bluuebunny/crossref_metadata_2025 huggingface dataset:
From normal population to prediabetes and diabetes: study of influencing factors and prediction models
Authors: Gong Di , Chen Xiaohong , Yang Lin , Zhang Yongjian , Zhong Qianqian , Liu Jing , Yan Chen , Cai Yongjiang , Yang Weihua , Wang Jiantao
Published: October 2023

Objective

The purpose of this study is to investigate the independent influencing factors of the transition from normal population to prediabetes, and from prediabetes to diabetes, and to further construct clinical prediction models to provide a basis for the prevention and management of prediabetes and diabetes.

Materials and methods

The data for this study were based on clinical information of participants from the Health Management Center of Peking University Shenzhen Hospital. Participants were classified into normal group, prediabetes group, and diabetes group according to their functional status of glucose metabolism. Spearman’s correlation coefficients were calculated for the variables, and a matrix diagram was plotted. Further, univariate and multivariate logistic regression analysis were conducted to explore the independent influencing factors. The independent influencing factors were used as predictors to construct the full-variable prediction model (Full.model) and simplified prediction model (Simplified.model).

Results

This study included a total of 5310 subjects and 22 variables, among which there were 1593(30%) in the normal group, 3150(59.3%) in the prediabetes group, and 567(10.7%) in the diabetes group. The results of the multivariable logistic regression analysis showed that there were significant differences in 9 variables between the normal group and the prediabetes group, including age(Age), body mass index(BMI), systolic blood pressure(SBP), urinary glucose(U.GLU), urinary protein(PRO), total protein(TP), globulin(GLB), alanine aminotransferase(ALT), and high-density lipoprotein cholesterol(HDL-C). There were significant differences in 7 variables between the prediabetes group and the diabetes group, including Age, BMI, SBP, U.GLU, PRO, triglycerides(TG), and HDL.C. The Full.model and Simplified.model constructed based on the above influencing factors had moderate discriminative power in both the training set and the test set.

Conclusion

Age, BMI, SBP, U.GLU, PRO, TP, and ALT are independent risk factors, while GLB and HDL.C are independent protective factors for the development of prediabetes in the normal population. Age, BMI, SBP, U.GLU, PRO, and TG are independent risk factors, while HDL.C is an independent protective factor for the progression from prediabetes to diabetes. The Full.model and Simplified.model developed based on these influencing factors have moderate discriminative power.
Intrauterine food restriction impairs the lipogenesis process in the mesenteric adipocytes from low-birth-weight rats into adulthood
Authors: Andreotti Sandra , Komino Ayumi Cristina Medeiros , de Fatima Silva Flaviane , Ramos Ana Paula Almeida , Gil Noemi Lourenço , Azevedo Gabriela Araujo , Sertié Rogerio Antonio Laurato , Lima Fabio Bessa , Landgraf Richardt Gama , Landgraf Maristella Almeida
Published: October 2023

Background

Intrauterine food restriction (IFR) during pregnancy is associated with low birth weight (LBW) and obesity in adulthood. It is known that white adipose tissue (WAT) plays critical metabolic and endocrine functions; however, this tissue’s behavior before weight gain and obesity into adulthood is poorly studied. Thus, we evaluated the repercussions of IFR on the lipogenesis and lipolysis processes in the offspring and described the effects on WAT inflammatory cytokine production and secretion.

Methods

We induced IFR by providing gestating rats with 50% of the necessary chow daily amount during all gestational periods. After birth, we monitored the offspring for 12 weeks. The capacity of isolated fat cells from mesenteric white adipose tissue (meWAT) to perform lipogenesis (14C-labeled glucose incorporation into lipids) and lipolysis (with or without isoproterenol) was assessed. The expression levels of genes linked to these processes were measured by real-time PCR. In parallel, Multiplex assays were conducted to analyze pro-inflammatory markers, such as IL-1, IL-6, and TNF-α, in the meWAT.

Results

Twelve-week-old LBW rats presented elevated serum triacylglycerol (TAG) content and attenuated lipogenesis and lipolysis compared to control animals. Inflammatory cytokine levels were increased in the meWAT of LBW rats, evidenced by augmented secretion by adipocytes and upregulated gene and protein expression by the tissue. However, there were no significant alterations in the serum cytokines content from the LBW group. Additionally, liver weight, TAG content in the hepatocytes and serum glucocorticoid levels were increased in the LBW group.

