bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel highly efficient absolute optical resolution method by serial combination of two asymmetric reactions from acetylene monomers having racemic substituents
Authors: Tang Yanan , Liu Lijia , Suzuki Junpei , Teraguchi Masahiro , Kaneko Takashi , Aoki Toshiki 
Published: January 2022

AbstractFor general optical resolution, an optical resolution agent is necessary, and the best agent should be selected for each racemic compound. In this study, we will report that a novel optical resolution method by circularly polarized light (CPL) without any optical resolution agents has been developed by serially connecting two enantioselective reactions. These reactions we developed are the enantiomer‐selective helix‐sense‐selective polymerization (ES‐HSSP) and helix‐sense‐selective highly selective photocyclic aromatization (SCAT) by CPL (HS‐SCAT). Since this significantly unique EPHS method (EPHS = ES‐HSSP + HS‐SCAT) does not need any optical resolution agents, any cocatalysts, and solvents for the selective decomposition reaction (HS‐SCAT), this process is quite simple and convenient. Since this process does not include any decomposition of the target racemates themselves, both enantiomers could be obtained. The optical yields for isolated compounds that were enantiomerically separated by the EPHS method were very high, for example, 78%ee, 93%ee, and 85%ee for menthol, phenethyl alcohol, and 2‐butanol, respectively. In addition, their chemical yields were around 85% to 94%. Therefore, the EPHS method was found to show an excellent performance and can be applied to actual optical resolution for a wide range of racemic compounds. This is the first absolute optical resolution by CPL showing high optical and chemical yields and expected to become a practical optical resolution method.
Polar Substitutions on the Surface of a Lipase Substantially Improve Tolerance in Organic Solvents
Authors: Cui Haiyang , Vedder Markus , Zhang Lingling , Jaeger Karl‐Erich , Schwaneberg Ulrich , Davari Mehdi D. 
Published: January 2022

AbstractBiocatalysis in organic solvents (OSs) enables more efficient routes to the synthesis of various valuable chemicals. However, OSs often reduce enzymatic activity, which limits the use of enzymes in OSs. Herein, we report a comprehensive understanding of interactions between surface polar substitutions and DMSO by integrating molecular dynamics (MD) simulations of 45 variants from Bacillus subtilis lipase A (BSLA) and substitution landscape into a “BSLA‐SSM” library. By systematically analyzing 39 structural‐, solvation‐, and interaction energy‐based observables, we discovered that hydration shell maintenance, DMSO reduction, and decreased local flexibility simultaneously govern the stability of polar variants in OS. Moreover, the fingerprints of 1631 polar‐related variants in three OSs demonstrated that substituting aromatic to polar amino acid(s) hold great potential to highly improve OSs resistance. Hence, surface polar engineering is a powerful strategy to generate OS‐tolerant lipases and other enzymes, thereby adapting the catalyst to the desired reaction and process with OSs.
Developmentally interdependent stretcher‐compressor relationship between the embryonic brain and the surrounding scalp in the preosteogenic head
Authors: Tsujikawa Koichiro , Saito Kanako , Nagasaka Arata , Miyata Takaki 
Published: January 2022

AbstractBackgroundHow developing brains mechanically interact with the surrounding embryonic scalp layers (ie, epidermal and mesenchymal) in the preosteogenic head remains unknown. Between embryonic day (E) 11 and E13 in mice, before ossification starts in the skull vault, the angle between the pons and the medulla decreases, raising the possibility that when the elastic scalp is directly pushed outward by the growing brain and thus stretched, it recoils inward in response, thereby confining and folding the brain.ResultsStress‐release tests showed that the E11‐13 scalp recoiled and that the in vivo prestretch prerequisite for this recoil was physically dependent on the brain (pressurization at 77‐93 Pa) and on actomyosin and elastin within the scalp. In scalp‐removed heads, brainstem folding was reduced, and the spreading of ink from the lateral ventricle to the spinal cord that occurred in scalp‐intact embryos (with >5 μL injection) was lost, suggesting roles of the embryonic scalp in brain morphogenesis and cerebrospinal fluid homeostasis. Under nonstretched conditions, scalp cell proliferation declined, while the restretching of the shrunken scalp rescued scalp cell proliferation.ConclusionsIn the embryonic mouse head before ossification, a stretcher‐compressor relationship elastically develops between the brain and the scalp, underlying their mechanically interdependent development.
What accounts for the high mortality of anorexia nervosa?
Authors: Mehler Philip S. , Watters Ashlie , Joiner Thomas , Krantz Mori J. 
Published: January 2022

