bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single-Point Insulin Sensitivity Estimator (SPISE) of 5.4 is a good predictor of both metabolic syndrome and insulin resistance in adolescents with obesity
Authors: Correa-Burrows Paulina , Matamoros Mariela , de Toro Valeria , Zepeda Diego , Arriaza Marta , Burrows Raquel
Published: February 2023

Background

The Single-Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity estimated using BMI and triglycerides and high-density lipoprotein cholesterol. We assessed the accuracy of SPISE to screen obesity-related cardiometabolic risk in children and adolescents.

Method

Cross-sectional validation study for a screening test in a sample of n=725 children and adolescents from an obesity clinic. Weight, height, waist circumference, blood arterial pressure, lipid profile, glucose, insulin and Tanner stage were measured. BMI, BMI for-age-and sex (BAZ), and HOMA-IR were estimated. HOMA-IR values ≥2.1 and ≥3.3 were considered IR in Tanner I-II, ≥3.3 for Tanner III-IV and ≥2.6 for Tanner V, respectively. Metabolic Syndrome (MetS) was diagnosed with the Cook phenotype. SPISE was estimated according to the following algorithm: [600* HDL^0.185/(TG^0.2* BMI^1.338)]. The optimal SPISE cut points for IR and MetS prediction were determined by ROC curve analysis.

Results

In prepubertal obese patients (9.2 ± 2.1y; 18.4% males), the prevalence of IR and MetS was 28.2% y 46.9%, respectively; 58% had severe obesity (BAZ ≥4 SD). In pubertal obese patients (12.6 ± 1.8y; 57% males), the prevalence of IR and MetS was 34.1% and 55.3%, respectively; 34% had severe obesity. In prepubertal children, a SPISE of 6.3 showed the highest sensitivity (73.2%) and specificity (80%) to screen individuals with IR (AUC: 0.80; LR +: 3.3). Likewise, a SPISE of 5.7 got the highest sensitivity (82.6%) and specificity (86.1%) to screen patients with MetS (AUC: 0.87; LR +: 5.4). In pubertal patients, a SPISE of 5.4 showed the highest sensitivity and specificity to screen children and adolescents with both IR (Sn: 76.1%; Sp: 77.5%; AUC: 0.8; LR +: 3.1) and MetS (Sn: 90.4%; Sp: 76.1%; AUC: 0.90; LR +: 3.5).

Conclusion

In children and adolescents with obesity, SPISE has good or very good performance in predicting IR and MetS. SPISE may be considered a relatively simple and low-cost diagnosis tool that can be helpful to identify patients with greater biological risk. In adolescents with obesity, the same cut point allows identification of those at higher risk of both IR and MetS.
Progress of new-onset diabetes after liver and kidney transplantation
Authors: Zhang Zhen , Sun Jianyun , Guo Meng , Yuan Xuemin
Published: February 2023

Organ transplantation is currently the most effective treatment for end-stage organ failure. Post transplantation diabetes mellitus (PTDM) is a severe complication after organ transplantation that seriously affects the short-term and long-term survival of recipients. However, PTDM is often overlooked or poorly managed in its early stage. This article provides an overview of the incidence, and pathogenesis of and risk factors for PTDM, aiming to gain a deeper understanding of PTDM and improve the quality of life of recipients.
Phenotypic and genotypic landscape of PROKR2 in neuroendocrine disorders
Authors: Martinez-Mayer Julian , Perez-Millan Maria Ines
Published: February 2023

Prokineticin receptor 2 (PROKR2) encodes for a G-protein-coupled receptor that can bind PROK1 and PROK2. Mice lacking Prokr2 have been shown to present abnormal olfactory bulb formation as well as defects in GnRH neuron migration. Patients carrying mutations in PROKR2 typically present hypogonadotropic hypogonadism, anosmia/hyposmia or Kallmann Syndrome. More recently variants in PROKR2 have been linked to several other endocrine disorders. In particular, several patients with pituitary disorders have been reported, ranging from mild phenotypes, such as isolated growth hormone deficiency, to more severe ones, such as septo-optic dysplasia. Here we summarize the changing landscape of PROKR2-related disease, the variants reported to date, and discuss their origin, classification and functional assessment.
Multi-time-scale economic scheduling method for electro-hydrogen integrated energy system based on day-ahead long-time-scale and intra-day MPC hierarchical rolling optimization
Authors: Zhang Leiqi , Dai Wuzhen , Zhao Bo , Zhang Xuesong , Liu Min , Wu Qiliang , Chen Jian
Published: February 2023

To build a clean, secure, and efficient energy system, the hydrogen energy is an important developing trend for the energy revolution, and electro-hydrogen coupling system is expected to play an important role in the future. To obtain the optimal economic scheduling of the electro-hydrogen integrated energy system (E-H IES), this paper firstly establishes a refined model of the electrolyzer and hydrogen fuel cell and then proposes an optimal scheduling model based on day-ahead long-time-scale optimization and intra-day model predictive control (MPC) hierarchical rolling optimization. In the day-ahead stage, a long-time-scale optimization considering the impact of multi-day forecast information is proposed when performing the day-ahead optimization to achieve the effect of inter-day energy transfer of hydrogen energy and improve the overall economic efficiency. In addition, during the intra-day stage, the MPC is adopted to implement hierarchical rolling optimization to track and correct the day-ahead schedule and achieve coordinated operation between multi-energy systems while taking into account the different energy transfer characteristics. Finally, the simulation results demonstrate the feasibility of the proposed optimal scheduling model and the effectiveness of the proposed multi-time scale economic scheduling method.
Adsorption of hexavalent chromium from water using graphene oxide/zinc molybdate nanocomposite: Study of kinetics and adsorption isotherms
Authors: K. S. Merija , Rahulan K. Mani , Sujatha R. Annie , Little Flower N. Angeline
Published: February 2023

