bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing GPCR Dimerization Using Peptides
Authors: Farooq Zara , Howell Lesley A. , McCormick Peter J.
Published: July 2022

G protein-coupled receptors (GPCRs) are the largest class of membrane proteins and the most common and extensively studied pharmacological target. Numerous studies over the last decade have confirmed that GPCRs do not only exist and function in their monomeric form but in fact, have the ability to form dimers or higher order oligomers with other GPCRs, as well as other classes of receptors. GPCR oligomers have become increasingly attractive to investigate as they have the ability to modulate the pharmacological responses of the receptors which in turn, could have important functional roles in diseases, such as cancer and several neurological & neuropsychiatric disorders. Despite the growing evidence in the field of GPCR oligomerisation, the lack of structural information, as well as targeting the ‘undruggable’ protein-protein interactions (PPIs) involved in these complexes, has presented difficulties. Outside the field of GPCRs, targeting PPIs has been widely studied, with a variety of techniques being investigated; from small-molecule inhibitors to disrupting peptides. In this review, we will demonstrate several physiologically relevant GPCR dimers and discuss an array of strategies and techniques that can be employed when targeting these complexes, as well as provide ideas for future development.
Plasma Levels of Neudesin and Glucose Metabolism in Obese and Overweight Children
Authors: Vergani Edoardo , Bruno Carmine , Cipolla Clelia , Currò Diego , Mancini Antonio
Published: July 2022

Childhood overweight and obesity are among the major health problems of modern times, especially in Western countries, due to their association with increased cardiovascular and cancer risk in adulthood. Neudesin, a recently discovered peptide secreted mainly in the brain and adipose tissue, is being investigated for its possible activity as a negative regulator of energy expenditure. We conducted a cross-sectional observational preliminary study with the aim of testing the hypothesis that plasma levels of neudesin can be modified in obese and overweight children and to evaluate any possible relationship between plasma neudesin levels and metabolic and anthropometric parameters. 34 Children (Tanner’s stage 1) were included and divided in two groups according to Cole’s criteria. Group A included obese and overweight children (23 patients, 17 females and 6 males, aged 4-10 years); Group B included healthy normal-weight children (11 subjects, 7 females and 4 males, aged 3-10 years). Metabolic (glucose and insulin, total, LDL- and HDL-cholesterol, triglycerides, uric acid) and hormonal (fT3, fT4, TSH, IGF-1, leptin) parameters were evaluated. HOMA-IR and QUICKI index and the area under the curve (AUC) of glucose and insulin after oral glucose load were calculated in obese and overweight children. Neudesin was measured by ELISA. Neudesin levels were significantly higher in obese/overweight children than in controls. In obese and overweight children, plasma neudesin levels were significantly directly correlated with blood glucose and glucose AUC. Taken together, these results, although preliminary, may suggest a possible age-related role of neudesin in glucose homeostasis in obese/overweight children.
Nomogram Prediction for the Risk of Diabetic Foot in Patients With Type 2 Diabetes Mellitus
Authors: Wang Jie , Xue Tong , Li Haopeng , Guo Shuai
Published: July 2022

Aims

To develop and validate a nomogram prediction model for the risk of diabetic foot in patients with type 2 diabetes mellitus (T2DM) and evaluate its clinical application value.

Methods

We retrospectively collected clinical data from 1,950 patients with T2DM from the Second Affiliated Hospital of Xi’an Jiaotong University between January 2012 and June 2021. The patients were divided into training cohort and validation cohort according to the random number table method at a ratio of 7:3. The independent risk factors for diabetic foot among patients with T2DM were identified by multivariate logistic regression analysis. Then, a nomogram prediction model was developed using the independent risk factors. The model performances were evaluated by the area under the receiver operating characteristic curve (AUC), calibration plot, Hosmer–Lemeshow test, and the decision curve analysis (DCA).

Results

Multivariate logistic regression analysis indicated that age, hemoglobin A1c (HbA1c), low-density lipoprotein (LDL), total cholesterol (TC), smoke, and drink were independent risk factors for diabetic foot among patients with T2DM (P < 0.05). The AUCs of training cohort and validation cohort were 0.806 (95% CI: 0.775∼0.837) and 0.857 (95% CI: 0.814∼0.899), respectively, suggesting good discrimination of the model. Calibration curves of training cohort and validation cohort showed a favorable consistency between the predicted probability and the actual probability. In addition, the P values of Hosmer–Lemeshow test for training cohort and validation cohort were 0.826 and 0.480, respectively, suggesting a high calibration of the model. When the threshold probability was set as 11.6% in the DCA curve, the clinical net benefits of training cohort and validation cohort were 58% and 65%, respectively, indicating good clinical usefulness of the model.

Conclusion

We developed and validated a user-friendly nomogram prediction model for the risk of diabetic foot in patients with T2DM. Nomograms may help clinicians early screen and identify patients at high risk of diabetic foot.
FGF21 Is Released During Increased Lipogenesis State Following Rapid-Onset Radioiodine-Induced Hypothyroidism
Authors: Szczepańska Ewa , Glinicki Piotr , Zgliczyński Wojciech , Słowińska-Srzednicka Jadwiga , Jastrzębska Helena , Gietka-Czernel Małgorzata
Published: July 2022

Background

FGF21 pharmacological treatment reverses fatty liver and lowers serum triglyceride concentration but FGF21 serum level is increased in hepatic steatosis. FGF21 secretion is induced by thyroid hormones in vitro.

