bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between cerebrovasoreactivity and stroke in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
Authors: Mukai Mao , Hamano Ai , Mizuta Ikuko , Yokota Isao , Watanabe-Hosomi Akiko , Matsuura Hiraku , Koizumi Takashi , Matsuura Jun , Ohara Tomoyuki , Matsushima Shigenori , Teramukai Satoshi , Yamada Kei , Mizuno Toshiki
Published: January 2023

Background

Impaired cerebrovasoreactivity is thought to play an important role in the pathophysiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to clarify the association between cerebrovascular reactivity and stroke in patients with CADASIL.

Methods

We retrospectively recruited 14 patients with CADASIL, eight of whom had symptomatic stroke. They underwent quantitative single-photon emission computed tomography using an autoradiographic method at rest and after acetazolamide (ACZ) administration. Regional cerebral blood flow (rCBF) in the cerebral cortex, lenticular nucleus, thalamus, and cerebellum was measured. We compared the rCBF parameters between patients with and without stroke.

Results

The baseline characteristics and magnetic resonance imaging findings were similar between the two groups, except for a higher frequency of pyramidal tract sign (75% vs. 0%) and a larger number of old lacunes (15.4 ± 8.8 vs. 2.2 ± 1.8) in the patients with stroke. Of the rCBF parameters measured, significantly lower flow (mL/100 g/min) was observed in ACZ-rCBF in the thalamus (35.6 ± 9.4 vs. 51.1 ± 7.6, p = 0.01) and ΔrCBF in the thalamus (10.6 ± 3.7 vs. 21.0 ± 7.9, p = 0.02) in the patients with stroke.

Conclusion

Cerebrovasoreactivity in the thalamus was significantly associated with stroke in patients with CADASIL.
Discovery of an evodiamine derivative for PI3K/AKT/GSK3β pathway activation and AD pathology improvement in mouse models
Authors: Pang Shuo , Li Siyuan , Cheng Hanzeng , Luo Zhuohui , Qi Xiaolong , Guan Feifei , Dong Wei , Gao Shan , Liu Ning , Gao Xiang , Pan Shuo , Zhang Xu , Zhang Li , Yang Yajun , Zhang Lianfeng
Published: January 2023

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive neurodegeneration and cognitive decline. Evodiamine, a main component in Chinese medicine, was found to improve cognitive impairment in AD model mice based on several intensive studies. However, evodiamine has high cytotoxicity and poor bioactivity. In this study, several evodiamine derivatives were synthesized via heterocyclic substitution and amide introduction and screened for cytotoxicity and antioxidant capacity. Under the same concentrations, compound 4c was found to exhibit lower cytotoxicity and higher activity against H2O2 and amyloid β oligomers (AβOs) than evodiamine in vitro and significantly improve the working memory and spatial memory of 3 x Tg and APP/PS1 AD mice. Subsequent RNA sequencing and pathway enrichment analysis showed that 4c affected AD-related genes and the AMPK and insulin signaling pathways. Furthermore, we confirmed that 4c recovered PI3K/AKT/GSK3β/Tau dysfunction in vivo and in vitro. In conclusion, 4c represents a potential lead compound for AD therapy based on the recovery of PI3K/AKT/GSK3β pathway dysfunction.
Ramadan diurnal intermittent fasting is associated with significant plasma metabolomics changes in subjects with overweight and obesity: A prospective cohort study
Authors: Madkour Mohamed , Giddey Alexander D. , Soares Nelson C. , Semreen Mohammad H. , Bustanji Yasser , Zeb Falak , Halwani Rabih , Faris MoezAlIslam E.
Published: January 2023

Introduction

During the holy month of Ramadan, adult healthy Muslims are mandated to abstain from dawn to sunset, with free eating at night hours that may extend up to 12 h. The current work was designed to investigate the metabolomics changes incurred upon the observance of Ramadan diurnal intermittent fasting (RDIF).

Methods

Twenty-five metabolically healthy participants with overweight and obesity (7 females and 18 males, with a mean age of 39.48 ± 10.0 years) were recruited for the study and were followed before and at the end of RDIF month. Dietary, anthropometric, biochemical, and physical activity assessments were performed before and at the end of the fasting month. The metabolomic assay was performed using liquid chromatography-mass spectrometry for the two-time points.

Results and discussion

Metabolomics assay revealed a significant reduction in a few metabolites. The analysis revealed that 27 metabolites differed significantly (P< 0.05) between pre-and post-RDIF. Among the differentially abundant metabolites, 23 showed a decrease with fasting, these included several amino acids such as aspartame, tryptophan, phenylalanine, histidine, and other metabolites including valeric acid, and cortisol. On the other hand, only four metabolites showed increased levels after RDIF including traumatic acid, 2-pyrrolidinone, PC[18:1(9Z)/18:1(9Z)], andL-sorbose. The MetaboAnalyst®platform reported that the top enriched metabolic pathways included: (1) histidine metabolism; (2) folate biosynthesis (3) phenylalanine, tyrosine, and tryptophan biosynthesis; (4) aminoacyltRNA biosynthesis; (5) caffeine metabolism; (6) vitamin B6metabolism; and several other pathways relating to lipid metabolisms such as arachidonic acid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. In conclusion, RDIF entails significant changes in various metabolic pathways that reflect different dietary and lifestyle behaviors practiced during the fasting month.
Bioactive components, pharmacological effects, and drug development of traditional herbal medicine Rubus chingii Hu (Fu-Pen-Zi)
Authors: He Beihui , Dai Linghao , Jin Li , Liu Yuan , Li Xiaojuan , Luo Minmin , Wang Zhian , Kai Guoyin
Published: January 2023

