bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated hypofractionated radiation for elderly or frail patients with a newly diagnosed glioblastoma: A pooled analysis of patient‐level data from 4 prospective trials
Authors: Perlow Haley K. , Prasad Rahul N. , Yang Mike , Klamer Brett , Matsui Jennifer , Marrazzo Livia , Detti Beatrice , Scorsetti Marta , Clerici Elena , Arnett Andrea , Beyer Sasha , Ammirati Mario , Chakravarti Arnab , Raval Raju R. , Brown Paul D. , Navarria Pierina , Scoccianti Silvia , Grecula John C. , Palmer Joshua D.
Published: March 2022

Background

The standard of care for elderly or frail patients with glioblastoma (GBM) is 40 Gy in 15 fractions of radiotherapy. However, this regimen has a lower biological effective dose (BED) compared with the Stupp regimen of 60 Gy in 30 fractions. It is hypothesized that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) is safe and efficacious.

Methods

Elderly or frail patients with GBM treated with 52.5 Gy in 15 fractions were pooled from 3 phase 1/2 studies and a prospective observational study. Overall survival (OS) and progression‐free survival (PFS) were defined time elapsing between surgery/biopsy and death from any cause or progression of disease.

Results

Sixty‐two newly diagnosed patients were eligible for this pooled analysis of individual patient data. The majority (66%) had a Karnofsky performance status (KPS) score <70. The median age was 73 years. The median OS and PFS were 10.3 and 6.9 months, respectively. Patients with KPS scores ≥70 and <70 had a median OS of 15.3 and 9.5 months, respectively. Concurrent chemotherapy was an independent prognostic factor for improved PFS and OS. Grade 3 neurologic toxicity was seen in 2 patients (3.2%). There was no grade 4/5 toxicity.

Conclusions

This is the only analysis of elderly/frail patients with GBM prospectively treated with a hypofractionated radiation regimen that is isoeffective to the Stupp regimen. Treatment was well tolerated and demonstrated excellent OS and PFS compared with historical studies. This regimen gives the elderly/frail population an alternative to regimens with a lower BED. Randomized trials are needed to validate these results.
Traffic prediction using MSSBiLS with self‐attention model
Authors: D Suvitha , M Vijayalakshmi
Published: March 2022

Due to gathering and examining a tremendous amount of traffic stream data, traffic blockage is the most important issue in the intelligent transportation framework. The main aim of this research work is “to find the appropriate deep learning time series models, to predict the future traffic of Denmark Aarhus city.” In this article, multivariate sequential stacked bidirectional LSTM with self‐attention model (MSSBiLS‐SA) is proposed to prevent the long term dependencies and also to reduce the error rate. Based on the traffic state, the high, medium, and low range of traffic is predicted to give the best route to the users, and visualization is performed with the help of the Android application. The proposed MSSBiLS‐SA attains higher accuracy 94.56% and 95.36%, sensitivity 88.74% and 92.5%, specificity 93.5% and 94.5%, precision 94.23% and 95.5%, F‐score 94.5% and 94.5%, and lower time complexity 10.19% and 12.43% shows better performance when compared with the existing methods, such as prediction and classification of traffic location analysis using optimized graph convolutional recurrent neural network and prediction and classification of traffic location analysis based multilayer perceptron network using long short term memory. Finally, the proposed method predicts and classifies the traffic location very accurately.
Properties of Bulk In‐Pt Intermetallic Compounds in Methanol Steam Reforming
Authors: Köwitsch Nicolas , Barth Stefan , Ploner Kevin , Blume Raoul , Teschner Detre , Penner Simon , Armbrüster Marc
Published: March 2022

Heterogeneous catalysts are often complex materials containing different compounds. While this can lead to highly beneficial interfaces, it is difficult to identify the role of single components. In methanol steam reforming (MSR), the interplay between intermetallic compounds, supporting oxides and redox reactions leads to highly active and CO2‐selective materials. Herein, the intrinsic catalytic properties of unsupported In3Pt2, In2Pt, and In7Pt3 as model systems for Pt/In2O3‐based catalytic materials in MSR are addressed. In2Pt was identified as the essential compound responsible for the reported excellent CO2‐selectivity of 99.5 % at 300 °C in supported systems, showing a CO2‐selectivity above 99 % even at 400 °C. Additionally, the partial oxidation of In7Pt3 revealed that too much In2O3 is detrimental for the catalytic properties. The study highlights the crucial role of intermetallic In−Pt compounds in Pt/In2O3 materials with excellent CO2‐selectivity.
Optimizing the Photovoltaic Performance of Organic Solar Cells for Indoor Light Harvesting
Authors: Cui Mengmeng , Lv Aifeng , Ma Zaifei
Published: March 2022

Organic solar cells (OSCs) harvesting indoor light are highly promising for emerging technologies, such as internet of things. Herein, the photovoltaic performance of PTB7‐Th:PC71BM solar cells constructed using “optimized (with 1,8‐diiodooctane (DIO))” and “non‐optimized (without DIO)” processing conditions are compared for indoor and outdoor applications. We find that in comparison to the “optimized” solar cell, the “non‐optimized” solar cell is less efficient under simulated solar light illumination (100 mW cm−2, spectral range 350–1100 nm), owing to significant bimolecular charge carrier recombination losses. However, under simulated indoor illumination (3.28 mW cm−2, spectral range 400–700 nm), bimolecular recombination losses are effective suppressed, thus the power conversion efficiency of the solar cell without DIO was increased to 14.7 %, higher than that of the solar cell with DIO (14.2 %). These results suggest that the common strategy used to optimize the OSCs could be undesired for indoor OSCs. We demonstrate that the efforts for realizing the desired “morphology” of the active layer for the outdoor OSCs may be unnecessary for indoor OSCs, allowing us to realize high‐efficiency indoor OSCs using a non‐halogenated solvent.
Path analysis from COVID‐19 perceptions to psychological health: The roles of critical distance and mastery
Authors: Faustino Bruno , Vasco António Branco , Farinha‐Fernandes António , Delgado João , Guerreiro José Carlos , Matos Marta
Published: March 2022

