bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Leptin and Earlier Stages of Nephropathy among Type 2 Diabetic Subjects in a Bangladeshi population
Authors: Karim Sheikh Anwarul , Jamal Samira , Ridwan Raihan Sheikh Mahee , Chowdhury Mohammad Alamgir Ahmed , Faroque Omar , Bishwash Kazol Baron , Ali Liaquat , Mehtab Hajera 
Published: January 2022

Objective: To evaluate the relationship of Serum Leptin and Early Nephropathy among uncontrolled type 2 Diabetes Mellitus patients of Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrinology and Metabolism (BIRDEM), Dhaka and Endocrinology department of Sylhet MAG Osmani Medical College (SOMC) & Hospital Sylhet, Bangladesh.
Methods: This study was carried out from January 2013 to December 2015 among 100 type 2 diabetic patients from the outpatient department (OPD) BIRDEM and SOMC hospital.
Results: 16 out of 30 controls and 65 out of 100 people with diabetes have a family history of diabetes. Early retinopathy and neuropathy were observed in 45.5% and 36.5% diabetic subjects. Mean±SD of serum urea in control subjects was 28.65±6.27; in diabetic subjects was 30.21±7.67. Serum creatinine in controls was 1.12±0.24, in diabetic subjects was 1.13±0.25. Serum leptin levels in control subjects {1.65 (0.05-8.66)} was lower than diabetic counterpart {1.21 (0.11-13.3)}. Leptin levels in male controls {(1.29 (0.05-2.49)} was significantly (P 0.000) lower than the female controls {4.03 (0.05-8.66)}.
Conclusion: It was evident that there was very little or no association between serum leptin level and the indices of renal function. No changes of circulating serum Leptin concentration in the earlier stages of Diabetic Nephropathy were found.
A Phase 1 study of GDC‐0134, a dual leucine zipper kinase inhibitor, in ALS
Authors: Katz Jonathan S. , Rothstein Jeffrey D. , Cudkowicz Merit E. , Genge Angela , Oskarsson Björn , Hains Avis B. , Chen Chen , Galanter Joshua , Burgess Braydon L. , Cho William , Kerchner Geoffrey A. , Yeh Felix L. , Ghosh Arundhati Sengupta , Cheeti Sravanthi , Brooks Logan , Honigberg Lee , Couch Jessica A. , Rothenberg Michael E. , Brunstein Flavia , Sharma Khema R. , van den Berg Leonard , Berry James D. , Glass Jonathan D. 
Published: January 2022

AbstractObjectiveDual leucine zipper kinase (DLK), which regulates the c‐Jun N‐terminal kinase pathway involved in axon degeneration and apoptosis following neuronal injury, is a potential therapeutic target in amyotrophic lateral sclerosis (ALS). This first‐in‐human study investigated safety, tolerability, and pharmacokinetics (PK) of oral GDC‐0134, a small‐molecule DLK inhibitor. Plasma neurofilament light chain (NFL) levels were explored in GDC‐0134‐treated ALS patients and DLK conditional knockout (cKO) mice.MethodsThe study included placebo‐controlled, single and multiple ascending‐dose (SAD; MAD) stages, and an open‐label safety expansion (OLE) with adaptive dosing for up to 48 weeks.ResultsForty‐nine patients were enrolled. GDC‐0134 (up to 1200 mg daily) was well tolerated in the SAD and MAD stages, with no serious adverse events (SAEs). In the OLE, three study drug‐related SAEs occurred: thrombocytopenia, dysesthesia (both Grade 3), and optic ischemic neuropathy (Grade 4); Grade ≤2 sensory neurological AEs led to dose reductions/discontinuations. GDC‐0134 exposure was dose‐proportional (median half‐life = 84 h). Patients showed GDC‐0134 exposure‐dependent plasma NFL elevations; DLK cKO mice also exhibited plasma NFL compared to wild‐type littermates.InterpretationThis trial characterized GDC‐0134 safety and PK, but no adequately tolerated dose was identified. NFL elevations in GDC‐0134‐treated patients and DLK cKO mice raised questions about interpretation of biomarkers affected by both disease and on‐target drug effects. The safety profile of GDC‐0134 was considered unacceptable and led to discontinuation of further drug development for ALS. Further work is necessary to understand relationships between neuroprotective and potentially therapeutic effects of DLK knockout/inhibition and NFL changes in patients with ALS.
The Learning Loop: Conceptualizing Just‐in‐Time Faculty Development
Authors: Yilmaz Yusuf , Papanagnou Dimitrios , Fornari Alice , Chan Teresa M. 
Published: January 2022