Conclusion

The results demonstrate that IFR throughout pregnancy yields LBW offspring characterized by inhibited lipogenesis and lipolysis and reduced meWAT lipid storage at 12 weeks. The increased serum TAG content may contribute to the augmented synthesis and secretion of pro-inflammatory markers detected in the LBW group.
Genetic diversity and runs of homozygosity analysis of Hetian sheep populations revealed by Illumina Ovine SNP50K BeadChip
Authors: Han Zhipeng , Zhou Wen , Zhang Lulu , Wang Ruotong , Liu Chunjie , Bai Xinyu , Liu Shudong
Published: October 2023

Hetian sheep have a long history and a wide distribution. They are renowned for their carpet-grade wool, which makes them a valuable genetic resource in China. The survey revealed that Hetian sheep primarily inhabit three distinct ecological environments: mountains (MTS), mountain–grasslands (MGTS), and grasslands (GTS). To understand the evolutionary relationships and germplasm characteristics of Hetian sheep in these diverse environments, we randomly selected 84 healthy adult ewes from each of these ecological regions. We obtained the Illumina Ovine SNP50K BeadChip by extracting DNA from Hetian sheep ear tissue using the phenol-chloroform method. Afterward, we conducted a population genetic structure and genetic diversity analysis of Hetian sheep using the Illumina Ovine SNP50K Beadchip. Principal component analysis (PCA) and neighbor-joining (NJ) phylogenetic analysis indicated that Hetian sheep in three different ecological environments exhibit distinct genetic distances. Admixture analysis indicated that MGTS and GTS share a common ancestral origins. Additionally, the linkage disequilibrium (LD) analysis indicated that M had the highest decay rate, while MG had the lowest decay rate. Furthermore, we identified the overlapping homozygous genomic regions of Hetian sheep in the three ecological environments through runs of homozygosity (ROH) analysis. We subsequently performed gene annotation and enrichment analysis on these overlapping genomic regions. In the MTS environment, we identified 31 candidate genes associated with high-altitude environmental adaptation. These genes are involved in bone cell generation, differentiation, and the maintenance of bone homeostasis (WNT6, WNT10A, and CHSY1); tooth and tongue development (LEF1, TP63, and PRDM16); and hearing and visual functions (RBP4, ATF6, and JAG1). In the GTS environment, we identified 22 candidate genes related to economic traits, including those associated with reproduction (PLA2G4F, ACVR1, and ADCY2) and growth (CAPN3, YAP1, and FGF9). Research indicates that Hetian sheep can be divided at the genomic level into three subtypes: MTS, MGTS, and GTS. This enhances the genetic diversity of Hetian sheep germplasm resources and provides guidance for the conservation of Hetian sheep breeds. Additionally, we have identified genes related to multiparous traits in MGTS and GTS, offering insights for the selection and breeding of multiparous Hetian sheep.
Case report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient
Authors: Gao Shan-Yu , Liu Yu-Xing , Dong Yi , Fan Liang-Liang , Ding Qi , Liu Lv
Published: October 2023

Background: Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear.

Method: We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family.

Results: A novel splice-altering variant (c.712–2A>G) in the WASHC5 gene was detected and further verified by RNA splicing analysis and Sanger sequencing. Real-time qPCR analysis showed that the expression of genes involved in the Wiskott–Aldrich syndrome protein and SCAR homolog (WASH) complex and endosomal and lysosomal systems was altered due to this variant.

Conclusion: A novel heterozygous splice-altering variant (c.712–2A>G) in the WASHC5 gene was detected in a Chinese family with HSP. Our study provided data for genetic counseling to this family and offered evidence that this splicing variant in the WASHC5 gene is significant in causing HSP.
Human CD79b+ neutrophils in the blood are associated with early-stage melanoma
Authors: Meyer Melissa A. , Dinh Huy Q. , Alimadadi Ahmad , Araujo Daniel J. , Chatterjee Nandini , Gutierrez Norma A. , Zhu Yanfang Peipei , Hunter Emma L. , Liang Shu , Seumois Gregory , Kiosses William B. , Catz Sergio D. , Vijayanand Pandurangan , Ottensmeier Christian , Hedrick Catherine C.
Published: October 2023

Purpose

Due to their abundance in the blood, low RNA content, and short lifespan, neutrophils have been classically considered to be one homogenous pool. However, recent work has found that mature neutrophils and neutrophil progenitors are composed of unique subsets exhibiting context-dependent functions. In this study, we ask if neutrophil heterogeneity is associated with melanoma incidence and/or disease stage.

Experimental design

Using mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning.

Results

We identified CD79b+ neutrophils (CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b+ neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b+ neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b+ neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis.

Conclusion

Our work suggests that CD79b+ neutrophils are associated with early-stage melanoma.
CLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells
Authors: Roy Sougata , Roy Sudeep , Mahata Bidesh , Pramanik Jhuma , Hennrich Marco L. , Gavin Anne-Claude , Teichmann Sarah A.
Published: October 2023

