bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new synthetic route for synthesis of 3‐substituted imidazo[1,5‐a]pyridines
Authors: Bori Jugal , Manivannan Vadivelu 
Published: January 2022

AbstractA new convenient route for the synthesis of 3‐substituted‐imidazo[1,5‐a]pyridines has been described as well as the scope and limitations of the method are evaluated. By reacting 2‐picolylamine and different aldehydes in presence of selenium dioxide as the oxidant, a series of 3‐substituted imidazo[1,5‐a]pyridines was isolated in good yields. Different kinds of aldehydes such as aliphatic, aromatic, heterocyclic as well as aromatic ring carrying some substituents have been used.
Biomarkers for drug development in propionic and methylmalonic acidemias
Authors: Longo Nicola , Sass Jörn Oliver , Jurecka Agnieszka , Vockley Jerry 
Published: January 2022

AbstractThere is an unmet need for the development and validation of biomarkers and surrogate endpoints for clinical trials in propionic acidemia (PA) and methylmalonic acidemia (MMA). This review examines the pathophysiology and clinical consequences of PA and MMA that could form the basis for potential biomarkers and surrogate endpoints. Changes in primary metabolites such as methylcitric acid (MCA), MCA:citric acid ratio, oxidation of 13C‐propionate (exhaled 13CO2), and propionylcarnitine (C3) have demonstrated clinical relevance in patients with PA or MMA. Methylmalonic acid, another primary metabolite, is a potential biomarker, but only in patients with MMA. Other potential biomarkers in patients with either PA and MMA include secondary metabolites, such as ammonium, or the mitochondrial disease marker, fibroblast growth factor 21. Additional research is needed to validate these biomarkers as surrogate endpoints, and to determine whether other metabolites or markers of organ damage could also be useful biomarkers for clinical trials of investigational drug treatments in patients with PA or MMA. This review examines the evidence supporting a variety of possible biomarkers for drug development in propionic and methylmalonic acidemias.
Value of T2 Mapping MRI for Prostate Cancer Detection and Classification
Authors: Klingebiel Maximilian , Schimmöller Lars , Weiland Elisabeth , Franiel Tobias , Jannusch Kai , Kirchner Julian , Hilbert Tom , Strecker Ralph , Arsov Christian , Wittsack Hans‐Jörg , Albers Peter , Antoch Gerald , Ullrich Tim 
Published: January 2022

BackgroundCurrently, multi‐parametric prostate MRI (mpMRI) consists of a qualitative T2, diffusion weighted, and dynamic contrast enhanced imaging. Quantification of T2 imaging might further standardize PCa detection and support artificial intelligence solutions.PurposeTo evaluate the value of T2 mapping to detect prostate cancer (PCa) and to differentiate PCa aggressiveness.Study TypeRetrospective single center cohort study.PopulationForty‐four consecutive patients (mean age 67 years; median PSA 7.9 ng/mL) with mpMRI and verified PCa by subsequent targeted plus systematic MR/ultrasound (US)‐fusion biopsy from February 2019 to December 2019.Field Strength/SequenceStandardized mpMRI at 3 T with an additionally acquired T2 mapping sequence.AssessmentPrimary endpoint was the analysis of quantitative T2 values and contrast differences/ratios (CD/CR) between PCa and benign tissue. Secondary objectives were the correlation between T2 values, ISUP grade, apparent diffusion coefficient (ADC) value, and PI‐RADS, and the evaluation of thresholds for differentiating PCa and clinically significant PCa (csPCa).Statistical TestsMann–Whitney test, Spearman's rank (rs) correlation, receiver operating curves, Youden's index (J), and AUC were performed. Statistical significance was defined as P < 0.05.ResultsMedian quantitative T2 values were significantly lower for PCa in PZ (85 msec) and PCa in TZ (75 msec) compared to benign PZ (141 msec) or TZ (97 msec) (P < 0.001). CD/CR between PCa and benign PZ (51.2/1.77), respectively TZ (19.8/1.29), differed significantly (P < 0.001). The best T2‐mapping threshold for PCa/csPCa detection was for TZ 81/86 msec (J = 0.929/1.0), and for PZ 110 msec (J = 0.834/0.905). Quantitative T2 values of PCa did not correlate significantly with the ISUP grade (rs = 0.186; P = 0.226), ADC value (rs = 0.138; P = 0.372), or PI‐RADS (rs = 0.132; P = 0.392).Data ConclusionQuantitative T2 values could differentiate PCa in TZ and PZ and might support standardization of mpMRI of the prostate. Different thresholds seem to apply for PZ and TZ lesions. However, in the present study quantitative T2 values were not able to indicate PCa aggressiveness.Level of Evidence2Technical EfficacyStage 2
Coastal salt marsh restoration drives element composition of soils toward its original state by recovering soil organic matter
Authors: Wang Guodong , Jiang Ming , Wang Ming 
Published: January 2022

