bluuebunny/crossref_metadata_2025 huggingface dataset:
The IVIG treatment response in autoimmune polyendocrine syndromes type 2 with anti-GAD65 antibody-associated stiff person syndrome: a case report and literature review
Authors: Yang Yulong , Jiang Hailin , Yang Wenming , Wang Han , Wang Meixia , Li Xiang , Huang Peng , Fang Shuzhen , Hao Wenjie , Yang Yue , Zhao Furong , He Wei
Published: January 2025

Autoimmune polyendocrine syndromes (APS) is a rare group of disorders caused by impaired function of multiple endocrine glands due to disruption of immune tolerance. Of which, type 2 (APS-2) is the most common. Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA). Anti-GAD antibodies are associated with various neurological disorders, including stiff person syndrome (SPS). SPS is characterized by axial muscle stiffness, rigidity, and intermittent painful muscle spasms, with a prevalence of one to two in a million, making it an extremely rare neurological disorder. The comorbidity of APS-2 with SPS is even rarer. Most practicing neurologists encounter only one or two cases of APS-2 combined with anti-GAD65 antibody-associated SPS in their careers, resulting in underdiagnosis and undertreatment, leading to severe disability and suffering. This case report describes a young male who initially exhibited hair loss, vitiligo, and previously unreported eosinophilia. Before his diagnosis, he was admitted multiple times, with symptoms improving following the addition of intravenous immunoglobulin (IVIG) therapy to a poor treatment regimen. This paper aims to increase physicians’ awareness of this condition, enhancing the likelihood of early diagnosis and treatment.
Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy
Authors: Tzaban Shay , Stern Ori , Zisman Elad , Eisenberg Galit , Klein Shiri , Frankenburg Shoshana , Lotem Michal
Published: January 2025

Alternative splicing (AS) is a mechanism that generates translational diversity within a genome. Equally important is the dynamic adaptability of the splicing machinery, which can give preference to one isoform over others encoded by a single gene. These isoform preferences change in response to the cell’s state and function. Particularly significant is the impact of physiological alternative splicing in T lymphocytes, where specific isoforms can enhance or reduce the cells’ reactivity to stimuli. This process makes splicing isoforms defining features of cell states, exemplified by CD45 splice isoforms, which characterize the transition from naïve to memory states. Two developments have accelerated the use of AS dynamics for therapeutic interventions: advancements in long-read RNA sequencing and progress in nucleic acid chemical modifications. Improved oligonucleotide stability has enabled their use in directing splicing to specific sites or modifying sequences to enhance or silence particular splicing events. This review highlights immune regulatory splicing patterns with potential significance for enhancing anticancer immunotherapy.
VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens
Authors: Carri Ibel , Schwab Erika , Trivino Juan Carlos , von Euw Erika M. , Nielsen Morten , Mordoh José , Barrio María Marcela
Published: January 2025

VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient’s private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL’s somatic mutations and human polymorphisms remain unexplored. To study these immunogens, we performed whole-exome sequencing of paired tumor and germinal samples from four vaccinated patients and the vaccine cells. VACCIMEL variants were called by comparing the vaccine and the patient’s exomes, and non-synonymous coding variants were used to predict T cell epitopes. Candidates were ranked based on their mRNA expression in VACCIMEL, predicted peptide-HLA (pHLA) presentation, and pHLA stability. Then, the immune responses to prioritized epitope candidates were tested using IFNγ ELISpot assays on vaccinated patients’ PBMC samples. The comparison of the vaccine with the patients’ germinal exomes revealed on average 9481 coding non-synonymous variants, suggesting that VACCIMEL offers a high number of potential antigens. Between 0,05 and 0,2% of these variants were also found in the tumors of three vaccinated patients; however, one patient with a high tumor mutational burden (TMB) shared 19,5% somatic variants. The assessment of T cell responses showed that vaccinated patients mounted highly diverse responses against VACCIMEL peptides. Notably, effector T cells targeting the patient’s tumor antigens, comprising neoantigens and TAA, were found in higher frequencies than T cells targeting VACCIMEL-exclusive antigens. On the other hand, we observed that the immunogenic epitopes are not conserved across patients, despite sharing HLA and that immune responses fluctuate over time. Finally, a positive correlation between VACCIMEL antigen expression and the intensity of the T cell responses was found. Our results demonstrate that the immune system simultaneously responds to a high number of antigens, either vaccinal or private, proving that immune responses against epitopes not expressed in the patient’s tumors were not detrimental to the immune recognition of neoantigens and TAA.
Tumor-associated lymphatic vessel density is a postoperative prognostic biomarker of hepatobiliary cancers: a systematic review and meta-analysis
Authors: Li Jin , Liang Yu-Bo , Wang Qing-Bo , Li Yu-Kai , Chen Xing-Ming , Luo Wan-Ling , Lakang Yawhan , Yang Zi-Sheng , Wang Yan , Li Zhi-Wei , Ke Yang
Published: January 2025

Purpose

This study aimed to investigate whether tumor-associated lymphatic vessel density (LVD) could predict the survival of patients with hepato-biliary-pancreatic (HBP) cancers after radical resection.

