bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidating the mechanisms and mitigation strategies for six-phthalate-induced toxicity in male germ cells
Authors: Kim Seok-Man , Kim Yong-Hee , Han Gil Un , Kim Seul Gi , Kim Bang-Jin , Moon Sung-Hwan , Shin Seung Hee , Ryu Buom-Yong
Published: July 2024

Phthalate esters (PAEs) are primary plasticizers and endocrine-disrupting chemicals (EDCs) that are extensively used in numerous everyday consumer products. Although the adverse effects of single PAEs have been studied, our understanding of the effect of multiple phthalate exposure on male germ cell vitality remains limited. Therefore, this study aimed to investigate the collective effects of a mixture of PAEs (MP) comprising diethyl-, bis (2-ethylhexyl)-, dibutyl-, diisononyl-, diisobutyl-, and benzyl butyl-phthalates in the proportions of 35, 21, 15, 15, 8, and 5%, respectively, on differentiated male germ cells using GC-1 spermatogonia (spg) cells. As a mixture, MP substantially hindered GC-1 spg cell proliferation at 3.13 μg/mL, with a half-maximal inhibitory concentration of 16.9 μg/mL. Treatment with 25 μg/mL MP significantly induced reactive oxygen species generation and promoted apoptosis. Furthermore, MP activated autophagy and suppressed phosphorylation of phosphoinositide 3-kinase, protein kinase B, and mammalian target of rapamycin (mTOR). The triple inhibitor combination treatment comprising parthenolide, N-acetylcysteine, and 3-methyladenine effectively reversed MP-induced GC-1 spg cell proliferation inhibition, mitigated apoptosis and autophagy, and restored mTOR phosphorylation. This study is the first to elucidate the mechanism underlying MP-induced male germ cell toxicity and the restoration of male germ cell proliferation mediated by chemical inhibitors. Therefore, it provides valuable insights into the existing literature by proposing a combinatorial toxicity mitigation strategy to counteract male germ cell toxicity induced by various EDCs exposure.
Clinical course and prognostic factors of Pneumocystis pneumonia with respiratory failure in non-HIV patients
Authors: Li Jun , Mu Xiangdong , Li Haichao , Liu Xinmin
Published: July 2024

Background

Compared with Human Immunodeficiency Virus (HIV) patients, non-HIV patients with Pneumocystis pneumonia (PCP) have more rapid onset, more rapid progression, and higher mortality.

Objectives

To investigate the predictive value of variables obtained upon hospital admission for in-hospital death and 90-day outcomes in non-HIV-PCP patients with respiratory failure (RF).

Methods

This was a single center retrospective study in a tertiary care institution over 15 years. It included all adults inpatients (≥18 years old) with laboratory confirmed non-HIV-PCP with RF who were discharged or died from Peking University First Hospital between April 1st, 2007 and November 1st, 2022. Epidemiological, clinical, laboratory, imaging and outcome data were collected from patient records.

Results

In this study, a total of 146 non-HIV-PCP patients with RF were included. There were 57 patients (39%) died during hospitalization, 44 patients (53%) died in Intensive care unit (ICU). A total of 137 patients completed 90 days of follow-up, of which 58 (42.3%) died. The multivariable regression analysis revealed that a CD8+ T cell count <115/μl (P=0.009), bronchoalveolar lavage fluid (BALF)-neutrophil percentage ≥50% (P=0.047), the time from corticosteroids withdrawal to symptom onset ≤5 days (P=0.012), and the time from visit to initiation of sulfonamides ≥2 days (P=0.011) were independent risk factors for in-hospital death. Furthermore, a CD8+ T cell count < 115/μl (P=0.001) and the time from visit to initiation of sulfonamides therapy ≥2 days (P=0.033) was independently associated with 90-day all-cause death.

Conclusions

A low CD8+ T cell count in peripheral blood, a high percentage of BALF-neutrophils, a short time from corticosteroids withdrawal to symptom onset, and a long time from visit to initiation of sulfonamides are associated with poor prognosis in non-HIV-PCP patients with RF.
Mapping knowledge landscapes and research frontiers of gastrointestinal microbiota and bone metabolism: a text-mining study
Authors: Wu Haiyang , Sun Zaijie , Guo Qiang , Li Cheng
Published: July 2024

Introduction

Extensive research efforts have been dedicated to elucidating the intricate pathways by which gastrointestinal microbiota and their metabolites exert influence on the processes of bone formation. Nonetheless, a notable gap exists in the literature concerning a bibliometric analysis of research trends at the nexus of gastrointestinal microbiota and bone metabolism.

Methods

To address this scholarly void, the present study employs a suite of bibliometric tools including online platforms, CiteSpace and VOSviewer to scrutinize the pertinent literature in the realm of gastrointestinal microbiota and bone metabolism.