AbstractLarge areas of coastal wetlands have been restored recently throughout the world; it is important to know if restoration practice recovers original levels of biogeochemical functioning in coastal wetlands. We did samplings in five sites in the Liaohe River Delta, China. Each site had three salt marsh types: natural, restored, and degraded. We measured the concentrations of 43 elements and environmental variables including soil organic matter, soil electrical conductivity, soil pH, soil salinity, and soil water content. Concentrations of 39 elements differed significantly between salt marsh types. The values of the concentrations of 39 elements in the restored salt marshes were all in between those of natural and degraded salt marshes. Soil organic matter and the relative abundance of most elements including nutrients and metals increased simultaneously during restoration. Redundancy analysis indicated that soil organic matter explained 72.1% of the total variation in element composition. Our findings indicated that the recovery of soil biogeochemical functioning in salt marshes was driven by the accumulation of soil organic matter during restoration. It may take a very long time for the soil composition and biogeochemistry to reach the original levels prior to disturbance.
Virtual Screening Inhibitors of Ubiquitin‐specific Protease 7 Combining Pharmacophore Modeling and Molecular Docking
Authors: Zhang Siyu , Wang Yifan , Liu Lu , Zhao Guangjian , Sun Yujie , Wang Juan , Liu Fang , Wang Peng , Xu Ximing 
Published: January 2022

AbstractUbiquitin‐specific protease 7 (USP7) is one of the most extensively studied deubiquitinases. USP7 exhibits a high expression signature in various malignant tumors, suggesting that it is a marker of tumor prognosis and a potential drug target for anti‐tumor therapy. In this study, virtual screening based on pharmacophore model and biological evaluation have been applied for the discovery of novel USP7 inhibitors targeting the catalytic active site. The TS‐4 was screened from 215,480 small molecules and was found to have USP7 inhibitory activity. Preliminary in vitro studies disclosed its antiproliferative activity on human colon cancer cell lines (HCT‐116 and RKO), compared with normal colon cell line (CCD841CoN). Molecular dynamics (MD) simulation revealed the combine mechanism between USP7 with the TS‐4. The TS‐4 formed stable interactions with Asp295, Phe409 and Tyr514, which were critical to enhance its biological activity. This compound will serve as a promising hit compound for facilitating the further design of novel USP7 inhibitors.
Burden of central nervous system complications in sickle cell disease: A systematic review and meta‐analysis
Authors: Lee Soyon , Lucas Sedge , Proudman David , Nellesen Dave , Paulose Jincy , Sheehan Vivien A. 
Published: January 2022

AbstractSickle cell disease (SCD) patients are at high risk of central nervous system (CNS) complications and may experience significant morbidity. The study was conducted to describe the comprehensive burden of SCD‐related CNS complications and to identify patient‐reported outcome (PRO) instruments for future research. The review included 32 studies published from January 2000 to 2020, evaluating humanistic and economic outcomes. Twenty‐three studies reported humanistic outcomes, 16 of which measured cognitive function using Wechsler Intelligence Scales. A meta‐analysis was conducted, finding full‐scale intelligence quotient (IQ) was significantly lower in: overt stroke versus controls: −12.6 (p < .001); silent cerebral infarct (SCI) versus controls: −5.7 (p < .001); overt stroke versus SCI: −9.4 (p = .008); and any event versus controls: −7.6 (p < .001). This review quantified the cognitive deficits associated with CNS complications in pediatric SCD populations and highlights the need for improved prevention/treatment. As PRO evidence was limited, we discussed areas for future research.
Underlying genetic etiologies of congenital diaphragmatic hernia
Authors: Scott Daryl A. , Gofin Yoel , Berry Aliska M. , Adams April D. 
Published: January 2022

