bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil compounding promotes the improvement of aeolian sandy soil in the Mu Us Sandy Land
Authors: Chen Shichao , Chen Xue , Zuo Hejun , Yan Min , Wang Haibing , Li Xiaole
Published: August 2024

Aeolian sandy soil and loess soil of the Mu Us Sandy Land are used as the research material in this study to investigate the effect of soil compounding on the improvement of aeolian sandy soil and to provide a feasible approach for sand prevention and sand control. In particular, loess soils were compounded at 0%, 20%, 40%, 60%, 80%, and 100% by volume percentage of the compounded soils. The improvement benefits of compounded soils on their textural properties, water-holding capacity, and fertilizer-retention capacity at different blending ratios were evaluated. The results showed that following the compounding of aeolian sandy and loess soils, with the increase of the loess proportion, the texture type of the compounded soil transforms from sandy soil to loamy sandy soil to sandy loam to loamy soil to powdery loam. Moreover, granular gradation was observed, the bulk density gradually decreased, the capillary porosity gradually increased, and the performance of water- and fertilizer-holding properties gradually increased and strengthened. The spatial variability of compounded soil bulk density, capillary porosity, and the water-holding and fertilizer-retention properties was almost entirely controlled by the proportion of loess soil. A theoretical basis is provided in this study for aeolian sandy soil improvement in the Mu Us Sandy Land that can be extended to similar areas, providing a feasible sand management approach.
Divergent effects of itaconate isomers on Coxiella burnetii growth in macrophages and in axenic culture
Authors: Siddique Md Nur A Alam , Kellermeier Fabian , Ölke Martha , Zhao Mingming , Büssow Konrad , Oefner Peter J. , Lührmann Anja , Dettmer Katja , Lang Roland
Published: August 2024

Aconitate decarboxylase-1 (ACOD1) is expressed by activated macrophages and generates itaconate that exerts anti-microbial and immunoregulatory effects. ACOD1-itaconate is essential for macrophage-mediated control of the intracellular pathogen Coxiella (C.) burnetii, which causes Q fever. Two isomers of itaconate, mesaconate and citraconate, have overlapping yet distinct activity on macrophage metabolism and inflammatory gene expression. Here, we found that all three isomers inhibited the growth of C. burnetii in axenic culture in ACCM-2 medium. However, only itaconate reduced C. burnetii replication efficiently in Acod1-/- macrophages. In contrast, addition of citraconate strongly increased C. burnetii replication in Acod1+/- macrophages, whereas mesaconate weakly enhanced bacterial burden in Acod1-/- macrophages. Analysis of intracellular isomers showed that exogenous citraconate and mesaconate inhibited the generation of itaconate by infected Acod1+/- macrophages. Uptake of added isomers into Acod1-/- macrophages was increased after infection for itaconate and mesaconate, but not for citraconate. Mesaconate, but not citraconate, competed with itaconate for uptake into macrophages. Taken together, inhibition of itaconate generation by macrophages and interference with the uptake of extracellular itaconate could be identified as potential mechanisms behind the divergent effects of citraconate and mesaconate on C. burnetii replication in macrophages or in axenic culture.
The Nectin family ligands, PVRL2 and PVR, in cancer immunology and immunotherapy
Authors: Murakami Kosuke , Ganguly Sudipto
Published: August 2024

In recent years, immunotherapy has emerged as a crucial component of cancer treatment. However, its efficacy remains limited across various cancer types, highlighting unmet needs. Poliovirus receptor-related 2 (PVRL2) and Poliovirus receptor (PVR) are members of the Nectin and Nectin-like Molecules family, known for their role as cell-cell adhesion molecules. With the development of immunotherapy, their involvement in tumor immune mechanisms as immune checkpoint factors has garnered significant attention. PVRL2 and PVR are predominantly expressed on tumor cells and antigen-presenting cells, binding to PVRIG and TIGIT, respectively, which are primarily found on T and NK cells, thereby suppressing antitumor immunity. Notably, gynecological cancers such as ovarian and endometrial cancers exhibit high expression levels of PVRL2 and PVR, with similar trends observed in various other solid and hematologic tumors. Targeting these immune checkpoint pathways offers a promising therapeutic avenue, potentially in combination with existing treatments. However, the immunomodulatory mechanism involving these bindings, known as the DNAM-1 axis, is complex, underscoring the importance of understanding it for developing novel therapies. This article comprehensively reviews the immunomodulatory mechanisms centered on PVRL2 and PVR, elucidating their implications for various cancer types.
T-regulatory cells require Sin3a for stable expression of Foxp3
Authors: Christensen Lanette M. , Akimova Tatiana , Wang Liqing , Han Rongxiang , Samanta Arabinda , Di Giorgio Eros , Hancock Wayne W.
Published: August 2024

