bluuebunny/crossref_metadata_2025 huggingface dataset:
Important and achieved competence for Swedish vocational teachers: A survey with teachers and principals
Authors: Antera Sofia , Teräs Marianne , Nilsson Staffan , Rehn Helena
Published: February 2022

Vocational teachers have a key role in the professional growth of vocational students, making their competence an important factor in the quality of VET. This study explores how principals and vocational teachers identify important and achieved competencies in relation to vocational teachers’ work. The data was collected through an online questionnaire, centred in two types of competence, competence important for teachers (important competence) and competence they consider they have already developed (achieved competence). For each type, a set of 27 competencies was evaluated on a Likert-scale by 370 participants, including both teachers and principals. The statistical analysis was primarily descriptive. The findings indicated that good communication with students, assessment of students’ knowledge, skills and abilities, and creating conditions for learning, are the three most important and achieved competencies in VET teachers’ work. On the contrary, previous teaching experience, working experience with adults and migrants, and the competence related to recruitment of students and marketing of the school, were seen as the least important and achieved ones. Different actors, meaning principals and teachers, reached an agreement on these findings. Future research should look into the reasons behind the selection of specific competence as important and the processes of competence development.
Uncertainty Visualization: Concepts, Methods, and Applications in Biological Data Visualization
Authors: Weiskopf Daniel
Published: February 2022

This paper provides an overview of uncertainty visualization in general, along with specific examples of applications in bioinformatics. Starting from a processing and interaction pipeline of visualization, components are discussed that are relevant for handling and visualizing uncertainty introduced with the original data and at later stages in the pipeline, which shows the importance of making the stages of the pipeline aware of uncertainty and allowing them to propagate uncertainty. We detail concepts and methods for visual mappings of uncertainty, distinguishing between explicit and implict representations of distributions, different ways to show summary statistics, and combined or hybrid visualizations. The basic concepts are illustrated for several examples of graph visualization under uncertainty. Finally, this review paper discusses implications for the visualization of biological data and future research directions.
Prognostic Nomograms Predicting Risk of Keratoconus in Very Asymmetric Ectasia: Combined Corneal Tomographic and Biomechanical Assessments
Authors: Zhang Xiaoyu , Ding Lan , Sun Ling , Huang Yangyi , Han Tian , Qian Yishan , Zhou Xingtao
Published: February 2022

Purpose: The aim of the study was to develop and validate a prognostic nomogram for subclinical keratoconus diagnosis using corneal tomographic and biomechanical integration assessments.

Design: This is a retrospective case–control study.

Methods:Setting: The study was carried out in a hospital setting. Patients: The study included patients with very asymmetric ectasia (VAE) and normal controls. Patients with VAE had defined clinical ectasia in one eye and normal topography (VAE-NT) in the fellow eye, and VAE-NT eyes were selected for analysis. VAE-NT was defined as stratified stage 0 using the ABCD keratoconus grading system. The normal control group was selected from corneal refractive surgery candidates at our clinic, and the right eye was enrolled. Observation Procedures: Scheimpflug-based corneal tomography (Pentacam) and corneal biomechanical assessment (Corvis ST) were performed. Main Outcome Measures: We performed multiple logistic regression analysis and constructed a simple nomogram via the stepwise method. The receiver operating characteristic (ROC) curve and discrimination and calibration of prognostic nomogram were performed by 500 bootstrap resamplings to assess the determination and clinical value, respectively.

Results: A total of 59 VAE-NT and 142 normal eyes were enrolled. For differentiating normal and VAE-NT eyes, the values of specificity, sensitivity, and area under the ROC (AUROC) were 0.725, 0.610, and 0.713 for tomographic parameters, 0.886, 0.632, and 0.811 for biomechanical parameters, and 0.871, 0.754, and 0.849 for combined parameters, respectively. Combined parameters showed better predictability than separated tomographic or biomechanical parameters.

Conclusion: Our nomogram developed with combined tomographic and biomechanical parameters demonstrated a plausible, capable, and widely implementable tool to predict risk of keratoconus. The identification of at-risk patients can provide advanced strategies to epitomize ectasia susceptibility.
HPS6 Regulates the Biogenesis of Weibel–Palade Body in Endothelial Cells Through Trafficking v-ATPase to Its Limiting Membrane
Authors: Lu Jiran , Ma Jing , Hao Zhenhua , Li Wei
Published: February 2022

The Weibel–Palade body (WPB) is one of the lysosome-related organelles (LROs) in endothelial cells, whose main content is von Willebrand factor (vWF). The biogenesis of LROs is regulated by the Hermansky–Pudlak syndrome (HPS) protein-associated complexes through transporting cargo proteins to WPBs. Our previous studies have shown that HPS6, a subunit of BLOC-2 complex, is likely involved in the maturation of WPBs. However, the underlying mechanism remains unknown. In this study, we found that the knockdown of HPS6 in human umbilical vein endothelial cells (HUVECs) resulted in misshaped WPBs, decreased WPB number, and impaired vWF tubulation, which are similar to the characteristics of HPS6-deficient mouse endothelial cells. We observed similar morphological changes of WPBs in HUVECs after the knockdown of ATP6V0D1 (a subunit of v-ATPase). Furthermore, we found that HPS6 interacted with ATP6V0D1, suggesting that HPS6 transports ATP6V0D1 to the WPB limiting membrane for the assembly of the v-ATPase complex to maintain its acidic luminal pH, which is critical for the formation of vWF tubules during WPB maturation. In conclusion, HPS6 likely regulates the biogenesis of WPBs by participating in the trafficking of v-ATPase to the WPB membrane.
CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways
Authors: Wang Zeyu , Zhang Jingwei , Zhang Hao , Dai Ziyu , Liang Xisong , Li Shuwang , Peng Renjun , Zhang Xun , Liu Fangkun , Liu Zhixiong , Yang Kui , Cheng Quan
Published: February 2022