Objective

The Coronavirus disease 2019 (COVID‐19) pandemic was previously associated with psychopathological symptoms. However, the psychological mechanisms underlying these associations are largely unexplored. Previous studies suggested associations between metacognitive abilities (e.g., mastery) and symptomatology, which may have impacts on COVID‐19 perceptions. This study aims to explore, using path analysis, the mediational role of Critical Distance (differentiation and decentration abilities) and Mastery on the relationships between COVID‐19 perceptions and psychological well‐being and distress.

Methods

In a cross‐sectional design, 227 participants (M = 34.21, SD = 10.9) filled self‐report questionnaires.

Results

Metacognitive abilities were negatively correlated with psychopathological symptoms. Both Critical Distance and Mastery mediated the path from COVID‐19 perceived severity and anxiety to psychological distress and well‐being. Critical Distance seems to augment Mastery which tends to increase psychological well‐being and limited psychological distress.

Conclusions

Metacognition seems to play a mediational role on the relationship between COVID‐19 perceptions and mental health. Clinical psychologists and psychotherapists may enhance psychological interventions regarding COVID‐19 psychopathological symptomatology by working on metacognitive Critical Distance and Mastery abilities.
Fluorescence Intensity Fluctuation Analysis of Protein Oligomerization in Cell Membranes
Authors: Killeen Tom D. , Rahman Sadia , Badu Dammar N. , Biener Gabriel , Stoneman Michael R. , Raicu Valerică
Published: March 2022

Fluorescence fluctuation spectroscopy (FFS) encompasses a bevy of techniques that involve analyzing fluorescence intensity fluctuations occurring due to fluorescently labeled molecules diffusing in and out of a microscope's focal region. Statistical analysis of these fluctuations may reveal the oligomerization (i.e., association) state of said molecules. We have recently developed a new FFS‐based method, termed Two‐Dimensional Fluorescence Intensity Fluctuation (2D FIF) spectrometry, which provides quantitative information on the size and stability of protein oligomers as a function of receptor concentration. This article describes protocols for employing FIF spectrometry to quantify the oligomerization of a membrane protein of interest, with specific instructions regarding cell preparation, image acquisition, and analysis of images given in detail. Application of the FIF Spectrometry Suite, a software package designed for applying FIF analysis on fluorescence images, is emphasized in the protocol. Also discussed in detail is the identification, removal, and/or analysis of inhomogeneous regions of the membrane that appear as bright spots. The 2D FIF approach is particularly suited to assess the effects of agonists and antagonists on the oligomeric size of membrane receptors of interest. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Preparation of live cells expressing protein constructs

Basic Protocol 2: Image acquisition and noise correction

Basic Protocol 3: Drawing and segmenting regions of interest

Basic Protocol 4: Calculating the molecular brightness and concentration of individual image segments

Basic Protocol 5: Combining data subsets using a manual procedure (Optional)

Alternate Protocol 1: Combining data subsets using the advanced FIF spectrometry suite (Optional; alternative to Basic Protocol 5)

Basic Protocol 6: Performing meta‐analysis of brightness spectrograms

Alternate Protocol 2: Performing meta‐analysis of brightness spectrograms (alternative to Basic Protocol 6)

Basic Protocol 7: Spot extraction and analysis using a manual procedure or by writing a program (Optional)

Alternate Protocol 3: Automated spot extraction and analysis (Optional; alternative to Protocol 7)

Support Protocol: Monomeric brightness determination
Determining the Effects of Neddylation on Cullin‐RING Ligase–Dependent Protein Ubiquitination
Authors: Wang Kankan , Liu Xing
Published: March 2022

As the largest family of ubiquitin (Ub) E3 ligases, cullin‐RING ligases (CRLs) play crucial roles in various cellular processes, and their activities are tightly regulated by orchestrated mechanisms. Neddylation, the conjugation of a Ub‐like protein NEDD8 to a target protein such as the cullin, represents a key regulatory mechanism for CRLs. Biochemical and structural studies of a few CRLs have revealed that cullin neddylation alters the CRL conformation and activates CRL‐dependent protein ubiquitination. Here, using CUL2‐RING ligase (CRL2) as an example, we describe our protocols for the preparation of recombinant CUL2 with or without NEDD8 conjugation, which is further used to quantitatively determine the effect of neddylation on CRL2‐dependent protein ubiquitinationin vitro. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Expression and purification of CUL2•RBX1 fromEscherichia coli

Support Protocol: Further purification of CUL2•RBX1 with additional chromatography on an FPLC system

Basic Protocol 2: Reconstitution of cullin neddylation for quantitative ubiquitination assayin vitro
Impurity profiling of methamphetamine synthesized from methyl α‐acetylphenylacetate
Authors: Langone Deanna , Painter Ben , Nash Clark , Hulshof Janneke , Oldenhof Sander , Johnston Martin R. , Kirkbride K. Paul
Published: March 2022

The group of P2P precursors including α‐phenylacetoacetonitrile (APAAN), α‐phenylacetoamide (APAA) and methyl α‐acetylphenylacetate (MAPA) has become increasingly popular in Europe and other parts of the world in the last decade. Previous investigations have reported the use of APAAN in the synthesis of amphetamine and methamphetamine and identified a range of characteristic impurities. This research has expanded upon the current literature by investigating the use of MAPA in the synthesis of methamphetamine.