AbstractBackgroundAs technology advances, the gap between learning and doing continues to close—especially for frontline academic faculty and clinician educators. For busy clinician faculty members, it can be difficult to find time to engage in skills and professional development. Competing interests between clinical care and various forms of academic work (e.g., research, administration, education) all create challenges for traditional group‐based and/or didactic faculty development.MethodsThe authors engaged in a synthetic narrative review of literature from several unrelated fields: learning technologies, medical education/health professions education, general/higher education. The aim for this review was to synthesize this pre‐existing literature to propose a new conceptual model.ResultsThe authors propose a new conceptual model, theJust‐In‐Time Learning Loop, to guide the development of online faculty development for just‐in‐time delivery.ConclusionsTheJust‐In‐Time Learning Loopis a new conceptual framework that may be of use to those engaging in online, digital learning design. Faculty developers, especially in emergency medicine, can integrate leading concepts from the technology‐enhanced learning field (e.g., microlearning, micro‐credentialing, badging) to create new types of learning experiences for their end‐users.
The Journal Club 3.0: A qualitative, multisite study examining a new educational paradigm in the era of open educational resources
Authors: Ting Daniel K. , Bailey Britt H. , Scheuermeyer Frank X. , Harris Devin R. , Chan Teresa M. 
Published: January 2022

AbstractBackgroundThe journal club is a ubiquitous and time‐honored tradition within medical education. However, in recent years, open educational resources (OERs) have become increasingly influential in how physicians interact with the medical literature across multiple specialties. The authors sought to explore how emergency medicine (EM) resident physicians reconcile different perspectives across OERs into their educational experience at the journal club.MethodsFrom January 2018 to September 2019, the authors enrolled 25 EM residents from four teaching sites associated with the University of British Columbia, Canada, to participate in either a focus group (seven residents) or individual interviews (18 residents). The authors used a snowball sampling technique. Using a constructivist grounded theory analysis, two investigators independently reviewed transcripts, meeting regularly to discuss themes until sufficiency was achieved.ResultsThe study data expand the theoretical understanding of the resident journal club experience. Residents used multiple sources including OERs to learn about new evidence in the specialty. The rise of OERs helped residents to focus on developing critical appraisal skills and social bonds during the journal club. The local journal club gained a new relevancy in acting as a quality control mechanism against the premature adoption of research findings discussed in OERs.DiscussionTo date, most educators assume that residents prepare for a journal club by reading the selected articles and applying knowledge from their previous education. Instead, our findings suggest a more dynamic experience that integrates OERs. OERs enhance the journal club experience by allowing junior residents to more easily participate in discussions and to broaden the discussion to multiple clinical settings. Understanding these processes could inform future educational strategies around the journal club.
Hydrodynamics of an inverse liquid–solid circulating conventional fluidized bed
Authors: Nan Tian , Zhu Jesse 
Published: January 2022

AbstractAn inverse liquid–solid circulating conventional fluidized bed (I‐CCFB) is realized by injecting particles from the top of a conventional liquid–solid fluidized bed (0.076 m ID and 5.4 m height) that is operated in a newly developed circulating conventional fluidization regime located between the conventional and circulating fluidization regimes. The I‐CCFB can achieve a higher solids holdup compared to both conventional and circulating liquid–solid fluidized beds. A new parameter, the bed intensification factor, is defined to quantify the increased solids holdup observed with external solids circulation. The Richardson–Zaki equation is shown to be applicable to the I‐CCFB regime and can be used to correlate the slip velocity and solids holdup, both of which increase with the solids circulation rate. A new flow regime map is presented, including the I‐CCFB and a variety of other liquid–solid fluidized beds.
Geometric Criterion of Topological Phase Transition for Non‐Hermitian Systems
Authors: Fan Annan , Liang Shi‐Dong 
Published: January 2022

AbstractA geometric criterion of the topological phase transition for non‐Hermitian systems is proposed, based on the length of the boundary of the bulk band in the complex energy plane for non‐Hermitian systems. For 1D systems, it is found that the topological phase transition occurs when the derivatives of the length with respect to parameters are discontinuous. For 2D systems, when the length is discontinuous, the topological phase transitions between the gapped and gapless phases occur. When the derivatives of the length with respect to parameters are discontinuous, the topological phase transition between the gapless and gapless phases occur. These nonanalytic behaviors of the length in the complex energy plane provide a signal to detect the topological phase transitions, which is demonstrated by the 1D non‐Hermitian Su–Schrieffer–Heeger model and the 2D non‐Hermitian Chern insulator model. This geometric criterion provides an efficient insight into the global topological invariant from a geometric local object in the complex energy plane for non‐Hermitian systems.
Direct and Unified Access to Carbon Radicals from Aliphatic Alcohols by Cost‐Efficient Titanium‐Mediated Homolytic C−OH Bond Cleavage
Authors: Suga Takuya , Takahashi Yuuki , Miki Chinatsu , Ukaji Yutaka 
Published: January 2022

