bluuebunny/crossref_metadata_2025 huggingface dataset:
QCR7 affects the virulence of Candida albicans and the uptake of multiple carbon sources present in different host niches
Authors: Zeng Lingbing , Huang Yongcheng , Tan Junjun , Peng Jun , Hu Niya , Liu Qiong , Cao YanLi , Zhang Yuping , Chen Junzhu , Huang Xiaotian
Published: February 2023

Background

Candida albicans is a commensal yeast that may cause life-threatening infections. Studies have shown that the cytochrome b-c1 complex subunit 7 gene (QCR7) of C. albicans encodes a protein that forms a component of the mitochondrial electron transport chain complex III, making it an important target for studying the virulence of this yeast. However, to the best of our knowledge, the functions of QCR7 have not yet been characterized.

Methods

A QCR7 knockout strain was constructed using SN152, and BALb/c mice were used as model animals to determine the role of QCR7 in the virulence of C. albicans. Subsequently, the effects of QCR7 on mitochondrial functions and use of carbon sources were investigated. Next, its mutant biofilm formation and hyphal growth maintenance were compared with those of the wild type. Furthermore, the transcriptome of the qcr7Δ/Δ mutant was compared with that of the WT strain to explore pathogenic mechanisms.

Results

Defective QCR7 reduced recruitment of inflammatory cells and attenuated the virulence of C. albicans infection in vivo. Furthermore, the mutant influenced the use of multiple alternative carbon sources that exist in several host niches (GlcNAc, lactic acid, and amino acid, etc.). Moreover, it led to mitochondrial dysfunction. Furthermore, the QCR7 knockout strain showed defects in biofilm formation or the maintenance of filamentous growth. The overexpression of cell-surface-associated genes (HWP1, YWP1, XOG1, and SAP6) can restore defective virulence phenotypes and the carbon-source utilization of qcr7Δ/Δ.

Conclusion

This study provides new insights into the mitochondria-based metabolism of C. albicans, accounting for its virulence and the use of variable carbon sources that promote C. albicans to colonize host niches.
Pyrite chemistry records a multistage ore forming system at the Proterozoic George Fisher massive sulfide Zn-Pb-Ag deposit, Mount Isa, Australia
Authors: Rieger Philip , Magnall Joseph M. , Gleeson Sarah A. , Oelze Marcus
Published: February 2023

Trace element (TE) analysis of pyrite via LA-ICP-MS can be used to reconstruct the conditions of pyrite formation in complex mineral systems. The Carpentaria province in northern Australia is host to some of the world’s highest value Zn-Pb (+Ag, Cu) deposits. The genesis of many of these deposits is controversial, with competing models of single-vs. multi-stage ore formation. In this study, LA-ICP-MS data of paragenetically constrained pyrite from the George Fisher Zn-Pb-Ag deposit has been analysed to investigate the chemistry of different stages of ore formation. Pyrite from correlative unmineralized host rocks has also been analysed to investigate evidence of distal hydrothermal anomalism. All LA-ICP-MS data have been statistically evaluated (principal component analysis) and interpreted together with whole rock lithogeochemical data of the same samples. Pre-ore diagenetic pyrite is compositionally similar to other Proterozoic diagenetic pyrite, with some evidence of minor hydrothermal anomalism that with further analysis could help define distal alteration. Pyrite from the different ore stages are compositionally distinct, consistent with a multi-stage system. Ore stage 1 pyrite exceeds background contents of Co, Cu, Zn, As, Ag, Sb, Tl, and Pb and has elevated Co/Ni ratios, whereas only Ni and Co are above background abundances in ore stage 2 and 3 pyrite, of which only ore stage 3 pyrite has high Co/Ni ratios. Ore stage 1 pyrite has a similar composition to hydrothermal pyrite in the undeformed northern Carpentaria CD-type deposits and was likely syn-diagenesis. Ore stage 2 was syn-deformation, and resulted in replacement and recrystallization of pre-existing pyrite, and the expulsion of incompatible TEs. Ore stage 3 formed via a later Cu-Zn-Pb mineralizing event that resulted in a new geochemically distinct generation of Co-rich pyrite. Overall, this study demonstrates the value of paragenetically-constrained pyrite TE data for refining genetic models in complex sediment hosted mineral systems.
Preoperative ultrasound identification and localization of the inferior parathyroid glands in thyroid surgery
Authors: Chen Ruyue , Zhang Kaining , Liu Ju , Guo Ling , Liu Kailin , Geng Chong
Published: February 2023

Introduction

The parathyroid glands are important endocrine glands for maintaining calcium and phosphorus metabolism, and they are vulnerable to accidental injuries during thyroid cancer surgery. The aim of this retrospective study was to investigate the application of high-frequency ultrasound imaging for preoperative anatomical localization of the parathyroid glands in patients with thyroid cancer and to analyze the protective effect of this technique on the parathyroid glands and its effect on reducing postoperative complications.

Materials and methods

A total of 165 patients who were operated for thyroid cancer in our hospital were included. The patients were assigned into two groups according to the time period of surgery: Control group, May 2018 to February 2021 (before the application of ultrasound localization of parathyroid in our hospital); PUS group, March 2021 to May 2022. In PUS group, preoperative ultrasound was used to determine the size and location of bilateral inferior parathyroid glands to help surgeons identify and protect the parathyroid glands during operation. We compared the preoperative ultrasound results with the intraoperative observations. Preoperative and first day postoperative serum calcium and PTH were measured in both groups.