Rubus chingii Hu (Chinese Raspberry), known as Fu-Pen-Zi in Chinese, a woody perennial plant of the genus Rubus in the Rosaceae family, has specific nutritional and medicinal values, which is considered food-medicine herb in China for thousands of years to treat impotence, premature ejaculation, enuresis, frequent urination, and other diseases. This review aims to summarize recent advances in the bioactive components, pharmacological effects, and drug development and utilization of Rubus chingii Hu, hoping to provide useful support for its further research and clinical application. The bioactive components in Rubus chingii Hu contain mainly terpenoids, flavonoids, alkaloids, phenolic acids, polysaccharides, and steroids. The main pharmacological effects are their anti-oxidant, anti-inflammatory, and anti-tumor capacity on human health. Rubus chingii Hu is a very valuable food-medicine herb. The development of Rubus chingii Hu–related drugs is relatively single, which is limited to traditional Chinese medicine and prescriptions. Therefore, it is vital to pay interest to Rubus chingii Hu and its bioactive components in the future and extend its scientific application.
Common factors influencing childhood undernutrition and their comparison between Sylhet, the most vulnerable region, and other parts of Bangladesh: Evidence from BDHS 2007–18 rounds
Authors: Sanin Kazi Istiaque , Khanam Mansura , Rita Razia Sultana , Haque Md. Ahshanul , Ahmed Tahmeed
Published: January 2023

Introduction

Undernourishment is disproportionately spread within Bangladesh, making some regions like Sylhet more vulnerable than the rest of the country. We aimed to assess the trend of diverse associated factors related to childhood stunting, wasting, and being underweight. Furthermore, we have compared the estimated factors between Sylhet, the most vulnerable region, and other parts of Bangladesh.

Methods

We performed a secondary data analysis where data were derived from the nationally representative cross-sectional surveys: Bangladesh demographic and health survey (BDHS) 2007, 2011, 2014, and 2017–18 rounds. The outcome variables were childhood undernutrition, including stunting, wasting, and being underweight. Descriptive statistics such as mean, standard deviation, frequency, and proportion were used to summarize the data. All variables were summarized by BDHS survey time points. We used multiple logistic regression models to measure the associated factors with childhood stunting, wasting, and being underweight.

Results

The percentage of children under the age of 5 years who were stunted declined from 40% in 2007 to 31% in 2018. Similar trends are observed in the decrease in the percentage of underweight children, dropping from 39% in 2007 to 22% in 2018. Wasting dropped to 8% in 2018 after years of critically high levels (17%). According to the results of the regression analyses, urban residence, child’s age and gender, morbidity, maternal BMI, maternal and paternal education, decision-making ability, use of contraceptives, the occurrence of domestic violence, antenatal care, c-section, and birth interval, as well as geographic region, were all linked to childhood malnutrition.

Conclusion

The Sylhet division falls short in several critical associated indicators, including parental education, maternal BMI, obtaining at least four ANC, women empowerment, and usage of contraceptives. Policymakers must concentrate on region-specific planning and proper intervention to achieve a more uniform improvement across the country.
Guishaozichuan granules can attenuate asthma in rats via the MUC5AC/EGFR signaling pathway
Authors: Gao Qinqin , Feng Chenran , Shi Qi , Wang Qingling , Ding Zitong , Chu Huilun , Kong Deming , Yin Xingbin , Ni Jian , Sun Wenyan , Li Youlin
Published: January 2023

Background: Guishaozichuan (GSZC) granules are a traditional Chinese medicine formulation created by Professor Li (Chinese–Japanese Friendship Hospital, Beijing, China) we studied the effect of GSZC granules in rats suffering from asthma.

Methods: Specific pathogen-free Sprague–Dawley rats were divided randomly into seven groups. Ovalbumin (OVA) and Al (OH)3 gel were used to create an asthma model. On day 1, rats were injected with OVA (10 mg) and an Al(OH)3 gel suspension (100 mg). One week later, rats were sensitized again. On day 15, rats were given aerosolized OVA (1%) for 30 min/day for 10 days. Gastric administration of OVA was 1 h before nebulization. At 24 h after the last stimulation, changes in airway resistance (RI) and dynamic compliance (Cdyn) in rat lungs were measured after challenge with methacholine at increasing concentrations. The contents of immunoglobulin (Ig)E, interleukin (IL)-4, IL-5, IL-13, and IL-17 in serum were measured by enzyme-linked immunosorbent assays. The percentage of eosinophils (EOS) and the white blood cell (WBC) count in bronchoalveolar lavage fluid (BALF) were counted under an optical microscope. Pathologic alterations in lung tissue were evaluated by optical microscopy, and lung injury score calculated. Expression of mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) and epidermal growth factor receptor (EGFR) in lung tissue was measured by immunohistochemistry. mRNA expression of MUC5AC and EGFR in lung tissue was measured by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results: GSZC granules reduced RI markedly and improved Cdyn, decreased serum levels of IgE, IL-4, IL-5, IL-13, IL-17, %EOS and the WBC count in BALF. GSZC granules alleviated lung-tissue damage, diminished the Inflammation Score, and reduced mRNA and protein expression of MUC5AC and EGFR in lung tissue.

