bluuebunny/crossref_metadata_2025 huggingface dataset:
Importancia del COVID-19 en la atención estomatológica
Authors: Funes-Rumiche Italo
Published: February 2022

La pandemia por COVID-19 representa un reto para los servicios de salud y ha producido un colapso de estos en muchas partes del mundo y el cirujano dentista no ha estado al margen de esta situación y ha jugado un rol importante, produciéndose una serie de cambios y reforzando otros, como las medidas de bioseguridad, para una atención estomatológica segura.  En la siguiente revisión de la literatura, se muestra la preponderancia que tiene la cavidad bucal en la enfermedad del COVID-19 tanto en la infectividad y severidad en la presentación de los síntomas. así mismo se discute el riesgo de la labor que cumple el cirujano dentista y cómo nuestra profesión puede ayudar a mitigar los contagios a través de la disminución de la carga viral con el uso de determinados productos tienen una sólida base científica con investigaciones realizadas para demostrar esta acción.
Feasibility Study of Biogas Production and Applications using Rural Biomass in Northern Queensland, Australia.
Authors: Ansari Ammar Arif , Khalid Ahmed , Correia Cavin Hansel , Dheen Manush , Talal Ribal , Elshamy Yousef , Doucet Florian
Published: February 2022

Cape York, in Northern Queensland, Australia, is a remote area with a limited supply of energy, making it very hard for the locals to have an easier life. Locals use diesel as a fuel for transportation which is economically harmful to the environment due to the carbon emissions. The research team found a solution for these problems and decided to design a biogas plant, which will be environmentally friendly, cost-effective, and will produce job opportunities for the locals. The plant aims to produce biogas from the raw manure of the cattle from the farms in Cairns, a nearby neighborhood. The long-term plan of the plant is to be sustainable and profitable. The business plan predicts the break-even point of the business as 4 months and the payback period as less than a year.
CRISPR/Cas12a-Enhanced Loop-Mediated Isothermal Amplification for the Visual Detection of Shigella flexneri
Authors: Shi Yaoqiang , Kang Lan , Mu Rongrong , Xu Min , Duan Xiaoqiong , Li Yujia , Yang Chunhui , Ding Jia-Wei , Wang Qinghua , Li Shilin
Published: February 2022

Shigella flexneri is a serious threat to global public health, and a rapid detection method is urgently needed. The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) system is widely used in gene editing, gene therapy, and in vitro diagnosis. Here, we combined loop-mediated isothermal amplification (LAMP) and CRISPR/Cas12a to develop a novel diagnostic test (CRISPR/Cas12a-E-LAMP) for the diagnosis of S. flexneri. The CRISPR/Cas12a-E-LAMP protocol conducts LAMP reaction for S. flexneri templates followed by CRISPR/Cas12a detection of predefined target sequences. LAMP primers and sgRNAs were designed to the highly conserved gene hypothetical protein (accession: AE014073, region: 4170556–4171,068) of S. flexneri. After the LAMP reaction at 60°C for 20 min, the pre-loaded CRISPR/Cas12a regents were mixed with the LAMP products in one tube at 37°C for 20 min, and the final results can be viewed by naked eyes with a total time of 40 min. The sensitivity of CRISPR/Cas12a-E-LAMP to detect S. flexneri was 4 × 100 copies/μl plasmids and without cross-reaction with other six closely related non-S. flexneri. Therefore, the CRISPR/Cas12a-E-LAMP assay is a useful method for the reliable and quick diagnosis of S. flexneri and may be applied in other pathogen infection detection.
BCL2A1 and CCL18 Are Predictive Biomarkers of Cisplatin Chemotherapy and Immunotherapy in Colon Cancer Patients
Authors: Yue Taohua , Liu Xiangzheng , Zuo Shuai , Zhu Jing , Li Jichang , Liu Yucun , Chen Shanwen , Wang Pengyuan
Published: February 2022

Background: Cisplatin enhances the antitumor T cell response, and the combination of PD-L1 blockade produces a synergistic therapeutic effect. However, the clinical correlation between cisplatin and immunotherapy in colon cancer (CC) is unknown.

Methods: Using the “pRRophetic” package, we calculated the IC50 of cisplatin. The correlation between cisplatin IC50, cisplatin resistance–related genes (CCL18 and BCL2A1), and immunotherapy were preliminarily verified in TCGA and further validated in independent cohorts (GSE39582 and GSE17538), cisplatin-resistant CC cell line DLD1, and our own clinical specimens. Classification performance was evaluated using the AUC value of the ROC curve. Scores of immune signatures, autophagy, ferroptosis, and stemness were quantified using the ssGSEA algorithm.

Results: Based on respective medians of three CC cohorts, patients were divided into high- and low-IC50 groups. Compared with the high IC50 group, the low-IC50 group had significantly higher tumor microenvironment (TME) scores and lower tumor purity. Most co-signaling molecules were upregulated in low IC50 group. CC patients with good immunotherapy efficacy (MSI, dMMR, and more TMB) were more attributable to the low-IC50 group. Among seven shared differentially expressed cisplatin resistance–related genes, CCL18 and BCL2A1 had the best predictive efficacy of the above immunotherapy biomarkers. For wet experimental verification, compared with cisplatin-resistant DLD1, similar to PD-L1, CCL18 and BCL2A1 were significantly upregulated in wild-type DLD1. In our own CC tissues, the mRNA expression of CCL18, BCL2A1, and PD-L1 in dMMR were significantly increased. The high group of CCL18 or BCL2A1 had a higher proportion of MSI, dMMR, and more TMB. IC50, CCL18, BCL2A1, and PD-L1 were closely related to scores of immune-related pathways, immune signatures, autophagy, ferroptosis, and stemness. The microRNA shared by BCL2A1 and PD-L1, hsa-miR-137, were significantly associated with CCL18, BCL2A1, and PD-L1, and downregulated in low-IC50 group. The activity of the TOLL-like receptor signaling pathway affected the sensitivity of CC patients to cisplatin and immunotherapy. For subtype analysis, immune C2, immune C6, HM-indel, HM-SNV, C18, and C20 were equally sensitive to cisplatin chemotherapy and immunotherapy.

