bluuebunny/crossref_metadata_2025 huggingface dataset:
Relato de la experiencia en Argentina de la adaptación de un programa estandarizado guiado por la recuperación en salud mental
Authors: Geffner Norma Irene , Agrest Martín , Garber Epstein Paula
Published: August 2021

El concepto de recuperación, su conceptualización y consideración para las prácticas en el campo de la salud mental, pese a su signiﬁcativo desarrollo a nivel mundial, están pendientes en América Latina. Como consecuencia, se registran demoras para implementar cambios estructurales en la atención especializada y las personas usuarias del sistema de salud mental se ven privadas de prácticas basadas en la evidencia que podrían alentar sus procesos de recuperación. Una historia de violencia estatal y crisis económicas cíclicas atentaron contra la continuidad de invalorables prácticas comunitarias que, particularmente en Argentina, fueron borradas por mucho tiempo a partir del golpe de estado de 1976.   Este artículo describe el proceso de adaptación cultural para Argentina del programa Illness Management and Recovery llevado a cabo por un equipo conformado por personas usuarias de servicios de salud mental, ex usuarios y profesionales. Esta adaptación se plantea como un puente entre el legado de prácticas comunitarias latinoamericanas en salud mental y las nuevas prácticas basadas en la evidencia que surgen con la incorporación de la voz y la experiencia de las personas usuarias al campo de la salud mental. Finalmente, se incluyen reflexiones sobre la experiencia de adaptación y recomendaciones para la futura implementación local del programa renombrado como “Programa Activo para la Recuperación”.
Peer Support in Behavioral Health care: why it can work in the Latinx context
Authors: Rojas Perez Oscar Fernando , Reis Graziela , Costa Mark , Ocasio Luz , Diaz Annette , Guy Kimberly , Restrepo-Toro Maria , Bellamy Chyrell
Published: August 2021

Las personas de origenes latinoamericanos son menos propensas a comprometerse con el cuidado de salud mental y la participación en servicios de salud mental, comparado a otros grupos raciales y étnicos. Las bajas tasas de participación en servicios de salud mental en parte de la comunidad Latinx en los Estados Unidos (EE. UU.) se puede atribuir parcialmente alfuncionamiento de los sistemas de cuidado, los cuales no son sensibles a la cultura Latinx o al español como lengua. Las Investigaciones han demostrado que intervenciones centradas en la cultura, que promueven los valores culturales de la comunidad Latinx, informan una mayor participación y satisfacción en el tratamiento y los servicios de salud mental. Un enfoque efectivo, informado por la cultura, que puede mejorar la participación de la comunidad Latinx en servicios de salud mental es el apoyo de compañerxs. En el enfoque de apoyo de pares, se contrata a personas con experiencias vividas en salud mental y adicciones como compañeros de apoyo para ayudar a quienes han vivido experiencias similares. Los estudios de investigación que miden la efectividad de los enfoques de apoyo entre pares han mostrado mejoras en las vidas de quienes reciben el apoyo, ayudando con el sentido de esperanza, calidad de vida, y bienestar. Los resultados también han demostrado disminución de hospitalizaciones, visitas a la sala de emergencia y menor uso de sustancias y participación en actividades criminales. El apoyo entre compañerxs en el contexto Latinx parece un ajuste natural dados sus valores colectivos compartidos (p. ej., simpatía, personalismo, respeto, confianza, familismo). Este articulo discute como los valores de apoyo entre compañerxs se relacionan con los valores colectivistas; y como se pueden infundir más los valores Latinx en el entrenamiento, desarrollo y supervisión de los compañerxs de apoyo para mejorar el cuidado de salud mental informado por la cultura.
Recovery e os grupos de ajuda e suporte mútuos em saúde mental: análise de uma experiência.
Authors: Pereira Figueiredo Angela
Published: August 2021

Para o artigo, é realizado um recorte dos resultados da pesquisa que originou a dissertação “’Nada sobre nós, sem nós’: Empoderamento e recovery em um estudo de um grupo de ajuda e suporte mútuos em saúde mental no município do Rio de Janeiro-RJ”, dando enfoque às experiências de usuários e usuárias de um grupo de ajuda e suporte mútuos em saúde mental, priorizando algumas de suas narrativas, associadas a seus processos de recovery. Considerando a realidade das práticas de saúde mental, seus limites e desafios, visa-se contribuir para os avanços no campo, priorizando as experiências brasileiras de protagonismo de usuários e usuárias de serviços, tal como os grupos de ajuda e suporte mútuos. Foi utilizado o método de pesquisa participante com os sete usuários e as cinco usuárias do grupo básico de facilitadores do programa. Para analisar os processos de recovery no dispositivo grupal em foco, é necessário contextualizá-los a partir da nossa realidade de reforma psiquiátrica. Como resultados, foram abordadas as questões mais gerais sobre o funcionamento do grupo, os temas e as questões da vida cotidiana, as questões relacionadas ao trabalho, a relação com os serviços de saúde mental e com evidências e indicadores de efetividade. A discussão dos desafios e efeitos do trabalho com o grupo para seus processos de protagonismo é importante para que possamos avançar nas políticas e práticas de saúde mental, considerando especificamente a relevância do processo de recovery no contexto brasileiro, dando visibilidade às práticas de protagonismo de usuários e usuárias de serviços.
Aberrant Expression of Circulating MicroRNA Leads to the Dysregulation of Alpha-Synuclein and Other Pathogenic Genes in Parkinson’s Disease
Authors: Cai Meng , Chai Songshan , Xiong Tao , Wei Jun , Mao Weibing , Zhu Yasha , Li Xiang , Wei Wei , Dai Xuan , Yang Bangkun , Liu Wen , Shu Bing , Wang Mengyang , Lu Taojunjin , Cai Yuankun , Zheng Zhixin , Mei Zhimin , Zhou Yixuan , Yang Jingyi , Zhao Jingwei , Shen Lei , Ho Joshua Wing Kei , Chen Jincao , Xiong Nanxiang
Published: August 2021