Results and discussion

Examination of the temporal distribution of publications spanning from 2000 to 2023 reveals a discernible upward trajectory in research output, characterized by an average annual growth rate of 19.2%. Notably, China and the United States emerge as primary contributors. Predominant among contributing institutions are Emory University, Harvard University, and the University of California. Pacifici R from Emory University contributed the most research with 15 publications. In the realm of academic journals, Nutrients emerges as the foremost publisher, followed closely by Frontiers in Microbiology and PLOS One. And PLOS One attains the highest average citations of 32.48. Analysis of highly cited papers underscores a burgeoning interest in the therapeutic potential of probiotics or probiotic blends in modulating bone metabolism by augmenting host immune responses. Notably, significant research attention has coalesced around the therapeutic interventions of probiotics, particularly Lactobacillus reuteri, in osteoporosis, as well as the role of gastrointestinal microbiota in the etiology and progression of osteoarthritis. Keyword analysis reveals prevalent terms including gut microbiota, osteoporosis, bone density, probiotics, inflammation, SCFAs, metabolism, osteoarthritis, calcium absorption, obesity, double-blind, prebiotics, mechanisms, postmenopausal women, supplementation, risk factors, oxidative stress, and immune system. Future research endeavors warrant a nuanced exploration of topics such as inflammation, obesity, SCFAs, postmenopausal osteoporosis, skeletal muscle, oxidative stress, double-blind trials, and pathogenic mechanisms. In summary, this study presents a comprehensive bibliometric analysis of global research on the interplay between gastrointestinal microbiota and bone metabolism, offering valuable insights for scholars, particularly nascent researchers, embarking on analogous investigations within this domain.
Ten-year trajectory of coronary artery calcification and risk of cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis
Authors: Xie Changming , Luo Dongling , Liu Guodu , Chen Jie , Huang Hui
Published: July 2024

Background

Whether and how coronary artery calcium (CAC) progress contributes to cardiovascular outcomes has not been fully elucidated. The aim of this study was to identify different patterns of CAC change and evaluate the associations with different cardiovascular outcomes.

Methods

Data from the Multi-Ethnic Study of Atherosclerosis study were analyzed. Participants with at least three CT measurements were included. The main study outcome is hard cardiovascular disease (CVD). CAC scores were determined as phantom-adjusted Agatston scores. A group-based trajectory model was used to identify latent groups and estimated the hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional regression models.

Results

A total of 3,616 participants were finally enrolled [mean age 60.55 (SD 9.54) years, 47.76% men and 39.30% Caucasian]. Four distinct trajectories in CAC were identified: class 1, low-stable (24.17%); class 2, low-increasing (27.60%); class 3, moderate-increasing (30.56%); and class 4, elevated-increasing (17.67%). During 13.58 (SD 2.25) years of follow-up, 291 cases of hard CVD occurred. The event rates of hard CVD per 1,000 person-years were 2.23 (95% CI 1.53–3.25), 4.60 (95% CI 3.60–5.89), 7.67 (95% CI 6.38–9.21) and 10.37 (95% CI 8.41–12.80) for classes 1–4, respectively. Compared to participants assigned to class 1, the full-adjusted HRs of hard CVD for classes 2–4 were 2.10 (95% CI 1.33–3.01), 3.17 (95% CI 2.07–4.87), and 4.30 (95% CI 2.73–6.78), respectively. The graded positive associations with hard CVD were consistently observed in subgroups of age, sex, and race, with the presence or absence of hypertension or diabetes. By analyzing potential risk factors for distinctive CAC trajectories, risk factors for the onset and progression of CAC could possibly differ: age, male sex, history of hypertension, and diabetes are consistently associated with the low-, moderate-, and elevated-increasing trajectories. However, Caucasian race, cigarette smoking, and a higher body mass index was related only to risk of progression but not to incident CAC.

Conclusion

In this multi-ethnic population-based cohort, four unique trajectories in CAC change over a 10-year span were identified. These findings signal an underlying high-risk population and may inspire future studies on risk management.
Development of a digital mental health intervention for youth with ADHD: exploring youth perspectives on wants, needs, and barriers
Authors: Storetvedt Maren Helene Rinke , Kahlon Smiti , Berg Karin , Sundfjord Ingeborg Alvheim , Nordgreen Tine
Published: July 2024

Background

Attention deficit hyperactivity disorder (ADHD) is a mental health disorder affecting five to eight percent of children and youth worldwide. Inattention, impulsivity, and hyperactivity are core symptoms, which often leads to comorbid disorders and impairments. Increased prevalence of ADHD among youth requires development of accessible and scalable interventions. Digital interventions for ADHD show promising results for adults, yet insight into youths perspectives and needs from digital ADHD interventions is lacking. This study is set in a person-based approach and explore what youths want and need from a therapist-guided digital intervention for ADHD.

Methods

Exploratory individual interviews were conducted with youths aged 13–16 years diagnosed with ADHD (N = 16). Participants with an ADHD diagnosis were recruited primarily via social media. The interview guide was based on research, treatment guidelines, and clinical expertise. The study applied reflexive thematic analysis, within a Big Q framework. Codes and themes were generated in Nvivo.

Results

Four main themes and sub-themes were generated: (1) Tailoring the intervention to youths with ADHD (Push the right buttons; Stumbling blocks), (2) Managing ADHD (Planning and Focus; Regulation and Balance; Social interactions), (3) Me and my ADHD (Insight and Understanding; Accept and Normalization), and (4) Balance between support and independence.