Conclusion: GSZC granules could improve bronchial hyperresponsiveness, bronchial inflammation, and histopathologic damage in the lungs of rats suffering from asthma. This phenomenon may be related to its regulation of cytokine levels and the MUC5AC/EGFR signaling pathway.
Acetylsalicylic acid reduces cigarette smoke withdrawal-induced anxiety in rats via modulating the expression of NFĸB, GLT-1, and xCT
Authors: Hammad Alaa M. , Alzaghari Lujain F. , Alfaraj Malek , Al-Qerem Walid , Talib Wamidh H. , Alasmari Fawaz , Amawi Haneen , Hall F. Scott
Published: January 2023

Background: Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems.

Objective: We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions, prefrontal cortex (PFC) and nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure were assessed using open field (OF) and light/dark (LD) tests to assess withdrawal-induced anxiety-like behavior.

Methods: Sprague-Dawley rats were randomly assigned to five experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with acetylsalicylic acid (ASA) (15 mg/kg and 30 mg/kg, respectively), and a group treated only with ASA (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral tests were conducted weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or ASA 45 min before cigarette exposure for 11 days.

Results: Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg ASA attenuated this effect. Cigarette smoke exposure increased the relative mRNA and protein expression of nuclear factor ĸB (NFĸB) in PFC and NAc, and ASA treatment reversed this effect. Also, cigarette smoke decreased the relative mRNA and protein expression of glutamate transporter1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while ASA treatment normalized their expression.

Conclusion: Cigarette smoke caused neuroinflammation, alterations in glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by acetylsalicylic acid treatment.
Mapping knowledge landscapes and emerging trends of sonodynamic therapy: A bibliometric and visualized study
Authors: Wu Zhenjiang , Cheng Kunming , Shen Zefeng , Lu Yanqiu , Wang Hongtao , Wang Guolei , Wang Yulin , Yang Weiguang , Sun Zaijie , Guo Qiang , Wu Haiyang
Published: January 2023

Background: Ultrasound-triggered sonodynamic therapy (SDT), as a non-invasive approach, has attracted considerable attention in a wide variety of malignant tumors and other diseases. Over the past 2 decades, the number of scientific publications on SDT has increased rapidly. However, there is still a lack of one comprehensive report that summarizes the global research trends and knowledge landscapes in the field of SDT in detail. Thus, we performed a bibliometric analysis on SDT from 2000 to 2021 to track the current hotspots and highlight future directions.

Methods: We collected publications on SDT research from the Web of Science Core Collection database. The annual number of publications and citations, major contributors, popular journals, international collaborations, co-cited references and co-occurrence keywords were analyzed and visualized with CiteSpace, VOSviewer, and R-bibliometrix.

Results: A total of 701 publications were included. The annual publication output increased from 5 in 2000 to 175 in 2021, and the average growth rate was 18.4%. China was the most productive country with 463 documents (66.05%), and Harbin Medical University was the most prolific institution (N = 73). Ultrasound in Medicine and Biology published the most papers related to SDT. Materials Science, and Chemistry were the research areas receiving the most interest. All the keywords were divided into four different clusters including studies on mechanisms, studies on drug delivery and nanoparticles, studies on cancer therapy, as well as studies on ultrasound and sonosensitizers. In addition to nanomaterials-related studies including nanoparticles, mesoporous silica nanoparticles, nanosheets, liposomes, microbubble and TiO2 nanoparticle, the following research directions such as immunogenic cell death, metal-organic framework, photothermal therapy, hypoxia, tumor microenvironment, chemodynamic therapy, combination therapy, tumor resistance, intensity focused ultrasound, drug delivery, and Staphylococcus aureus also deserve further attention and may continue to explode in the future.

Conclusion: SDT has a bright future in the field of cancer treatment, and nanomaterials have increasingly influenced the SDT field with the development of nano-technology. Overall, this comprehensive bibliometric study was the first attempt to analyze the field of SDT, which could provide valuable references for later researchers to better understand the global research trends, hotspots and frontiers in this domain.
Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives
Authors: Liu Zherui , Zhu Yun , Xie Huan , Zou Zhengsheng
Published: January 2023

In recent years, cancer immunotherapy has made remarkable achievements. Immune checkpoint inhibitors (ICIs) have been used successfully in several types of cancer in the past decade. However, expanded indication and increased use of Immune checkpoint inhibitors have resulted in increased reports of toxicity called immune-related adverse events (irAEs). Due to the unique immunological characteristics of the liver, a hepatic immune-related adverse events has also been reported, which is usually termed Immune-mediated hepatitis (IMH). So far, it is generally considered that the mechanism of IMH induced by Immune checkpoint inhibitors is mainly the overactivation of T cells. It has been reported that the incidence of IMH ranges from 1% to 15%. Because of the lack of specific markers, a diagnosis of exclusion of IMH is critical. Although most IMH is mild and recoverable, several death cases have been reported, which has been increasingly concerned. This review summarizes the current understanding of the pathophysiology, epidemiology, diagnosis, management and prognosis of IMH caused by Immune checkpoint inhibitors. It also discusses the controversial issues in IMH, such as the role of liver biopsy, grading criteria, risk factors, rational treatment strategies with steroids, and the timing of Immune checkpoint inhibitors rechallenging, which may provide helpful information for IMH in future clinical practice.
Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management
Authors: Mazzierli Tommaso , Allegretta Federica , Maffini Enrico , Allinovi Marco
Published: January 2023