A group of circulating microRNAs (miRNAs) have been implicated in the pathogenesis of Parkinson’s disease. However, a comprehensive study of the interactions between pathogenic miRNAs and their downstream Parkinson’s disease (PD)-related target genes has not been performed. Here, we identified the miRNA expression profiles in the plasma and circulating exosomes of Parkinson’s disease patients using next-generation RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses showed that the miRNA target genes were enriched in axon guidance, neurotrophin signaling, cellular senescence, and the Transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) signaling pathways. Furthermore, a group of aberrantly expressed miRNAs were selected and further validated in individual patient plasma, human neural stem cells (NSCs) and a rat model of PD. More importantly, the full scope of the regulatory network between these miRNAs and their PD-related gene targets in human neural stem cells was examined, and the findings revealed a similar but still varied downstream regulatory cascade involving many known PD-associated genes. Additionally, miR-23b-3p was identified as a novel direct regulator of alpha-synuclein, which is possibly the key component in PD. Our current study, for the first time, provides a glimpse into the regulatory network of pathogenic miRNAs and their PD-related gene targets in PD. Moreover, these PD-associated miRNAs may serve as biomarkers and novel therapeutic targets for PD.
Prioritizing Susceptible Genes for Thyroid Cancer Based on Gene Interaction Network
Authors: Zhong Lin-kun , Xie Chang-lian , Jiang Shan , Deng Xing-yan , Gan Xiao-xiong , Feng Jian-hua , Cai Wen-song , Liu Chi-zhuai , Shen Fei , Miao Jian-hang , Xu Bo
Published: August 2021

Thyroid cancer ranks second in the incidence rate of endocrine malignant cancer. Thyroid cancer is usually asymptomatic at the initial stage, which makes patients easily miss the early treatment time. Combining genetic testing with imaging can greatly improve the diagnostic efficiency of thyroid cancer. Researchers have discovered many genes related to thyroid cancer. However, the effects of these genes on thyroid cancer are different. We hypothesize that there is a stronger interaction between the core genes that cause thyroid cancer. Based on this hypothesis, we constructed an interaction network of thyroid cancer-related genes. We traversed the network through random walks, and sorted thyroid cancer-related genes through ADNN which is fusion of Adaboost and deep neural network (DNN). In addition, we discovered more thyroid cancer-related genes by ADNN. In order to verify the accuracy of ADNN, we conducted a fivefold cross-validation. ADNN achieved AUC of 0.85 and AUPR of 0.81, which are more accurate than other methods.
Asian Winter Monsoon Imprint on the Water Column Structure at the Northern South China Sea Coast
Authors: Zhang Yancheng , Zhu Kai , Huang Chao , Kong Deming , He Yuxin , Wang Huanye , Liu Weiguo , Xie Zhouqing , Wei Gangjian , Liu Zhonghui
Published: August 2021

Coastal regions of the northern South China Sea (SCS) strongly interact with the Asian monsoon circulation (AMC). Thus, variations of sea surface temperature (SST) here are newly suggested to document AMC changes in an effective manner, but additional physical parameters of oceanic conditions, probably also in relation to the AMC system, remain poorly understood. In this study, we analyzed glycerol dialkyl glycerol tetraethers (GDGTs) from a well-dated sediment core YJ, retrieved at the northern SCS coast, to further scrutinize the intrinsic response of water column to winter AMC strength. It shows that within the time frame of past ∼1,000 years, the tetraether index of lipids with 86 carbon atoms (TEX86) and published alkenone (U37K′) temperature records together confirm a reduced thermal gradient during the Little Ice Age (LIA), in comparison to that during the Medieval Climate Anomaly (MCA). Considering concurrent variations of the branched and isoprenoid tetraether (BIT) and the ratio of archaeol to caldarchaeol (ACE), for example, with decreased values (<∼0.3) for the former and relatively high values for the latter at the LIA, indicative of stratification and salinity changes, respectively, these multiple lines of evidence thereby call for well mixing of onsite water at site YJ correspondingly. Our results suggest that winter AMC strength is a critical factor for mixing subsurface waters and modifying thermal/saline conditions at the northern SCS coasts through the last millennium and also, perhaps, on longer timescales.
Differential Morphological Diagnosis of Various Forms of Congenital Hyperinsulinism in Children
Authors: Mitrofanova Lubov Borisovna , Perminova Anastasia Arkadyevna , Ryzhkova Daria Viktorovna , Sukhotskaya Anna Andreyevna , Bairov Vladimir Gireyevich , Nikitina Irina Leorovna
Published: August 2021

Introduction

Congenital hyperinsulinism (CHI) has diffuse (CHI-D), focal (CHI-F) and atypical (CHI-A) forms. Surgical management depends on preoperative [18F]-DOPA PET/CT and intraoperative morphological differential diagnosis of CHI forms. Objective: to improve differential diagnosis of CHI forms by comparative analysis [18F]-DOPA PET/CT data, as well as cytological, histological and immunohistochemical analysis (CHIA).