Hexavalent chromium is one of the most hazardous contaminants that threaten the environment. The present research work involves the synthesis of Graphene Oxide/Zinc molybdate (GO/ZM) nanocomposite by wet chemical route. The structure and morphology of the synthesized samples were analysed by various characterization techniques such as X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), UV-Vis Spectroscopy, and High-Resolution Transmission Electron Microscopy (HR-TEM), Brunauer-Emmett-Teller (BET) surface area analysis, Barrett-Joyner-Halenda (BJH) pore size analysis and Raman Spectroscopy. The efficiency of the prepared samples for removing hexavalent chromium from the water was investigated by performing batch adsorption studies. The maximum adsorption capacity was optimum at using 6 mg adsorbent, under conditions pH 2 with contact time for 120 min and temperature 283 K. Two isotherm models and two kinetic models were used to study the adsorption mechanism of Cr(VI) ions adsorption on the surface of GO/ZM nanocomposite. The results of isotherm and kinetic modelling shows that the adsorption of Cr(VI) using GO/ZM nanocomposite was well described by Freundlich Isotherm model with higher correlation coefficient (R2 = .985) and follows pseudo second order kinetic model.
Knowledge mining for the differentiation pattern with respect to the productivity and trophic status of some selected lakes of Western Himalayas
Authors: Kumar Rakesh , Jindal Rajinder , Kulharia Mahesh , Sharma Amit Kumar , Thakur Kushal , Brar Bhavna , Mahajan Danish , Sharma Ankita , Kumar Sunil , Sharma Dixit
Published: February 2023

The present study deals with an account of the primary productivity and trophic status of Rewalsar, Kuntbhyog, and Prashar lakes of Western Himalayas. Seasonal variations in gross primary productivity (GPP) (g C m–2 day–1), net primary productivity (NPP, respiration (R), and the NPP/R ratio have been studied and compared with hydrobiological factors. Among various factors, temperature, light, nutrients, and chlorophyll a were accountable for high productivity. Nygaard’s trophic state indices were calculated. GPP showed a positive relationship with water temperature, penetration of light, nitrate, and with phosphate. The extensive range of the compound index observed in Rewalsar (12.00–20.00) and Kuntbhyog lakes (12.50–18.00) confirmed their eutrophic nature. Based on the trophic classification of waters and on the basis of productivity, Nygaard’s trophic state indices, and richness of nutrients, Rewalsar and Kuntbhyog lakes could be categorized as eutrophic, whereas Prashar Lake, as oligo-eutrophic. Based on the presence, absence, frequency of appearance, and abundance of different organisms recorded during the present investigation, bioindicators of trophic status have been determined.
Rare immune diseases paving the road for genome editing-based precision medicine
Authors: Pavel-Dinu Mara , Borna Simon , Bacchetta Rosa
Published: February 2023

Clustered regularly interspaced short palindromic repeats (CRISPR) genome editing platform heralds a new era of gene therapy. Innovative treatments for life-threatening monogenic diseases of the blood and immune system are transitioning from semi-random gene addition to precise modification of defective genes. As these therapies enter first-in-human clinical trials, their long-term safety and efficacy will inform the future generation of genome editing-based medicine. Here we discuss the significance of Inborn Errors of Immunity as disease prototypes for establishing and advancing precision medicine. We will review the feasibility of clustered regularly interspaced short palindromic repeats-based genome editing platforms to modify the DNA sequence of primary cells and describe two emerging genome editing approaches to treat RAG2 deficiency, a primary immunodeficiency, and FOXP3 deficiency, a primary immune regulatory disorder.
Integrated bioinformatic analyses investigate macrophage-M1-related biomarkers and tuberculosis therapeutic drugs
Authors: Deng Siqi , Shen Shijie , Liu Keyu , El-Ashram Saeed , Alouffi Abdulaziz , Cenci-Goga Beniamino Terzo , Ye Guomin , Cao Chengzhang , Luo Tingting , Zhang Hui , Li Weimin , Li Siyuan , Zhang Wanjiang , Wu Jiangdong , Chen Chuangfu
Published: February 2023

Tuberculosis (TB) is a common infectious disease linked to host genetics and the innate immune response. It is vital to investigate new molecular mechanisms and efficient biomarkers for Tuberculosis because the pathophysiology of the disease is still unclear, and there aren’t any precise diagnostic tools. This study downloaded three blood datasets from the GEO database, two of which (GSE19435 and 83456) were used to build a weighted gene co-expression network for searching hub genes associated with macrophage M1 by the CIBERSORT and WGCNA algorithms. Furthermore, 994 differentially expressed genes (DEGs) were extracted from healthy and TB samples, four of which were associated with macrophage M1, naming RTP4, CXCL10, CD38, and IFI44. They were confirmed as upregulation in TB samples by external dataset validation (GSE34608) and quantitative real-time PCR analysis (qRT-PCR). CMap was used to predict potential therapeutic compounds for tuberculosis using 300 differentially expressed genes (150 downregulated and 150 upregulated genes), and six small molecules (RWJ-21757, phenamil, benzanthrone, TG-101348, metyrapone, and WT-161) with a higher confidence value were extracted. We used in-depth bioinformatics analysis to investigate significant macrophage M1-related genes and promising anti-Tuberculosis therapeutic compounds. However, more clinical trials were necessary to determine their effect on Tuberculosis.
Diversity and abundance of bacterial and fungal communities in rhizospheric soil from smallholder banana producing agroecosystems in Kenya
Authors: Wahome Caroline N. , Maingi John M. , Ombori Omwoyo , Njeru Ezekiel Mugendi , Muthini Morris , Kimiti Jacinta Malia
Published: February 2023

