bluuebunny/crossref_metadata_2025 huggingface dataset:
Casual associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines
Authors: Wu Shuyun , Yi Jiazhi , Wu Bin
Published: May 2024

Background

Previous observational epidemiological studies have suggested a potential association between thyroid function and inflammatory bowel disease (IBD). However, the findings remain inconclusive, and whether this association is causal remains uncertain. The objective of this study is to investigate the causal association between thyroid function and IBD.

Methods

Genome-wide association studies (GWAS) involving seven indicators of thyroid function, IBD, and 41 cytokines were analyzed. Bidirectional two-sample Mendelian randomization (MR) and multivariable MR were conducted to examine the causal relationship between thyroid function and IBD and to explore the potential mechanisms underlying the associations.

Results

Genetically determined hypothyroidism significantly reduced the risk of CD (odds ratio [OR] = 0.761, 95% CI: 0.655–0.882, p < 0.001). Genetically determined reference-range TSH was found to have a suggestive causal effect on IBD (OR = 0.931, 95% CI: 0.888–0.976, p = 0.003), (Crohn disease) CD (OR = 0.915, 95% CI: 0.857–0.977, p = 0.008), and ulcerative colitis (UC) (OR =0.910, 95% CI: 0.830–0.997, p = 0.043). In reverse MR analysis, both IBD and CD appeared to have a suggestive causal effect on the fT3/fT4 ratio (OR = 1.002, p = 0.013 and OR = 1.001, p = 0.015, respectively). Among 41 cytokines, hypothyroidism had a significant impact on interferon-inducible protein-10 (IP-10) (OR = 1.465, 95% CI: 1.094–1.962, p = 0.010). The results of multivariable MR showed that IP-10 may mediate the causal effects of hypothyroidism with CD.

Conclusion

Our results suggest that an elevated TSH level reduces the risk of CD, with IP-10 potentially mediating this association. This highlights the pituitary-thyroid axis could serve as a potential therapeutic strategy for CD.
Exploratory metabolomic analysis for characterizing the metabolic profile of the urinary bladder under estrogen deprivation
Authors: Zhang Wei , Yang Qingbo , Song Yingying , Liu Wenheng , Li Yao
Published: May 2024

Background

Estrogen homeostasis is crucial for bladder function, and estrogen deprivation resulting from menopause, ovariectomy or ovarian dysfunction may lead to various bladder dysfunctions. However, the specific mechanisms are not fully understood.

Methods

We simulated estrogen deprivation using a rat ovariectomy model and supplemented estrogen through subcutaneous injections. The metabolic characteristics of bladder tissue were analyzed using non-targeted metabolomics, followed by bioinformatics analysis to preliminarily reveal the association between estrogen deprivation and bladder function.

Results

We successfully established a rat model with estrogen deprivation and, through multivariate analysis and validation, identified several promising biomarkers represented by 3, 5-tetradecadiencarnitine, lysoPC (15:0), and cortisol. Furthermore, we explored estrogen deprivation-related metabolic changes in the bladder primarily characterized by amino acid metabolism imbalance.

Conclusion

This study, for the first time, depicts the metabolic landscape of bladder resulting from estrogen deprivation, providing an important experimental basis for future research on bladder dysfunctions caused by menopause.
An improved decentralized control strategy for a PV hybrid energy storage system in an LVDC microgrid
Authors: Li Jianbiao , Chen Yong , Wu Yue , Cheng Xu , Yang Ruixiong
Published: May 2024

This paper introduces an improved decentralized control strategy for a photovoltaic (PV) hybrid energy storage (HES) system (HESS) in a DC microgrid. The power sharing method of the HES system is discussed in depth. The basic principle of virtual resistance and capacitance droop (VRCD) control, which consists of virtual resistance droop (VRD) and virtual capacitance droop (VCD) control, is analyzed in detail to achieve the decoupling of the HES system for high- and low-frequency load power distribution. For the virtual capacitance control loop, the voltage compensator is added to achieve terminal voltage restoration of the supercapacitor (SC). For the virtual resistance control loop, in order to solve the problems of the unbalanced state of charge (SOC) of battery storage, a virtual resistance droop control based on a novel adaptive function is introduced. Finally, a model of the HESS in a DC microgrid is built in a real-time emulator to verify the effectiveness of the proposed control strategy.
Successful treatment with tislelizumab plus chemotherapy for SMARCA4-deficient undifferentiated tumor: a case report
Authors: Dong Wen , Dai Anli , Wu Zhijun , Wang Jiangtao , Wu Tao , Du Yangfeng , Tian Wei , Zheng Jiang , Zhang Yan , Wang Hongming , Cai Juan , Dong Susu , Zhou Yan , Li Siyan , Xiao Zemin
Published: May 2024

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT.
Intracranial infection caused by Mycobacterium rhodesiae with specific imaging findings and good response to medication: a case report and literature review
Authors: Chen Siwei , Sun Wei , Liu Ran , Yao Lanqiu , Peng Qing
Published: May 2024