AbstractCongenital diaphragmatic hernia (CDH) is often detectable prenatally. Advances in genetic testing have made it possible to obtain a molecular diagnosis in many fetuses with CDH. Here, we review the aneuploidies, copy number variants (CNVs), and single genes that have been clearly associated with CDH. We suggest that array‐based CNV analysis, with or without a chromosome analysis, is the optimal test for identifying chromosomal abnormalities and CNVs in fetuses with CDH. To identify causative sequence variants, whole exome sequencing (WES) is the most comprehensive strategy currently available. Whole genome sequencing (WGS) with CNV analysis has the potential to become the most efficient and effective means of identifying an underlying diagnosis but is not yet routinely available for prenatal diagnosis. We describe how to overcome and address the diagnostic and clinical uncertainty that may remain after genetic testing, and review how a molecular diagnosis may impact recurrence risk estimations, mortality rates, and the availability and outcomes of fetal therapy. We conclude that after the prenatal detection of CDH, patients should be counseled about the possible genetic causes of the CDH, and the genetic testing modalities available to them, in accordance with generally accepted guidelines for pretest counseling in the prenatal setting.
Prenatal diagnosis of VACTERL association in the first trimester
Authors: Zhang Wen , Chen Jiao 
Published: January 2022

Key pointsWhat's already known about this topic?

Only four cases of VACTERL association diagnosed in the first trimester have been reported

What does this study add?

We show that VACTERL association can present with a broad range of findings, including anal atresia, foot dysplasia, hemivertebrae, a single umbilical artery, and closed spina bifida

VACTERL association can be suspected at the time of a first trimester ultrasound
Recent Progress and Future Perspectives of Carbon Dots in the Detection, Degradation, and Enhancement of Drugs
Authors: Korah Binila K. , Chacko Anu Rose , Abraham Thomas , Mathew Beena 
Published: January 2022

AbstractCarbon dots (CDs) are new types of nanoparticles with sizes less than 10 nm in diameter. CDs with their unique properties can detect, degrade, and surprisingly enhance drugs. This review focuses on three major aspects of CD‐drug interactions: detection, degradation, and enhancement of drugs using CDs. The review begins with a brief account of the significant development milestones, the synthetic approaches adopted, and modification methods. The detection section of the review moves on to a classified presentation of modified and unmodified CDs in drug detection, as well as an examination of the tactics and background hypotheses required to confirm the mechanism. Following that, specific attention is paid to the structural and optical features of CD/photocatalytic systems, as well as a summary of CD's role in photocatalytic degradation. A thorough examination of the changes in photocatalyst properties when they are composited with CDs, is also carried out, as well as the characterization techniques used to confirm the presence of CDs. Even though the enhancement section is still in its infancy, special attention is paid to pique readers’ interest in further research in that field. Finally, new paths are proposed based on the gaps, challenges, and future perspectives.
A remote ethnography methodology to gain packaging behaviour insights
Authors: Clark Nikki , Trimingham Rhoda , Wilson Garrath T. 
Published: January 2022

AbstractRemote ethnography requires the observation of human interaction in the natural world without the researcher being present. Well‐established in industrial and user experience design remote ethnography provides insight into the user's behaviour whilst completing a specific task in a defined environment. Designers in established fields such as Design for Sustainable Behaviour have applied this behavioural understanding to develop interventions to positively adapt unsustainable behaviours. Existing research techniques have evidenced limitations in fully understanding consumer packaging disposal behaviour, with a clear gap in behavioural insights with packaging used out of the home. A novel mixed‐methods approach was developed using remote ethnography to explore consumer food‐to‐go packaging disposal behaviour out of the home, providing insights which could be evaluated for their application within the packaging development process. In explaining the new methodological approach, this paper (a) proposes a mixed‐methods approach by which packaging developers can better understand packaging disposal behaviour out of the home, (b) explains this research method in the context of a food‐to‐go packaging disposal case study and (c) evaluates the value of the mixed‐methods approach within the food packaging development process.
Violating the standard assumption underlying the process monitoring: Perfect measurements
Authors: Rehman Aqeel ur , Shabbir Javid , Munir Tahir , Ahmad Shabbir , Riaz Muhammad 
Published: January 2022