Lower-grade glioma (LGG) is one of the most common primary tumor types in adults. The chemokine-like factor (CKLF)-like Marvel transmembrane domain-containing (CMTM) family is widely expressed in the immune system and can modulate tumor progression. However, the role of the CMTM family in LGG remains unknown. A total of 508 LGG patients from The Cancer Genome Atlas (TCGA) database were used as a training cohort, and 155 LGG patients from the Chinese Glioma Genome Atlas (CGGA) array database, 142 LGG patients from the CGGA RNA-sequencing database, and 168 LGG patients from the GSE108474 database were used as the validation cohorts. Patients were subdivided into two groups using consensus clustering. The ENET algorithm was applied to build a scoring model based on the cluster model. Finally, ESTIMATE, CIBERSORT, and xCell algorithms were performed to define the tumor immune landscape. The expression levels of the CMTM family genes were associated with glioma grades and isocitrate dehydrogenase (IDH) status. Patients in cluster 2 and the high-risk score group exhibited a poor prognosis and were enriched with higher grade, wild-type IDH (IDH-WT), 1p19q non-codeletion, MGMT promoter unmethylation, and IDH-WT subtype. Patients in cluster 1 and low-risk score group were associated with high tumor purity and reduced immune cell infiltration. Enrichment pathways analysis indicated that several essential pathways involved in tumor progression were associated with the expression of CMTM family genes. Importantly, PD-1, PD-L1, and PD-L2 expression levels were increased in cluster 2 and high-risk groups. Therefore, the CMTM family contributes to LGG progression through modulating tumor immune landscape.
Morphological Phenotyping of Organotropic Brain- and Bone-Seeking Triple Negative Metastatic Breast Tumor Cells
Authors: DeCastro Ariana Joy L. , Pranda Marina A. , Gray Kelsey M. , Merlo-Coyne John , Girma Nathaniel , Hurwitz Madelyn , Zhang Yuji , Stroka Kimberly M.
Published: February 2022

Triple negative breast cancer (TNBC) follows a non-random pattern of metastasis to the bone and brain tissue. Prior work has found that brain-seeking breast tumor cells display altered proteomic profiles, leading to alterations in pathways related to cell signaling, cell cycle, metabolism, and extracellular matrix remodeling. Given the unique microenvironmental characteristics of brain and bone tissue, we hypothesized that brain- or bone-seeking TNBC cells may have altered morphologic or migratory phenotypes from each other, or from the parental TNBC cells, as a function of the biochemical or mechanical microenvironment. In this study, we utilized TNBC cells (MDA-MB-231) that were conditioned to metastasize solely to brain (MDA-BR) or bone (MDA-BO) tissue. We quantified characteristics such as cell morphology, migration, and stiffness in response to cues that partially mimic their final metastatic niche. We have shown that MDA-BO cells have a distinct protrusive morphology not found in MDA-P or MDA-BR. Further, MDA-BO cells migrate over a larger area when on a collagen I (abundant in bone tissue) substrate when compared to fibronectin (abundant in brain tissue). However, migration in highly confined environments was similar across the cell types. Modest differences were found in the stiffness of MDA-BR and MDA-BO cells plated on collagen I vs. fibronectin-coated surfaces. Lastly, MDA-BO cells were found to have larger focal adhesion area and density in comparison with the other two cell types. These results initiate a quantitative profile of mechanobiological phenotypes in TNBC, with future impacts aiming to help predict metastatic propensities to organ-specific sites in a clinical setting.
Indolethylamine-N-Methyltransferase Inhibits Proliferation and Promotes Apoptosis of Human Prostate Cancer Cells: A Mechanistic Exploration
Authors: Jianfeng Wang , Yutao Wang , Jianbin Bi
Published: February 2022

Indolethylamine-N-methyltransferase (INMT) is a methyltransferase downregulated in lung cancer, meningioma, and prostate cancer; however, its role and mechanism in prostate cancer remain unclear. By analyzing The Cancer Genome Atlas (TCGA)-PRAD, we found that the expression of INMT in prostate cancer was lower than that of adjacent non-cancerous prostate tissues and was significantly correlated with lymph node metastasis Gleason score, PSA expression, and survival. Combined with the GSE46602 cohorts for pathway enrichment analysis, we found that INMT was involved in regulating the MAPK, TGFβ, and Wnt signaling pathways. After overexpression of INMT in prostate cancer cell lines 22Rv1 and PC-3, we found an effect of INMT on these tumor signal pathways; overexpression of INMT inhibited the proliferation of prostate cancer cells and promoted apoptosis. Using the ESTIMATE algorithm, we found that with the increase of INMT expression, immune and stromal scores in the tumor microenvironment increased, immune response intensity increased, and tumor purity decreased. The difference in INMT expression affected the proportion of several immune cells. According to PRISM and CTRP2.0, the potential therapeutic agents associated with the INMT expression subgroup in TCGA were predicted. The area under the curve (AUC) values of 26 compounds positively correlated with the expression of INMT, while the AUC values of 14 compounds were negatively correlated with the expression of INMT. These findings suggest that INMT may affect prostate cancer’s occurrence, development, and drug sensitivity via various tumor signaling pathways and tumor microenvironments.
The Intricate Crosstalk Between Insulin and Pancreatic Ductal Adenocarcinoma: A Review From Clinical to Molecular
Authors: Deng Junyuan , Guo Yujie , Du Jiali , Gu Jichun , Kong Lei , Tao Boan , Li Ji , Fu Deliang
Published: February 2022