Pregnenolone (P5) is synthesized as the first bioactive steroid in the mitochondria from cholesterol. Clusters of differentiation 4 (CD4+) and Clusters of differentiation 8 (CD8+) immune cells synthesize P5 de novo; P5, in turn, play important role in immune homeostasis and regulation. However, P5’s biochemical mode of action in immune cells is still emerging. We envisage that revealing the complete spectrum of P5 target proteins in immune cells would have multifold applications, not only in basic understanding of steroids biochemistry in immune cells but also in developing new therapeutic applications. We employed a CLICK-enabled probe to capture P5-binding proteins in live T helper cell type 2 (Th2) cells. Subsequently, using high-throughput quantitative proteomics, we identified the P5 interactome in CD4+ Th2 cells. Our study revealed P5’s mode of action in CD4+ immune cells. We identified novel proteins from mitochondrial and endoplasmic reticulum membranes to be the primary mediators of P5’s biochemistry in CD4+ and to concur with our earlier finding in CD8+ immune cells. Applying advanced computational algorithms and molecular simulations, we were able to generate near-native maps of P5–protein key molecular interactions. We showed bonds and interactions between key amino acids and P5, which revealed the importance of ionic bond, hydrophobic interactions, and water channels. We point out that our results can lead to designing of novel molecular therapeutics strategies.
Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as an adjuvant therapy for ctDNA-positive gastric and gastroesophageal junction adenocarcinoma: a protocol for a randomized, controlled, multicenter phase II clinical trial (EXPLORING study)
Authors: Chen Yizhang , Zhang Jiaguang , Han Gaohua , Tang Jie , Guo Fen , Li Wei , Xie Li , Xu Hao , Zhang Xinyi , Tian Yitong , Pan Lanlan , Shu Yongqian , Ma Ling , Chen Xiaofeng
Published: October 2023

Background

The efficacy of current adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. ctDNA could serve as a potential marker to identify patients who are at higher risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly improve clinical outcome, albeit such evidence is rare in GA/GEJA. Here, we intend to explore the clinical benefit of the reinforcement of adjuvant immunotherapy and antiangiogenics alongside with chemotherapy in patients who are deemed in high risk of recurrence by ctDNA analysis, which might shed light on further improvements in adjuvant therapy for GA/GEJA.

Methods/Design

This study is designed as a prospective, multicenter, randomized, controlled phase II study in patients histologically or cytologically diagnosed with GA/GEJA who underwent D2 gastrectomy and achieved R0 or R1 resection. From February 2022, a total of 300 stage III patients will be enrolled and subjected according to ctDNA sequencing results, and those with positive results will subsequently be randomized 1:1 to arm A or B. Patients in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while patients in arm B will receive XELOX alone for 6-8 cycles. ctDNA-negative patients will be assigned to arm C, and patients who are ctDNA positive but failed in randomization will be assigned to arm D. Patients in arms C and D will receive the investigator’s choice of therapy. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the DFS of ctDNA positive patients versus ctDNA negative patients, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules on the treatment response, adverse events (AEs), and the impact of nutrition status or exercise on recurrence.

Discussion

We expect that ctDNA would be a strong prognostic factor and ctDNA-positive patients are at higher risk of relapse than ctDNA-negative patients. The addition of anlotinib and penpulimab to XELOX, may contribute to delaying relapse in ctDNA-positive patients.

Trial registration

https://www.clinicaltrials.gov, identifier NCT05494060.
IRAK-4 inhibition: emavusertib for the treatment of lymphoid and myeloid malignancies
Authors: Parrondo Ricardo D. , Iqbal Madiha , Von Roemeling Reinhard , Von Roemeling Christina , Tun Han W.
Published: October 2023

Several studies have identified mutations in the MYD88L265P gene as a key driver mutation in several B-cell lymphomas. B-cell lymphomas that harbor the MYD88L265P mutation form a complex with phosphorylated Bruton’s tyrosine kinase (BTK) and are responsive to BTK inhibition. However, BTK inhibition in B-cell lymphomas rarely results in a complete response and most patients experience eventual disease relapse. Persistent survival signaling though downstream molecules such as interleukin 1 receptor-associated kinase 4 (IRAK-4), an integral part of the “myddosome” complex, has been shown to be constitutively active in B-cell lymphoma patients treated with BTK inhibitors. Emerging evidence is demonstrating the therapeutic benefit of IRAK-4 inhibition in B-cell lymphomas, along with possibly reversing BTK inhibitor resistance. While MYD88 gene mutations are not present in myeloid malignancies, downstream overexpression of the oncogenic long form of IRAK-4 has been found in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), particularly in AML and MDS that harbor mutations in splicing factors U2AF1 and SF3B1. These data suggest that the anti-leukemic activity of IRAK-4 inhibition can be exploited in relapsed/refractory (R/R) AML/MDS. In this review article, we discuss the currently available pre-clinical and clinical data of emavusertib, a selective, orally bioavailable IRAK-4 inhibitor in the treatment of R/R B-cell lymphomas and myeloid malignancies.
The promiscuous development of an unconventional Qa1b-restricted T cell population
Authors: Manoharan Valerio Michael , Arana Kathya , Guan Jian , Chan Shiao Wei , Yang Xiaokun , Kurd Nadia , Lee Angus , Shastri Nilabh , Coscoy Laurent , Robey Ellen A.
Published: October 2023

MHC-E restricted CD8 T cells show promise in vaccine settings, but their development and specificity remain poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa-1b) that is presented in response to loss of the MHC I processing enzyme ERAAP, termed QFL T cells. We find that mature QFL thymocytes are predominantly CD8αβ+CD4-, show signs of agonist selection, and give rise to both CD8αα and CD8αβ intraepithelial lymphocytes (IEL), as well as memory phenotype CD8αβ T cells. QFL T cells require the MHC I subunit β-2 microglobulin (β2m), but do not require Qa1b or classical MHC I for positive selection. However, QFL thymocytes do require Qa1b for agonist selection and full functionality. Our data highlight the relaxed requirements for positive selection of an MHC-E restricted T cell population and suggest a CD8αβ+CD4- pathway for development of CD8αα IELs.
Dysbiosis of the gut microbiota as a susceptibility factor for Kawasaki disease
Authors: Teramoto Yoshiki , Akagawa Shohei , Hori Shin-ichiro , Tsuji Shoji , Higasa Koichiro , Kaneko Kazunari
Published: October 2023

Introduction

Gut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD.