Histone deacetylases 1 and 2 play a major role in the transcriptional regulation of T-regulatory (Treg) cells via interactions with a myriad of coregulatory factors. Sin3a has been well established as a Hdac1/2 cofactor, while its role within Tregs has not been established. In this study, the effects of conditional deletion of Sin3a within Foxp3+ Tregs were evaluated. Developmental deletion of Sin3a from Foxp3+ Tregs resulted in the rapid onset of fatal autoimmunity. Treg numbers were greatly reduced, while residual Tregs had impaired suppressive function. Mice also showed effector T-cell activation, autoantibody production, and widespread tissue injury. Mechanistically, Sin3a deletion resulted in decreased transcription of Foxp3 with a complete lack of CNS2 CpG demethylation. In addition, Foxp3 protein stability was impaired with an increased ex-Treg population. Thus, Sin3a plays a critical role in the maintenance of Treg identity and function and is essential for the expression and stability of Foxp3.
Polyneuropathy in systemic sclerosis: exploring the causes and biomarkers
Authors: Ivanova Kristīne , Zolovs Maksims , Blennow Kaj , Zetterberg Henrik , Kurjāne Nataļja , Ķēniņa Viktorija
Published: August 2024

Introduction

Systemic sclerosis (SSc) is a rare autoimmune disease with multiple organ involvement; however, the contribution of the nervous system (NS) remains relatively understudied. There are no specific data on the role of the autoimmune response and inflammation in the development of peripheral nerve system (PNS) damage in SSc and markers to assess this damage have yet to be identified.

Objectives

The primary objective of this study was to define the autoimmune mechanisms that lead to neuropathy by identifying antibodies (Abs) that target certain component of the NS or are associated with SSc. The secondary objective was to identify markers of NS damage that correlate with the detection and progression of polyneuropathy (PNP).

Methods

This study included patients diagnosed with SSc who met ACR/EULAR 2013 classification criteria at two leading Latvian hospitals between January 2016 and December 2021. Patients underwent a nerve conduction study (NCS). The SSc-associated Abs, Abs against myelin-associated glycoprotein (MAG) and anti-ganglioside Abs (GM1, GM2, GD1a, GD1b and GQ1b) were analysed. Potential serum PNS biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), fibroblast growth factor 21 (FGF21) and growth/differentiation factor 15 (GDF15)—were measured.

Results

We recruited 103 Caucasian patients diagnosed with SSc. SSc-associated Abs did not differ significantly between patients with and without PNP (p > 0.05). Anti-MAG and anti-ganglioside Abs in patients with PNP did not present a significant increase above the reference range. NfL, GFAP and GDF15 were significantly elevated in the presence of PNP (p < 0.05), with a moderate to high effect size (r = 0.36–0.65). Our regression analysis revealed a strong association between the HAQ-DI score, older age, male gender and the risk of developing PNP.

Conclusion

The development of PNP in patients with SSc is most likely due to ageing, natural progression and the sequelae of the disease. Several serum biomarkers—NfL, GFAP and GDF15—could be used as relevant diagnostic biomarkers for PNP in patients with SSc. Future studies are warranted to validate the diagnostic efficacy of these biomarkers and to unravel the complex interplay of factors leading to PNP in patients with SSc.
Rapid campimetry - a novel robust kinetic approach for visual field screening in glaucoma
Authors: Al-Nosairy Khaldoon O. , Rodenbeck Katharina , Vorholt Sophie , Djouoma Nidele , Thieme Hagen , Müller Fabian , Hoffmann Michael B.
Published: August 2024

Purpose

To investigate the robustness and variability of a novel kinetic visual field (VF) screening method termed rapid campimetry (RC).

Methods

In RC visual field (VF) screening is enabled via kinetic-based testing on any computer (10°/4.7 s at 40-cm viewing distance) and high contrast in a dark room (1 cd/cm2). In experiment (1): 30 participants [20 healthy participants (HC), 5 glaucoma patients (GLA) and 5 patients with cataract (CAT)] were included to test the intra-session variability (fatigue effect) and the following effects on RC: room illumination (140 cd/m2), ±3 D refractive errors, media opacity. In experiment (2): Inter-session variability (1–3 weeks apart) was assessed in 10 HC and 10 GLA. Since RC detects absolute scotomas, the outcome measure was the size of physiological (blindspot) and pathological (glaucoma) scotomas in degrees. A repeated measures ANOVA was employed in experiment 1 and intraclass correlation (ICC) in experiment 2.

Results

Neither the size of the blindspot nor the VF defects differed significantly between the different testing conditions. For intra-session variability, the average bias of blindspot size was −0.6 ± 2.5°, limits of agreement (LOA), in comparison to 0.3 ± 1.5° for VF defects, both with ICC of 0.86 and 0.93, respectively. For the inter-session repeatability, the average bias and LOA for blindspot size was 0.2 ± 3.85° in comparison 1.6 ± 3.1° for VF defects, both with ICC of 0.87 and 0.91, respectively.