Materials and Methods

The study included 35 CHI patients aged 3.2 ± 2.0 months; 10 patients who died from congenital heart disease at the age of 3.2 ± 2.9 months (control group). We used PET/CT, CHIA of pancreas with antibodies to ChrA, insulin, Isl1, Nkx2.2, SST, NeuroD1, SSTR2, SSTR5, DR1, DR2, DR5; fluorescence microscopy with NeuroD1/ChrA, Isl1/insulin, insulin/SSTR2, DR2/NeuroD1 cocktails.

Results

Intraoperative examination of pancreatic smears showed the presence of large nuclei, on average, in: 14.5 ± 3.5 cells of CHI-F; 8.4 ± 1.1 of CHI-D; and 4.5 ± 0.7 of control group (from 10 fields of view, x400). The percentage of Isl1+ and NeuroD1+endocrinocytes significantly differed from that in the control for all forms of CHI. The percentage of NeuroD1+exocrinocytes was also significantly higher than in the control. The proportion of ChrA+ and DR2+endocrinocytes was higher in CHI-D than in CHI-F, while the proportion of insulin+cells was higher in CHI-A. The number of SST+cells was significantly higher in CHI-D and CHI-F than in CHI-A.

Conclusion

For intraoperative differential diagnosis of CHI forms, in addition to frozen sections, quantitative cytological analysis can be used. In quantitative immunohistochemistry, CHI forms differ in the expression of ChrA, insulin, SST and DR2. The development of a NeuroD1 inhibitor would be advisable for targeted therapy of CHI.
Metabolic Functions of G Protein-Coupled Receptors and β-Arrestin-Mediated Signaling Pathways in the Pathophysiology of Type 2 Diabetes and Obesity
Authors: Oliveira de Souza Camila , Sun Xuenan , Oh Dayoung
Published: August 2021

Seven transmembrane receptors (7TMRs), often termed G protein-coupled receptors (GPCRs), are the most common target of therapeutic drugs used today. Many studies suggest that distinct members of the GPCR superfamily represent potential targets for the treatment of various metabolic disorders including obesity and type 2 diabetes (T2D). GPCRs typically activate different classes of heterotrimeric G proteins, which can be subgrouped into four major functional types: Gαs, Gαi, Gαq/11, and G12/13, in response to agonist binding. Accumulating evidence suggests that GPCRs can also initiate β-arrestin-dependent, G protein-independent signaling. Thus, the physiological outcome of activating a certain GPCR in a particular tissue may also be modulated by β-arrestin-dependent, but G protein-independent signaling pathways. In this review, we will focus on the role of G protein- and β-arrestin-dependent signaling pathways in the development of obesity and T2D-related metabolic disorders.
Research on Dynamic Equivalent SOC Estimation of Hybrid Energy Storage System Based on Sliding Mode Observer
Authors: Wang Yifei , Jiang Wei , Zhu Chengwei , Xu Zhiqi , Deng Yifan
Published: August 2021

This article proposes a sliding mode observer based dynamic equivalent state of charge (ESOC) estimation method for hybrid energy storage system (HESS). Since different types of energy storage components and power electronics circuit are coupled in the HESS, the traditional SOC estimation method cannot reflect the real-time operation characteristics of the HESS. To tackle this problem, a sliding mode observer based on the model of the HESS is built in this article. By collecting the corresponding voltage and current signals, the internal parameters of energy storage elements can be observed accurately in real time. The dynamic ESOC is further defined with the idea of real-time charge balance to reflect the accurate available capacity of the HESS. Finally, the simulation results based on MATLAB/Simulink model are given to verify the feasibility of the proposed dynamic ESOC.
Rapid Identification of Common Poisonous Plants in China Using DNA Barcodes
Authors: Wang Jie , Zhao Jinquan , Yu Weisen , Wang Shuangyu , Bu Shuhua , Shi Xuexiang , Zhang Xiuyun
Published: August 2021

Toxic plants have been a major threat to public health in China. However, identification and tracing of poisoned species with traditional methods are unreliable due to the destruction of plant morphology by cooking and chewing. DNA barcoding is independent of environmental factors and morphological limitations, making it a powerful tool to accurately identify species. In our study, a total of 83 materials from 26 genera and 31 species of 13 families were collected and 13 plant materials were subjected to simulated gastric fluid digestion. Four markers (rbcL, trnH-psbA, matK, and ITS) were amplified and sequenced for all untreated and mock-digested samples. The effectiveness of DNA barcoding for the identification of toxic plants was assessed using Basic Local Alignment Search Tool (BLAST) method, PWG-Distance method, and Tree-Building (NJ) method. Except for the matK region, the amplification success rate of the remaining three regions was high, but the sequencing of trnH-psbA and ITS was less satisfactory. Meanwhile, matK was prone to be more difficult to amplify and sequence because of simulated gastric fluid. Among the three methods applied, BLAST method showed lower recognition rates, while PWG-Distance and Tree-Building methods showed little difference in recognition rates. Overall, ITS had the highest recognition rate among individual loci. Among the combined loci, rbcL + ITS had the highest species recognition rate. However, the ITS region may not be suitable for DNA analysis of gastric contents and the combination of loci does not significantly improve species resolution. In addition, identification of species to the genus level is sufficient to aid in the clinical management of most poisoning events. Considering primer versatility, DNA sequence quality, species identification ability, experimental cost and speed of analysis, we recommend rbcL as the best single marker for clinical identification and also suggest the BLAST method for analysis. Our current results suggest that DNA barcoding can rapidly identify and trace toxic species and has great potential for clinical applications. In addition, we suggest the creation of a proprietary database containing morphological, toxicological and molecular information to better apply DNA barcoding technology in clinical diagnostics.
Skin Resident Memory T Cells May Play Critical Role in Delayed-Type Drug Hypersensitivity Reactions
Authors: Schunkert Elisa Maria , Shah Pranali Nitin , Divito Sherrie Jill
Published: August 2021