In this study methamphetamine was synthesized via three common clandestine methods: the Leuckart synthesis and two reductive amination methods. We report the identification of seven impurities, four of which are methyl ester equivalents of impurities previously reported for the detection of APAAN. These are methyl 2‐phenylbut‐2‐enoate, methyl 2‐phenyl‐3‐hydroxybutanoate, methyl 3‐(methylamino)‐2‐phenylbut‐2‐enoate and methyl 3‐(methylamino)‐2‐phenylbutanoate. The other impurities identified are ethyl ester compounds formed via transesterification of the methyl ester due to the reaction solvent. This susceptibility for transesterification suggests that identification of the pre‐precursor used may not always be straightforward and may be dependent on the reaction conditions employed. Of the impurities reported, methyl 3‐(methylamino)‐2‐phenylbutanoate was deemed to be a potentially reliable impurity for detection of the use of MAPA; however, it is expected that lower levels of characteristic impurities may be detected in methamphetamine synthesized from MAPA than that from APAAN.
Building integral projection models with nonindependent vital rates
Authors: Fung Yik Leung , Newman Ken , King Ruth , de Valpine Perry
Published: March 2022

Population dynamics are functions of several demographic processes including survival, reproduction, somatic growth, and maturation. The rates or probabilities for these processes can vary by time, by location, and by individual. These processes can co‐vary and interact to varying degrees, e.g., an animal can only reproduce when it is in a particular maturation state. Population dynamics models that treat the processes as independent may yield somewhat biased or imprecise parameter estimates, as well as predictions of population abundances or densities. However, commonly used integral projection models (IPMs) typically assume independence across these demographic processes. We examine several approaches for modelling between process dependence in IPMs and include cases where the processes co‐vary as a function of time (temporal variation), co‐vary within each individual (individual heterogeneity), and combinations of these (temporal variation and individual heterogeneity). We compare our methods to conventional IPMs, which treat vital rates independent, using simulations and a case study of Soay sheep (Ovis aries). In particular, our results indicate that correlation between vital rates can moderately affect variability of some population‐level statistics. Therefore, including such dependent structures is generally advisable when fitting IPMs to ascertain whether or not such between vital rate dependencies exist, which in turn can have subsequent impact on population management or life‐history evolution.
A framework for soil microbial ecology in urban ecosystems
Authors: Nugent Andie , Allison Steven D.
Published: March 2022

Nearly all ecosystems host diverse microbiomes that support vital ecosystem processes. At the same time, these ecosystems and their microbiomes are increasingly altered by human activities, particularly in highly managed urban environments. While microbial ecologists are beginning to understand the drivers of microbial assembly and the link between community structure and function in many ecosystems, few of these advances have been applied to urban ecosystems. In this synthesis, we review research on the urban soil microbiome and develop a framework to integrate soil microbial communities with urban ecosystem function. We identify disturbance, altered resources, and heterogeneity as key drivers through which human activities including urban development affect soils and their resident microorganisms. Steep environmental gradients in many urban systems present a unique opportunity to address fundamental questions in microbial ecology, such as how microbes respond to stress and how biogeochemical rates relate to microbial diversity and composition. Soil microbiomes in cities also provide ecosystem services and harms, making it crucial to understand how human activity drives those functions and the consequences for environmental and human health. We argue that much‐needed integration across disturbance ecology, urban ecology, and microbial ecology will help generate practical and equitable strategies for managing ecosystem benefits in cities where most humans now live.
Experimental analysis of energy, performance and noise emissions for biodiesel fuel obtained from animal waste fat
Authors: Öğüt Hüseyin , Oğuz Hidayet , Aydın Fatih
Published: March 2022

Animal fats are one of the biodiesel raw materials. In this study, biodiesel was produced from horse fat by transesterification method and the produced biodiesel was mixed with euro diesel at 5% by volume, and experimental fuels in the form of D100 and D95B5 were obtained. Fuel properties of test fuels were determined. In addition, using the experimental fuels in a single‐cylinder, four‐stroke, water‐cooled diesel engine, the data obtained by investigating the engine performances, energy analysis, and noise emissions were presented with graphics and interpreted. In the experiment results; D95B5 fuel produced 0.68% more torque than D100 fuel at maximum torque value and D95B5 fuel produced 4.06% more power than D100 fuel at maximum engine power. In the minimum specific fuel consumption values, D100 fuel consumed 4.70% less fuel than D95B5 fuel. In terms of energy analysis, results are given for the maximum torque speed 1200 rpm, minimum specific fuel consumption speed 1200 rpm, and maximum power speed 2000 rpm for the experimental fuels. In terms of noise emissions, the engine made 0.56% less noise in the use of D95B5 fuel compared to the use of D100 fuel and 0.20% less noise at the maximum torque speed values, according to the average values of the maximum power cycle. As a result, adding 5% horse fat biodiesel to diesel fuel has yielded positive results in terms of engine performance, energy analysis and noise emission. This type of fuel can be used in diesel engines without any modification.
A certification tool for on‐grid net zero energy consumption buildings
Authors: Güğül Gül Nihal , Bora Beyza Nur
Published: March 2022