Results

Our preoperative parathyroid ultrasound identification technique has more than 90% accuracy (true positive rate) to confirm the location of parathyroid gland compared to intraoperative observations. Postoperative biochemical results showed a better Ca2+ [2.12(0.17) vs. 2.05(0.31), P=0.03] and PTH [27.48(14.88) vs. 23.27(16.58), P=0.005] levels at first day post-operation in PUS group compared to control group. We also found a reduced risk of at least one type of hypoparathyroidism after surgery in control group:26 cases (31.0%) vs. 41 cases (50.6%), p=0.016.

Conclusion

Ultrasound localization of the parathyroid glands can help in the localization, identification and in situ preservation of the parathyroid glands during thyroidectomy. It can effectively reduce the risk of hypoparathyroidism after thyroid surgery.
Evolutionary game and simulation analysis on management synergy in China’s coal emergency coordination
Authors: Shi Peizhe , Hao Yu , Sun Chaolun , Zhang LiJun
Published: February 2023

Once coal mine accidents occur, a series of chain reactions will bring radiation effects that are difficult to solve in the short term to the normal operation of the economy and society. Therefore, the post-disaster management of coal mine accident is particularly important. Coal mine emergency response involves many stakeholders, and it needs various regions, departments to achieve multi-agent, multi-level effective collaboration to ensure that the coal mine accidents are controlled as soon as possible. Local governments and coal mine enterprises are the main forces in the post-accident emergency management of coal mines, but the differences in their interest motives, preferences and cognitive structures make it difficult for the relevant emergency managers to make correct decisions in the complex accident management environment, therefore, the game relationship between conflict and cooperation among related subjects is explored based on the perspective of game theory. This study establishes a game model of coal mine accident response behavior between coal mining enterprises and local governments, and quantitatively adopts the method of numerical simulation analysis to conduct in-depth analysis of the influencing factors of their decision-making behavior. The results reveal that: 1) the establishment of an information sharing mechanism is an important condition for local governments to efficiently and quickly start the incident response process for coal mine accidents; 2) Under the proper supervision of local government, the impact of the reduction of emergency response cost on the active response of coal mining enterprises is more significant and direct, that is, The cost of emergency response is the decisive factor affecting the incident response work of coal mining company; 3) the establishment of emergency cost compensation mechanism and incentive mechanism should also be the focus of local governments in formulating emergency coordination policies in the future. This study provides scientifc and reasonable management suggestions in line with the actual situation of China and provides a useful reference for local government to formulate the optimal strategy for emergency coordination in coal mine emergencies, to improve the motivation of each coordinating subjects and to improve the current situation of emergency coordination in China’s coal mines.
Clinical features and genetic spectrum of Chinese patients with hereditary spastic paraplegia: A 14-year study
Authors: Yu Weiyi , He Ji , Liu Xiangyi , Wu Jieying , Cai Xiying , Zhang Yingshuang , Liu Xiaoxuan , Fan Dongsheng
Published: February 2023

Background: Hereditary spastic paraplegia (HSP) constitutes a group of clinically and genetically rare neurodegenerative diseases characterized by progressive corticospinal tract degeneration. The phenotypes and genotypes of HSP are still expanding. In this study, we aimed to analyse the differential diagnosis, clinical features, and genetic distributions of a Chinese HSP patients in a 14-year cohort and to improve our understanding of the disease.

Methods: The clinical data of patients with a primary diagnosis of HSP at the initial visit to the Department of the Neurology, Peking University Third Hospital, from 2008 to 2022 were retrospectively collected. Next-generation sequencing gene panels (NGS) combined with a multiplex ligation-amplification assay (MLPA) were conducted. Epidemiological and clinical features and candidate variants in HSP-related genes were analyzed and summarized.

Results: 54 cases (probands from 25 different pedigrees and 29 sporadic cases) from 95 patients with a primary diagnosis of HSP were finally confirmed to have a clinical diagnosis of HSP based on clinical criteria, including their clinical findings, family history and long-term follow-up. Earlier disease onset was associated with longer diagnostic delay and longer disease duration and was associated with a lower risk of loss of ability to walk independently. In addition, 20 candidate variants in reported HSP-related genes were identified in these clinically diagnosed HSP patients, including variants in SPAST, ALT1, WASHC5, SPG11, B4GALNT1, and REEP1. The genetic diagnostic rate in these 54 patients was 35.18%.

Conclusion: Hereditary spastic paraplegia has high clinical and genetic heterogeneity and is prone to misdiagnosis. Long-term follow-up and genetic testing can partially assist in diagnosing HSP. Our study summarized the clinical features of Chinese HSP patients in a 14-year cohort, expanded the genotype spectrum, and improved our understanding of the disease.
Prognostic markers of ferroptosis-related long non-coding RNA in lung adenocarcinomas
Authors: Mao Kaimin , Tang Ri , Wu Yali , Zhang Zhiyun , Gao Yuan , Huang Huijing
Published: February 2023