Drug-induced thrombotic microangiopathy (DITMA) represents 10%–13% of all thrombotic microangiopathy (TMA) cases and about 20%–30% of secondary TMAs, just behind pregnancy-related and infection-related forms. Although the list of drugs potentially involved as causative for TMA are rapidly increasing, the scientific literature on DITMA is quite scarce (mostly as individual case reports or little case series), leading to poor knowledge of pathophysiological mechanisms and clinical management. In this review, we focused on these critical aspects regarding DITMA. We provided an updated list of TMA-associated drugs that we selected from a scientific literature review, including only those drugs with a definite or probable causal association with TMA. The list of drugs is heterogeneous and could help physicians from several different areas to be familiar with DITMA. We describe the clinical features of DITMA, presenting the full spectrum of clinical manifestations, from systemic to kidney-limited forms. We also analyze the association between signs/symptoms (i.e., malignant hypertension, thrombocytopenia) and specific DITMA causative drugs (i.e., interferon, ticlopidine). We highlighted their multiple different pathophysiological mechanisms, being frequently classified as immune-mediated (idiosyncratic) and dose-related/toxic. In particular, to clarify the role of the complement system and genetic deregulation of the related genes, we conducted a revision of the scientific literature searching for DITMA cases who underwent renal biopsy and/or genetic analysis for complement genes. We identified a complement deposition in renal biopsies in half of the patients (37/66; 57%), with some drugs associated with major deposits (i.e., gemcitabine and ramucirumab), particularly in capillary vessels (24/27; 88%), and other with absent deposits (tyrosine kinase inhibitors and intraocular anti-VEGF). We also found out that, differently from other secondary TMAs (such as pregnancy-related-TMA and malignant hypertension TMA), complement genetic pathological mutations are rarely involved in DITMA (2/122, 1.6%). These data suggest a variable non-genetic complement hyperactivation in DITMA, which probably depends on the causative drug involved. Finally, based on recent literature data, we proposed a treatment approach for DITMA, highlighting the importance of drug withdrawal and the role of therapeutic plasma-exchange (TPE), rituximab, and anti-complementary therapy.
Comparison of efficacy of anti-diabetics on non-diabetic NAFLD: A network meta-analysis
Authors: Jin Dachuan , Cui Zhongfeng , Jin Shunqin , Zhou Tao , Guo Baoqiang , Gao Peng , Li Guangming
Published: January 2023

Objective: This study aimed to assess the efficacy of currently used anti-diabetic medications in the treatment of non-alcoholic fatty liver disease (NAFLD) without diabetes. DESIGN: The efficacy of various anti-diabetic medicines on non-alcoholic fatty liver disease in the absence of diabetes was evaluated by searching Pubmed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCT) only. The methodological quality was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2), and the data were analyzed using Stata software (version 15.1). Results: All papers published between the time of the pooling and September 2022 were searched. There were a total of 18 randomized controlled studies with a total sample size of 1141 cases. The outcomes of interest included variations in alanine transaminase (ALT) and aspartate transaminase (AST). Rosiglitazone (SUCRA: 100%) and vildagliptin (SUCRA: 99.9%) were the best anti-diabetic medicines to improve ALT and AST, respectively, in patients with NAFLD without diabetes, according to the findings of this network meta-analysis. Conclusion: In accordance with the Network Ranking plot, Rosiglitazone was the best anti-diabetic medicine for improving ALT, and vildagliptin was the best for improving AST in patients with non-diabetic NAFLD.
Genome-wide analyses of platinum-induced ototoxicity in childhood cancer patients: Results of GO-CAT and United Kingdom MAGIC consortia
Authors: Hurkmans Evelien G. E. , Klumpers Marije J. , Dello Russo Cinzia , De Witte Ward , Guchelaar Henk-Jan , Gelderblom Hans , Cleton-Jansen Anne-Marie , Vermeulen Sita H. , Kaal Suzanne , van der Graaf Winette T. A. , Flucke Uta , Gidding Corrie E. M. , Schreuder Hendrik W. B. , de Bont Eveline S. J. M. , Caron Huib N. , Gattuso Giovanna , Schiavello Elisabetta , Terenziani Monica , Massimino Maura , McCowage Geoff , Nagabushan Sumanth , Limaye Anuja , Rose Victoria , Catchpoole Daniel , Jorgensen Andrea L. , Barton Christopher , Delaney Lucy , Hawcutt Daniel B. , Pirmohamed Munir , Pizer Barry , Coenen Marieke J. H. , te Loo D. Maroeska W. M.
Published: January 2023