Discussion

The findings suggest that youths with ADHD prefer stimulating and interactive treatment and are aversive to overwhelming, passive content. The intervention and therapist should encourage empowerment by supporting the youths autonomy in managing their ADHD. Future research is needed to investigate feasibility for person-based approaches to digital mental health treatments. Furthermore, parent perspectives on digital treatment for youths with ADHD should be investigated.
Assessing fall risk in osteoporosis patients: a comparative study of age-matched fallers and nonfallers
Authors: Moon Seong Hyun , Doshi Krupa B. , Lockhart Thurmon
Published: July 2024

This study aimed to investigate sway parameters and physical activity level of the age/gender-matched older adults with osteoporosis faller and nonfaller patients. By examining these factors, our objective was to understand how these faller and nonfaller groups with osteoporosis differed particularly in terms of balance capabilities and their impact on physical activity levels. We recruited 24 patients with osteoporosis: 12 who reported a fall within a year before recruitment (fallers) and 12 without falls (nonfallers). Given the close association between biochemical markers of musculoskeletal health such as serum calcium, parathyroid hormone (PTH), Vitamin D, and renal function, we compared these markers in both groups. As a result, elderly individuals with osteoporosis and with a history of falls within the preceding year indicated significantly higher sway velocity (P = 0.012*), sway area (P < 0.001*), and sway path length (P = 0.012*). Furthermore, fallers had significantly lower calcium (P = 0.02*) and Parathyroid hormone (PTH) (P = 0.02*), as well as higher Alkaline Phosphatase (ALP) (P = 0.02*) as compared to nonfallers despite similar vitamin D and creatinine levels. In conclusion, diminished biochemical factors in the osteoporosis faller group could possibly cause postural instability resulting in lower physical activity levels in the osteoporosis fall group and increasing the risk of falls.
Numerical simulation of groundwater in hyporheic zone with coupled parameter stochastic scheme
Authors: Wang Jing , Wang Tianye , Zhao Shougang , Sun Ruidong , Lan Yan , Zhang Yibo , Du Mengke , Zhang Taihe , Wu Jinyu , Zhang Quanfu
Published: July 2024

Groundwater numerical modeling is a crucial scientific tool for understanding groundwater circulation and supporting regional water resource planning and management. The effectiveness of these models depends largely on the accuracy of hydrogeological parameters within aquifers, which are often spatially heterogeneous and randomly distributed due to complex geological and tectonic factors. Traditional modeling approaches frequently overlook this randomness, compromising the precision and resolution of groundwater simulations. This study focuses on a section of the Qingshui River in the Huaihe River Basin. Using field and laboratory data, probability distribution functions for key parameters like hydraulic conductivity, specific yield, and specific storage were developed. These functions were integrated into the groundwater model to reflect the inherent stochastic nature of aquifer properties. This integration significantly enhanced model accuracy, reducing the root mean square error of simulated water levels from 0.47–1.43 m to 0.13–0.16 m and improving the Nash-Sutcliffe efficiency coefficients (NSE) from −2.96–0.73 to 0.94–0.98. Additionally, the model facilitated analysis of the interactions between river and groundwater, particularly in the hyporheic zone, under various scenarios. It identified spatial and temporal variations in groundwater recharge dynamics and delay effects at different distances from the river channel. For instance, recharge rates at 50 m and 150 m from the river were 0.295 m/day and 0.015 m/day, respectively, indicating stronger recharge closer to the river. The study also assessed the impact of varying river flows, riverbed permeability, and irrigation practices on water exchanges between the river and groundwater. These factors were found to significantly influence the intensity of water exchange, seepage, and groundwater reserves. This research provides valuable insights for managing river-groundwater interactions and analyzing the ecological environment of surrounding groundwater systems, underscoring the importance of incorporating stochastic characteristics into groundwater modeling.
It’s mathematics all the way down: revealing mathematical activity in non-formal learning spaces
Authors: Williams-Pierce Caro , Katırcı Nihal , Simpson Amber , Shokeen Ekta , Bih Janet
Published: July 2024

We offer this synthesized framework as a tool to reveal mathematical activity in a non-formal making-space. In particular, we connect research at different grain sizes to illustrate and explain how mathematics plays a crucial, if often implicit, role in making activities. We begin by describing the Approximate Number System and the Ratio-Processing System, and explaining how those systems connect to both embodied cognition and Thompson’s (1994) conceptualization of quantities. Then, we examine how prediction and anticipation relate, with a particular emphasis on how social feedback guided the emergent mathematical activity. We offer this framework as a way to perceive, account for, and understand the multi-layered nature of experiencing mathematical activities.
The impact of cultural capital on school performance
Authors: Nunes Alexandre Chaves , Andrade Josemberg Moura de
Published: July 2024

Introduction

We define cultural capital as a set of assets or resources accumulated over a lifetime through relationships and events in the family environment. We analyze cultural capital under two dimensions: static cultural capital (SCC) and relational cultural capital (RCC). The objective of this study was to verify the effect that cultural capital has on students' academic performance.

Method

The research included the participation of 11,795 students who were classified into four levels of cultural capital, in each of the two dimensions: G1–Critical, G2–Low, G3–Medium, and G4–High. Statistical analyses such as ANOVA, Student's t-test and factorial design showed the impact of cultural capital in the combination of the different groups with the subjects of Portuguese and mathematics.