Nontuberculous mycobacteria (NTM) are exceedingly rare etiological agents of intracranial infections. Among them, Mycobacterium rhodesiae stands out as an even less common pathogen. In this paper, we report the first documented case of a central nervous system (CNS) infection in humans caused by Mycobacterium rhodesiae, which has specific imaging findings and good response to the therapy by using Linezolid, Clarithromycin, and Minocycline. The diagnosis was facilitated by a comprehensive multimodal approach, incorporating multisite imaging, cerebrospinal fluid analysis via next-generation sequencing (NGS), and targeted genetic testing. Furthermore, this paper provides a derivation of the clinical characteristics observed in other documented instances of CNS infections attributable to NTM and based on a review of the current literature. Our experience contributes to the evidence that is needed to understand the full spectrum of NTM-related CNS pathologies and underscores the importance of a multidisciplinary diagnostic process in atypical presentations of intracranial infections.
Rare taxa mediate microbial carbon and nutrient limitation in the rhizosphere and bulk soil under sugarcane–peanut intercropping systems
Authors: Fu Yue , Tang Xiumei , Sun Tingting , Lin Litao , Wu Lixue , Zhang Tian , Gong Yifei , Li Yuting , Wu Haining , Xiong Jun , Tang Ronghua
Published: May 2024

Introduction

Microbial carbon (C) and nutrient limitation exert key influences on soil organic carbon (SOC) and nutrient cycling through enzyme production for C and nutrient acquisition. However, the intercropping effects on microbial C and nutrient limitation and its driving factors between rhizosphere and bulk soil are unclear.

Methods

Therefore, we conducted a field experiment that covered sugarcane–peanut intercropping with sole sugarcane and peanut as controls and to explore microbial C and nutrient limitation based on the vector analysis of enzyme stoichiometry; in addition, microbial diversity was investigated in the rhizosphere and bulk soil. High throughput sequencing was used to analyze soil bacterial and fungal diversity through the 16S rRNA gene and internal transcribed spacer (ITS) gene at a phylum level.

Results

Our results showed that sugarcane–peanut intercropping alleviated microbial C limitation in all soils, whereas enhanced microbial phosphorus (P) limitation solely in bulk soil. Microbial P limitation was also stronger in the rhizosphere than in bulk soil. These results revealed that sugarcane-peanut intercropping and rhizosphere promoted soil P decomposition and facilitated soil nutrient cycles. The Pearson correlation results showed that microbial C limitation was primarily correlated with fungal diversity and fungal rare taxa (Rozellomycota, Chyltridiomycota, and Calcarisporiellomycota) in rhizosphere soil and was correlated with bacterial diversity and most rare taxa in bulk soil. Microbial P limitation was solely related to rare taxa (Patescibacteria and Glomeromycota) in rhizosphere soil and related to microbial diversity and most rare taxa in bulk soil. The variation partitioning analysis further indicated that microbial C and P limitation was explained by rare taxa (7%–35%) and the interactions of rare and abundant taxa (65%–93%).

Conclusion

This study indicated the different intercropping effects on microbial C and nutrient limitation in the rhizosphere and bulk soil and emphasized the importance of microbial diversity, particularly rare taxa.
Clinical and prognostic implications of hyaluronic acid in patients with COVID-19 reinfection and first infection
Authors: Li Yanyan , Han Ming , Li Xin
Published: May 2024

Objective

Previous research has shown that human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promote coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA). However, the association of HA with mortality and long COVID in SARS-CoV-2 reinfection and first infection is unclear.

Methods

Patients with COVID-19 at Beijing Ditan Hospital from September 2023 to November 2023 were consecutively enrolled. SARS-CoV-2 reinfections were matched 1:2 with first infections using a nearest neighbor propensity score matching algorithm. We compared the hospital outcomes between patients with COVID-19 reinfection and first infection. The association between HA levels and mortality and long COVID in the matched cohort was analyzed.

Results

The reinfection rate among COVID-19 hospitalized patients was 25.4% (62 cases). After propensity score matching, we found that reinfection was associated with a better clinical course and prognosis, including lower levels of C-reactive protein and erythrocyte sedimentation rate, fewer cases of bilateral lung infiltration and respiratory failure, and shorter viral clearance time and duration of symptoms (p < 0.05). HA levels were significantly higher in patients with primary infection [128.0 (90.5, 185.0) vs. 94.5 (62.0, 167.3), p = 0.008], those with prolonged viral clearance time [90.5 (61.5, 130.8) vs. 130.0 (95.0, 188.0), p < 0.001], and deceased patients [105.5 (76.8, 164.5) vs. 188.0 (118.0, 208.0), p = 0.002]. Further analysis showed that HA was an independent predictor of death (AUC: 0.789), and the risk of death increased by 4.435 times (OR = 5.435, 95% CI = 1.205–24.510, p = 0.028) in patients with high HA levels. We found that patients with HA levels above 116 ng/mL had an increased risk of death. However, the incidence of long COVID was similar in the different HA level groups (p > 0.05).