Methods

A systematic search was conducted using PubMed, Embase, and Cochrane Library from the inception to July 31, 2024 for literature that reported the role of LVD in overall survival (OS) and recurrence-free survival (RFS) of patients with HBP cancers after radical resection.

Results

Ten studies with 761 patients were included for the meta-analysis. The results indicated that a higher level of LVD was associated with worse OS (hazard ratio, HR = 2.87, 95% CI 1.63 to 5.04) and worse RFS (HR = 3.18, 95% CI 1.41 to 7.17) in HBP cancers. Subgroup analysis based on pathological types revealed that a higher level of LVD was significantly related to worse OS in hepatocellular carcinoma (HCC) (HR = 2.35, 95% CI 1.16 to 4.78), cholangiocarcinoma (HR = 4.65, 95% CI 1.70 to 12.70), and gallbladder cancer patients (HR = 4.64, 95% CI 1.37 to 15.71). The levels of LVD were not significantly associated with OS in pancreatic adenocarcinoma patients after radical resection (HR = 1.08, 95% CI 0.61 to 1.89). Similarly, a higher level of LVD was significantly associated with worse RFS in HCC (HR = 1.92, 95% CI 1.01 to 3.65) and cholangiocarcinoma patients (HR = 4.54, 95% CI 2.10 to 9.83).

Conclusions

A higher level of LVD was a biomarker for the prediction of worse OS and RFS in patients with hepatobiliary cancers after radical resection.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024571167.
Integrating single cell analysis and machine learning methods reveals stem cell-related gene S100A10 as an important target for prediction of liver cancer diagnosis and immunotherapy
Authors: Huang Shenjun , Tu Tingting
Published: January 2025

Background

Hepatocellular carcinoma (LIHC) poses a significant health challenge worldwide, primarily due to late-stage diagnosis and the limited effectiveness of current therapies. Cancer stem cells are known to play a role in tumor development, metastasis, and resistance to treatment. A thorough understanding of genes associated with stem cells is crucial for improving the diagnostic precision of LIHC and for the advancement of effective immunotherapy approaches.

Method

This research combines single-cell RNA sequencing with machine learning techniques to identify vital stem cell-associated genes that could act as prognostic biomarkers and therapeutic targets for LIHC. We analyzed various datasets, applying negative matrix factorization alongside machine learning algorithms to reveal gene expression patterns and construct diagnostic models. The XGBoost algorithm was specifically utilized to identify key regulatory genes related to stem cells in LIHC, and the expression levels and prognostic significance of these genes were validated experimentally.

Results

Our single-cell analysis identified 16 differential prognostic genes associated with liver cancer stem cells. Cluster analysis and diagnostic models constructed using various machine learning techniques confirmed the significance of these 16 genes in the diagnosis and immunotherapy of LIHC. Notably, the XGBoost algorithm identified S100A10 as the stem cell-related gene most relevant to the prognosis of LIHC patients. Experimental validation further supports S100A10 as a potential prognostic marker for this cancer type. Additionally, S100A10 shows a positive correlation with the stem cell marker POU5F1.

Conclusion

The results of this study highlight S100A10 as an essential predictor for liver cancer diagnosis and treatment response, particularly regarding immunotherapy. This research offers valuable insights into the molecular mechanisms underlying LIHC and suggests S100A10 as a promising target for enhancing treatment outcomes in liver cancer patients.
Targeting autophagy to enhance chemotherapy and immunotherapy in oral cancer
Authors: Zeng Xiaoli , Chen Yue , Wang Jing , He Miao , Qiu Junyao , Huang Yun
Published: January 2025

Oral cancer is a highly malignant disease characterized by recurrence, metastasis, and poor prognosis. Autophagy, a catabolic process induced under stress conditions, has been shown to play a dual role in oral cancer development and therapy. Recent studies have identified that autophagy activation in oral epithelial cells suppresses cancer cell survival by inhibiting key pathways such as the mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK), while activating the adenosine monophosphate-activated protein kinase (AMPK) pathway. Inducing autophagy promotes degradation of eukaryotic initiation factor 4E, thus reducing metastasis and enhancing the efficacy of chemotherapy, radiotherapy, and immunotherapy. Furthermore, autophagy induction can modulate the tumor immune microenvironment and enhance antitumor immunity. This review comprehensively summarizes the relationship between autophagy and oral cancer, focusing on its mechanisms and therapeutic potential when combined with conventional treatments. While promising, the precise mechanisms and clinical applications of autophagy inducers in oral cancer therapy remain to be elucidated, offering new directions for future research to improve treatment outcomes and reduce recurrence.
Bilingual acquisition during school years: predictors of achievement in the societal and heritage language
Authors: Grose-Hodge Magdalena , Dabrowska Ewa , Divjak Dagmar
Published: January 2025

