bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Characteristics of Short-Stature Patients With Collagen Gene Mutation and the Therapeutic Response to rhGH
Authors: Chen Meiping , Miao Hui , Liang Hanting , Ke Xiaoan , Yang Hongbo , Gong Fengying , Wang Linjie , Duan Lian , Chen Shi , Pan Hui , Zhu Huijuan
Published: February 2022

Context

Clinical genetic evaluation has been demonstrated as an important tool to elucidate the causes of growth disorders. Genetic defects of collagen formation (the collagenopathies) have been reported to be associated with short stature and skeletal dysplasias. Etiological diagnosis of skeletal abnormality-related short stature is challenging, and less is known about recombinant human growth hormone (rhGH) therapy.

Objective

This is a single-center cohort study which aims at exploring the genetic architecture of short-stature children with skeletal abnormalities and evaluating the frequency of collagenopathies to determine their phenotype, including the rhGH treatment response.

Patients and Methods

One hundred and six children with short stature and skeletal abnormalities were enrolled who were evaluated by next-generation sequencing (NGS) to detect variants in the skeletal collagen genes including COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, and COL11A2. The results were evaluated using American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical characteristics and rhGH treatment response were summarized.

Results

Twenty-four pathogenic or likely pathogenic variants of collagen genes were found in 26 of 106 (24.5%) short-stature patients with skeletal abnormalities, of which COL2A1 mutations were the most common, accounting for about 57.7%. Other frequent mutations associated with skeletal development include FGFR3, ACAN, NPR2, COMP, and FBN1 in 12.2%, 0.9%, 0.8%, 0.4%, and 0.4%, respectively, resulting in significantly different degrees of short stature. An overview of clinical features of collagenopathies showed growth retardation, skeletal abnormalities, and heterogeneous syndromic abnormalities involving facial, eye, hearing, and cardiac abnormalities. The average height of 9 patients who received rhGH treatment improved from a median of -3.2 ± 0.9 SDS to -2.2 ± 1.3 SDS after 2.8 ± 2.1 years. The most significant height improvement of 2.3 SDS and 1.7 SDS was also seen in two patients who had been treated for more than 6 years.

Conclusions

A proband-based NGS revealed that distinct genetic architecture underlies short stature in varying degrees and clinical features. Skeletal abnormality-related short stature involving multiple systems should be tested for skeletal collagen gene mutation. Limited rhGH treatment data indicate an improved growth rate and height, and close monitoring of adverse reactions such as scoliosis is required.
A Machine Learning Framework With an Intelligent Algorithm for Predicting the Isentropic Efficiency of a Hydraulic Diaphragm Metering Pump in the Organic Rankine Cycle System
Authors: Ping Xu , Yao Baofeng , Niu Kai , Yuan Meng
Published: February 2022

The pump provides the necessary pressure and flow for the organic Rankine cycle (ORC) system. The traditional methods have obvious limitations when analyzing the time-varying characteristics of the key operating parameters of the pump. This study first introduces the scatter plot analysis method to analyze and evaluate the time-varying and coupling characteristics of the hydraulic diaphragm metering pump. Then, a machine learning-fitting algorithm hybrid model is constructed to solve and verify the actual matching correlation equation of the key operating parameters. In addition, the complicated non-linear relationship brings great challenges to obtaining the limit value of the pump isentropic efficiency. This study introduces the bilinear interpolation algorithm to systematically analyze the change trend between operating parameters and isentropic efficiency. Based on the wavelet neural network (WNN) with momentum term and particle swarm optimization-adaptive inertia weight adjusting (PSO-AIWA), a machine learning framework with an intelligent algorithm is constructed. Under this framework, the maximum isentropic efficiency of the pump can be stabilized at 70.22–74.67% under all working conditions. Through the theoretical analysis model, the effectiveness of this framework is evaluated. Finally, the optimal cycle parameters are evaluated. This study can provide direct significance for the analysis and optimization of the actual performance of the ORC system.
Applicability of Flow Resistance Formulae for Sand-Bed Channels: An Assessment Using a Very Large Data Set
Authors: Peng Hao , Huang He Qing , Yu Guoan , Zhang Hongwu
Published: February 2022

Among numerous flow resistance formulae for sand-bed channels, this study selected five for evaluation and in order to cover flow conditions in sand-bed river channels as widely as possible, a total of 1,636 sets of field measures were collected from the hydrological stations of two large river systems of China—the Yellow and Yangtze Rivers, in addition to the data compiled by Brownlie. The performance of the selected formulae in yielding the values of Manning resistance coefficient n was evaluated against the total of 6,805 datasets. In many cases, the formula of Ma et al. yielded unreasonable n values of <0, while that of Deng et al. and formulae 1 and 2 of Zhang et al. yielded n values with large errors. The formula of Wu and Wang yielded n values varying within the scope only in the case of n < 0.04. By dividing the absolute relative errors (AREs) from the selected formulae into six groups of 0–0.05, 0.05–1, 0.1–0.2, 0.2–0.5, 0.5–1, and >1, it can be found that, for all five selected formulae, ARE occurred in the group 0.2–0.5 occupied the largest percentage, while in each of the adjacent groups of 0.5–1 and 0.1–0.2 it also occupied a very large percentage. Hence, all five formulae still need to improve their predicting ability.
Changes in Behaviour and Proxies of Physiology Suggest Individual Variation in the Building of Migratory Phenotypes in Preparation for Long-Distance Flights
Authors: Handby Tess , Slezacek Julia , Lupi Sara , Colhoun Kendrew , Harrison Xavier A. , Bearhop Stuart
Published: February 2022