In agroecosystems, microbial communities play a crucial role in delivery of various ecosystem services. These microbial communities are affected by several factors such as soil physicochemical properties which contribute to the diversity of bacterial and fungal communities. In this study, we investigated the soil physicochemical parameters and the diversity and abundance of bacterial and fungal communities in rhizospheric soil collected from banana growing regions in Kisii, Nyamira and Embu Counties of Kenya. Rhizospheric soil samples from the three regions showed significant differences at (P= 0.01) with the lowest recorded pH being 4.43 in Embu County. Based on Next-generation sequencing results, there was a significant diversity and abundance of bacterial division Proteobacteria while the predominant fungal division was basidiomycota, Several genera in the fungal division such as Penicillium and Cladosporium as well as bacterial genera such as Acidobacterium and Pseudomonas sp. were those associated with soil. There were several plant pathogenic and beneficial bacteria and fungi. Based on redundancy analysis (RDA) the distribution of these microbes was affected negatively by soil parameters such as total organic carbon (TOC) and pH. In conclusion, Soil health and continuous mono-cropping systems play a significant role in the diversity and abundance of both beneficial and harmful soil microbes. Metagenomics approaches in studying microbial communities in agroecosystems is a revolutionary approach which will aid in the development of sustainable tools in agriculture that improve microbiome structures as well as overall productivity.
Grouper cGAS is a negative regulator of STING-mediated interferon response
Authors: Zhang Luhao , Zhang Xin , Liao Jiaming , Xu Linting , Kang Shaozhu , Chen Hong , Sun Mengshi , Wu Siting , Xu Zhuqing , Wei Shina , Qin Qiwei , Wei Jingguang
Published: February 2023

Cyclic GMP-AMP synthase (cGAS) is one of the classical pattern recognition receptors that recognizes mainly intracytoplasmic DNA. cGAS induces type I IFN responses to the cGAS-STING signaling pathway. To investigate the roles of cGAS-STING signaling pathway in grouper, a cGAS homolog (named EccGAS) was cloned and identified from orange-spotted grouper (Epinephelus coioides). The open reading frame (ORF) of EccGAS is 1695 bp, encodes 575 amino acids, and contains a Mab-21 typical structural domain. EccGAS is homologous to Sebastes umbrosus and humans at 71.8% and 41.49%, respectively. EccGAS mRNA is abundant in the blood, skin, and gills. It is uniformly distributed in the cytoplasm and colocalized in the endoplasmic reticulum and mitochondria. Silencing of EccGAS inhibited the replication of Singapore grouper iridovirus (SGIV) in grouper spleen (GS) cells and enhanced the expression of interferon-related factors. Furthermore, EccGAS inhibited EcSTING-mediated interferon response and interacted with EcSTING, EcTAK1, EcTBK1, and EcIRF3. These results suggest that EccGAS may be a negative regulator of the cGAS-STING signaling pathway of fish.
Single-cell RNA-seq revealing the immune features of donor liver during liver transplantation
Authors: Shan Yi , Qi Debin , Zhang Lei , Wu Lixue , Li Wenfang , Liu Hao , Li Tao , Fu Zhiren , Bao Haili , Song Shaohua
Published: February 2023

Immune cells, including T and B cells, are key factors in the success of liver transplantation. And the repertoire of T cells and B cells plays an essential function in mechanism of the immune response associated with organ transplantation. An exploration of their expression and distribution in donor organs could contribute to a better understanding of the altered immune microenvironment in grafts. In this study, using single-cell 5’ RNA sequence and single-cell T cell receptor (TCR)/B cell receptor (BCR) repertoire sequence, we profiled immune cells and TCR/BCR repertoire in three pairs of donor livers pre- and post-transplantation. By annotating different immune cell types, we investigated the functional properties of monocytes/Kupffer cells, T cells and B cells in grafts. Bioinformatic characterization of differentially expressed genes (DEGs) between the transcriptomes of these cell subclusters were performed to explore the role of immune cells in inflammatory response or rejection. In addition, we also observed shifts in TCR/BCR repertoire after transplantation. In conclusion, we profiled the immune cell transcriptomics and TCR/BCR immune repertoire of liver grafts during transplantation, which may offer novel strategies for monitoring recipient immune function and treatment of rejection after liver transplantation.
Distribution and Characteristics of Microplastics in Barnacles and Wild Bivalves on the Coast of the Yellow Sea, China
Authors: Zhang Tao , Song Kexin , Meng Liting , Tang Ruikai , Song Tongtong , Huang Wei , Feng Zhihua
Published: February 2023