There are vast individual differences in heritage bilinguals' linguistic skills. It is not clear, however, to what extent this variation can be attributed to experience, cognitive ability or motivation. This study investigates factors influencing the acquisition of both Polish (HL = Heritage Language) and English (SocL = Societal Language) of school-age children, examining the role of motivation, linguistic experience, and language aptitude. We collected and analyzed speech samples from 7- to 12-year-old participants (n = 78) residing in the UK to derive linguistic measures of fluency, syntactic complexity and lexical diversity in both languages. Additionally, a receptive grammar test was administered. Independent variables were obtained via parental questionnaires, a motivation survey and a language aptitude test. To identify predictors of heritage bilingual acquisition, we conducted least squares linear regression analyses for each language area and applied backward stepwise selection to reduce the models. Results show that predictors differ between languages and linguistic areas. Our findings highlight the role of language aptitude in bilingual development, challenge assumptions that motivation to use HL might detract from SocL development, and suggest that HL acquisition can support, rather than hinder, societal language development, as bilingual children draw on their metalinguistic awareness and cognitive skills across both languages.
Study on dynamic mechanical properties of frozen weakly cemented rock under lateral constraint
Authors: Li Weiyu , Fang Shizheng , Zhu Ye , Li Guangming
Published: January 2025

Weakly cemented red sandstone is common in the construction of shaft engineering in western China. Based on the actual working conditions, the dynamic mechanical behavior of this kind of rock under the combined action of multiple variables was studied. Based on the freezing temperature of the freezing method for shaft construction, the experimental temperature gradient was set at 25°C to −25°C. Using an modified split Hopkinson pressure bar (SHPB) experimental system, the dynamic mechanical response of frozen weak-cemented red sandstone under lateral constraints was studied. Taking dynamic and static stress fields and temperature fields as the entry point, the relationship between dynamic load, confining pressure, temperature, and dynamic mechanical characteristics parameters of weakly cemented rock is established, and the strain rate effect, lateral constraint effect, and negative temperature effect of dynamic compressive strength are analyzed. The research results show that: 1) The confining pressure changes synchronously with the axial dynamic load, and undergoes three stages: rapid increase, slow increase, and unloading rebound. 2) Under the combined effects of multiple variables, the dynamic mechanical behavior of the rock shows obvious compaction and rebound characteristics. 3) The dynamic compressive strength of the rock is jointly affected by strain rate, confining pressure, and temperature. Among them, lateral constraints have a strengthening effect. The dynamic compressive strength increases exponentially with increasing strain rate, and increases first and then decreases with decreasing temperature. At the same time, the degree of rock fragmentation is consistent with its strength characteristics. The research results have certain reference significance for the engineering design and safe operation and maintenance of frozen rock structures under dynamic loading.
Correlation between hepatic steatosis severity diagnosed by ultrasound and metabolic indexes in elderly patients with MAFLD
Authors: Liang Zhitang , Huang Renhao , Zhang Lingyun
Published: January 2025

Objective

To explore the connection between metabolic parameters and the severity of hepatic steatosis determined through ultrasound in elderly individuals with metabolic dysfunction-associated fatty liver disease (MAFLD).

Methods

4,663 senior individuals who were 65 years of age or older were included in this research. They were examined physically at the Ninghai Street Community Health Service Center in Yantai City between June 7, 2021, and October 15, 2021. There were two categories of individuals identified: the MAFLD group (n = 2,985) and the non-MAFLD group (n = 1,678). Based on liver ultrasonography results, individuals in the MAFLD group were further separated into three groups: mild (n = 2,104), moderate (n = 766), and severe (n = 115). To identify indicators of risk for the severity of hepatic steatosis, metabolic data was contrasted between the groups employing logistic regression.

Results

In comparison to the non-MAFLD group, the MAFLD group showed significantly elevated levels of body mass index (BMI), blood pressure, gender, age, lipid profile, alanine transaminase (ALT), and fasting blood glucose (FBG; p < 0.05). Among individuals with MAFLD, there was a positive correlation between BMI, FBG, ALT, and aspartate transaminase (AST) levels and the severity of hepatic steatosis (p < 0.05). Logistic regression analysis indicated that BMI, female gender, FBG, ALT, triglycerides (TG), and serum uric acid (SUA) constituted risk factors for increased severity of hepatic steatosis in MAFLD.

Conclusion

The severity of hepatic steatosis in elderly MAFLD patients is significantly correlated with female gender, BMI, ALT, FBG, TG, and SUA.
Ligating the varicose vein trunk for bleeding stomal varices in portal hypertension: a case report
Authors: Sun Jialiang , Tan Zhanhai , Zhang Jifa
Published: January 2025

Introduction

In colostomy-related complications, variceal hemorrhage particularly induced by cirrhosis and portal hypertension is seldom encountered. The onset of peristome variceal hemorrhage necessitates swift and effective intervention to prevent potentially life-threatening outcomes such as hemorrhagic shock and recurrent stoma bleeding.

Case presentation

This report details a case of repeated varicose vein hemorrhage around the stoma in a patient with liver cirrhosis. Abdominal enhanced CT images revealed that the stomal varices originated from a branch of the inferior mesenteric vein, with vein balls encompassing the stoma. The patient was acquired with successful hemostasis through high ligation of the various vein primary trunk, and stripping of the vein balls around stoma, along with intracutaneously suturing of the sub-abdominal wall varicose veins. When the stoma bag was changed it was observed that the skin surrounding the stoma was flat, the mucosa was red, and the varicose venous mass had vanished. After 2 months of follow-up, the stomal function was doing well without any rebleeding episodes.