Conclusion

RC was robust to suboptimal testing VF conditions and showed good-to-excellent reliability between VF testing visits holding high potential for teleophthalmology.
Intracerebral inoculation of healthy non-transgenic rats with a single aliquot of oligomeric amyloid-β (1–42) profoundly and progressively alters brain function throughout life
Authors: Kramer Marco , Hoang Thu-Huong , Yang Honghong , Shchyglo Olena , Böge Juliane , Neubacher Ute , Colitti-Klausnitzer Jens , Manahan-Vaughan Denise
Published: August 2024

One of the puzzling aspects of sporadic Alzheimer’s disease (AD) is how it commences. Changes in one key brain peptide, amyloid-beta (Aβ), accompany disease progression, but whether this comprises a trigger or a consequence of AD is still a topic of debate. It is clear however that the cerebral presence of oligomeric Aβ (1–42) is a key factor in early AD-pathogenesis. Furthermore, treatment of rodent brains with oligomeric Aβ (1–42) either in vitro or in vivo, acutely impairs hippocampal synaptic plasticity, creating a link between Aβ-pathology and learning impairments. Here, we show that a once-off inoculation of the brains of healthy adult rats with oligomeric Aβ (1–42) exerts debilitating effects on the long-term viability of the hippocampus, one of the primary targets of AD. Changes are progressive: months after treatment, synaptic plasticity, neuronal firing and spatial learning are impaired and expression of plasticity-related proteins are changed, in the absence of amyloid plaques. Early changes relate to activation of microglia, whereas later changes are associated with a reconstruction of astroglial morphology. These data suggest that a disruption of Aβ homeostasis may suffice to trigger an irreversible cascade, underlying progressive loss of hippocampal function, that parallels the early stages of AD.
Genome-wide sequencing identified extrachromosomal circular DNA as a transcription factor-binding motif of the senescence genes that govern replicative senescence in human mesenchymal stem cells
Authors: Yang Wei , Ji Wei , Liao Boyu , Li Zhongbo , Wang Jian , Lin Haishu , Wang Jingbo , He Qian
Published: August 2024

Introduction

Mesenchymal stem cells (MSCs) have long been postulated as an important source cell in regenerative medicine. During subculture expansion, mesenchymal stem cell (MSC) senescence diminishes their multi-differentiation capabilities, leading to a loss of therapeutic potential. Up to date, the extrachromosomal circular DNAs (eccDNAs) have been demonstrated to be involved in senescence but the roles of eccDNAs during MSC.

Methods

Here we explored eccDNA profiles in human bone marrow MSCs (BM-MSCs). EccDNA and mRNA was purified and sequenced, followed by quantification and functional annotation. Moreover, we mapped our datasets with the downloading enhancer and transcription factor-regulated genes to explore the potential role of eccDNAs.

Results

Sequentially, gene annotation analysis revealed that the majority of eccDNA were mapped in the intron regions with limited BM-MSC enhancer overlaps. We discovered that these eccDNA motifs in senescent BMSCs acted as motifs for binding transcription factors (TFs) of senescence-related genes.

Discussion

These findings are highly significant for identifying biomarkers of senescence and therapeutic targets in mesenchymal stem cells (MSCs) for future clinical applications. The potential of eccDNA as a stable therapeutic target for senescence-related disorders warrants further investigation, particularly exploring chemically synthesized eccDNAs as transcription factor regulatory elements to reverse cellular senescence.
The role of SIRT3 in homeostasis and cellular health
Authors: Trinh Dennison , Al Halabi Lina , Brar Harsimar , Kametani Marie , Nash Joanne E.
Published: August 2024

Mitochondria are responsible for maintaining cellular energy levels, and play a major role in regulating homeostasis, which ensures physiological function from the molecular to whole animal. Sirtuin 3 (SIRT3) is the major protein deacetylase of mitochondria. SIRT3 serves as a nutrient sensor; under conditions of mild metabolic stress, SIRT3 activity is increased. Within the mitochondria, SIRT3 regulates every complex of the electron transport chain, the tricarboxylic acid (TCA) and urea cycles, as well as the mitochondria membrane potential, and other free radical scavengers. This article reviews the role of SIRT3 in regulating homeostasis, and thus physiological function. We discuss the role of SIRT3 in regulating reactive oxygen species (ROS), ATP, immunological function and mitochondria dynamics.
The diagnostic value of contrast-enhanced transcranial Doppler and contrast-enhanced transthoracic echocardiography for right to left shunt in patent foramen ovale: a systematic review and meta-analysis
Authors: Zhang Dian , Jiang Li , Chen Yue-Nan , Pan Mei-Fang
Published: August 2024

Purpose

To evaluate and compare the diagnostic value of contrast-enhanced transcranial Doppler (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) for right to left shunt (RLS) in patent foramen ovale (PFO) by meta-analysis.

Methods

The literature included in the Cochrane Library, PubMed, and Embase were searched by using “contrast-enhanced transcranial Doppler (c-TCD), contrast-enhanced transthoracic echocardiography (c-TTE), patent foramen ovale (PFO), and right to left shunt (RLS)” as the keywords from inception through April 30, 2024. The diagnostic accuracy research quality assessment tool (QUADAS-2) was used to evaluate the quality of the included literature. The combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and Diagnostic odds ratio (DOR) were pooled, and a comprehensive ROC curve analysis was performed. Statistical software StataSE 12.0 and Meta-Disc 1.4 were used for data analysis.