Barnacles and bivalves are two well-known sessile invertebrates that play important roles in marine ecosystems. Microplastic (MP) pollution has attracted widespread attention. Barnacles and wild bivalves are smaller than farmed individuals; thus, they may be more sensitive to MPs. However, less is known about the abundance and spatial distribution of MPs in wild bivalves along with the coastal areas of China. This study evaluates MP pollution in the most abundant bivalves and barnacles (Crassostrea gigas, Ostrea cucullata, Mytilus edulis, and Balanus albicostatus) at five stations in the intertidal zone of the Yellow Sea. B. albicostatus was divided into ecotype A and ecotype B. The abundance of MPs in barnacles, wild bivalves barnacles, and wild bivalves varied from 0 to 2.25 items/individual and 0 to 118.21 items/g. O. cucullata and B. albicostatus (ecotype A) had the highest abundance of MPs, with average abundances of 0.56 ± 0.36 items/individual and 21.59 ± 27.26 items/g, respectively. The types of MPs found in bivalves and barnacles include fibers, fragments, films, and microbeads. The most abundant size was less than 1,000 μm, which accounted for 53% of the total MPs. Cellophane (CP), polypropylene (PP), polyethylene (PE), and polyethylene terephthalate (PET) were the main polymer types in bivalves and barnacles. This study suggests that the abundance of MPs in wild bivalves is close to that of farmed bivalves with commercial specifications, despite their smaller size. The MP abundance of barnacles in the Yellow Sea is higher than that in other areas in terms of items per gram. In addition, the ecological type may affect the ability of barnacles to accumulate MPs. Ingestion of MPs by barnacles and wild bivalves should be of concern because they may enter the human body through the food web and may pose a potential threat to human health.
High SARS-CoV-2 Infection Rates Among Special Forces Police Units During the Early Phase of the COVID-19 Pandemic in Ecuador
Authors: Ortiz-Prado Esteban , Andrade Felipe , Vasconez Eduardo , Escobar-Espinosa Cristina , Vallejo-Janeta Alexander Paolo , Freire-Paspuel Byron , Coronel Barbara , Galvis Heberson , Morales-Jadan Diana , Rivera-Olivero Ismar A. , Lozada Tannya , Henriquez-Trujillo Aquiles R. , Garcia-Bereguiain Miguel Angel ,   the UDLA-COVID-19 Team
Published: February 2023

Background

At the beginning of the COVID-19 pandemic, health workers and first-responders, such as police officers, were in charge of trying to contain a disease that was unknown at that time. The lack of information and the tremendous need to contain new outbreaks put police officers at higher risk.

Methodology

A cross-sectional study was conducted to describe SARS-CoV-2 infection rates among Police Special Forces Officers in Quito, Ecuador. In this study, 163 community-dwelling police officers from elite divisions voluntarily participated in our SARS-CoV-2 detection program using reverse transcription quantitative real-time PCR (RT-qPCR).

Results

A total of 20 out of 163 police officers tested positive for SARS-CoV-2, yielding an infection rate of 12.3%. Within this cohort, 10% (2/20) of SARS-CoV-2 positive individuals were potentially super spreaders with viral loads over 108 copies/ul. About 85% of the SARS-CoV-2 positive individuals were asymptomatic and 15% reported mild symptoms related to COVID-19.

Conclusions

We found a high SARS-CoV-2 infection rate within the special forces police officers that, beyond a high health risk for themselves, their families, and coworkers. Our results point out the need for permanent SARS-CoV-2 testing among asymptomatic essential workers and first-responders to avoid local outbreaks and to prevent work-place absenteeism among police special units.
Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC)
Authors: Patterson Bruce K. , Yogendra Ram , Guevara-Coto Jose , Mora-Rodriguez Rodrigo A. , Osgood Eric , Bream John , Parikh Purvi , Kreimer Mark , Jeffers Devon , Rutland Cedric , Kaplan Gary , Zgoda Michael
Published: February 2023

Post-acute sequelae of COVID (PASC), or long COVID, is a multisystem complication of SARS-CoV-2 infection that continues to debilitate millions worldwide thus highlighting the public health importance of identifying effective therapeutics to alleviate this illness. One explanation behind PASC may be attributed to the recent discovery of persistent S1 protein subunit of SARS-CoV-2 in CD16+ monocytes up to 15 months after infection. CD16+ monocytes, which express both CCR5 and fractalkine receptors (CX3CR1), play a role in vascular homeostasis and endothelial immune surveillance. We propose targeting these receptors using the CCR5 antagonist, maraviroc, along with pravastatin, a fractalkine inhibitor, could disrupt the monocytic-endothelial-platelet axis that may be central to the etiology of PASC. Using five validated clinical scales (NYHA, MRC Dyspnea, COMPASS-31, modified Rankin, and Fatigue Severity Score) to measure 18 participants’ response to treatment, we observed significant clinical improvement in 6 to 12 weeks on a combination of maraviroc 300 mg per oral twice a day and pravastatin 10 mg per oral daily. Subjective neurological, autonomic, respiratory, cardiac and fatigue symptoms scores all decreased which correlated with statistically significant decreases in vascular markers sCD40L and VEGF. These findings suggest that by interrupting the monocytic-endothelial-platelet axis, maraviroc and pravastatin may restore the immune dysregulation observed in PASC and could be potential therapeutic options. This sets the framework for a future double-blinded, placebo-controlled randomized trial to further investigate the drug efficacy of maraviroc and pravastatin in treating PASC.
Improvement of antioxidant activity and active ingredient of Dendrobium officinale via microbial fermentation
Authors: Yu Gen , Xie QingFen , Su WenFeng , Dai Shuang , Deng XinYi , Gu QuLiang , Liu Shan , Yun JeonYun , Xiang WenHao , Xiong Yang , Yang GuanDong , Ren Yifei , Li He
Published: February 2023