Conclusions: CC patients sensitive to cisplatin chemotherapy were also sensitive to immunotherapy. CCL18 and BCL2A1 were novel biomarkers for cisplatin and immunotherapy.
Comparison of the Performance of Phenotypic Methods for the Detection of Carbapenem-Resistant Enterobacteriaceae (CRE) in Clinical Practice
Authors: Zhang Zhijie , Wang Dayan , Li Yahui , Liu Yong , Qin Xiaosong
Published: February 2022

In order to investigate the diagnostic performance characteristics of four phenotypic assays in detecting carbapenem-resistant Enterobacteriaceae (CRE), we collected the CRE strains from infected patients. The results of carbapenemase gene detection, blaKPC-2, blaOXA-23, blaNDM-1, blaNDM-4, blaNDM-5, blaIMP-4, and blaIMP-8, were used as a standard to evaluate the performances of combined disk test (CDT), modified carbapenem inactivation method(mCIM)/EDTA-modified carbapenem inactivation method(eCIM), NG-Test CARBA 5 (CARBA), and color developing immunoassay (CDI). The compliance of phenotype results based on CDT, mCIM/eCIM, CARBA, and CDI with genetic detection results was 94% (231/247), 95% (235/247), 98% (242/247), and 99% (246/247), respectively. CDT demonstrated a low specificity for carbapenemase detection, low negative predictive value (NPV), and low sensitivity for metallo-β-lactamase (79%, 55%, and 88%, respectively); it also failed to accurately detect IMP. The mCIM/eCIM assay had serious problems in detecting OXA-23-like carbapenemases. The sensitivity and specificity of CARBA and CDI were higher than those of the first two methods. However, CARBA did not cover the detection of OXA-23, while CDI cannot detect IMP-8, resulting in low NPVs (70% and 88%, respectively). In conclusion, CARBA and CDI assays are highly accurate except individual rare genes and allow direct genotype detections. CDT and mCIM/eCIM assays are moderately accurate and can only distinguish serine-β-lactamases from metallo-β-lactamases. Laboratories should choose the appropriate method that meets their needs based on its characteristic.
Mercury Isotopes in Shale Gas From Wufeng-Longmaxi Shale Formation of Sichuan Basin, Southern China: A Preliminary Investigation
Authors: Tang Shunlin , Ding Yuxiang , Zhu Guangyou , Feng Xinbin , Zhang Huaishun , Li Penggao
Published: February 2022

A series of investigations have been conducted concerning the study of traditional stable isotopes and rare gas stable isotopes in natural gas. However, little is known regarding non-traditional stable isotopes of mercury in natural gas, especially in the development and utilization of shale gas in recent years. In fact, the presence of mercury in natural gas (including shale gas) provides a basis for research on mercury isotopes. Mercury was extracted from shale gas at the Wufeng-Longmaxi Formation in the YS108 block of the Zhaotong National shale gas demonstration area in the Sichuan Basin by using an acid potassium permanganate solution, followed by the analysis of mercury content and stable isotope composition. The mercury content in the marine shale gas at the Wufeng-Longmaxi Formation ranged from 171 to 2,906 ng/m3, with an average of 1,551.08 ± 787.08 ng/m3 (n = 37, 1 SD). The Δ199Hg values of mercury stable isotopes range from 02‰ to 0.39‰, with an average of 22‰ ± 0.08‰ (n = 37, 1 SD); the δ202Hg values range from −1.68‰ to −0.04‰, with an average of −0.87‰ ± 0.31‰ (n = 37, 1 SD), which are significantly different from the Δ199Hg and δ202Hg information of coalbed gas, but similar to the Δ199Hg and δ202Hg information of terrestrial oil-type gas and the Δ199Hg in the main hydrocarbon-forming organic matter of lower organisms such as algae (t-test, p > 0.05). This indicates that terrestrial target strata with abundant algae or strata with positive Δ199Hg are the target strata for the exploration of terrestrial oil and gas.
Tree Stories: Assessment Making as Relationally Respecting, Dynamically Listening with Care, and Inviting Celebratory Journeying
Authors: Brown Donna L.
Published: February 2022