Increased insulin level (or “hyperinsulinemia”) is a common phenomenon in pancreatic ductal adenocarcinoma (PDA) patients and signals poor clinical outcomes. Insulin is safe in low PDA risk population, while insulin significantly promotes PDA risk in high PDA risk population. The correlation between insulin and PDA is a reciprocal self-reinforcing relationship. On the one hand, pancreatic cancer cells synthesize multiple molecules to cause elevated peripheral insulin resistance, thus enhancing hyperinsulinemia. On the other hand, insulin promotes pancreatic cancer initiation and sustains PDA development by eliciting tumorigenic inflammation, regulating lipid and glucose metabolic reprogram, overcoming apoptosis through the crosstalk with IGF-1, stimulating cancer metastasis, and activating tumor microenvironment formation (inflammation, fibrosis, and angiogenesis). Currently, taking glucose sensitizing agents, including metformin, SGLT-2 inhibitor, and GLP-1 agonist, is an effective way of lowering insulin levels and controlling PDA development at the same time. In the future, new drugs targeting insulin-related signal pathways may pave a novel way for suppressing PDA initiation and progression.
Signaling Dynamics of TSHR-Specific CAR-T Cells Revealed by FRET-Based Biosensors
Authors: Zhou Jing , Chen Jiangqing , Huang Yanjie , Gao Xiaofei , Zhou Chun , Meng Xianhui , Sun Jie
Published: February 2022

Although most patients with thyroid cancers have good prognosis and long-term survival, some patients are refractory to traditional therapeutic approaches and face a high risk of mortality. CAR-T therapy provides an attractive strategy to treat these patients. Considering the limited expression in thyroid tissues, thyroid-stimulating hormone receptor (TSHR) has been considered as a promising candidate as CAR-T target. However, it is still a challenge to find the optimal CAR design for the treatment of thyroid cancers. Dynamic signaling cascade is initiated by CAR molecules during CAR-T cell activation. The development of FRET-based biosensors enables us to detect the signaling dynamics of key kinases during CAR-T cell activation with high spatiotemporal resolution. Here using the ZAP70 and ERK biosensors, we visualized the dynamics of ZAP70 and ERK activities in TSHR-specific CAR-T cells upon antigen stimulation. We first constructed several TSHR-targeting CARs for the treatment of advanced thyroid cancers. The TSHR CAR-T cells with CD28 or 4-1BB co-stimulatory signaling domains exhibited potent cytotoxicity in vitro. By FRET imaging, we observed rapid increase of ZAP70 and ERK activities in TSHR CAR-T cells upon target cell binding. Even though CD28-based CAR-T cells had similar ZAP70 activation dynamics as 4-1BB-based CAR-T cells, they displayed slightly enhanced ERK activation, which may contribute to their faster anti-tumor kinetics in vivo. These results demonstrated the efficacy of TSHR CAR-T cells to treat advanced thyroid cancers. Our study indicated the potential of applying FRET biosensors to optimize the design of CAR for effective CAR-T therapy.
Early Deletion of Neurod1 Alters Neuronal Lineage Potential and Diminishes Neurogenesis in the Inner Ear
Authors: Filova Iva , Bohuslavova Romana , Tavakoli Mitra , Yamoah Ebenezer N. , Fritzsch Bernd , Pavlinkova Gabriela
Published: February 2022

Neuronal development in the inner ear is initiated by expression of the proneural basic Helix-Loop-Helix (bHLH) transcription factor Neurogenin1 that specifies neuronal precursors in the otocyst. The initial specification of the neuroblasts within the otic epithelium is followed by the expression of an additional bHLH factor, Neurod1. Although NEUROD1 is essential for inner ear neuronal development, the different aspects of the temporal and spatial requirements of NEUROD1 for the inner ear and, mainly, for auditory neuron development are not fully understood. In this study, using Foxg1Cre for the early elimination of Neurod1 in the mouse otocyst, we showed that Neurod1 deletion results in a massive reduction of differentiating neurons in the otic ganglion at E10.5, and in the diminished vestibular and rudimental spiral ganglia at E13.5. Attenuated neuronal development was associated with reduced and disorganized sensory epithelia, formation of ectopic hair cells, and the shortened cochlea in the inner ear. Central projections of inner ear neurons with conditional Neurod1 deletion are reduced, unsegregated, disorganized, and interconnecting the vestibular and auditory systems. In line with decreased afferent input from auditory neurons, the volume of cochlear nuclei was reduced by 60% in Neurod1 mutant mice. Finally, our data demonstrate that early elimination of Neurod1 affects the neuronal lineage potential and alters the generation of inner ear neurons and cochlear afferents with a profound effect on the first auditory nuclei, the cochlear nuclei.
Home Away From Home: Bioengineering Advancements to Mimic the Developmental and Adult Stem Cell Niche
Authors: Barhouse Patrick S. , Andrade Melisa J. , Smith Quinton
Published: February 2022