This study used brewer’s yeast to ferment Dendrobium officinale and single-factor and orthogonal experiments were conducted to determine the optimal fermentation conditions. The antioxidant capacity of Dendrobium fermentation solution was also investigated by in vitro experiments, which showed that different concentrations of fermentation solution could effectively enhance the total antioxidant capacity of cells. The fermentation liquid was found to contain seven sugar compounds including glucose, galactose, rhamnose, arabinose, and xylose using gas chromatography–mass spectrometry (GC–MS) and high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF-MS), with the highest concentrations of glucose and galactose at 194.628 and 103.899 μg/ml, respectively. The external fermentation liquid also contained six flavonoids with apigenin glycosides as the main structure and four phenolic acids including gallic acid, protocatechuic acid, catechol, and sessile pentosidine B.
Gray matter reduction is associated with cognitive dysfunction in depressed patients comorbid with subclinical hypothyroidism
Authors: Zhao Shuai , Du Yishan , Zhang Yu , Wang Xiaoqin , Xia Yi , Sun Hao , Huang Yinghong , Zou Haowen , Wang Xumiao , Chen Zhilu , Zhou Hongliang , Yan Rui , Tang Hao , Lu Qing , Yao Zhijian
Published: February 2023

Introduction

To explore the association between regional gray matter volume (GMV) and cognitive impairments and ascertain whether the regional brain alterations related to cognitive impairments occur in major depressive disorder (MDD) patients with comorbid subclinical hypothyroidism (SHypo).

Methods

We enrolled 32 MDD patients, 32 MDD patients with comorbid SHypo, and 32 normal controls and subjected them to thyroid function tests, neurocognitive tests, and magnetic resonance imaging (MRI). Using voxel-based morphometry (VBM) analysis, we examined the pattern of gray matter (GM) in these participants. We also used ANOVA to detect group differences and partial correlation to explore the potential association between GMV alterations and cognitive tests in comorbid patients.

Results

The comorbid patients exhibited significantly smaller GMV in the right middle frontal gyrus (MFG) than the non-comorbid group. Furthermore, the partial correlation analysis showed that GMV of the right MFG was associated with poor executive function (EF) performance in comorbid patients.

Conclusion

These findings provide valuable insight into the relationship between the alteration of GMV and cognitive dysfunction of MDD patients with comorbid SHypo.
Neural network aided flexible joint optimization with design of experiment method for nuclear power plant inspection robot
Authors: Wang Gang , Li Jiawei , Ma Xinmeng , Chen Xi , Wang Jixin , Han Songjie , Pan Biye , Tian Ruxiao
Published: February 2023

Introduction

The flexible joint is a crucial component for the inspection robot to flexible interaction with nuclear power facilities. This paper proposed a neural network aided flexible joint structure optimization method with the Design of Experiment (DOE) method for the nuclear power plant inspection robot.

Methods

With this method, the joint's dual-spiral flexible coupler was optimized regarding the minimum mean square error of the stiffness. The optimal flexible coupler was demonstrated and tested. The neural network method can be used for the modeling of the parameterized flexible coupler with regard to the geometrical parameters as well as the load on the base of the DOE result.

Results

With the aid of the neural network model of the stiffness, the dual-spiral flexible coupler structure can be fully optimized to a target stiffness, 450 Nm/rad in this case, and a given error level, 0.3% in the current case, with regard to the different loads. The optimal coupler is fabricated with wire electrical discharge machining (EDM) and tested.

Discussion

The experimental results demonstrate that the load and angular displacement keep a good linear relationship in the given load range and this optimization method can be used as an effective method and tool in the joint design process.
Ethnodemographic characterization of stroke incidence and burden of disease in hospital discharge records in Ecuador
Authors: Carrington Sarah J. , Romero-Alvarez Daniel , Coral-Almeida Marco , Vela Andrea , Henríquez-Trujillo Aquiles Rodrigo , Mascialino Guido
Published: February 2023

Introduction

Stroke is the second most common cause of death and disability-adjusted life years (DALYs) globally. However, the incidence and impact of stroke by ethnicity and gender is frequently distinct. This is particularly the case in Ecuador where geographic and economic marginalization are often correlated with ethnic marginalization and the extent to which females lack the same opportunities as their male counterparts. The aim of this paper is to investigate the differential impacts in terms of stroke diagnosis and burden of disease by ethnicity and gender, using hospital discharge records over the years 2015–2020.

Methods

This paper calculates stroke incidence, and fatality rates using hospital discharge and death records over the years 2015–2020. The DALY package in R was employed to calculate the Disability Adjusted Life Years lost due to stroke in Ecuador.

Results

The results show that while the incidence rate of stroke in males (64.96 per 100,000 persons-year) is higher than that for females on average (57.84 per 100,000 persons-year), males accounted for 52.41% of all stroke cases and 53% of all surviving cases. Thus, hospital data suggests that females had a higher death rate when compared to males. Case fatality rates also differed significantly by ethnicity. The highest fatality rate corresponded to the Montubio ethnic group (87.65%), followed by Afrodescendants (67.21%). The estimated burden of disease of stroke calculated using Ecuadorian hospital records (2015–2020) varied from 1,468 to 2,991 DALY per 1,000 population on average.