Conclusion

Serum HA may serve as a novel biomarker for predicting COVID-19 mortality in patients with SARS-CoV-2 reinfection and first infection. However, HA levels may not be associated with long COVID.
ACTL6A: unraveling its prognostic impact and paving the way for targeted therapeutics in carcinogenesis
Authors: Eid Refaat A. , Mamdouh Farag , Abdulsahib Waleed K. , Alshaya Dalal Sulaiman , Al-Salmi Fawziah A. , Ali Alghamdi Maha , Jafri Ibrahim , Fayad Eman , Alsharif Ghadi , Zaki Mohamed Samir A. , Alshehri Mohammed A. , Noreldin Ahmed E. , Alaa Eldeen Muhammad
Published: May 2024

Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools.

Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models.

Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection.

Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.
Impairment of entorhinal cortex network activity in Alzheimer’s disease
Authors: Karimani Farnaz , Asgari Taei Afsaneh , Abolghasemi-Dehaghani Mohammad-Reza , Safari Mir-Shahram , Dargahi Leila
Published: May 2024

The entorhinal cortex (EC) stands out as a critical brain region affected in the early phases of Alzheimer’s disease (AD), with some of the disease’s pathological processes originating from this area, making it one of the most crucial brain regions in AD. Recent research highlights disruptions in the brain’s network activity, characterized by heightened excitability and irregular oscillations, may contribute to cognitive impairment. These disruptions are proposed not only as potential therapeutic targets but also as early biomarkers for AD. In this paper, we will begin with a review of the anatomy and function of EC, highlighting its selective vulnerability in AD. Subsequently, we will discuss the disruption of EC network activity, exploring changes in excitability and neuronal oscillations in this region during AD and hypothesize that, considering the advancements in neuromodulation techniques, addressing the disturbances in the network activity of the EC could offer fresh insights for both the diagnosis and treatment of AD.
Enhanced organic photovoltaic-based retinal prosthesis using a cathode-modified structure with plasmonic silver nanoparticles: a computational study
Authors: Rahmani Ali , Eom Kyungsik
Published: May 2024

Introduction

Organic interfaces have recently emerged as a breakthrough trend in biomedical applications, demonstrating exceptional performance in stimulating retinal neuronal cells owing to their high flexibility and compatibility with tissues. However, the primary challenge associated with organic photovoltaics is their low efficiency compared to that of their inorganic counterparts. Among different approaches, embedding plasmonic metal nanoparticles (NPs) in active or buffer layers can efficiently improve photovoltaic cell performance.

Methods

A cathode decorated with silver nanoparticles is introduced to increase the absorption Phenomenon and improve the interface performance as a computational study. In addition to embedding spherical silver nanoparticles in the active layer (A-AgNPs), a monolayer array of spherical AgNPs in the cathode electrode (K-AgNPs) is incorporated. In this configuration, the large K-AgNPs play dual roles: acting as cathode electrode and serving as plasmonic centers to increase light trapping and absorption. The bulk heterojunction PCPDTBT:PCBM is chosen as the active layer due to its favorable electronic properties.

Results

Our computational analysis demonstrates a notable 10% enhancement in the photovoltaic cell current density for the developed structure with K-AgNPs in contrast to without them. Additionally, the simulation results reveal that the modeled device achieves a two-fold efficiency of the bare photovoltaic cell (without A-AgNPs and K-AgNPs), which is particularly evident at a low intensity of 0.26 mW/mm2.

Discussion

This study aims to propose an efficient epiretinal prosthesis structure using a different strategy for plasmonic effects rather than conventional methods, such as incorporating NPs into the active or buffer layer. This structure can prevent the harmful side effects of using large metal NPs (r > 10 nm) in the active layer during exciton quenching, charge trapping, and recombination, which deteriorate the power conversion efficiency (PCE).
Investigation of the differential susceptibility of extraocular muscles in patients diagnosed with ocular myasthenia gravis based on the computerized diplopia test and the Ocular Motor Nerve Palsy Scale
Authors: Fan Yi-fei , Tu Sai-jun , Liu Yani , Li Xue-mei , Liu Tie-juan , Zhou Ling-yun
Published: May 2024

Introduction

The pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two novel tools to discern this pattern.

Methods

A retrospective analysis was conducted to collect and organize clinical data from 43 patients diagnosed with ocular myasthenia gravis. Each patient underwent both the computerized diplopia test and the Ocular Motor Nerve Palsy Scale assessment to evaluate the involvement of extraocular muscles.

Results

Among the patients, there were 30 male and 13 female individuals, with a total of 113 affected extraocular muscles identified. Among all the affected extraocular muscles, the involvement of the levator palpebrae superioris muscle accounted for 35.40%, medial rectus muscle 7.7%, lateral rectus muscle 16.81%, superior rectus muscle 13.27%, inferior rectus muscle 12.39%, superior oblique muscle 1.77%, and inferior oblique muscle 2.65% of the total affected extraocular muscles. The positivity rates of the Neostigmine test were 89.19%, AChR antibody detection was 59.38%, and repetitive nerve stimulation was 34.38%. The AChR antibody positive rate among patients with only diplopia was 100%; among those with only ptosis, it was 80%; and among those with both diplopia and ptosis, it was 86.67%.