Conclusion

In this instance, decompensated cirrhosis led to stomal varices and recurrent bleeding, which was initially managed with local compression and suture therapy but resulted in rebleeding. Our team’s approach through blocking the primary trunk of variceal vein via a minimal incision under local anesthesia may offer a new treatment strategy for patients with poor liver function who cannot withstand the trauma associated with general anesthesia and major surgery.
Prospects for the diagnosis and treatment of sarcopenia in the Philippines
Authors: Sun Ji , Zhang Weixin , Han Peipei
Published: January 2025

Over the past decade, the elderly Filipino population has significantly increased, rising from 4.6 million seniors, which was approximately 6% of the total population in 2000, to 6.5 million, or around 6.9% of the population in 2010. Projections suggest that by 2030, the percentage of the population aged 60 and above will increase to between 10 and 19%, indicating a significant demographic shift toward an aging population. This shift from a predominantly young population to a rapidly growing elderly demographic underscores the urgent need for effective health promotion and management programs targeting older adults. Sarcopenia, a muscle-wasting disorder, represents a significant global health challenge, particularly affecting the elderly. In the Philippines, the impact of sarcopenia is expected to become more pronounced, potentially straining both individuals and the national healthcare system over the next 15 years, despite the country’s relatively younger overall population. Despite the expanding research on sarcopenia in the Philippines, there remains an urgent need to raise awareness and implement proactive measures to address this escalating health issue.
Long-term trends in the burden of pulmonary arterial hypertension in China and worldwide: new insights based on GBD 2021
Authors: Xu Zhehao , Ding Jia , Liang Ruiyun , Xie Shuangfeng
Published: January 2025

Background

Pulmonary arterial hypertension (PAH) poses a significant health challenge globally, with China experiencing a notable increase in its burden. Understanding the trends and factors contributing to PAH is crucial for developing effective public health strategies.

Methods

This study utilized data from the Global Burden of Disease (GBD) 2021 database to estimate the burden of PAH in China and worldwide from 1990 to 2021. A Bayesian age-period-cohort (BAPC) model was employed to analyze differences in PAH burden across age, gender, and time periods, and to project global epidemiological trends until 2036.

Results

From 1990 to 2021, the incidence and prevalence of PAH in China increased by 80.59% and 86.74%, respectively. The age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) showed an annual percentage change (AAPC) of -0.07% and 0.25%, respectively. Conversely, the age-standardized disability-adjusted life year (DALY) rate and age-standardized mortality rate (ASMR) have been declining since 1990, with AAPC of -1.90% and -1.26%, respectively. Females and the 50–70 years age group experienced a higher PAH burden compared to males. Projections indicate that ASPR, ASMR, and age-standardized death rate (ASDR) will stabilize with minimal variation over the next decade.

Discussion

The findings highlight the age-related burden of PAH in China, particularly affecting older populations and women. The projected stabilization of PAH metrics over the next decade underscores the need for continued monitoring and targeted interventions. This study’s comprehensive analysis of PAH burden over three decades provides valuable insights for policymakers and healthcare providers, necessitating concerted efforts to address this critical health issue.
Neurological impact of HIV/AIDS and substance use alters brain function and structure
Authors: Haorah James , Malaroviyam Samikkannu , Iyappan Hemavathi , Samikkannu Thangavel
Published: January 2025

Human immunodeficiency virus (HIV) infection is the cause of acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy (cART) has successfully controlled AIDS, but HIV-associated neurocognitive disorders (HANDs) remain prevalent among people with HIV. HIV infection is often associated with substance use, which promotes HIV transmission and viral replication and exacerbates HANDs even in the era of cART. Thus, the comorbid effects of substance use exacerbate the neuropathogenesis of HANDs. Unraveling the mechanism(s) of this comorbid exacerbation at the molecular, cell-type, and brain region levels may provide a better understanding of HAND persistence. This review aims to highlight the comorbid effects of HIV and substance use in specific brain regions and cell types involved in the persistence of HANDs. This review includes an overview of post-translational modifications, alterations in microglia-specific biomarkers, and possible mechanistic pathways that may link epigenomic modifications to functional protein alterations in microglia. The impairment of the microglial proteins that are involved in neural circuit function appears to contribute to the breakdown of cellular communication and neurodegeneration in HANDs. The epigenetic modification of N-terminal acetylation is currently understudied, which is discussed in brief to demonstrate the important role of this epigenetic modification in infected microglia within specific brain regions. The discussion also explores whether combined antiretroviral therapy is effective in preventing HIV infection or substance-use-mediated post-translational modifications and protein alterations in the persistence of neuropathogenesis in HANDs.
High-flow nasal cannula oxygen therapy versus non-invasive ventilation in healthy respiratory physicians: a non-randomized study
Authors: Ye Hong , Xiang Dandan , Zhu Xiangyu , Du Xiuwei , Shang Shengyun , Xu Jing , Li Yu , Cheng Yunyun , Yang Zhongfei
Published: January 2025

Background

High-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) are commonly used for respiratory support. This study aims to first establish whether to use HFNC or NIV based on comfort levels, and subsequently evaluate diaphragmatic function under equivalent comfort levels to determine the optimal modality for clinical application.

Methods

A self-controlled, non-randomized study was conducted with 10 healthy respiratory physicians as participants. Each subject was exposed to different HFNC settings, including flow rates of 20, 40, and 60 L/min at both 33 and 37°C. Additionally, participants were assessed under NIV mode. Comfort levels as the primary outcome were evaluated using the Visual Numerical Scale (VNS). Meanwhile, vital signs and diaphragmatic mobility were monitored through an electrocardiograph and ultrasound.