Through my recent Master of Education journey, I am becoming increasingly awake to the ways in which I value “place” when thinking of my autobiographical beginnings, teaching, learning, and assessment making alongside children. As a forest and nature kindergarten teacher in a K–6 elementary school, who is facing increasing class sizes, classroom complexity, parental anxieties, and children’s wide-awakeness to all these influences, I worry about early childhood development and the knowing that each of us, from an early age, holds embodied experiences which guide us and either nurture or hinder our development. I see the importance of co-creating environments to invite children, parents, and educators to think collaboratively, and emergently to come to learning and knowing and assessment making. Basso (1996) writes, “relationships to places are lived most often in the company of other people, and it is on these communal occasions – when places are sensed together – that native views of the physical world become accessible to strangers” (p. 109). We teach and learn in social contexts across time and in the world of formal education on landscapes called schools. However, my hope is for schools to be thought of in a broader context, which bends and sways as we ground ourselves in experiential pedagogies (Dewey, 1938). Pedagogies which are always in the midst and in the making. Narrative beginnings matter. With this thinking, we become awake to knowing that our collective approaches to the education of young children will significantly affect future leaders and the environment which sustains us. My current research puzzling for the purpose of this special issue is as follows: in what ways can land-based, place-based, emergent, and playful experiential learning approaches in school outdoor settings increase child, family, and teacher collaboration? What role might assessment making have in this collaboration and the child’s learning? Do the stories that children come to live and tell through this collaboration and their dynamic interaction with one another, their families and teachers, and more-than-human beings influence the lives they are making in the present in their early years of schooling i.e., K–3, and into their futures?
The Role of Lactate Exercise Test and Fasting Plasma C-Peptide Levels in the Diagnosis of Mitochondrial Diabetes: Analysis of Clinical Characteristics of 12 Patients With Mitochondrial Diabetes in a Single Center With Long-Term Follow-Up
Authors: Zhao Yuan , Zhang Ying , Qi Mengya , Ping Fan , Zhang Huabing , Xu Lingling , Li Wei , Li Yuxiu
Published: February 2022

Objective

The aim of this study was to analyze the clinical characteristics and the pattern of long-term changes of fasting plasma C-peptide in patients with mitochondrial diabetes (MD), and to provide guidance for the diagnosis and treatment of MD.

Methods

We retrieved MD patients with long-term follow-up at Peking Union Medical College Hospital from January 2005 to July 2021 through the medical record retrieval system and retrospectively analyzed their clinical data, biochemical parameters, fasting plasma C-peptide, glycosylated hemoglobin and treatment regimens. Non-parametric receiver operating characteristic (ROC) curves were used to assess the relationship between exercise test-related plasma lactate levels and suffering from MD.

Results

A total of 12 MD patients were included, with clinical characteristics of early-onset, normal or low body weight, hearing loss, maternal inheritance, and negative islet-related autoantibodies. In addition, patients with MD exhibited significantly higher mean plasma lactate levels immediately after exercise compared to patients with type 1 diabetes mellitus (T1DM) (8.39 ± 2.75 vs. 3.53 ± 1.47 mmol/L, p=0.003) and delayed recovery time after exercise (6.02 ± 2.65 vs. 2.17 ± 1.27 mmol/L, p=0.011). The optimal cut-off points identified were 5.5 and 3.4 mmol/L for plasma lactate levels immediately after and 30 minutes after exercise, respectively. The fasting plasma C-peptide levels decreased as a negative exponential function with disease progression (Y= 1.343*e-0.07776X, R2 = 0.4154). Treatment regimens in MD patients were varied, with no metformin users and a weak correlation between insulin dosage and body weight.

Conclusions

The increased level of plasma lactate during exercise or its delayed recovery after exercise would contribute to the diagnosis of MD. Changes of fasting plasma C-peptide in MD patients over the course of the disease indicated a rapid decline in the early stages, followed by a gradual slowing rate of decline.
A Concurrent Fault Diagnosis Method of Transformer Based on Graph Convolutional Network and Knowledge Graph
Authors: Liu Liqing , Wang Bo , Ma Fuqi , Zheng Quan , Yao Liangzhong , Zhang Chi , Mohamed Mohamed A.
Published: February 2022

In complex power systems, when power equipment fails, multiple concurrent failures usually occur instead of a single failure. Concurrent failures are so common and hidden in complex systems that diagnosis requires not only analysis of failure characteristics, but also correlation between failures. Therefore, in this paper, a concurrent fault diagnosis method is proposed for power equipment based on graph neural networks and knowledge graphs. First, an electrical equipment failure knowledge map is created based on operational and maintenance records to emphasize the relevance of the failed equipment or component. Next, a lightweight graph neural network model is built to detect concurrent faults in the graph data. Finally, a city’s transformer concurrent fault is taken as an example for simulation and validation. Simulation results show that the accuracy and acquisition rate of graph neural network mining in Knowledge Graph is superior to traditional algorithms such as convolutional neural networks, which can achieve the effectiveness and robustness of concurrent fault mining.
The Effect of PPARγ rs1801282 Variant on Mortality Risk Among Asians With Chronic Kidney Disease: A Cohort Study and Meta-Analysis
Authors: Chen Wei-Teing , Chiu Chih-Chien , Tsai Dung-Jang , Ko Pi-Shao , Lee Meng-Chang , Lin Hsiao-Ting , Chen Ying-Kai , Su Wen , Lin Yuh-Feng , Su Sui-Lung
Published: February 2022

Background: Chronic kidney disease (CKD) is a public health issue, and an independent risk factor for cardiovascular disease. The peroxisome proliferator-activated receptor gamma (PPARG) plays an important role in the cardiovascular system. Previous studies have examined one important exon polymorphism, Pro12Ala, in PPARG with respect to mortality of CKD patients, but the results were inconsistent and current evidence is insufficient to support a strong conclusion. This study aimed to examine the correlation between Pro12Ala gene polymorphism and mortality among Asians with CKD by trial sequential analysis (TSA).

Methods: The research was divided into observational research and meta-analysis. For the cohort study, 767 subjects from dialysis centers in Taipei were selected as samples, and tracked from December 2015 to February 2017. For the meta-analysis, relevant literature from “PubMed” and “Embase” databases (until December 2016), was searched and TSA was used to verify the results. In order to achieve the best evidence hierarchies, our retrospective cohort study was added to the meta-analysis and the TSA.