Long-distance migration in birds is a complex syndrome that involves high energy costs and, in some species, substantial physiological re-organisation. Such flexible migratory phenotypes are commonly associated with bird species flying non-stop across vast ecological barriers, where there are few opportunities to stop and refuelen route. Prior to making migratory flights, some species have been found to atrophy organs that are not required (e.g., digestive organs) and grow those associated with powering flight (pectora muscles and heart), presumably to optimise costs. However, most studies of this flexibility have required sacrificing study animals and this has limited our capacity to measure individual variation and its potential consequences. Here we investigate the behavioural and, indirectly, physiological adaptation of an arctic breeding long-distance migrant the light-bellied brent gooseBranta bernicla hrota, during spring staging in southwest Iceland. We use a sequential sampling approach to record behavioural observations and conduct stable isotope analysis of faecal samples from uniquely marked individuals to assess protein catabolism. Individuals showed a three-phase fuel deposition process, with initial slow intake rates followed by hyperphagia and then a period of inactivity immediately prior to migratory departure (despite multiple days with favourable wind conditions). The C:N ratio and δ15N values in faeces were significantly linked to fat deposition during the latter stages and suggests catabolism (reorganisation of proteins) occurring prior to departure. Our results suggest a strategic delay in migratory departure to enable reorganisation into a flying phenotype and that the extent of this varies among individuals.
A Scaling Approach to Understand the Dynamics of Fat and Lean Mass in Refueling Migrant Songbirds Measured by Quantitative Magnetic Resonance
Authors: Guglielmo Christopher G. , Morbey Yolanda E. , Kennedy Lisa V. , Deakin Jessica E. , Brown J. Morgan , Beauchamp Andrew T.
Published: February 2022

Fat contributes most of the energy for migratory flight of birds, whereas lean body tissues (muscles and organs) contribute amino acids and water to maintain metabolic and osmotic homeostasis. During refueling at stopover sites, both fat and lean mass are recovered, but the dynamics of this recovery are poorly understood. We used non-invasive quantitative magnetic resonance (QMR) analysis to measure fat and lean mass of > 3,500 individuals of 25 songbird species during six spring and three autumn migration seasons between 2009 and 2019 at Long Point, ON, Canada. We used allometric scaling analysis and linear mixed-effects modeling of body composition data at both the population level (single capture) and the individual level (recapture). In the population-level analysis, lean mass scaled hypoallometrically with body mass, such that for every 20% increase in body mass, lean mass was predicted to increase by 12.1% in spring and 12.8% in autumn. Fat scaled hyperallometrically with body mass, such that for every 20% increase in body mass, fat mass was predicted to increase by 144% in spring and 136% in autumn. At the individual level, these allometric relationships were more extreme. As a result of this differential allometry, at low body masses, lean and fat mass contributes nearly equally to changes in mass, but at high body mass fat deposition becomes progressively more dominant. Spring migrants deposited relatively more fat than autumn migrants, and in autumn juvenile birds tended to have greater lean mass than adults. Our findings show that lean mass deposition during refueling by songbirds is substantial, and in line with the losses of protein expected in flight. The process of fat and lean mass deposition is characterized by non-linear dynamics which are influenced by the current body composition, season, and, to a lesser extent, age. The patterns suggest that the need for dietary protein to rebuild lean mass will be greater when body mass is low, during autumn migration, and in juvenile birds.
Predicting Mutational Status of Driver and Suppressor Genes Directly from Histopathology With Deep Learning: A Systematic Study Across 23 Solid Tumor Types
Authors: Loeffler Chiara Maria Lavinia , Gaisa Nadine T. , Muti Hannah Sophie , van Treeck Marko , Echle Amelie , Ghaffari Laleh Narmin , Trautwein Christian , Heij Lara R. , Grabsch Heike I. , Ortiz Bruechle Nadina , Kather Jakob Nikolas
Published: February 2022

In the last four years, advances in Deep Learning technology have enabled the inference of selected mutational alterations directly from routine histopathology slides. In particular, recent studies have shown that genetic changes in clinically relevant driver genes are reflected in the histological phenotype of solid tumors and can be inferred by analysing routine Haematoxylin and Eosin (H&E) stained tissue sections with Deep Learning. However, these studies mostly focused on selected individual genes in selected tumor types. In addition, genetic changes in solid tumors primarily act by changing signaling pathways that regulate cell behaviour. In this study, we hypothesized that Deep Learning networks can be trained to directly predict alterations of genes and pathways across a spectrum of solid tumors. We manually outlined tumor tissue in H&E-stained tissue sections from 7,829 patients with 23 different tumor types from The Cancer Genome Atlas. We then trained convolutional neural networks in an end-to-end way to detect alterations in the most clinically relevant pathways or genes, directly from histology images. Using this automatic approach, we found that alterations in 12 out of 14 clinically relevant pathways and numerous single gene alterations appear to be detectable in tissue sections, many of which have not been reported before. Interestingly, we show that the prediction performance for single gene alterations is better than that for pathway alterations. Collectively, these data demonstrate the predictability of genetic alterations directly from routine cancer histology images and show that individual genes leave a stronger morphological signature than genetic pathways.
Identification and Verification of Necroptosis-Related Gene Signature and Associated Regulatory Axis in Breast Cancer
Authors: Hu Ting , Zhao Xiangwang , Zhao Yanxia , Cheng Jing , Xiong Jie , Lu Chong
Published: February 2022

Background: Breast invasive carcinoma (BRCA) is the second leading cause of malignancy death among women. Necroptosis is a newly discovered mechanism of cell death involved in the progression and prognosis of cancer. The role of necroptosis-related genes (NRGs) in BRCA is still a mystery.