Results

HFNC at a flow rate of 20 L/min provided greater comfort than NIV. However, as the flow rate increased, this comfort benefit decreased. At 40 L/min, comfort levels were similar between HFNC and NIV, while at 60 L/min, HFNC was less comfortable than NIV. Notably, temperature variations between 33 and 37°C had no significant effect on comfort. In addition, under conditions of similar comfort, HFNC demonstrated slightly greater diaphragmatic mobility compared to NIV.

Conclusion

Our study indicated HFNC was the preferred choice for providing respiratory support at low to moderate flow rates in healthy volunteers not requiring respiratory support. By contrast, at higher flow rates, NIV discomfort was lower than HFNC discomfort.
Case report: Trauma-induced Klebsiella pneumoniae invasive syndrome presenting with liver abscess, lung abscess, endophthalmitis, and purulent meningitis
Authors: Chen Hong-qiao , Mo Zhen-hua , Wei Wu-xiao
Published: January 2025

Purpose

This study aims to explore the underlying causes, diagnostic strategies, and treatment approaches of trauma-induced Klebsiella pneumoniae invasive syndrome (KPIS) through a rare case report. By highlighting the role of trauma as a potential trigger for KPIS, particularly in high-risk populations such as individuals with diabetes, this study seeks to provide valuable insights for improving clinical outcomes and promoting public health awareness.

Background

Klebsiella pneumoniae invasive syndrome is a multi-organ infectious disease commonly associated with complications such as liver abscess, lung abscess, endophthalmitis, and purulent meningitis, with high mortality and disability rates. In recent years, the incidence of KPIS has been increasing, particularly in the Asia-Pacific region, and is closely linked to hypervirulent Klebsiella pneumoniae (hvKp) infections. While extensive research has focused on the risk of KPIS in patients with underlying conditions such as diabetes, trauma-induced KPIS remains exceedingly rare, with limited understanding of its pathophysiology and clinical management. Trauma may facilitate invasive infections by disrupting immune barriers and compromising local tissue integrity, creating entry points for pathogens.

Case presentation

This study reports a case of a 72-year-old male who developed multiple infections, including liver abscess, lung abscess, left endophthalmitis, and purulent meningitis, following a traumatic fall. The patient had a history of poorly controlled diabetes mellitus. A diagnosis of KPIS caused by hvKp was confirmed through bacterial cultures and a positive string test. Imaging studies revealed multi-organ involvement. Given the complexity of the patient’s condition, a comprehensive treatment regimen, including broad-spectrum antibiotics, was implemented with significant therapeutic success. The patient showed marked improvement and continued follow-up after discharge, with a notable resolution of the infections.

Conclusion

This case highlights the significance of trauma as a potential trigger for KPIS, particularly in patients with high-risk underlying conditions such as diabetes. Early recognition and the implementation of individualized anti-infective treatment are crucial for reducing mortality and improving prognosis in KPIS patients. Future research should further investigate the relationship between trauma and hvKp infections and develop more comprehensive diagnostic and therapeutic guidelines.
Endoscopic surgery affects the gut microbiota and its metabolism in breast cancer patients
Authors: Li Jingtai , Gao Fangfang , Li Runwei , Chen Zhilin , Chen Guoping , Fan Pingming , Du Guankui
Published: January 2025

Background

Despite the advantages of endoscopic surgery in reducing trauma and enhancing recovery for breast cancer patients, its impact on gut microbiota, which is crucial for health and estrogen metabolism, remains unclear. Further investigation is necessary to fully understand this impact and its implications.

Materials and methods

Between June and December 2022, fecal samples were collected from 20 patients who underwent endoscopic surgery. The gut microbiota composition was determined using 16S rRNA sequencing, while the metabolites were analyzed through liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatics and statistical analyses were employed to identify significant alterations in microbial taxa abundance and to assess intergroup differences. These analyses included t-tests for pairwise comparisons, one-way ANOVA for multiple group comparisons, and chi-square tests for categorical data analysis.

Results

Endoscopic surgery in breast cancer patients subtly changed gut microbiota diversity and composition. Post-surgery, there was a reduction in Lachnospiraceae, Monoglobaceae and Firmicutes to Bacteroides ratios. Shifts in metabolites were also observed, the changed metabolites impacted pathways such as primary bile biosynthesis and Ascorbate and aldarate metabolism, with PE(PGD1/18:1(9Z)) identified as a key differential metabolite that increased post-surgery. Azasetron, tyramine glucuronide, DL-DOPA, phthalide, acetophenazine, aciclovir, creatinine bicarbonate, and 4-oxo-L-proline being associated with distinct bacterial taxa.