Delayed-type drug hypersensitivity reactions (dtDHR) are immune-mediated reactions with skin and visceral manifestations ranging from mild to severe. Clinical care is negatively impacted by a limited understanding of disease pathogenesis. Though T cells are believed to orchestrate disease, the type of T cell and the location and mechanism of T cell activation remain unknown. Resident memory T cells (TRM) are a unique T cell population potentially well situated to act as key mediators in disease pathogenesis, but significant obstacles to defining, identifying, and testing TRMin dtDHR preclude definitive conclusions at this time. Deeper mechanistic interrogation to address these unanswered questions is necessary, as involvement of TRMin disease has significant implications for prediction, diagnosis, and treatment of disease.
Serum Protein Electrophoresis May Be Used as a Screening Tool for Antibody Deficiency in Children and Adolescents
Authors: Piza Cristina Frias Sartorelli de Toledo , Aranda Carolina Sanchez , Solé Dirceu , Jolles Stephen , Condino-Neto Antonio
Published: August 2021

Background

Patients with antibody deficiency may experience exceptionally long diagnostic delays, increasing the risk of life-threatening infections, end-organ damage, mortality, and health costs.

Objective

This study aimed to analyze serum protein electrophoresis and verify the correlation between calculated globulin (CG, total protein minus albumin levels) or electrophoretically determined serum gamma globulin fraction (Gamma) with IgG levels in children and adolescents under 18 years old (yo).

Methods

We analyzed serum protein electrophoresis (GC or Gamma) and IgG levels from 1215 children and adolescents under 18 yo, classified into 5 age groups. We verified the correlation between CG or Gamma with serum IgG levels.

Results

Serum IgG levels varied according to age groups (from 4.3 ± 2.3 g/l in children under 6 months old to 11.4 ± 3.2 g/l in adolescents in the 10-<18 yo group). CG sensitivity and specificity to detect IgG below the reference range for all patients were 93.1% and 81.8%, respectively, and varied according to age group. Gamma sensitivity and specificity for all patients were 100% and 87.8%, respectively, and varied according to age group as well. We found serum IgG levels below the age reference level in 29 patients (2.4% of the cases) using CG or Gamma levels.

Conclusion

Both CG and Gamma levels may be of utility as a screening tool for earlier diagnosis of antibody deficiency in children and adolescents under 18 yo.
Novel Method for the Estimation of Vertical Temperature Profiles Using a Coastal Acoustic Tomography System
Authors: Park Yeongbin , Jeon Chanhyung , Song Hajin , Choi Youngseok , Chae Jeong-Yeob , Lee Eun-Joo , Kim Jin Sung , Park Jae-Hun
Published: August 2021

Systems based on remote sensing technology, which use reciprocal acoustic signals to continuously monitor changes in the coastal oceanic environment, are referred to as coastal acoustic tomography (CAT) systems. These systems have been applied in regions in which heavy ship traffics, fishing and marine aquaculture activities make it difficult to establish in situ oceanic sensor moorings. Conventionally, CAT measurements were used to successfully produce horizontal maps of the depth-averaged current velocity and temperature in these coastal regions without attempting to produce a vertical temperature profile. This prompted us to propose a new method for vertical temperature profile estimation (VTPE) from CAT data using the available sea surface temperature (SST), near-bottom temperature (NBT), and water depth. The VTPE method was validated using data-assimilated and tide-included high-resolution ocean model outputs, including tide data, by comparing the estimated and simulated temperatures. Measurements were performed in the southern coastal region of Korea, where two CAT stations were moored to establish a continuous coastal ocean monitoring system. The validation results revealed that the algorithm performed well across all seasons. Sensitivity tests of the VTPE method with reasonable realistic random errors in the SST, NBT, and acoustic travel time measurements demonstrate that the method is applicable to CAT observation data because the monthly mean root-mean-squared difference (RMSD) for the vertical profiles for February, May, August, and November were 0.23, 0.30, 0.50, and 0.24°C, respectively. The VTPE method was applied to the CAT observation datasets acquired in February and August. The transceivers at the CAT stations were at depths 11 and 6 m on average. The RMSD between the estimated and observed temperatures in the middle layer (∼3 m depth) between two stations in February and August were 0.08 and 0.60°C, respectively, the accuracy of which is sufficient in largely time-varying coastal environments. We provide a novel method for continuous coastal subsurface environmental monitoring without interrupting maritime traffic, fishing, and marine aquaculture activities.
Holistic Design of Energy Pile Bridge Deicing System With Ontology-Based Multiobjective Decision Making
Authors: Zhang Peng , Cui Chunyi , Li Chaoji , Zhang Cheng , Liu Hailong
Published: August 2021