Results: The combined sample size for Asian was 1,685 after adding our cohort study, and there was no significant correlation between PPARG Pro12Ala and mortality by the allele model (RR: 0.85, 95% CI: 0.39–1.83, I2 = 79.3%). Under the parameter setting with the RR value of 1.5, TSA estimation presented that the cumulative sample size entered into the futility area, and it confirmed the conclusion in this study.

Conclusion: We found that PPARG Pro12Ala gene polymorphism was not related to mortality in CKD Asians patients, and validated our conclusion using TSA after adding our sample.
Unmet Need for Contraception Among Female Sex Workers Initiating Oral Pre-Exposure Prophylaxis for HIV Prevention During Kenya's National Scale-Up: Results From a Programmatic Surveillance Study
Authors: Kamau Mercy , Musau Abednego , Were Daniel , Waruguru Gladys , Kabue Mark , Mutegi Jane , Plotkin Marya , Reed Jason
Published: February 2022

Background

Female sex workers (FSWs) experience a higher risk for both HIV acquisition and unwanted pregnancies compared to women in the general population. Pre-exposure prophylaxis (PrEP) for HIV prevention offers protection against HIV infection but has no contraceptive effect. We examined the determinants of unmet need for contraception among FSWs who initiated PrEP to inform programs and policies to optimize contraceptive services and avert unwanted pregnancy among this high-risk group.

Materials and Methods

A cross-sectional analysis was conducted on routine, de-identified client data from a large-scale PrEP service delivery project, from February 2017 to December 2019. Data were collected from FSWs during clinic visits using Ministry of Health approved tools. Records for all 17,456 FSWs initiated on PrEP from 79 health facilities in 10 counties across three geographic clusters with high and medium HIV incidence were examined for eligibility for the analysis. Unmet need for non-barrier contraception was defined as not being pregnant, not currently using the non-barrier contraceptive method, and not trying to conceive or intending to have a child in the near future. Univariate and multivariable regression analyses were conducted with selected variables to examine associations.

Results

In the 79 sites, eligible records from 17,063 FSWs who initiated PrEP were included. Two-thirds were under 30 years, and the majority were not married and had received PrEP at drop-in centers. Overall, the unmet need for non-barrier contraception was 52.6%, higher for those under 20 years of age (60.9%) and those served in public and private health facilities (67.4 and 83.2%, respectively) rather than drop-in centers (50.6%). Women from the Nairobi and Coast cluster regions reported a higher unmet need for contraception compared to those from the Lake region. All these associations were significant (p < 0.05) at the multivariate level.

Conclusions

The high unmet need for non-barrier contraception among FSWs initiating PrEP highlights the need for integrated delivery of contraception services within PrEP programs. Identifying groups with a high unmet need could lead to higher success in an integrated program. Two recommended approaches include training healthcare providers to deliver clear contraception messaging during PrEP initiation and making a range of contraceptives accessible within PrEP services for high-risk groups. Furthermore, accelerated research on multipurpose prevention technologies is necessary to reduce the burden on individuals using multiple prevention products concurrently.
Microstructure and Mechanical Properties of Li2Si2O5 Whisker-Reinforced Glass-Ceramics
Authors: Yan Jingyu , Liu Xiaoming , Wu Xiuping , Wu Xiao , Zhang Yanjie , Li Bing
Published: February 2022

Lithium disilicate (Li2Si2O5) glass-ceramics are an ideal material for dental restoration; however, their intrinsic brittleness and low defect tolerance limit the scope of their clinical applications. In this study, Li2Si2O5 whiskers were creatively synthesized via a mild-condition hydrothermal reaction. Self-reinforced Li2Si2O5 glass-ceramics were sintered by introducing the Li2Si2O5 whiskers, and their effects on phase, microstructure, and mechanical properties were systematically studied. The crystal-growth and toughening mechanisms were also discussed. The results showed that the Li2Si2O5 whiskers played an important role in inducing crystallization, and improving the microstructure and properties of the glass-ceramics. With increasing amounts of Li2Si2O5 whiskers, the crystallinities increased slightly, and the average crystal size also increased. The microstructure was composed of crystals of bimodal size distributions, in which some large, rod-like Li2Si2O5 crystals epitaxially grew along with the whiskers, and small crystals directly crystallized from the parent glass-ceramic powders. The Li2Si2O5 glass-ceramics exhibited high flexural strength (389.5 ± 11.77 MPa, LDW3), and fracture toughness (3.46 ± 0.10 MPa·m1/2, LDW5). The improved properties were attributed mainly to crack deflection and bridge-toughening mechanisms.
Identification of the Signature Genes and Network of Reactive Oxygen Species Related Genes and DNA Repair Genes in Lung Adenocarcinoma
Authors: Zhao Ye , Feng Hai-Ming , Yan Wei-Jian , Qin Yu
Published: February 2022