Results

The results led us to conclude that: (1) cultural capital, in both dimensions, impacts the students' academic performance, both in Portuguese, F(3, 11764) = 9.516, with p < 0.001 and η2 = 0.002, F(3, 11764) = 42.349, with p < 0.001 and η2 = 0.011, and in mathematics, F(3, 11764) = 13,728, with p < 0.001 and η2 = 0.003, and F(3, 11764) = 28.138, with p < 0.001 and η2 = 0.007, and; 2. RCC linearly impacts student performance as SCC is increased, F(9, 11771) = 1.869, with p = 0.052 and η2 = 0.001.

Conclusion

(1) cultural capital impacts students' academic performance, but most notably in the Portuguese language discipline. (2) The dimensions of cultural capital behave differently and the excess of SCC, without the presence of RCC, impacts the reduction of medium performance. (3) The RCC linearly impacts student performance as the SCC is increased.
The therapeutic mechanism of Compound Lurong Jiangu Capsule for the treatment of cadmium-induced osteoporosis: network pharmacology and experimental verification
Authors: Zhou Ya-shuang , Huang Jian , Cao Wen-xuan , Yu Ao-xue , Li Pan , Liang Jin-ling , Leng Xiang-yang , Jin Jian , Yu Peng , Liu Jia
Published: July 2024

Background

Among bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmium-induced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain.

Objective

Network pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP.

Method

The active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herb-compound-target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What’s more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB).

Results

106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo, while CLJC rescued these phenotypes.

Conclusion

This study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway.
Identification and functional characteristics of a novel splicing heterozygote variant of COL2A1 associated with Stickler syndrome type I
Authors: Gong Yujing , Zhu Weijian , Zhu Mianmian , Chen Dan , Wu Sunke , Hu Sisi , Luo Yi , Jiang Yiyi , Zhu Ting , Wang Dan
Published: July 2024

Background

Stickler syndrome type I (STL1) is an autosomal dominant disorder characterized by ocular, auditory, orofacial, and skeletal anomalies. The main causes of STL1 are variants in the COL2A1 gene, which encodes a type II collagen precursor protein. The specific focus of this study was on a newborn from China diagnosed with STL1, with the aim of providing novel insights into the effects of a newly identified intronic variant in the COL2A1 gene on pre-mRNA splicing.

Methods

Trio whole exome sequencing was used to identify the causative variant in the family. The identified variant was validated using Sanger sequencing. Bioinformatics programs were used to predict the pathogenicity of the candidate variant. Additionally, an in vitro minigene assay was used to investigate the effects of the identified variant on RNA splicing.

Results

The proband with STL1 had a novel heterozygous splicing variant in the intron nine acceptor donor site of COL2A1 (c.655-2A>G). This splice junction variant resulted in aberrant COL2A1 mRNA splicing, leading to the skipping of exon 10 and the production of a shorter protein that may lack the last 18 native amino acids.

Conclusion

The c.655-2A>G variant in the COL2A1 gene leads to STL1 through abnormal splicing. By expanding the spectrum of variants in the COL2A1 gene, this finding improves the clinical understanding of STL1 and provides guidance for early diagnosis and disease counseling.
The association between IGF-1 levels and four types of osteoarthritis: a bidirectional and two-step mendelian randomization study
Authors: Pan Xiaohan , Cheng Minghuang , Li Dongxu , Liu Zeyu , Yao Qi , Jiang Wei , Zhang Xiaojun , Hao Jie
Published: July 2024

Background

Insulin-like Growth Factor-1 (IGF-1) plays a crucial role in the growth and metabolic functions of various tissues and cells in the body. Recently, there has been increased attention to the association between IGF-1 and osteoarthritis (OA). However, there is controversy in current research regarding the correlation between IGF-1 levels and OA. Furthermore, the specific manner in which Body Mass Index (BMI), a key risk factor for OA, mediates the impact of IGF-1 levels on OA remains unclear.

Object

This study aimed to investigate the bidirectional causal link between IGF-1 levels and OA in four body regions, and to explore how BMI influences the impact of IGF-1 on these types of OA.

Method

Two-sample Mendelian Randomization (MR) and its combined forms were utilized to investigate the bidirectional relationship between IGF-1 levels and four types of OA, as well as the mediating role of BMI in the impact of IGF-1 levels on OA. Data from various Genome-Wide Association Studies (GWAS) and multiple analytical methods, including inverse variance weighted, MR-Egger regression, and weighted median were utilized. Sensitivity analyses, such as MR-Egger intercept, Cochran Q test, leave-one-out, and MR-PRESSO, were conducted to ensure the robustness of the results.

Results

Higher IGF-1 levels are correlated with an increased risk for knee (OR, 1.07; 95% CI, 1.01–1.03; p = 1.49e-01; q = 9.86e-03), hip (OR, 1.13; 95% CI, 1.06–1.20; p = 7.61e-05; q = 7.44e-05), and hand OA (OR, 1.09; 95% CI, 1.01–1.17; p = 1.88e-02; q = 1.15e-02), but not spine OA but not spine OA (OR, 1.05; 95% CI, 0.99–1.10; p = 9.20e-02; q = 5.52e-02). Different types of OA do not affect IGF-1 levels. BMI mediates the increase in OA risk associated with higher IGF-1, including indirect spine OA risk through BMI.