Methods: LASSO Cox regression analysis was performed to construct a prognostic necroptosis-related signature. A ceRNA was constructed to explore the potential lncRNA-miRNA-mRNA regulatory axis in BRCA.

Results: A total of 63 necroptosis-related genes were differentially expressed in BRCA. We also summarized the genetic mutation landscape of NRGs in BRCA. BRCA patients with low expression of BCL2 and LEF1, as well as high expression of PLK1 and BNIP3, had a poor OS, DSS, and DFS. A necroptosis-related prognostic signature with four genes (BCL2, LEF1, PLK1, and BNIP3) was constructed, and it could serve as a prognosis biomarker in BRCA, predicting the OS rate with medium to high accuracy. Moreover, the risk score was correlated with immune infiltration in BRCA. Further comprehensive analysis revealed that the expression of BCL2, LEF1, PLK1, and BNIP3 was correlated with tumor mutation burden, microsatellite instability, drug sensitivity, and pathology stage. Previous studies have been extensively studied. The roles of LEF1, PLK1, and BNIP3 in BRCA and BCL2 were selected for further analysis. We then constructed a ceRNA network, which identified an lncRNA LINC00665/miR-181c-5p/BCL2 regulatory axis for BRCA.

Conclusion: The bioinformatics method was performed to develop a prognostic necroptosis-related prognostic signature containing four genes (BCL2, LEF1, PLK1, and BNIP3) in BRCA. We also constructed a ceRNA network and identified an lncRNA LINC00665/miR-181c-5p/BCL2 regulatory axis for BRCA. Further in vivo and in vitro studies should be conducted to verify these results.
Islet Autoimmunity in Adults With Impaired Glucose Tolerance and Recently Diagnosed, Treatment Naïve Type 2 Diabetes in the Restoring Insulin SEcretion (RISE) Study
Authors: Brooks-Worrell Barbara M. , Tjaden Ashley H. , Edelstein Sharon L. , Palomino Brenda , Utzschneider Kristina M. , Arslanian Silva , Mather Kieren J. , Buchanan Thomas A. , Nadeau Kristen J. , Atkinson Karen , Barengolts Elena , Kahn Steven E. , Palmer Jerry P. ,   The RISE Consortium
Published: February 2022

The presence of islet autoantibodies and islet reactive T cells (T+) in adults with established type 2 diabetes (T2D) have been shown to identify those patients with more severe β-cell dysfunction. However, at what stage in the progression toward clinical T2D does islet autoimmunity emerge as an important component influencing β-cell dysfunction? In this ancillary study to the Restoring Insulin SEcretion (RISE) Study, we investigated the prevalence of and association with β-cell dysfunction of T+ and autoantibodies to the 65 kDa glutamic acid decarboxylase antigen (GADA) in obese pre-diabetes adults with impaired glucose tolerance (IGT) and recently diagnosed treatment naïve (Ndx) T2D. We further investigated the effect of 12 months of RISE interventions (metformin or liraglutide plus metformin, or with 3 months of insulin glargine followed by 9 months of metformin or placebo) on islet autoimmune reactivity. We observed GADA(+) in 1.6% of NdxT2D and 4.6% of IGT at baseline, and in 1.6% of NdxT2D and 5.3% of IGT at 12 months, but no significant associations between GADA(+) and β-cell function. T(+) was observed in 50% of NdxT2D and 60.4% of IGT at baseline, and in 68.4% of NdxT2D and 83.9% of IGT at 12 months. T(+) NdxT2D were observed to have significantly higher fasting glucose (p = 0.004), and 2 h glucose (p = 0.0032), but significantly lower steady state C-peptide (sscpep, p = 0.007) compared to T(−) NdxT2D. T(+) IGT participants demonstrated lower but not significant (p = 0.025) acute (first phase) C-peptide response to glucose (ACPRg) compared to T(−) IGT. With metformin treatment, T(+) participants were observed to have a significantly lower Hemoglobin A1c (HbA1c, p = 0.002) and fasting C-peptide (p = 0.002) compared to T(−), whereas T(+) treated with liraglutide + metformin had significantly lower sscpep (p = 0.010) compared to T(−) participants. In the placebo group, T(+) participants demonstrated significantly lower ACPRg (p = 0.001) compared to T(−) participants. In summary, T(+) were found in a large percentage of obese pre-diabetes adults with IGT and in recently diagnosed T2D. Moreover, T(+) were significantly correlated with treatment effects and β-cell dysfunction. Our results demonstrate that T(+) are an important component in T2D.
Deletion of Vhl in Dmp1-Expressing Cells Causes Microenvironmental Impairment of B Cell Lymphopoiesis
Authors: Chicana Betsabel , Abbasizadeh Nastaran , Burns Christian , Taglinao Hanna , Spencer Joel A. , Manilay Jennifer O.
Published: February 2022