Discussion

Differences in the burden of disease by ethnic group are likely to reflect differential access to care by region and socio-economic group, both of which are frequently correlated with ethnic composition in Ecuador. Equitable access to health services remains an important challenge in the country. The gender discrepancy in fatality rates suggests that there is a need for targeted educational campaigns to identify stroke signs early, especially in the female population.
Combination of platelet-to-lymphocyte ratio and D-dimer for the identification of cardiogenic cerebral embolism in non-valvular atrial fibrillation
Authors: Shi Yachen , Xuan Chenhao , Ji Wei , Wang Feng , Huang Jin , Li Lei , Wang Hui , Deng Jingyu , Shao Junfei , Chen Kefei , Mao Xuqiang , Xu Qinghua , You Yiping , Xi Guangjun
Published: February 2023

Background

Non-valvular atrial fibrillation (NVAF) is the most common cause of cardiogenic cerebral embolism (CCE). However, the underlying mechanism between cerebral embolism and NVAF is indefinite, and there is no effective and convenient biomarker to identify potential risk of CCE in patients with NVAF in clinic. The present study aims to identify risk factors for interpreting the potential association of CCE with NVAF and providing valuable biomarkers to predict the risk of CCE for NVAF patients.

Methods

641 NVAF patients diagnosed with CCE and 284 NVAF patients without any history of stroke were recruited in the present study. Clinical data including demographic characteristics, medical history, and clinical assessments, were recorded. Meanwhile, Blood cell counts, lipid profiles, high-sensitivity C-reactive protein, and coagulation function-related indicators were measured. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to build a composite indicator model based on the blood risk factors.

Results

(1) CCE patients had significantly increased neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and D-dimer levels as compared with patients in the NVAF group, and these three indicators can distinguish CCE patients from ones in the NVAF group with an area under the curve (AUC) value of over 0.750, respectively. (2) Using the LASSO model, a composite indicator, i.e., the risk score, was determined based on PLR and D-dimer and displayed differential power for distinguishing CCE patients from NVAF patients with an AUC value of over 0.934. (3) The risk score was positively correlated with the National Institutes of Health Stroke Scale and CHADS2 scores in CCE patients. (4) There was a significant association between the change value of the risk score and the recurrence time of stroke in initial CCE patients.

Conclusions

The PLR and D-dimer represent an aggravated process of inflammation and thrombosis in the occurrence of CCE after NVAF. The combination of these two risk factors can contribute to identifying the risk of CCE for patients with NVAF with an accuracy of 93.4%, and the greater in change of composite indicator, the shorter in the recurrence of CCE for NVAF patients.
Neuropathic pain experience in symptomatic and presymptomatic subjects carrying a transthyretin gene mutation
Authors: Tozza Stefano , Luigetti Marco , Antonini Giovanni , Mazzeo Anna , Severi Daniele , Di Paolantonio Andrea , Leonardi Luca , Russo Massimo , Romano Angela , Forcina Francesca , Gentile Luca , Nolano Maria , Mattia Consalvo , Manganelli Fiore
Published: February 2023

Introduction

Pain is a common symptom of hereditary transthyretin amyloidosis (ATTRv), however, its occurrence in late-onset ATTRv has not been investigated thoroughly. Our aim was to describe the pain experience and its impact on quality of life (QoL) in symptomatic patients and presymptomatic carriers harboring a transthyretin (TTR) gene mutation with a late-onset phenotype.

Materials and methods

Study participants (aged ≥18 years) were consecutively recruited from four Italian centers. Clinical disability was assessed using the Familial Amyloid Polyneuropathy (FAP) stage and Neuropathy Impairment Score (NIS). The Norfolk questionnaire evaluated QoL and the Compound Autonomic Dysfunction Test assessed autonomic involvement. Neuropathic pain was screened using the Douleur Neuropathique 4 (DN4) questionnaire, and pain intensity and its impact on daily activity were assessed using the Brief Pain Inventory severity and interference subscores. Data on the type of TTR mutation, presence of cardiomyopathy, treatment, and Body Mass Index (BMI) were collected.

Results

Overall, 102 subjects with TTR mutations (mean age ± SD 63.6 ± 13.5 years) were recruited, including 78 symptomatic patients (68.1 ± 10.9 years) and 24 presymptomatic carriers (49 ± 10.3 years). Pain was reported by 75.5% of all subjects, but was more frequent in symptomatic patients than in presymptomatic carriers (85.9 vs. 41.6%, respectively). Pain exhibited neuropathic features (DN4≥4) in 69.2% of symptomatic patients and in 8.3% of presymptomatic carriers. Subjects with neuropathic pain were older (p = 0.015) had worse FAP stage (p < 0.001), higher NIS scores (p < 0.001), greater autonomic involvement (p = 0.003), and a lower QoL (p < 0.001) than those without neuropathic pain. Neuropathic pain was associated with higher pain severity (p < 0.001) and had a significant negative impact on daily activities (p < 0.001) Neuropathic pain was not associated with gender, mutation type, TTR therapy, or BMI.

Conclusion

Approximately 70% of late-onset ATTRv patients complained of neuropathic pain (DN4≥4) that worsened as peripheral neuropathy progressed and increasingly interfered with daily activities and QoL. Notably, 8% of presymptomatic carriers complained of neuropathic pain. These results suggest that assessment of neuropathic pain may be useful to monitor disease progression and identify early manifestations of ATTRv.
Effects of traditional Chinese medicine combined with modern rehabilitation therapies on motor function in children with cerebral palsy: A systematic review and meta-analysis
Authors: Chen Zhengquan , Huang Zefan , Li Xin , Deng Weiwei , Gao Miao , Jin Mengdie , Zhou Xuan , Du Qing
Published: February 2023

Objective

Traditional Chinese Medicine (TCM) has considerable experience in the treatment of cerebral palsy (CP), but little evidence shows the effect of a combination of TCM and modern rehabilitation therapies on CP. This systematic review aims to evaluate the effect of integrated TCM and modern rehabilitation therapies on motor development in children with CP.