Purpose

To determine the influence of thyroid hormones and metabolic changes secondary to thyroid dysfunction on FGF21 secretion in humans.

Materials and Methods

This was a case-control study. 82 hyperthyroid and 15 hypothyroid patients were recruited together with 25 healthy controls. Of those with hyperthyroidism, 56 received radioiodine treatment and 42 of them achieved hypothyroidism and then euthyroidism within one year following therapy. Radioiodine-induced hypothyroidism developed abruptly within a six week interval between clinic visits. FGF21 serum levels were determined with an ELISA method.

Results

Serum FGF21 levels did not differ in hyper- and hypothyroid patients in comparison to controls [median 103.25 (interquartile range, 60.90-189.48) and 86.10 (54.05-251.02) vs 85.20 (58.00-116.80) pg/mL P=0.200 and 0.503, respectively]. In hyperthyroid patients treated with radioiodine, serum FGF21 levels increased significantly in rapid-onset hypothyroidism in comparison to the hyperthyroid and euthyroid phase [median 160.55 (interquartile range, 92.48 - 259.35) vs 119.55 (67.78-192.32) and 104.43 (55.93-231.93) pg/mL, P=0.034 and 0.033, respectively]. The rising serum FGF21 level correlated positively with serum triglycerides (Spearman coefficient rs=0.36, P=0.017) and inversely with serum SHBG (rs=-0.41, P=0.007), but did not correlate with thyroid hormone levels.

Conclusions

There was a transient increase in FGF21 serum level during rapid-onset hypothyroidism following radioiodine treatment. There was no association between FGF21 serum level and thyroid hormones. In radioiodine-induced hypothyroidism, the rising serum FGF21 concentration correlated positively with rising serum triglycerides and negatively with falling SHBG, reflecting increased hepatic lipogenesis.
Robust Load Frequency Control of Hybrid Solar Power Systems Using Optimization Techniques
Authors: Mahboob Ul Hassan Syed , Ramli Makbul A. M. , Milyani Ahmad H.
Published: July 2022

It is necessary to predict solar photovoltaic (PV) output and load profile to guarantee the security, stability, and reliability of hybrid solar power systems. Severe frequency fluctuations in hybrid solar systems are expected due to the intermittent nature of the solar photovoltaic (PV) output and the unexpected variation in load. This paper proposes designing a PID controller along with the integration of a battery energy storage system (BESS) and plug-in hybrid electric vehicle (PHEV) for frequency damping in the hybrid solar power system. The solar PV output is predicted with high accuracy using artificial neural networks (ANN) given that solar irradiance and cell temperature are inputs to the model. The variation in load is also forecasted considering the factors affecting the load using ANN. Optimum values of the PID controller have been found using genetic algorithm, particle swarm optimization, artificial bee colony, and firefly algorithm considering integral absolute error (IAE), integral square error (ISE), and integral time absolute error (ITAE) objective functions. IAE, ISE, ITAE, Rise time, settling time, peak overshoot and maximum frequency deviation have been measured for comparison and effectiveness. The transient behavior has been further improved by utilizing the power from BESS/PHEV to the power system. The results demonstrate the efficacy of the suggested design for frequency control using the genetic algorithm method along with ISE objective function compared with those obtained from the conventional, particle swarm optimization, artificial bee colony, and firefly algorithm techniques.
Performance Verification of Bayesian Network–Based Security Risk Management and Control System for Power Trading Institutions
Authors: Kong Shuqin , Tian Lin , Sheng Jiansheng , Lu En , Luo Jingqing , Xu Yun
Published: July 2022

Risk in power trading is unavoidable for various reasons. The impact of this risk would vary based on the trading characteristics that mainly depend on the market design and power purchase agreements. So, a security risk management and control system for power trading institutions based on a Bayesian network is designed to reduce the risk of power trading projects. As a part of the network, we first provided the overall architecture of the risk management and control system, which includes a malicious network behaviour detection module, controller selection module, data transmission module, and management and control result visualisation module. Second, the hardware test design was implemented by analysing each module’s working principle and function. Based on the hardware design of the system, the regression analysis method is used to evaluate the risk of power transactions, followed by market fluctuation prediction to obtain the prediction result induced risks. The relationship between security risks and risk-influencing factors is analysed using the Bayesian network. The initial list of risks is established, the uncertain risk factors are reasoned, and the security risk management and control model of power trading institutions is tested to achieve the goal of risk management and control. The experimental results show that this method’s risk management and control efficiency are high. At the same time, this method effectively realised comprehensive risk identification by reducing the loss to power enterprises and has near-practical application value.
Spatio-Temporal Convolutional Network Based Identification of Voltage-Coupling Commutation Failures in Multi-Infeed HVDC Systems
Authors: Wang Xiaohui , Lin Renmao , Song Kaige , Han Jiyao
Published: July 2022