The inherent self-organizing capacity of pluripotent and adult stem cell populations has advanced our fundamental understanding of processes that drive human development, homeostasis, regeneration, and disease progression. Translating these principles into in vitro model systems has been achieved with the advent of organoid technology, driving innovation to harness patient-specific, cell-laden regenerative constructs that can be engineered to augment or replace diseased tissue. While developmental organization and regenerative adult stem cell niches are tightly regulated in vivo, in vitro analogs lack defined architecture and presentation of physicochemical cues, leading to the unhindered arrangement of mini-tissues that lack complete physiological mimicry. This review aims to highlight the recent integrative engineering approaches that elicit spatio-temporal control of the extracellular niche to direct the structural and functional maturation of pluripotent and adult stem cell derivatives. While the advances presented here leverage multi-pronged strategies ranging from synthetic biology to microfabrication technologies, the methods converge on recreating the biochemical and biophysical milieu of the native tissue to be modeled or regenerated.
Directed Evolution Pipeline for the Improvement of Orthogonal Translation Machinery for Genetic Code Expansion at Sense Codons
Authors: Biddle Wil , Schwark David G. , Schmitt Margaret A. , Fisk John D.
Published: February 2022

The expansion of the genetic code beyond a single type of noncanonical amino acid (ncAA) is hindered by inefficient machinery for reassigning the meaning of sense codons. A major obstacle to using directed evolution to improve the efficiency of sense codon reassignment is that fractional sense codon reassignments lead to heterogeneous mixtures of full-length proteins with either a ncAA or a natural amino acid incorporated in response to the targeted codon. In stop codon suppression systems, missed incorporations lead to truncated proteins; improvements in activity may be inferred from increased protein yields or the production of downstream reporters. In sense codon reassignment, the heterogeneous proteins produced greatly complicate the development of screens for variants of the orthogonal machinery with improved activity. We describe the use of a previously-reported fluorescence-based screen for sense codon reassignment as the first step in a directed evolution workflow to improve the incorporation of a ncAA in response to the Arg AGG sense codon. We first screened a library with diversity introduced into both the orthogonal Methanocaldococcus jannaschii tyrosyl tRNA anticodon loop and the cognate aminoacyl tRNA synthetase (aaRS) anticodon binding domain for variants that improved incorporation of tyrosine in response to the AGG codon. The most efficient variants produced fluorescent proteins at levels indistinguishable from the E. coli translation machinery decoding tyrosine codons. Mutations to the M. jannaschii aaRS that were found to improve tyrosine incorporation were transplanted onto a M. jannaschii aaRS evolved for the incorporation of para-azidophenylalanine. Improved ncAA incorporation was evident using fluorescence- and mass-based reporters. The described workflow is generalizable and should enable the rapid tailoring of orthogonal machinery capable of activating diverse ncAAs to any sense codon target. We evaluated the selection based improvements of the orthogonal pair in a host genomically engineered for reduced target codon competition. Using this particular system for evaluation of arginine AGG codon reassignment, however, E. coli strains with genomes engineered to remove competing tRNAs did not outperform a standard laboratory E. coli strain in sense codon reassignment.
Directed Discovery of Tetrapeptide Emulsifiers
Authors: Scott Gary G. , Börner Tim , Leser Martin E. , Wooster Tim J. , Tuttle Tell
Published: February 2022

Oil in water emulsions are an important class of soft material that are used in the food, cosmetic, and biomedical industries. These materials are formed through the use of emulsifiers that are able to stabilize oil droplets in water. Historically emulsifiers have been developed from lipids or from large biomolecules such as proteins. However, the ability to use short peptides, which have favorable degradability and toxicity profiles is seen as an attractive alternative. In this work, we demonstrate that it is possible to design emulsifiers from short (tetra) peptides that have tunability (i.e., the surface activity of the emulsion can be tuned according to the peptide primary sequence). This design process is achieved by applying coarse grain molecular dynamics simulation to consecutively reduce the molecular search space from the 83,521 candidates initially considered in the screen to four top ranking candidates that were then studied experimentally. The results of the experimental study correspond well to the predicted results from the computational screening verifying the potential of this screening methodology to be applied to a range of different molecular systems.
Relationships Between Bronchodilators, Steroids, Antiarrhythmic Drugs, Antidepressants, and Benzodiazepines and Heart Disease and Ischemic Stroke in Patients With Predominant Bronchiectasis and Asthma
Authors: Yeh Jun-Jun , Lai Mei-Chu , Yang Yu-Cih , Hsu Chung-Y. , Kao Chia-Hung
Published: February 2022

Objective

We investigated the effects of medication on heart disease and ischemic stroke (HDS) risk in patients with predominant bronchiectasis-asthma combination (BCAS).

Methods

BCAS and non-BCAS cohorts (N = 588 and 1,118, respectively) were retrospectively enrolled. The cumulative incidence of HDS was analyzed using Cox proportional regression; propensity scores were estimated using non-parsimonious multivariable logistic regression. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for HDS were calculated, adjusting for sex, age, comorbidities, and medication {long- and short-acting β2 agonists and muscarinic antagonists (LABAs/SABAs and LAMAs/SAMAs), steroids [inhaled corticosteroid steroids (ICSs), oral steroids (OSs)], antiarrhythmics, antidepressants (fluoxetine), benzodiazepines (alprazolam, fludiazepam), statins and antihypertensive drugs (diuretics, cardioselective beta blockers, calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEi), angiotensin II blockers)}.