The contributions of skeletal cells to the processes of B cell development in the bone marrow (BM) have not been completely described. The von-Hippel Lindau protein (VHL) plays a key role in cellular responses to hypoxia. Previous work showed thatDmp1-Cre;Vhlconditional knockout mice (VhlcKO), which deletesVhlin subsets of mesenchymal stem cells, late osteoblasts and osteocytes, display dysregulated bone growth and reduction in B cells. Here, we investigated the mechanisms underlying the B cell defects using flow cytometry and high-resolution imaging. In theVhlcKO BM, B cell progenitors were increased in frequency and number, whereas Hardy Fractions B-F were decreased.VhlcKO Fractions B-C cells showed increased apoptosis and quiescence. Reciprocal BM chimeras confirmed a B cell-extrinsic source of theVhlcKO B cell defects. In support of this,VhlcKO BM supernatant contained reduced CXCL12 and elevated EPO levels. Intravital andex vivoimaging revealedVhlcKO BM blood vessels with increased diameter, volume, and a diminished blood-BM barrier. Staining ofVhlcKO B cells with an intracellular hypoxic marker indicated the natural existence of distinct B cell microenvironments that differ in local oxygen tensions and that the B cell developmental defects inVhlcKO BM are not initiated by hypoxia. Our studies identify novel mechanisms linking altered bone homeostasis with drastic BM microenvironmental changes that dysregulate B cell development.
A Novel Glucocorticoid and Androgen Receptor Modulator Reduces Viral Entry and Innate Immune Inflammatory Responses in the Syrian Hamster Model of SARS-CoV-2 Infection
Authors: Rocha Savannah M. , Fagre Anna C. , Latham Amanda S. , Cummings Jason E. , Aboellail Tawfik A. , Reigan Philip , Aldaz Devin A. , McDermott Casey P. , Popichak Katriana A. , Kading Rebekah C. , Schountz Tony , Theise Neil D. , Slayden Richard A. , Tjalkens Ronald B.
Published: February 2022

Despite significant research efforts, treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain limited. This is due in part to a lack of therapeutics that increase host defense to the virus. Replication of SARS-CoV-2 in lung tissue is associated with marked infiltration of macrophages and activation of innate immune inflammatory responses that amplify tissue injury. Antagonists of the androgen (AR) and glucocorticoid (GR) receptors have shown efficacy in models of COVID-19 and in clinical studies because the cell surface proteins required for viral entry, angiotensin converting enzyme 2 (ACE2) and the transmembrane protease, serine 2 (TMPRSS2), are transcriptionally regulated by these receptors. We postulated that the GR and AR modulator, PT150, would reduce infectivity of SARS-CoV-2 and prevent inflammatory lung injury in the Syrian golden hamster model of COVID-19 by down-regulating expression of critical genes regulated through these receptors. Animals were infected intranasally with 2.5 × 104 TCID50/ml equivalents of SARS-CoV-2 (strain 2019-nCoV/USA-WA1/2020) and PT150 was administered by oral gavage at 30 and 100 mg/Kg/day for a total of 7 days. Animals were examined at 3, 5 and 7 days post-infection (DPI) for lung histopathology, viral load and production of proteins regulating the progression of SARS-CoV-2 infection. Results indicated that oral administration of PT150 caused a dose-dependent decrease in replication of SARS-CoV-2 in lung, as well as in expression of ACE2 and TMPRSS2. Lung hypercellularity and infiltration of macrophages and CD4+ T-cells were dramatically decreased in PT150-treated animals, as was tissue damage and expression of IL-6. Molecular docking studies suggest that PT150 binds to the co-activator interface of the ligand-binding domain of both AR and GR, thereby acting as an allosteric modulator and transcriptional repressor of these receptors. Phylogenetic analysis of AR and GR revealed a high degree of sequence identity maintained across multiple species, including humans, suggesting that the mechanism of action and therapeutic efficacy observed in Syrian hamsters would likely be predictive of positive outcomes in patients. PT150 is therefore a strong candidate for further clinical development for the treatment of COVID-19 across variants of SARS-CoV-2.
Antagonistic Antibody Targeting TNFR2 Inhibits Regulatory T Cell Function to Promote Anti-Tumor Activity
Authors: Chen Yonglin , Jia Manxue , Wang Sharon , Xu Sherry , He Nanhai
Published: February 2022

Infiltration of regulatory T cells (Tregs) in the tumor microenvironment suppresses anti-tumor immune response, and promotes tumor progression. Tumor necrosis factor receptor‐2 (TNFR2), which is highly expressed on Tregs, activates Tregs through nuclear factor kappa B (NF-κB) pathway. Moreover, TNFR2+ Tregs have been shown to be most suppressive among all Tregs populations in tumor. Due to the unique expression pattern and function of TNFR2 on Tregs, a TNFR2 blocking antibody is expected to compromise Tregs function, relieve Tregs-mediated immunosuppression, and hence to enhance anti-tumor immune response. AN3025 is an antagonistic anti-human TNFR2 (hTNFR2) antibody that is currently under preclinical development. This study investigates the immunomodulatory and anti-tumor activity of AN3025. AN3025 was generated through rabbit immunization with extracellular domain of human TNFR2 and subsequent humanization by complementarity-determining regions (CDRs) grafting. AN3025 binds to the extracellular domain of both human and cynomolgus with sub-nanomolar affinity and specificity, but not mouse or rat TNFR2. AN3025 inhibited tumor necrosis factor alpha (TNFα) induced cell death of hTNFR2-overexpressing Jurkat cells by competing with TNFα for binding to hTNFR2. In the Tregs/T effector co-culture assay, AN3025 increased T effector proliferation and enhanced interferon gamma (IFNγ) production. As a monotherapy, AN3025 significantly inhibited MC38 tumor growth in TNFR2 humanized mouse model. Subsequent flow cytometry (FACS) and immunohistochemistry (IHC) analysis revealed that administration of AN3025 led to decreased Tregs population, increased CD4+ and CD8+ T cell numbers in the tumor. The anti-tumor activity of AN3025 was dependent on the existence of CD4+ and CD8+ T cells, as depletion of CD4+ and CD8+ T cells abolished the anti-tumor activity of AN3025. In addition, AN3025 in combination with anti-PD-1 antibody demonstrated stronger in-vivo anti-tumor activity. The potent anti-tumor efficacy of AN3025, either as a monotherapy or in combination with anti-PD-1 antibody, supports its further clinical development for the treatment of various human tumors.
Identification of Targets of Transcription Factor WRINKLED1-Like Related to Lipid Biosynthesis From Marine Microalga Dunaliella parva
Authors: Shang Changhua , Pang Bingbing , Yu Hongling , Gan Shanling , Li Yujia
Published: February 2022