Conclusion

The study elucidates the bidirectional causality between IGF-1 levels and OA in various body parts, highlighting BMI’s mediating role in the impact of IGF-1 levels on OA. This provides valuable insights for OA prevention, diagnosis, and treatment strategies. Future research will expand our study to include a broader spectrum of ethnicities and explore the underlying mechanisms involved.
Identification of shared genetic risks underlying metabolic syndrome and its related traits in the Korean population
Authors: Kim Jun Young , Cho Yoon Shin
Published: July 2024

Introduction: Observational studies have demonstrated strong correlations between metabolic syndrome (MetS) and its related traits. To gain insight into the genetic architecture and molecular mechanism of MetS, we investigated the shared genetic basis of MetS and its related traits and further tested their causal relationships.

Methods: Using summary statistics from genome-wide association analyses of about 72,000 subjects from the Korean Genome and Epidemiological Study (KoGES), we conducted genome-wide multi-trait analyses to quantify the overall genetic correlation and Mendelian randomization analyses to infer the causal relationships between traits of interest.

Results: Genetic correlation analyses revealed a significant correlation of MetS with its related traits, such as obesity traits (body mass index and waist circumference), lipid traits (triglyceride and high-density lipoprotein cholesterol), glycemic traits (fasting plasma glucose and hemoglobin A1C), and blood pressure (systolic and diastolic). Mendelian randomization analyses further demonstrated that the MetS-related traits showing significant overall genetic correlation with MetS could be genetically determined risk factors for MetS.

Discussion: Our study suggests a shared genetic basis of MetS and its related traits and provides novel insights into the biological mechanisms underlying these complex traits. Our findings further inform public health interventions by supporting the important role of the management of metabolic risk factors such as obesity, unhealthy lipid profiles, diabetes, and high blood pressure in the prevention of MetS.
Generative adversarial networks synthetic optical coherence tomography images as an education tool for image diagnosis of macular diseases: a randomized trial
Authors: Peng Jie , Xie Xiaoling , Lu Zupeng , Xu Yu , Xie Meng , Luo Li , Xiao Haodong , Ye Hongfei , Chen Li , Yang Jianlong , Zhang Mingzhi , Zhao Peiquan , Zheng Ce
Published: July 2024

Purpose

This study aimed to evaluate the effectiveness of generative adversarial networks (GANs) in creating synthetic OCT images as an educational tool for teaching image diagnosis of macular diseases to medical students and ophthalmic residents.

Methods

In this randomized trial, 20 fifth-year medical students and 20 ophthalmic residents were enrolled and randomly assigned (1:1 allocation) into Group real OCT and Group GANs OCT. All participants had a pretest to assess their educational background, followed by a 30-min smartphone-based education program using GANs or real OCT images for macular disease recognition training. Two additional tests were scheduled: one 5 min after the training to assess short-term performance, and another 1 week later to assess long-term performance. Scores and time consumption were recorded and compared. After all the tests, participants completed an anonymous subjective questionnaire.

Results

Group GANs OCT scores increased from 80.0 (46.0 to 85.5) to 92.0 (81.0 to 95.5) 5 min after training (p < 0.001) and 92.30 ± 5.36 1 week after training (p < 0.001). Similarly, Group real OCT scores increased from 66.00 ± 19.52 to 92.90 ± 5.71 (p < 0.001), respectively. When compared between two groups, no statistically significant difference was found in test scores, score improvements, or time consumption. After training, medical students had a significantly higher score improvement than residents (p < 0.001).

Conclusion

The education tool using synthetic OCT images had a similar educational ability compared to that using real OCT images, which improved the interpretation ability of ophthalmic residents and medical students in both short-term and long-term performances. The smartphone-based educational tool could be widely promoted for educational applications.

Clinical trial registration: https://www.chictr.org.cn, Chinese Clinical Trial Registry [No. ChiCTR 2100053195].
Acne treatment: research progress and new perspectives
Authors: Li Yuwei , Hu Xinhong , Dong Gaohong , Wang Xiaoxia , Liu Tao
Published: July 2024