Methods

Fecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.

Results

For alpha diversity, Faith’s phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray–Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini–Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of Ruminococcus gnavus group and lower relative abundance of Blautia.

Discussion and conclusion

Ruminococcus gnavus group reportedly includes pro-inflammatory bacteria. In contrast, Blautia suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of Blautia in parallel with increased abundance of Ruminococcus gnavus group might be a susceptibility factor for KD.
Early detection of deterioration in COVID-19 patients by continuous ward respiratory rate monitoring: a pilot prospective cohort study
Authors: Rivas Eva , López-Baamonde Manuel , Sanahuja Josep , Del Rio Elena , Ramis Tomeu , Recasens Anna , López Antonio , Arias Marilyn , Kampakis Stylianos , Lauteslager Timo , Awara Osama , Mascha Edward J. , Soriano Alex , Badía Joan Ramon , Castro Pedro , Sessler Daniel I.
Published: October 2023

Background

Tachypnea is among the earliest signs of pulmonary decompensation. Contactless continuous respiratory rate monitoring might be useful in isolated COVID-19 patients admitted in wards. We therefore aimed to determine whether continuous monitoring of respiratory patterns in hospitalized patients with COVID-19 predicts subsequent need for increased respiratory support.

Methods

Single-center pilot prospective cohort study in COVID-19 patients who were cared for in routine wards. COVID-19 patients who had at least one escalation of pulmonary management were matched to three non-escalated patients. Contactless respiratory monitoring was instituted after patients enrolled, and continued for 15 days unless hospital discharge, initiation of invasive mechanical ventilation, or death occurred. Clinicians were blinded to respiratory rate data from the continuous monitor. The exposures were respiratory features over rolling periods of 30 min, 24 h, and 72 h before respiratory care escalation. The primary outcome was a subsequent escalation in ventilatory support beyond a Venturi mask.

Results

Among 125 included patients, 13 exhibited at least one escalation and were each matched to three non-escalated patients. A total of 28 escalation events were matched to 84 non-escalation episodes. The 30-min mean respiratory rate in escalated patients was 23 breaths per minute (bpm) ranging from 13 to 40 bpm, similar to the 22 bpm in non-escalated patients, although with less variability (range 14 to 31 bpm). However, higher respiratory rate variability, especially skewness over 1 day, was associated with higher incidence of escalation events. Our overall model, based on continuous data, had a moderate accuracy with an AUC 0.81 (95%CI: 0.73, 0.88) and a good specificity 0.93 (95%CI: 0.87, 0.99).

Conclusion

Our pilot observational study suggests that respiratory rate variability as detected with continuous monitoring is associated with subsequent care escalation during the following 24 h. Continuous respiratory monitoring thus appears to be a valuable increment over intermittent monitoring.

Strengths and limitations

Our study was the initial evaluation of Circadia contactless respiratory monitoring in COVID-19 patients who are at special risk of pulmonary deterioration. The major limitation is that the analysis was largely post hoc and thus needs to be confirmed in an out-of-sample population.
Genetic causal relationship between gut microbiome and psoriatic arthritis: a bidirectional two-sample Mendelian randomization study
Authors: Qian Xinyu , Fu Zhida , Diao Chaoyue , Zhang Wenbo , Tao Weiyu , Hu Jiaqi , Zhang Shuqing , Zhao Dongbao
Published: October 2023

Background

Several observational studies have suggested a potential relationship between gut microbiome and psoriatic arthritis (PsA). However, the causality of this relationship still remains unclear. We aim to explore if the specific gut microbiome is causally associated with PsA at the genetic level and offer valuable insights into the etiology of PsA.

Methods

In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal effects of the gut microbiome on PsA. Publicly accessible genome-wide association study summary data of gut microbiome were obtained from the MiBioGen consortium (n = 14,306), while the summary statistics of psoriatic arthropathies were sourced from the FinnGen consortium R8 release data (2,776 cases and 221,323 controls). The primary analytical method employed was inverse variance weighted (IVW), complemented by supplementary methods including MR-Egger, weighted median, weighted mode, maximum likelihood, MR-PRESSO, and cML-MA. Reverse MR analysis was performed on the bacteria that were found to be causally associated with PsA in forward MR analysis. Cochran’s IVW Q statistic was utilized to assess the heterogeneity of instrumental variables among the selected single nucleotide polymorphisms.