AbstractThe presence of the measurement errors is a rule rather than an exception in any process monitoring context. Since the observations are generally observed, in quick manner, by some measuring process and are time ordered. Moreover, their presence contributes negatively towards the performance of the usual control charting schemes. Therefore, it will be naïve and may lead to invalid conclusions to devise a control structure, without taking them into account, at first place, and then counteracting their adverse effect. This paper studies the foregoing impact on the performance of two eminent charts, for mean or average parameter of a process, namely: Crosier CUSUM and Dual CUSUM charts. With growing intensity of the error variation, a deteriorating performance of the said charts has been observed. The average run length (ARL) behaviors, zero‐state, and steady‐state, of both charts are studied, using Monte‐Carlo simulation algorithm, under different situations for the effect of measurement errors. Also, extra quadratic loss, relative ARL and performance comparison index (abbreviated as EQL, RARL, and PCI, respectively) are used to evaluate the performance of the charts. Repeated measurements are employed, as a remedial scheme, for the effect of measurement errors. An illustrative example is incorporated to elucidate the study.
PFAS Experts Symposium 2: PFAS Toxicology and Risk Assessment in 2021—Contemporary issues in human and ecological risk assessment of PFAS
Authors: Zodrow Jean , Vedagiri Usha , Sorell Tamara , McIntosh Lisa , Larson Emily , Hall Linda , Dourson Michael , Dell Linda , Cox Douglas , Barfoot Krista , Anderson Janet 
Published: January 2022

AbstractThis paper summarizes key information on topics of contemporary interest in human and ecological per‐ and polyfluoroalkyl substance (PFAS) risk assessment, which were discussed at the PFAS Experts Symposium 2. For human health, the discussion focused on the toxicologic and epidemiologic endpoints and exposure assumptions that contribute to differences in PFAS regulatory criteria. For ecological risk, the discussion assessed the current state of the science available to support ecological screening levels and identified key data gaps and uncertainties in our understanding of ecological exposure and toxicity. Finally, the paper summarizes a panel discussion that addressed the challenges and uncertainties of regulating PFAS as a class.
Energy shaping control for systems with underactuation degrees two by controlled Lagrangian method
Authors: Liu Ce 
Published: January 2022

AbstractThis article investigates underactuated systems' energy shaping control by controlled Lagrangian (CL) method. The existence of CL based control depends on a set of matching conditions, which are usually in terms of partial differential equations (PDEs). In this work, the matching conditions are derived and simplified for underactuation‐degrees‐two systems. Moreover, the solvability conditions are provided for a class of systems satisfying Assumptions 1 and 2, based on which the controlled energy could be explicitly solved. By the proposed matching solution method, the desired equilibrium can be effectively assigned. The proposed matching controller is implemented for a strongly coupled single rigid body system with six degrees of freedom for the first time. Smooth state feedback control laws guaranteeing asymptotic stability of the system are presented. The range of the control parameters could be obtained based on the positive definiteness of reshaped closed‐loop energy. Simulations for comparison with relate work show the effectiveness of the theoretical results.
Enzyme‐Loaded Hemin/G‐Quadruplex‐Modified ZIF‐90 Metal–Organic Framework Nanoparticles: Bioreactor Nanozymes for the Cascaded Oxidation of N‐hydroxy‐l‐arginine and Sensing Applications
Authors: Chen Chaochao , Vázquez‐González Margarita , O'Hagan Michael P. , Ouyang Yu , Wang Zhanhui , Willner Itamar 
Published: January 2022

AbstractBiocatalytic cascades are challenging to operate in homogeneous solution, where diffusional mass transport hinders efficient communication between the reactive components. There is great interest in developing devices to perform such transformations in confined environments, which increase the efficiency of the cascaded process by generating high local concentrations of the reactive species. Herein, a bioreactor‐nanozyme assembly is introduced for the cascaded aerobic oxidation of N‐hydroxy‐l‐arginine (NOHA) to citrulline in the presence of glucose. The reaction mimics a key step in the nitric oxide synthase oxidation of l‐arginine in nature. The system consists of glucose oxidase (GOx)‐loaded hemin/G‐quadruplex (hemin/G4)‐modified ZIF‐90 metal–organic framework nanoparticles. The aerobic oxidation of glucose by GOx yields H2O2 that fuels the hemin/G4‐catalyzed oxidation of NOHA into citrulline. The process driven by the bioreactor‐nanozyme system is ≈sixfold enhanced compared to the homogeneous mixture of the biocatalysts, due to its operation in the confined environment of the nanoparticles. Extension to a three‐step cascade is then demonstrated using a bioreactor composed of β‐galactosidase/GOx‐loaded hemin/G4‐modified ZIF‐90 nanoparticles activating the cascaded oxidation of NOHA to citrulline, in the presence of lactose. Moreover, the bioreactor‐nanozyme hybrid is applied as a functional optical sensor of glucose, using fluorescence or chemiluminescence as readout signals.
Ion Migration in Organic–Inorganic Hybrid Perovskite Solar Cells: Current Understanding and Perspectives
Authors: Zhu Weike , Wang Shurong , Zhang Xin , Wang Aili , Wu Cheng , Hao Feng 
Published: January 2022