WRINKLED1 (WRI1) is an important transcription factor controlling lipid biosynthesis. To elucidate the function of Dunaliella parva WRI1-like (WRI1-like) (i. e., DpWRI1-like), the targets of DpWRI1-like were identified by chromatin immunoprecipitation sequencing. The results showed that DpWRI1-like regulated many target genes involved in carbohydrate metabolism, lipid metabolism, photosynthesis, and transcription factor. It was proposed that DpWRI1-like participated in a regulatory network controlling lipid biosynthesis. This work laid a good foundation for a deep understanding of the regulatory mechanism of DpWRI1-like in D. parva.
Novel Natural Surfactant-Based Fatty Acids and Their Corrosion-Inhibitive Characteristics for Carbon Steel-Induced Sweet Corrosion: Detailed Practical and Computational Explorations
Authors: Abd El-Lateef Hany M. , El-Beltagi Hossam S. , Mohamed Mohamed Maged Elsayed , Kandeel Mahmoud , Bakir Esam , Toghan Arafat , Shalabi Kamal , Tantawy Ahmed H. , Khalaf Mai M.
Published: February 2022

Steel alloys are significant industrial substances, but they generally suffer severe corrosion under harsh conditions. Using inhibitors is an efficacious method to impede corrosion. So, in this study, two novel natural surfactants based on soybean oil have been synthesized by a facile route, namely, 1-(bis(2-hydroxyethyl)amino)-1-oxooctadecan-9-yl sulfate 2-hydroxyethan-1-aminium (CSM) and–N-(C2H4-OH)2; 1-(bis(2-hydroxyethyl)amino)-1-oxooctadecan-9-yl sulfate bis(2-hydroxyethyl)aminium (CSD), and their chemical structures were elucidated by physical–chemical approaches, Fourier transform infrared (FT-IR) spectroscopy, and surface activity measurements. The inhibitive effect of natural surfactants (CSM and CSD) on the C-steel corrosion in CO2-saturated 3.5% NaCl has been estimated in this investigation by electrochemical and surface analyses including electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), linear polarization resistance (LPR) corrosion rate, X-ray photoelectron spectroscopy (XPS), and field-emission scanning electron microscope/energy-dispersive X-ray spectroscopy (FESEM/EDX) approaches. The EIS study reveals the value ofRpaugmented to an increase of 913.5 Ω cm2with a protection capacity of 96.1% at 150 ppm (CSD). The outcomes of PDP suggested that CSM and CSD are mixed-type inhibitors. XPS and FESEM/EDX analyses determined the protective film formation on a metal interface having undamaged surface morphology and more homogeneities in the occurrence of the surfactant. Moreover, the adsorption of natural surfactants on the metal substrate takes place based on the model of Langmuir isotherm. Density functional theory (DFT) calculations and Monte Carlo (MC) simulations were selected for attaining basic atomic/electronic-scale details about the prepared surfactants, which support the practical findings. This study is intended to investigate the protection of C-steel using sweet service conditions with green extract surfactants.
Self-Regulated Learning Practice of Undergraduate Students in Health Professions Programs
Authors: Chitra Ebenezer , Hidayah Norul , Chandratilake Madawa , Nadarajah Vishna Devi
Published: February 2022

Background

University students are expected to take charge of their learning without being dependent on teachers. Self-regulated learning (SRL) is the process by which students direct their learning to achieve their set targets and goals in a timely and controlled manner. This study was undertaken to explore the practice of SRL by undergraduate students from different programs in a health science focused university during COVID-19 pandemic.

Method

Thirty-three undergraduate students of five health professions education programs were recruited to take part in focus group discussions to explore their SRL practice with online learning. Their responses were subjected to thematic analysis.

Result

Our students appeared to practice SRL, going through the phases of forethought and goal setting, performance and self-reflection. They set goals for academic as well as personal development in the university. Academic goals like achieving target GPA or marks were achieved by following different study techniques, personal management including time management, and by creating a conducive learning environment. Personal development such as interpersonal skills, social networking was achieved through socializing and participating in extracurricular activities. The students also engaged in self-reflection and analysis of their own performance followed by designing strategies to manage the challenges they faced.