Cascading commutation failures (CFs) pose severe risks in multi-infeed high voltage direct current (HVDC) systems. Different from the single or concurrent CF, not only the time-relevance of signals but also the spatio coupling and even control correlation of HVDCs will attribute to the cascading CFs. The conventional approaches to identify them tend to fall into a dilemma due to their complicated dynamics, wide-area coupling and vague threshold of judgement. In this paper, a deep-learning method based on the data-driven idea is proposed to recognize the cascading CFs. It analyzes the crucial factors leading to the cascading relationship of multiple HVDCs, while classifying them into time and space signals. To extract the inherent correlation between HVDCs as well as the time relevance in question, a spatio-temporal convolutional network (STCN) is formulated. The data generated in case of faults with diverse severity are applied to train STCN. Finally, the proposed framework and STCN method are validated by a customized IEEE 39 bus system and a practical power grid.
Strength and Energy Evolution Law of Deep-Buried Granite Under Triaxial Conditions
Authors: Guo Guangtao , Xu Dingping , Feng Guangliang , Wu Xiaogang , Zhou Yuxin
Published: July 2022

With the increasing global demand for clean and renewable energy sources, many underground hydropower caverns are built in deep mountain valleys in high-stress regions. The evolution of the mechanical properties of the surrounding rock of underground caverns under high-stress excavation requires urgent investigation. According to the deep-buried granite in the underground caverns of the Shuangjiangkou hydropower station, triaxial tests under confining pressures of 10, 30, 40, and 50 MPa were conducted by the MTS815 rock mechanics test system. Based on the stress–strain curve, the evolution law of the strength parameters of rock samples with the crack volume strain and energy with the energy consumption ratio under different confining pressures was analyzed. Our results showed that the stress–strain curve of the sample is divided into five stages with four characteristic points: the closed point, initiation point, volume expansion point, and peak point. The strength of each stage increases with an increase in the confining pressure. In addition, the failure of this granite is characterized by apparent shear failure. The internal friction angle and the cohesion increase rapidly with the increase in the crack volume strain, and they gradually tend to be constant. Furthermore, the confining pressure profoundly influences energy evolution during the loading in the stable and unstable crack growth stages. In these stages, total energy, dissipated energy, and elastic strain energy increase with an increase in the confining pressure. Finally, the energy consumption ratio can represent the preliminary criterion of rock failure in terms of energy. With the increase in the confining pressure, the energy consumption ratio of rock samples gradually increases to approximately 1.0 at the peak stress point. The research results can provide a reference for the instability prediction of surrounding rock masses of high-stress underground caverns.
Floral and Bird Excreta Semiochemicals Attract Western Carpenter Ants
Authors: Renyard Asim , Gries Regine , Cooper Stephanie L. , Gooding Claire E. , Breen Jenelle C. , Alamsetti Santosh Kumar , Munoz Ashley , Gries Gerhard
Published: July 2022

Ant colonies have vast and diverse nutritional needs but forager ants have limited mobility to meet these needs. Forager ants would accrue significant energy savings if they were able to sense and orient toward odor plumes of both carbohydrate and protein food sources. Moreover, if worker ants, like other flightless insects, had reduced olfactory acuity, they would not recognize the specific odor signatures of diverse carbohydrate and protein sources, but they may be able to orient toward those odorants that are shared between (macronutrient) food sources. Using the Western carpenter ant, Camponotus modoc, as a model species, we tested the hypotheses that (1) food sources rich in carbohydrates (aphid honeydew, floral nectar) and rich in proteins (bird excreta, house mouse carrion, cow liver infested or not with fly maggots) all prompt long-distance, anemotactic attraction of worker ants, and (2) attraction of ants to plant inflorescences (fireweed, Chamaenerion angustifolium; thimbleberry, Rubus parviflorus; and hardhack, Spiraea douglasii) is mediated by shared floral odorants. In moving-air Y-tube olfactometer bioassays, ants were attracted to two of four carbohydrate sources (thimbleberry and fireweed), and one of four protein sources (bird excreta). Headspace volatiles of these three attractive sources were analyzed by gas chromatography-mass spectrometry, and synthetic odor blends of thimbleberry (7 components), fireweed (23 components), and bird excreta (38 components) were prepared. In Y-tube olfactometer bioassays, synthetic blends of thimbleberry and fireweed but not of bird excreta attracted ants, indicating that only the two floral blends contained all essential attractants. A blend of components shared between thimbleberry and fireweed was not attractive to ants. Our data support the conclusion that C. modoc worker ants can sense and orient toward both carbohydrate and protein food sources. As ants were selective in their responses to carbohydrate and protein resources, it seems that they can discern between specific food odor profiles and that they have good, rather than poor, olfactory acuity.
Multiple Machine Learning Methods Reveal Key Biomarkers of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment
Authors: Zhu Jie , Sanford Larry D. , Ren Rong , Zhang Ye , Tang Xiangdong
Published: July 2022

Obstructive sleep apnea (OSA) is a worldwide health issue that affects more than 400 million people. Given the limitations inherent in the current conventional diagnosis of OSA based on symptoms report, novel diagnostic approaches are required to complement existing techniques. Recent advances in gene sequencing technology have made it possible to identify a greater number of genes linked to OSA. We identified key genes in OSA and CPAP treatment by screening differentially expressed genes (DEGs) using the Gene Expression Omnibus (GEO) database and employing machine learning algorithms. None of these genes had previously been implicated in OSA. Moreover, a new diagnostic model of OSA was developed, and its diagnostic accuracy was verified in independent datasets. By performing Single Sample Gene Set Enrichment Analysis (ssGSEA) and Counting Relative Subsets of RNA Transcripts (CIBERSORT), we identified possible immunologic mechanisms, which led us to conclude that patients with high OSA risk tend to have elevated inflammation levels that can be brought down by CPAP treatment.
Case Report: Pathogenesis With a Rare RHOA A161E Mutation in a Patient With Angioimmunoblastic T-Cell Lymphoma
Authors: Cao Lihong , Tong Hongyan , Liu Xing , Xu Yingqing , Yu Fang , Pan Qi , Lai Jin , Huang Jian , Qin Jiayue , Jin Jie
Published: July 2022

Angioimmunoblastic T-cell lymphoma (AITL) genomic abnormalities are highly disease-specific, and the ras homology family member A (RHOA) gene is one of the most recurrent mutated genes, especially for RHOA G17V mutation site. Here, we identified a rare RHOA A161E mutation in an AITL patient through gene sequencing platforms. The patient presented with persistent hypereosinophilia, asymptomatic or symptomatic mildly for over 3 years. At diagnosis, this patient manifested night sweats, weight loss, multiple lymphadenopathies, and enlargement of the liver and spleen. We performed a retrospective genetic mutation analysis by whole-exome sequencing (WES) and droplet digital PCR (ddPCR) on serial gastric, intestinal, and lymph node specimens. The genetic mutation testing result demonstrated that a rare RHOA A161E mutation was found, which was elevated significantly on diagnosis related to AITL pathogenesis. Our case confirms that genetic mutation testing is helpful for diagnostic classification in AITL and dynamic monitoring of gene mutations at multiple time points may facilitate early detection of disease diagnosis.
Altered Intestinal Microbiomes and Lipid Metabolism in Patients With Prolonged Disorders of Consciousness
Authors: Yu Jie , Cheng Qisheng , He Fangping , Meng Fanxia , Yu Yamei , Xu Chuan , Wen Xinrui , Hong Lirong , Gao Jian , Li Jingqi , Pan Gang , Li Ming D. , Luo Benyan
Published: July 2022

The intestinal microbiota regulate the brain function of the host through the production of a myriad of metabolites and are associated with various neurological diseases. Understanding the intestinal microbiome of patients with prolonged disorders of consciousness (DoC) is important for the evaluation and treatment of the disease. To investigate the differences in the intestinal microbiome and short-chain fatty acids (SCFAs) among patients in a vegetative state (VS), a minimally conscious state (MCS), and emerged from MCS (EMCS), as well as the influence of antibiotics on these patients, 16S ribosomal RNA (16S rRNA) sequencing and targeted lipidomics were performed on fecal samples from patients; in addition, analysis of the electroencephalogram (EEG) signals was performed to evaluate the brain function of these patients. The results showed that the intestinal microbiome of the three groups differed greatly, and some microbial communities showed a reduced production of SCFAs in VS patients compared to the other two groups. Moreover, reduced microbial communities and five major SCFAs, along with attenuated brain functional connectivity, were observed in MCS patients who were treated with antibiotics compared to those who did not receive antibiotic treatment, but not in the other pairwise comparisons. Finally, three genus-level microbiota—Faecailbacterium, Enterococcus, and Methanobrevibacter—were considered as potential biomarkers to distinguish MCS from VS patients, with high accuracy both in the discovery and validation cohorts. Together, our findings improved the understanding of patients with prolonged DoC from the intestinal microbiome perspective and provided a new reference for the exploration of therapeutic targets.
Circulating T Cell Activation and Exhaustion Markers Are Associated With Radiation Pneumonitis and Poor Survival in Non-Small-Cell Lung Cancer
Authors: Berg Janna , Halvorsen Ann Rita , Bengtson May-Bente , Lindberg Morten , Halvorsen Bente , Aukrust Pål , Helland Åslaug , Ueland Thor
Published: July 2022

Introduction

Persistent inflammation and immune activation in the lungs are associated with adverse outcomes such as radiation pneumonitis (RP) and poor survival in non-small-cell lung cancer (NSCLC) patients. However, it is unknown how this is reflected by leukocyte activation markers in serum.

Objective

The aim was to evaluate the serum levels of activation of different leukocyte subsets and to examine those in relation to the pathogenesis of RP and survival in NSCLC.

Methods

We analyzed the serum levels of MPO, sCD25, sTIM-3, sPD-L1, sCD14, sCD163, CCL19 and CCL21 in 66 inoperable NSCLC patients with stage IA-IIIA disease. The patients were treated with stereotactic body radiation therapy (SBRT) or concurrent chemoradiation therapy (CCRT), followed by regular blood sampling for 12 months after treatment and for 5 years for survival.