Results

Compared with the non-BCAS cohort, the BCAS cohort taking LABAs, SABAs, SAMAs, ICSs, OSs, antiarrhythmics, and alprazolam had an elevated HDS risk [aHRs (95% CIs): 2.36 (1.25–4.33), 2.65 (1.87–3.75), 2.66 (1.74–4.05), 2.53 (1.61–3.99), 1.76 (1.43–2.18), 9.88 (3.27–30.5), and 1.73 (1.15–2.58), respectively except fludiazepam 1.33 (0.73–2.40)]. The aHRs (95% CIs) for LABAs ≤ 30 days, DDDs <415, ICSs ≤ 30 days were 1.10 (0.38–3.15), 2.95 (0.22–38.8), 1.45 (0.76–2.77). The aHRs (95% CIs) for current and recent alprazolam were 1.78 (1.09–2.93) and 777.8 (1.34–451590.0); for current and past fludiazepam were 1.39 (0.75–2.59) and 1.29 (0.42–4.01) and for past alprazolam was 1.57 (0.55–4.46); respectively. The aHRs (95% CIs) for alprazolam >30 DDDs, fludiazepam >20 DDDs, ICSs ≦415 DDDs, and OSs DDDs ≦15 were 1.60 (0.78–3.29), 2.43 (0.90–6.55), 5.02 (1.76–14.3), and 2.28 (1.43–3.62), respectively.

Conclusion

The bronchodilators, steroids, and antiarrhythmics were associated with higher risk of HDS, even low dose use of steroids. However, the current use of LABAs/ICSs were not associated with HDS. Benzodiazepines were relatively safe, except for current or recent alprazolam use. Notably, taking confounders into account is crucial in observational studies.
Evidence of User-Expert Gaps in Health App Ratings and Implications for Practice
Authors: de Chantal Pier-Luc , Chagnon Alexandre , Cardinal Michael , Faieta Julie , Guertin Alexandre
Published: February 2022

Searching the commercial Google Play Store and App Store is one of the most common strategies for discovering mobile applications for digital health, both among consumers and healthcare professionals. However, several studies have suggested a possible mismatch between this strategy and the objective of finding apps in physical and mental health that are both clinically relevant and reliable from a privacy standpoint. This study provides direct evidence of a gap between the five-star user rating system and expert ratings from a curated library of over 1,200 apps that cover both physical and mental health. An objective metric is derived to assess the strength of the user-expert gap for each app, which in turn allows identifying missed opportunities—low user ratings and high expert ratings—and overrated apps—high user ratings and low expert ratings. Implications for practice and care delivery are discussed.
Exercise Therapy for People With Sarcopenic Obesity: Myokines and Adipokines as Effective Actors
Authors: Alizadeh Pahlavani Hamed
Published: February 2022

Sarcopenic obesity is defined as a multifactorial disease in aging with decreased body muscle, decreased muscle strength, decreased independence, increased fat mass, due to decreased physical activity, changes in adipokines and myokines, and decreased satellite cells. People with sarcopenic obesity cause harmful changes in myokines and adipokines. These changes are due to a decrease interleukin-10 (IL-10), interleukin-15 (IL-15), insulin-like growth factor hormone (IGF-1), irisin, leukemia inhibitory factor (LIF), fibroblast growth factor-21 (FGF-21), adiponectin, and apelin. While factors such as myostatin, leptin, interleukin-6 (IL-6), interleukin-8 (IL-8), and resistin increase. The consequences of these changes are an increase in inflammatory factors, increased degradation of muscle proteins, increased fat mass, and decreased muscle tissue, which exacerbates sarcopenia obesity. In contrast, exercise, especially strength training, reverses this process, which includes increasing muscle protein synthesis, increasing myogenesis, increasing mitochondrial biogenesis, increasing brown fat, reducing white fat, reducing inflammatory factors, and reducing muscle atrophy. Since some people with chronic diseases are not able to do high-intensity strength training, exercises with blood flow restriction (BFR) are newly recommended. Numerous studies have shown that low-intensity BFR training produces the same increase in hypertrophy and muscle strength such as high-intensity strength training. Therefore, it seems that exercise interventions with BFR can be an effective way to prevent the exacerbation of sarcopenia obesity. However, due to limited studies on adipokines and exercises with BFR in people with sarcopenic obesity, more research is needed.
Low-Carbon Economic Dispatch for Integrated Energy System Through the Dynamic Reward and Penalty Carbon Emission Pricing Mechanism
Authors: Wu Yingjun , Shi Zhanyu , Lin Zhiwei , Zhao Xiang , Xue Tao , Shao Junjie
Published: February 2022

The integrated energy system (IES) plays a key role in energy conservation and emission reduction. In order to realize the low-carbon economic dispatch of the IES, current studies usually utilize the fixed and the ladder-type pricing mechanism-based carbon emission unit cost (CEUC) in the optimal dispatch model. However, those mechanisms fail to take carbon emissions levels of the system into account, and the relevant parameters, such as the interval length, are hard to set. In order to tackle this challenge, a CEUC model with a dynamic reward and penalty pricing mechanism (DRPPM) is constructed. And then an optimal dispatch model to minimize the comprehensive operation cost, including the carbon emission cost, the energy purchasing cost, and the equipment operation cost, is proposed. At last, an actual electricity–heat–cooling–gas IES is employed to analyze the impact of parameters of the CEUC model on the dispatch.
Experimental and Numerical Study on the Combustion Characteristics of a Laminar Non-Premixed Methane Jet Flame in Oxygen/Carbon Dioxide Coflow
Authors: Zhang Fan , Li Xing , Xie Shengrong , Wang Junxiong , Wang Xiaohan
Published: February 2022