Conclusion

The involvement of the extraocular muscles is not uniform. The levator palpebrae superioris exhibits the highest incidence rate, followed by the four rectus muscles and two oblique muscles. The inferior oblique involvement typically occurs when four or more EOMs are affected. Moreover, the levator palpebrae superioris and medial rectus show a higher tendency for bilateral involvement compared with other extraocular muscles.
Improving rehabilitation motivation and motor learning ability of stroke patients using different reward strategies: study protocol for a single-center, randomized controlled trial
Authors: Zhao Jingwang , Guo Jiangling , Chen Yeping , Li Wenxi , Zhou Ping , Zhu Guangyue , Han Peipei , Xu Dongsheng
Published: May 2024

Background

Stroke survivors often face challenges in motor learning and motivation during rehabilitation, which can impede their recovery progress. Traditional rehabilitation methods vary in effectiveness, prompting the exploration of novel approaches such as reward strategies. Previous research indicates that rewards can enhance rehabilitation motivation and facilitate motor learning. However, most reward paradigms have utilized fixed reward amounts, which also have limitations. Exploring alternative, more effective reward strategies, such as probabilistic rewards, is warranted to optimize stroke patient rehabilitation.

Methods

A total of 81 stroke patients will be recruited and randomly assigned to control, fixed reward, or probabilistic reward groups at a ratio of 1:1:1 using a randomized number table method. Participants will undergo 10 days of daily hand motor function rehabilitation training, with sessions lasting 20 min each. The training will involve pegboard tests and box and block tests. Control group participants will receive standard training, while fixed reward group members will receive monetary incentives for completing tests, and probabilistic reward group members will have the chance to win monetary rewards through a lottery box. Rehabilitation motivation and motor performance and functional near-infrared spectroscopy brain imaging will be conducted at designated time points. The primary outcome measure is the stroke rehabilitation motivation scale, and the second outcome measures include motor performance, simple test for evaluating hand function, motivation and pleasure scale self-report, and Pittsburgh rehabilitation participation scale.

Discussion

Reward-based training enhance rehabilitation participation and adherence, it also improve motor learning speed and memory retention of stroke patients. The fixed reward applied in the past studies could diminish the sensitivity of stroke patients to rewards, while probabilistic reward may provide unpredictable or variable incentives or reinforcements for motor rehabilitation. This study will compare the efficacy of different reward strategies in enhancing motor learning ability and rehabilitation motivation among stroke patients. By conducting a randomized controlled trial, the study seeks to provide valuable insights into optimizing stroke rehabilitation protocols and improving patient outcomes.

Clinical Trial Registration:https://www.chictr.org.cn/, ChiCTR2400082419.
Linking artificial sweetener intake with kidney function: insights from NHANES 2003–2006 and findings from Mendelian randomization research
Authors: Ran Zhuoling , Zheng Yuxuan , Yu Lin , Zhang Yuxian , Zhang Zhenjiang , Li Huijie , Li Xuhan , Song Jing , Zhang Li , Zhang Ran , Lu Chang , Gong Yang , Gong Jian
Published: May 2024

Background

The current investigation examines the association between artificial sweetener (AS) consumption and the likelihood of developing chronic kidney disease (CKD), along with its impact on kidney function.

Methods

We utilized data from the National Health and Nutrition Examination Survey from 2003–2006 to conduct covariance analysis and weighted adjusted logistic regression, aiming to assess the association between artificial sweetener intake and CKD risk, as well as kidney function indicators. Subsequently, we employed Mendelian randomization methods to validate the causal relationship between the intake of artificial sweeteners, CKD risk, and kidney function indicators. Instrumental variable analysis using inverse-variance weighting and Robust adjusted profile score were the primary analytical methods employed.

Results

A total of 20,470 participants were included in the study, with 1,257 participants ultimately included in the analysis. In all adjusted logistic regression models, no significant association was found between the intake of artificial sweeteners and CKD risk. Similarly, the summary odds ratios (OR) for each unit change in genetically predicted CKD risk were 2.14 (95% CI: 0.83, 5.21, p = 0.092), 1.41 (95% CI: 0.54, 3.63, p = 0.482), and 1.50 (95% CI: 0.50, 4.52, p = 0.468) for the impact of artificial sweeteners added to cereals, tea, and coffee, respectively. It was only observed that adding artificial sweeteners to coffee was associated with a modest reduction in urinary albumin-to-creatinine ratio (OR = 0.94, 95% CI: −0.108, −0.022, p = 0.003), the effect appeared to be relatively small and may not directly impact the individual level.