Reactive Oxygen Species (ROS) are present in excess amounts in patients with tumors, and these ROS can kill and destroy tumor cells. Therefore, tumor cells upregulate ROS-related genes to protect them and reduce their destructing effects. Cancer cells already damaged by ROS can be repaired by expressing DNA repair genes consequently promoting their proliferation. The present study aimed to identify the signature genes of and regulating network of ROS-related genes and DNA repair genes in lung adenocarcinoma (LUAD) using transcriptomic data of public databases. The LUAD transcriptome data in the TCGA database and gene expressions from Gene Expression Omnibus (GEO) were analyzed and samples were clustered into 5 ROS-related categories and 6 DNA repair categories. Survival analysis revealed a significant difference in patient survival between the two classification methods. In addition, the samples corresponding to the two categories overlap, thus, the gene expression profile of the same sample with different categories and survival prognosis was further explored, and the connection between ROS-related and DNA repair genes was investigated. The interactive sample recombination classification was used, revealing that the patient's prognosis was worse when the ROS-related and DNA repair genes were expressed at the same time. The further research on the potential regulatory network of the two categories of genes and the correlation analysis revealed that ROS-related genes and DNA repair genes have a mutual regulatory relationship. The ROS-related genes namely NQO1, TXNRD1, and PRDX4 could establish links with other DNA repair genes through the DNA repair gene NEIL3, thereby balancing the level of ROS. Therefore, targeting ROS-related genes and DNA repair genes might be a promising strategy in the treatment of LUAD. Finally, a survival prognostic model of ROS-related genes and DNA repair genes was established (TERT, PRKDC, PTTG1, SMUG1, TXNRD1, CAT, H2AFX, and PFKP). The risk score obtained from our survival prognostic model could be used as an independent prognostic factor in LUAD patients.
Malnutrition and Risk of Mortality in Ischemic Stroke Patients Treated With Intravenous Thrombolysis
Authors: Tang Haiyan , Gong Fan , Guo Hongquan , Dai Zheng , Wang Jun , Liu Bin , Li Tingting , Tang Xianbiao , Dong Junru , Pan Song , Wang Mingzhe , Sun Yan , Qin Baofeng , Zhang Jingsi , Zhu Xuyin , Tian Jun , Fei Zhimin , Lu Gendi , Liu Dezhi
Published: February 2022

Background and Purpose

Malnutrition is highly prevalent in ischemic stroke patients. We aimed to investigate whether malnutrition indexes may be useful in predicting mortality at 90 days in ischemic stroke patients treated with intravenous thrombolysis.

Methods

We retrospectively analyzed consecutive patients who underwent thrombolytic therapy at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI).

Results

Of 979 patients (mean age, 66.8 years; males, 63.6%) included in this study, 91 (9.3%; 95% confidence interval [CI]: 8.4–10.2%) died at 3-month follow up. According to the CONUT, GNRI, and PNI scores, 9.9, 33.7, and 7.0% of patients were moderately or severely malnourished, respectively; 64.0% were at least mildly malnourished by at least 1 malnutrition index. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of mortality for CONUT scores (adjusted odds ratio [OR] 16.16, 95%CI, 7.86-67.11; P < 0.001), GNRI scores (adjusted OR 9.82, 4.10-23.51; P < 0.001) and PNI scores (adjusted OR 12.74, 5.56-29.19; P < 0.001). Similar results were found when the malnutrition scores were analyzed as continuous variables. Adding the three malnutrition indexes to models containing conventional risk factors significantly improved risk reclassification for 3-month mortality.

Conclusion

Our study showed that malnutrition may be associated with a higher risk of mortality at 3 months in ischemic stroke after intravenous thrombolysis.
Glucagon-Like Peptide 1 Receptor Agonists – Potential Game Changers in the Treatment of Glaucoma?
Authors: Mouhammad Zaynab Ahmad , Vohra Rupali , Horwitz Anna , Thein Anna-Sophie , Rovelt Jens , Cvenkel Barbara , Williams Pete A. , Azuara-Blanco Augusto , Kolko Miriam
Published: February 2022

Glaucoma is a common ocular neurodegenerative disease characterized by the progressive loss of retinal ganglion cells and their axons. It is the most common cause of irreversible blindness. With an increasing number of glaucoma patients and disease progression despite treatment, it is paramount to develop new and effective therapeutics. Emerging new candidates are the receptor agonists of the incretin hormone glucagon-like-peptide-1 (GLP-1), originally used for the treatment of diabetes. GLP-1 receptor (GLP-1R) agonists have shown neuroprotective effects in preclinical and clinical studies on neurodegenerative diseases in both the brain (e.g., Alzheimer’s disease, Parkinson’s disease, stroke and diabetic neuropathy) and the eye (e.g., diabetic retinopathy and AMD). However, there are currently very few studies investigating the protective effects of GLP-1R agonists in the treatment of specifically glaucoma. Based on a literature search on PubMed, the Cochrane Library, and ClinicalTrials.gov, this review aims to summarize current clinical literature on GLP-1 receptor agonists in the treatment of neurodegenerative diseases to elucidate their potential in future anti-glaucomatous treatment strategies.
Neural Control of Stopping and Stabilizing the Arm
Authors: Jayasinghe Shanie A. L. , Scheidt Robert A. , Sainburg Robert L.
Published: February 2022

Stopping is a crucial yet under-studied action for planning and producing meaningful and efficient movements. In this review, we discuss classical human psychophysics studies as well as those using engineered systems that aim to develop models of motor control of the upper limb. We present evidence for a hybrid model of motor control, which has an evolutionary advantage due to division of labor between cerebral hemispheres. Stopping is a fundamental aspect of movement that deserves more attention in research than it currently receives. Such research may provide a basis for understanding arm stabilization deficits that can occur following central nervous system (CNS) damage.
Prospective Associations of Tea Consumption With Risk of Cognitive Decline in the Elderly: A 1-Year Follow-Up Study in China
Authors: Li Wei , Yue Ling , Xiao Shifu
Published: February 2022

Background

Previous studies show that the consumption of tea is associated with several beneficial outcomes for brain health, but there is little data among the elderly in China.