Results

A total of 8,536 articles were retrieved, and 9 articles that met all inclusion criteria were included in this meta-analysis. The meta-analysis results show that the combined sensitivity, specificity, PLR, NLR, DOR, and area under the SROC curve of c-TCD for the diagnose of PFO-RLS were 0.91 (95% CI, 0.88–0.93), 0.87 (95% CI: 0.84–0.91), 6.0 (95% CI, 2.78–12.96), 0.10 (95% CI, 0.06–0.18), 91.61 (95% CI, 26.55–316.10), and 0.9681, respectively; the corresponding values of c-TTE were 0.86 (95% CI, 0.84–0.89), 0.88 (95% CI, 0.84–0.91), 5.21 (95% CI, 2.55–10.63), 0.16 (95% CI, 0.09–0.31), 71.43 (95% CI, 22.85–223.23), and 0.9532. The ROC curve shows that c-TCD has slightly higher diagnostic value for PFO than c-TTE, but there is no significant statistical difference (Z = 0.622, p > 0.05). Deek funnel pattern showed no significant publication bias.

Conclusion

Both c-TCD and c-TTE have high diagnostic values for PFO-RLS. However, c-TCD has slightly higher sensitivity and lower specificity in diagnosing PFO-RLS compared to c-TTE.

Systematic review registration: identifier [CRD42024544169].
A bibliometric analysis of transcranial alternating current stimulation
Authors: Wu Cheng-Fan , Shen Chao , Wang Zhao-Di , Gong Yan , Zhou Lu-Han , Qian Wen-Jun , Tang Tong
Published: August 2024

Background

Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACS-related publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research.

Material and methods

The database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references.

Results

A total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg (n = 50). According to Bradford’s law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications (n = 40), while Antal, A was the author with the highest number of co-citations (n = 391) and betweenness centrality (n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends.

Conclusion

tACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field.
Visual motion sensitivity as an indicator of diabetic retinopathy in type 2 diabetes mellitus
Authors: Zhang Tianlin , Ying Haojiang , Wang Huiqun , Zhao Fouxi , Pan Qiying , Zhan Qingqing , Zhang Fuyan , An Qinyu , Liu Tao , Hu Yuandong , Zhang Yang
Published: August 2024

Objectives

This current study is based on a set of visual motion sensitivity tests, investigating the correlation between visual motion sensitivity and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM), thereby furnishing a scientific rationale for preventing and controlling DR.

Methods

This research was conducted by a combination of questionnaire collection and on-site investigation that involved 542 T2DM recruited from a community. The visual motion sensitivity determined the visual motion perception of the participants across three spatial frequencies (low, medium, and high) for both the first- and second-order contrast. The logistic regression model was adopted to investigate the relationship between visual motion sensitivity and DR prevalence. Besides, the Pearson correlation analysis was used to analyze the factors influencing visual motion sensitivity and restricted cubic spline (RCS) functions to assess the dose–response relationship between visual motion sensitivity and glycated hemoglobin.

Results

Among 542 subjects, there are 162 cases of DR, with a prevalence rate of 29.89%. After adjusting factors of age, gender, glycated hemoglobin, duration of diabetes, BMI, and hypertension, we found that the decline in first- and second-order high spatial frequency sensitivity increased the risk for DR [odds ratio (OR): 1.519 (1.065, 2.168), 1.249 (1.068, 1.460)]. The decline in perceptual ability of second-order low, medium, and high spatial frequency sensitivity is a risk factor for moderate to severe DR [OR: 1.556 (1.116, 2.168), 1.388 (1.066, 1.806), 1.476 (1.139, 1.912)]. The first-order and the second-order high spatial frequency sensitivity are significantly positively correlated with glycated hemoglobin (r = 0.105, p = 0.015 and r = 0.119, p = 0.005, respectively).

Conclusion

Visual motion sensitivity especially for the second-order high spatial frequency stimuli emerges as a significant predictor of DR in T2DM, offering a sensitive diagnostic tool for early detection.
Variation in the distribution of large-scale spatiotemporal patterns of activity across brain states
Authors: Meyer-Baese Lisa , Anumba Nmachi , Bolt T. , Daley L. , LaGrow T. J. , Zhang Xiaodi , Xu Nan , Pan Wen-Ju , Schumacher E. H. , Keilholz Shella
Published: August 2024

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.
Folic acid for the primary prevention of stroke: a systematic review and meta-analysis
Authors: Yang Jianjian , Wang Jia , Li Bo , Zhang Yaxi
Published: August 2024

Objectives

Results from studies were inconsistent with regard to the effect of folic acid on the primary prevention of stroke. The aim of this study was to analyze the association between folic acid and the primary prevention of stroke using the data from observational studies and randomized controlled trials (RCTs).