Energy efficiency in buildings sector can provide influential solutions to the threats arising from the increase in carbon emissions. Since efficient design of the buildings and equipping them with renewable systems increases the final cost, strategies should be developed to encourage building owners. The first stage of these strategies is certification of these buildings. However, modeling of the buildings equipped with renewable systems is possible with the use of more than one software and requires detailed technical expertise. An easy‐to‐use software, where all calculations are conducted in a single software, will be useful in the spread of certification processes. For this reason, in this study, an easy‐to‐use software has been developed that can be used during the certification of zero energy buildings which eliminates the requirement of more than one software. The software makes use of the climate, electricity consumption, building, and renewable system properties data to predict the energy demand and production, and generate zero energy consumption building certificate. The heating demand, photovoltaic (PV) and wind system estimate of the software are verified by using real data and R2 values are calculated as 0.92, 0.97, and 0.98 respectively. A certificated passive and zero energy consumption building is modeled in the developed software as a case study building and NZEB certificate was awarded to the building by the software. Therefore, in this study, an easy‐to‐use software is developed and verified to certificate the on‐grid zero energy buildings that eliminates requirement of detailed technical knowledge and usage of more than one software.
UHPLC‐ESI‐QTOF‐MS2 analysis of Acacia pennata extract and its effects on glycemic indices, lipid profile, pancreatic and hepatorenal alterations in nicotinamide/streptozotocin‐induced diabetic rats
Authors: Shao Hui , Xiao Minmin , Zha Zheng , Olatunji Opeyemi Joshua
Published: March 2022

Diabetes mellitus (DM) is a chronic disorder associated with severe metabolic derangement and comorbidities. The constant increase in the global population of diabetic patients coupled with some prevailing side effects associated with synthetic antidiabetic drugs has necessitated the urgent need for the search for alternative antidiabetic regimens. This study investigated the antidiabetic, antioxidant, and pancreatic protective effects of the Acacia pennata extract (APE) against nicotinamide/streptozotocin induced DM in rats. The antidiabetic activity of APE was evaluated and investigated at doses of 100 and 400 mg/kg body weight, while metformin (150 mg/kg bw) was used as a standard drug. APE markedly decreased blood glucose level, homeostatic model assessment for insulin resistance, serum total cholesterol, triglycerides, low‐density lipoprotein, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, and alanine phosphatase levels. Additionally, treatment with APE increased the body weight, serum insulin concentration, and high‐density lipoprotein. Moreover, activities of pancreatic superoxide dismutase, catalase, and glutathione peroxidase were increased, while the altered pancreatic architecture in the histopathological examination was notably restored in the treated rats. Ultra‐high performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight mass spectrometry (UHPLC‐ESI‐QTOF‐MS) analysis of APE showcases the prevailing presence of polyphenolic compounds. Conclusively, this study showed the beneficial effects of the Acacia pennata in controlling metabolic derangement, pancreatic and hepatorenal dysfunction in diabetic rats.
Bioactive content and phenolic compounds of common medlar (Mespilus germanica L.) and Stern’s medlar (M. canescens Phipps)
Authors: Sadeghinejad Zeinab , Erfani‐Moghadam Javad , Khadivi Ali
Published: March 2022

Medlar (Mespilus) is an important fruit and is rich in nutritional and medical properties. Bioactive content and phenolic compounds of leaf, fruit, and seed samples of common medlar (M. germanica) and Stern’s medlar (M. canescens) were studied. The coefficient of variation showed high values among all the characters and was more than 50.00%, ranging from 59.74 to 196.81%. The leaf of M. canescens showed the highest total phenolic content (14.73 mg/g dry weight, DW) and followed by 13.70 mg/g DW in the seed of M. germanica collected from Ilam province, Iran. The highest flavonoid content was observed in fruits of M. germanica collected from the north of Iran (0.90 mg/g DW), and followed by the leaf of M. canescens (0.53 mg/g DW). The phenolic compounds showed strong variation. Principal component analysis showed that four PCs explained 95.07% of the observed total variance. Ward dendrogram indicated two different clusters based on the characters measured, indicating high variation among the accessions. The current investigation clearly showed the potential value of the common medlar (M. germanica) and Stern’s medlar (M. canescens) germplasm, as different medlar organs are significant sources of phenolic compounds and high antioxidant activity. Therefore, these species can be considered suitable sources of natural antioxidants, and may show potential future use in food and nutraceutical supplement formulations.
Why are the prices of European‐style derivatives greater than the prices of American‐style derivatives?
Authors: Jin Xuejun , Zhao Jingyu , Luo Xingguo
Published: March 2022

The prices of European‐style derivative warrants in Hong Kong are generally higher than those of identical American‐style options. We show that liquidity differences have strong explanatory power for this overpricing behavior, especially for low moneyness and long‐term derivatives. Other causative factors include counterparty credit risk, investor preference, information asymmetry, volatility discovery, exercise style, market makers' behavior, and investor sentiment. We also find a big gap in market‐wide liquidity between the two markets. Specifically, lower liquidity results in the weaker efficiency of the options market compared with the derivative warrants market.
Effectiveness of gabapentin in reducing opioid requirements after radiation in head and neck cancer in a single institution
Authors: Gilley David R. , Clark Andrew D. , Wieser Maggie E. , Bollig Craig A. , Dooley Laura M. , Biedermann Gregory B.
Published: March 2022

Background

Gabapentin has been shown to reduce opioid use in head and neck cancer patients. Here, we examine the efficacy of prophylactic gabapentin at reducing opioid use in these patients at our institution.