Conclusion

Our study does not support a causal relationship between artificial sweetener intake and the risk of CKD. However, due to the limitations and potential confounding factors, these findings need to be further validated through larger sample sizes in observational studies and Mendelian randomization analyses.
Mathematical model of MMC chemotherapy for non-invasive bladder cancer treatment
Authors: Yosef Marom , Bunimovich-Mendrazitsky Svetlana
Published: May 2024

Mitomycin-C (MMC) chemotherapy is a well-established anti-cancer treatment for non-muscle-invasive bladder cancer (NMIBC). However, despite comprehensive biological research, the complete mechanism of action and an ideal regimen of MMC have not been elucidated. In this study, we present a theoretical investigation of NMIBC growth and its treatment by continuous administration of MMC chemotherapy. Using temporal ordinary differential equations (ODEs) to describe cell populations and drug molecules, we formulated the first mathematical model of tumor-immune interactions in the treatment of MMC for NMIBC, based on biological sources. Several hypothetical scenarios for NMIBC under the assumption that tumor size correlates with cell count are presented, depicting the evolution of tumors classified as small, medium, and large. These scenarios align qualitatively with clinical observations of lower recurrence rates for tumor size ≤ 30[mm] with MMC treatment, demonstrating that cure appears up to a theoretical x[mm] tumor size threshold, given specific parameters within a feasible biological range. The unique use of mole units allows to introduce a new method for theoretical pre-treatment assessments by determining MMC drug doses required for a cure. In this way, our approach provides initial steps toward personalized MMC chemotherapy for NMIBC patients, offering the possibility of new insights and potentially holding the key to unlocking some of its mysteries.
MYCN in human development and diseases
Authors: Nishio Yosuke , Kato Kohji , Oishi Hisashi , Takahashi Yoshiyuki , Saitoh Shinji
Published: May 2024

Somatic mutations in MYCN have been identified across various tumors, playing pivotal roles in tumorigenesis, tumor progression, and unfavorable prognoses. Despite its established notoriety as an oncogenic driver, there is a growing interest in exploring the involvement of MYCN in human development. While MYCN variants have traditionally been associated with Feingold syndrome type 1, recent discoveries highlight gain-of-function variants, specifically p.(Thr58Met) and p.(Pro60Leu), as the cause for megalencephaly-polydactyly syndrome. The elucidation of cellular and murine analytical data from both loss-of-function (Feingold syndrome model) and gain-of-function models (megalencephaly-polydactyly syndrome model) is significantly contributing to a comprehensive understanding of the physiological role of MYCN in human development and pathogenesis. This review discusses the MYCN’s functional implications for human development by reviewing the clinical characteristics of these distinct syndromes, Feingold syndrome, and megalencephaly-polydactyly syndrome, providing valuable insights into the understanding of pathophysiological backgrounds of other syndromes associated with the MYCN pathway and the overall comprehension of MYCN’s role in human development.
High salt diet alleviates disease severity in native experimental autoimmune uveitis
Authors: Derluyn Naomi , Foucart Vincent , Verce Marko , Abdo Rami , Vaudoisey Louis , Lipski Deborah , Flamand Véronique , Everard Amandine , Bruyns Catherine , Willermain François
Published: May 2024

Background

Recent studies reported a link between high salt diet (HSD) and clinical exacerbation in mouse models of autoimmune diseases, mainly through the induction of pathogenic Th17 cells and/or HSD-induced dysbiosis. However, the topic remains controversial and not fully understood.

Purpose

In this study, we investigated the effects of HSD on the development of experimental autoimmune uveitis (EAU) in C57BL/6J mice.

Methods and results

Unexpectedly, our data showed a significant attenuating effect of HSD on disease severity of native EAU, induced by direct immunization with IRBP peptide. That said, HSD had no effect on EAU disease severity induced by adoptive transfer of semi-purified auto-reactive IRBP-specific T lymphocytes. Accordingly, HSD did not affect IRBP-specific systemic afferent immune response as attested by no HSD-linked changes in T lymphocytes proliferation, cytokine production and Treg proportion. Gut microbiota analysis from cecal samples in naïve and EAU mice demonstrated that HSD affected differentially α-diversity between groups, whereas β-diversity was significantly modified in all groups. Unknown Tannerellaceae was the only taxon associated to HSD exposure in all treatment groups. Interestingly, a significantly higher abundance of unknown Gastranaerophilales, with potential anti-inflammatory properties, appeared in HSD-fed native EAU mice, only.

Discussion

In conclusion, our study suggests a possible impact of HSD on gut microbiota composition and consequently on development and clinical severity of EAU. Further studies are required to investigate the potential beneficial role of Gastranaerophilales in EAU.
Predictors of neonatal near-misses in Worabe Comprehensive Specialized Hospital, Southern Ethiopia
Authors: Yasin Shemsu , Abdisa Lemesa , Roba Hirbo Shore , Tura Abera Kenay
Published: May 2024

Background

Neonatal deaths are still a major leading cause of social and economic crises. Identifying neonatal near-miss events and identifying their predictors is crucial to developing comprehensive and pertinent strategies to alleviate neonatal morbidity and death. However, neither neonatal near-miss events nor their predictors were analyzed in the study area. Therefore, this study is aimed at assessing the predictors of neonatal near-misses among neonates born at Worabe Comprehensive Specialized Hospital, Southern Ethiopia, in 2021

Methods

A hospital-based unmatched case-control study was conducted from 10 November 2021 to 30 November 2021. A pre-tested, structured, and standard abstraction checklist was used to collect the data. After checking the data for completeness and consistency, it was coded and entered into Epi-Data 3.1 and then exported to Stata version 14 for analysis. All independent variables with a p-value ≤0.25 in bivariable binary logistic regression were entered into a multivariable analysis to control the confounding. Variables with p-values <0.05 were considered statistically significant.