Even though the energy piles have been applied for the bridge deicing system, the traditional design approach is commonly a single-domain and objective-oriented method and is consequently lacking means to comprehensively consider all the relevant factors, such as life-cycle cost, investment payback cycle, carbon emissions, etc. This paper presents a holistic design scheme for the energy pile deicing system of bridge decks. In this paper, a holistic designing tool, namely, OntoBDDS, was developed based on ontology method and SWRL rules. It can automatically provide financial, safety, and heat flux information for designers to evaluate and optimize the design scheme of a deicing system in the early design stage of a bridge. After semantic and syntactical validation of the OntoBDDS system, a case study was also conducted to demonstrate how to leverage knowledge query to provide a series of design alternatives autonomously through considering different design parameters. This case study also verified the practicability and feasibility of the OntoBDDS holistic decision-making system and indicated its potential to be applied for other engineering problems when dealing with multiobjective holistic design making.
Reduced Levels of miR-342-5p in Plasma Are Associated With Worse Cognitive Evolution in Patients With Mild Alzheimer’s Disease
Authors: Dakterzada Farida , David Benítez Iván , Targa Adriano , Lladó Albert , Torres Gerard , Romero Leila , de Gonzalo-Calvo David , Moncusí-Moix Anna , Tort-Merino Adria , Huerto Raquel , Sánchez-de-la-Torre Manuel , Barbé Ferran , Piñol-Ripoll Gerard
Published: August 2021

Background

Progressive cognitive decline is the most relevant clinical symptom of Alzheimer’s disease (AD). However, the rate of cognitive decline is highly variable between patients. Synaptic deficits are the neuropathological event most correlated with cognitive impairment in AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD.

Methods

We analyzed 754 plasma miRNAs from 19 women diagnosed with mild AD using TaqMan low-density array cards. The patients were grouped based on the rate of decline in the MMSE score after 2 years [<4 points (N = 11) and ≥4 points (N = 8)]. The differentially expressed miRNAs between the two groups were validated in an independent cohort of men and women (N = 53) with mild AD using RT-qPCR.

Results

In the discovery cohort, 17 miRNAs were differentially expressed according to the fold change between patients with faster declines in cognition and those with slower declines. miR-342-5p demonstrated differential expression between the groups and a good correlation with the rate of cognitive decline in the validation cohort (r = −0.28; p = 0.026). This miRNA had a lower expression level in patients who suffered from more severe decline than in those who were cognitively more stable after 2 years (p = 0.049).

Conclusion

Lower levels of miR-342-5p in plasma were associated with faster cognitive decline in patients with mild AD after 2 years of follow-up.
Costs Related to Frontotemporal Dementia in Latin America: A Scoping Review of Economic Health Studies
Authors: Alva-Dìaz Carlos , Malaga Marco , Rodriguez-Calienes Aaron , Morán-Mariños Cristian , Velásquez-Rimachi Victor , Custodio Nilton
Published: August 2021

Introduction: Frontotemporal dementia (FTD) is a complex syndrome characterized by changes in behavior, language, executive control, and motor symptoms. Its annual economic burden per patient in developed countries has been classified as considerable, amounting to US$119,654 per patient, almost double the patient costs reported for Alzheimer's disease. However, there is little information regarding cost-of-illness (COI) for FTD in Latin-America (LA).

Aim: To describe the costs related to FTD in LA.

Methods: We included COI studies on FTD conducted in LA published in English, Spanish, or Portuguese from inception to September 2020. We carried out a systematic search in Pubmed/Medline, Scopus, Web of Science, Scielo, Cochrane, and gray literature. For quality assessment, we used a COI assessment tool available in the literature. All costs were reported in USD for 1 year and adjusted for inflation.

Results: We included three studies from Argentina, Brazil, and Peru. Direct costs (DCs) included medication (from US$959.20 to US$ 4,279.20), health care costs (from US$ 2,275.80 to US$7,856.16), and caregiver costs (from US$9,634.00 to US$28,730.28). Indirect costs (ICs) amounted to US$43,076.88.

Conclusions: In LA countries, the reporting of costs related to FTD continues to be oriented toward DCs. They remain lower than in developed countries, possibly due to the limited health budget allocated. Only one Brazilian report analyzed ICs, representing the highest percentage of the total costs. Therefore, studies on the COI of this disease in LA are essential, focusing on both out-of-pocket spending and the potential economic loss to patients' homes and families.
The Corticospinal Excitability Can Be Predicted by Spontaneous Electroencephalography Oscillations
Authors: Cai Guiyuan , Wu Manfeng , Ding Qian , Lin Tuo , Li Wanqi , Jing Yinghua , Chen Hongying , Cai Huiting , Yuan Tifei , Xu Guangqing , Lan Yue
Published: August 2021

Transcranial magnetic stimulation (TMS) has a wide range of clinical applications, and there is growing interest in neural oscillations and corticospinal excitability determined by TMS. Previous studies have shown that corticospinal excitability is influenced by fluctuations of brain oscillations in the sensorimotor region, but it is unclear whether brain network activity modulates corticospinal excitability. Here, we addressed this question by recording electroencephalography (EEG) and TMS measurements in 32 healthy individuals. The resting motor threshold (RMT) and active motor threshold (AMT) were determined as markers of corticospinal excitability. The least absolute shrinkage and selection operator (LASSO) was used to identify significant EEG metrics and then correlation analysis was performed. The analysis revealed that alpha2 power in the sensorimotor region was inversely correlated with RMT and AMT. Innovatively, graph theory was used to construct a brain network, and the relationship between the brain network and corticospinal excitability was explored. It was found that the global efficiency in the theta band was positively correlated with RMT. Additionally, the global efficiency in the alpha2 band was negatively correlated with RMT and AMT. These findings indicated that corticospinal excitability can be modulated by the power spectrum in sensorimotor regions and the global efficiency of functional networks. EEG network analysis can provide a useful supplement for studying the association between EEG oscillations and corticospinal excitability.
YY1 Promotes Telomerase Activity and Laryngeal Squamous Cell Carcinoma Progression Through Impairment of GAS5-Mediated p53 Stability
Authors: Wei Xudong , Liu Fenglei , Jiang Xuelian , Xu Xiaoyan , Zhou Tianhao , Kang Chengfang
Published: August 2021