Hearing loss (ototoxicity) is a major adverse effect of cisplatin and carboplatin chemotherapy. The aim of this study is to identify novel genetic variants that play a role in platinum-induced ototoxicity. Therefore, a genome-wide association study was performed in the Genetics of Childhood Cancer Treatment (GO-CAT) cohort (n = 261) and the United Kingdom Molecular Genetics of Adverse Drug Reactions in Children Study (United Kingdom MAGIC) cohort (n = 248). Results of both cohorts were combined in a meta-analysis. In primary analysis, patients with SIOP Boston Ototoxicity Scale grade ≥1 were considered cases, and patients with grade 0 were controls. Variants with a p-value <10−5 were replicated in previously published data by the PanCareLIFE cohort (n = 390). No genome-wide significant associations were found, but variants in TSPAN5, RBBP4P5, AC010090.1 and RNU6-38P were suggestively associated with platinum-induced ototoxicity. The lowest p-value was found for rs7671702 in TSPAN5 (odds ratio 2.0 (95% confidence interval 1.5–2.7), p-value 5.0 × 10−7). None of the associations were significant in the replication cohort, although the effect directions were consistent among all cohorts. Validation and functional understanding of these genetic variants could lead to more insights in the development of platinum-induced ototoxicity.
Impact of KvLQT1 potassium channel modulation on alveolar fluid homeostasis in an animal model of thiourea-induced lung edema
Authors: Aubin Vega Mélissa , Girault Alban , Adam Damien , Chebli Jasmine , Privé Anik , Maillé Émilie , Robichaud Annette , Brochiero Emmanuelle
Published: January 2023

Alveolar ion and fluid absorption is essential for lung homeostasis in healthy conditions as well as for the resorption of lung edema, a key feature of acute respiratory distress syndrome. Liquid absorption is driven by active transepithelial sodium transport, through apical ENaC Na+ channels and basolateral Na+/K+-ATPase. Our previous work unveiled that KvLQT1 K+ channels also participate in the control of Na+/liquid absorption in alveolar epithelial cells. Our aim was to further investigate the function of KvLQT1 channels and their interplay with other channels/transporters involved in ion/liquid transport in vivo using adult wild-type (WT) and KvLQT1 knock-out (KO) mice under physiological conditions and after thiourea-induced lung edema. A slight but significant increase in water lung content (WLC) was observed in naïve KvLQT1-KO mice, relative to WT littermates, whereas lung function was generally preserved and histological structure unaltered. Following thiourea-induced lung edema, KvLQT1-KO did not worsen WLC or lung function. Similarly, lung edema was not aggravated by the administration of a KvLQT1 inhibitor (chromanol). However, KvLQT1 activation (R-L3) significantly reduced WLC in thiourea-challenged WT mice. The benefits of R-L3 were prevented in KO or chromanol-treated WT mice. Furthermore, R-L3 treatment had no effect on thiourea-induced endothelial barrier alteration but restored or enhanced the levels of epithelial alveolar AQP5, Na+/K+-ATPase, and ENaC expressions. Altogether, the results indicate the benefits of KvLQT1 activation in the resolution of lung edema, probably through the observed up-regulation of epithelial alveolar channels/transporters involved in ion/water transport.
Identification and immunological characterization of endoplasmic reticulum stress-related molecular subtypes in bronchopulmonary dysplasia based on machine learning
Authors: Tao Ziyu , Mao Yan , Hu Yifang , Tang Xinfang , Wang Jimei , Zeng Ni , Bao Yunlei , Luo Fei , Wu Chuyan , Jiang Feng
Published: January 2023

Introduction: Bronchopulmonary dysplasia (BPD) is a life-threatening lung illness that affects premature infants and has a high incidence and mortality. Using interpretable machine learning, we aimed to investigate the involvement of endoplasmic reticulum (ER) stress-related genes (ERSGs) in BPD patients.

Methods: We evaluated the expression profiles of endoplasmic reticulum stress-related genes and immune features in bronchopulmonary dysplasia using the GSE32472 dataset. The endoplasmic reticulum stress-related gene-based molecular clusters and associated immune cell infiltration were studied using 62 bronchopulmonary dysplasia samples. Cluster-specific differentially expressed genes (DEGs) were identified utilizing the WGCNA technique. The optimum machine model was applied after comparing its performance with that of the generalized linear model, the extreme Gradient Boosting, the support vector machine (SVM) model, and the random forest model. Validation of the prediction efficiency was done by the use of a calibration curve, nomogram, decision curve analysis, and an external data set.

Results: The bronchopulmonary dysplasia samples were compared to the control samples, and the dysregulated endoplasmic reticulum stress-related genes and activated immunological responses were analyzed. In bronchopulmonary dysplasia, two distinct molecular clusters associated with endoplasmic reticulum stress were identified. The analysis of immune cell infiltration indicated a considerable difference in levels of immunity between the various clusters. As measured by residual and root mean square error, as well as the area under the curve, the support vector machine machine model showed the greatest discriminative capacity. In the end, an support vector machine model integrating five genes was developed, and its performance was shown to be excellent on an external validation dataset. The effectiveness in predicting bronchopulmonary dysplasia subtypes was further established by decision curves, calibration curves, and nomogram analyses.