Results

In this study, 134 neonatal near-miss cases and 268 controls were involved. The identified predictors of neonatal near-misses were rural residence [adjusted odds ratio (AOR): 2.01; 95% confidence interval (CI): 1.31–5.84], no antenatal care (ANC) follow-up visits (AOR: 2.98; 95% CI: 1.77–5.56), antepartum hemorrhage (AOR: 2.12; 95% CI: 1.18–4.07), premature rupture of the membrane (AOR: 2.55; 95% CI: 1.54–5.67), and non-vertex fetal presentation (AOR: 3.05; 95% CI: 1.93–5.42).

Conclusion

The current study identified rural residents, no ANC visits, antepartum hemorrhage, premature rupture of membrane, and non-vertex fetal presentation as being significantly associated with neonatal near-miss cases. As a result, local health planners and healthcare practitioners must collaborate in enhancing maternal healthcare services, focusing specifically on the early identification of issues and appropriate treatment.
A mild phenotype associated with KCNQ1 p.V205M mediated long QT syndrome in First Nations children of Northern British Columbia: effect of additional variants and considerations for management
Authors: Bene Watts Simona , Gauthier Barbara , Erickson Anders C. , Morrison Julie , Sebastian Mavis , Gillman Lawrence , McIntosh Sarah , Ens Connie , Sherwin Elizabeth , McCormick Rod , Sanatani Shubhayan , Arbour Laura
Published: May 2024

Introduction

Congenital Long QT Syndrome (LQTS) is common in a First Nations community in Northern British Columbia due to the founder variant KCNQ1 p.V205M. Although well characterized molecularly and clinically in adults, no data have been previously reported on the pediatric population. The phenotype in adults has been shown to be modified by a splice site variant in KCNQ1 (p.L353L). The CPT1A p.P479L metabolic variant, also common in Northern Indigenous populations, is associated with hypoglycemia and infant death. Since hypoglycemia can affect the corrected QT interval (QTc) and may confer risk for seizures (also associated with LQTS), we sought to determine the effect of all three variants on the LQTS phenotype in children within our First Nations cohort.

Methods

As part of a larger study assessing those with LQTS and their relatives in a Northern BC First Nation, we assessed those entering the study from birth to age 18 years. We compared the corrected peak QTc and potential cardiac events (syncope/seizures) of 186 children from birth to 18 years, with and without the KCNQ1 (p.V205M and p.L353L) and CPT1A variants, alone and in combination. Linear and logistic regression and student t-tests were applied as appropriate.

Results

Only the KCNQ1 p.V205M variant conferred a significant increase in peak QTc 23.8 ms (p < 0.001) above baseline, with females increased by 30.1 ms (p < 0.001) and males by 18.9 ms (p < 0.01). There was no evidence of interaction effects with the other two variants studied. Although the p.V205M variant was not significantly associated with syncope/seizures, the odds of having a seizure/syncope were significantly increased for those homozygous for CPT1A p.P479L compared to homozygous wild type (Odds Ratio [OR]3.0 [95% confidence interval (CI) 1.2–7.7]; p = 0.019).

Conclusion

While the KCNQ1 p.V205M variant prolongs the peak QTc, especially in females, the CPT1A p.P479L variant is more strongly associated with loss of consciousness events. These findings suggest that effect of the KCNQ1 p.V205M variant is mild in this cohort, which may have implications for standard management. Our findings also suggest the CPT1A p.P479L variant is a risk factor for seizures and possibly syncope, which may mimic a long QT phenotype.
Development of a new hazard scoring system in primary neuronal cell cultures for drug-induced acute neuronal toxicity identification in early drug discovery
Authors: Kreir Mohamed , Putri Dea , Tekle Fetene , Pibiri Francesca , d’Ydewalle Constantin , Van Ammel Karel , Geys Helena , Teisman Ard , Gallacher David J. , Lu Hua Rong
Published: May 2024

We investigated drug-induced acute neuronal electrophysiological changes using Micro-Electrode arrays (MEA) to rat primary neuronal cell cultures. Data based on 6-key MEA parameters were analyzed for plate-to-plate vehicle variability, effects of positive and negative controls, as well as data from over 100 reference drugs, mostly known to have pharmacological phenotypic and clinical outcomes. A Least Absolute Shrinkage and Selection Operator (LASSO) regression, coupled with expert evaluation helped to identify the 6-key parameters from many other MEA parameters to evaluate the drug-induced acute neuronal changes. Calculating the statistical tolerance intervals for negative-positive control effects on those 4-key parameters helped us to develop a new weighted hazard scoring system on drug-induced potential central nervous system (CNS) adverse effects (AEs). The weighted total score, integrating the effects of a drug candidate on the identified six-pivotal parameters, simply determines if the testing compound/concentration induces potential CNS AEs. Hereto, it uses four different categories of hazard scores: non-neuroactive, neuroactive, hazard, or high hazard categories. This new scoring system was successfully applied to differentiate the new compounds with or without CNS AEs, and the results were correlated with the outcome of in vivo studies in mice for one internal program. Furthermore, the Random Forest classification method was used to obtain the probability that the effect of a compound is either inhibitory or excitatory. In conclusion, this new neuronal scoring system on the cell assay is actively applied in the early de-risking of drug development and reduces the use of animals and associated costs.
Safety classification of herbal medicine use among hypertensive patients: a systematic review and meta-analysis
Authors: Choi Dain , Im Hyea Bin , Choi Soo Jeung , Han Dongwoon
Published: May 2024