AbstractThe exact medical complications, leading to the well‐known high risk of death in patients with anorexia nervosa (AN), remain elusive. Such deaths are often abrupt with no satisfactory explanation. Suspected causes include cardiac QTc prolongation and, in turn, torsade de pointes (TdP). Psychotropic medications often prescribed to these patients are linked to QTc prolongation. AN is also presumed to cause heart failure due to malnutrition with increased susceptibility to QTc prolongation, and TdP, resulting in sudden cardiac death. Recent literature, however, is conflicting, and the likely cause of death may involve other cardiac abnormalities, such as low heart rate, abnormal heart rate variability, or increased QT dispersion. With an ongoing gap in research explaining the high mortality rate in AN, a compelling need to define the exact proximate causes of death in these patients remains. Because low serum potassium is the most common trigger for TdP, we postulate the early signal of sudden cardiac death, especially in patients with AN who purge, is hypokalemia. We also speculate that hypoglycemia could be a major factor in the sudden death of patients with AN as well as bradycardia or sinus arrest. A path forward to elucidate potential causes is offered.
Food insecurity is associated with eating disorders independent of depression and anxiety: Findings from the 2020–2021 Healthy Minds Study
Authors: Zickgraf Hana F. , Hazzard Vivienne M. , O'Connor Shannon M. 
Published: January 2022

AbstractObjectiveTo examine the association between food insecurity and eating disorder (ED) risk independent of co‐occurring anxiety/depression.MethodData were provided by 121,627 undergraduate/graduate students who participated in the 2020–2021 Healthy Minds Study (HMS). Participants responded to questionnaire measures of food insecurity and risk for EDs, depression, and anxiety. Established cut‐offs were used to identify students with food insecurity and probable psychopathology. Separate modified Poisson regressions adjusted for age, gender, race/ethnicity, and socioeconomic background examined the association between food insecurity and each form of psychopathology. The association between food insecurity and probable ED was then examined in a regression further adjusted for probable depression and anxiety.ResultsFood insecurity was significantly associated with all three forms of psychopathology when examined separately (prevalence ratios ranged from 1.41 to 1.54, all p’s < .001). When accounting for probable depression/anxiety, food insecurity was significantly associated with 1.19 times greater prevalence of a probable ED (p < .001).DiscussionThe association between food insecurity and EDs was replicated in a large, national sample of university students. To our knowledge, this is the first study to examine the independence of this relationship after adjusting for depression/anxiety. This finding supports the hypothesis that specific mechanisms, rather than general psychological distress, likely underlie the food insecurity–ED relationship.
Sensitized and Self‐Sensitized Photocatalytic Carbon Dioxide Reduction Under Visible Light with Ruthenium Catalysts Shows Enhancements with More Conjugated Pincer Ligands
Authors: Das Sanjit , Nugegoda Dinesh , Yao Wenzhi , Qu Fengrui , Figgins Matthew T. , Lamb Robert W. , Webster Charles Edwin , Delcamp Jared H. , Papish Elizabeth T. 
Published: January 2022

