2–87.4] vs. 87.1%, [95% CI, 83.4–90.9] in patients with negative MRD, p < .001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5‐year event‐free survival (33.3% [95% CI, 11.6–96.1] vs. 83.0% [95% CI, 77.5–88.9] in the other 192 male patients, p < .001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2–14.5], p < .001).ConclusionsThese data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL.