bluuebunny/crossref_metadata_2025 huggingface dataset:
Mismatch repair gene MSH6 correlates with the prognosis, immune status and immune checkpoint inhibitors response of endometrial cancer
Authors: Zhou Lin-Zhi , Xiao Hong-Qi , Chen Jie
Published: February 2024

Objective

Many patients treated with immune checkpoint inhibitors (ICIs) developed primary or secondary drug resistance for unknown reasons. This study investigates whether mismatch repair (MMR) genes are responsible for this therapeutic restriction.

Methods

We obtained the transcriptional, clinical and single nucleotide polymorphism data for endometrial cancer (EC) from The Cancer Genome Atlas and the immunophenoscore data of EC from The Cancer Immunome Atlas, then analyzed in R to evaluate the relationship between MMR genes and clinicopathological features, prognosis, immune infiltration, immune checkpoint expression and responsiveness to ICIs in EC. We used differentially expressed genes in the MSH6 high and low expression groups to conduct GO and KEGG analyses to explore the impact of MSH6 on the biological functions of EC. Finally, we verified the bioinformatics results with in vitro experiments.

Results

Our analyses showed that compared with the high MSH6 expression group, the low MSH6 expression group had better survival outcomes and less aggressive clinicopathological features. In the multivariate Cox analysis, MSH6 was the only independent risk factor that could predict the prognosis of EC. Besides, the low MSH6 expression group also had a higher immune score, more active immune infiltration and higher immune checkpoint expression, resulting in better responsiveness to ICIs treatment, consistent with the enrichment of GO terms and KEGG pathways related to immune response in this group. Meanwhile, the GO and KEGG enrichment results of the MSH6 high expression group were associated with cell cycle, DNA damage repair and tumorigenesis. To exclude the influence of MSH6 mutations, we performed the previous analyses on the MSH6 wild-type tumor samples and obtained consistent results. In vitro experiments also confirmed that after knocking down MSH6 in endometrial cancer cells, their proliferation, migration and invasion abilities were weakened, while the expression levels of PD-L1 and PD-L2 were elevated. In comparison, overexpression of MSH6 showed an opposite trend.

Conclusion

Reduced MSH6 expression could serve as a potential biomarker for predicting better prognosis, active immune status, higher immune checkpoint expression level and better responsiveness to ICIs treatment in EC. MSH6 may become a potential target for treating solid tumors.
Guanylate-binding protein-5 is involved in inflammasome activation by bacterial DNA but only the cooperation of multiple GBPs accounts for control of Brucella abortus infection
Authors: Marinho Fabio V. , Brito Camila , de Araujo Ana Carolina V. S. C. , Oliveira Sergio C.
Published: February 2024

Introduction

Guanylate-binding proteins (GBPs) are produced in response to pro-inflammatory signals, mainly interferons. The most studied cluster of GBPs in mice is on chromosome 3. It comprises the genes for GBP1-to-3, GBP5 and GBP7. In humans, all GBPs are present in a single cluster on chromosome 1. Brucella abortus is a Gram-negative bacterium known to cause brucellosis, a debilitating disease that affects both humans and animals. Our group demonstrated previously that GBPs present on murine chromosome 3 (GBPchr3) is important to disrupt Brucella-containing vacuole and GBP5 itself is important to Brucella intracellular LPS recognition. In this work, we investigated further the role of GBPs during B. abortus infection.

Methods and results

We observed that all GBPs from murine chromosome 3 are significantly upregulated in response to B. abortus infection in mouse bone marrow-derived macrophages. Of note, GBP5 presents the highest expression level in all time points evaluated. However, only GBPchr3-/- cells presented increased bacterial burden compared to wild-type macrophages. Brucella DNA is an important Pathogen-Associated Molecular Pattern that could be available for inflammasome activation after BCV disruption mediated by GBPs. In this regard, we observed reduced IL-1β production in the absence of GBP2 or GBP5, as well as in GBPchr3-/- murine macrophages. Similar result was showed by THP-1 macrophages with downregulation of GBP2 and GBP5 mediated by siRNA. Furthermore, significant reduction on caspase-1 p20 levels, LDH release and Gasdermin-D conversion into its mature form (p30 N-terminal subunit) was observed only in GBPchr3-/- macrophages. In an in vivo perspective, we found that GBPchr3-/- mice had increased B. abortus burden and higher number of granulomas per area of liver tissue, indicating increased disease severity.

Discussion/conclusion

Altogether, these results demonstrate that although GBP5 presents a high expression pattern and is involved in inflammasome activation by bacterial DNA in macrophages, the cooperation of multiple GBPs from murine chromosome 3 is necessary for full control of Brucella abortus infection.
Role of innate T cells in necrotizing enterocolitis
Authors: Liu Jianyun , Joseph Sharon , Manohar Krishna , Lee Jasmine , Brokaw John P. , Shelley W. Christopher , Markel Troy A.
Published: February 2024

Necrotizing enterocolitis (NEC) is a destructive gastrointestinal disease primarily affecting preterm babies. Despite advancements in neonatal care, NEC remains a significant cause of morbidity and mortality in neonatal intensive care units worldwide and the etiology of NEC is still unclear. Risk factors for NEC include prematurity, very low birth weight, feeding with formula, intestinal dysbiosis and bacterial infection. A review of the literature would suggest that supplementation of prebiotics and probiotics prevents NEC by altering the immune responses. Innate T cells, a highly conserved subpopulation of T cells that responds quickly to stimulation, develops differently from conventional T cells in neonates. This review aims to provide a succinct overview of innate T cells in neonates, encompassing their phenotypic characteristics, functional roles, likely involvement in the pathogenesis of NEC, and potential therapeutic implications.
Cross-linking lignin and cellulose with polymers using siloxane compounds
Authors: Grade Samantha , Zhang Xavier , Yang Che-Hao , Oduro Isaac , Wang Chenxi
Published: February 2024

Siloxanes are a group of substances characterized by Si-O-Si functional group. Siloxanes can react with alcohols to form Si-O-C bond. Siloxanes have been widely used as crossing linking agents and graft copolymers as well as additives for plastics. Lignin contains both phenolic and aliphatic hydroxy groups which have the potential to instigate bonding with siloxane compounds. However, there has not been any attempt to apply siloxanes as crosslinking agents for biobased composite formation. This manuscript presents the first study of applying siloxanes compounds to lignin and Cellulose nanofibers (CNF) with respective PLA, PETG, and HDPE to prepare biocomposites. Both Tetramethyl Tetraphenyl Trisiloxane (TTT) and Tetraethoxysilane (TEOS) were used as cross-linking agents. We have successfully incorporated 20 wt% lignin and 10 wt% CNF into the biocomposite filaments. The tensile properties of ensuing biocomposite were investigated. The objective of this work is to demonstrate the potential of lignin and CNF as a sustainable co-polymer to improve the properties of PLA/PETG/HDPE-based materials for 3D printing. This paper will also discuss the challenges and opportunities associated with the use of lignin in 3D printing, including the effect of lignin and CNF content on the mechanical and thermal properties, the compatibility of lignin and CNF with PLA/PETG/HDPE, and the potential for further optimization of the cross-linking chemistry using TTT and TEOS.
Evaluation of a creatinine clearance correction equation based on body fat mass in older Japanese patients with diabetes
Authors: Utsumi Sara , Kondo Yuki , Harada Yoshihiko , Yoshida Akira , Nishimura Hiroyuki , Narita Yuki , Irie Tetsumi , Jinnouchi Hideaki , Ishitsuka Yoichi , Hirata Sumio
Published: February 2024

Background

The estimation of creatinine clearance (CCr) in older adult patients with diabetes is subject to deviations from the results of actual measurements because of changes in body composition. In the present study, we aimed to create a correction for the equation used for the estimation of CCr in older adult Asian patients with diabetes using body composition parameters.

Methods

We enrolled 50 older Japanese patients with diabetes in whom the measured values of CCr were compared with values estimated using the Cockcroft-Gault equation. The relationships between the error in the estimated CCr and body composition parameters were investigated, and the Cockcroft-Gault equation was corrected using the appropriate parameters. To evaluate the generalizability of the corrected equation, the utility of the Cockcroft-Gault equation, which was corrected on the basis of body composition measured using a household body composition meter, was also investigated.

Results

Body fat mass (BFM) was closely correlated with the error in the estimated CCr. The BFM-corrected Cockcroft-Gault equation was more accurate than the original equation. Similarly, the error became smaller using BFM measured with a household body composition meter.

Conclusion

The BFM-corrected Cockcroft-Gault equation may provide an accurate method of estimating CCr that can be used in general practice.
Failure to reduce the risk of postoperative lower genital tract infection with perioperative antibiotic prophylaxis during induced abortion: a real-world study
Authors: Ding Jing , Zhang Yan , Gu XiangYing , Che Yan
Published: February 2024

Objective

This study aimed to evaluate perioperative antibiotic use for induced abortion and its association with lower genital tract infections (LGTI) two weeks post-surgery in China.

Methods

We conducted a prospective cohort study of women seeking induced abortion. We interviewed participants on the day of surgery and two weeks after, and evaluated preoperative tests, gynecological exams, perioperative antibiotic usage, postoperative vaginal microbiota, and LGTI diagnosis. Multivariate logistic regression was used to assess the association between the perioperative antibiotic use and LGTI risk.

Results

We recruited 8,190 women undergoing induced abortion at 27 participating hospitals. Of these, 95% had gynecological exams, but over 80% lacked tests for vaginal microbiota, chlamydia, and gonorrhea. Approximately 20% of those examined had increased vaginal discharge and abnormal vaginal cleanliness. The positive rates for gram-positive rods, fungi, and trichomonas were 38.6, 2.4, and 0.3%, respectively. More than three-quarters (78.5%) of participants received antibiotics, mainly second-gen cephalosporins (36.8%) and nitroimidazoles (12.3%). LGTI rates two weeks post-surgery were 2.7% for antibiotic recipients and 3.1% for non-recipients, with no statistically significant difference (p > 0.05). Logistic regression showed no association between perioperative antibiotic use and LGTI risk (OR = 1.01, 95% CI 0.59–1.74). However, this risk increased with abnormal preoperative discharge tests (OR = 1.39, 95% CI 1.04–1.86).