Conclusion: We developed a potential prediction model to assess the risk of endoplasmic reticulum stress subtypes and the clinical outcomes of bronchopulmonary dysplasia patients, and our work comprehensively revealed the complex association between endoplasmic reticulum stress and bronchopulmonary dysplasia.
An assessment of heart rate and blood pressure asymmetry in the diagnosis of vasovagal syncope in females
Authors: Pawłowski Rafał , Zalewski Paweł , Newton Julia , Piątkowska Agnieszka , Koźluk Edward , Opolski Grzegorz , Buszko Katarzyna
Published: January 2023

Introduction: Heart Rate Asymmetry (HRA) describes a phenomenon of differences between accelerations and decelerations in human heart rate. Methods used for HRA assessment can be further implemented in the evaluation of asymmetry in blood pressure variations (Blood Pressure Asymmetry—BPA).

Methods: We have analyzed retrospectively the series of heartbeat intervals extracted from ECG and beat-to-beat blood pressure signals from 16 vasovagal patients (age: 32.1 ± 13.3; BMI: 21.6 ± 3.8; all female) and 19 healthy subjects (age: 34.6 ± 7.6; BMI: 22.1 ± 3.4; all female) who have undergone tilt test (70°). Asymmetry was evaluated with Poincaré plot-based methods for 5 min recordings from supine and tilt stages of the test. The analyzed biosignals were heart rate (RR), diastolic (dBP) and systolic Blood Pressure (sBP) and Pulse Pressure (PP). In the paper we explored the differences between healthy and vasovagal women.

Results: The changes of HRA indicators between supine and tilt were observed only in the control group (Porta Index p = 0.026 and Guzik Index p = 0.005). No significant differences in beat-to-beat variability (i.e. spread of points across the line of identity in Poincaré plot—SD1) of dBP was noted between supine and tilt in the vasovagal group (p = 0.433 in comparison to p = 0.014 in healthy females). Moreover, in vasovagal patients the PP was significantly different (supine: 41.47; tilt: 39.27 mmHg) comparing to healthy subjects (supine: 35.87; tilt: 33.50 mmHg) in supine (p = 0.019) and in tilt (p = 0.014).

Discussion: Analysis of HRA and BPA represents a promising method for the evaluation of cardiovascular response to orthostatic stressors, however currently it is difficult to determine a subject’s underlying health condition based only on these parameters.
Psychosomatic response to acute emotional stress in healthy students
Authors: García Pagès Esther , Arza Adriana , Lazaro Jesús , Puig Carlos , Castro Thais , Ottaviano Manuel , Arredondo Maria Teresa , Bernal Maria Luisa , López-Antón Raúl , Cámara Concepción De La , Gil Eduardo , Laguna Pablo , Bailón Raquel , Aguiló Jordi , Garzón-Rey Jorge Mario
Published: January 2023

The multidimensionality of the stress response has shown the complexity of this phenomenon and therefore the impossibility of finding a unique biomarker among the physiological variables related to stress. An experimental study was designed and performed to guarantee the correct synchronous and concurrent measure of psychometric tests, biochemical variables and physiological features related to acute emotional stress. The population studied corresponds to a group of 120 university students between 20 and 30 years of age, with healthy habits and without a diagnosis of chronic or psychiatric illnesses. Following the protocol of the experimental pilot, each participant reached a relaxing state and a stress state in two sessions of measurement for equivalent periods. Both states are correctly achieved evidenced by the psychometric test results and the biochemical variables. A Stress Reference Scale is proposed based on these two sets of variables. Then, aiming for a non-invasive and continuous approach, the Acute Stress Model correlated to the previous scale is also proposed, supported only by physiological signals. Preliminary results support the feasibility of measuring/quantifying the stress level. Although the results are limited to the population and stimulus type, the procedure and methodological analysis used for the assessment of acute stress in young people can be extrapolated to other populations and types of stress.
A simple and efficient strategy to produce transgene-free gene edited plants in one generation using paraquat resistant 1 as a selection marker
Authors: Kong Xiangjiu , Pan Wenbo , Zhang Tingyu , Liu Lijing , Zhang Huawei
Published: January 2023

Introduction

DNA integration is a key factor limiting the marketing of CRISPR/Cas9-mediated gene edited crops. Several strategies have been established to obtain transgene-free gene edited plants; however, these strategies are usually time-consuming, technically difficult, providing low mutagenesis efficiency, and/or including a narrow host range.

Method

To overcome such issues, we established a paraquat resistant 1 (PAR1)-based positive screening (PARS) strategy, which achieved efficient screening of transgene-free gene edited plants.

Results

With PARS, the screening efficiency of mutant increased by 2.81-fold on average, and approximately 10% of T1 plants selected via PARS were transgenefree. Moreover, heritable transgene-free mutations at target loci were identified in the T1 generation.