Methods

A retrospective study of patients receiving radiation was performed, using patients from our previous study as controls. Risk factors for opioid use at 3 and 6 months were determined using univariate and multivariate analyses.

Results

In total, 53/185 patients were treated with gabapentin, 39.6% of which took opioids at 3 months vs. 58.3% in the non‐gabapentin cohort (p = 0.021). Gabapentin was independently associated with less opioid use on multivariate analysis at 3 months (OR 0.47, 95% CI 0.24–0.9). Gastrostomy tube dependence and pretreatment opioid use were associated with chronic opioid use despite gabapentin.

Conclusions

Gabapentin is effective at expediting opioid tapering in head and neck cancer patients who are not gastrostomy tube dependent or taking opioids pretreatment.
Association between social determinants of health and rates of liver transplantation in individuals with cirrhosis
Authors: Flemming Jennifer A. , Muaddi Hala , Djerboua Maja , Neves Paula , Sapisochin Gonzalo , Selzner Nazia
Published: March 2022

Background and Aims

This study evaluated the association between neighborhood‐level social determinants of health (SDOH) and liver transplantation (LT) among patients with cirrhosis who have universal access to health care.

Approach and Results

This was a retrospective population‐based cohort study from 2000–2019 using administrative health care data from Ontario, Canada. Adults aged 18–70 years with newly decompensated cirrhosis and/or HCC were identified using validated coding. The associations between five neighborhood level SDOH quintiles and LT were assessed with multivariate Fine‐Gray competing risks regression to generate subdistribution HRs (sHRs) where death competes with LT. Overall, n = 38,719 individuals formed the cohort (median age 57 years, 67% male), and n = 2788 (7%) received LT after a median of 23 months (interquartile range 3–68). Due to an interaction, results were stratified by sex. After multivariable regression and comparing those in the lowest versus highest quintiles, individuals living in the most materially resource‐deprived areas (female sHR, 0.61; 95% CI, 0.49–0.76; male sHR, 0.55; 95% CI, 0.48–0.64), most residentially unstable neighborhoods (female sHR, 0.61; 95% CI, 0.49–0.75; male sHR, 0.56; 95% CI, 0.49–0.65), and lowest‐income neighborhoods (female sHR, 0.57; 95% CI, 0.46–0.7; male sHR, 0.58; 95% CI, 0.50–0.67) had ~40% reduced subhazard for LT (p < 0.01 for all). No associations were found between neighborhoods with the most diverse immigrant or racial minority populations or age and labor force quintiles and LT.

Conclusions

This information highlights an urgent need to evaluate how SDOH influence rates of LT, with the overarching goal to develop strategies to overcome inequalities.
Single‐cell transcriptomics reveals conserved cell identities and fibrogenic phenotypes in zebrafish and human liver
Authors: Morrison Joshua K. , DeRossi Charles , Alter Isaac L. , Nayar Shikha , Giri Mamta , Zhang Chi , Cho Judy H. , Chu Jaime
Published: March 2022

The mechanisms underlying liver fibrosis are multifaceted and remain elusive with no approved antifibrotic treatments available. The adult zebrafish has been an underutilized tool to study liver fibrosis. We aimed to characterize the single‐cell transcriptome of the adult zebrafish liver to determine its utility as a model for studying liver fibrosis. We used single‐cell RNA sequencing (scRNA‐seq) of adult zebrafish liver to study the molecular and cellular dynamics at a single‐cell level. We performed a comparative analysis to scRNA‐seq of human liver with a focus on hepatic stellate cells (HSCs), the driver cells in liver fibrosis. scRNA‐seq reveals transcriptionally unique populations of hepatic cell types that comprise the zebrafish liver. Joint clustering with human liver scRNA‐seq data demonstrates high conservation of transcriptional profiles and human marker genes in zebrafish. Human and zebrafish HSCs show conservation of transcriptional profiles, and we uncover collectin subfamily member 11 (colec11) as a novel, conserved marker for zebrafish HSCs. To demonstrate the power of scRNA‐seq to study liver fibrosis using zebrafish, we performed scRNA‐seq on our zebrafish model of a pediatric liver disease with mutation in mannose phosphate isomerase (MPI) and characteristic early liver fibrosis. We found fibrosis signaling pathways and upstream regulators conserved across MPI‐depleted zebrafish and human HSCs. CellPhoneDB analysis of zebrafish transcriptome identified neuropilin 1 as a potential driver of liver fibrosis. Conclusion: This study establishes the first scRNA‐seq atlas of the adult zebrafish liver, highlights the high degree of similarity to human liver, and strengthens its value as a model to study liver fibrosis.
Advances in modelling large river basins in cold regions with Modélisation Environmentale Communautaire—Surface and Hydrology (MESH), the Canadian hydrological land surface scheme
Authors: Wheater Howard S. , Pomeroy John W. , Pietroniro Alain , Davison Bruce , Elshamy Mohamed , Yassin Fuad , Rokaya Prabin , Fayad Abbas , Tesemma Zelalem , Princz Daniel , Loukili Youssef , DeBeer Chris M. , Ireson Andrew M. , Razavi Saman , Lindenschmidt Karl‐Erich , Elshorbagy Amin , MacDonald Matthew , Abdelhamed Mohamed , Haghnegahdar Amin , Bahrami Ala
Published: March 2022