AbstractLow‐valent Ti‐mediated homolytic C−O bond cleavage offers unified access to carbon radicals from ubiquitous non‐activated tertiary, secondary, and even primary alcohols. In contrast to the representative Ti reagents, which were ineffective for this purpose, “TiCl2(cat)”/Zn (cat=catecholate) was found to be specifically active. This method was applied to the addition reactions of radicals to alkenes and exhibited high generality and yields. More than 50 combinations were examined. The excellent cost‐efficiency and accessibility of “TiCl2(cat)”/Zn further enhance its applicability. Control experiments proved the presence of a carbon radical intermediate and excluded the pathway via alkyl chlorides. Further mechanistic study indicated that the 1 : 2 complex of alkoxide (R−O−) and TiIII is an active species in the C−O cleavage.
Fabricating bimodal microcellular structure in polystyrene/carbon nanotube/glass‐fiber hybrid nanocomposite foam by microwave‐assisted heating: A proof‐of‐concept study
Authors: Shahbazi Mehrnaz , Aghvami‐Panah Mohammad , Panahi‐Sarmad Mahyar , Seraji Amir Abbas , Zeraatkar Ali , Ghaffarian Anbaran Reza , Xiao Xueliang 
Published: January 2022

AbstractIn the current study, polystyrene/carbon nanotubes/glass fiber (PS/CNT/GF) hybrid foam with a bimodal cellular‐structure has been fabricated via microwave heating as a novel energy source. Microwave‐assisted (MA) samples not only demonstrated the lowest density as compared to traditional methods but also represented superior compressive mechanical properties. Since the bimodal morphology has not been seen so far, the role of selective microwave heating has been thoroughly investigated from the microstructural point of view. Accordingly, the amount of receiving microwave radiations to heat up the system is controllable via the CNTs (as nucleating agents and absorbers) as well as radiation time. Moreover, 1–15 wt% fibers were incorporated to enhance mechanical performance, which led to turning uniform cellular structure to the bimodal pattern, and its cell morphological was studied thereafter. Electrical conductivity and dielectric permittivity properties have not been deprived of bimodality benefits which have been rigorously proven.
Design, synthesis, in silico ADMET, docking, and antiproliferative evaluations of [1,2,4]triazolo[4,3‐c]quinazolines as classical DNA intercalators
Authors: Alesawy Mohamed S. , Ibrahim Mohamed‐Kamal , Eissa Ibrahim H. , El‐Adl Khaled 
Published: January 2022

AbstractEleven novel [1,2,4]triazolo[4,3‐c]quinazolines were designed, synthesized, and evaluated against HepG2 and HCT‐116 cells. The molecular design was performed to investigate the binding mode of the proposed compounds with the DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling. HCT‐116 was found to be the most sensitive cell line to the influence of the new derivatives. In particular, compounds 6f and 6e were found to be the most potent derivatives over all the tested compounds against the two HepG2 and HCT116 cancer cell lines, with IC50 = 23.44 ± 2.9, 12.63 ± 1.2, and 25.80 ± 2.1, and 14.32 ± 1.5 µM, respectively. Although compounds 6f and 6e displayed less activity than doxorubicin (IC50 = 7.94 ± 0.6 and 8.07 ± 0.8 µM, respectively), both could be useful as a template for future design, optimization, and investigation to produce more potent anticancer analogs. The most active derivatives 6a, 6c, 6e, and 6f were evaluated for their DNA‐binding activities. Compound 6f displayed the highest binding affinity. This compound potently intercalates DNA at a decreased IC50 value (54.08 µM). Compounds 6a, 6c, and 6e exhibited good DNA‐binding affinities, with IC50 values of 79.35, 84.08, and 59.35 µM, respectively. Furthermore, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles were calculated for the four most active compounds in comparison to doxorubicin as a reference drug. Our derivatives 6a, 6c, 6e, and 6f displayed very good in‐silico‐predicted ADMET profiles. Doxorubicin violates three of Lipinski's rules, our derivatives 6a, 6c, 6e, and 6f do not violate any rule.
Reactive Extraction of Gallic Acid Using Trioctylamine and Tributyl Phosphate with Natural Oils
Authors: Pandey Shitanshu , Wasewar Kailas S. , Datta Dipaloy , Kumar Sushil 
Published: January 2022