Conclusion

Undergraduates of health professions programs appear to show evidence of practicing SRL. Although impacted by COVID-19 induced lockdown and online learning, they seem to have strategized and achieved their goals through individualized SRL processes. Promoting and fostering an atmosphere of SRL in universities to cater to the needs of the students would help them be more successful in their careers.
Role-Playing Between Environmental Pollutants and Human Gut Microbiota: A Complex Bidirectional Interaction
Authors: Giambò Federica , Costa Chiara , Teodoro Michele , Fenga Concettina
Published: February 2022

There is a growing interest in the characterization of the involvement of toxicant and pollutant exposures in the development and the progression of several diseases such as obesity, diabetes, cancer, as well as in the disruption of the immune and reproductive homeostasis. The gut microbiota is considered a pivotal player against the toxic properties of chemicals with the establishment of a dynamic bidirectional relationship, underlining the toxicological significance of this mutual interplay. In fact, several environmental chemicals have been demonstrated to affect the composition, the biodiversity of the intestinal microbiota together with the underlining modulated metabolic pathways, which may play an important role in tailoring the microbiotype of an individual. In this review, we aimed to discuss the latest updates concerning the environmental chemicals–microbiota dual interaction, toward the identification of a distinctiveness of the gut microbial community, which, in turn, may allow to adopt personalized preventive strategies to improve risk assessment for more susceptible workers.
Effects of Nalbuphine on Gastrointestinal Function in Post-Operative Critical Ill Patients Admitted to the ICU: A Multicenter Randomized Controlled Trial
Authors: Yan Yun , Lei Chong , Su Binxiao , Dong Enxia , Wang Guangming , Li Bin , Li Xinyu , Li Aiguang , Gan Guifen , Chen Yu , Zhang Xijing
Published: February 2022

Background

Gastrointestinal (GI) function can be a significant problem in critically ill patients and is associated with detrimental outcomes. The administration of opioids for pain reduction is thought to contribute to GI dysfunction. We tested whether nalbuphine, a mixed agonist/antagonist opioid modulator, can promote GI recovery in postoperative critical patients admitted to the intensive care unit (ICU) and compared it with fentanyl, a selective mu opioid receptor (MOR) agonist.

Methods

This is a multicenter, single-blind, randomized controlled trial to investigate whether nalbuphine improves the GI recovery in ICU patients after surgery, and compared it with fentanyl. The primary outcome was the time to first defecation. Secondary outcomes included the use of sedatives, enemas or laxatives, the acute gastrointestinal injury (AGI) grade, the incidence of vomiting, and the lengths of ICU and hospital stays.

Results

We randomized 436 patients, and a total of 369 patients were included in the modified intention-to-treat population (mITT) (185 to the nalbuphine group and 184 to the fentanyl group). The baseline demographic characteristics of the two groups were comparable after randomization. There was no significant difference in the time to defecation between the two groups [hazard ratio (HR) 0.94, 95% CI 0.74–1.19, p = 0.62]. There was no significant difference in the secondary outcomes between the two groups.

Conclusion

We found no evidence that nalbuphine administration can improve the GI function in postoperative critical patients admitted to the ICU compared with fentanyl. However, the CI was wide and we could not exclude the clinically important difference.
Selection and Warning of Evidence-Based Antidiabetic Medications for Patients With Chronic Liver Disease
Authors: Yen Fu-Shun , Hsu Chih-Cheng , Wei James Cheng-Chung , Hou Ming-Chih , Hwu Chii-Min
Published: February 2022

The global prevalence of chronic liver disease and diabetes mellitus (DM) has gradually increased potentially due to changes in diet and lifestyle. The choice of antidiabetic medications for patients with coexisting DM and chronic liver disease is complicated. Severe liver injury may decrease the metabolism of antidiabetic medications, resulting in elevated drug concentrations and adverse effects. The choice of antidiabetic medications in patients with chronic liver disease has not been well studied. The long-term outcomes of antidiabetic medications in patients with chronic liver disease have gained attention recently. Herein, we reviewed relevant articles to extend our understanding on the selection and warning of antidiabetic medications for patients with chronic liver disease.
A Whole-Genome Sequencing-Based Study to Delineate the Risk and Characteristics of Tuberculosis Transmission in an Insular Population Over 10 Years in Shanghai
Authors: Wang Min , Zhang Yangyi , Huang Cheng , Li Jing , Shen Xin , Zhao Genming , Jiang Yuan , Pan Qichao
Published: February 2022

Background

Tuberculosis (TB) has remained a tough problem in China. This study aims to identify the risk of tuberculosis transmission and to assess its characteristics.

Methods

We performed a molecular epidemiological study for patients with culture-positive Mycobacterium tuberculosis (M. tuberculosis) in Shanghai, from 2009 to 2018. Demographic information was obtained from the Tuberculosis Information Management System. Whole-genome sequencing (WGS) was conducted with a threshold of 12 single-nucleotide polymorphisms (SNPs) to distinguish the genomic cluster. To analyze the characteristics of TB transmission, the contact investigation for clustered cases was performed.

Results

In total, 94 (27.25%) of the 345 enrolled patients were grouped into 42 genomic clusters, indicating local transmission of M. tuberculosis strains. Compared to a health system delay <14 days, patients with a health system delay ≥14 days [adjusted odds ratios (AOR) = 2.57, 95% confidence interval (CI): 1.34–4.95] were more likely to be clustered. Patients under 65 years old (AOR = 3.11, 95% CI: 1.76–5.49), residents (AOR = 2.43, 95% CI: 1.18–4.99), and Beijing genotype strains (AOR = 3.35, 95% CI: 1.32–8.53) were associated with increased risk of clustering. Interestingly, patients with resistance to isoniazid (AOR = 2.36, 95% CI: 1.15–4.88) had a higher risk of transmission. Sixteen confirmed/probable epidemiological links were identified. Local transmission of imported cases and household transmission were prominent.