Conclusion

Most Chinese women undergoing induced abortion used perioperative antibiotics, but this did not significantly reduce LGTI risk. Instead, this risk was related to abnormal preoperative discharge tests. Standardization of perioperative antibiotic use for induced abortion is recommended, and prophylactic treatment in Chinese abortion services warrants further investigation.
Concept for intrathecal delivery of brain recording and stimulation device
Authors: Chapman Daniel P. , Wu Jian-Young
Published: February 2024

Neurological disorders are common, yet many neurological diseases don't have efficacious treatments. The protected nature of the brain both anatomically and physiologically through the blood brain barrier (BBB) make it exceptionally hard to access. Recent advancements in interventional approaches, like the Stentrode™, have opened the possibility of using the cerebral vasculature as a highway for minimally invasive therapeutic delivery to the brain. Despite the immense success that the Stentrode™ has faced recently, it is limited to major cerebral vasculature and exists outside the BBB, making drug eluting configurations largely ineffective. The present study seeks to identify a separate anatomical pathway for therapeutic delivery to the deep brain using the ventricular system. The intrathecal route, in which drug pumps and spinal cord stimulators are delivered through a lumbar puncture, is a well-established route for delivering therapies to the spinal cord as high as C1. The present study identifies an extension of this anatomical pathway through the foramen of Magendie and into the brains ventricular system. To test this pathway, a narrow self-expanding electrical recording device was manufactured and its potential to navigate the ventricular system was assessed on human anatomical brain samples. While the results of this paper are largely preliminary and a substantial amount of safety and efficacy data is needed, this paper identifies an important anatomical pathway for delivery of therapeutic and diagnostics tools to the brain that is minimally invasive, can access limbic structures, and is within the BBB.
The incremental value of Mycobacterium tuberculosis trace nucleic acid detection in CT-guided percutaneous biopsy needle rinse solutions for the diagnosis of tuberculosis
Authors: Li Zihui , Wang Bing , Du Boping , Sun Qi , Wang Dongpo , Wei Rongrong , Li Chenghai , Zhu Chuanzhi , Jia Hongyan , Xing Aiying , Zhang Zongde , Pan Liping , Hou Dailun
Published: February 2024

Introduction

Tuberculosis (TB) diagnosis still faces challenges with high proportion of bacteriologic test negative incidences worldwide. We assessed the diagnostic value of digital PCR (dPCR) analysis of ultramicro Mycobacterium tuberculosis (M.tb) nucleic acid in CT-guided percutaneous biopsy needle rinse solution (BNRS) for TB.

Methods

BNRS specimens were consecutively collected and total DNA was purified. The concentrations of M.tb-specific IS6110 and IS1081 were quantified using droplet dPCR. The diagnostic performances of BNRS-dPCR and its sensitivity in comparison with conventional tests were analyzed.

Results

A total of 106 patients were enrolled, 63 of whom were TB (48 definite and 15 clinically suspected TB) and 43 were non-TB. The sensitivity of BNRS IS6110 OR IS1081-dPCR for total, confirmed and clinically suspected TB was 66.7%, 68.8% and 60.0%, respectively, with a specificity of 97.7%. Its sensitivity was higher than that of conventional etiological tests, including smear microscopy, mycobacterial culture and Xpert using sputum and BALF samples. The positive detection rate in TB patients increased from 39.3% for biopsy AFB test alone to 73.2% when combined with BNRS-dPCR, and from 71.4% for biopsy M.tb molecular detection alone to 85.7% when combined with BNRS-dPCR.

Conclusion

Our results preliminarily indicated that BNRS IS6110 OR IS1081-dPCR is a feasible etiological test, which has the potential to be used as a supplementary method to augment the diagnostic yield of biopsy and improve TB diagnosis.
Diversity of Wickerhamomyces (Wickerhamomycetaceae, Saccharomycetales) in China with the description of four new species
Authors: Chai Chun-Yue , Ke Tao , Niu Qiu-Hong , Hui Feng-Li
Published: February 2024

Wickerhamomyces is a well-known genus of the family Wickerhamomycetaceae in the class Ascomycetes. These fungi can survive in a variety of substrates and environments and perform many valuable roles in both industrial processes and the natural ecosystems. During our investigation of yeast diversity associated with plant materials, 53 Wickerhamomyces isolates were obtained from rotting wood and plant leaves collected in Fujian, Guizhou, Henan, and Yunnan Provinces of China. Isolates were identified as 14 Wickerhamomyces species, including 1 species known previously to occur in China (W. anomalus), 9 new record species in China (W. arborarius, W. ciferrii, W. edaphicus, W. lynferdii, W. pijperi, W. subpelliculosa, W. xylosica, W. strasburgensis, and W. sydowiorum), and 4 novel species (W. guiyangensis sp. nov., W. paramyanmarensis sp. nov., W. quanzhouensis sp. nov., and W. phyllophilus sp. nov.). This study presents a detailed account of these new species, illustrating their morphology and analyzing their phylogenetic relationships with other Wickerhamomyces species. Our study is the first comprehensive study on Wickerhamomyces species associated with plant materials from tropical and subtropical China. The results of this study update our understanding of the phylogenetic relationships, systematics, and ecology of Wickerhamomyces.
Detection and genetic diversity of subgroup K avian leukosis virus in local chicken breeds in Jiangxi from 2021 to 2023
Authors: Zhang Fanfan , Li Haiqin , Lin Cui , Wei Yue , Zhang Weihong , Wu Yanping , Kang Zhaofeng
Published: February 2024

Avian leukosis virus subgroup K (ALV-K) is a new subgroup of avian leukosis virus (ALV) that was first identified in Chinese native chickens in recent years. To further understand the molecular epidemiology and evolutionary diversity of ALV-K, this study investigated the molecular epidemiology of 73,664 chicken plasma samples collected from Jiangxi native chicken flocks. The results showed that ALV-J was the most predominant ALV subtype in Jiangxi native chickens, with a high positivity rate of 4.34%. From 2021 to 2023, there was a gradual upward trend in the proportion of positive numbers of ALV-K among ALV-positive samples, and there was a trend of outbreaks. ALV-J and ALV-K were the main co-infection patterns. Genetic evolutionary analysis based on ALV-K gp85 gene showed that the isolated ALV-K in this study were distributed in various branches of the evolutionary tree with genetic diversity. The homology results showed that the amino acid homology of the isolated ALV-K gp85 gene ranged from 33.9 to 88.1% with the reference strains of subtypes A, B, C, D, E, and J, and from 91.9 to 100% with the other ALV-K reference strains. Multiple mutations were present in the ALV-K gp85, and especially significant mutations were found in the highly variable region hr2. The results of ALV-K replication efficiency showed that the replication efficiency of ALV-K was significantly lower than that of ALV-J. These results enriched the genome sequence data of ALV-K in Chinese geoducks, and laid the foundation for further research on the pathogenesis and prevention of ALV-K.
Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study
Authors: Han Shuai , Gao Jiapei , Wang Zi , Xiao Yinggang , Ge Yali , Liang Yongxin , Gao Ju
Published: February 2024

Background

Previous researches have suggested a significant connection between the gut microbiota/immune cells and morphine tolerance (MT), but there is still uncertainty regarding their causal relationship. Hence, our objective is to inverstigate this causal association and reveal the impact of gut microbiota/immune cells on the risk of developing MT using a two-sample Mendelian randomization (MR) study.

Methods

We conducted a comprehensive analysis using genome-wide association study (GWAS) summary statistics for gut microbiota, immune cells, and MT. The main approach employed was the inverse variance-weighted (IVW) method in MR. To assess horizontal pleiotropy and remove outlier single-nucleotide polymorphisms (SNPs), we utilized the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) technique as well as MR-Egger regression. Heterogeneity detection was performed using Cochran’s Q-test. Additionally, leave-one-out analysis was carried out to determine if any single SNP drove the causal association signals. Finally, we conducted a reverse MR to evaluate the potential of reverse causation.

Results

We discovered that 6 gut microbial taxa and 16 immune cells were causally related to MT (p < 0.05). Among them, 2 bacterial features and 9 immunophenotypes retained a strong causal relationship with lower risk of MT: genus. Lachnospiraceae NK4A136group (OR: 0.962, 95% CI: 0.940–0.987, p = 0.030), genus. RuminococcaceaeUCG011 (OR: 0.960, 95% CI: 0.946–0.976, p = 0.003), BAFF-R on B cell (OR: 0.972, 95% CI: 0.947–0.998, p = 0.013). Furthermore, 4 bacterial features and 7 immunophenotypes were identified to be significantly associated with MT risk: genus. Flavonifractor (OR: 1.044, 95% CI: 1.017–1.069, p = 0.029), genus. Prevotella9 (OR: 1.054, 95% CI: 1.020–1.090, p = 0.037), B cell % CD3-lymphocyte (OR: 1.976, 95% CI: 1.027–1.129, p = 0.026). The Cochrane’s Q test revealed no heterogeneity (p > 0.05). Furthermore, the MR-Egger and MR-PRESSO analyses reveal no instances of horizontal pleiotropy (p > 0.05). Besides, leave-one-out analysis confirmed the robustness of MR results. After adding BMI to the multivariate MR analysis, the gut microbial taxa and immune cells exposure-outcome effect were attenuated.

Conclusion

Our research confirm the potential link between gut microbiota and immune cells with MT, shedding light on the mechanism by which gut microbiota and immune cells may contribute to MT. These findings lay the groundwork for future investigations into targeted prevention strategies.
The blue light-dependent LOV-protein LdaP of Dinoroseobacter shibae acts as antirepressor of the PpsR repressor, regulating photosynthetic gene cluster expression
Authors: Pucelik Saskia , Becker Miriam , Heyber Steffi , Wöhlbrand Lars , Rabus Ralf , Jahn Dieter , Härtig Elisabeth
Published: February 2024

In the marine α-proteobacterium Dinoroseobacter shibae more than 40 genes of the aerobic anoxygenic photosynthesis are regulated in a light-dependent manner. A genome-wide screen of 5,605 clones from a D. shibae transposon library for loss of pigmentation and changes in bacteriochlorophyll absorbance identified 179 mutant clones. The gene encoding the LOV-domain containing protein Dshi_1135 was identified by its colorless phenotype. The mutant phenotype was complemented by the expression of a Dshi_1135-strep fusion protein in trans. The recombinantly produced and chromatographically purified Dshi_1135 protein was able to undergo a blue light-induced photocycle mediated by bound FMN. Transcriptome analyses revealed an essential role for Dshi_1135 in the light-dependent expression of the photosynthetic gene cluster. Interactomic studies identified the repressor protein PpsR as an interaction partner of Dshi_1135. The physical contact between PpsR and the Dshi_1135 protein was verified in vivo using the bacterial adenylate cyclase-based two-hybrid system. In addition, the antirepressor function of the Dshi_1135 protein was demonstrated in vivo testing of a bchF-lacZ reporter gene fusion in a heterologous Escherichia coli-based host system. We therefore propose to rename the Dshi_1135 protein to LdaP (light-dependent antirepressor of PpsR). Using the bacterial two-hybrid system, it was also shown that cobalamin (B12) is essential for the interaction of the antirepressor PpaA with PpsR. A regulatory model for the photosynthetic gene cluster in D. shibae was derived, including the repressor PpsR, the light-dependent antirepressor LdaP and the B12-dependent antirepressor PpaA.
Identification of important modules and biomarkers in tuberculosis based on WGCNA
Authors: Dong Jing , Song Ruixue , Shang Xuetian , Wang Yingchao , Liu Qiuyue , Zhang Zhiguo , Jia Hongyan , Huang Mailing , Zhu Chuanzhi , Sun Qi , Du Boping , Xing Aiying , Li Zihui , Zhang Lanyue , Pan Liping , Zhang Zongde
Published: February 2024

Background

Tuberculosis (TB) is a significant public health concern, particularly in China. Long noncoding RNAs (lncRNAs) can provide abundant pathological information regarding etiology and could include candidate biomarkers for diagnosis of TB. However, data regarding lncRNA expression profiles and specific lncRNAs associated with TB are limited.

Methods

We performed ceRNA-microarray analysis to determine the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs). Weighted gene co-expression network analysis (WGCNA) was then conducted to identify the critical module and genes associated with TB. Other bioinformatics analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and co-expression networks, were conducted to explore the function of the critical module. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to validate the candidate biomarkers, and receiver operating characteristic analysis was used to assess the diagnostic performance of the candidate biomarkers.

Results

Based on 8 TB patients and 9 healthy controls (HCs), a total of 1,372 differentially expressed lncRNAs were identified, including 738 upregulated lncRNAs and 634 downregulated lncRNAs. Among all lncRNAs and mRNAs in the microarray, the top 25% lncRNAs (3729) and top 25% mRNAs (2824), which exhibited higher median expression values, were incorporated into the WGCNA. The analysis generated 16 co-expression modules, among which the blue module was highly correlated with TB. GO and KEGG analyses showed that the blue module was significantly enriched in infection and immunity. Subsequently, considering module membership values (>0.85), gene significance values (>0.90) and fold-change value (>2 or < 0.5) as selection criteria, the top 10 upregulated lncRNAs and top 10 downregulated lncRNAs in the blue module were considered as potential biomarkers. The candidates were then validated in an independent validation sample set (31 TB patients and 32 HCs). The expression levels of 8 candidates differed significantly between TB patients and HCs. The lncRNAs ABHD17B (area under the curve [AUC] = 1.000) and ENST00000607464.1 (AUC = 1.000) were the best lncRNAs in distinguishing TB patients from HCs.

Conclusion

This study characterized the lncRNA profiles of TB patients and identified a significant module associated with TB as well as novel potential biomarkers for TB diagnosis.
Potential mechanisms of exercise for relieving inflammatory pain: a literature review of animal studies
Authors: Wu Minmin , Song Wenjing , Zhang Mei , Teng Lili , Tang Qiang , Zhu Luwen
Published: February 2024

Inflammatory pain (IP) is one of the most prevalent and intractable human conditions, and it leads to progressive dysfunction and reduced quality of life. Additionally, IP is incredibly challenging to treat successfully with drugs or surgery. The development of IP is complex and multifactorial, and peripheral and central sensitization may influence chronicity and treatment resistance in IP. Understanding the mechanisms underlying IP is vital for developing novel therapies. Strong evidence suggests that exercise can be a first-line relief for patients with IP during rehabilitation. However, the mechanisms through which exercise improves IP remain unclear. Here, we reviewed the current animal experimental evidence for an exercise intervention in IP and proposed biological mechanisms for the effects of synaptic plasticity in the anterior cingulate cortex, endocannabinoids, spinal dorsal horn excitability balance, immune cell polarization balance, cytokines, and glial cells. This information will contribute to basic science and strengthen the scientific basis for exercise therapy prescriptions for IP in clinical practice.
Exergames as a rehabilitation tool to enhance the upper limbs functionality and performance in chronic stroke survivors: a preliminary study
Authors: Vismara Luca , Ferraris Claudia , Amprimo Gianluca , Pettiti Giuseppe , Buffone Francesca , Tarantino Andrea Gianmaria , Mauro Alessandro , Priano Lorenzo
Published: February 2024

Introduction

Post-stroke hemiplegia commonly occurs in stroke survivors, negatively impacting the quality of life. Despite the benefits of initial specific post-acute treatments at the hospitals, motor functions, and physical mobility need to be constantly stimulated to avoid regression and subsequent hospitalizations for further rehabilitation treatments.

Method

This preliminary study proposes using gamified tasks in a virtual environment to stimulate and maintain upper limb mobility through a single RGB-D camera-based vision system (using Microsoft Azure Kinect DK). This solution is suitable for easy deployment and use in home environments. A cohort of 10 post-stroke subjects attended a 2-week gaming protocol consisting of Lateral Weightlifting (LWL) and Frontal Weightlifting (FWL) gamified tasks and gait as the instrumental evaluation task.

Results and discussion

Despite its short duration, there were statistically significant results (p < 0.05) between the baseline (T0) and the end of the protocol (TF) for Berg Balance Scale and Time Up-and-Go (9.8 and −12.3%, respectively). LWL and FWL showed significant results for unilateral executions: rate in FWL had an overall improvement of 38.5% (p < 0.001) and 34.9% (p < 0.01) for the paretic and non-paretic arm, respectively; similarly, rate in LWL improved by 19.9% (p < 0.05) for the paretic arm and 29.9% (p < 0.01) for non-paretic arm. Instead, bilateral executions had significant results for rate and speed: considering FWL, there was an improvement in rate with p < 0.01 (31.7% for paretic arm and 37.4% for non-paretic arm), whereas speed improved by 31.2% (p < 0.05) and 41.7% (p < 0.001) for the paretic and non-paretic arm, respectively; likewise, LWL showed improvement in rate with p < 0.001 (29.0% for paretic arm and 27.8% for non-paretic arm) and in speed with 23.6% (p < 0.05) and 23.5% (p < 0.01) for the paretic and non-paretic arms, respectively. No significant results were recorded for gait task, although an overall good improvement was detected for arm swing asymmetry (−22.6%). Hence, this study suggests the potential benefits of continuous stimulation of upper limb function through gamified exercises and performance monitoring over medium-long periods in the home environment, thus facilitating the patient's general mobility in daily activities.
Decreased quality of life in Duchenne muscular disease patients related to functional neurological and cardiac impairment
Authors: Juříková Lenka , Masárová Lucia , Panovský Roman , Pešl Martin , Revendová Kamila Žondra , Volný Ondřej , Feitová Věra , Holeček Tomaš , Kincl Vladimír , Danhofer Pavlína , Voháňka Stanislav , Haberlová Jana , Podolská Karolína
Published: February 2024

In this prospective study involving 37 Duchenne muscular dystrophy (DMD) patients aged 8–18 years and older, we examined the impact of neurological and cardiac factors on quality of life (QoL). Our findings revealed a negative correlation between upper limb movement and overall mobility, self-service, and usual activities. Ambulatory and non-ambulatory DMD patients showed significant differences in mobility-related parameters. Cardiac evaluations demonstrated associations between mitral annular plane systolic excursion (MAPSE) and mobility-related aspects. The PEDSQL 3.0 neuromuscular model questionnaire further highlighted age-related and movement-related correlations with QoL. The loss of ambulatory status and reduced upper limb movement were negatively associated with QoL, while upper limb movement positively correlated with septal MAPSE. However, no significant associations were found between MAPSE and anxiety/depression. These findings underscore the multifaceted impact of DMD on QoL and emphasize the importance of considering both neurological and cardiac factors in comprehensive patient care.
Assessment of blood one-carbon metabolism indexes during mid-to-late pregnancy in 397 Chinese pregnant women
Authors: Zhang Rong , Wu Xiangyi , Lu Lu , Hu Rui , Teng Yue , Pan Lina , Zeng Xiaoling , Jiang Wei , Li Wei , Dong Ling , Zhu Wenli
Published: February 2024

Objectives

One-carbon metabolism (OCM) significantly influences fetal growth and neurodevelopment through transferring methyl group to biomolecules, during which folate, methionine, choline and betaine function as methyl donor nutrients, while vitamin B2, B6, B12 function as enzyme cofactors, and homocysteine (Hcy) and S-adenosyl methionine (SAM) are functional metabolites. This study aimed to assess blood OCM index levels and explore their relationships among Chinese pregnant women.

Methods

Data were obtained from the baseline of the Mother–Child Nutrition and Health Cohort Study. Pregnant women, voluntarily recruited from September 2020 to June 2022 during antenatal examinations in five Chinese cities at 24–32 gestational weeks, provided fasting venous blood samples. Measurements included RBC and serum folate, serum vitamin B2, B6, B12, choline, betaine, methionine, total Hcy (tHcy), and plasma SAM. Sociodemographic characteristics and pregnancy-related conditions were collected via a self-designed questionnaire.

Results

Of 397 participants, 82.6% were in mid-pregnancy (24–27 gestational weeks) and 17.4% were in late-pregnancy (28–32 gestational weeks). Serum folate, vitamin B6, and B12 deficiencies were 2.5, 1.3, and 8.3%, respectively. Elevated tHcy (≥10 μmol/L) was observed in 1.8% of pregnant women. Elderly pregnant women (aged 35 and above) exhibited significantly lower serum methionine levels (p < 0.05), while multiparous women had lower RBC folate levels (p < 0.05), and lower serum methionine and vitamin B12 levels (p < 0.10, not statistically significant). Partial correlation analysis revealed positive associations between RBC folate and cofactor vitamin B12 (r = 0.244, p < 0.05) in the folate cycle, as well as significant correlations between two methyl donor paths [serum folate was significantly related to serum choline (r = 0.172) and betaine (r = 0.193)]. As functional biomarkers of OCM, serum tHcy exhibited negative associations with RBC folate (β = −0.330, p < 0.05) and vitamin B6 (β = −0.317, p < 0.05), and plasma SAM displayed a positive association with serum betaine (β = 0.610, p < 0.05), while negatively associated with serum vitamin B6 (β = −0.181, p < 0.05).