Results

Nineteen (29%) patients developed RP, which occurred more frequently and earlier in patients receiving CCRT than in those receiving SBRT. Increases in sCD25, sTIM-3 and CCL21 levels were observed at the last 6 months of follow-up in patients who had RP after SBRT. Patients who had RP after CCRT had higher sTIM-3 levels during the first 3 months of follow-up. Baseline sCD25 was independently associated with both 2- and 5-year mortality outcomes, while baseline sTIM-3 was independently associated with 2-year mortality.

Conclusion

We showed that T cell activation and exhaustion markers such as sCD25 and sTIM-3 are enhanced in patients developing RP and are associated with poor survival in NSCLC.
Nociception-Dependent CCL21 Induces Dorsal Root Ganglia Axonal Growth via CCR7-ERK Activation
Authors: Mesquida-Veny Francina , Martínez-Torres Sara , Del Rio Jose Antonio , Hervera Arnau
Published: July 2022

While chemokines were originally described for their ability to induce cell migration, many studies show how these proteins also take part in many other cell functions, acting as adaptable messengers in the communication between a diversity of cell types. In the nervous system, chemokines participate both in physiological and pathological processes, and while their expression is often described on glial and immune cells, growing evidence describes the expression of chemokines and their receptors in neurons, highlighting their potential in auto- and paracrine signalling. In this study we analysed the role of nociception in the neuronal chemokinome, and in turn their role in axonal growth. We found that stimulating TRPV1+ nociceptors induces a transient increase in CCL21. Interestingly we also found that CCL21 enhances neurite growth of large diameter proprioceptors in vitro. Consistent with this, we show that proprioceptors express the CCL21 receptor CCR7, and a CCR7 neutralizing antibody dose-dependently attenuates CCL21-induced neurite outgrowth. Mechanistically, we found that CCL21 binds locally to its receptor CCR7 at the growth cone, activating the downstream MEK-ERK pathway, that in turn activates N-WASP, triggering actin filament ramification in the growth cone, resulting in increased axonal growth.
The Role of T Helper 22 Cells in Dermatological Disorders
Authors: Pan Yu , Du Dan , Wang Lian , Wang Xiaoyun , He Gu , Jiang Xian
Published: July 2022

T helper 22 (Th22) cells are a newly identified subset of CD4+ T cells that secrete the effector cytokine interleukin 22 (IL-22) upon specific antigen stimulation, barely with IFN-γ or IL-17. Increasing studies have demonstrated that Th22 cells and IL-22 play essential roles in skin barrier defense and skin disease pathogenesis since the IL-22 receptor is widely expressed in the skin, especially in keratinocytes. Herein, we reviewed the characterization, differentiation, and biological activities of Th22 cells and elucidated their roles in skin health and disease. We mainly focused on the intricate crosstalk between Th22 cells and keratinocytes and provided potential therapeutic strategies targeting the Th22/IL-22 signaling pathway.
The Role of Gut Microbiota in Some Liver Diseases: From an Immunological Perspective
Authors: Wang Li , Cao Zheng-Min , Zhang Li-Li , Li Juan-mei , Lv Wen-liang
Published: July 2022

Gut microbiota is a microecosystem composed of various microorganisms. It plays an important role in human metabolism, and its metabolites affect different tissues and organs. Intestinal flora maintains the intestinal mucosal barrier and interacts with the immune system. The liver is closely linked to the intestine by the gut-liver axis. As the first organ that comes into contact with blood from the intestine, the liver will be deeply influenced by the gut microbiota and its metabolites, and the intestinal leakage and the imbalance of the flora are the trigger of the pathological reaction of the liver. In this paper, we discuss the role of gut microbiota and its metabolites in the pathogenesis and development of autoimmune liver diseases((including autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), metabolic liver disease such as non-alcoholic fatty liver disease, cirrhosisits and its complications, and liver cancer from the perspective of immune mechanism. And the recent progress in the treatment of these diseases was reviewed from the perspective of gut microbiota.
Necroptosis Identifies Novel Molecular Phenotypes and Influences Tumor Immune Microenvironment of Lung Adenocarcinoma
Authors: Zhao Chen , Xiong Kewei , Adam Abdalla , Ji Zhiqiang , Li Xiangpan
Published: July 2022

This study aims to investigate the immune and epigenetic mutational landscape of necroptosis in lung adenocarcinoma (LUAD), identify novel molecular phenotypes, and develop a prognostic scoring system based on necroptosis regulatory molecules for a better understanding of the tumor immune microenvironment (TIME) in LUAD. Based on the Cancer Genome Atlas and Gene Expression Omnibus database, a total of 29 overlapped necroptosis-related genes were enrolled to classify patients into different necroptosis phenotypes using unsupervised consensus clustering. We systematically correlated the phenotypes with clinical features, immunocyte infiltrating levels, and epigenetic mutation characteristics. A novel scoring system was then constructed, termed NecroScore, to quantify necroptosis of LUAD by principal component analysis. Three distinct necroptosis phenotypes were confirmed. Two clusters with high expression of necroptosis-related regulators were “hot tumors”, while another phenotype with low expression was a “cold tumor”. Molecular characteristics, including mutational frequency and types, copy number variation, and regulon activity differed significantly among the subtypes. The NecroScore, as an independent prognostic factor (HR=1.086, 95%CI=1.040-1.133, p<0.001), was able to predict the survival outcomes and show that patients with higher scores experienced a poorer prognosis. It could also evaluate the responses to immunotherapy and chemotherapeutic efficiency.