Acne is a chronic inflammatory skin disease that primarily affects adolescents and is attributed to various factors, including hormonal changes, genetic predisposition, and environmental influences. It typically manifests in areas rich in sebaceous glands such as the face, chest, and back. Symptoms of acne can range from mild to severe and may present as pimples, pustules, nodules, cysts, and scarring. The appearance of acne can significantly impact both the physical and mental well-being of patients, potentially leading to feelings of anxiety, depression, and social withdrawal. The pathogenesis of acne is multifaceted involving genetic predisposition as well as environmental factors such as hormonal imbalances, inflammation, abnormal follicular sebaceous unit keratinization, proliferation of follicular microorganisms like Propionibacterium acnes, increased sebum production, and dietary influences. Traditional treatment methods for acne include topical drug therapy, oral drug therapy, photoelectric therapy, and chemical peeling. With ongoing research into the pathogenesis of acne, treatment methods are rapidly evolving with novel antibiotics, probiotics, biological agents, topical anti-androgen drugs, topical vitamin A acid metabolism blockers, antimicrobial peptides, immunotherapy, micro-needling, and micro-needling patches. This article aims to provide a comprehensive review of recent advancements in acne treatment.
Molecular evolutionary analysis of novel NSP4 mono-reassortant G1P[8]-E2 rotavirus strains that caused a discontinuous epidemic in Japan in 2015 and 2018
Authors: Fujii Yoshiki , Tsugawa Takeshi , Fukuda Yuya , Adachi Shuhei , Honjo Saho , Akane Yusuke , Kondo Kenji , Sakai Yoshiyuki , Tanaka Toju , Sato Toshiya , Higasidate Yoshihito , Kubo Noriaki , Mori Toshihiko , Kato Shinsuke , Hamada Ryo , Kikuchi Masayoshi , Tahara Yasuo , Nagai Kazushige , Ohara Toshio , Yoshida Masaki , Nakata Shuji , Noguchi Atsuko , Kikuchi Wakako , Hamada Hiromichi , Tokutake-Hirose Shoko , Fujimori Makoto , Muramatsu Masamichi
Published: July 2024

In the 2010s, several unusual rotavirus strains emerged, causing epidemics worldwide. This study reports a comprehensive molecular epidemiological study of rotaviruses in Japan based on full-genome analysis. From 2014 to 2019, a total of 489 rotavirus-positive stool specimens were identified, and the associated viral genomes were analyzed by next-generation sequencing. The genotype constellations of those strains were classified into nine patterns (G1P[8] (Wa), G1P[8]-E2, G1P[8] (DS-1), G2P[4] (DS-1), G3P[8] (Wa), G3P[8] (DS-1), G8P[8] (DS-1), G9P[8] (Wa), and G9P[8]-E2). The major prevalent genotype differed by year, comprising G8P[8] (DS-1) (37% of that year’s isolates) in 2014, G1P[8] (DS-1) (65%) in 2015, G9P[8] (Wa) (72%) in 2016, G3P[8] (DS-1) (66%) in 2017, G1P[8]-E2 (53%) in 2018, and G9P[8] (Wa) (26%) in 2019. The G1P[8]-E2 strains (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1) isolated from a total of 42 specimens in discontinuous years (2015 and 2018), which were the newly-emerged NSP4 mono-reassortant strains. Based on the results of the Bayesian evolutionary analyses, G1P[8]-E2 and G9P[8]-E2 were hypothesized to have been generated from distinct independent inter-genogroup reassortment events. The G1 strains detected in this study were classified into multiple clusters, depending on the year of detection. A comparison of the predicted amino acid sequences of the VP7 epitopes revealed that the G1 strains detected in different years encoded VP7 epitopes harboring distinct mutations. These mutations may be responsible for immune escape and annual changes in the prevalent strains.
Efficacy of sodium hypochlorite in overcoming antimicrobial resistance and eradicating biofilms in clinical pathogens from pressure ulcers
Authors: Fabrizio Giorgia , Sivori Francesca , Cavallo Ilaria , Truglio Mauro , Toma Luigi , Sperati Francesca , Francalancia Massimo , Obregon Francisco , Pamparau Luisa , Kovacs Daniela , Pimpinelli Fulvia , Di Domenico Enea Gino
Published: July 2024

Sodium hypochlorite (NaOCl) is widely recognized for its broad-spectrum antimicrobial efficacy in skin wound care. This study investigates the effectiveness of NaOCl against a range of bacterial and fungal isolates from pressure ulcer (PU) patients.

We analyzed 20 bacterial isolates from PU patients, comprising carbapenem-resistant Klebsiella pneumoniae (CRKP), multidrug-resistant Acinetobacter baumannii (MDRAB), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), along with 5 Candida albicans isolates. Antibiotic resistance profiles were determined using standard susceptibility testing. Whole-genome sequencing (WGS) was employed to identify antimicrobial resistance genes (ARGs) and disinfectant resistance genes (DRGs). Genetic determinants of biofilm formation were also assessed. The antimicrobial activity of NaOCl was evaluated by determining the minimum inhibitory concentration (MIC) and the minimal biofilm eradication concentration (MBEC) for both planktonic and biofilm-associated cells.

CRKP and MDRAB showed resistance to fluoroquinolones and carbapenems, while MRSA exhibited resistance to β-lactams and levofloxacin. MSSA displayed a comparatively lower resistance profile. WGS identified significant numbers of ARGs in CRKP and MDRAB, with fewer DRGs compared to MRSA and MSSA. All isolates possessed genes associated with fimbriae production and adhesion, correlating with pronounced biofilm biomass production. NaOCl demonstrated substantial antimicrobial activity against both planktonic cells and biofilms. The MIC90 for planktonic bacterial cells was 0.125 mg/mL, and the MBEC90 ranged from 0.225 to 0.5 mg/mL. For planktonic C. albicans, the MIC90 was 0.150 mg/mL, and the MBEC90 was 0.250 mg/mL.