Conclusion

The blood OCM exhibited imbalances during mid-to-late pregnancy, characterized by lower levels of folate, vitamin B6, and B12, alongside elevated tHcy levels. Adequate folate and vitamin B6 emerged as significant predictors of lower tHcy levels. Additionally, serum betaine showed a positive correlation with plasma SAM. This suggests the importance of not only ensuring sufficient folate but also optimizing other OCM-related nutrients throughout pregnancy.
Unveiling the therapeutic symphony of probiotics, prebiotics, and postbiotics in gut-immune harmony
Authors: Zhou Pengjun , Chen Chunlan , Patil Sandip , Dong Shaowei
Published: February 2024

The gut microbiota and immune system interaction play a crucial role in maintaining overall health. Probiotics, prebiotics, and postbiotics have emerged as promising therapeutic approaches to positively influence this complex axis and enhance health outcomes. Probiotics, as live bacteria, promote the growth of immune cells, shape immune responses, and maintain gut barrier integrity. They modify the gut microbiota by fostering beneficial bacteria while suppressing harmful ones. Additionally, probiotics interact with the immune system, increasing immune cell activity and anti-inflammatory cytokine production. Prebiotics, as indigestible fibers, selectively nourish beneficial microorganisms in the gut, enhancing gut microbial diversity and activity. This, in turn, improves gut health and boosts immune responses while controlling inflammation through its immunomodulatory properties. Postbiotics, produced during probiotic fermentation, such as short-chain fatty acids and antimicrobial peptides, positively impact gut health and modulate immune responses. Ensuring quality control and standardization will be essential for successful clinical implementation of these interventions. Overall, understanding and harnessing the gut microbiota-immune system interplay offer promising avenues for improving digestive and immunological health.
Vitamin B12 analogues from gut microbes and diet differentially impact commensal propionate producers of the human gut
Authors: Kundra Palni , Greppi Anna , Duppenthaler Monica , Plüss Serafina , Pugin Benoit , Lacroix Christophe , Geirnaert Annelies
Published: February 2024

To produce the health-associated metabolite propionate, gut microbes require vitamin B12 as a cofactor to convert succinate to propionate. B12 is sourced in the human gut from the unabsorbed dietary fraction and in situ microbial production. However, experimental data for B12 production by gut microbes is scarce, especially on their produced B12-analogues. Further, the promotion of propionate production by microbially-produced and dietary B12 is not yet fully understood. Here, we demonstrated B12 production in 6 out of 8 in silico predicted B12-producing bacteria from the human gut. Next, we showed in vitro that B12 produced by Blautia hydrogenotrophica, Marvinbryantia formatexigens, and Blautia producta promoted succinate to propionate conversion of two prevalent B12-auxotrophic gut bacteria, Akkermansia muciniphila and Bacteroides thetaiotaomicron. Finally, we examined the propiogenic effect of commercially available B12-analogues present in the human diet (cyano-B12, adenosyl-B12 and hydroxy-B12) at two doses. The low dose resulted in partial conversion of succinate to propionate for A. muciniphila when grown with adenosyl-B12 (14.6 ± 2.4 mM succinate and 18.7 ± 0.6 mM propionate) and hydroxy-B12 (13.0 ± 1.1 mM and 21.9 ± 1.2 mM), in comparison to cyano-B12 (0.7 ± 0.1 mM and 34.1 ± 0.1 mM). Higher doses of adenosyl-B12 and hydroxy-B12 resulted in significantly more conversion of succinate to propionate in both propionate-producing species, compared to the low dose. B12 analogues have different potential to impact the propionate metabolism of prevalent propionate producers in the gut. These results could contribute to strategies for managing gut disorders associated with decreased propionate production.
Deep learning-assisted ultrasonic diagnosis of cervical lymph node metastasis of thyroid cancer: a retrospective study of 3059 patients
Authors: Zhao Hai Na , Yin Hao , Liu Jing Yan , Song Lin Lin , Peng Yu Lan , Ma Bu Yun
Published: February 2024

Objective

This study aimed to develop a deep learning system to identify and differentiate the metastatic cervical lymph nodes (CLNs) of thyroid cancer.

Methods

From January 2014 to December 2020, 3059 consecutive patients with suspected with metastatic CLNs of thyroid cancer were retrospectively enrolled in this study. All CLNs were confirmed by fine needle aspiration. The patients were randomly divided into the training (1228 benign and 1284 metastatic CLNs) and test (307 benign and 240 metastatic CLNs) groups. Grayscale ultrasonic images were used to develop and test the performance of the Y-Net deep learning model. We used the Y-Net network model to segment and differentiate the lymph nodes. The Dice coefficient was used to evaluate the segmentation efficiency. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the classification efficiency.

Results

In the test set, the median Dice coefficient was 0.832. The sensitivity, specificity, accuracy, PPV, and NPV were 57.25%, 87.08%, 72.03%, 81.87%, and 66.67%, respectively. We also used the Y-Net classified branch to evaluate the classification efficiency of the LNs ultrasonic images. The classification branch model had sensitivity, specificity, accuracy, PPV, and NPV of 84.78%, 80.23%, 82.45%, 79.35%, and 85.61%, respectively. For the original ultrasonic reports, the sensitivity, specificity, accuracy, PPV, and NPV were 95.14%, 34.3%, 64.66%, 59.02%, 87.71%, respectively. The Y-Net model yielded better accuracy than the original ultrasonic reports.