In conclusion, necroptosis-related molecules are correlated with genome diversity in pan-cancer, playing a significant role in forming the TIME of LUAD. Necroptosis phenotypes can distinguish different TIME and molecular features, and the NecroScore is a promising biomarker for predicting prognosis, as well as immuno- and chemotherapeutic benefits in LUAD.
Remnant Cholesterol and Dyslipidemia Are Risk Factors for Guillain–Barré Syndrome and Severe Guillain–Barré Syndrome by Promoting Monocyte Activation
Authors: Ding Yaowei , Wang Lijuan , Sun Jialu , Shi Yijun , Li Guoge , Luan Xin , Zheng Guanghui , Zhang Guojun
Published: July 2022

Background

Guillain–Barré syndrome (GBS) is the most common severe acute paralytic neuropathy, with a mortality rate of 5% and permanent sequelae rate of 10%. Currently, the cause of GBS remains unclear. Therefore, we sought to determine potential predictors for GBS and its severity.

Methods

A case–control study was performed at Tiantan Hospital in Beijing from January 2017 to December 2021. Laboratory and clinical characteristics were assessed in recruited GBS patients and healthy control individuals (matched by sex and age). The potential risk factors for GBS and severe GBS were assessed using a logistic regression analysis. The mRNA levels of toll-like receptor 4 (TLR4), toll-like receptor 2 (TLR2) and nuclear factor κB (NF-κB) in GBS patients and control PBMCs were detected by fluorescence quantitative PCR. THP-1 cells were costimulated with LPS and free cholesterol to demonstrate the effect of free cholesterol on monocyte activation.

Results

A total of 147 GBS patients and 153 healthy individuals were included in the study. Logistic regression analyses showed that preceding infection, alcohol consumption, remnant cholesterol, homocysteine and the dyslipidemia index were correlated with a higher risk of GBS. In contrast, increased HDL cholesterol was correlated with a lower risk of GBS. Moreover, remnant cholesterol and the dyslipidemia index were significantly correlated with severe GBS. The mRNA levels of TLR4, TLR2 and NF-κB in the PBMCs of GBS patients were significantly higher than those of healthy individuals. LPS activated THP-1 cells, and free cholesterol treatment increased the expression of TLR4, TLR2, NF-κB and IL-1β mRNA in LPS-activated THP-1 cells.

Conclusion

Dyslipidemia was correlated with the risk of GBS and severe GBS. Remnant cholesterol may promote the activation of monocytes in GBS patients. It may be valuable to control lipid levels in the prevention of GBS and severe GBS.
The Syndemic of Substance Use, High-Risk Sexual Behavior, and Violence: A Qualitative Exploration of the Intersections and Implications for HIV/STI Prevention Among Key Populations in Lagos, Nigeria
Authors: Dirisu Osasuyi , Adediran Mayokun , Omole Adekemi , Akinola Akinwumi , Ebenso Bassey , Shoyemi Elizabeth , Eluwa George , Tun Waimar , Adebajo Sylvia
Published: July 2022

Background

Key populations (KP) are defined groups with an increased risk of HIV due to specific higher risk behaviours. KP who use substances engage in risky behaviors that may play a co-active role in HIV transmission and acquisition in Nigeria. This qualitative study explored the 'syndemics' of substance use, sexual risk behavior, violence and HIV infection among KP who use substances.

Methods

Nineteen sexually active men who have sex with men [MSM] and 18 female sex workers [FSW] aged 16 years and older who use substances were purposively selected to participate in sixteen in-depth interviews and two focus groups. We utilized a syndemic framework to explore the interaction of socio-economic factors, substance use and high-risk sexual practices. The interviews were audio-recorded, transcribed, organized in NVIVO 11 and analyzed using thematic analysis.

Results

Majority (95%) were non-injection substance users (primarily alcohol and marijuana); a few KP also used cocaine and heroin. Sixty percent of participants were between 16-24 years. Substance use utilities and trajectories were heavily influenced by KP social networks. They used substances as a coping strategy for both physical and emotional issues as well as to enhance sex work and sexual activities. Key HIV/STI risk drivers in the settings of substance use during sexual intercourse that emerged from this study include multiple sexual partnerships, condom-less sex, transactional sex, intergenerational sex, double penetration, rimming, and sexual violence. Poverty and adverse socio-economic conditions were identified as drivers of high-risk sexual practices as higher sexual risks attracted higher financial rewards.