Ferroptosis is a recently established type of iron-dependent programmed cell death. Growing studies have focused on the function of ferroptosis in cancers, including lung adenocarcinoma (LUAD). However, the factors involved in the regulation of ferroptosis-related genes are not fully understood. In this study, we collected data from lung adenocarcinoma datasets of the Cancer Genome Atlas (TCGA-LUAD). The expression profiles of 60 ferroptosis-related genes were screened, and two differentially expressed ferroptosis subtypes were identified. We found the two ferroptosis subtypes can predict clinical outcomes and therapeutic responses in LUAD patients. Furthermore, key long non-coding RNAs (lncRNAs) were screened by single factor Cox and least absolute shrinkage and selection operator (LASSO) based on which co-expressed with the 60 ferroptosis-related genes. We then established a risk score model which included 13 LUAD ferroptosis-related lncRNAs with a multi-factor Cox regression. The risk score model showed a good performance in evaluating the outcome of LUAD. What’s more, we divided TCGA-LUAD tumor samples into two groups with high- and low-risk scores and further explored the differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration among different LUAD tumor risk score groups and evaluate the predictive ability of risk score for immunotherapy benefit. Our findings provide good support for immunotherapy in LUAD in the future.
CD40LG and GZMB were correlated with adipose tissue macrophage infiltration and involved in obstructive sleep apnea related metabolic dysregulation: Evidence from bioinformatics analysis
Authors: Ming Xiaoping , Cai Weisong , Li Zhen , Yang Xiuping , Yang Minlan , Pan Dingyu , Chen Xiong
Published: February 2023

Both obesity and obstructive sleep apnea (OSA) can lead to metabolic dysregulation and systemic inflammation. Similar to obesity, increasing evidence has revealed that immune infiltration in the visceral adipose tissue (VAT) is associated with obstructive sleep apnea-related morbidity. However, the pathological changes and potential molecular mechanisms in visceral adipose tissue of obstructive sleep apnea patients need to be further studied. Herein, by bioinformatics analysis and clinical validation methods, including the immune-related differentially expressed genes (IRDEGs) analysis, protein-protein interaction network (PPI), functional enrichment analysis, a devolution algorithm (CIBERSORT), spearman’s correlation analysis, polymerase chain reaction (PCR), Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), we identified and validated 10 hub IRDEGs, the relative mRNA expression of four hub genes (CRP, CD40LG, CCL20, and GZMB), and the protein expression level of two hub genes (CD40LG and GZMB) were consistent with the bioinformatics analysis results. Immune infiltration results further revealed that obstructive sleep apnea patients contained a higher proportion of pro-inflammatory M1 macrophages and a lower proportion of M2 macrophages. Spearman’s correlation analysis showed that CD40LG was positively correlated with M1 macrophages and GZMB was negatively correlated with M2 macrophages. CD40LG and GZMB might play a vital role in the visceral adipose tissue homeostasis of obstructive sleep apnea patients. Their interaction with macrophages and involved pathways not only provides new insights for understanding molecular mechanisms but also be of great significance in discovering novel small molecules or other promising candidates as immunotherapies of OSA-associated metabolic complications.
Association of normal weight obesity phenotype with inflammatory markers: A systematic review and meta-analysis
Authors: Mohammadian Khonsari Nami , Baygi Fereshteh , Tabatabaei-Malazy Ozra , Mohammadpoor Nami Sahar , Ehsani Amir , Asadi Sasan , Qorbani Mostafa
Published: February 2023

Background

Individuals with normal weight could suffer from obesity based on their body fat percentage (also known as normal weight obesity (NWO)), thus being at risk of significant morbidity and mortality compared to the general population. It seems that inflammatory pathways and chronic inflammation are significant contributors to the pathogenicity of NWO. This study aimed to assess and pool the association of proinflammatory and anti-inflammatory cytokines with NWO.

Methods

In this systematic review and meta-analysis, online international databases (PubMed, Scopus, EMBASE, Web of Science, and Google Scholar) were searched until August 2022. All observational studies with an English full text comparing the mean levels of proinflammatory and anti-inflammatory cytokines (e.g., C-reactive protein (CRP), various types of interleukins (IL) s, tumor necrosis factor-alpha (TNF)) and white blood cell (WBC) count, in subjects with NWO and “normal weight non-obese (NWNO)” were included. Two researchers independently screened, reviewed and assessed the quality of included studies. The remaining articles’ data were extracted post-screening. The heterogeneity between studies was assessed using the I2 and Cochran’s Q tests. A random effect model meta-analysis was used to pool the standardized mean difference (SMD) as an effect size.

Results

From the initial 559 studies, 21 and 19 were included in the qualitative and quantitative synthesis, respectively. In the systematic review, 8 studies reported a significant association between various proinflammatory cytokines (CRP, IL6, IL1β, and TNFα) and NWO. According to random-effect meta-analysis, the association between NWO with CRP (SMD: 0.60, 95% CI: 0.30, 0.91) and IL6 (SMD: 0.90, 95%CI: 0.14, 1.66) was statistically significant. Moreover, the mean level of TNFα in subjects with NWO and NWNO did not differ significantly (SMD: 0.67, 95% CI: -0.36, 1.70).