AbstractA new method to synthesize complexes of the type [(CNC)RuII(NN)L]n+ has been introduced, where CNC is a tridentate pincer composed of two (benz)imidazole derived NHC rings and a pyridyl ring, NN is a bidentate aromatic diimine ligand, L=bromide or acetonitrile, and n=1 or 2. Following this new method a series of six new complexes has been synthesized and characterized by spectroscopic, analytic, crystallographic, and computational methods. Their electrochemical properties have been studied via cyclic voltammetry under both N2 and CO2 atmospheres. Photocatalytic reduction of CO2 to CO was performed using these complexes both in the presence (sensitized) and absence (self‐sensitized) of an external photosensitizer. This study evaluates the effect of different CNC, NN, and L ligands in sensitized and self‐sensitized photocatalysis. Catalysts bearing the benzimidazole derived CNC pincer show much better activity for both sensitized and self‐sensitized photocatalysis as compared to catalysts bearing the imidazole derived CNC pincer. Furthermore, self‐sensitized photocatalysis requires a diimine ligand for CO2 reduction with catalyst 2ACN being the most active catalyst in this series with TON=85 and TOF=22 h−1 with an electron donating 4,4′‐dimethyl‐2,2′‐bipyridyl (dmb) ligand and a benzimidazole derived CNC pincer.
A Facile Synthetic Strategy for Decavanadate and Transition Metal Based All‐Inorganic Coordination Polymers and Insights into Their Electrocatalytic OER Activity
Authors: Kar Aranya , Sharma Lalita , Kumar Akash , Halder Aditi , Pradeep Chullikkattil P. 
Published: January 2022

AbstractThis study reports a facile synthetic strategy for decavanadate ([V10O28]6−) cluster‐based all inorganic coordination polymers (CPs) containing earth‐abundant and redox‐active transition metals and their electrocatalytic oxygen evolution reaction (OER) activity. The first series of such isomorphous compounds containing the transition metals Mn, Co, and Ni, {(H2O)2K‐μ‐(H2O)3Mn(H2O)3}2n[V10O28]n (1), {(H2O)2K‐μ‐(H2O)3Co(H2O)3}2n[V10O28]n (2) and {(H2O)2K‐μ‐(H2O)3Ni(H2O)3}2n[V10O28]n (3), have been synthesized and structurally characterized. In these polymeric compounds, the [V10O28]6− clusters are interlaced and inter‐connected by {(H2O)2K‐μ‐(H2O)3‐M(H2O)3}+3 units leading to a linear chain‐like arrangement. Each of such chains is further interconnected to adjacent chains by bonding K+ ions with a [V10O28]6− cluster of the adjacent chain leading to a two‐dimensional (2D) sheet‐like arrangement. Hydrogen bonding interactions between the coordinated water molecules and the cluster oxygens further interconnect the adjacent sheets. All these compounds 1–3 are shown to catalyze the oxygen evolution reaction (OER) under alkaline (0.1 M KOH) conditions. Among the three, the Ni‐based catalyst 3 exhibited the best OER activity with a moderate overpotential of 270 mV at onset, a low Tafel slope of 89 mV dec−1, and a turnover frequency (TOF) of 7.5 s−1, which is comparable to similar Keggin POM‐based systems reported so far. The CPs were not highly stable under the OER conditions employed. The post‐catalytic analyses indicated the ‘precatalyst’ nature of these compounds in alkaline media forming V‐doped metal oxyhydroxides as the OER active species under the turnover conditions. Thus, this study provides a new and facile strategy for synthesizing [V10O28]6−cluster and transition metal‐based all‐inorganic CPs and insights into their OER electrocatalytic activities for the first time.
Versatile Activity of a Copper(II) Complex Bearing a N4‐Tetradentate Schiff Base Ligand with Reduced Oxygen Species
Authors: Richezzi Micaela , Ferreyra Joaquín , Puzzolo Juan , Milesi Lisandro , Palopoli Claudia M. , Moreno Diego M. , Hureau Christelle , Signorella Sandra R. 
Published: January 2022