Background

The use of herbal medicines (HMs) for the treatment of hypertension (HTN) is increasing globally, but research on the potential adverse effects and safety of HMs in HTN patients is limited. Therefore, this systematic review and meta-analysis aim to determine the global prevalence of HM usage among HTN patients and assess the safety of identified herbs based on current scientific evidence.

Methods

The PubMed/MEDLINE, EMBASE (Ovid), and Cumulated Index to Nursing and Allied Health Literature (CINAHL) databases were searched for cross-sectional studies on the use of HM among HTN patients. Our review includes studies published in English up to the year 2023. After extracting and appraising the data from the studies, a meta-analysis was conducted using the Stata version 16.0 to estimate the pooled prevalence of HM use in patients with HTN (PROSPERO: CRD42023405537). The safety classification of the identified HM was done based on the existing scientific literature.

Results

This study analyzed 37 cross-sectional studies from 21 countries and found that 37.8% of HTN patients used HM to manage their health. The prevalence of HM use varied significantly based on publication year and geographical region. Among the 71 identified herbs, Allium sativum L., Hibiscus sabdariffa L., and Olea europaea L. were the most commonly used. However, four herbs were identified as contraindicated, 50 herbs required caution, and only 11 herbs were considered safe for use.

Conclusion

The study highlights the potential risks of toxicities and adverse effects associated with HM use in the treatment of HTN. Ensuring patient safety involves using safe HMs in appropriate doses and avoiding contraindicated HMs. Future research should focus on identifying commonly used herbs, especially in resource-limited countries with poor HTN management, and additional clinical research is required to assess the toxicity and safety of commonly used HMs.
Efficiency and controllability of stochastic boolean function generation by a random network of non-linear nanoparticle junctions
Authors: Martini G. , Tentori E. , Mirigliano M. , Galli D. E. , Milani P. , Mambretti F.
Published: May 2024

Amid efforts to address energy consumption in modern computing systems, one promising approach takes advantage of random networks of non-linear nanoscale junctions formed by nanoparticles as substrates for neuromorphic computing. These networks exhibit emergent complexity and collective behaviors akin to biological neural networks, characterized by self-organization, redundancy, and non-linearity. Based on this foundation, a generalization of n-inputs devices has been proposed, where the associated weights depend on all the input values. This model, called receptron, has demonstrated its capability to generate Boolean functions as output, representing a significant breakthrough in unconventional computing methods. In this work, we characterize and present two actual implementations of this paradigm. One approach leverages the nanoscale properties of cluster-assembled Au films, while the other utilizes the recently introduced Stochastic Resistor Network (SRN) model. We first provide a concise overview of the electrical properties of these systems, emphasizing the insights gained from the SRN regarding the physical processes within real nanostructured gold films at a coarse-grained scale. Furthermore, we present evidence indicating the minimum complexity level required by the SRN model to achieve a stochastic dynamics adequate to effectively model a novel component for logic systems. To support our argument that these systems are preferable to conventional random search algorithms, we discuss quantitative criteria based on Information-theoretic tools. This suggests a practical means to steer the stochastic dynamics of the system in a controlled way, thus focusing its random exploration where it is most useful.
Photosynthetic adaptation strategies in peppers under continuous lighting: insights into photosystem protection
Authors: Lanoue Jason , St. Louis Sarah , Little Celeste , Hao Xiuming
Published: May 2024