The combustion characteristics of laminar non-premixed CH4 jet flame in an O2/CO2 coflows with different oxygen mole fractions were studied experimentally. The flame heights at different oxygen concentrations and fuel jet velocity were obtained. The experimental observation shows that the luminosity of the CH4 jet flame in O2/CO2 coflow is different from that of the flame in air stream. A two-dimensional numerical study of a laminar non-premixed CH4 jet flame in the O2/CO2 coflow with the O2 mole fraction of 0.35 was conducted to analyze the effects of CO2 dilution on the flame. The distribution of OH radicals in the flame was measured experimentally using planar laser-induced fluorescence (PLIF) to validate the computational method adopted in this work, and the computational and experimental results of the OH distributions showed good consistency at various fuel flow velocities. Three artificial species were created in the numerical experiment to analyze the effects of the chemical reactions, third-body collisions, and transport properties of CO2 on the height, width, and temperature distribution of the flame. The results showed that CO2 participation in chemical reactions exerts significant effects on the flame. However, the influences of the third-body effects and transport properties of CO2 on the jet flame are unremarkable. The global reaction pathways and distributions of important species in the laminar non-premixed CH4 jet flame were analyzed in detail to investigate the influence mechanisms of CO2 on the flame height and temperature. The entire flame can be divided into two oxidation parts, which separated by the boundary of the HCCO. The H, O, and OH concentrations and distributions in different parts of the flame were influenced by CO2 dilution, resulting in different flame heights and temperature distributions.
Environmental Regulation and Employment in Resource-Based Cities in China: The Threshold Effect of Industrial Structure Transformation
Authors: Qin Bingtao , Liu Lei , Yang Le , Ge Liming
Published: February 2022

Resource-based cities in China face the dual pressure of environmental pollution and unemployment. Therefore, it is necessary to measure the effect of environmental regulation on employment. In this study, we first analyzed the theoretical mechanism of employment effects of environmental regulation. Second, we constructed a nonlinear panel threshold regression model with industrial structure rationalization and optimization as the threshold variables and used data from 115 resource-based prefecture-level cities to empirically examine the impact of environmental regulation on employment. The results demonstrate that 1) There is a significant threshold effect between environmental regulation and employment in resource-based cities, with the rationalization and optimization of the industrial structure gradually crossing the threshold from a low threshold to a high threshold, and the impact of environmental regulation on employment has gradually changed from an inhibitory effect to a promotion effect; 2) This conclusion still holds after the robustness test and the division of life cycles of different types of resource-based cities; 3) The coal resource cities as a representative of this kind of resource-based cities with serious environmental pollution, strengthening environmental regulation, have an obvious role in promoting employment. This study enriches the research content of environmental regulation on employment and provides useful references for rational improvement of unemployment in China.
Antibiotic Resistance, Biofilm Formation and Detection of mexA/mexB Efflux-Pump Genes Among Clinical Isolates of Pseudomonas aeruginosa in a Tertiary Care Hospital, Nepal
Authors: Bhandari Sirjana , Adhikari Sanjib , Karki Deepa , Chand Arun Bahadur , Sapkota Sanjeep , Dhungel Binod , Banjara Megha Raj , Joshi Prakash , Lekhak Binod , Rijal Komal Raj
Published: February 2022

Efflux-pump system and biofilm formation are two important mechanisms Pseudomonas aeruginosa deploys to escape the effects of antibiotics. The current study was undertaken from September 2019 to March 2020 at a tertiary-care hospital in Kathmandu in order to ascertain the burden of P. aeruginosa in clinical specimens, examine their biofilm-forming ability and determine their antibiotic susceptibility pattern along with the possession of two efflux-pump genes-mexA and mexB. Altogether 2820 clinical specimens were collected aseptically from the patients attending the hospital and processed according to standard microbiological procedures. Identification of P. aeruginosa was done by Gram stain microscopy and an array of biochemical tests. All the P. aeruginosa isolates were subjected to in vitro antibiotic susceptibility testing and their biofilm-forming ability was also examined. Presence of mexA and mexB efflux-pump genes was analyzed by Polymerase Chain Reaction (PCR) using specific primers. Out of 603 culture positive isolates, 31 (5.14%) were found to be P. aeruginosa, of which 55% were multi-drug resistant (MDR). Out of 13 commonly used antibiotics tested by Kirby-Bauer disc diffusion method, greatest resistance was shown against piperacillin-tazobactam 15 (48.4%) and ceftazidime 15 (48.4%), and least against meropenem 6 (19.4%) and ofloxacin 5 (16.2%). Of all 17 MDR isolates subjected to biofilm detection, strong biofilm formation was exhibited by 11 (65%) and 14 (82%) isolates with microtiter plate method and tube method respectively. Out of 17 isolates tested, 12 (70.6%) isolates possessed mexA and mexB genes indicating the presence of active efflux-pump system. Higher number of the isolates recovered from sputum 7 (58.3%) and pus 5 (41.7%) possessed mexA/mexB genes while the genes were not detected at all in the isolates recovered from the urine (p<0.05). This study assessed no significant association between biofilm production and multi-drug resistance (p>0.05). Adoption of stern measures by the concerned authorities to curb the incidence of multi-drug resistant and biofilm-forming isolates is recommended to prevent their dissemination in the hospital settings.
River Plume Rooted on the Sea-Floor: Seasonal and Spring-Neap Variability of the Pearl River Plume Front
Authors: Zhi Haihang , Wu Hui , Wu Jiaxue , Zhang Wenxia , Wang Yihe
Published: February 2022