Methods

Eligible publications published until June 2024 were searched in the database of PubMed, Web of Science and Embase. This study included all observational studies and RCTs of folic acid with first stroke as the reporting endpoints. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled in the random-effects model to assess the effect of folic acid on the primary prevention of stroke.

Results

Results from 12 observational publications with 16 research, including 312,320 participants, were combined to explore the association between dietary folic acid intake and the primary prevention of stroke. The results showed that high dietary folic acid intake was associated with a 17% reduction in stroke incidence (RR:0.83; 95% CI: 0.73–0.94), and the effect of dietary folic acid was greater in areas without grain fortification (RR:0.80; 95% CI: 0.67–0.95). The pooled results from 12 RCTs, totaling 75,042 participants, indicated that folic acid supplementation was not associated with the stroke primary prevention (RR:0.92; 95% CI: 0.80–1.05), but folic acid supplementation was effective in areas without grain fortification (RR:0.78; 95% CI: 0.68–0.89).

Conclusion

Our meta-analysis demonstrated that dietary folic acid is effective in stroke primary prevention, and folic acid supplementation is effective in stroke primary prevention only in areas without grain fortification.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024516991.
Changes in vitamin D status among adults from the COVID-19 pandemic to post-pandemic normality
Authors: Chen Yanzhao , Kong Guilian
Published: August 2024

Introduction

The COVID-19 pandemic has prompted widespread lockdown measures globally, significantly impacting daily activities and outdoor exposure. This study investigates the effect of the pandemic on vitamin D levels and the prevalence of vitamin D deficiency in the adult population, with a focus on gender-specific differences.

Methods

A total of 1525 adults from Henan Provincial People’s Hospital were included. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured using the Elecsys® Vitamin D total kit on the Roche Cobas® 8000 analyzer. The Clinical Application Consensus on Vitamin D and Its Analogs defined deficiency as 25(OH)D levels below 20 ng/ml. Statistical analysis was performed using SPSS 23.0 and GraphPad Prism 8 software.

Results

The overall 25(OH)D levels increased from 18.14 ng/ml [IQR: 13.78, 23.68] in 2022 to 19.15 ng/ml [IQR: 14.88, 25.01] in 2023 (p=0.004). Males exhibited significant improvement in 25(OH)D levels from 18.01 ng/ml [IQR: 14.10, 23.53] in 2022 to 20.49 ng/ml [IQR: 16.11, 26.01] in 2023 (p<0.001). The prevalence of vitamin D deficiency decreased from 62% in 2022 to 54.9% in 2023 (p=0.009), with a notable reduction in males (64.1% in 2022 to 47.2% in 2023). Among 168 individuals tested in both years, 25(OH)D levels increased from 20.73 ± 9.37 ng/ml in 2022 to 22.28 ± 8.59 ng/ml in 2023 (p=0.012), and the deficiency rate decreased from 58.3% in 2022 to 47.0% in 2023 (p=0.038). The 40–49 age group showed significant improvement in 25(OH)D levels from 16.10 ng/ml [IQR: 12.41, 21.18] in 2022 to 18.28 ng/ml [IQR: 13.91, 23.86] in 2023 (p=0.005), with a reduction in deficiency rate from 72.8% to 59.9% (p=0.02). Furthermore, in February, March, and April, 2022, 25(OH)D levels were significantly lower compared to 2023 (p<0.001, p=0.002, p<0.001, respectively), accompanied by a higher prevalence of vitamin D deficiency (p<0.001, p=0.015, p<0.001, respectively).

Discussion

This study demonstrates that the COVID-19 pandemic significantly impacted vitamin D levels, leading to an increased prevalence of deficiency, particularly among males. These findings highlight the critical importance of maintaining sufficient outdoor activities to ensure adequate vitamin D levels. The data underscore the need for public health strategies to address potential deficiencies during prolonged periods of limited outdoor exposure.
Update on non-infectious uveitis treatment: anti-TNF-alpha and beyond
Authors: Chauhan Khushboo , Tyagi Mudit
Published: August 2024

Non-infectious uveitis (NIU) encompasses a range of conditions marked by inflammation within various layers of the eye. NIU is a significant contributor to irreversible vision loss among the working-age population in developed countries. The aim of treating uveitis is to manage inflammation, prevent its recurrences and to restore or salvage vision. Presently, the standard treatment protocol for NIU involves initiating corticosteroids as the primary therapeutic agents, although more aggressive approaches and steroid sparing agent may be necessary in certain cases. These advanced treatments option include synthetic immunosuppressants like antimetabolites, calcineurin inhibitors and alkylating agents. For patients who exhibit an intolerance or resistance to corticosteroids and conventional immunosuppressive therapies, biologic agents have emerged as a promising alternative. Notably, among the biologic treatments evaluated, TNF-α inhibitors, anti-CD20 therapy and alkylating agents have shown considerable efficacy. In this review, we delve into the latest evidence surrounding the effectiveness of biologic therapy and introduce novel therapeutic strategies targeting immune components as potential avenues for advancing treatment of NIU.
Prevalence and determinants of fetal macrosomia in Bangladesh
Authors: Islam Md. Zahidul , Chowdhury Mohammad Rocky Khan , Billah Baki , Rashid Mamunur , Kabir Russell , Hasan Mehedi , Kader Manzur
Published: August 2024

Background

Fetal macrosomia, marked by excessive birth weight, is a significant public health issue in developing countries, yet it has received less attention compared to low birth weight. This study aims to determine the prevalence of fetal macrosomia in Bangladesh and its associated factors.