AbstractThe reactivity of the Cu(II) complex of N,N’‐bis(pyridin‐2‐ylmethylene)propane‐1,3‐diamine (py2pn), [Cu(py2pn)(ClO4)2], toward O2.− and H2O2 has been examined. The complex reacts with O2.− with fast second order kinetics, kMcF=4.05×106 M−1 s−1, employing the Cu(II)/Cu(I) couple proved by spectroscopic detection of the reduced form at low temperature. At −40 °C in DMF, the reaction of the complex with H2O2/Et3N yields an stable end‐on Cu(II)‐hydroperoxide, with kOOH=0.31 min−1, the formation of which has been established by DFT calculations, electronic and EPR spectra. At room temperature, the end‐on Cu(II)‐hydroperoxide reacts with a second Cu(II) complex to evolve O2, with kCAT=83.2 M−2 s−1. The Cu(II)‐hydroperoxide can mediate phenol oxidation, probably through a trigonal bipyramidal ternary transition state based on DFT analysis, favored over catalase activity when low proportion of catalyst is used. In these reactions, structural constraints imposed by the ligand distort the coordination geometry of the metal and controls reactivity.
Inhibition of Cathepsin B by Ferrocenyl Indenes Highlights a new Pharmacological Facet of Ferrocifens
Authors: Sanz Garcia Juan , Gaschard Marie , Navizet Isabelle , Sahihi Mehdi , Top Siden , Wang Yong , Pigeon Pascal , Vessières Anne , Salmain Michèle , Jaouen Gérard 
Published: January 2022

AbstractThe family of ferrocifens initially built up from the anti‐oestrogen tamoxifen shows a broad antitumor activity bothin vitroandin vivo. Their mechanism of action relies on the presence of the redox motif [ferrocene‐ene‐phenol] that, under oxidative conditions, generates reactive oxygen species (ROS) and affords electrophilic quinone methides (QMs) having the ability to alkylate biological nucleophiles and in turn elicit a strong antiproliferative activity. In this context, the cysteine protease cathepsin B was initially presumed to be a target for ferrocenyl QMs.In vitroenzymatic assays ruled out this hypothesis but unexpectedly revealed that other ferrocifen metabolites, i. e. ferrocenyl indenes, acted as moderate inhibitors of cathepsin B. These experimental results were nicely confirmed by molecular docking calculations, that showed that the monophenol ferrocenyl indene and to a lower extent the diphenol interacted with the active site of cathepsin B, making it an unanticipated target of ferrocifens.
A Novel Nanoparticles‐based Electrochemical Sensing Platform for Sensitive Detection of Oral Anticoagulant; Edoxaban in Human Plasma
Authors: Ayish Nada S. , Marzouk Hoda M. , El‐Zeany Badr A. , Fayed Ahmed S. 
Published: January 2022

AbstractDuring COVID‐19 pandemic, coagulopathy have been reported as a potential threat to most infected patients. Edoxaban (EDX) is a direct oral anticoagulant that is recently added to most COVID‐19 treatment protocols either as therapy or prophylaxis. Herein, a novel nanoparticles modified glassy carbon potentiometric sensor was developed for the selective quantitation of EDX in human plasma. The electrochemical performance of the proposed sensor was assessed and compared to nanoparticle free sensor. An enhancement in electrode performance including: detection limit (3.39×10−6 mol L−1), response time (8.0±2.0 s) and improved selectivity. The proposed sensor was able to determine EDX in pure form, pharmaceutical formulation and human plasma.
Home treatment as an add‐on to family‐based treatment in adolescents with anorexia nervosa: A pilot study
Authors: Pauli Dagmar , Flütsch Nicole , Hilti Nadine , Schräer Christiane , Soumana Mariama , Häberling Isabelle , Berger Gregor 
Published: January 2022