The buoyant river plume front exhibits substantial variability in the sea surface under energetic external forcing. Although highly dynamic, the river plume is often “rooted” at specific locations through the bottom river plume front. In this study, we addressed this mechanism using the Pearl River plume as an example based on a well-validated numerical model. With this model, we described the spatiotemporal characteristics of the Pearl River salinity front. It was found that, although the surface Pearl River plume features bimodal extension in summer and winter seasons, owing to the reversal of the seasonal monsoon wind, there is a relatively stable bottom front extending from the river mouth to the downstream region (i.e., in the direction of propagation of Kelvin Wave). The occurrence probability of the bottom front showed that the front location varies only slightly and fixes at ∼8-m isobath. The Empirical Orthogonal Function (EOF) analysis demonstrated that runoff, wind, and tide are major regulating factors. These three factors jointly control the strength and position of the bottom front. In particular, the bottom front moves offshore during the spring tide but onshore during the neap tide, respectively, indicating a different mechanism from the classic frontal trapping theory. The sensitivity experiment without tide indicated that the bottom plume front shrinks significantly, and the river plume becomes more dynamic since it is no longer rooted on the seafloor.
Comparative Transcriptome Reveals the Molecular Regulation Mechanism of Charybdis japonica to High- and Low-Temperature Stresses
Authors: Lou Fangrui , Wang Yuju , Han Zhiqiang , Shui Bonian
Published: February 2022

Intertidal organisms are more sensitive to temperature stresses (whether high or low temperatures). As an intertidal crustacean, the optimal survival temperature ranges of Charybdis japonica are from 20 to 27°C. In this study, C. japonica was selected as the research species to better explore the molecular regulatory mechanisms of intertidal crustaceans to temperature stresses. The transcriptomes of C. japonica exposed to three temperature gradients (12, 20, and 28°C) were sequenced. A total of 69.22 Gb clean transcriptome reads were obtained from nine libraries and then de novo assembled to 52,972 unigenes with a mean length of 1080.23 bp and an N50 length of 1,775 bp. A total of 20,121 unigenes were successfully matched with at least one protein database. The transcriptome structure was predicted, and 12,125 coding sequences and 12,854 simple sequence repeats (SSRs) were obtained. The gene expression level of C. japonica at 20°C was used as control, and 548 and 90 unigenes were significantly differentially expressed at 28 and 12°C, respectively. A total of 720 unigenes were significantly differentially expressed at 28°C compared with 12°C. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation showed that genes related to cell structure, metabolism, and protein folding and hormone synthesis might be involved in the regulation of temperature stress in C. japonica. Our results reveal for the first time the response of C. japonicas to low- and high- temperature stresses at the transcriptome level. The results provide fundamental information for revealing the temperature regulation mechanisms of C. japonica and other intertidal crustaceans. Furthermore, the present study enhances our understanding of how temperature fluctuations will affect the survival of marine crustaceans.
Antimicrobial Activity of Remineralizing Ion-Doped Amorphous Calcium Phosphates for Preventive Dentistry
Authors: Degli Esposti Lorenzo , Ionescu Andrei C. , Carella Francesca , Adamiano Alessio , Brambilla Eugenio , Iafisco Michele
Published: February 2022

We have synthesized citrate-stabilized amorphous calcium phosphates doped with fluoride (F-ACP), strontium (Sr-ACP), and zinc (Zn-ACP) ions. ACP based materials were proven to have excellent remineralizing action on demineralized dental hard tissues while F−, Sr2+, and Zn2+ ions are known to have antimicrobial activity, so the aim of our work was to produce multipurpose materials for preventive dentistry that inhibit cariogenic bacteria and remineralize dental enamel and dentin. Doping ions were successfully incorporated into ACP up to 2 wt.% F− and 12 wt.% Sr2+ or Zn2+ without altering ACP physical-chemical properties. Evaluation of viability of Streptococcus Mutans biofilm treated with ion-doped ACP materials showed that F-ACP and Sr-ACP have a direct inhibitory effect while Zn-ACP has a negligible effect. The different antibacterial activity was correlated to the ion-release properties of the materials, as in conditions mimicking a cariogenic environment F-ACP and Sr-ACP have a release of ca. 5–7% of total F− or Sr2+ while only ca. 1% of total Zn2+ is released. All ion-doped ACP materials are able to remineralize in vitro demineralized human enamel slabs by epitaxial deposition of a new ion-doped crystalline phase in direct contact with the pristine one. Enamel slabs remineralized with F-ACP has an antibacterial/bacteriostatic action, proving that F-ACP acts as preventive antimicrobial agent. Overall, our work demonstrates the high potential of ACP doped with antibacterial ions for the preventive treatment of dental caries.
Reintubation Summation Calculation: A Predictive Score for Extubation Failure in Critically Ill Patients
Authors: Bansal Vikas , Smischney Nathan J. , Kashyap Rahul , Li Zhuo , Marquez Alberto , Diedrich Daniel A. , Siegel Jason L. , Sen Ayan , Tomlinson Amanda D. , Venegas-Borsellino Carla P. , Freeman William David
Published: February 2022

Objective

To derive and validate a multivariate risk score for the prediction of respiratory failure after extubation.

Patients and methods

We performed a retrospective cohort study of adult patients admitted to the intensive care unit from January 1, 2006, to December 31, 2015, who received mechanical ventilation for ≥48 h. Extubation failure was defined as the need for reintubation within 72 h after extubation. Multivariate logistic regression model coefficient estimates generated the Re-Intubation Summation Calculation (RISC) score.