Methods

We systematically searched five databases up to June 2022, including PubMed, the Cumulative Index to Nursing and Allied Health, Cochrane Library, Embase, and Web of Science. Gross motor function measure (GMFM) and Peabody Development Motor Scales-II were the primary outcomes to evaluate motor development. Secondary outcomes included the joint range of motion, the Modified Ashworth scale (MAS), the Berg balance scale, and Activities of Daily living (ADL). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were used to determine intergroup differences.

Results

A total of 2,211 participants from 22 trials were enrolled in this study. Among these, one study was at a low risk of bias and seven studies showed a high risk of bias. Significant improvements were found in GMFM-66 (WMD 9.33; 95% CI 0.14–18.52, P < 0.05, I2 = 92.1%), GMFM-88 (WMD 8.24; 95% CI 3.25–13.24, P < 0.01, I2 = 0.0%), Berg balance scale (WMD 4.42; 95% CI 1.21–7.63, P < 0.01, I2 = 96.7%), and ADL (WMD 3.78; 95% CI 2.12–5.43, P < 0.01, I2 = 58.8%). No adverse events were reported during the TCM intervention in the included studies. The quality of evidence was high to low.

Conclusion

Integrated TCM and modern rehabilitation therapies may be an effective and safe intervention protocol to improve gross motor function, muscle tone, and the functional independence of children with CP. However, our results should be interpreted carefully because of the heterogeneity between the included studies.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022345470.
Spatiotemporal profile of altered neural reactivity to food images in obesity: Reward system is altered automatically and predicts efficacy of weight loss intervention
Authors: Poghosyan Vahe , Ioannou Stephanos , Al-Amri Khalid M. , Al-Mashhadi Sufana A. , Al-Mohammed Fedaa , Al-Otaibi Tahani , Al-Saeed Wjoud
Published: February 2023

Introduction

Obesity presents a significant public health problem. Brain plays a central role in etiology and maintenance of obesity. Prior neuroimaging studies have found that individuals with obesity exhibit altered neural responses to images of food within the brain reward system and related brain networks. However, little is known about the dynamics of these neural responses or their relationship to later weight change. In particular, it is unknown if in obesity, the altered reward response to food images emerges early and automatically, or later, in the controlled stage of processing. It also remains unclear if the pretreatment reward system reactivity to food images is predictive of subsequent weight loss intervention outcome.

Methods

In this study, we presented high-calorie and low-calorie food, and nonfood images to individuals with obesity, who were then prescribed lifestyle changes, and matched normal-weight controls, and examined neural reactivity using magnetoencephalography (MEG). We performed whole-brain analysis to explore and characterize large-scale dynamics of brain systems affected in obesity, and tested two specific hypotheses: (1) in obese individuals, the altered reward system reactivity to food images occurs early and automatically, and (2) pretreatment reward system reactivity predicts the outcome of lifestyle weight loss intervention, with reduced activity associated with successful weight loss.

Results

We identified a distributed set of brain regions and their precise temporal dynamics that showed altered response patterns in obesity. Specifically, we found reduced neural reactivity to food images in brain networks of reward and cognitive control, and elevated reactivity in regions of attentional control and visual processing. The hypoactivity in reward system emerged early, in the automatic stage of processing (< 150 ms post-stimulus). Reduced reward and attention responsivity, and elevated neural cognitive control were predictive of weight loss after six months in treatment.

Discussion

In summary, we have identified, for the first time with high temporal resolution, the large-scale dynamics of brain reactivity to food images in obese versus normal-weight individuals, and have confirmed both our hypotheses. These findings have important implications for our understanding of neurocognition and eating behavior in obesity, and can facilitate development of novel integrated treatment strategies, including tailored cognitive-behavioral and pharmacological therapies.
A developmental approach to diversifying neuroscience through effective mentorship practices: perspectives on cross-identity mentorship and a critical call to action
Authors: Hill-Jarrett Tanisha G. , Ng Rowena , Cardenas-Iniguez Carlos , Akinsanya Jemima , Blanco Ismary , Borland Johnathan M. , Brown James S. , Clemons Tameka , Cushnie Adriana K. , Garcia Jacqueline , George Brianna , Hassinan Cera W. , Hines Timothy J. , Landayan Dan , McCorkle Taylor A. , Meckel Katherine R. , Metcalfe Mariajose , Montoya Samantha A. , Rose Deborah K. , Warren Desmond R.
Published: February 2023

Many early-career neuroscientists with diverse identities may not have mentors who are more advanced in the neuroscience pipeline and have a congruent identity due to historic biases, laws, and policies impacting access to education. Cross-identity mentoring relationships pose challenges and power imbalances that impact the retention of diverse early career neuroscientists, but also hold the potential for a mutually enriching and collaborative relationship that fosters the mentee’s success. Additionally, the barriers faced by diverse mentees and their mentorship needs may evolve with career progression and require developmental considerations. This article provides perspectives on factors that impact cross-identity mentorship from individuals participating in Diversifying the Community of Neuroscience (CNS)—a longitudinal, National Institute of Neurological Disorders and Stroke (NINDS) R25 neuroscience mentorship program developed to increase diversity in the neurosciences. Participants in Diversifying CNS were comprised of 14 graduate students, postdoctoral fellows, and early career faculty who completed an online qualitative survey on cross-identity mentorship practices that impact their experience in neuroscience fields. Qualitative survey data were analyzed using inductive thematic analysis and resulted in four themes across career levels: (1) approach to mentorship and interpersonal dynamics, (2) allyship and management of power imbalance, (3) academic sponsorship, and (4) institutional barriers impacting navigation of academia. These themes, along with identified mentorship needs by developmental stage, provide insights mentors can use to better support the success of their mentees with diverse intersectional identities. As highlighted in our discussion, a mentor’s awareness of systemic barriers along with active allyship are foundational for their role.
Neural mechanism underlies CYLD modulation of morphology and synaptic function of medium spiny neurons in dorsolateral striatum
Authors: Tan Shu-yi , Jiang Jin-xiang , Huang Hui-xian , Mo Xiu-ping , Feng Jing-ru , Chen Yu , Yang Li , Long Cheng
Published: February 2023