AbstractObjectiveThis pilot study examines the feasibility and the effectiveness of add‐on home treatment (HT) to family‐based treatment (FBT) in adolescents with anorexia nervosa (AN). The HT intervention is delivered by specialised nurses and aims at supporting patients and parents to re‐establish family meals in the home environment.MethodWe performed a 3‐month study in AN patients with a waiting‐list control design comparing 45 (43 females, 2 males) adolescents receiving FBT augmented with HT compared to 22 (21 females, 1 male) participants receiving FBT alone on the waiting list for additional HT. Eating disorder diagnosis, psychopathology and severity of clinical symptoms were assessed using the Eating Disorder Examination (EDE) interview, the Eating Disorders Inventory (EDI‐2) and clinical parameters (BMI, menstrual status, level of over‐exercising) at baseline and after 3 months.ResultsAfter 3 months of treatment, both treatment groups showed a significant early weight gain, a reduction in the rate of AN diagnoses assessed with the EDE interview and a reduction in EDI‐2 total scores. The combined HT/FBT group showed a significantly greater increase in BMI than the FBT‐only group. In the combined HT/FBT group, none of the patients had to be admitted to hospital, while three (13.6%) of the FBT‐only group had to be referred to inpatient treatment.DiscussionOur results suggest that HT augmented FBT might be useful compared to FBT alone in terms of early weight gain and might reduce the risk of hospital admission in adolescent AN.
Comparative Physicochemical, Microbiological, Antioxidant, and Sensory properties of pre‐ and post‐fermented yoghurt enriched with olive leaf and its extract
Authors: Pourghorban Samira , Yadegarian Linda , Jalili Maryam , Rashidi Ladan 
Published: January 2022

AbstractThis study investigated the comparative effect of yoghurt samples enriched with different concentrations of olive leaf powder (OLP) (0.1, 0.5, 1, and 1.5 mg/ml) and its extract (OLE) (0.5, 1, 3, and 5 mg/ml) on the microbiological, sensory, physicochemical, and antioxidant properties of pre‐ and post‐fermented samples during 21 days of storage. Sensory evaluation showed that concentrations lower than 1.5 and 5 mg/ml of OLP and OLE, respectively, were acceptable. Adding OLP or OLE did not have an influence on yoghurt starter culture bacteria (p > .05). All enriched samples significantly showed higher acidity and lower pH compared with control samples (p < .05). The most important polyphenols were oleuropein (from 0.132 to 0.224 and 0.373 to 0.413 mg/g for 0.5 and 3 mg/ml of OLE, from 0.194 to 0.321 mg/g and 0.413 to 1.280 mg/g for 0.5 and 1 mg/ml of OLP, respectively) and catechin (from 0.369 to 0.382 and 0.461 to 0.477 mg/g for 0.5 and 3 mg/ml of OLE, from 0.386 to 0.405 mg/g and 0.310 to 0.710 mg/g for 0.5 and 1 mg/ml of OLP, respectively) in enriched yoghurts. Adding OLP or OLE increased shelf life, antioxidant activity percentage (AA%), and total phenol content (TPC) of enriched samples (p < .05). During 21 days of storage of all samples, TPC, AA%, and pH decreased and TTA increased.
The expression and function of glutamate aspartate transporters in Bergmann glia are decreased in neuronal nitric oxide synthase‐knockout mice during postnatal development
Authors: Tellios Vasiliki , Maksoud Matthew J. E. , Lu Wei‐Yang 
Published: January 2022