AbstractExperimental and theoretical perspectives of reactive extraction of gallic acid (GA) from aqueous solutions using tri‐n‐butyl phosphate (TBP) and tri‐n‐octylamine (TOA) as extractant dissolved in three nontoxic natural oils, namely, rice bran oil, sunflower oil, and soybean oil, are investigated. The solvent's extractability is observed in an order of sunflower oil > rice bran oil > soybean oil and rice bran oil > sunflower oil > soybean oil with TOA and TBP, respectively. The theoretical insights of reaction mechanisms for the extraction of GA are estimated in the form of overall equilibrium constants (KE), stoichiometric coefficients (m), individual equilibrium constants (K11, K12, K21), and concentrations (C11, C12, and C21) of various complexes formed between extractant and acid.
Temperature and water activity control in a lipase catalyzed esterification process using nonlinear model predictive control
Authors: Zulkeflee Siti Asyura , Rohman Fakhrony Sholahudin , Sata Suhairi Abdul , Aziz Norashid 
Published: January 2022

AbstractControlling the batch esterification process is a difficult task because the kinetics of the process incorporate intrinsic nonlinearity, process uncertainty, and model mismatch. The model predictive control (MPC) was created and used in the lipase‐catalyzed esterification process in this study. The Autoregressive with Exogenous Input (ARX) and Nonlinear Autoregressive with Exogenous Input (NARX) models were embedded in the MPC. The controller's goal is to manipulate the jacket flow rate and air flow rate, respectively, to control reactor temperature and water activity. To identify the best controller performance, the ARX‐MPC and NARX‐MPC parameters of horizon time (P), number of control moves (M), and weighting factor (wk and rk) were tuned in tracking set point. In terms of set point tracking, disturbance rejection, and robustness test, the best‐tuned ARX‐MPC and NARX‐MPC controllers were assessed and compared. Due to smaller integral square error (ISE), quicker settling time, streamlined response, and manipulated variables remaining within their permitted constraints, the NARX‐MPC controller outperformed the ARX‐MPC controller.
Axially Chiral Dodecanuclear Lanthanide Clusters Constructed by “Bottom‐Up” Self‐assembly for Enantioselective Sensing
Authors: Zhao Honglei , Cui Dongxu , Kou Junning , Gao Haijuan , Yu Guanghui , Sun Chunyi , Wang Xinlong , Su Zhongmin 
Published: January 2022

Comprehensive SummaryVia the bottom‐up synthetic strategy, we synthesized a pair of dodecanuclear metal clusters of Eu12(C2O4)9(R/S‐BNP)18(EtOH)6(H2O)6·8EtOH·7H2O (complex 2), which represent the largest axial chiral lanthanide metal clusters. In the structure, rare four‐pointed star coordination mode of oxalic acid is reported by this work. In addition, as a fluorescence sensor, the complex 2 exhibits high enantioselectivity for R‐/S‐BINOL‐TF2 (EF = 2.87) and other chiral binaphthyl derivatives.
Proteomic differences among patients with heart failure taking furosemide or torsemide
Authors: Cooper Lauren B. , Bruce Scott , Psotka Mitchell , Mentz Robert , Bell Rachel , Seliger Stephen L. , O'Connor Christopher , deFilippi Christopher 
Published: January 2022

AbstractBackgroundLoop diuretics are commonly used for patients with heart failure (HF) but it remains unknown if one loop diuretic is clinically superior.HypothesisBiomarkers and proteomics provide insight to how different loop diuretics may differentially affect outcomes.MethodsBlood and urine were collected from outpatients with HF who were taking torsemide or furosemide for >30 days. Differences were assessed in cardiac, renal, and inflammatory biomarkers and soluble protein panels using the Olink Cardiovascular III and inflammation panels.ResultsOf 78 subjects, 55 (71%) were treated with furosemide and 23 (29%) with torsemide, and 25 provided a urine sample (15 treated with furosemide, 10 with torsemide). Patients taking torsemide were older (68 vs 64 years) with a lower mean eGFR (46 vs 54 ml/min/1.73 m2), a higher proportion were women (39% vs 24%) and Black (43% vs 27%). In plasma, levels of hs‐cTnT, NT‐proBNP, and hsCRP were not significantly different between groups. In urine, there were significant differences in urinary albumin, β‐2M, and NGAL, with higher levels in the torsemide‐treated patients. Of 184 proteins testing in Olink panels, in plasma, 156 (85%) were higher in patients taking torsemide but none were significantly different after correcting for false discovery.ConclusionsWe show differences in urinary biomarkers but few differences in plasma biomarkers among HF patients on different loop diuretics. Olink technology can detect differences in plasma protein levels from multiple biologic domains. These findings raise the importance of defining differences in mechanisms of action of each diuretic in an appropriately powered study.
Anti‐LINGO‐1 antibody treatment alleviates cognitive deficits and promotes maturation of oligodendrocytes in the hippocampus of APP/PS1 mice
Authors: Yang Hao , Jiang Lin , Zhang Yi , Liang Xin , Tang Jing , He Qi , Luo Yan‐Min , Zhou Chun‐Ni , Zhu Lin , Zhang Shan‐Shan , Xiao Kai , Zhu Pei‐Lin , Wang Jin , Li Yue , Chao Feng‐Lei , Tang Yong 
Published: January 2022