Conclusion

The findings of this study show that NWO was associated with high levels of CRP and IL6. Therefore, inflammatory pathways may play a role in the pathogenicity of NWO.
Syrian hamster as an ideal animal model for evaluation of cancer immunotherapy
Authors: Jia Yangyang , Wang Yanru , Dunmall Louisa S Chard , Lemoine Nicholas R. , Wang Pengju , Wang Yaohe
Published: February 2023

Cancer immunotherapy (CIT) has emerged as an exciting new pillar of cancer treatment. Although benefits have been achieved in individual patients, the overall response rate is still not satisfactory. To address this, an ideal preclinical animal model for evaluating CIT is urgently needed. Syrian hamsters present similar features to humans with regard to their anatomy, physiology, and pathology. Notably, the histological features and pathological progression of tumors and the complexity of the tumor microenvironment are equivalent to the human scenario. This article reviews the current tumor models in Syrian hamster and the latest progress in their application to development of tumor treatments including immune checkpoint inhibitors, cytokines, adoptive cell therapy, cancer vaccines, and oncolytic viruses. This progress strongly advocates Syrian hamster as an ideal animal model for development and assessment of CIT for human cancer treatments. Additionally, the challenges of the Syrian hamster as an animal model for CIT are also discussed.
Characteristics of pathology and transcriptome profiling reveal features of immune response of acutely infected and asymptomatic infected of carp edema virus in Koi
Authors: Ouyang Ping , Ren Yongqiang , Zhou Yongheng , Li Qiunan , Huang Xiaoli , Chen Defang , Geng Yi , Guo Hongrui , Fang Jing , Deng Huidan , Lai Weiming , Chen Zhengli , Shu Gang , Yin Lizi
Published: February 2023

Koi sleepy disease (KSD) is a high mortality and infection viral disease caused by carp edema virus (CEV), which was a serious threat to aquaculture of common carp and export trade of Koi worldwide. Asymptomatic infection is an important cause of the difficulty in preventing KSD and its worldwide spread, because asymptomatic infection can be activated under appropriate condition. However, the understanding of the molecular correlates of these infections is still unknown. The purpose of this study was to compare the pathology change, enzyme activity, immunoglobulin activity, host and viral gene expression differences in acutely infected and cohabiting asymptomatic Koi infected with CEV. Healthy Koi were used as a control. The gross pathology, histopathology and ultrastructural pathology showed the difference and characteristics damage to the tissues of Koi under different infection conditions. Periodic Acid-Schiff stain (PAS), enzyme activity and immunoglobulin activity revealed changes in the immune response of gill tissue between acutely infected, asymptomatic infected and healthy Koi. A total of 111 and 2484 upregulated genes and 257 and 4940 downregulated genes were founded in healthy Koi vs asymptomatic infected Koi and healthy Koi vs acutely infected Koi, respectively. Additionally, 878 upregulated genes and 1089 downregulated genes were identified in asymptomatic vs. acutely infected Koi. Immune gene categories and their corresponding genes in different comparison groups were revealed. A total of 3, 59 and 28 immune-related genes were identified in the group of healthy Koi vs asymptomatic infected Koi, healthy Koi vs acutely infected Koi and asymptomatic infected Koi vs acutely infected Koi, respectively. Nineteen immune-related genes have the same expression manner both in healthy Koi vs acutely infected Koi and asymptomatic Koi vs acutely infected Koi, while 9 immune-related genes were differentially expressed only in asymptomatic Koi vs acutely infected Koi, which may play a role in viral reactivation. In addition, 8 differentially expressed genes (DEGs) were validated by quantitative reverse transcription PCR (RT-qPCR), and the results were consistent with the RNA-Seq results. In conclusion, the data obtained in this study provide new evidence for further elucidating CEV-host interactions and the CEV infection mechanism and will facilitate the implementation of integrated strategies for controlling CEV infection and spread.
Myeloidcells in the immunosuppressive microenvironment in glioblastoma: The characteristics and therapeutic strategies
Authors: Huang Boyuan , Zhang Jin , Zong Wenjing , Chen Sisi , Zong Zhitao , Zeng Xiaojun , Zhang Hongbo
Published: February 2023

Glioblastoma (GBM) is the most common and lethal malignant tumor of the central nervous system in adults. Conventional therapies, including surgery, radiotherapy, and chemotherapy, have limited success in ameliorating patient survival. The immunosuppressive tumor microenvironment, which is infiltrated by a variety of myeloid cells, has been considered a crucial obstacle to current treatment. Recently, immunotherapy, which has achieved great success in hematological malignancies and some solid cancers, has garnered extensive attention for the treatment of GBM. In this review, we will present evidence on the features and functions of different populations of myeloid cells, and on current clinical advances in immunotherapies for glioblastoma.
Effects of low-temperature stress on intestinal structure, enzyme activities and metabolomic analysis of juvenile golden pompano (Trachinotus ovatus)
Authors: Li Rong-xin , Amenyogbe Eric , Lu Yi , Jin Jing-hui , Xie Rui-tao , Huang Jian-sheng
Published: February 2023