Results

IVW estimates revealed that Ruminococcaceae_UCG-002 (odds ratio (OR) = 0.792, 95% confidence interval (CI), 0.643–0.977, p = 0.029) exhibited a protective effect on PsA. Conversely, Blautia (OR = 1.362, 95% CI, 1.008–1.842, p = 0.044), Eubacterium_fissicatena_group (OR = 1.28, 95% CI, 1.075–1.524, p = 0.006), and Methanobrevibacter (OR = 1.31, 95% CI, 1.059–1.621, p = 0.013) showed a positive correlation with the risk of PsA. No significant heterogeneity, horizontal pleiotropy, or outliers were observed, and the results of the MR analysis remained unaffected by any single nucleotide polymorphisms. According to the results of reverse MR analysis, no significant causal effect of PsA was found on gut microbiome.

Conclusion

This study establishes for the first time a causal relationship between the gut microbiome and PsA, providing potential valuable strategies for the prevention and treatment of PsA. Further randomized controlled trials are urgently warranted to support the targeted protective mechanisms of probiotics on PsA.
Detection of neuron-derived cfDNA in blood plasma: a new diagnostic approach for neurodegenerative conditions
Authors: Pollard Chad , Aston Kenneth , Emery Benjamin R. , Hill Jonathon , Jenkins Timothy
Published: October 2023

Neurodegenerative diseases, such as Alzheimer’s disease (AD), pose significant challenges in early diagnosis, leading to irreversible brain damage and cognitive decline. In this study, we present a novel diagnostic approach that utilizes whole molecule analysis of neuron-derived cell-free DNA (cfDNA) as a biomarker for early detection of neurodegenerative diseases. By analyzing Differential Methylation Regions (DMRs) between purified cortical neurons and blood plasma samples, we identified robust biomarkers that accurately distinguish between neuronal and non-neuronal cfDNA. The use of cfDNA offers the advantage of convenient and minimally invasive sample collection compared to traditional cerebrospinal fluid or tissue biopsies, making this approach more accessible and patient friendly. Targeted sequencing at the identified DMR locus demonstrated that a conservative cutoff of 5% of neuron-derived cfDNA in blood plasma accurately identifies 100% of patients diagnosed with AD, showing promising potential for early disease detection. Additionally, this method effectively differentiated between patients with mild cognitive impairment (MCI) who later progressed to AD and those who did not, highlighting its prognostic capabilities. Importantly, the differentiation between patients with neurodegenerative diseases and healthy controls demonstrated the specificity of our approach. Furthermore, this cfDNA-based diagnostic strategy outperforms recently developed protein-based assays, which often lack accuracy and convenience. While our current approach focused on a limited set of loci, future research should explore the development of a more comprehensive model incorporating multiple loci to increase diagnostic accuracy further. Although certain limitations, such as technical variance associated with PCR amplification and bisulfite conversion, need to be addressed, this study emphasizes the potential of cfDNA analysis as a valuable tool for pre-symptomatic detection and monitoring of neurodegenerative diseases. With further development and validation, this innovative diagnostic strategy has the potential to significantly impact the field of neurodegenerative disease research and patient care, offering a promising avenue for early intervention and personalized therapeutic approaches.
Change in sensory integration and regularity of postural sway with the suspensory strategy during static standing balance
Authors: Jiang Linjing , Kasahara Satoshi , Ishida Tomoya , Koshino Yuta , Chiba Ami , Yoshimi Kazumasa , Wei Yuting , Samukawa Mina , Tohyama Harukazu
Published: October 2023

Background and aim

The suspensory strategy, a method for controlling postural balance in the vertical direction of the center of mass (COM), is considered by the elderly as a means of balance control. The vertical COM control might alter the sensory integration and regularity of postural sway, which in turn impacts balance. However, to date, this was not confirmed. Thus, this study aimed at investigating the influence of the suspensory strategy achieved through knee flexion on the static standing balance.

Methods

Nineteen participants were monitored at knee flexion angles of 0°, 15°, and 65°. Time-frequency analysis and sample entropy were employed to analyze the COM data. Time-frequency analysis was utilized to assess the energy content across various frequency bands and corresponding percentage of energy within each frequency band. The outcomes of time-frequency are hypothesized to reflect the balance-related sensory input and sensory weights. Sample entropy was applied to evaluate the regularity of the COM displacement patterns.

Results

Knee flexion led to a decreased COM height. The highest energy content was observed at 65° knee flexion, in contrast with the lowest energy observed at 0° in both the anterior–posterior (AP) and medial-lateral (ML) directions. Additionally, the ultra-low-frequency band was more pronounced at 65° than that at 0° or 15° in the ML direction. Furthermore, the COM amplitudes were notably higher at 65° than those at 0° and 15° in the AP and ML directions, respectively. The sample entropy values were lower at 65° and 15° than those at 0° in the ML direction, with the lowest value observed at 65° in the vertical direction.