These results highlight the challenge in treating biofilm-associated infections and underscore the potential of NaOCl as a robust antimicrobial agent against difficult-to-treat biofilm infections at concentrations lower than those typically found in commercial disinfectants.
Metabolomics highlights biochemical perturbations occurring in the kidney and liver of mice administered a human dose of colistin
Authors: Barla I. , Dagla I. V. , Daskalopoulou A. , Panagiotopoulou M. , Kritikaki M. , Dalezis P. , Thomaidis N. , Tsarbopoulos A. , Trafalis D. , Gikas E.
Published: July 2024

Introduction: Colistin (CMS) is used for the curation of infections caused by multidrug-resistant bacteria. CMS is constrained by toxicity, particularly in kidney and neuronal cells. The recommended human doses are 2.5–5 mg/kg/day, and the toxicity is linked to higher doses. So far, the in vivo toxicity studies have used doses even 10-fold higher than human doses. It is essential to investigate the impact of metabolic response of doses, that are comparable to human doses, to identify biomarkers of latent toxicity. The innovation of the current study is the in vivo stimulation of CMS's impact using a range of CMS doses that have never been investigated before, i.e., 1 and 1.5 mg/kg. The 1 and 1.5 mg/kg, administered in mice, correspond to the therapeutic and toxic human doses, based on previous expertise of our team, regarding the human exposure. The study mainly focused on the biochemical impact of CMS on the metabolome, and on the alterations provoked by 50%-fold of dose increase. The main objectives were i) the comprehension of the biochemical changes resulting after CMS administration and ii) from its dose increase; and iii) the determination of dose-related metabolites that could be considered as toxicity monitoring biomarkers.

Methods: The in vivo experiment employed two doses of CMS versus a control group treated with normal saline, and samples of plasma, kidney, and liver were analysed with a UPLC-MS-based metabolomics protocol. Both univariate and multivariate statistical approaches (PCA, OPLS-DA, PLS regression, ROC) and pathway analysis were combined for the data interpretation.

Results: The results pointed out six dose-responding metabolites (PAA, DA4S, 2,8-DHA, etc.), dysregulation of renal dopamine, and extended perturbations in renal purine metabolism. Also, the study determined altered levels of liver suberylglycine, a metabolite linked to hepatic steatosis. One of the most intriguing findings was the detection of elevated levels of renal xanthine and uric acid, that act as AChE activators, leading to the rapid degradation of acetylcholine. This evidence provides a naïve hypothesis, for the potential association between the CMS induced nephrotoxicity and CMS induced 39 neurotoxicity, that should be further investigated.
Retrospective analysis of nystagmus characteristics and clinical applications of positional testing in patients with cupulolithiasis of the posterior semicircular canal in benign paroxysmal positional vertigo
Authors: Wu Jing , Zou Yihuai , Xu Wenyan , Ma Hongming , Huang Lixian , Zhao Bo , Sun Liman
Published: July 2024

Objective

This study aimed to investigate the characteristics of positional nystagmus in patients with cupulolithiasis of the posterior semicircular canal-benign paroxysmal positional vertigo (PC-BPPV-cu) to improve clinical diagnostic accuracy.

Methods

This study retrospectively analyzed 128 cases of PC-BPPV-cu and 128 cases of canalolithiasis of BPPV (PC-BPPV-ca). General data, intensity, distribution, and the correlation of positional nystagmus were compared between the two groups.

Results

Compared to the PC-BPPV-ca group, more cases from the PC-BPPV-cu group initially presented in the emergency department (P < 0.05). The most frequent positional nystagmus induced by PC-BPPV-cu was torsional-upbeat nystagmus, characterized by the upper pole of the affected eye beating toward the lower ear and vertically upward (387 cases, 59.7%). It was followed by torsional-downbeat nystagmus, characterized by the upper pole of the unaffected eye beating toward the lower ear and vertically downward (164 cases, 25.3%). The former represented posterior canal excitatory nystagmus (PC-EN), while the latter represented posterior canal inhibitory nystagmus (PC-IN). In the PC-BPPV-cu group, PC-EN was most easily caused by the Half Dix–Hallpike (HH) maneuver on the affected side, while PC-IN was most easily induced by a face-down position (FDP) on the unaffected side at approximately 45° angle (45° FDP). The vertical slow phase velocity (v-SPV) of positional nystagmus was more potent in the affected HH than in other positions with PC-EN (all P < 0.05); the v-SPV of positional nystagmus was greater in the 45° FDP than in different positions with PC-IN (all P < 0.05); the v-SPV of the affected Dix–Hallpike (DH) maneuver in the PC-BPPV-ca group was significantly greater than that of the affected HH maneuver in the PC-BPPV-cu group (P < 0.05). The a priori analysis showed that the strongest correlation with HH positional nystagmus was observed in the affected side roll test, followed by the DH maneuver.

Conclusion

In the PC-BPPV-cu group, the HH maneuver most easily induced PC-EN on the affected side, and PC-IN was most easily induced by the 45° FDP. In some cases of PC-BPPV-cu, significant nystagmus was not observed to be induced in the DH position on the affected side; however, vertical rotation nystagmus was induced in the roll-test position on the affected side. In such cases, PC-BPPV-cu diagnosis should be considered, and HH and 45° FDP tests should be conducted to support the diagnosis.
Influence of short-term hypoxia exposure on dynamic visual acuity
Authors: Wang Yuchen , Xie Jiaxing , Yu Xinli , Liu Yihe , Wang Zesong , Guo Anqi , Ding Yi , Zhou Xinzuo , Liu Siru , Li Jiaxi , Zhou Chengkai , Li Yuanhong , Liu Ziyuan , Li Xuemin , Ding Li
Published: July 2024

Background

To quantify the changes in dynamic visual acuity (DVA) and explain the hidden reasons after acute exposure to hypobaric hypoxia status.