Cold regions provide water resources for half the global population yet face rapid change. Their hydrology is dominated by snow, ice and frozen soils, and climate warming is having profound effects. Hydrological models have a key role in predicting changing water resources but are challenged in cold regions. Ground‐based data to quantify meteorological forcing and constrain model parameterization are limited, while hydrological processes are complex, often controlled by phase change energetics. River flows are impacted by poorly quantified human activities. This paper discusses the scientific and technical challenges of the large‐scale modelling of cold region systems and reports recent modelling developments, focussing on MESH, the Canadian community hydrological land surface scheme. New cold region process representations include improved blowing snow transport and sublimation, lateral land‐surface flow, prairie pothole pond storage dynamics, frozen ground infiltration and thermodynamics, and improved glacier modelling. New algorithms to represent water management include multistage reservoir operation. Parameterization has been supported by field observations and remotely sensed data; new methods for parameter identification have been used to evaluate model uncertainty and support regionalization. Additionally, MESH has been linked to broader decision‐support frameworks, including river ice simulation and hydrological forecasting. The paper also reports various applications to the Saskatchewan and Mackenzie River basins in western Canada (0.4 and 1.8 million km2). These basins arise in glaciated mountain headwaters, are partly underlain by permafrost, and include remote and incompletely understood forested, wetland, agricultural and tundra ecoregions. These illustrate the current capabilities and limitations of cold region modelling, and the extraordinary challenges to prediction, including the need to overcoming biases in forcing data sets, which can have disproportionate effects on the simulated hydrology.
Transitioning to the maternal death surveillance and response system from maternal death review in Ghana: Challenges and lessons learned
Authors: Compaoré Rachidatou , Kouanda Seni , Kuma‐Aboagye Patrick , Sagoe‐Moses Isabella , Brew Gladys , Deganus Sylvia , Srofenyo Emmanuel , Dansowaa Doe Roseline , Nkurunziza Triphonie , Tall Fatim
Published: March 2022

Objective

To assess the current system of maternal death review (MDR) in Ghana and identify the achievements, challenges, and gaps that will assist in transitioning to the maternal death surveillance and response system (MDSR).

Methods

A secondary analysis of data from a cross‐sectional study on MDSR implementation was conducted between September and October 2018. The MDSR cycle served as an analytical framework to measure the country's performance in implementing MDSR. Common facilitating or hindering factors were also identified.

Results

The MDR system is moderately strong at regional level with timely receipt of data and regular review meetings and reports in most regions. At district level the MDR system is less well implemented, although there is evidence of good communication with regional teams in providing timely data. Communication between districts and communities about maternal deaths seemed to be poor in general. There was no MDR committee at national level and the recommendations made were poorly implemented.

Conclusion

MDRs in Ghana were structurally sound, but recommendations were poorly implemented. Leadership at the national level needs to be developed to ensure that the current system could transition to an MDSR system.
Undifferentiated pleomorphic sarcoma of the retroperitoneum mimicking a cortisol‐ and catecholamine‐secreting adrenal tumor
Authors: Fuu Takayoshi , Yano Akihiro , Urakami Shinji
Published: March 2022

Introduction

Retroperitoneal tumors with endocrine abnormalities are suspected to be functional adrenal tumors. Retroperitoneal soft tissue sarcomas are rare tumors, without endocrine potential.

Case presentation

A 60‐year‐old male was referred for a 15 cm mass in the left suprarenal space. His plasma cortisol and catecholamine levels were elevated. He underwent open left adrenalectomy with radical nephrectomy and his endocrinological abnormalities were improved. Pathological findings suggested that it had originated from the retroperitoneal fat tissue, and a diagnosis of undifferentiated pleomorphic sarcoma was made based on the results of immunohistochemical analysis and fluorescence in situ hybridization. Interestingly, neither cortisol nor catecholamine was elevated when, 6 months after surgery, local recurrence developed.

Conclusion

This is the first reported case of undifferentiated pleomorphic sarcoma accompanied by high levels of cortisol and catecholamine. We should keep in mind the possibility of tumors like retroperitoneal soft tissue sarcomas inducing endocrine abnormalities.
Weighted‐Centroid localization using LoRaWAN network on large outdoor areas
Authors: Telles Guilherme Pazetto , Rayel Ohara Kerusauskas , Moritz Guilherme Luiz
Published: March 2022

In this work, we show that simple RSSI algorithms as Weighted Centroid (WC) may have similar performance than machine learning methods to estimate node localization in large areas using LoRaWAN. The results are also compared to previous studies on a database provided from the city of Antwerp.
Impact of airborne total suspended particles (TSP) and fine particulate matter (PM2.5)‐induced developmental toxicity in zebrafish (Danio rerio) embryos
Authors: Jia Zhi‐li , Zhu Cheng‐yue , Rajendran R. Samuel , Xia Qing , Liu Ke‐chun , Zhang Yun
Published: March 2022