Conclusion

The suspensory strategy could enhance the sensory input and cause sensory reweighting, culminating in a more regular balance control. Such suspensory strategy-induced postural control modifications may potentially provide balance benefits for people with declining balance-related sensory, central processing, and musculoskeletal system functions.
Advancing the interfacing performances of chronically implantable neural probes in the era of CMOS neuroelectronics
Authors: Perna Alberto , Angotzi Gian Nicola , Berdondini Luca , Ribeiro João Filipe
Published: October 2023

Tissue penetrating microelectrode neural probes can record electrophysiological brain signals at resolutions down to single neurons, making them invaluable tools for neuroscience research and Brain-Computer-Interfaces (BCIs). The known gradual decrease of their electrical interfacing performances in chronic settings, however, remains a major challenge. A key factor leading to such decay is Foreign Body Reaction (FBR), which is the cascade of biological responses that occurs in the brain in the presence of a tissue damaging artificial device. Interestingly, the recent adoption of Complementary Metal Oxide Semiconductor (CMOS) technology to realize implantable neural probes capable of monitoring hundreds to thousands of neurons simultaneously, may open new opportunities to face the FBR challenge. Indeed, this shift from passive Micro Electro-Mechanical Systems (MEMS) to active CMOS neural probe technologies creates important, yet unexplored, opportunities to tune probe features such as the mechanical properties of the probe, its layout, size, and surface physicochemical properties, to minimize tissue damage and consequently FBR. Here, we will first review relevant literature on FBR to provide a better understanding of the processes and sources underlying this tissue response. Methods to assess FBR will be described, including conventional approaches based on the imaging of biomarkers, and more recent transcriptomics technologies. Then, we will consider emerging opportunities offered by the features of CMOS probes. Finally, we will describe a prototypical neural probe that may meet the needs for advancing clinical BCIs, and we propose axial insertion force as a potential metric to assess the influence of probe features on acute tissue damage and to control the implantation procedure to minimize iatrogenic injury and subsequent FBR.
Fructose intake and its association with relative telomere length: an exploratory study among healthy Lebanese adults
Authors: Messerlian Nairie , Zgheib Nathalie , Chokor Fatima Al Zahraa , Nasrallah Mona , Tamim Hani , Nasreddine Lara
Published: October 2023

Introduction

Shorter relative telomere length (RTL) has been associated with increased incidence of morbidity. Although still disputed, available evidence suggests that dietary factors, including sugar-sweetened beverages (SSB) may be linked with shorter RTL. It was argued that the link between SSB and RTL may be explained by the sugar content of these beverages, and specifically fructose given its impact on oxidative stress and the inflammatory response. However, none of the existing studies have examined the specific link between fructose intake and RTL. This exploratory study aimed at (1) assessing the intake of dietary fructose (total, added and natural) in Lebanese healthy adults and (2) examining dietary fructose as a predictor of short telomere length.

Methods

Following a cross-sectional design (n = 282), anthropometric and biochemical data were collected. RTL was assessed by utilizing real-time polymerase chain reaction (RT-qPCR) to amplify both telomere and single-copy gene segments. Dietary intake was evaluated using a culture-specific food frequency questionnaire (FFQ). Intakes of added fructose, naturally-occurring fructose, and total fructose were estimated.

Results

Mean intakes of added and natural fructose were of 39.03 ± 34.12 and 12.28 ± 8.59 g/day, respectively, representing 4.80 ± 3.56 and 1.78 ± 1.41% of total energy intake (EI). Mean total fructose intake was of 51.31 ± 35.55 g/day, contributing 6.58 ± 3.71% EI. Higher intakes of total and added fructose were significantly associated with shorter RTL 2nd RTL tertile as compared to the 3rd RTL tertile; relative risk ratio (RRR) = 3.10 [95% confidence interval (CI): 1.38, 6.94] and RRR = 2.33 (95% CI: 1.02, 5.36), respectively after adjustment for confounders identified using a directed acyclic graph (DAG).

Conclusion

In conclusion, although we could not observe a dose-dependent relation between fructose intakes and RTL shortening and although the study is limited by its small sample size, the findings suggest that total and added dietary fructose intakes may be associated with shorter RTL. Larger studies, of longitudinal nature, are needed to further confirm the study findings.
Are there differences between Mediterranean diet and the consumption of harmful substances on quality of life?—an explanatory model in secondary education regarding gender
Authors: Melguizo-Ibáñez Eduardo , Zurita-Ortega Félix , Ubago-Jiménez José Luis , Badicu Georgian , Yagin Fatma Hilal , González-Valero Gabriel , Ardigò Luca Paolo , Puertas-Molero Pilar
Published: October 2023

Background

Adolescence is a key life stage in human development. It is during this stage of development that healthy and physical behaviors are acquired that will last into adulthood. Gender differences in the acquisition of these behaviors have been observed. This research aims to (a) study the levels of Mediterranean diet adherence, quality of life and alcohol and tobacco consumption as regarding the gender of the participants and (b) study the effects of the variable adherence to the Mediterranean diet, alcohol consumption and tobacco consumption on quality of life as a function of the gender of the participants.

Methods

A non-experimental, cross-sectional, exploratory study was carried out in a sample of 1,057 Spanish adolescents (Average Age = 14.19; Standard Deviation = 2.87).

Results

The comparative analysis shows that the male teenagers shows a higher Mediterranean diet adherence compared to the male adolescents (p ≤ 0.05) and a higher consumption of alcoholic beverages (p ≤ 0.05). On the contrary, adolescent girls show a higher consumption of alcoholic beverages than male participants (p ≤ 0.05). The exploratory analysis indicates that for boys, alcohol consumption has a beneficial effect on the quality of life of adolescents (β = 0.904; p ≤ 0.001).