Conclusion

Breast cancer patients undergoing endoscopic surgery experience a shift in their gut microbiota and metabolic profiles. Therefore, postoperative management, with a particular focus on the adjustment of the gut microbiota, is crucial for enhancing patient recovery and health outcomes.
Complex bacterial diversity of Guaymas Basin hydrothermal sediments revealed by synthetic long-read sequencing (LoopSeq)
Authors: Hinkle John E. , Chanton Jeffrey P. , Moynihan Molly A. , Ruff S. Emil , Teske Andreas
Published: January 2025

Hydrothermal sediments host phylogenetically diverse and physiologically complex microbial communities. Previous studies of microbial community structure in hydrothermal sediments have typically used short-read sequencing approaches. To improve on these approaches, we use LoopSeq, a high-throughput synthetic long-read sequencing method that has yielded promising results in analyses of microbial ecosystems, such as the human gut microbiome. In this study, LoopSeq is used to obtain near-full length (approximately 1,400–1,500 nucleotides) bacterial 16S rRNA gene sequences from hydrothermal sediments in Guaymas Basin. Based on these sequences, high-quality alignments and phylogenetic analyses provided new insights into previously unrecognized taxonomic diversity of sulfur-cycling microorganisms and their distribution along a lateral hydrothermal gradient. Detailed phylogenies for free-living and syntrophic sulfur-cycling bacterial lineages identified well-supported monophyletic clusters that have implications for the taxonomic classification of these groups. Particularly, we identify clusters within Candidatus Desulfofervidus that represent unexplored physiological and genomic diversity. In general, LoopSeq-derived 16S rRNA gene sequences aligned consistently with reference sequences in GenBank; however, chimeras were prevalent in sequences as affiliated with the thermophilic Candidatus Desulfofervidus and Thermodesulfobacterium, and in smaller numbers within the sulfur-oxidizing family Beggiatoaceae. Our analysis of sediments along a well-documented thermal and geochemical gradient show how lineages affiliated with different sulfur-cycling taxonomic groups persist throughout surficial hydrothermal sediments in the Guaymas Basin.
Unveiling the role of BON domain-containing proteins in antibiotic resistance
Authors: Sun Shengwei , Chen Jinju
Published: January 2025

The alarming rise of antibiotic-resistant Gram-negative bacteria poses a global health crisis. Their unique outer membrane restricts antibiotic access. While diffusion porins are well-studied, the role of BON domain-containing proteins (BDCPs) in resistance remains unexplored. We analyze protein databases, revealing widespread BDCP distribution across environmental bacteria. We further describe their conserved core domain structure, a key for understanding antibiotic transport. Elucidating the genetic and biochemical basis of BDCPs offers a novel target to combat antibiotic resistance and restore bacterial susceptibility to antibiotics.
Exploring the alleviating effects of Bifidobacterium metabolite lactic acid on non-alcoholic steatohepatitis through the gut-liver axis
Authors: Zhao Hongmei , Zhou Juan , Yuan Lingzhi , Sun Zhiyi , Liu Yi , Zhao Xinyu , Ye Feng
Published: January 2025

Objective

This study investigates the protective effects of lactic acid, a metabolite of Bifidobacterium, on non-alcoholic fatty liver disease (NAFLD) induced by a high-sugar, high-fat diet (HFD) in mice, in the context of the gut-liver axis.

Methods

A NAFLD mouse model was established using a HFD, and different intervention groups were set up to study the protective effects of Bifidobacterium and its metabolite lactic acid. The groups included a control group, NAFLD group, Bifidobacterium treatment group, Glyceraldehyde-3-P (G-3P) co-treatment group, and NOD-like receptor family pyrin domain containing 3 (NLRP3) overexpression group. The evaluation of liver function and lipid metabolism was conducted using the liver-to-body weight ratio, histological staining, and biochemical assays. Enzyme-linked immunosorbent assay (ELISA) was performed to measure inflammatory cytokines, and western blotting was used to analyze the expression of NLRP3 inflammasome and autophagy-related molecules. In vitro, an NAFLD cell model was established using oleic acid, with cells treated with lactic acid and NLRP3 overexpression to assess lipid droplet accumulation and inflammation.

Results

In vivo findings indicated that, in comparison to CBX group (Control group without antibiotic treatment), NAFLD/CBX group (NAFLD group without antibiotic administration) and NAFLD/ABX group (NAFLD group with antibiotic administration) exhibited increased liver-to-body weight ratio, higher lipid droplet accumulation, aggravated liver histopathological damage, and elevated levels of AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase), TC (Total Cholesterol), TG (Triglycerides), LDL-C (Low-Density Lipoprotein Cholesterol), IL-6 (Interleukin-6), TNF-α (Tumor Necrosis Factor-alpha), IL-1β (Interleukin-1 beta), and NLRP3-related molecules, while HDL-C (High-Density Lipoprotein Cholesterol) levels significantly decreased. Intervention with Bifidobacterium significantly reversed these adverse changes. Further addition of G-3P led to more pronounced improvement in NAFLD symptoms, while overexpression of NLRP3 weakened the protective effects of Bifidobacterium. In vitro results indicated that Ole group exhibited heightened lipid droplet accumulation and expression of NLRP3 inflammasome-related molecules relative to the control group. Treatment with lactic acid effectively reversed these changes; however, the protective effect of lactic acid was significantly weakened with NLRP3 overexpression.