Airborne total suspended particles (TSP) and particulate matter (PM2.5) threaten global health and their potential impact on cardiovascular and respiratory diseases are extensively studied. Recent studies attest premature deaths, low birth weight, and congenital anomalies in the fetus of pregnant women exposed to air pollution. In this regard, only few studies have explored the effects of TSP and PM2.5 on cardiovascular and cerebrovascular development. As both TSP and PM2.5 differ in size and composition, this study is attempted to assess the variability in toxicity effects between TSP and PM2.5 on the development of cardiovascular and cerebrovascular systems and the underlying mechanisms in a zebrafish model. To explore the potential toxic effects of TSP and PM2.5, zebrafish embryos/larvae were exposed to 25, 50, 100, 200, and 400 μg/ml of TSP and PM2.5 from 24 to 120 hpf (hours post‐fertilization). Both TSP and PM2.5 exposure increased the rate of mortality, malformations, and oxidative stress, whereas locomotor behavior, heart rate, blood flow velocity, development of cardiovasculature and neurovasculature, and dopaminergic neurons were reduced. The expression of genes involved in endoplasmic reticulum stress (ERS), Wnt signaling, and central nervous system (CNS) development were altered in a dose‐ and time‐dependent manner. This study provides evidence for acute exposure to TSP and PM2.5‐induced cardiovascular and neurodevelopmental toxicity, attributed to enhanced oxidative stress and aberrant gene expression. Comparatively, the effects of PM2.5 were more pronounced than TSP.
Antioxidant for treatment of diabetic complications: A meta‐analysis and systematic review
Authors: Zhong Ou , Hu Jialin , Wang Jinyuan , Tan Yongpeng , Hu Linlin , Lei Xiaocan
Published: March 2022

Antioxidants may provide a complementary treatment for patients with chronic diseases. Nevertheless, studies that have measured the effects of antioxidant on diabetes complications have provided conflicting results. This study aimed to elucidate the association between antioxidant and diabetic complications and to develop robust evidence for clinical decisions by systematic reviews and meta‐analysis. PubMed, Embase, The Cochrane Library, Web of Science, Scopus databases were searched to collect clinical studies related to the efficacy of antioxidants in the treatment of diabetes complications from inception to May 5, 2021. Statistical meta‐analyses were performed using the RevMan 5.4 software. Stata16 software was used to detect publication bias. The data of diabetic nephropathy (DN), diabetic nonalcoholic fatty liver disease (NAFLD), and diabetic periodontitis were collected to analyze the effect of antioxidant on diabetes and the above three complications. The meta‐analysis results showed that antioxidant treatment was associated with significantly changes in the fasting plasma glucose (FPG) (standardized mean difference [SMD]: − 0.21 [95% confidence interval [CI]: − 0.33, −0.10], p < 0.001), hemoglobin A1c (HbA1c) (MD: − 0.41 [95% CI: − 0.63, −0.18], p < 0.001), total antioxidant capacity (TAC) (SMD: 0.44 [95% CI: 0.24, 0.63], p < 0.001) and malondialdehyde (MDA) (SMD: − 0.82 [95% CI: − 1.24, −0.41], p < 0.001) than the control group. Antioxidant supplements have the potential to treat three complications of diabetes. In conclusion, the meta‐analysis results indicate that antioxidant treatment is effective clinically for diabetes mellitus and its complications.
Novel classification and risk model based on ferroptosis‐related lncRNAs to predict oncologic outcomes for gastric cancer patients
Authors: Yue Qingfang , Bai Jun , Wang Fei , Xue Fei , Li Lianxiang , Duan Xianglong
Published: March 2022

Gastric cancer (GC) is a highly heterogeneous malignancy, characterized by high mortality and poor prognosis. Ferroptosis is a newly defined nonapoptotic programmed cell death mechanism that has been implicated in the development of various pathological conditions. We aimed to identify ferroptosis‐related long noncoding RNA (lncRNAs) that might be used to predict GC prognosis. The data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. Two subtypes, C1 and C2, were identified, which had significant variations in prognosis and immune cell infiltrations. Differentially expressed genes between the subtypes were found to be involved in multiple tumor‐associated pathways. Subsequently, a training dataset and a testing dataset were created from the TCGA dataset. A predictive model for GC patients based on six ferroptosis‐related lncRNAs (including STX18‐AS1, MIR99AHG, LINC01197, LINC00968, LINC00865, and LEF1‐AS1) was developed. The model could stratify patients into a high‐ and low‐risk group, showing good predictive performance. The testing dataset, entire TCGA dataset, and GSE62254 cohort both confirmed the predictive value of the model. Compared to the clinical parameters (including gender, age, and grade), the risk model was an independent risk factor for GC patients. Moreover, a nomogram (containing our risk score model and clinical parameters) was constructed, which might provide great potential to improve prediction accuracy. Moreover, the single‐sample gene set enrichment analysis revealed that the high‐risk group was linked to various signaling pathways involved in the regulation of GC progression. Conclusively, a novel classification and risk model based on ferroptosis‐related lncRNAs that can predict oncologic outcomes for GC patients has been developed.
Identification of acridinedione scaffolds as potential inhibitor of DENV‐2 C protein: An in silico strategy to combat dengue
Authors: Kumar Sachin , Bhardwaj Vijay K. , Singh Rahul , Das Pralay , Purohit Rituraj
Published: March 2022