Results

The 6,161 included patients were randomly divided into 2 sets: derivation (n = 3,080) and validation (n = 3,081). Predictors of extubation failure in the derivation set included body mass index <18.5 kg/m2 [odds ratio (OR), 1.91; 95% CI, 1.12–3.26; P = 0.02], threshold of Glasgow Coma Scale of at least 10 (OR, 1.68; 95% CI, 1.31–2.16; P < 0.001), mean airway pressure at 1 min of spontaneous breathing trial <10 cmH2O (OR, 2.11; 95% CI, 1.68–2.66; P < 0.001), fluid balance ≥1,500 mL 24 h preceding extubation (OR, 2.36; 95% CI, 1.87–2.96; P < 0.001), and total mechanical ventilation days ≥5 (OR, 3.94; 95% CI 3.04–5.11; P < 0.001). The C-index for the derivation and validation sets were 0.72 (95% CI, 0.70–0.75) and 0.72 (95% CI, 0.69–0.75). Multivariate logistic regression demonstrated that an increase of 1 in RISC score increased odds of extubation failure 1.6-fold (OR, 1.58; 95% CI, 1.47–1.69; P < 0.001).

Conclusion

RISC predicts extubation failure in mechanically ventilated patients in the intensive care unit using several clinically relevant variables available in the electronic medical record but requires a larger validation cohort before widespread clinical implementation.
Single Dose Gonadotropin-Releasing Hormone Agonist Luteal Support in Fresh Embryo Transfer: Variation in Timing, Type, and Dosage
Authors: Abu Muhammad Azrai , Alexander Jojinah Vindah , Abdul Karim Abdul Kadir , Ahmad Mohd Faizal , Omar Mohd Hashim
Published: February 2022

Objectives

To evaluate the effects of the addition of single-dose GnRH agonist to the routine progestogens use for luteal phase support on IVF outcome as compared to progestogens only.

Methods

This is a retrospective case-control study on selected patients who underwent IVF treatment with fresh embryo transfer (ET) under Medically Assisted Conception Unit, University Kebangsaan Malaysia Medical Center for the period of June 2015–June 2018. A higher dose of 0.2 mg subcutaneous Decapeptyl was administered 2 days before fresh ET concurrent with routine progestogen support. Patients with different luteal phase regimes, frozen embryo transfer and medical records with missing data were excluded. Their medical records were reviewed, and data analyzed. The pregnancy outcomes measured included biochemical pregnancy rates, clinical pregnancy rates, live birth rates and miscarriage rates.

Results

A total of 786 patients were analyzed. Four hundred forty-four patients were given luteal phase support with progestogens and GnRH agonist, whereas 342 patients served as control were given progestogens only. The study group showed higher biochemical pregnancy rate (47.7 vs. 44.4%,), clinical pregnancy rate (25.7 vs. 23.4%) and livebirth rate (24.3 vs. 22.2%), respectively but not statistically significant. The rate of miscarriage among the study group was lower (4.5% vs 9.4%) compared to the progestogen group alone. Nonetheless, the OHSS rate was slightly increased in the study group (4.5 vs. 3.5%) despite using a mild stimulation protocol.

Conclusions

New regime of GnRH agonist luteal support in addition to the standard progestogen support was found to be beneficial in overall IVF outcome.
Multi-Biofunctional Properties of Phytofabricated Selenium Nanoparticles From Carica papaya Fruit Extract: Antioxidant, Antimicrobial, Antimycotoxin, Anticancer, and Biocompatibility
Authors: Vundela Swetha Reddy , Kalagatur Naveen Kumar , Nagaraj Anusuya , Kadirvelu Krishna , Chandranayaka Siddaiah , Kondapalli Kasturi , Hashem Abeer , Abd_Allah Elsayed Fathi , Poda Sudhakar
Published: February 2022

The present study focused on phytofabrication of selenium nanoparticles (SeNPs) from Carica papaya extract and exploration of their multi-biofunctional features. Total phenolics and flavonoids of C. papaya fruit extract were determined as 23.30 ± 1.88 mg gallic acid equivalents and 19.21 ± 0.44 mg quercetin equivalents per gram, respectively, which suggested that C. papaya fruit extract could be a competitive reducing and stabilizing agent during phytofabrication of nanoparticles. UV–Vis and FTIR spectroscopy showed the formation of SeNPs from sodium selenite, which could be related to the reducing and stabilizing activities of C. papaya fruit extract. The SeNPs were found to be stable with a Zeta potential of −32 mV. The average hydrodynamic size of SeNPs was found as 159 nm by dynamic light scattering. The SeNPs showed a broader XRD pattern with no sharp Bragg’s peaks and found to be amorphous. SEM showed that SeNPs were spherical in shape and EDX pattern showed that SeNPs were made up of Se (71.81%), C (11.41%), and O (14.88%). The HR-TEM picture showed that SeNPs were spherical in morphology and have a size range of 101–137 nm. The SeNPs exhibited potent antioxidant activity and their EC50 values (effective concentration required to inhibit 50% of radicals) were 45.65 ± 2.01 and 43.06 ± 3.80 μg/ml in DPPH and ABTS assays, respectively. The antimicrobial action of SeNPs was found as a broad spectrum and suppressed microbial pathogens in ascending order: fungi > Gram-positive bacteria > Gram-negative bacteria. The SeNPs have been demonstrated to reduce the growth and ochratoxin A (OTA) of mycotoxigenic Aspergillus ochraceus and Penicillium verrucosum at 40 μg/ml in broth culture, which is noteworthy. The SeNPs reduced cancer cell proliferation (RAW 264.7, Caco-2, MCF-7, and IMR-32) more preferentially than normal cells (Vero), found to be highly biocompatible. Lower doses of SeNPs (up to 50 μg/ml) were shown to be less toxic and did not cause death in Danio rerio (zebrafish) embryos, implying that lower doses of SeNPs could be beneficial for biological purposes. The present study concluded that phytofabricated SeNPs have multiple biofunctional properties, including antioxidant, antimicrobial, antimycotoxin, and anticancer activities, as well as high biocompatibility.