Methods

The study utilized data from 4,754 women with complete birth weight information of their children from the Bangladesh Multiple Indicator Cluster Survey (MICS) −2019, defining fetal macrosomia as newborns with a birth weight ≥4,000 g regardless of gestational age. Bivariate logistic regression assessed associations between independent variables and fetal macrosomia, presenting adjusted odds ratios (AOR) and a 95% confidence interval (CI), while controlling for potential confounders such as women's age, wealth index, education, healthcare utilization, comorbidities, newborn sex, and place of residence.

Results

The prevalence of fetal macrosomia was 11.6%. Significant associations with fetal macrosomia included higher maternal age group (30–34 years) (AOR = 1.36, 95% CI = 1.07–1.74), secondary level of mother's education (AOR = 1.95, 95% CI = 1.43–2.66), experienced physical attacks (AOR = 1.41, 95% CI = 1.06–1.88), hypertension during pregnancy (AOR = 1.54, 95% CI = 1.15–2.07), and rural residence (AOR = 1.25, 95% CI = 1.15–1.49). Female infants had 18% lower odds of being macrosomic compared to male infants (AOR = 0.82, 95% CI = 0.72–0.93).

Conclusion

One in ten infants in Bangladesh are born with macrosomia, necessitating a multi-faceted approach involving improving maternal nutrition, promoting healthy lifestyles, enhancing access to quality prenatal care, and addressing socioeconomic, residential, and healthcare system challenges, underlining the importance of further community-based research to expand the study's scope.
Analgesia strategy for inguinal hernia repair in children: a systematic review and network meta-analysis of randomized clinical trials based on regional blocks
Authors: Xue Xing , Zhou Yuxin , Yu Na , Yang Zhihua
Published: August 2024

Background and objective

Despite its acknowledged benefits, the selection of an optimal regional block for analgesia pediatric hernia surgery remains a subject of debate. This study endeavored to conduct a network meta-analysis and systematic review of randomized clinical trials, aiming to amalgamate insights from both direct and indirect comparisons concerning the analgesic effectiveness and safety of various regional blocks post-inguinal hernia repair in children.

Method

A comprehensive literature search was performed across PubMed, EMBASE, Web of Science, and the Cochrane Library up to 12 November 2022 by two independent reviewers, employing a standardized protocol. The inclusion criteria encompassed randomized trials focusing on children undergoing inguinal hernia repair utilizing either local infiltration analgesia or regional analgesia. The primary outcomes assessed were pain scores at 2, 6, and 24 h post-operation.

Results

The initial search yielded 281 records relating to 1,137 patients. The analysis of ranking probability indicated that Paravertebral Block (PVB) holds the highest likelihood (88% and 48%) of being the most effective in alleviating pain at 2 h and 6 h post-surgery. Trans vs. Abdominis Plane Block (TAPB) emerged as the superior choice for mitigating pain (83%) and decreasing morphine consumption (93%) at 24 h following the operation. Local Anesthetic Infiltration (LAI) was identified as the most effective in shortening the hospital stay, with a 90% probability.

Conclusions

Regional anesthesia significantly enhances postoperative pain management in pediatric inguinal hernia repair surgery. For short-term postoperative pain relief, PVB emerges as the most effective technique. Meanwhile, TAPB provides more prolonged analgesia. Although TAPB does not exhibit a pronounced advantage in short-term analgesia, its simplicity and the absence of a need for a special position render it a viable option. However, the interpretation of these results should be approached with caution due to the presence of limited data and heterogeneity.

Systematic Review Registration

PROSPERO (CRD42022376435; www.crd.york.ac.uk/prospero).
Potential association between M694V homozygous mutation in familial Mediterranean fever and eosinophilic intestinal inflammation: a pediatric case series
Authors: Dingulu G. , Berrebi D. , Martinez-Vinson C. , Dumaine C. , Melki I. , Viala J. , Valtuile Z. , Vinit C. , Hugot J. P. , Meinzer U.
Published: August 2024