Conclusion

Lactic acid can alleviate lipid metabolism disorders in NAFLD induced by diet through the inhibition of inflammation mediated by the NLRP3 inflammasome and the regulation of the autophagy process.
ASFV infection induces lipid metabolic disturbances and promotes viral replication
Authors: Chu Xuefei , Ge Shengqiang , Li Yingchao , Zhang Qin , Cui Xinyu , Zuo Yuanyuan , Li Ruihong , Sun Hongtao , Yin Lei , Wang Zhenzhong , Li Jinming , Xiao Yihong , Wang Zhiliang
Published: January 2025

Introduction

African swine fever is a highly transmissible and lethal infectious disease caused by the African swine fever virus (ASFV), which has considerably impacted the global swine industry. Lipid metabolism plays a vital role in sustaining lipid and energy homeostasis within cells and influences the viral life cycle.

Methods and results

In this study, we found that ASFV infection disrupts lipid metabolism in the host. Transcriptomic analysis of cells infected with ASFV revealed that the levels of lipid metabolism significantly changed as the duration of the infection progressed. The intracellular cholesterol levels of the host exhibited a pattern similar to the viral growth curve during the course of infection. Notably, increased cholesterol levels promoted ASFV replication in host cells, whereas inhibition of the cholesterol biosynthesis pathway markedly reduced intracellular ASFV replication.

Discussion

The findings of this study showed that ASFV led to lipid metabolism disturbances to facilitate its replication, which is useful for revealing the mechanism underlying ASFV infection.
Irisin reshapes bone metabolic homeostasis to delay age-related osteoporosis by regulating the multipotent differentiation of BMSCs via Wnt pathway
Authors: Xing Shangman , Ma Yifan , Song Bing , Bai Min , Wang Kexin , Song Wenjing , Cao Tingting , Guo Chao , Zhang Yanying , Wang Zhandong , Wang Yongfeng
Published: January 2025

Introduction

Bone aging is linked to changes in the lineage differentiation of bone marrow stem cells (BMSCs), which show a heightened tendency to differentiate into adipocytes instead of osteoblasts. The therapeutic potential of irisin in addressing age-related diseases has garnered significant attention. More significantly, irisin has the capacity to enhance bone mass recovery and sustain overall bone health. Its mechanism of action in preventing osteoporosis has generated considerable interest within the research community. Nonetheless, the targeting effect of irisin on age-related osteoporosis and its underlying molecular biological mechanisms remain unclear.

Methods

The specific role of irisin in osteogenic-adipogenic differentiation in young or aging BMSCs was evaluated by multiple cells staining and quantitative real-time PCR (RT-qPCR) analysis. RNA-seq and protein Western blotting excavated and validated the key pathway by which irisin influences the fate determination of aging BMSCs. The macroscopic and microscopic changes of bone tissue in aging mice were examined using Micro-computed tomography (Micro-CT) and morphological staining.

Results

It was noted that irisin affected the multilineage differentiation of BMSCs in a manner dependent on the dosage. Simultaneously, the Wnt signaling pathway might be a crucial mechanism through which irisin sustains the bone-fat balance in aging BMSCs and mitigates the decline in pluripotency. In vivo, irisin reduced bone marrow fat deposition in aging mice and effectively alleviating the occurrence of bone loss.

Conclusion

Irisin mediates the Wnt signaling pathway, thereby influencing the fate determination of BMSCs. In addition, it is essential for preserving metabolic equilibrium in the bone marrow microenvironment and significantly contributes to overall bone health. The findings provide new evidence for the use of iris extract in the treatment of age-related osteoporosis.
Potential biomarkers for cerebral small vessel disease with cognitive impairment: a systematic review and meta-analysis
Authors: Liao Libin , Huang Weiquan , Ma Rongchao , He Xuan , Su Moxi , Sha Dujuan
Published: January 2025

Cerebral small vessel disease (CSVD) is a common factor in age-related diseases such as stroke and dementia, and about half of dementia patients worldwide are caused by CSVD. CSVD-related cognitive impairment (CSVD-CI) affects more and more elderly people, resulting in economic losses and burdens on families and society. In recent years, circulating biomarkers have made breakthroughs and played an increasingly important role in the diagnosis, progression, and prognosis of CSVD-associated cognitive impairment, and are expected to be applied to the early clinical detection, diagnosis, and treatment of patients with cerebral small vessel disease. Through a systematic review and meta-analysis, this study aimed to assess the relationship between circulating factors and cognitive impairment associated with cerebral small vessel disease, especially the possibility of becoming the potential biomarkers for diagnosis. Articles published before November 2023 were searched in four databases, PubMed, Web of Science, Embase, and Cochrane Library, to identify all relevant studies reporting circulating markers in patients with CSVD. Twenty-nine articles out of 2,911 were finalized for this study. We meta-analyzed 2 or more articles that were jointly considered to be circulating biomarkers of CSVD-CI and summarized a total of 4 possible biomarkers: homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2), and neurofilament protein light chain (NfL). The results revealed that patients in the CSVD-related cognitive impairment group had significantly higher levels of Hcy and hs-CRP than those in the CSVD-without cognitive impairment group, whereas there was no statistically significant difference in Lp-PLA2 and NfL between the two groups. Therefore, Hcy, hs-CRP may be considered circulating markers of cognitive impairment associated with cerebral small vessel disease.
Understanding gender differences in reasoning and specific paradigm using meta-analysis of neuroimaging
Authors: Chen Lina , Zheng Zeqing , Liang Jin , Lin Yuerui , Miao Qingqing
Published: January 2025