AbstractOrganic–inorganic hybrid perovskite (OIHPs) solar cells are the most promising alternatives to traditional silicon solar cells, with a certified power conversion efficiency beyond 25%. However, the poor stability of OHIPs is one of the thorniest obstacles that hinder its commercial development. Among all the factors affecting stability, ion migration is prominent because it is unavoidable and intrinsic in OHIPs. Therefore, it is important to understand the mechanism for ion migration and regulation strategies. Herein, the types of ions that may migrate in OHIPs are first discussed; afterward, the migrating channels are demonstrated. The effects of ion migration are further elaborated. While ion migration can facilitate the p–i–n structure in some cases, the current hysteresis and other adverse effects such as phase segregation in OHIPs attract widespread attention. Based on these, several recent strategies to suppress the ion migration are enumerated, including the introduction of alkali cations, organic additives, grain boundaries passivation, and employment of low‐dimensional perovskites. Finally, the prospect for further modulating the ion migration and more stable perovskite solar cells is proposed.
Accelerated Hydrogen “Spill‐Over” Enhances Anode Performance of Tensile Strained Pd‐Based Fuel Cell Electrocatalysts
Authors: Yin Huiming , Shen Yongli , Xi Wei , Liu Xizheng , Yin Shuai , Jia Jiankuo , Zhang Jian , Ding Yi 
Published: January 2022

AbstractDevelopment of efficient electrocatalysts usually relies on half‐cell electrochemical tests for rapid material screening, which however are not always consistent with the associated full cell evaluation. This study designs a tensile‐strained Pd anode and reveals that with a lower apparent activity toward the hydrogen oxidation reaction as compared to the unstrained one, it exhibits a surprisingly high activity in proton exchange membrane fuel cells (PEMFCs). With an ultralow Pd loading of 4.5 µg cm−2, the tensile‐strained Pd achieves a maximum power density of 1048 mW cm−2, indicating a 30‐fold improvement in power efficiency than that of commercial Pd/C, nearly four times of that of the unstrained one. This discrepancy can be ascribed to the hydrogen‐rich surface in the H2 atmosphere of PEMFCs owing to the accelerated hydrogen “spill‐over” in the tensile‐strained Pd with a standout hydrogen storage property.
A classification of the aquatic Podostemaceae subfamily Tristichoideae, with a new genus based on ITS and matK phylogeny and morphological characters
Authors: Koi Satoshi , Uniyal Prem Lal , Kato Masahiro 
Published: January 2022

AbstractThe submerged lithophilous Podostemaceae show remarkable variation in phenotypic characters. Taxonomic estimation of the characters alone may not have produced a natural classification of subfamily Tristichoideae. Among the genera, Cussetia and Indotristicha have not been examined by detailed morphological observations and molecular analyses. The present ITS and/or matK phylogenies indicated that Cussetia carinata is close to Terniopsis with high support, and Indotristicha tirunelveliana and Dalzellia form a clade with robust support, while the congeneric I. ramosissima was separated from the clade. Cussetia differs from Terniopsis by having many, alternately 3‐whorled, carinate bracts and heteromorphic shoots, whereas they share the capped root and 3‐stichous leaves. The habitat of C. carinata is the deepest under water in the family. Indotristicha tirunelveliana differs from Dalzellia in the holdfasts, shoots, ramuli, phyllotaxis and cupules. Based on the consistent phylogeny and morphological variation, the genus Cussetia is accepted and a new genus for I. tirunelveliana is proposed. The emended seven genera were characterized primarily by vegetative characters. Tabulated diagnostic characters, a synopsis and a key to genera is presented.