Yin Yang 1 (YY1) is a key transcription factor that exerts functional roles in the cell biological process of various cancers. The current study aimed to elucidate the role and mechanism of YY1 in laryngeal squamous cell carcinoma (LSCC). YY1 mRNA and protein expression in human LSCC cell lines was detected by RT-qPCR and Western blot analysis. An interaction of YY1, GAS5, and p53 protein stability was predicted and confirmed by bioinformatics, ChIP, Co-IP, RIP, and FISH assays. Following loss- and gain-function assays, LSCC cell proliferation, colony formation, cell cycle, telomere length and telomerase activity were evaluated by CCK-8 assay, colony formation assay, flow cytometry, and PCR-ELISA, respectively. Nude mice were xenografted with the tumor in vivo. LSCC cell lines presented with upregulated expression of YY1, downregulated GAS5 expression, and decreased p53 stability. YY1 inhibited the expression of GAS5, which in turn recruited p300 and bound to p53, thus stabilizing it. Moreover, YY1 could directly interact with p300 and suppressp53 stability, leading to enhancement of cell proliferation, telomere length and telomerase activity in vitro along with tumor growth in vivo. Collectively, YY1 can stimulate proliferation and telomerase activity of LSCC cells through suppression of GAS5-dependent p53 stabilization or by decreasing p53 stability via a direct interaction with p300, suggesting that YY1 presents a therapeutic target as a potential oncogene in LSCC development and progression.
From Immunogenic Cell Death to Immunogenic Modulation: Select Chemotherapy Regimens Induce a Spectrum of Immune-Enhancing Activities in the Tumor Microenvironment
Authors: Fabian Kellsye P. , Wolfson Benjamin , Hodge James W.
Published: August 2021

Cancer treatment has rapidly entered the age of immunotherapy, and it is becoming clear that the effective therapy of established tumors necessitates rational multi-combination immunotherapy strategies. But even in the advent of immunotherapy, the clinical role of standard-of-care chemotherapy regimens still remains significant and may be complementary to emerging immunotherapeutic approaches. Depending on dose, schedule, and agent, chemotherapy can induce immunogenic cell death, resulting in the release of tumor antigens to stimulate an immune response, or immunogenic modulation, sensitizing surviving tumor cells to immune cell killing. While these have been previously defined as distinct processes, in this review we examine the published mechanisms supporting both immunogenic cell death and immunogenic modulation and propose they be reclassified as similar effects termed “immunogenic cell stress.”

Treatment-induced immunogenic cell stress is an important result of cytotoxic chemotherapy and future research should consider immunogenic cell stress as a whole rather than just immunogenic cell death or immunogenic modulation. Cancer treatment strategies should be designed specifically to take advantage of these effects in combination immunotherapy, and novel chemotherapy regimens should be designed and investigated to potentially induce all aspects of immunogenic cell stress.
Short-Chain Naphthoquinone Protects Against Both Acute and Spontaneous Chronic Murine Colitis by Alleviating Inflammatory Responses
Authors: Shastri Sonia , Shinde Tanvi , Woolley Krystel L. , Smith Jason A. , Gueven Nuri , Eri Rajaraman
Published: August 2021

Ulcerative colitis (UC) is characterised by chronic, relapsing, idiopathic, and multifactorial colon inflammation. Recent evidence suggests that mitochondrial dysfunction plays a critical role in the onset and recurrence of this disease. Previous reports highlighted the potential of short-chain quinones (SCQs) for the treatment of mitochondrial dysfunction due to their reversible redox characteristics. We hypothesised that a recently described potent mitoprotective SCQ (UTA77) could ameliorate UC symptoms and pathology. In a dextran sodium sulphate- (DSS-) induced acute colitis model in C57BL/6J mice, UTA77 substantially improved DSS-induced body weight loss, disease activity index (DAI), colon length, and histopathology. UTA77 administration also significantly increased the expression of tight junction (TJ) proteins occludin and zona-occludin 1 (ZO-1), which preserved intestinal barrier integrity. Similar responses were observed in the spontaneous Winnie model of chronic colitis, where UTA77 significantly improved DAI, colon length, and histopathology. Furthermore, UTA77 potently suppressed elevated levels of proinflammatory cytokines and chemokines in colonic explants of both DSS-treated and Winnie mice. These results strongly suggest that UTA77 or its derivatives could be a promising novel therapeutic approach for the treatment of human UC.
Characterization of Compound-Specific, Concentration-Independent Biophysical Properties of Sodium Channel Inhibitor Mechanism of Action Using Automated Patch-Clamp Electrophysiology
Authors: Pesti Krisztina , Földi Mátyás C. , Zboray Katalin , Toth Adam V. , Lukacs Peter , Mike Arpad
Published: August 2021