Conclusion

Health system delay is a crucial factor for TB transmission. Patients with resistance to isoniazid should be priority targets for contact investigation to reduce transmission.
Frontal White Matter Hyperintensities Effect on Default Mode Network Connectivity in Acute Mild Traumatic Brain Injury
Authors: Zhang Danbin , Zhu Pingyi , Yin Bo , Zhao Pinghui , Wang Shan , Ye Limei , Bai Lijun , Yan Zhihan , Bai Guanghui
Published: February 2022

The functional connectivity of the brain depends not only on the structural integrity of the cortex but also on the white matter pathways between cortical areas. White matter hyperintensities (WMH), caused by chronic hypoperfusion in the white matter, play a role in the outcome of traumatic brain injury (TBI) and other neurodegenerative disorders. Herein, we investigate how the location and volume of WMH affect the default-mode network (DMN) connectivity in acute mild TBI (mTBI) patients. Forty-six patients with acute mTBI and 46 matched healthy controls were enrolled in the study. All participants underwent T2-weighted fluid-attenuated inversion recovery magnetic resonance imaging (MRI), resting-state functional MRI (fMRI),and neuropsychological assessments. The volume and location of WMH were recorded. The relationships between the WMH volume and clinical assessments were evaluated using Spearman’s correlation. Patients with higher frontal lobe WMH volume had more severe post-concussion symptoms and poorer information processing speed. Moreover, these patients had significantly lower functional connectivity in the right middle temporal gyrus, left middle frontal gyrus, right superior frontal gyrus, and left anterior cingulate cortex, compared with patients with low frontal lobe WMH volume. Compared to the controls, the patients with high frontal WMH volume exhibited significantly lower functional connectivity in the right inferior temporal gyrus, left anterior cingulate cortex, and right superior frontal gyrus. These findings suggest that frontal lobe WMH volume may modulate the functional connectivity within the DMN. Therefore, the WMH volume in specific regions of the brain, particularly the frontal and parietal lobes, may accelerate the process of aging and cognitive impairment may be a useful biomarker for the diagnosis and prognosis of acute mTBI.
Cerebral Blood Flow Alterations in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Arterial Spin Labeling Studies
Authors: Liu Jieke , Yang Xi , Li Yong , Xu Hao , Ren Jing , Zhou Peng
Published: February 2022

Objective

Arterial spin labeling (ASL) studies have revealed inconsistent regional cerebral blood flow (CBF) alterations in patients with type 2 diabetes mellitus (T2DM). The aim of this systematic review and meta-analysis was to identify concordant regional CBF alterations in T2DM.

Methods

A systematic review was conducted to the published literatures comparing cerebral perfusion between patients with T2DM and healthy controls using ASL. The seed-based d mapping (SDM) was further used to perform quantitative meta-analysis on voxel-based literatures and to estimate the regional CBF alterations in patients with T2DM. Metaregression was performed to explore the associations between clinical characteristics and cerebral perfusion alterations.

Results

A total of 13 studies with 14 reports were included in the systematic review and 7 studies with 7 reports were included in the quantitative meta-analysis. The qualitative review found widespread CBF reduction in cerebral lobes in T2DM. The meta-analysis found increased regional CBF in right supplementary motor area and decreased regional CBF in bilateral middle occipital gyrus, left caudate nucleus, right superior parietal gyrus, and left calcarine fissure/surrounding cortex in T2DM.

Conclusion

The patterns of cerebral perfusion alterations, characterized by the decreased CBF in occipital and parietal lobes, might be the neuropathology of visual impairment and cognitive aging in T2DM.
Evidence Mapping Based on Systematic Reviews of Repetitive Transcranial Magnetic Stimulation on the Motor Cortex for Neuropathic Pain
Authors: Zang Yaning , Zhang Yongni , Lai Xigui , Yang Yujie , Guo Jiabao , Gu Shanshan , Zhu Yi
Published: February 2022

Background and Objective

There is vast published literature proposing repetitive transcranial magnetic stimulation (rTMS) technology on the motor cortex (M1) for the treatment of neuropathic pain (NP). Systematic reviews (SRs) focus on a specific problem and do not provide a comprehensive overview of a research area. This study aimed to summarize and analyze the evidence of rTMS on the M1 for NP treatment through a new synthesis method called evidence mapping.

Methods

Searches were conducted in PubMed, EMBASE, Epistemonikos, and The Cochrane Library to identify the studies that summarized the effectiveness of rTMS for NP. The study type was restricted to SRs with or without meta-analysis. All literature published before January 23, 2021, was included. Two reviewers independently screened the literature, assessed the methodological quality, and extracted the data. The methodological quality of the included SRs was assessed by using the A Measurement Tool to Assess Systematic Reviews (AMSTAR-2). Data were extracted following a defined population, intervention, comparison, and outcome (PICO) framework from primary studies that included SRs. The same PICO was categorized into PICOs according to interventions [frequency, number of sessions (short: 1–5 sessions, medium: 5–10 sessions, and long: >10 sessions)] and compared. The evidence map was presented in tables and a bubble plot.

Results

A total of 38 SRs met the eligibility criteria. After duplicate primary studies were removed, these reviews included 70 primary studies that met the scope of evidence mapping. According to the AMSTAR-2 assessment, the quality of the included SRs was critically low. Of these studies, 34 SRs scored “critically low” in terms of methodological quality, 2 SR scored “low,” 1 SR scored “moderate,” and 1 SR scored “high.”