Water temperature plays a crucial role in the growth, survival, and reproduction of fish species, as they make up the majority of aquatic fauna. In this study, the effects of low temperature were studied on the functional state of juvenile golden pompano (Trachinotus ovatus) under low-temperature stress. The study was conducted at 28°C in the control group and 18°C in the cold group for 14 d to determine the intestinal tissue, digestive and antioxidant enzyme activities, and metabolites of juvenile fish. The results showed that: (1) the swelling degree of the muscle layer deepened and was congested with a longer low-temperature stress period. The folds were sparse, from slight swelling to shedding and deformation. The intestinal mucosa was necrotic and had vacuoles, and the number gradually increased. Serious erosion of the villi occurred. (2) The specific activities of digestive enzymes showed a downward trend. (3) The intestinal superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity showed an upward trend. The intestinal catalase (CAT) activity showed a downward trend. (4) Compared with the control group, there were 28 metabolites in the cold group showing significant differences, among which Z, 11Z, 14Z-eicosatrienoic acid, stearic acid, and adrenic acid showed an upward trend. In contrast, spermidine and uracil showed a downward trend. Among the enriched metabolic pathways, the main differential pathways were unsaturated fatty acid biosynthesis, fatty acid biosynthesis, linoleic acid metabolism, pyrimidine metabolism, and β-alanine metabolism. According to metabolomic analysis, under low-temperature stress, the fish body improved the synthesis of unsaturated fatty acids and saturated fatty acids to adapt to a low-temperature environment and consumed spermidine to improve its immune ability to clear the peroxide generated by the synthesis of unsaturated fatty acids in the body so that the cells were protected from oxidative damage. After 14 days, low-temperature stress affected metabolites and enzyme activity indices in juvenile golden pompano. Low-temperature stress causes changes in intestinal antioxidants and digestive enzymes and damage intestinal tissues. As a result of this exploration of how low temperatures affect the juvenile golden pompano, the foundation is laid for future studies, such as the molecular mechanisms of low-temperature adaptation in fish species.
Immunocytochemical characterization of ex vivo cultured conjunctival explants; marker validation for the identification of squamous epithelial cells and goblet cells
Authors: Van Acker Sara I. , Van den Bogerd Bert , Haagdorens Michel , Koppen Carina , Pintelon Isabel
Published: February 2023

Tissue-engineered products are at the cutting edge of innovation considering their potential to functionally and structurally repair various tissue defects when the body’s own regenerative capacity is exhausted. At the ocular surface, the wound healing response to extensive conjunctival damage results in tissue repair with structural alterations or permanent scar formation rather than regeneration of the physiological conjunctiva. Conjunctival tissue engineering therefore represents a promising therapeutic option to reconstruct the ocular surface in severe cicatrizing pathologies. During the rapid race to be a pioneer, it seems that one of the fundamental steps of tissue engineering has been neglected; a proper cellular characterization of the tissue-engineered equivalents, both morphologically and functionally. Currently, no consensus has been reached on an identification strategy and/or markers for the characterization of cultured squamous epithelial and goblet cells. This study therefore evaluated the accuracy of promising markers to identify differentiated conjunctival-derived cells in human primary explant cultures through immunocytochemistry, including keratins (i.e., K7, K13, and K19) and mucins (i.e., MUC1, MUC5AC, and PAS-positivity). Comparison of the in vivo and in vitro cellular profiles revealed that the widely used goblet cell marker K7 does not function adequately in an in vitro setting. The other investigated markers offer a powerful tool to distinguish cultured squamous epithelial cells (i.e., MUC1 and K13), goblet cells (i.e., MUC5AC and PAS-staining), and conjunctival-derived cells in general (i.e., K19). In conclusion, this study emphasizes the power alongside potential pitfalls of conjunctival markers to assess the clinical safety and efficacy of conjunctival tissue-engineered products.
Dry eye disease severity and impact on quality of life in type II diabetes mellitus
Authors: Zhmud Tetiana , Malachkova Natalia , Rejdak Robert , Costagliola Ciro , Concilio Marina , Drozhzhyna Galyna , Toro Mario Damiano , Veretelnyk Svitlana
Published: February 2023

Aim

To assess the severity of dry eye disease (DED) in humans, its impact on quality of life (QoL) and to grade the damage incurred by the anterior ocular surface in patients diagnosed with type 2 diabetes mellitus (T2DM).

Patients and methods

Forty-six patients (mean age ± SD = 63.8 ± 6.7 years) diagnosed with T2DM were enrolled in the experimental group and 26 healthy individuals constituted the control group (67.9 ± 8.9 years). The diagnosis and gradation of DED were conducted in accordance with the International Task Force severity grading scheme. Disease-specific questionnaires were used to obtain the Ocular Surface Disease Index (OSDI) and assess the negative effects of the disease on the patient’s QoL. The severity of conjunctival redness and corneal/conjunctival staining was assessed by Efron and Oxford scales, respectively.

Results

According to OSDI scores, the entire experimental group presented symptoms of DED: 54.4% were diagnosed with mild DED and 46.6% with moderately severe DED. No cases of severe DED were diagnosed in either the experimental or control group. In the control group, 57.7% of individuals did not have the disease. A significant difference between the experimental and control groups was recorded for both OSDI scores (p  < 0.01) and health-related QoL (p < 0.01). It was observed that keratopathy influenced the mean OSDI values of patients. The mean OSDI value was 25.14 ± 3 in the experimental group diagnosed with keratopathy, 19.3 ± 3.5 in the subgroup with no indications of corneal injury (p = 0.000002), and 13.0 ± 3.0 in the control group (p  <  0.000002). Based on the DEWS scheme, a grade I severity level was observed in 46% of control subjects and 33% of patients diagnosed with T2DM (p = 0.4915); grades II and III were detected in the bulk of the experimental group (p = 0.0051; p = 0.1707). None of the subjects in the control or experimental groups manifested grade IV severity of DED.