We have developed an automated patch-clamp protocol that allows high information content screening of sodium channel inhibitor compounds. We have observed that individual compounds had their specific signature patterns of inhibition, which were manifested irrespective of the concentration. Our aim in this study was to quantify these properties. Primary biophysical data, such as onset rate, the shift of the half inactivation voltage, or the delay of recovery from inactivation, are concentration-dependent. We wanted to derive compound-specific properties, therefore, we had to neutralize the effect of concentration. This study describes how this is done, and shows how compound-specific properties reflect the mechanism of action, including binding dynamics, cooperativity, and interaction with the membrane phase. We illustrate the method using four well-known sodium channel inhibitor compounds, riluzole, lidocaine, benzocaine, and bupivacaine. Compound-specific biophysical properties may also serve as a basis for deriving parameters for kinetic modeling of drug action. We discuss how knowledge about the mechanism of action may help to predict the frequency-dependence of individual compounds, as well as their potential persistent current component selectivity. The analysis method described in this study, together with the experimental protocol described in the accompanying paper, allows screening for inhibitor compounds with specific kinetic properties, or with specific mechanisms of inhibition.
Development and Validation of a Prediction Model for Elevated Arterial Stiffness in Chinese Patients With Diabetes Using Machine Learning
Authors: Li Qingqing , Xie Wenhui , Li Liping , Wang Lijing , You Qinyi , Chen Lu , Li Jing , Ke Yilang , Fang Jun , Liu Libin , Hong Huashan
Published: August 2021

Background

Arterial stiffness assessed by pulse wave velocity is a major risk factor for cardiovascular diseases. The incidence of cardiovascular events remains high in diabetics. However, a clinical prediction model for elevated arterial stiffness using machine learning to identify subjects consequently at higher risk remains to be developed.

Methods

Least absolute shrinkage and selection operator and support vector machine-recursive feature elimination were used for feature selection. Four machine learning algorithms were used to construct a prediction model, and their performance was compared based on the area under the receiver operating characteristic curve metric in a discovery dataset (n = 760). The model with the best performance was selected and validated in an independent dataset (n = 912) from the Dryad Digital Repository (https://doi.org/10.5061/dryad.m484p). To apply our model to clinical practice, we built a free and user-friendly web online tool.

Results

The predictive model includes the predictors: age, systolic blood pressure, diastolic blood pressure, and body mass index. In the discovery cohort, the gradient boosting-based model outperformed other methods in the elevated arterial stiffness prediction. In the validation cohort, the gradient boosting model showed a good discrimination capacity. A cutoff value of 0.46 for the elevated arterial stiffness risk score in the gradient boosting model resulted in a good specificity (0.813 in the discovery data and 0.761 in the validation data) and sensitivity (0.875 and 0.738, respectively) trade-off points.

Conclusion

The gradient boosting-based prediction system presents a good classification in elevated arterial stiffness prediction. The web online tool makes our gradient boosting-based model easily accessible for further clinical studies and utilization.
Pericytes: Intrinsic Transportation Engineers of the CNS Microcirculation
Authors: Eltanahy Ahmed M. , Koluib Yara A. , Gonzales Albert
Published: August 2021

Pericytes in the brain are candidate regulators of microcirculatory blood flow because they are strategically positioned along the microvasculature, contain contractile proteins, respond rapidly to neuronal activation, and synchronize microvascular dynamics and neurovascular coupling within the capillary network. Analyses of mice with defects in pericyte generation demonstrate that pericytes are necessary for the formation of the blood-brain barrier, development of the glymphatic system, immune homeostasis, and white matter function. The development, identity, specialization, and progeny of different subtypes of pericytes, however, remain unclear. Pericytes perform brain-wide ‘transportation engineering’ functions in the capillary network, instructing, integrating, and coordinating signals within the cellular communicome in the neurovascular unit to efficiently distribute oxygen and nutrients (‘goods and services’) throughout the microvasculature (‘transportation grid’). In this review, we identify emerging challenges in pericyte biology and shed light on potential pericyte-targeted therapeutic strategies.
Genetic Regulation of Vessel Morphology in Populus
Authors: Rodriguez-Zaccaro F. Daniela , Henry Isabelle M. , Groover Andrew
Published: August 2021

During secondary growth, forest trees can modify the anatomy of the wood produced by the vascular cambium in response to environmental conditions. Notably, the trees of the model angiosperm genus, Populus, reduce the risk of cavitation and hydraulic failure under water stress by producing water-conducting vessel elements with narrow lumens, which are more numerous and more interconnected with each other. Here, we determined the genetic architecture of vessel traits affecting hydraulic physiology and resilience to water stress. Vessel traits were measured for clonally replicated genotypes of a unique Populus deltoides x nigra population carrying genomically defined insertions and deletions that create gene dosage variation. We found significant phenotypic variation for all traits measured (mean vessel diameter, height-corrected mean vessel diameter, vessel frequency, height-corrected vessel frequency, vessel grouping index, and mean vessel circularity), and that all traits were under genetic control and showed moderate heritability values, ranging from 0.32 to 0.53. Whole-genome scans of correlations between gene dosage and phenotypic traits identified quantitative trait loci for tree height, mean vessel diameter, height-corrected mean vessel diameter, height-corrected vessel frequency, and vessel grouping index. Our results demonstrate that vessel traits affecting hydraulic physiology are under genetic control, and both pleiotropic and trait-specific quantitative trait loci are found for these traits.
Dietary Habits of Older Adults in Serbia: Findings From the National Health Survey
Authors: Stosovic Dragana , Vasiljevic Nadja , Jovanovic Verica , Cirkovic Andja , Paunovic Katarina , Davidovic Dragana
Published: August 2021

Objectives: Adults aged 65 years and older comprise one fifth of the Serbian population. Many of them have multiple, often diet-related comorbidities. We aimed to investigate their dietary habits by comparing them with younger adults' and to determine the relation of the differing ones to demographic, socioeconomic and health factors.