Objective

The objective was to explore the longitudinal relationship between tea consumption and the risk of cognitive decline.

Methods

The current data was obtained from the China Longitudinal Aging Study (CLAS), and a total of 3,246 residents aged 60 years and above were recruited in this study. Some of them (N = 111) underwent a standard T1-weighted magnetic resonance imaging (MRI), from which the volumes of the corpus callosum (CC) and hippocampus were calculated, and detailed tea consumption information was obtained through a standardized questionnaire at baseline. The cognitive diagnosis of each participant was made by attending psychiatrists at baseline and follow-up. Their overall cognitive function was assessed by the Montreal Cognitive Assessment (MoCA), while their associative learning ability was assessed by an associative learning test (ALT). Finally, 1,545 elderly with normal cognitive function completed the baseline and follow-up assessment and were included in the final study.

Results

After controlling gender, education, smoking, take exercise and hobbies, we found that the elderly with tea consumption habits had a lower incidence rate of cognitive decline (p = 0.002, OR = 0.604, 95%CI:0.437~0.836) and tea consumption was negatively correlated with the change scores of MoCA (r = −0.056, p = 0.029). What's more, the CC_posterior volume of tea drinkers was significantly smaller than that of non-tea drinkers, while the baseline ALT score of tea drinkers was significantly higher than that of non-tea drinkers. The results of correlation analysis showed that the CC_posterior volume was significantly correlated with ALT change score (r = −0.319, p = 0.010).

Conclusions

The habit of tea consumption is associated with less incidence of cognitive impairment among the Chinese elderly, and it may prevent a decline in memory and associative learning by affecting the volume of the posterior corpus callosum.
Genetically-Guided Medical Nutrition Therapy in Type 2 Diabetes Mellitus and Pre-diabetes: A Series of n-of-1 Superiority Trials
Authors: Gkouskou Kalliopi K. , Grammatikopoulou Maria G. , Lazou Evgenia , Sanoudou Despina , Goulis Dimitrios G. , Eliopoulos Aristides G.
Published: February 2022

Type 2 diabetes mellitus (T2DM) is a heterogeneous metabolic disorder of multifactorial etiology that includes genetic and dietary influences. By addressing the latter, medical nutrition therapy (MNT) contributes to the management of T2DM or pre-diabetes toward achieving glycaemic control and improved insulin sensitivity. However, the clinical outcomes of MNT vary and may further benefit from personalized nutritional plans that take into consideration genetic variations associated with individual responses to macronutrients. The aim of the present series of n-of-1 trials was to assess the effects of genetically-guided vs. conventional MNT on patients with pre-diabetes or T2DM. A quasi-experimental, cross-over design was adopted in three Caucasian adult men with either diagnosis. Complete diet, bioclinical and anthropometric assessment was performed and a conventional MNT, based on the clinical practice guidelines was applied for 8 weeks. After a week of “wash-out,” a precision MNT was prescribed for an additional 8-week period, based on the genetic characteristics of each patient. Outcomes of interest included changes in body weight (BW), fasting plasma glucose (FPG), and blood pressure (BP). Collectively, the trials indicated improvements in BW, FPG, BP, and glycosylated hemoglobin (HbA1c) following the genetically-guided precision MNT intervention. Moreover, both patients with pre-diabetes experienced remission of the condition. We conclude that improved BW loss and glycemic control can be achieved in patients with pre-diabetes/T2DM, by coupling MNT to their genetic makeup, guiding optimal diet, macronutrient composition, exercise and oral nutrient supplementation in a personalized manner.
Raw and Cooked Vegetable Consumption and Risk of Cardiovascular Disease: A Study of 400,000 Adults in UK Biobank
Authors: Feng Qi , Kim Jean H. , Omiyale Wemimo , Bešević Jelena , Conroy Megan , May Margaret , Yang Zuyao , Wong Samuel Yeung-shan , Tsoi Kelvin Kam-fai , Allen Naomi , Lacey Ben
Published: February 2022

Objectives

Higher levels of vegetable consumption have been associated with a lower risk of cardiovascular disease (CVD), but the independent effect of raw and cooked vegetable consumption remains unclear.

Methods

From the UK Biobank cohort, 399,586 participants without prior CVD were included in the analysis. Raw and cooked vegetable intakes were measured with a validated dietary questionnaire at baseline. Multivariable Cox regression was used to estimate the associations between vegetable intake and CVD incidence and mortality, adjusted for socioeconomic status, health status, and lifestyle factors. The potential effect of residual confounding was assessed by calculating the percentage reduction in the likelihood ratio (LR) statistics after adjustment for the confounders.

Results

The mean age was 56 years and 55% were women. Mean intakes of raw and cooked vegetables were 2.3 and 2.8 tablespoons/day, respectively. During 12 years of follow-up, 18,052 major CVD events and 4,406 CVD deaths occurred. Raw vegetable intake was inversely associated with both CVD incidence (adjusted hazard ratio (HR) [95% CI] for the highest vs. lowest intake: 0.89 [0.83–0.95]) and CVD mortality (0.85 [0.74–0.97]), while cooked vegetable intake was not (1.00 [0.91–1.09] and 0.96 [0.80–1.13], respectively). Adjustment for potential confounders reduced the LR statistics for the associations of raw vegetables with CVD incidence and mortality by 82 and 87%, respectively.