Conclusion

In comparison to healthy adults, DED adversely impacts the QoL of type 2 DM patients, regardless of the disease’s association with keratopathy.
Prognostication of progressive pulmonary fibrosis in connective tissue disease-associated interstitial lung diseases: A cohort study
Authors: Chiu Yu-Hsiang , Koops Maaike F. M. , Voortman Mareye , van Es H. Wouter , Langezaal Lucianne C. M. , Welsing Paco M. J. , Jamnitski Anna , Wind Anne E. , van Laar Jacob M. , Grutters Jan C. , Spierings Julia
Published: February 2023

Background

Connective tissue diseases-associated interstitial lung disease (CTD-ILD) is a heterogeneous condition that impairs quality of life and is associated with premature death. Progressive pulmonary fibrosis (PPF) has been identified as an important risk factor for poor prognosis. However, different criteria for PPF are used in clinical studies, which may complicate comparison between trials and translation of study findings into clinical practice.

Methods

This is a retrospective single center study in patients with CTD-ILD. The prognostic relevance of PPF definitions, including INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified progressive fibrosing (simplified PF) criteria, were examined in this cohort and validated in the other reported Dutch CTD-ILD cohort.

Results

A total of 230 patients with CTD-ILD were included and the median follow-up period was six (3—9) years. Mortality risk was independently associated with age (adjusted HR 1.07, p < 0.001), smoking history (adjusted HR 1.90, p = 0.045), extent of fibrosis on high-resolution computed tomography (HRCT) at baseline (adjusted HR 1.05, p = 0.018) and baseline DLCO (adjusted HR 0.97, p = 0.013). Patients with regular pulmonary function tests in the first 2 years (adjusted HR 0.42, p = 0.002) had a better survival. The prognostic relevance for survival was similar between the three PPF criteria in the two cohorts.

Conclusion

Higher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis, while regular pulmonary function evaluation was associated with better survival. The INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified PF criteria revealed similar prognostication.
Roles of gut microbiome in epilepsy risk: A Mendelian randomization study
Authors: Zeng Youjie , Cao Si , Yang Heng
Published: February 2023

Background

Recent studies have suggested an association between gut microbiomes (GMs) and epilepsy. However, the GM taxa identified in different studies are variable. In addition, observational studies cannot indicate causality. Therefore, our study aimed to explore the causal association of GMs with epilepsy and identify the most influential GM taxa.

Methods

We conducted a Mendelian randomization (MR) study using summary statistics from genome-wide association studies (GWAS) of 211 GM taxa and epilepsy. The GWAS summary statistics for 211 GM taxa (from phylum to genus level) were generated by the MiBioGen consortium, while the FinnGen consortium provided the GWAS summary statistics for epilepsy. The primary analytical method to assess causality was the inverse-variance weighted (IVW) approach. To complement the IVW method, we also applied four additional MR methods: MR-Egger, weighted median, simple mode, and weighted. In addition, we conducted sensitivity analyses using Cochrane’s Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.

Results

We evaluated the causal effect of 211 GM taxa (from phylum to genus level) on epilepsy, generalized epilepsy, and focal epilepsy. After using the Bonferroni method for multiple testing correction, Class Betaproteobacteria [odds ratio (OR) = 1.357, 95% confidence interval (CI): 1.126–1.635, p = 0.001] and Order Burkholderiales (OR = 1.336, 95% CI: 1.112–1.606, p = 0.002). In addition, 21 nominally significant causal relationships were also identified. Further, the MR-Egger intercept test and MR-PRESSO global test suggested that our MR analysis was unaffected by horizontal pleiotropy (p > 0.05). Finally, the leave-one-out analysis suggested the robustness of the results.

Conclusion

Through the MR study, we analyzed the causal relationship of 211 GM taxa with epilepsy and determined the specific intestinal flora associated with increased epilepsy risk. Our findings may provide helpful biomarkers for disease progression and potential candidate therapeutic targets for epilepsy. In addition, in-depth analysis of large-scale microbiome GWAS datasets based on metagenomics sequencing is necessary for future studies.
Metabolic profiling and transcriptome analysis provide insights into the accumulation of flavonoids in chayote fruit during storage
Authors: Pu YuTing , Wang Cheng , Jiang YongWen , Wang XiaoJing , Ai YuJie , Zhuang WeiBing
Published: February 2023

Chayote (Sechium edulel) fruits are rich in flavonoids, folate, and low-calorie food. However, studies about the flavonoids and the corresponding regulatory mechanism of flavonoid synthesis in chayote fruits was still unclear. In present study, an integrated transcriptome and metabolite analysis of chayote fruits at three different storage stages were conducted to explore the flavonoid compositions and gene expression associated with flavonoid synthesis. Through the UPLC-MS/MS analysis, a total of 57 flavonoid compounds were detected. Of these, 42 flavonoid glycosides were significantly differential accumulation in chayote fruits at three different storage stages. Many genes associated with flavonoid synthesis were differentially expressed in chayote fruits at three different storage stages through RNA-seq analysis, including structural genes and some TFs. There was a high correlation between RNA-seq analysis and metabolite profiling, and the expression level of candidate genes in the flavonoid synthesis pathway were consistent with the dynamic changes of flavonoids. In addition, one R2R3-MYB transcription factor, FSG0057100, was defined as the critical regulatory gene of flavonoid synthesis. Furthermore, exogenous application of phenylalanine increased the total content of flavonoids and promoted some flavonoid biosynthesis-related gene expression in chayote fruits. The above results not only make us better understand the molecular mechanism of flavonoid synthesis in chayote fruits, but also contribute to the promotion and application of chayote products.
Effects of individualized dietary counseling on nutritional status and quality of life in post-discharge patients after surgery for gastric cancer: A randomized clinical trial
Authors: Yan Hongxia , He Fang , Wei Jianjian , Zhang Qiuxiang , Guo Chunguang , Ni Jinnv , Yang Fangyu , Chen Yingtai
Published: February 2023

Background

Currently, the supporting evidence for dietary counseling is insufficient. The aim of this study is to evaluate the impact of individualized dietary counseling on nutritional outcomes and quality of life (QOL) in patients undergoing surgery for gastric cancer.