Familial Mediterranean fever (FMF) is the most common hereditary systemic auto-inflammatory disease. Digestive complaint is a common feature during FMF attacks. Nevertheless, digestive complaint in attack-free period has scarcely been studied. This retrospective monocentric study aimed to describe the clinical, histological, and genetic features of pediatric patients with FMF who underwent endo-colonoscopy in this setting. Out of 115 patients with a diagnosis of FMF, 10 (8, 7%) underwent endoscopy or colonoscopy. All displayed homozygote MEFV M694V mutation and presented chronic abdominal pain, iron deficiency, and/or growth retardation. On the histological level, all patients displayed low-grade mucosal inflammation, characterized by a moderate eosinophilic infiltrate in the lamina propria sometimes associated with increased crypt apoptosis. The proportion of patients explored with endoscopy or colonoscopy was 0.4 patients per year in our center, compared with 5.7 patients per year nationwide. This study identified a specific intestinal phenotype that does not respond to the criteria of classical inflammatory bowel disease: pediatric FMF pediatric patients with homozygous MEFV M694V, abdominal pain, iron deficiency, and growth retardation should benefit from specialized gastroenterological advice.
Design, synthesis and structure-activity relationship (SAR) studies of an unusual class of non-cationic fatty amine-tripeptide conjugates as novel synthetic antimicrobial agents
Authors: Hernández-Ortiz Noelia , Sánchez-Murcia Pedro A. , Gil-Campillo Celia , Domenech Mirian , Lucena-Agell Daniel , Hortigüela Rafael , Velázquez Sonsoles , Camarasa María José , Bustamante Noemí , de Castro Sonia , Menéndez Margarita
Published: August 2024

Cationic ultrashort lipopeptides (USLPs) are promising antimicrobial candidates to combat multidrug-resistant bacteria. Using DICAMs, a newly synthesized family of tripeptides with net charges from −2 to +1 and a fatty amine conjugated to the C-terminus, we demonstrate that anionic and neutral zwitterionic USLPs can possess potent antimicrobial and membrane-disrupting activities against prevalent human pathogens such as Streptococcus pneumoniae and Streptococcus pyogenes. The strongest antimicrobials completely halt bacterial growth at low micromolar concentrations, reduce bacterial survival by several orders of magnitude, and may kill planktonic cells and biofilms. All of them comprise either an anionic or neutral zwitterionic peptide attached to a long fatty amine (16–18 carbon atoms) and show a preference for anionic lipid membranes enriched in phosphatidylglycerol (PG), which excludes electrostatic interactions as the main driving force for DICAM action. Hence, the hydrophobic contacts provided by the long aliphatic chains of their fatty amines are needed for DICAM’s membrane insertion, while negative-charge shielding by salt counterions would reduce electrostatic repulsions. Additionally, we show that other components of the bacterial envelope, including the capsular polysaccharide, can influence the microbicidal activity of DICAMs. Several promising candidates with good-to-tolerable therapeutic ratios are identified as potential agents against S. pneumoniae and S. pyogenes. Structural characteristics that determine the preference for a specific pathogen or decrease DICAM toxicity have also been investigated.
Cross-talks between perivascular adipose tissue and neighbors: multifaceted nature of nereids
Authors: Li Yujuan , Chen Zhang , Xiao Ying , Li Xinzhi
Published: August 2024

Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT’s regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.
Using spectral continuity to extract breathing rate from heart rate and its applications in sleep physiology
Authors: Orphanides Gregoris A. , Karittevlis Christodoulos , Alsadder Lujain , Ioannides Andreas A.
Published: August 2024

Introduction: ECG Derived Respiration (EDR) are a set of methods used for extracting the breathing rate from the Electrocardiogram (ECG). Recent studies revealed a tight connection between breathing rate and more specifically the breathing patterns during sleep and several related pathologies. Yet, while breathing rate and more specifically the breathing pattern is recognised as a vital sign it is less employed than Electroencephalography (EEG) and heart rate in sleep and polysomnography studies.

Methods: This study utilised open-access data from the ISRUC sleep database to test a novel spectral-based EDR technique (scEDR). In contrast to previous approaches, the novel method emphasizes spectral continuity and not only the power of the different spectral peaks. scEDR is then compared against a more widely used spectral EDR method that selects the frequency with the highest power as the respiratory frequency (Max Power EDR).

Results: scEDR yielded improved performance against the more widely used Max Power EDR in terms of accuracy across all sleep stages and the whole sleep. This study further explores the breathing rate across sleep stages, providing evidence in support of a putative sleep stage "REM0" which was previously proposed based on analysis of the Heart Rate Variability (HRV) but not yet widely discussed. Most importantly, this study observes that the frequency distribution of the heart rate during REM0 is closer to REM than other NREM periods even though most of REM0 was previously classified as NREM sleep by sleep experts following either the original or revised sleep staging criteria.