Conclusions

Higher intakes of raw, but not cooked, vegetables were associated with lower CVD risk. Residual confounding is likely to account for much, if not all, of the observed associations. This study suggests the need to reappraise the evidence on the burden of CVD disease attributable to low vegetable intake in the high-income populations.
Single-Cell Transcriptome Comparison of Bladder Cancer Reveals Its Ecosystem
Authors: Luo Yongxiang , Tao Tao , Tao Ran , Huang Guixiao , Wu Song
Published: February 2022

Bladder carcinoma (BLCA) is a highly heterogeneous disease, and the underlying biological behavior is still poorly understood. Here, single-cell RNA sequencing was performed on four clinical samples of different grades from three patients, and 26,792 cell transcriptomes were obtained revealing different tumor ecosystems. We found that N-glycan biosynthesis pathway was activated in high-grade tumor, but TNF-related pathway was activated in cystitis glandularis. The tumor microenvironment (TME) of different samples showed great heterogeneity. Notably, cystitis glandularis was dominated by T cells, low-grade and high-grade tumors by macrophages, while TME in patient with high-grade relapse by stromal cells. Our research provides single-cell transcriptome profiles of cystitis glandularis and BLCA in different clinical states, and the biological program revealed by single-cell data can be used as biomarkers related to clinical prognosis in independent cohorts.
Identification of Lactate-Related Gene Signature for Prediction of Progression and Immunotherapeutic Response in Skin Cutaneous Melanoma
Authors: Xie Yalin , Zhang Jie , Li Mengna , Zhang Yu , Li Qian , Zheng Yue , Lai Wei
Published: February 2022

Skin cutaneous melanoma (SKCM) is a skin cancer type characterized by a high degree of immune cell infiltration. The potential function of lactate, a main metabolic product in the tumor microenvironment (TME) of SKCM, remains unclear. In this study, we systemically analyzed the predictive value of lactate-related genes (LRGs) for prognosis and response to immune checkpoint inhibitors (ICIs) in SKCM patients included from The Cancer Genome Atlas (TCGA) database. Cluster 3, by consensus clustering for 61 LRGs, manifested a worse clinical outcome, attributed to the overexpression of malignancy marks. In addition, we created a prognostic prediction model for high- and low-risk patients and verified its performance in a validation cohort, GSE65904. Between TME and the risk model, we found a negative relation of the immunocyte infiltration levels with patients’ risk scores. The low-risk cases had higher ICI expression and could benefit better from ICIs relative to the high-risk cases. Thus, the lactate-related prognosis risk signature may comprehensively provide a basis for future investigations on immunotherapeutic treatment for SKCM.
LncRNA PCGEM1 in Human Cancers: Functions, Mechanisms and Promising Clinical Utility
Authors: Su Yuanshuai , Gu Xinyu , Zheng Qiuxian , Zhu Lingxiao , Lu Juan , Li Lanjuan
Published: February 2022

As novel members of the noncoding RNA family, long noncoding RNAs (lncRNAs) have been widely reported to function as powerful regulators in gene expression processes, including chromosome remodeling, transcription interference and posttranscriptional modification. With the rapid development of metagenomic sequencing, numerous studies have indicated that the dysregulation of lncRNAs is closely associated with diverse human diseases, especially cancers. Prostate Gene Expression Marker 1 (PCGEM1), a recently identified lncRNA, has been reported to play a crucial role in the initiation and progression of multiple tumors by interacting with pivotal regulators of tumor-related signaling pathways. In this review, we will retrospectively review the recent studies of the expression of lncRNA PCGEM1 in human cancers and comprehensively describe the underlying regulatory mechanism by which PCGEM1 functions in tumors. More importantly, based on the relationship between PCGEM1 and cancers, the potential application of PCGEM1 in clinical diagnosis, prognosis and therapeutic treatment will also be highlighted.
Bibliometric Analysis of Ferroptosis in Stroke From 2013 to 2021
Authors: Chen Yuhua , Long Tianlin , Xu Quanhua , Zhang Chi
Published: February 2022

Background: Stroke is a major cause of long-term disability and death, but the clinical therapeutic strategy for stroke is limited and more research must be conducted to explore the possible avenues for stroke treatment and recovery. Since ferroptosis is defined, its role in the body has become the focus of attention and discussion, including in stroke.

Methods: In this work, we aim to systematically discuss the “ferroptosis in stroke” research by bibliometric analysis. Documents were retrieved from the Web of Science Core Collection database on October 30, 2021. Statistical analysis and visualization analysis were conducted by the VOSviewer 1.6.15.

Results: Ninety-nine documents were identified for bibliometric analysis. Research on “ferroptosis in stroke” has been rapidly developing and has remained the focus of many scholars and organizations in the last few years, but the Chinese groups in this field still lacked collaboration with others. Documents and citation analysis suggested that Rajiv R. Ratan and Brent R. Stockwell are active researchers, and the research by Qingzhang Tuo, Ishraq Alim, and Qian Li are more important drivers in the development of the field. Keywords associated with lipid peroxidation, ferroptosis, iron, oxidative stress, and cell death had high frequency, but apoptosis, necroptosis, pyroptosis, and autophagy had scant research, and there may be more research ideas in the future by scholars.