Methods

This study was a prospective, single-center, randomized controlled trial. The patients after surgery for gastric cancer were randomly assigned (1:1) to the intervention group and the control group. In the intervention group, patients receive individualized dietary counseling based on individual calorie needs and symptom assessment at 24 h before discharge, 14, 21, 30, and 60 days postoperatively. Patients in the control group received routine dietary counseling. The primary endpoint was body mass index (BMI) loss at 30, 60, and 90 days after surgery; the secondary endpoints were calorie and protein intake at 30 and 60 days after surgery, blood parameters, the 90-day readmission rate, and QOL at 90 days after surgery.

Results

One hundred thirty patients were enrolled; 67 patients were assigned to the intervention group and 63 patients to the control group. Compared with the control group, patients in the intervention group were significantly less BMI loss at 30 days (−0.84 ± 0.65 vs. −1.29 ± 0.83), 60 days (−1.29 ± 0.92 vs. −1.77 ± 1.13), and 90 days (−1.37 ± 1.05 vs. −1.92 ± 1.66) after surgery (all P< 0.05). Subgroups analysis by surgery type showed that the intervention could significantly reduce BMI loss in patients undergoing total and proximal gastrectomy at 30 days (−0.75 ± 0.47 vs. −1.55 ± 1.10), 60 days (−1.59 ± 1.02 vs. −2.55 ± 1.16), and 90 days (−1.44 ± 1.19 vs. −3.26 ± 1.46) after surgery (all P< 0.05). At 60 days after surgery, calorie goals were reached in 35 patients (77.8%) in the intervention group and 14 patients (40.0%) in the control group (P = 0.001), and protein goals were reached in 40 patients (88.9%) in the intervention group and 17 patients (48.6%) in the control group (P< 0.001). Regarding the QOL at 90 days after surgery, the patients in the intervention group had a significantly lower level of fatigue, shortness of breath and stomach pain, better physical function, and cognitive function (P< 0.05).

Conclusions

Post-discharge individualized dietary counseling is an effective intervention to reduce post-gastrectomy patient weight loss and to elevate calorie intake, protein intake, and QOL.
Overcoming CEP85L-ROS1, MKRN1-BRAF and MET amplification as rare, acquired resistance mutations to Osimertinib
Authors: Kian Waleed , Krayim Bilal , Alsana Hadel , Giles Betsy , Purim Ofer , Alguayn Wafeek , Alguayn Farouq , Peled Nir , Roisman Laila C.
Published: February 2023

Lung cancer is the most common cancer-related cause of death worldwide, most of which are non-small cell lung cancers (NSCLC). Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. Treatment plans for NSCLC, specifically adenocarcinomas, rely heavily on the presence or absence of specific actionable driver mutations. Liquid biopsy can guide the treatment protocol to detect the presence of various mechanisms of resistance to treatment. We report three NSCLC EGFR mutated cases, each treated with Osimertinib in a combination therapy regimen to combat resistance mechanisms. The first patient presented with EGFR L858R/L833V compound mutation with MET amplification alongside CEP85L-ROS1 fusion gene, the second with EGFR exon 19del and MKRN1-BRAF fusion, and the last EGFR L858R/V834L compound mutation with MET amplification. Each regimen utilized a tyrosine kinase inhibitor or monoclonal antibody in addition to osimertinib and allowed for a prompt and relatively durable treatment response.
Clinical, radiological, and genetic characterization of SLC13A5 variants in Saudi families: Genotype phenotype correlation and brief review of the literature
Authors: AlQudairy Hanan , AlDhalaan Hesham , AlRuways Sarah , AlMutairi Nouf , AlNakiyah Maha , AlGhofaili Reema , AlBakheet Albandary , Alomrani Adeeb , Alharbi Omar A. , Tous Ehab , AlSayed Moeen , AlZaidan Hamad , AlRasheed Maha M. , AlOdaib Ali , Kaya Namik
Published: February 2023

Background

SLC13A5 (solute carrier family 13, member 5) encodes sodium/citrate cotransporter, which mainly localizes in cellular plasma membranes in the frontal cortex, retina, and liver. Pathogenic variants of the gene cause an autosomal recessive syndrome known as “developmental and epileptic encephalopathy 25 with amelogenesis imperfecta.”

Results

Here, we have investigated six patients from three different consanguineous Saudi families. The affected individuals presented with neonatal seizures, developmental delay, and significant defects in tooth development. Some patients showed other clinical features such as muscle weakness, motor difficulties, intellectual disability, microcephaly, and speech problems in addition to additional abnormalities revealed by electroencephalography (EEGs) and magnetic resonance imaging (MRI). One of the MRI findings was related to cortical thickening in the frontal lobe. To diagnose and study the genetic defects of the patients, whole exome sequencing (WES) coupled with confirmatory Sanger sequencing was utilized. Iterative filtering identified two variants of SLC13A5, one of which is novel, in the families. Families 1 and 2 had the same insertion (a previously reported mutation), leading to a frameshift and premature stop codon. The third family had a novel splice site variant. Confirmatory Sanger sequencing corroborated WES results and indicated full segregation of the variants in the corresponding families. The patients’ conditions were poorly controlled by multiple antiepileptics as they needed constant care.