Discussion: Based on the results of the analysis, this study proposes scEDR as a potential low-cost and non-invasive method for extracting the breathing rate using the heart rate during sleep with further studies required to validate its accuracy in awake subjects. In this study, the autonomic balance across different sleep stages, including REM0, was examined using HRV as a metric. The results suggest that sympathetic activity decreases as sleep progresses to NREM3 until it reaches a level similar to the awake state in REM through a transition from REM0.
Comparative transcriptome analysis of persimmon somatic mutants (Diospyros kaki) identifies regulatory networks for fruit maturation and size
Authors: Ban Seunghyun , Suh Hye-young , Lee Su Hyeon , Kim Si-Hong , Oh Sewon , Jung Je Hyeong
Published: August 2024

Bud sports in fruit crops often result in new cultivars with unique traits, such as distinct fruit size and color, compared to their parent plants. This study investigates the phenotypic differences and gene expression patterns in Tonewase and Ohtanenashi persimmon bud sports compared to those in their parent, Hiratanenashi, based on RNA-seq data. Tonewase is characterized by early maturation, whereas Ohtanenashi is noted for its larger fruit size. Despite the importance of these traits in determining fruit quality, their molecular bases in persimmons have been understudied. We compared transcriptome-level differences during fruit development between the bud sport samples and their original cultivar. Comprehensive transcriptome analyses identified 15,814 differentially expressed genes and 26 modules via weighted gene co-expression network analysis. Certain modules exhibited unique expression patterns specific to the different cultivars during fruit development, likely contributing to the phenotypic differences observed. Specifically, M11, M16, M22, and M23 were uniquely expressed in Tonewase, whereas M13 and M24 showed distinct patterns in Ohtanenashi. By focusing on genes with distinct expression profiles, we aimed to uncover the genetic basis of cultivar-specific traits. Our findings suggest that changes in the expression of genes associated with ethylene and cell wall pathways may drive Tonewase’s earlier maturation, whereas genes related to the cell cycle within the M24 module appear crucial for Ohtanenashi’s larger fruit size. Additionally, ethylene and transcription factor genes within this module may contribute to the increased fruit size observed. This study elucidates the differences in transcriptomic changes during fruit development between the two bud sport samples and their original cultivar, enhancing our understanding of the genetic determinants influencing fruit size and maturation.
Mindfulness and mechanisms of attention in a neutral and palatable food context
Authors: Logemann-Molnár Zsófia , Veres-Székely Anna , Demetrovics Zsolt , Logemann H. N. Alexander
Published: August 2024

Introduction

Mindfulness has been associated with benefits on cognitive processes, including attention. However, the exact relationship between mindfulness, components of attention, and the role of reward context has not yet been fully elucidated, which is relevant, especially in the context of addiction. In the current study, we specifically evaluated the relationship between dispositional mindfulness and the balance between voluntary (top-down), and stimulus-driven (bottom-up) attention. In addition, we explored whether the relationship was mediated by asymmetry of frontal brain activity, an index of approach tendencies, and varies as a function of reward context.

Methods

In total, 95 participants (30 male, 65 female) with a mean age of 25.87 (SD = 7.38) participated. Resting-state electrophysiological activity was recorded using EEG, and participants were assessed on dispositional mindfulness, and performed the visuospatial cueing (VSC) task, which indexed voluntary- and stimulus-driven attention in a neutral and palatable food (reward) context. In the endogenous VSC task, a central cue signals the likely location of a subsequent target. The validity effect represents the benefit of valid cueing relative to the costs of invalid cueing in terms of response time.

Results and discussion

Dispositional mindfulness was associated with a reduced validity effect, plausibly reflecting a combination of reduced voluntary attention and increased stimulus-driven attention, irrespective of condition. The relationship between dispositional mindfulness and visuospatial attention could not be explained by asymmetry of frontal brain activity.
Characteristics of eye disorders induced by atypical antipsychotics: a real-world study from 2016 to 2022 based on Food and Drug Administration Adverse Event Reporting System
Authors: Mu Chao , Chen Li
Published: August 2024

Background

Common atypical antipsychotics include risperidone, paliperidone, olanzapine, lurasidone, quetiapine, clozapine, aripiprazole, ziprasidone, asenapine, brexpiprazole, and cariprazine. Previous studies on ocular adverse reactions of antipsychotics were mainly focused on typical antipsychotics. Systematic research on atypical antipsychotics remains limited.

Objective

This study aimed to evaluate the potential risks of different atypical antipsychotics causing ocular side effects by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods

Extract reports from the FAERS from the first quarter of 2016 to the fourth quarter of 2022 were obtained. Data mining of eye disorders associated with atypical antipsychotics was carried out using The Reporting Odds Ratio (ROR) method and The Medicines and Healthcare Products Regulatory Agency (MHRA) method to determine positive signals.

Results

FAERS reports for 9913783 cases were included in these 28 quarters. 64 defined ocular adverse events were classified into 10 categories according to High-Level Group Terms (HLGT).

Conclusions

There were differences in the types and severity of ocular-related adverse events associated with atypical antipsychotics. Ocular neuromuscular-related adverse events were found among all 11 atypical antipsychotics. Olanzapine had the highest signal intensity in oculogyric crisis. Aripiprazole had the highest signal strength in blepharospasm. Cariprazine was associated with cataract-related ocular adverse reactions. In terms of the types of adverse events, our study found that aripiprazole was associated with 28 types of ocular adverse events, followed by quetiapine. Clozapine was only associated with two types of ocular adverse events.