Discussion

Based on the previous reports and our data, we know that paraquat is toxic to all green plants, PAR1 is conserved among all plant species tested, and the transient expression of Cas9 editor can produce transgene-free gene edited plants. Thus, we assume that the PARS strategy established here has the potential to be widely used to screen transgene-free mutants in various crops using diverse CRISPR/Cas9 delivery approaches.
Small G Protein StRab5b positively regulates potato resistance to Phytophthora infestans
Authors: Tian Zaimin , Zhang Zhiwei , Kang Liru , Li Min , Zhang Jian , Feng Yan , Yin Jiang , Gong Xuechen , Zhao Jun
Published: January 2023

Rabproteins are the largest members of the small G protein family and are widely distributed in eukaryotes. It comprises eight subfamilies and is responsible for regulating vesicle transport, plant growth and development, and biotic and abiotic stress responses. In this study, the small G protein gene StRab5b was cloned from potato, and its biological information, expression profile and induced expression level, overexpression and gene silencing were examined on regulating potato resistance to Phytophthora infestans using PCR, qPCR and Virus-induced gene silencing (VIGS). Our results indicate that the amino acid of StRab5b shows the highest and lowest homology with NbRab5b in N. benthamiana and StRab in potato respectively. StRab5b expression varied among different potato tissues and varieties, and was induced by P. infestans infection. Transiently ectopic expression of StRab5b in N. benthamiana enhanced its resistance to P. infestans, whereas, silencing of StRab5b and its homologous gene facilitated pathogen infection in potato and N. benthamiana respectively. Furthermore, stable expression of the StRab5b gene in potatoes enhanced its redox-stress response capacity, as manifested by the accumulation of H2O2 in infected leaves and subsequent increase in the activity and expression of ROS scavenging enzymes, thereby attenuating the development of P. infestans and ultimately reducing the lesions on infected potato leaves. In addition, the LOX gene transcripts and JA level were upregulated rapidly after inoculation with P. infestans. Collectively, our results suggest that StRab5b positively regulates the resistance against potato late blight (PLB) via JA-mediated defense signaling pathway.
The influence of family socio-economic status on learning engagement of college students majoring in preschool education: The mediating role of parental autonomy support and the moderating effect of psychological capital
Authors: Qiu Yuan , Ye Pingzhi
Published: January 2023

Objective

To explore the relationship between family socio-economic status and learning engagement of college students majoring in preschool education, as well as the mediating role of parental autonomy support and the moderating role of psychological capital.

Methods

A sample of 986 college students majoring in preschool education from Guangdong Province and Jiangxi Province were investigated by family socio-economic status questionnaire, learning engagement questionnaire, parental autonomy support questionnaire and psychological capital questionnaire.

Results

First, there was a significant positive correlation between family socio-economic status and learning engagement (β = 0.09, p < 0.05). Second, parental autonomy support played a completely mediating role between family socio-economic status and learning engagement (β = 0.05, p < 0.01). Third, the relationship between parental autonomy support and learning engagement was moderated by psychological capital, and students with high psychological capital had higher learning engagement (β = 0.24, p < 0.001).

Conclusion

Family socio-economic status could directly affect learning engagement, and could also indirectly affect learning engagement through psychological capital level moderating parental autonomy support. Our findings highlight the importance of creating an autonomous supportive family environment and focusing on the learning of students from low socio-economic status. Meanwhile, stimulating students’ psychological capital should be regarded as a part of education and teaching.
Visuospatial working memory capacity moderates the relationship between anxiety and OCD related checking behaviors
Authors: Wang Pengchong , Yan Zijun , Chen Tao , Cao Wenwen , Yang Xiangyun , Meng Fanqiang , Liu Yuqing , Li Zhanjiang
Published: January 2023

Background

Compulsive checking behavior is the most prevalent compulsive behavior in patients with obsessive-compulsive disorder (OCD). While some studies have shown that anxiety and executive function influence compulsive checking behavior, the relationship between these constructs is inconclusive. Hence, we sought to explore the interplay between executive function, anxiety and compulsive checking behavior.

Materials and methods

47 healthy participants (HC) and 51 patients with OCD participated in the study. Symptoms and emotional states were assessed using the Yale-Brown Obsessive Compulsive Scale, the Obsessive-Compulsive Inventory-Revised, the Beck Anxiety Inventory, and the Beck Depression Inventory. Participants also completed three tests of neuropsychological functioning: the Stop Signal Task, the Spatial working memory Task, and the Wisconsin card sorting test. We analyzed the relationships between anxiety, executive function, and compulsive checking symptoms.

Results

Patients with OCD showed significantly greater anxiety (p < 0.001) and impairments in visuospatial working memory function (p = 0.030) compared to HC participants, while inhibition and set-shifting were not significantly different between the two groups. Visuospatial working memory was negatively related to compulsive checking behavior (p = 0.016). Visuospatial working memory also played a moderating role in the positive relationship between anxiety and compulsive checking behavior (β = −0.281, p = 0.022).

Conclusion

Anxiety symptoms play an important role in explaining compulsive checking behavior in patients with OCD who have relatively weak visuospatial working memory ability. These findings provide a foundation for further research regarding the roles of emotion and cognitive inflexibility in compulsive checking behavior in patients with OCD.
Reduced impact of nonverbal cues during integration of verbal and nonverbal emotional information in adults with high-functioning autism
Authors: Pelzl Michael Alexander , Travers-Podmaniczky Gabrielle , Brück Carolin , Jacob Heike , Hoffmann Jonatan , Martinelli Anne , Hölz Lea , Wabersich-Flad Dominik , Wildgruber Dirk
Published: January 2023

Background

When receiving mismatching nonverbal and verbal signals, most people tend to base their judgment regarding the current emotional state of others primarily on nonverbal information. However, individuals with high-functioning autism (HFA) have been described as having difficulties interpreting nonverbal signals. Recognizing emotional states correctly is highly important for successful social interaction. Alterations in perception of nonverbal emotional cues presumably contribute to misunderstanding and impairments in social interactions.