Conclusions and Recommendations

Findings indicate that KP were more inclined to engage in high-risk sexual practices after the use of substances, potentially increasing HIV risk. The syndemic of substance use, high-risk sexual behavior, adverse socio-economic situations, and violence intersect to limit HIV prevention efforts among KP. The behavioural disinhibition effects of substances as well as social and structural drivers should be considered in the design of targeted KP HIV prevention programs. HIV intervention programs in Nigeria may yield better outcomes if they address the nexus of sexual risk behavior and substance use as well as knowledge and appropriate use of HIV prophylaxis.
Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients
Authors: Damanti Sarah , Cilla Marta , Cilona Maria , Fici Aldo , Merolla Aurora , Pacioni Giacomo , De Lorenzo Rebecca , Martinenghi Sabina , Vitali Giordano , Magnaghi Cristiano , Fumagalli Anna , Gennaro Mazza Mario , Benedetti Francesco , Tresoldi Moreno , Rovere Querini Patrizia
Published: July 2022

Background

A motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals.

Methods

This was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia.

Results

A total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23–1432.49, p = 0.003]; (ii) malnutrition (MNA-SF: adjusted B –5.63, 95% CI –8.39 to –2.87, p < 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10–15.13, p = 0.003), impaired muscle performance (SPPB: B –3.47, 95% CI –6.33 to –0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52–619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37–813413358.35, p < 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87–1782.53, p = 0.009) at 1-month follow-up; (iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32–8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17–12.07, p = 0.005) at 3-month follow-up; and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44–1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009).

Conclusion

The precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.
Copy Number Variation Analysis of 5p Deletion Provides Accurate Prenatal Diagnosis and Reveals Candidate Pathogenic Genes
Authors: Chu Guoming , Li Pingping , Wen Juan , Zheng Gaoyan , Zhao Yanyan , He Rong
Published: July 2022

Objective

5p deletion syndrome, that characterized by cat-like cry and peculiar timbre of voice, is believed to be one of the most common pathogenic copy number variations (CNVs). Variable critical regions on 5p involving a variety of genes contribute to the phenotypic heterogeneity without specific correlation. The objective of this study was to examine the genotype–phenotype correlation of 5p deletion syndrome, and to redefine 5p deletion syndrome relevant regions. In addition, we demonstrate the potential use of whole genome sequencing (WGS) to identify chromosomal breakpoints in prenatal diagnosis.

Methods

Three families with women undergoing prenatal diagnosis and two children were recruited. Karyotyping, CNV-seq, fluorescence in situ hybridization, WGS, and Sanger sequencing were performed to identify the chromosomal disorder.

Results

We reported three families and two children with CNVs of 5p deletion or combined 6p duplication. Five different sizes of 5p deletion were detected and their pathogenicity was determined, including 5p15.33-p15.31 [1–7,700,000, family1-variant of uncertain significance (VUS)], 5p15.33 (1–3,220,000, family 2-VUS), 5p15.33-p15.31 (1–7,040,000, family 3-VUS), 5p15.33-p15.31 (1–8,740,000, child 1-pathogenic) and 5p15.31-p15.1 (8,520,001–18,080,000, child 2-pathogenic). One duplication at 6p25.3-p24.3 (1–10,420,000) was detected and determined as likely pathogenic. The chromosomal breakpoints in family 3 were successfully identified by WGS.

Conclusion

Some critical genes that were supposed to be causative of the symptoms were identified. Relevant region in 5p deletion syndrome was redefined, and the chr5:7,700,000–8,740,000 region was supposed to be responsible for the cat-like cry. The great potential of WGS in detecting chromosomal translocations was demonstrated. Our findings may pave the way for further research on the prevention, diagnosis, and treatment of related diseases.
Analysis of Optic Nerve in Adults With Amblyopia Using OCTA
Authors: Lu Hui , Zhang Tonggang , Yue Tao , Li Xiaoqin , Ma Bingfen , Liu Hongxia
Published: July 2022

Objective

The aim was to quantify and compare papillary and peripapillary vessel density in amblyopic eyes of adults and age-matched controls.

Methods

This cross-sectional study involved 20 eyes from 10 subjects with anisometropic amblyopia and 12 eyes of 6 age- and gender-matched healthy controls. Optical coherence tomography angiography (OCTA) was performed on all participants. SPSS 20 was used for data analysis.

Results

The mean subject age was 35.7 ± 10.04 years (range 18–47) in the amblyopia group and 34.67 ± 6.92 years (range 23–42) in the control group. The diopter of amblyopia ranges from +3 to +5 ds. The mean inside optic disk capillary vessel density (CVD) was 41.88 ± 6.55% in amblyopic eyes, 49.23 ± 6.55% in fellow eyes, and 50.23 ± 4% in control eyes (p < 0.05). The mean inside optic disk all vessel density (AVD) was 52.97 ± 6.71% in amblyopic eyes, 59.87 ± 4.59% in fellow eyes, and 60.45 ± 2.8% in control eyes (p < 0.05). The amblyopic eye of participants showed a decrease in vessel density in the inside optic disk than in the fellow eyes and healthy subjects.