Conclusion

Evidence mapping is a useful methodology to provide a comprehensive and reliable overview of studies on rTMS for NP. Evidence mapping also shows that further investigations are necessary to highlight the optimal stimulation protocols and standardize all parameters to fill the evidence gaps of rTMS. Given that the methodological quality of most included SRs was “critically low,” further investigations are advised to improve the methodological quality and the reporting process of SRs.
Parameter Estimation of Two Spiking Neuron Models With Meta-Heuristic Optimization Algorithms
Authors: AbdelAty Amr M. , Fouda Mohammed E. , Eltawil Ahmed
Published: February 2022

The automatic fitting of spiking neuron models to experimental data is a challenging problem. The integrate and fire model and Hodgkin–Huxley (HH) models represent the two complexity extremes of spiking neural models. Between these two extremes lies two and three differential-equation-based models. In this work, we investigate the problem of parameter estimation of two simple neuron models with a sharp reset in order to fit the spike timing of electro-physiological recordings based on two problem formulations. Five optimization algorithms are investigated; three of them have not been used to tackle this problem before. The new algorithms show improved fitting when compared with the old ones in both problems under investigation. The improvement in fitness function is between 5 and 8%, which is achieved by using the new algorithms while also being more consistent between independent trials. Furthermore, a new problem formulation is investigated that uses a lower number of search space variables when compared to the ones reported in related literature.
“Sound” Decisions: The Combined Role of Ambient Noise and Cognitive Regulation on the Neurophysiology of Food Cravings
Authors: Peng-Li Danni , Alves Da Mota Patricia , Correa Camile Maria Costa , Chan Raymond C. K. , Byrne Derek Victor , Wang Qian Janice
Published: February 2022

Our ability to evaluate long-term goals over immediate rewards is manifested in the brain’s decision circuit. Simplistically, it can be divided into a fast, impulsive, reward “system 1” and a slow, deliberate, control “system 2.” In a noisy eating environment, our cognitive resources may get depleted, potentially leading to cognitive overload, emotional arousal, and consequently more rash decisions, such as unhealthy food choices. Here, we investigated the combined impact of cognitive regulation and ambient noise on food cravings through neurophysiological activity. Thirty-seven participants were recruited for an adapted version of the Regulation of Craving (ROC) task. All participants underwent two sessions of the ROC task; once with soft ambient restaurant noise (∼50 dB) and once with loud ambient restaurant noise (∼70 dB), while data from electroencephalography (EEG), electrodermal activity (EDA), and self-reported craving were collected for all palatable food images presented in the task. The results indicated that thinking about future (“later”) consequences vs. immediate (“now”) sensations associated with the food decreased cravings, which were mediated by frontal EEG alpha power. Likewise, “later” trials also increased frontal alpha asymmetry (FAA) —an index for emotional motivation. Furthermore, loud (vs. soft) noise increased alpha, beta, and theta activity, but for theta activity, this was solely occurring during “later” trials. Similarly, EDA signal peak probability was also higher during loud noise. Collectively, our findings suggest that the presence of loud ambient noise in conjunction with prospective thinking can lead to the highest emotional arousal and cognitive load as measured by EDA and EEG, respectively, both of which are important in regulating cravings and decisions. Thus, exploring the combined effects of interoceptive regulation and exteroceptive cues on food-related decision-making could be methodologically advantageous in consumer neuroscience and entail theoretical, commercial, and managerial implications.
Electrophysiological Properties of Human Cortical Organoids: Current State of the Art and Future Directions
Authors: Zourray Clara , Kurian Manju A. , Barral Serena , Lignani Gabriele
Published: February 2022

Human cortical development is an intricate process resulting in the generation of many interacting cell types and long-range connections to and from other brain regions. Human stem cell-derived cortical organoids are now becoming widely used to model human cortical development both in physiological and pathological conditions, as they offer the advantage of recapitulating human-specific aspects of corticogenesis that were previously inaccessible. Understanding the electrophysiological properties and functional maturation of neurons derived from human cortical organoids is key to ensure their physiological and pathological relevance. Here we review existing data on the electrophysiological properties of neurons in human cortical organoids, as well as recent advances in the complexity of cortical organoid modeling that have led to improvements in functional maturation at single neuron and neuronal network levels. Eventually, a more comprehensive and standardized electrophysiological characterization of these models will allow to better understand human neurophysiology, model diseases and test novel treatments.
Metabolomics of Rice Bran Differentially Impacted by Fermentation With Six Probiotics Demonstrates Key Nutrient Changes for Enhancing Gut Health
Authors: Seyoum Yohannes , Humblot Christèle , Baxter Bridget A. , Nealon Nora Jean , Weber Annika M. , Ryan Elizabeth P.
Published: February 2022

The consumption of rice bran has been shown to have a positive effect on nutritional status and prevention of chronic diseases related to hundreds of metabolites with bioactivity. Consumption after fermentation can lead to specific beneficial effects, yet is lacking complete characterization when fermented with diverse strains. The objective of this study was to examine the effect of fermentation on the rice bran metabolite profile. Bacterial probiotics (Bifidobacterium longum, Limosilactobacillus fermentum, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus and, Escherichia coli) were used to ferment rice bran alone or after incubation with yeast probiotic Saccharomyces boulardii. Fermented rice bran was methanol extracted and analyzed by UPLC-MS/MS. The metabolome of the two fermentation types was deeply modified when compared with non-fermented rice bran. The two-step fermentation provided alternative substrate to the bacteria in a few cases. Key metabolites of high nutritional value (essential amino acids, vitamins) and gut health (arabinose, maltotriose) were identified.