Reasoning is a fundamental cognitive process that allows individuals to make inferences, decisions, and solve problems. Understanding the neural mechanisms of reasoning and the gender differences in these mechanisms is crucial for comprehending the neural foundations of reasoning and promoting gender equality in cognitive processing. This study conducted an Activation Likelihood Estimation (ALE) meta-analysis of 275 studies, revealing that reasoning involves multiple brain regions, including the parts of frontal, parietal, occipital, temporal lobes, limbic system, and subcortical areas. These findings indicate that reasoning is a complex cognitive process requiring the coordinated activity of multiple brain regions. Additionally, 25 studies focusing on the Wisconsin Card Sorting Test (WCST) paradigm confirmed the importance of these regions in reasoning processes. The gender-specific activation results indicate that males and females utilize different neural networks during reasoning and WCST tasks. While significant differences exist in specific regions, the overall activation patterns do not show marked gender differences. Notably, females exhibit greater activation in the limbic system compared to males, suggesting that emotional states may play a more prominent role for females when engaging in reasoning tasks.
Association between hypertension and hearing loss: a systemic review and meta-analysis
Authors: Jin Xiaohua , Xu Xianpeng , Wang Jingjing , Liu Xinghong , Deng Xinxing , Xie Hui
Published: January 2025

Objective

To systematically evaluate the association between hypertension and hearing loss.

Methods

A standardized search for studies on hypertension and hearing loss in PubMed, Embase, Scopus, and Web of Science was performed using subject terms, free terms, and keyword combinations for the period of library construction to March 2024. Meta-analysis was performed using RevMan 5.4 and STATA 18.0.

Results

A total of 12 studies were included, assessing 594,676 participants. The combined OR using the random effects model was 1.849 (95% CI: 1.549, 2.208). Heterogeneity in this analysis was high (I2 = 98%, p < 0.1), and by sensitivity analysis we found that the heterogeneity may have originated from 3 studies, the removal of which significantly reduced the heterogeneity and had a small effect on the effect size [OR (95%CI): 1.893 (1.834, 1.953), I2 = 0.0%, p = 0.465].

Conclusion

Hypertension may be one of the risk factors for hearing loss. Identification of hypertension can help in early assessment and management of hearing loss risk.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023460001.
Impact of in-hospital COVID-19 quarantine policy changes on quality of acute stroke care: a single center experience
Authors: Kim Minkyung , Lee Keon-Joo , Kim Seong-Eun , Kim Hokyu , Han Jung Hoon , Kim Han Jun , Oh Kyungmi , Park Sung-Jun , Kim Chi Kyung , Cho Young-Duck
Published: January 2025

Introduction

The COVID-19 pandemic is known to impact in-hospital processes for acute stroke patients, potentially resulting in delays due to quarantine and screening measures. The purpose of this study was to determine effects of changes in in-hospital quarantine policies on quality of care for acute stroke patients.

Methods

Hyperacute ischemic stroke patients who were admitted to Korea University Guro Hospital between January 2019 and February 2021 via the emergency department were included in this study. All had neurological symptoms within 6 h before arrival. As a mandatory COVID-19 real-time PCR screening test was implemented in March 2020, changes in quality indicators according to the progress of COVID-19 pandemic and changes in in-hospital quarantine policy, including door-to-image time (DIT), door-to-referral time, door-to-needle time (DNT), door-to-puncture time (DPT), and functional outcomes (discharge and 3-month modified Rankin’s scale) were determined.

Results

A total of 268 hyperacute stroke patients were analyzed. The number of hyperacute stroke patients gradually decreased as the pandemic progressed. Time indicators, including door-to-referral time, DIT, and DPT during the pandemic were increased. When pre-and post-COVID-19 screening epochs were compared, DIT, door-to-neurologist referral time, and DPT showed numerical increases. However, after accounting for potential confounders, a significant delay in DIT was found to be associated with the in-hospital COVID-19 quarantine policy.

Discussion

Our study showed that enhancing in-hospital COVID-19 quarantine measures might increase the response time for hyperacute stroke care, suggesting an impact on the quality of care.
Ancillary tests for brain death
Authors: Duvuru Shyam , Sanker Vivek , Mishra Rajeeb Kumar , Sharma Arvind K. , Lim Shir Lynn , Baskar Nisha , Sharma Vijay K.
Published: January 2025

Background

Ancillary tests are often used in the determination of death by neurologic criteria (DNC), especially when the clinical examination is inconclusive. DNC is widely accepted, as defined by the comprehensive report of the World Brain Death Project. However, there are several medical, legal, religious, ethical, and social controversies. Accordingly, “premature” and “delayed” diagnoses of brain death attract these issues.

Methods

Depending upon the availability and experience of the managing medical teams, various ancillary tests are employed for an early and supplementary diagnosis of brain death.

Results

We describe the practicality, test performance, and utility of some of the commonly employed ancillary tests for the diagnosis of brain death in clinical practice, along with their case examples.

Conclusion

Brain death is a clinical diagnosis determined by history, physical examination, and adherence to recommended criteria. All ancillary investigations are used as supplementary tests with variable accuracy parameters. These ancillary tests often facilitate an early and “timely” diagnosis of brain death.