Conclusion

In this case, participants show differences in the levels of Mediterranean diet adherence, consumption of harmful substances and quality of life according to gender. Likewise, there are different effects between the variables according to gender. Therefore, gender is a key factor to consider during adolescence.
Carbohydrate antigen 125 in congestive heart failure: ready for clinical application?
Authors: Feng Rui , Zhang Zhenlu , Fan Qingkun
Published: October 2023

Congestion is the permanent mechanism driving disease progression in patients with acute heart failure (AHF) and also is an important treatment target. However, distinguishing between the two different phenotypes (intravascular congestion and tissue congestion) for personalized treatment remains challenging. Historically, carbohydrate antigen 125 (CA125) has been a frequently used biomarker for the screening, diagnosis, and prognosis of ovarian cancer. Interestingly, CA125 is highly sensitive to tissue congestion and shows potential for clinical monitoring and optimal treatment of congestive heart failure (HF). Furthermore, in terms of right heart function parameters, CA125 levels are more advantageous than other biomarkers of HF. CA125 is expected to become a new biological alternative marker for congestive HF and thereby is expected be widely used in clinical practice.
The efficacy and safety of 5-fluorouracil/cisplatin/vincristine as a multi-agent chemotherapy regimen in gestational trophoblastic neoplasia
Authors: Wang Lu , Wang Qian , Xu Zhen , Yang Linli , Wang Wuliang
Published: October 2023

Objective

To determine the efficacy and safety of the 5-fluorouracil (5-FU), cisplatin, and vincristine (FPV) chemotherapy regimen in patients with gestational trophoblastic neoplasia (GTN).

Methods

We performed a retrospective study of 96 GTN patients with International Federation of Gynecology and Obstetrics (FIGO) scores of 5 or greater in the Second Affiliated Hospital of Zhengzhou University from October 2013 to October 2019, including 54 patients who received FPV chemotherapy and 42 who received 5-FU/actinomycin D/vincristine (FAV) chemotherapy. A pulsed intravenous device was used to administer 5-FU. The clinical characteristics, adverse events, and response rates were compared between the groups.

Results

The patients in the FPV and FAV groups received a total of 228 and 190 courses of chemotherapy, respectively. Complete response (CR) was found in 88.89% (48/54) and 90.48% (38/42) of patients in the FPV group and FAV group, respectively (p = 0.801). Both chemotherapy regimens yielded CR in all low-risk patients (100% vs. 100%), whereas 86.67% and 88.24% of high-risk patients achieved CR (FPV vs. FAV, p = 0.836), respectively. The most common adverse events (AEs) were myelosuppression and gastrointestinal reactions including neutropenia (83.97%), anemia (60.05%), and nausea (46.41%). In comparison to those in the FAV group, patients in the FPV group reported higher rates of grade 1/2 nausea (53.51% vs. 37.89%, p = 0.001), hepatotoxicity (28.95% vs. 17.89%, p = 0.008), oral mucositis (23.25% vs. 10.53%, p = 0.001), and grade 3/4 neutropenia (47.37% vs. 27.37%, p < 0.001), while grade 1/2 diarrhea (7.46% vs. 13.68%, p = 0.037) and grade 3/4 oral mucositis (0 vs. 6.32%, p < 0.001) were much more common in the FAV group. The rate of overall survival at 5 years was 96.8% in the FPV group and 97.3% in the FAV group (p = 0.760), whereas the 5-year disease-free survival rates were 95.9% and 93.9% (p = 0.754), respectively.

Conclusion

The FPV and FAV regimens with pulsed intravenous 5-FU yielded comparable CR rates and tolerability in patients with GTN with FIGO scores of >5. Further randomized controlled trials are warranted to validate their efficacy.
Gastroesophageal reflux and PPI exposure alter gut microbiota in very young infants
Authors: Francis Denease , Chawla Anupama , LaComb Joseph F. , Markarian Katherine , Robertson Charles E. , Frank Daniel N. , Gathungu Grace N.
Published: October 2023

Importance

Infants with symptomatic Gastroesophageal reflux are treated with pharmacological therapy that includes proton pump inhibitors (PPI) with clinical improvement. The alterations to gut microbiome profiles in comparison to infants without reflux is not known.

Objective

To determine the effect of PPI therapy on gut bacterial richness, diversity, and proportions of specific taxa in infants when compared to infants not exposed to acid suppressive therapy.

Design, setting, and participants

This cohort study was conducted at the Stony Brook Hospital in Stony Brook, NY between February 2016, and June 2019. Infants meeting inclusion criteria were enrolled in a consecutive fashion.

Results

A total of 76 Infants were recruited and 60 were enrolled in the study, Twenty nine infants met clinical criteria for reflux and were treated with PPI therapy: median [IQR] gestation: 38.0 weeks [34.7–39.6 weeks]; median [IQR] birthweight: 2.95 Kg [2.2–3.4]; 14 [46.7%] male) and 29 infant were healthy controls median [IQR] gestation: 39.1 weeks [38–40 weeks]; median [IQR] birthweight: 3.3 Kg [2.2–3.4]; 17 [58.6%] male); 58 stool samples from 58 infants were analyzed. There were differences in Shannon diversity between the reflux and control groups. The reflux group that was exposed to PPI therapy had increased relative abundance of a diverse set of genera belonging to the phylum Firmicutes. On the other hand, the control group microbiota was dominated by Bifidobacterium, and a comparatively lower level of enrichment and abundance of microbial taxa was observed in this group of infants.