Although the deubiquitinase cylindromatosis (CYLD), an abundant protein in the postsynaptic density fraction, plays a crucial role in mediating the synaptic activity of the striatum, the precise molecular mechanism remains largely unclear. Here, using a Cyld-knockout mouse model, we demonstrate that CYLD regulates dorsolateral striatum (DLS) neuronal morphology, firing activity, excitatory synaptic transmission, and plasticity of striatal medium spiny neurons via, likely, interaction with glutamate receptor 1 (GluA1) and glutamate receptor 2 (GluA2), two key subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). CYLD deficiency reduces levels of GluA1 and GluA2 surface protein and increases K63-linked ubiquitination, resulting in functional impairments both in AMPAR-mediated excitatory postsynaptic currents and in AMPAR-dependent long-term depression. The results demonstrate a functional association of CYLD with AMPAR activity, which strengthens our understanding of the role of CYLD in striatal neuronal activity.
The association of vitamin D status with oxidative stress biomarkers and matrix metalloproteinases in patients with knee osteoarthritis
Authors: Amirkhizi Farshad , Ghoreishy Seyed Mojtaba , Baker Emma , Hamedi-Shahraki Soudabeh , Asghari Somayyeh
Published: February 2023

Objective

The association of vitamin D status with osteoarthritis (OA) has been demonstrated previously. The current study was performed to examine the association of vitamin D status with oxidative stress markers and matrix metalloproteinases (MMPs) in patients with knee OA.

Methods

This case–control study was conducted on 124 subjects with mild to moderate knee OA and 65 healthy controls. Demographic data was collected from all participants at baseline. Serum levels of vitamin D as well as markers of oxidative stress including malondialdehyde (MDA), total oxidant status (TOS), superoxide dismutase (SOD), oxidative stress index (OSI), paraoxonase-1 (PON-1), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC) were evaluated for each participant. Furthermore, serum concentrations of MMP-1, MMP-3, MMP-13, and cartilage oligomeric matrix protein (COMP) were measured.

Results

The results of the present study indicated that individuals with vitamin D insufficiency had higher levels of MDA, TOS, SOD, and OSI as well as lower levels of PON-1 and TAC. Based on the linear regression analysis, serum vitamin D levels were inversely correlated with MDA, TOS, SOD, OSI, MMP-1, and MMP-13 and positively associated with TAC levels (p < 0.0001). Patients with sufficient vitamin D levels had lower MMP-1 and MMP-13 levels compared to patients with vitamin D insufficiency (p < 0.001 and p < 0.001, respectively).

Conclusion

Findings from this study showed a strong association between vitamin D deficiency and increased oxidative stress and MMPs activity in patients with knee OA.
Deep learning-based morphological feature analysis and the prognostic association study in colon adenocarcinoma histopathological images
Authors: Xiao Xiao , Wang Zuoheng , Kong Yan , Lu Hui
Published: February 2023

Colorectal cancer (CRC) is now the third most common malignancy to cause mortality worldwide, and its prognosis is of great importance. Recent CRC prognostic prediction studies mainly focused on biomarkers, radiometric images, and end-to-end deep learning methods, while only a few works paid attention to exploring the relationship between the quantitative morphological features of patients' tissue slides and their prognosis. However, existing few works in this area suffered from the drawback of choosing the cells randomly from the whole slides, which contain the non-tumor region that lakes information about prognosis. In addition, the existing works, which tried to demonstrate their biological interpretability using patients' transcriptome data, failed to show the biological meaning closely related to cancer. In this study, we proposed and evaluated a prognostic model using morphological features of cells in the tumor region. The features were first extracted by the software CellProfiler from the tumor region selected by Eff-Unet deep learning model. Features from different regions were then averaged for each patient as their representative, and the Lasso-Cox model was used to select the prognosis-related features. The prognostic prediction model was at last constructed using the selected prognosis-related features and was evaluated through KM estimate and cross-validation. In terms of biological meaning, Gene Ontology (GO) enrichment analysis of the expressed genes that correlated with the prognostically significant features was performed to show the biological interpretability of our model.With the help of tumor segmentation, our model achieved better statistical significance and better biological interpretability compared to the results without tumor segmentation. Statistically, the Kaplan Meier (KM) estimate of our model showed that the model using features in the tumor region has a higher C-index, a lower p-value, and a better performance on cross-validation than the model without tumor segmentation. In addition, revealing the pathway of the immune escape and the spread of the tumor, the model with tumor segmentation demonstrated a biological meaning much more related to cancer immunobiology than the model without tumor segmentation. Our prognostic prediction model using quantitive morphological features from tumor regions was almost as good as the TNM tumor staging system as they had a close C-index, and our model can be combined with the TNM tumor stage system to make a better prognostic prediction. And to the best of our knowledge, the biological mechanisms in our study were the most relevant to the immune mechanism of cancer compared to the previous studies.