Conclusion

Our present study revealed lower vessel density inside the optic disc of adult patients with anisometropic amblyopia. However, further studies are really needed to determine the clinical relevance of this finding.
Impact of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) GFR Estimating Equations on CKD Prevalence and Classification Among Asians
Authors: Betzler Bjorn Kaijun , Sultana Rehena , He Feng , Tham Yih Chung , Lim Cynthia Ciwei , Wang Ya Xing , Nangia Vinay , Tai E. Shyong , Rim Tyler Hyungtaek , Bikbov Mukharram M. , Jonas Jost B. , Kang Se Woong , Park Kyu Hyung , Cheng Ching-Yu , Sabanayagam Charumathi
Published: July 2022

Background

In 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR). However, this new equation is not ethnic-specific, and prevalence of CKD in Asians is known to differ from other ethnicities. This study evaluates the impact of the 2009 and 2021 creatinine-based eGFR equations on the prevalence of CKD in multiple Asian cohorts.

Methods

Eight population-based studies from China, India, Russia (Asian), Singapore and South Korea provided individual-level data (n = 67,233). GFR was estimated using both the 2009 CKD-EPI equation developed using creatinine, age, sex, and race (eGFRcr [2009, ASR]) and the 2021 CKD-EPI equation developed without race (eGFRcr [2021, AS]). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (G3-G5). Prevalence of eGFR categories was compared within each study and within subgroups of age, sex, body mass index (BMI), diabetes, and hypertension status. The extent of reclassification was examined using net reclassification improvement (NRI).

Findings

Of 67,233 adults, CKD prevalence was 8.6% (n = 5800/67,233) using eGFRcr (2009, ASR) and 6.4% (n = 4307/67,233) using eGFRcr (2021, AS). With the latter, CKD prevalence was reduced across all eight studies, ranging from −7.0% (95% CI −8.5% to −5.4%) to −0.4% (−1.3% to 0.5%), and across all subgroups except those in the BMI < 18.5% subgroup. Net reclassification index (NRI) was significant at −2.33% (p < 0.001). No individuals were reclassified as a higher (more severe) eGFR category, while 1.7%−4.2% of individuals with CKD were reclassified as one eGFR category lower when eGFRcr (2021, AS) rather than eGFRcr (2009, ASR) was used.

Interpretation

eGFRcr (2021, AS) consistently provided reduced CKD prevalence and higher estimation of GFR among Asian cohorts than eGFRcr (2009, ASR). Based on current risk-stratified approaches to CKD management, more patients reclassified to lower-risk GFR categories could help reduce inappropriate care and its associated adverse effects among Asian renal patients. Comparison of both equations to predict progression to renal failure or adverse outcomes using prospective studies are warranted.

Funding

National Medical Research Council, Singapore.
Combined Application of Manure and Chemical Fertilizers Alters Soil Environmental Variables and Improves Soil Fungal Community Composition and Rice Grain Yield
Authors: Iqbal Anas , Ali Izhar , Yuan Pengli , Khan Rayyan , Liang He , Wei Shanqing , Jiang Ligeng
Published: July 2022

Soil microorganisms play vital roles in energy flow and soil nutrient cycling and, thus, are important for crop production. A detailed understanding of the complex responses of microbial communities to diverse organic manure and chemical fertilizers (CFs) is crucial for agroecosystem sustainability. However, little is known about the response of soil fungal communities and soil nutrients to manure and CFs, especially under double-rice cropping systems. In this study, we investigated the effects of the application of combined manure and CFs to various fertilization strategies, such as no N fertilizer (Neg-CF); 100% chemical fertilizer (Pos-CF); 60% cattle manure (CM) + 40% CF (high-CM); 30% CM + 70% CF (low-CM); 60% poultry manure (PM) + 40% CF (high-PM), and 30% PM + 70% CF (low-PM) on soil fungal communities' structure and diversity, soil environmental variables, and rice yield. Results showed that synthetic fertilizer plus manure addition significantly increased the soil fertility and rice grain yield compared to sole CFs' application. Moreover, the addition of manure significantly changed the soil fungal community structure and increased the relative abundance of fungi such as phyla Ascomycota, Basidiomycota, Mortierellomycota, and Rozellomycota. The relative abundances dramatically differed at each taxonomic level, especially between manured and non-manured regimes. Principal coordinates analysis (PCoA) exhibited greater impacts of the addition of manure amendments than CFs on fungal community distributions. Redundancy analysis showed that the dominant fungal phyla were positively correlated with soil pH, soil organic C (SOC), total N, and microbial biomass C, and the fungal community structure was strongly affected by SOC. Network analysis explored positive relationships between microorganisms and could increase their adaptability in relevant environments. In addition, the structural equation model (SEM) shows the relationship between microbial biomass, soil nutrients, and rice grain yield. The SEM showed that soil nutrient contents and their availability directly affect rice grain yield, while soil fungi indirectly affect grain yield through microbial biomass production and nutrient levels. Our results suggest that manure application combined with CFs altered soil biochemical traits and soil fungal community structure and counteracted some of the adverse effects of the synthetic fertilizer. Overall, the findings of this research suggest that the integrated application of CF and manure is a better approach for improving soil health and rice yield.