Methods

To evaluate autism-specific differences in the relative impact of nonverbal and verbal cues, 18 adults with HFA (14 male and four female subjects, mean age 36.7 years (SD 11.4) and 18 age, gender and IQ-matched typically developed controls [14 m/4 f, mean age 36.4 years (SD 12.2)] rated the emotional state of speakers in video sequences with partly mismatching emotional signals. Standardized linear regression coefficients were calculated as a measure of the reliance on the nonverbal and verbal components of the videos for each participant. Regression coefficients were then compared between groups to test the hypothesis that autistic adults base their social evaluations less strongly on nonverbal information. Further exploratory analyses were performed for differences in valence ratings and response times.

Results

Compared to the typically developed control group, nonverbal cue reliance was reduced in adults with high-functioning autism [t(23.14) = −2.44, p = 0.01 (one-sided)]. Furthermore, the exploratory analyses showed a tendency to avoid extreme answers in the HFA group, observable via less positive as well as less negative valence ratings in response to emotional expressions of increasingly strong valence. In addition, response time was generally longer in HFA compared to the control group [F (1, 33) = 10.65, p = 0.004].

Conclusion

These findings suggest reduced impact of nonverbal cues and longer processing times in the analysis of multimodal emotional information, which may be associated with a subjectively lower relevance of this information and/or more processing difficulties for people with HFA. The less extreme answering tendency may indicate a lower sensitivity for nonverbal valence expression in HFA or result from a tendency to avoid incorrect answers when confronted with greater uncertainty in interpreting emotional states.
Changes in major psychiatric disorders in children and adolescents from 2001 to 2020: A retrospective single-center study
Authors: Zheng Hongyu , Jiang Xiaolu , Yang Rong , Wang Shuo , Zhong Hui
Published: January 2023

Objective

This study aimed to determine the hospitalization rates, length of stay, age at the time of admission, and sex distribution for major psychiatric disorders in children and adolescents and provide a reference for early intervention for these diseases and distribution of medical resources in hospitals.

Methods

We screened 4,423 patients in the child and adolescent wards of the Anhui Provincial Mental Health Center from 2001 to 2020, and examined the top four (81.1%) mental health disorders that accounted for the overall proportion of patients admitted, namely schizophrenia (SCZ) (45.7%), depressive disorder (DD) (14.5%), bipolar disorder (BD) (9.3%), and childhood emotional disorder (CED) (11.6%), and for each disorder, the percentage of hospitalization, length of stay, age at admission, and sex distribution were analyzed.

Results

From 2001 to 2020, there was a significantly decreasing trend in the proportion of hospitalizations for SCZ (p < 0.001) and an increasing trend for depression and CED (p < 0.001). In terms of length of stay, SCZ was significantly longer than the other three disorders (p < 0.001), whereas there was no significant difference between DD, BD, and CED, and there was no significant trend in length of stay for any of the four disorders. The age at admission for CED was significantly lower than that for the other three disorders (p < 0.001). There was a decreasing trend in the age at admission for DD (p = 0.011) and an increasing trend for BD (p = 0.001). A significant increase in the number of female patients admitted for SCZ, DD, and CED was observed, while there was no significant change in the sex ratio for BD.

Conclusion

Although there is a significant downward trend in the percentage of hospitalizations for SCZ, it is still the most common psychiatric disorder in children and adolescents. We observed a significant increase in the percentage of hospitalizations for DD and CED. In addition, the proportion of female patients being hospitalized is on the rise, and this aspect requires continuous attention.
A case-control study on depression, anxiety, and belief in sexual myths in trans women
Authors: Uyar Betul , Yucel Ilyas , Uyar Emre , Ateş Budak Elif , Kelle Ilker , Bulbuloglu Semra
Published: January 2023

Objective

The purpose of our study was to investigate depression, anxiety, and belief in sexual myths in trans women.

Methods

This is a prospective case-control study. The case group included 60 trans women who were referred to the Medical Biology and Genetics Department from various clinics of the research and training hospital where this study was conducted. The control group consisted of 60 healthy male individuals who presented to the same hospital for routine health follow-ups and collecting documents showing their health. In data collection, we used a Personal Information Form, the Sexual Myths Scale, and the Beck Depression and Anxiety Inventories. The IBM Statistical Package for the Social Sciences 25.0 was used to analyze the data.

Results

In the case group, 26.7% of the participants were sex workers, and all were single. While 46.7% of the participants in the case group were living with their families, 66.7% were smokers, and 13.3% were receiving hormone treatment. All 60 participants in the control group were also single. The participants in the control group had higher levels of believing sexual myths and lower levels of anxiety and depression than those in the case group (p = 0.000). The mean scores of the participants in the control group in the Sexual Orientation and Sexual Violence subscales of the Sexual Myths Scale were higher than the mean scores of those in the case group (p < 0.05).

Conclusion

The trans women who participated in this study had higher levels of anxiety and depression and lower levels of believing sexual myths than the control group. The mental health of trans women can be disrupted due to various treatments they are exposed to in society such as stigma, discrimination, and violence. Their higher anxiety and depression levels in this study could be explained by this exposure. This exposure could also have led to their lower total scores in the Sexual Myths Scale, as well as lower scores in the Sexual Violence and Sexual Orientation subscales.