Conclusion: Further exploration of the mechanisms of crosstalk between ferroptosis and other programmed cell death may improve clinical applications and therapeutic effects against stroke. Scholars will also continue to pay attention to and be interested in the hot topic “ferroptosis in stroke”, to produce more exciting results and provide new insights into the bottleneck of stroke treatment.
Current Use and Complementary Value of Combining in Vivo Imaging Modalities to Understand the Renoprotective Effects of Sodium-Glucose Cotransporter-2 Inhibitors at a Tissue Level
Authors: van der Hoek Sjoukje , Stevens Jasper
Published: February 2022

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed to treat diabetes and have been shown to improve renal and cardiovascular outcomes in patients with- but also without diabetes. The mechanisms underlying these beneficial effects are incompletely understood, as is the response variability between- and within patients. Imaging modalities allow in vivo quantitative assessment of physiological, pathophysiological, and pharmacological processes at kidney tissue level and are therefore increasingly being used in nephrology. They provide unique insights into the renoprotective effects of SGLT2i and the variability in response and may thus contribute to improved treatment of the individual patient. In this mini-review, we highlight current work and opportunities of renal imaging modalities to assess renal oxygenation and hypoxia, fibrosis as well as interaction between SGLT2i and their transporters. Although every modality allows quantitative assessment of particular parameters of interest, we conclude that especially the complementary value of combining imaging modalities in a single clinical trial aids in an integrated understanding of the pharmacology of SGLT2i and their response variability.
Is Therapeutic Drug Monitoring Relevant for Antidepressant Drug Therapy? Implications From a Systematic Review and Meta-Analysis With Focus on Moderating Factors
Authors: Funk Cleo S. M. , Hart Xenia M. , Gründer Gerhard , Hiemke Christoph , Elsner Björn , Kreutz Reinhold , Riemer Thomas G.
Published: February 2022

Inter-individual differences in antidepressant drug concentrations attained in blood may limit the efficacy of pharmacological treatment of depressive disorders. Therapeutic drug monitoring (TDM) enables to determine drug concentrations in blood and adjust antidepressant dosage accordingly. However, research on the underlying assumption of TDM, association between concentration and clinical effect, has yielded ambiguous results for antidepressants. It has been proposed that this ambiguity may be caused by methodological shortcomings in studies investigating the concentration-effect relationship. Guidelines recommend the use of TDM in antidepressant treatment as expert opinion. This reflects the lack of research, particularly systematic reviews and meta-analyses of randomized controlled trials, on the relationship between concentration and effect as well as on the benefits of the use of TDM in clinical practice. In this study, a systematic review and meta-analysis of randomized controlled trials has been performed to investigate the relationship between antidepressant concentration, efficacy, and side effects. It is the first meta-analytical approach to this subject and additionally considers methodological properties of primary studies as moderators of effect in quantitative analysis. Our results identified methodological shortcomings, namely the use of a flexible dose design and the exclusion of concentrations in lower- or subtherapeutic ranges, which significantly moderate the relationship between antidepressant concentration and efficacy. Such shortcomings obscure the evidence base of using TDM in clinical practice to guide antidepressant drug therapy. Further research should consider these findings to determine the relationship between concentration and efficacy and safety of antidepressant treatments, especially for newer antidepressants.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=246149, identifier: CRD42021246149.
COVID-19 Related Stress and Mental Health Outcomes 1 Year After the Peak of the Pandemic Outbreak in China: the Mediating Effect of Resilience and Social Support
Authors: Hu Jingchu , Huang Yiting , Liu Jiayu , Zheng Zhiying , Xu Xiuhua , Zhou Yunfei , Wang Jianhong
Published: February 2022

Background

COVID-19 outbreak have a long-term negative impact on mental health. Meanwhile, it may also provide opportunities for positive outcomes (e.g., post-traumatic growth). Resilience and social support could serve as psychological resources to protect individuals against the detrimental effects of the COVID-19 crisis and enable people to develop positive changes during challenging times.

Objective

By testing the roles of resilience and social support in the relationship between COVID-19 related stress and negative mental health outcomes (depression and anxiety), as well as the relationship between COVID-19 related stress and positive mental health outcomes (post-traumatic growth, PTG), this study aimed to investigate the psychological mechanisms involved in different mental health outcomes induced by COVID-19.

Methods

An online survey was conducted 1 year after the peak of the COVID-19 outbreak (from April to August 2021) in China. The survey includes demographic questionnaires and six scales: the Impact of Event Scale-Revised for COVID-19 (IES-RC), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), the Perceived Social Support Scale (PSSS), the Center for Epidemiological Studies Depression Scale (CES-D), the Generalized Anxiety Disorder scale (GAD-7) and the Posttraumatic Growth Inventory (PTGI). The structural equation model (SEM) was used to evaluate the relations and mechanisms between COVID-19 related stress and resilience, social support in depression, anxiety, and PTG.

Results

A total of 771 Chinese subjects completed the questionnaire, including 416 (54%) females. COVID-19 related stress was associated with anxiety (P < 0.001), PTG (P < 0.001), and depression (P < 0.001). Resilience was related to depression (P < 0.001), anxiety (P < 0.001), and PTG (P < 0.001). Social support was associated with depression (P < 0.001), anxiety (P < 0.001), and PTG (P < 0.001). Under SEM analysis, resilience mediated the effects of COVID-19 related stress on depression and post-traumatic growth. Social support mediated the impacts of COVID-19 related stress on post-traumatic growth, depression, and anxiety. The path coefficients of the mediation effects were statistically significant.

Conclusions

The current findings suggest that COVID-19 related stress has a double-edged effect on mental health. Depression, anxiety, and PTG coexist in Chinese individuals 1 year after the peak of the pandemic. Resilience and social support serve as important protective factors of mental health, safeguard people from the negative mental health outcomes of the COVID-19, and promote PTG.