Conclusion

The Y-Net model can be useful in assisting sonographers to improve the accuracy of the classification of ultrasound images of metastatic CLNs.
Malignant mixed mullerian tumors: a SEER database review of rurality and treatment modalities on disease outcome
Authors: Zadeh Neusha , Bhatt Arjun , Sripiparu Vaishnavi , Pasli Melisa , Edwards George , Larkins Michael C. , Peach M. Sean
Published: February 2024

Introduction

Malignant Mixed Mullerian Tumors (MMMT) are rare and poorly understood sarcomas with limited research on risk factors, pathogenesis, and optimal treatments. This study aimed to address this knowledge gap and explore the impact of community size, patient characteristics, disease characteristics, and treatment modalities on MMMT outcomes.

Methods

Using the Surveillance, Epidemiology, and End Results database (SEER), the largest SEER cohort to date of 3,352 MMMT patients was analyzed for demographic factors, treatment modalities, and histologic characteristics. Data was processed, including the removal of incomplete entries, and analyzed in Python 3.1 using packages scikit-learn, lifelines, and torch; log-rank analysis and Cox proportional hazards models were used to evaluate a number of demographic characteristics and disease characteristics for significance in regard to survival.

Results

Our study found adjuvant radiotherapy and chemotherapy significantly improved survival, with modest benefits from neoadjuvant chemotherapy. Our findings also suggest age at diagnosis, disease grade, and suburban versus rural geographic locations may play key roles in patient prognosis. On multivariable analysis both disease Grade and surgical treatment were significant factors.

Discussion

MMMTs remain challenging, but appropriate treatment appears to enhance survival. The present findings suggest opportunities for improved outcomes and treatment strategies for patients with MMMTs.
Multimodal machine learning models identify chemotherapy drugs with prospective clinical efficacy in dogs with relapsed B-cell lymphoma
Authors: Callegari A. John , Tsang Josephine , Park Stanley , Swartzfager Deanna , Kapoor Sheena , Choy Kevin , Lim Sungwon
Published: February 2024

Dogs with B-cell lymphoma typically respond well to first-line CHOP-based chemotherapy, but there is no standard of care for relapsed patients. To help veterinary oncologists select effective drugs for dogs with lymphoid malignancies such as B-cell lymphoma, we have developed multimodal machine learning models that integrate data from multiple tumor profiling modalities and predict the likelihood of a positive clinical response for 10 commonly used chemotherapy drugs. Here we report on clinical outcomes that occurred after oncologists received a prediction report generated by our models. Remarkably, we found that dogs that received drugs predicted to be effective by the models experienced better clinical outcomes by every metric we analyzed (overall response rate, complete response rate, duration of complete response, patient survival times) relative to other dogs in the study and relative to historical controls.
Tumor alkalization therapy: misconception or good therapeutics perspective? – the case of malignant ascites
Authors: Bogdanov Alexey , Verlov Nikolay , Bogdanov Andrey , Burdakov Vladimir , Semiletov Valeriy , Egorenkov Vitaliy , Volkov Nikita , Moiseyenko Vladimir
Published: February 2024

Tumor acidity has been identified as a key factor in promoting cancer progression, metastasis, and resistance. Tumor alkalization therapy has emerged as a potential strategy for cancer treatment. This article provides preclinical and clinical evidence for tumor alkalization therapy as a promising cancer treatment strategy. The potential of tumor alkalization therapy using sodium bicarbonate in the treatment of malignant ascites was studied. The concept of intraperitoneal perfusion with an alkalizing solution to increase the extracellular pH and its antitumor effect were explored. The significant extension in the overall survival of the Ehrlich ascites carcinoma mice treated with sodium bicarbonate solution compared to those treated with a sodium chloride solution was observed. In the sodium bicarbonate group, mice had a median survival of 30 days after tumor cell injection, which was significantly (p<0.05) different from the median survival of 18 days in the sodium chloride group and 14 days in the intact group. We also performed a case study of a patient with ovarian cancer malignant ascites resistant to previous lines of chemotherapy who underwent intraperitoneal perfusions with a sodium bicarbonate solution, resulting in a significant drop of CA-125 levels from 5600 U/mL to 2200 U/mL in and disappearance of ascites, indicating the potential effectiveness of the treatment. The preclinical and clinical results obtained using sodium bicarbonate perfusion in the treatment of malignant ascites represent a small yet significant contribution to the evolving field of tumor alkalization as a cancer therapy. They unequivocally affirm the good prospects of this concept.
Summary of biological research on hepatoblastoma: a scoping review
Authors: Wang Huan-sheng , Lao Jing , Jiang Ren-sen , Wang Bin , Ma Xiao-peng , Wang Jian-yao
Published: February 2024

Background

Hepatoblastoma is the most prevalent primary hepatic malignancy in children, comprising 80% of pediatric hepatic malignancies and 1% of all pediatric malignancies. However, traditional treatments have proven inadequate in effectively curing hepatoblastoma, leading to a poor prognosis.

Methods

A literature search was conducted on multiple electronic databases (PubMed and Google Scholar). A total of 86 articles were eligible for inclusion in this review.

Result

This review aims to consolidate recent developments in hepatoblastoma research, focusing on the latest advances in cancer-associated genomics, epigenetic studies, transcriptional programs and molecular subtypes. We also discuss the current treatment approaches and forthcoming strategies to address cancer-associated biological challenges.

Conclusion

To provide a comprehensive summary of the molecular mechanisms associated with hepatoblastoma occurrence, this review highlights three key aspects: genomics, epigenetics, and transcriptomics. Our review aims to facilitate the exploration of novel molecular mechanisms and the development of innovative clinical treatment strategies for hepatoblastoma.