Energy efficient lighting strategies have received increased interest from controlled environment producers. Long photoperiods (up to 24 h - continuous lighting (CL)) of lower light intensities could be used to achieve the desired daily light integral (DLI) with lower installed light capacity/capital costs and low electricity costs in regions with low night electricity prices. However, plants grown under CL tend to have higher carbohydrate and reactive oxygen species (ROS) levels which may lead to leaf chlorosis and down-regulation of photosynthesis. We hypothesize that the use of dynamic CL using a spectral change and/or light intensity change between day and night can negate CL-injury. In this experiment we set out to assess the impact of CL on pepper plants by subjecting them to white light during the day and up to 150 µmol m-2 s-1 of monochromatic blue light at night while controlling the DLI at the same level. Plants grown under all CL treatments had similar cumulative fruit number and weight compared to the 16h control indicating no reduction in production. Plants grown under CL had higher carbohydrate levels and ROS-scavenging capacity than plants grown under the 16h control. Conversely, the amount of photosynthetic pigment decreased with increasing nighttime blue light intensity. The maximum quantum yield of photosystem II (Fv/Fm), a metric often used to measure stress, was unaffected by light treatments. However, when light-adapted, the operating efficiency of photosystem II (ΦPSII) decreased and non-photochemical quenching (NPQ) increased with increasing nighttime blue light intensity. This suggests that both acclimated and instantaneous photochemistry during CL can be altered and is dependent on the nighttime light intensity. Furthermore, light-adapted chlorophyll fluorescence measurements may be more adept at detecting altered photochemical states than the conventional stress metric using dark-adapted measurements.
Comparative restriction enzyme analysis of methylation (CREAM) reveals methylome variability within a clonal in vitro cannabis population
Authors: Boissinot Justin , Adamek Kristian , Jones Andrew Maxwell Phineas , Normandeau Eric , Boyle Brian , Torkamaneh Davoud
Published: May 2024

The primary focus of medicinal cannabis research is to ensure the stability of cannabis lines for consistent administration of chemically uniform products to patients. In recent years, tissue culture has emerged as a valuable technique for genetic preservation and rapid multiplication of cannabis clones. However, there is concern that the physical and chemical conditions of the growing media can induce somaclonal variation, potentially impacting the viability and uniformity of clones. To address this concern, we developed Comparative Restriction Enzyme Analysis of Methylation (CREAM), a novel method to assess DNA methylation patterns and used it to study a population of 78 cannabis clones maintained in tissue culture. Through bioinformatics analysis of the methylome, we successfully detected 2,272 polymorphic methylated regions among the clones. Remarkably, our results demonstrated that DNA methylation patterns were preserved across subcultures within the clonal population, allowing us to distinguish between two subsets of clonal lines used in this study. These findings significantly contribute to our understanding of the epigenetic variability within clonal lines in medicinal cannabis produced through tissue culture techniques. This knowledge is crucial for understanding the effects of tissue culture on DNA methylation and ensuring the consistency and reliability of medicinal cannabis products with therapeutic properties. Additionally, the CREAM method is a fast and affordable technology to get a first glimpse at methylation in a biological system. It offers a valuable tool for studying epigenetic variation in other plant species, thereby facilitating broader applications in plant biotechnology and crop improvement.
Impacts of farming activities on carbon deposition based on fine soil subtype classification
Authors: Wang Qiuju , Zhang Dongdong , Jiao Feng , Zhang Haibin , Guo Zhenhua
Published: May 2024

Introduction

Soil has the highest carbon sink storage in terrestrial ecosystems but human farming activities affect soil carbon deposition. In this study, land cultivated for 70 years was selected. The premise of the experiment was that the soil could be finely categorized by subtype classification. We consider that farming activities affect the soil bacterial community and soil organic carbon (SOC) deposition differently in the three subtypes of albic black soils.

Methods

Ninety soil samples were collected and the soil bacterial community structure was analysed by high-throughput sequencing. Relative changes in SOC were explored and SOC content was analysed in association with bacterial concentrations.

Results

The results showed that the effects of farming activities on SOC deposition and soil bacterial communities differed among the soil subtypes. Carbohydrate organic carbon (COC) concentrations were significantly higher in the gleying subtype than in the typical and meadow subtypes. RB41, Candidatus-Omnitrophus and Ahniella were positively correlated with total organic carbon (TOC) in gleying shallow albic black soil. Corn soybean rotation have a positive effect on the deposition of soil carbon sinks in terrestrial ecosystems.

Discussion

The results of the present study provide a reference for rational land use to maintain sustainable development and also for the carbon cycle of the earth.
From first encounters to longitudinal exposure: a repeated exposure-test paradigm for monitoring speech adaptation
Authors: Xie Xin , Kurumada Chigusa
Published: May 2024

Perceptual difficulty with an unfamiliar accent can dissipate within short time scales (e.g., within minutes), reflecting rapid adaptation effects. At the same time, long-term familiarity with an accent is also known to yield stable perceptual benefits. However, whether the long-term effects reflect sustained, cumulative progression from shorter-term adaptation remains unknown. To fill this gap, we developed a web-based, repeated exposure-test paradigm. In this paradigm, short test blocks alternate with exposure blocks, and this exposure-test sequence is repeated multiple times. This design allows for the testing of adaptive speech perception both (a) within the first moments of encountering an unfamiliar accent and (b) over longer time scales such as days and weeks. In addition, we used a Bayesian ideal observer approach to select natural speech stimuli that increase the statistical power to detect adaptation. The current report presents results from a first application of this paradigm, investigating changes in the recognition accuracy of Mandarin-accented speech by native English listeners over five sessions spanning 3 weeks. We found that the recognition of an accent feature (a syllable-final /d/, as in feed, sounding/t/-like) improved steadily over the three-week period. Unexpectedly, however, the improvement was seen with or without exposure to the accent. We discuss possible reasons for this result and implications for conducting future longitudinal studies with repeated exposure and testing.