Methods: We performed a secondary analysis of 2013 Serbian National Health Survey data on 14,082 adults. Binary logistic regression was used to determine dietary habits associated with older age (≥65 years) compared to younger age (18–64 years) and to assess their independent predictors in older adults.

Results: Older adults more often reported everyday breakfast (OR = 2.085, 95%CI = 1.622–2.680) and brown/wholegrain bread consumption (OR = 1.681, 95% CI = 1.537–1.839), while using margarine (OR = 0.578, 95%CI = 0.397–0.839), discretionary salt (sometimes: OR = 0.648, 95%CI = 0.596–0.705, almost always: OR = 0.522, 95%CI = 0.445–0.614) and consuming fish (two or more times a week: OR = 0.465, 95%CI = 0.383–0.566) less frequently than younger adults. This was mainly positively related to urban environment, affluence, higher education and poor health.

Conclusion: Using nationally representative data, we found that older adults reported healthier dietary habits compared to younger adults, which requires timely public health action.
Do Advanced Therapies Have a Future in the Low- and Middle-Income Countries - The Case of Bulgaria, Romania, and Poland
Authors: Kamusheva Maria , Turcu-Stiolica Adina , Gierczyński Jakub , Subtirelu Mihaela-Simona , Czech Marcin , Petrova Guenka
Published: August 2021

Introduction: The significant therapeutic potential of the advanced therapies (ATs) has predetermined the increased interests in their development mainly in the context of rare diseases most of which are genetically determined. However, there are still many challenges in front of the health insurance funds related to the cost-effectiveness and budget impact issues of these therapies. Our aim was to review and analyze the potential of low- and middle-income countries for health technology assessment (HTA) of advanced therapies focusing on Bulgaria, Romania and Poland as reference countries. A literature review of the existing good practices related to HTA of advanced therapies across the world and comparison with the national reality were performed. A list of challenges and issues from the point of view of the payer institution of all analyzed countries was performed. Pilot recommendations on how to overcome the barriers were created based on the existing practices and the potential of the national system.

Discussion: 15 out of 80 articles identified in PubMed were found as applicable to the study scope as most of them were published in the period 2019–2021. Undoubtedly, the main challenges correspond to the high treatment costs, the uncertainty in clinical effectiveness, and poor HTA methodological approaches applicable for ATs worldwide. The issues identified for low and middle-income countries are similar having as well the lack of enough qualified health economists for the purposes of assessment and appraisal of HTA dossiers of the advanced therapies, lack of adequate existing separate financial programs for those therapies, and not preparedness of the health system and the society as a whole for such therapies.

Conclusions: Despite the difficulties and challenges, the advanced therapies can be defined as a futuristic therapy for which great discoveries are yet to come. Therefore, each country should consider the implementation of reliable and nationally oriented programs for HTA and adequate financial coverage of these therapies.
Single-Incision vs. Conventional Laparoscopic Surgery for Colorectal Cancer: An Update of a Systematic Review and Meta-Analysis
Authors: Yuan Ye , Jian Jianing , Jing Hailiang , Yan Ran , You Fengming , Fu Xi , Du Linke , Li Wenyuan
Published: August 2021

Background: Although the advantages of single-incision laparoscopic surgery have been reported in several meta-analyses, the low quality of studies included in the meta-analyses limits the reliability of such a conclusion. In recent years, the number of randomized controlled trials on the efficacy of SILS in colorectal cancer has been on the rise. This update systematic review and meta-analysis of RCTs aims to compare efficacy and safety of SILS and CLS in the patients with colorectal cancer.

Methods: Relevant data was searched on the CNKI, Wanfang, VIP, Sinomed, PubMed, Embase, and Cochrane CENTRAL databases from inception until February 5th, 2021. All RCTs comparing SILS and CLS were included. The main outcomes were 30 days of mortality, postoperative complications, intraoperative complications, whereas secondary outcomes were the number of lymph nodes removed, duration of hospital stay, intraoperative blood loss, abdominal incision length, reoperation, readmission, conversion to laparotomy, operation time and anastomotic leakage.

Results: A total of 10 RCTs were included, involving 1,133 participants. The quality of the included studies was generally high. No significant difference was found between SILS and CLS in the 30 days mortality rate. The results showed that SILS group had a lower rate of postoperative complications (RR = 0.67, 95% CI: 0.49–0.92), higher rate of intraoperative complications (RR = 2.26, 95%CI: 1.00–5.10), shorter length of abdominal incision (MD = −2.01, 95% CI:−2.42–1.61) (cm), longer operation time (MD = 11.90, 95% CI: 5.37–18.43) (minutes), shorter hospital stay (MD = −1.12, 95% CI: −1.89–0.34) (days) compared with CLS group. However, intraoperative blood loss (MD = −8.23, 95% CI: −16.75–0.29) (mL), number of lymph nodes removed (MD = −0.17, 95% CI: −0.79–0.45), conversion to laparotomy (RR=1.31, 95% CI: 0.48–3.60), reoperation (RR = 1.00, 95% CI: 0.30–3.33) and readmission (RR =1.15, 95% CI: 0.12–10.83) and anastomotic leakage were not significantly different between the two groups.

Conclusion: These results indicate that SILS did not has a comprehensive and obvious advantage over the CLS. Surgeons and patients should carefully weigh the pros and cons of the two surgical procedures. Further RCTs are needed to prove long-term outcomes of SILS in colorectal cancer.