Methods

The study group comprised 18 healthy male and 15 healthy female participants aged 20–24 years old. DVA was measured with the self-developed software of Meidixin (Tianjin) Co., Ltd. Measurements were taken at eight altitudes. Data analysis was performed using the Kolmogorov–Smirnov test, paired sample T-test, and two-way repeated measures analysis of variance (ANOVA) for repeated measurements.

Results

At constant altitude, DVA showed an overall decreasing trend with increasing angular velocity and a fluctuating decrease at the vast majority of altitudes. At constant angular velocities, DVA gradually increased with altitude, with the most pronounced increase in DVA at altitude 5, and thereafter a gradual decrease in DVA as altitude increased. Finally, as altitude decreased, DVA increased again and reached a higher level at the end of the experiment, which was superior to the DVA in the initial state.

Conclusion

Under a hypobaric hypoxic environment at high altitude, DVA was affected by the angular velocity and the degree of hypoxia, manifesting as an increase or decrease in DVA, which affects the pilot's observation of the display and control interfaces during the driving process, acquisition of information, and decision-making ability, which in turn may potentially jeopardize the safety of the flight.
Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS
Authors: Min Jin-Hong , Sarlus Heela , Harris Robert A.
Published: July 2024

The pathophysiology of ALS involves many signs of a disruption in copper homeostasis, with both excess free levels and functional deficiency likely occurring simultaneously. This is crucial, as many important physiological functions are performed by cuproenzymes. While it is unsurprising that many ALS symptoms are related to signs of copper deficiency, resulting in vascular, antioxidant system and mitochondrial oxidative respiration deficiencies, there are also signs of copper toxicity such as ROS generation and enhanced protein aggregation. We discuss how copper also plays a key role in proteostasis and interacts either directly or indirectly with many of the key aggregate-prone proteins implicated in ALS, such as TDP-43, C9ORF72, SOD1 and FUS as well as the effect of their aggregation on copper homeostasis. We suggest that loss of cuproprotein function is at the core of ALS pathology, a condition that is driven by a combination of unbound copper and ROS that can either initiate and/or accelerate protein aggregation. This could trigger a positive feedback cycle whereby protein aggregates trigger the aggregation of other proteins in a chain reaction that eventually captures elements of the proteostatic mechanisms in place to counteract them. The end result is an abundance of aggregated non-functional cuproproteins and chaperones alongside depleted intracellular copper stores, resulting in a general lack of cuproenzyme function. We then discuss the possible aetiology of ALS and illustrate how strong risk factors including environmental toxins such as BMAA and heavy metals can functionally behave to promote protein aggregation and disturb copper metabolism that likely drives this vicious cycle in sporadic ALS. From this synthesis, we propose restoration of copper balance using copper delivery agents in combination with chaperones/chaperone mimetics, perhaps in conjunction with the neuroprotective amino acid serine, as a promising strategy in the treatment of this incurable disease.
Anorexia and bulimia in relation to ulcerative colitis: a Mendelian randomization study
Authors: Su Qiang , Li Jian , Lu Yun , Wu Min , Liang Jiang , An Zhenxiang
Published: July 2024

Background

Evidence for anorexia and bulimia in relation to the risk of ulcerative colitis (UC) is limited and inconsistent. The objective of this research was to utilize bi-directional, two-sample Mendelian randomization (MR) analysis to predict the causal association between anorexia nervosa and bulimia nervosa with UC.

Methods

The genome-wide association studies (GWAS) provided data for anorexia and bulimia from the UK Biobank, utilizing single-nucleotide polymorphisms (SNP) as instrumental variables. Additionally, genetic associations with UC were collected from various sources including the FinnGen Biobank, the UK Biobank and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The main analytical approach utilized in this study was the inverse-variance-weighted (IVW) method. To evaluate horizontal pleiotropy, the researchers conducted MR-Egger regression and MR-PRESSO global test analyses. Additionally, heterogeneity was assessed using the Cochran’s Q test.

Results

This study found a negative association between genetically predicted bulimia (OR = 0.943, 95% CI: 0.893–0.996; p = 0.034) and the risk of UC in the IIBDGC dataset, indicating that individuals with bulimia have approximately a 5.7% lower risk of developing UC. No association was observed in the other two datasets. Conversely, genetically predicted anorexia was not found to be causally associated with UC. In bi-directional Mendelian randomization, UC from the IIBDGC dataset was negatively associated with the risk of anorexia (OR = 0.877, 95% CI: 0.797–0.965; p = 0.007), suggesting that UC patients have approximately a 12.3% lower risk of developing anorexia, but not causally associated with bulimia.

Conclusion

Genetically predicted bulimia may have a negative association with the onset of UC, while genetically predicted anorexia does not show a causal relationship with the development of UC. Conversely, genetically predicted UC may have a negative association with the development of anorexia.