AbstractLeucine‐rich repeat and immunoglobulin‐like domain‐containing nogo receptor‐interacting protein 1 (LINGO‐1), a negative regulator of oligodendrocyte differentiation and myelination, is associated with cognitive function, and its expression is highly upregulated in Alzheimer's disease (AD) patients. Anti‐LINGO‐1 antibody treatment can effectively antagonize the negative regulatory effect of LINGO‐1. In this study, we aim to assess the effect of anti‐LINGO‐1 antibody treatment on cognition and hippocampal oligodendrocytes in an AD transgenic animal model. First, 10‐month‐old male amyloid‐β (Aβ) protein precursor (APP)/presenilin 1 (PS1) mice were administered anti‐LINGO‐1 antibody for 8 weeks. Then, learning and memory abilities were assessed with the Morris water maze (MWM) and Y‐maze tests, and Aβ deposition and hippocampal oligodendrocytes were investigated by immunohistochemistry, immunofluorescence, and stereology. We found that anti‐LINGO‐1 antibody alleviated the deficits in spatial learning and memory abilities and working and reference memory abilities, decreased the density of LINGO‐1 positive cells, decreased Aβ deposition, significantly increased the number of mature oligodendrocytes and the density of myelin, reversed the abnormal increases in the number of oligodendrocyte lineage cells and the densities of oligodendrocytes precursor cells in APP/PS1 mice. Our results provide evidence that LINGO‐1 might be involved in the process of oligodendrocyte dysmaturity in the hippocampus of AD mice, and that antagonizing LINGO‐1 can alleviate cognitive deficits in APP/PS1 mice and decrease Aβ deposition and promote oligodendrocyte differentiation and maturation in the hippocampus of these mice. Our findings suggest that changes in LINGO‐1 and oligodendrocytes in the hippocampus play important roles in the pathogenesis of AD and that antagonizing LINGO‐1 might be a potential therapeutic strategy for AD.
Mechanochemical C−X/C−H Functionalization: An Alternative Strategic Access to Pharmaceuticals
Authors: Yang Xinjie , Wu Chongyang , Su Weike , Yu Jingbo 
Published: January 2022

AbstractIn the pursuit of clean pharmaceutical production, chemists in medicinal industry require access to new sustainable methodologies to reduce and even eliminate pollution, which is mainly produced by the overuse of organic solvents during chemical synthesis of active pharmaceutical ingredients (APIs). In this context, the solvent‐free/less mechanochemical functionalization of small molecules has gradually emerged as a powerful strategy for the green synthesis and modification of APIs, bioactive compounds, and functional materials. In this review, we present an overview of mechanochemical C−X/C−H functionalization applications to medicinal chemistry, involving cross‐coupling, cross‐dehydrogenative coupling, oxidative coupling (via C−H activation pathway), and direct coupling (via radical pathway) as key steps for the preparation of APIs and bioactive compounds.
Cucurbit[7]uril‐Catalyzed Controllable Pinacol Rearrangement with Activated Hydride Migration
Authors: Jin Ye , Li Min , Liu Mao , Ge Qingmei , Cong Hang , Tao Zhu 
Published: January 2022

AbstractA selective pinacol rearrangement of hydrobenzoin compounds was established through a heterogeneous catalysis strategy in the presence of cucurbit[7]uril. As an unexpected consequence, the ketone was generated as the sole product with the cucurbit[7]uril‐controlled hydride migration under optimized conditions. The five recycled runs suggested the catalytic activity of the cucurbit[7]uril remained. The experimental analysis and DFT calculation disclosed the important role of supramolecular encapsulation of substrates within the cavity of the macrocyclic host to fix the phenyl groups on hydrobenzoin compounds and trigger the hydride migration, therefore, ketone was the prior product.