Conclusions and relevance

We observed significant differences in both α- and β-diversity of the microbiome, when the two groups of infants were compared. The microbiome in the reflux group had more bacterial taxa and the duration of PPIs exposure was clearly associated with the diversity and abundance of gut microbes. These findings suggest that PPI exposure among infants results in early enrichment of the intestinal microbiome.
Exploring the dynamics of role transition of employees in family businesses through the evolutionary game theory
Authors: Zhang Linrong , Wu Mengyun , Li Shiyu , Liu Ruiwen , Zhu Yuqing
Published: October 2023

This investigation delves into the dynamic optimization of the progression from outsider to insider status within the context of family businesses. Utilizing a dynamic game model that incorporates three agents—leaders, insiders, and outsiders—it conducts a rigorous examination of the optimal pathway for the status transition of outsider employees in family businesses. The paramount objective of this study is to generate theoretical insights that may inform the optimization of human resources management and thereby bolster the overall performance of family businesses. The key findings of the research are as follows: 1) Outsider employees necessitate support from both leaders and insiders for a successful elevation in ranks. A collaborative relationship with insiders significantly enhances their performance. 2) The harmonious functioning of the workplace demands concerted efforts from all parties—leaders, insiders, and outsiders. The upward mobility of outsiders is contingent upon synergistic cooperation amongst all stakeholders. 3) A myriad of factors such as potential costs, benefits, and favoritism heavily influence the degree to which leaders endorse the upward mobility of outsiders. 4) Encouraging outsiders to move up in the ranks can instigate a sense of urgency among insiders, serving as a deterrent against complacency. This urgency can act as a catalyst for insiders to enhance their performance and mitigate the perceived threat to their own status.
OSC-CO2: coattention and cosegmentation framework for plant state change with multiple features
Authors: Quiñones Rubi , Samal Ashok , Das Choudhury Sruti , Muñoz-Arriola Francisco
Published: October 2023

Cosegmentation and coattention are extensions of traditional segmentation methods aimed at detecting a common object (or objects) in a group of images. Current cosegmentation and coattention methods are ineffective for objects, such as plants, that change their morphological state while being captured in different modalities and views. The Object State Change using Coattention-Cosegmentation (OSC-CO2) is an end-to-end unsupervised deep-learning framework that enhances traditional segmentation techniques, processing, analyzing, selecting, and combining suitable segmentation results that may contain most of our target object’s pixels, and then displaying a final segmented image. The framework leverages coattention-based convolutional neural networks (CNNs) and cosegmentation-based dense Conditional Random Fields (CRFs) to address segmentation accuracy in high-dimensional plant imagery with evolving plant objects. The efficacy of OSC-CO2 is demonstrated using plant growth sequences imaged with infrared, visible, and fluorescence cameras in multiple views using a remote sensing, high-throughput phenotyping platform, and is evaluated using Jaccard index and precision measures. We also introduce CosegPP+, a dataset that is structured and can provide quantitative information on the efficacy of our framework. Results show that OSC-CO2 out performed state-of-the art segmentation and cosegmentation methods by improving segementation accuracy by 3% to 45%.
PSTVd infection in Nicotiana benthamiana plants has a minor yet detectable effect on CG methylation
Authors: Tselika Martha , Belmezos Nektarios , Kallemi Paraskevi , Andronis Christos , Chiumenti Michela , Navarro Beatriz , Lavigne Matthieu , Di Serio Francesco , Kalantidis Kriton , Katsarou Konstantina
Published: October 2023

Viroids are small circular RNAs infecting a wide range of plants. They do not code for any protein or peptide and therefore rely on their structure for their biological cycle. Observed phenotypes of viroid infected plants are thought to occur through changes at the transcriptional/translational level of the host. A mechanism involved in such changes is RNA-directed DNA methylation (RdDM). Till today, there are contradictory works about viroids interference of RdDM. In this study, we investigated the epigenetic effect of viroid infection in Nicotiana benthamiana plants. Using potato spindle tuber viroid (PSTVd) as the triggering pathogen and via bioinformatic analyses, we identified endogenous gene promoters and transposable elements targeted by 24 nt host siRNAs that differentially accumulated in PSTVd-infected and healthy plants. The methylation status of these targets was evaluated following digestion with methylation-sensitive restriction enzymes coupled with PCR amplification, and bisulfite sequencing. In addition, we used Methylation Sensitive Amplification Polymorphism (MSAP) followed by sequencing (MSAP-seq) to study genomic DNA methylation of 5-methylcytosine (5mC) in CG sites upon viroid infection. In this study we identified a limited number of target loci differentially methylated upon PSTVd infection. These results enhance our understanding of the epigenetic host changes as a result of pospiviroid infection.