AbstractBergmann glia (BG) predominantly use glutamate/aspartate transporters (GLAST) for glutamate uptake in the cerebellum. Recently, nitric oxide (NO) treatment has been shown to upregulate GLAST function and increase glutamate uptake in vitro. We previously discovered that neuronal nitric oxide synthase knockout (nNOS−/−) mice displayed structural and functional neuronal abnormalities in the cerebellum during development, in addition to previously reported motor deficits. Although these developmental deficits have been identified in the nNOS−/− cerebellum, it is unknown whether BG morphology and GLAST expression are also affected in the absence of nNOS in vivo. This study is the first to characterize BG morphology and GLAST expression during development in nNOS−/− mice using immunohistochemistry and western blotting across postnatal development. Results showed that BG in nNOS−/− mice exhibited abnormal morphology and decreased GLAST expression compared with wildtype (WT) mice across postnatal development. Treating ex vivo WT cerebellar slices with the NOS inhibitor L‐NAME decreased GLAST expression while treating nNOS−/− slices with the slow‐release NO‐donor NOC‐18 increased GLAST expression when compared with their respective controls. In addition, treating primary BG isolated from WT mice with the selective nNOS inhibitor 7N decreased the membrane expression of GLAST and influx of Ca2+/Na+, while treating nNOS−/− BG with SNAP increased the membrane expression of GLAST and Ca2+/Na+ influx. Moreover, the effects of SNAP on GLAST expression and Ca2+/Na+ influx in nNOS−/− BG were significantly reduced by a PKG inhibitor. Together, these results reveal a novel role for nNOS/NO signaling in BG development, regulated by a PKG‐mediated mechanism.
Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans
Authors: Gunewardena Sumedha , Huck Ian , Walesky Chad , Robarts Dakota , Weinman Steven , Apte Udayan 
Published: January 2022

Abstract

Background and Aims
Hepatocyte nuclear factor 4 alpha (HNF4α) is indispensable for hepatocyte differentiation and critical for maintaining liver health. Here, we demonstrate that loss of HNF4α activity is a crucial step in the pathogenesis of chronic liver diseases (CLDs) that lead to development of HCC.

Approach and Results
We developed an HNF4α target gene signature, which can accurately determine HNF4α activity, and performed an exhaustive in silico analysis using hierarchical and K‐means clustering, survival, and rank‐order analysis of 30 independent data sets containing over 3500 individual samples. The association of changes in HNF4α activity to CLD progression of various etiologies, including HCV‐ and HBV‐induced liver cirrhosis (LC), NAFLD/NASH, and HCC, was determined. Results revealed a step‐wise reduction in HNF4α activity with each progressive stage of pathogenesis. Cluster analysis of LC gene expression data sets using the HNF4α signature showed that loss of HNF4α activity was associated with progression of Child‐Pugh class, faster decompensation, incidence of HCC, and lower survival with and without HCC. A moderate decrease in HNF4α activity was observed in NAFLD from normal liver, but a further significant decline was observed in patients from NAFLD to NASH. In HCC, loss of HNF4α activity was associated with advanced disease, increased inflammatory changes, portal vein thrombosis, and substantially lower survival.

Conclusions
In conclusion, these data indicate that loss of HNF4α function is a common event in the pathogenesis of CLDs leading to HCC and is important from both diagnostic and therapeutic standpoints.
The RSPO‐LGR4/5‐ZNRF3/RNF43 module in liver homeostasis, regeneration, and disease
Authors: Annunziato Stefano , Sun Tianliang , Tchorz Jan S. 
Published: January 2022

Abstract
WNT/β‐catenin signaling plays pivotal roles during liver development, homeostasis, and regeneration. Likewise, its deregulation disturbs metabolic liver zonation and is responsible for the development of a large number of hepatic tumors. Liver fibrosis, which has become a major health burden for society and a hallmark of NASH, can also be promoted by WNT/β‐catenin signaling. Upstream regulatory mechanisms controlling hepatic WNT/β‐catenin activity may constitute targets for the development of novel therapies addressing these life‐threatening conditions. The R‐spondin (RSPO)–leucine‐rich repeat‐containing G protein‐coupled receptor (LGR) 4/5–zinc and ring finger (ZNRF) 3/ring finger 43 (RNF43) module is fine‐tuning WNT/β‐catenin signaling in several tissues and is essential for hepatic WNT/β‐catenin activity. In this review article, we recapitulate the role of the RSPO‐LGR4/5‐ZNRF3/RNF43 module during liver development, homeostasis, metabolic zonation, regeneration, and disease. We further discuss the controversy around LGR5 as a liver stem cell marker.