Conclusion

Considering that recessive mutations are common in the Arab population, SLC13A5 screening should be prioritized in future patients harboring similar symptoms including defects in molar development.
Case report: Revascularization failure in NF1-related moyamoya syndrome after selumetinib: A possible pathophysiological correlation?
Authors: Chelleri Cristina , Scala Marcello , De Marco Patrizia , Traverso Monica , Ognibene Marzia , Bruno Irene , Piccolo Gianluca , Striano Pasquale , Severino Mariasavina , Zara Federico , Diana Maria Cristina , Pavanello Marco
Published: February 2023

Neurofibromatosis type 1 (NF1) is a neurocutaneous syndrome caused by pathogenic variants in the NF1 gene, encoding a multidomain inhibitor of Ras activity. Thus, NF1 is considered a RASopathy and drugs targeting the RAS/mitogen-activated protein kinase (MAPK) pathway, such as the MAP kinase (MEK) 1/2 inhibitor Selumetinib, are promising therapeutic options to treat NF1-associated tumors, especially plexiform neurofibromas and optic way gliomas. However, surgical treatment is often required for NF1-related cerebrovascular manifestations, such as moyamoya syndrome (MMS). We report a case of an 8-year-old patient receiving Selumetinib at the dose of 25 mg/m2 orally 2 times a day as a treatment for many plexiform neurofibromas. He suffered from two close strokes and brain MRI revealed a severe cerebral vasculopathy consistent with MMS, with marked stenosis of both the internal carotid arteries. A two-step surgical revascularization procedure was performed, consisting of a direct by-pass with an encephalo-mio-synangiosis (EMS) followed by encephalo-duro-arterio-synangiosis (EDAS). Surprisingly, despite the surgical technical success, follow-up MRI revealed lack of the expected revascularization. Selumetinib is a powerful therapeutic option in the treatment of severe NF1-related tumors. However, our findings suggest that this drug may interfere with cerebral neovascularization in patients with MMS requiring surgical revascularization. This is supported by the crucial role of the Vascular-Endothelial Growth Factor (VEGF), whose signaling pathway involve MAPK, as promoter of the neovascularization. Our observations suggest to adopt an imaging surveillance strategy to prevent unfavorable surgical outcome in patients with NF1-associated MMS receiving Selumetinib, and that priority should be given to surgical revascularization.
The greatest challenges and solutions to improve children's health and well-being worldwide in the next decade and beyond: Using complex systems and implementation science approaches
Authors: Tyack Zephanie
Published: February 2023

The health and well-being of children is paramount to health and well-being of society and is the foundation of health and well-being later in life. This paper presents the perspective that a complex systems approach that embeds implementation science is needed to address the rising challenges to child health and well-being in this decade (2020–2030) and beyond. Reflection on facilitators of the success of programs deemed promising to address child health and well-being in the past decade (2010–2020) is presented, to advance programs to address children’s health and well-being. A priority that needs to be addressed is developing, testing and using theories of child and family health and well-being (and related initiatives) that can be used to build on existing successes to make progress. Understanding context including further elucidating the drivers of child health and well-being at multiple levels of relevant systems (e.g., health, education, community) across the life course, and considering implications for caregivers also require greater consideration. Methods to address future challenges to child health and well-being include co-designing initiatives that support child health and well-being with children and families themselves rather than using predesigned initiatives, thoughtful outcome selection, and reporting the challenges of implementing future programs to promote learning. The approaches, priorities and methods presented can be used to design or refine interventions, models or care or community-based initiatives and provide new direction to fields of child health enquiry.
Niaoduqing alleviates podocyte injury in high glucose model via regulating multiple targets and AGE/RAGE pathway: Network pharmacology and experimental validation
Authors: Fang Yipeng , Zhang Yunfei , Jia Chenxi , Ren Chunhong , Zhao Xutao , Zhang Xin
Published: February 2023

Purpose: The aim of present study was to explore the pharmacological mechanisms of Niaoduqing granules on the treatment of podocyte injury in diabetic nephropathy (DN) via network pharmacology and experimental validation.

Methods: Active ingredients and related targets of Niaoduqing, as well as related genes of podocyte injury, proteinuria and DN, were obtained from public databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis were performed to investigate the potential mechanisms. High glucose (HG) -induced MPC5 cell injury model was treated with the major core active ingredients of Niaoduqing and used to validate the predicted targets and signaling pathways.

Results: Totally, 16 potential therapeutic targets were identified by intersecting the targets of Niaoduqing and disease, in which 7 of them were considered as the core targets via PPI network analysis. KEGG enrichment analysis showed that AGE-RAGE signaling pathway was identified as the most crucial signaling pathway. The results of in vitro experiments revealed that the treatment of Niaoduqing active ingredients significantly protected MPC5 cells from HG-induced apoptosis. Moreover, Niaoduqing could significantly attenuate the HG-induced activation of AGE-RAGE signaling pathway, whereas inhibited the over-expression of VEGF-A, ICAM-1, PTGS-2 and ACE in HG-induced MPC5 cells.

Conclusion: Niaoduqing might protect against podocyte injury in DN through regulating the activity of AGE/RAGE pathway and expression of multiple genes. Further clinical and animal experimental studies are necessary to confirm present findings.