Dengue is a prominent viral disease transmitted by mosquitoes to humans that affects mainly tropical and subtropical countries worldwide. The global spread of dengue virus (DENV) is mainly occurred by Aedes aegypti and Aedes albopictus mosquitoes. The dengue virus serotypes‐2 (DENV‐2) is a widely prevalent serotype of DENV, that causes the hemorrhagic fever and bleeding in the mucosa, which can be fatal. In the life cycle of DENV‐2, a structural capsid (DENV‐2 C) protein forms the nucleocapsid assembly and bind to the viral progeny RNA. For DENV‐2 maturation, the nucleocapsid is a vital component. We used virtual ligand screening to filter out the best in‐house synthesized acridinedione analogs (DSPD molecules) that could efficiently bind to DENV‐2 C protein. The molecular docking and dynamics simulations studies were performed to analyze the effect of DSPD molecules on DENV‐2 C protein after binding. Our findings showed that DSPD molecules strongly interacted with DENV‐2 C protein, as evident from molecular interactions and several time‐dependent molecular dynamics‐driven analyses. Moreover, this study was also supported by the thermodynamic binding free energy and steered molecular dynamics simulations. Therefore, we intend to suggest that the DSPD3 molecule could be used as a potential therapeutic molecule against dengue complications as compared to the cocrystallized inhibitor ST‐148. However, further studies are required to demonstrate the ability of DSPD3 to induce DENV‐2 C tetramer formation.
Analytical and clinical evaluation of the light‐initiated chemiluminescent assays for measurement of human thyroid hormones
Authors: Li Jing , Huang Youyuan , Xiang Guiming , Xu Enjun , Chen Tao , Yang Ming , Zhang Jie
Published: March 2022

Background

Light‐initiated chemiluminescent assay (LiCA) is a new homogeneous immunoassay. The aim of this study was to evaluate the analytical and clinical performance of the assays for the detection of thyroid hormones based on the fully automated LiCA 800 analyzer.

Methods

Analytical validations of the LiCA thyroid assays (TSH, FT3, FT4, T3, and T4) included precision, linearity, analytical sensitivity, interference, and method comparison applying the protocols of the Clinical and Laboratory Standards Institute (CLSI). The diagnostic performance was assessed by the receiver operating characteristic (ROC) curve analysis with different assay schemes for the diagnosis of hyperthyroidism and hypothyroidism.

Results

Within‐run and within‐lab precisions (%CV) of the five assays ranged from 1.06 to 6.40% at all concentrations evaluated. A satisfactory linearity was verified over the entire measuring range for TSH, T3, and T4 (R > 0.99, change in recovery <10%, p = 0.000 all). Paired‐comparison measurements presented a comparable assay for each of the five assays (R > 0.96, median bias <5%, p < 0.0001 all) between LiCA and Cobas across three institutes. The diagnostic accuracy of the LiCA assays for hyperthyroidism or hypothyroidism was quantified by the areas under curves (AUC) as 0.925 or 0.832 with the five‐assay panel (TSH, FT3, FT4, T3, and T4) and as 0.921 or 0.811 with the three‐assay panel (TSH, FT3, and FT4), respectively. No significant difference was found between the AUC of LiCA and that of DxI, Cobas, or Centaur (p > 0.3 all).

Conclusion

LiCA 800 provides a precise and high‐throughput immunoassay platform for detection of thyroid hormones. It is acceptable for clinical use.
The role of miRNAs as a big master regulator of signaling pathways involved in lymphoblastic leukemia
Authors: Bagheri Malihe , Sarabi Parisa Zia , Mondanizadeh Mahdieh
Published: March 2022

MicroRNAs (miRNAs) belong to small noncoding RNAs, which have long attracted researchers' attention because of their potency in acting either as oncogenes or tumor‐suppressors in cancers. acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are two known types of leukemia with high mortality rates in adults and children. On a molecular basis, various signaling pathways are active in both types, making researchers consider the potential role of miRNAs in activating or suppressing these pathways to further hinder cancer development. In this review, we summarized the potential miRNAs, especially circulating ones, involved in essential signaling pathways in the ALL and CLL patients which serve as biomarkers and valuable targets in the treatment fields.
Polygenic mechanisms underpinning the response to exercise‐induced muscle damage in humans: In vivo and in vitro evidence
Authors: Baumert Philipp , Cocks Matthew , Strauss Juliette A. , Shepherd Sam O. , Drust Barry , Lake Mark J. , Stewart Claire E. , Erskine Robert M.
Published: March 2022

We investigated whether 20 candidate single nucleotide polymorphisms (SNPs) were associated with in vivo exercise‐induced muscle damage (EIMD), and with an in vitro skeletal muscle stem cell wound healing assay. Sixty‐five young, untrained Caucasian adults performed 120 maximal eccentric knee‐extensions on an isokinetic dynamometer to induce EIMD. Maximal voluntary isometric/isokinetic knee‐extensor torque, knee joint range of motion (ROM), muscle soreness, serum creatine kinase activity and interleukin‐6 concentration were assessed before, directly after and 48 h after EIMD. Muscle stem cells were cultured from vastus lateralis biopsies from a separate cohort (n = 12), and markers of repair were measured in vitro. Participants were genotyped for all 20 SNPs using real‐time PCR. Seven SNPs were associated with the response to EIMD, and these were used to calculate a total genotype score, which enabled participants to be segregated into three polygenic groups: ‘preferential’ (more ‘protective’ alleles), ‘moderate’, and ‘non‐preferential’. The non‐preferential group was consistently weaker than the preferential group (1.93 ± 0.81 vs. 2.73 ± 0.59 N ∙ m/kg; P = 9.51 × 10−4) and demonstrated more muscle soreness (p = 0.011) and a larger decrease in knee joint ROM (p = 0.006) following EIMD. Two TTN‐AS1 SNPs in linkage disequilibrium were associated with in vivo EIMD (rs3731749, p ≤ 0.005) and accelerated muscle stem cell migration into the artificial wound in vitro (rs1001238, p ≤ 0.006). Thus, we have identified a polygenic profile, linked with both muscle weakness and poorer recovery following EIMD. Moreover, we provide evidence for a novel TTN gene‐cell‐skeletal muscle mechanism that may help explain some of the interindividual variability in the response to EIMD.