bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between rest-activity rhythm and diabetic retinopathy among US middle-age and older diabetic adults
Authors: Wang Zhijie , Wu Mengai , Li Haidong , Zheng Bin
Published: September 2024

Background

The disruption of circadian rhythm has been reported to aggravate the progression of diabetic retinopathy (DR). Rest-activity rhythm (RAR) is a widely used method for measuring individual circadian time influencing behavior. In this study, we sought to explore the potential association between RAR and the risk of DR.

Methods

Diabetic participants aged over 40 from 2011-2014 National Health and Nutrition Examination Survey (NHANES) were enrolled. Data from the wearable device ActiGraph GT3X was used to generate RAR metrics, including interdaily stability (IS), intradaily variability (IV), most active 10-hour period (M10), least active 5-hour period (L5), and Relative amplitude (RA). Weighted multivariable logistic regression analysis and restricted cubic spline analysis were conducted to examine the association between RAR metrics and DR risk. Sensitivity analysis was also conducted to examine the robustness of the findings. An unsupervised K-means clustering analysis was conducted to identify patterns in IV and M10.

Results

A total of 1,096 diabetic participants were enrolled, with a DR prevalence of 20.53%. The mean age of participants was 62.3 years, with 49.57% being male. After adjusting covariates, IV was positively associated with DR (β: 3.527, 95%CI: 1.371-9.073). Compared with the lowest quintile of IV, the highest quintile of IV had 136% higher odds of DR. In contrast, M10 was negatively associated with DR (β: 0.902, 95%CI: 0.828-0.982), with participants in the highest M10 quintile showing 48.8% lower odds of DR. Restricted cubic spline analysis confirmed that these associations were linear. Meanwhile, sensitivity analysis confirmed the robustness. K-means clustering identified three distinct clusters, with participants in Cluster C (high-IV, low-M10) had a significantly higher risk of DR comparing with Cluster A (low-IV, high-M10).

Conclusion

A more fragmented rhythm and lower peak activity level might be associated with an increased risk of DR. These findings indicate that maintaining a more rhythmic sleep-activity behavior might mitigate the development of DR. Further research is necessary to establish causality and understand the underlying mechanisms, and focus on whether interventions designed to enhance daily rhythm stability and increase diurnal activity level can effectively mitigate the risk of progression of DR.
Anti-Müllerian hormone: biology and role in endocrinology and cancers
Authors: Gowkielewicz Marek , Lipka Aleksandra , Zdanowski Wojciech , Waśniewski Tomasz , Majewska Marta , Carlberg Carsten
Published: September 2024

Anti-Müllerian hormone (AMH) is a peptide belonging to the transforming growth factor beta superfamily and acts exclusively through its receptor type 2 (AMHR2). From the 8th week of pregnancy, AMH is produced by Sertoli cells, and from the 23rd week of gestation, it is produced by granulosa cells of the ovary. AMH plays a critical role in regulating gonadotropin secretion, ovarian tissue responsiveness to pituitary hormones, and the pathogenesis of polycystic ovarian syndrome. It inhibits the transition from primordial to primary follicles and is considered the best marker of ovarian reserve. Therefore, measuring AMH concentration of the hormone is valuable in managing assisted reproductive technologies. AMH was initially discovered through its role in the degeneration of Müllerian ducts in male fetuses. However, due to its ability to inhibit the cell cycle and induce apoptosis, it has also garnered interest in oncology. For example, antibodies targeting AMHR2 are being investigated for their potential in diagnosing and treating various cancers. Additionally, AMH is present in motor neurons and functions as a protective and growth factor. Consequently, it is involved in learning and memory processes and may support the treatment of Alzheimer’s disease. This review aims to provide a comprehensive overview of the biology of AMH and its role in both endocrinology and oncology.
Voltage quality enhancement of distribution network based on unified power quality conditioner with BESS
Authors: Mei Yan , Xu Jiangbo , Peng Chen , Kong Weikang , Peng Gang , Song Guangyu
Published: September 2024

This article proposes a voltage compensation control strategy for the distribution network based on the unified power quality conditioner (UPQC) with battery energy storage systems (BESS) to achieve comprehensive management of the power quality and improve the system dynamic responses. Specifically, aiming at that amplitude and phase jump of the terminal voltage, a capacity configuration compensation scheme is proposed to achieve voltage vector compensation. The series converter is designed to compensate for the amplitude and phase of the load voltage. The parallel converter is designed to realize power compensation and ensure that the grid voltage and current are sinusoidal and in phase. A voltage control approach based on the nonlinear disturbance observer (NDO) is developed for BESS to stabilize the DC bus voltage and improve the anti-interference performance of the current. An NDO is designed to accomplish current disturbance tracking and provide disturbance feedforward compensation. Simulations validate that the proposed approach is effective and feasible.
Enhanced computed tomography radiomics predicts solute carrier family 7, member 11 in head and neck squamous cell carcinoma
Authors: Lv Jilian , Meng Xiangze , Li Yuanyuan , Zhang Rui , Zhao Yuan , Yang Xi , Wang Fang , Wang Xinbin
Published: September 2024

Introduction

Traditional prognostic indicators for head and neck squamous cell carcinoma (HNSCC), such as clinicopathological features, human papillomavirus status, and imaging examinations, often lack precision in guiding medical therapy. Therefore, discovering novel tumor biomarkers that can accurately assess prognosis and aid in personalized medical treatment for HNSCC is critical. Solute carrier family 7, member 11 (SLC7A11), is implicated in ferroptosis, and various malignant tumor therapies regulate its expression. However, the mechanisms regulating SLC7A11 expression, the transporter activity, and its specific role in controlling ferroptosis in cancer cells remain unknown. Thus, in this study, we aimed to develop an improved computed tomography (CT) radiomics model that could predict SLC7A11 expression in patients with HNSCC.

Methods

We used patient genomic data and corresponding augmented CT images for prognostic analysis and building models. Further, we investigated the potential molecular mechanisms underlying SLC7A11 expression in the immune microenvironment. Our radiomics model successfully predicted SLC7A11 mRNA expression in HNSCC tissues and elucidated its association with relevant genes and prognostic outcomes.

Results

SLC7A11 expression level was high within tumor tissues and was connected to the infiltration of eosinophil, CD8+ T-cell, and macrophages, which was associated with poor overall survival. Our models demonstrated robust predictive power. The distribution of radiomics scores (RAD scores) within the training and validation sets was markedly different between the high- and low-expression groups of SLC7A11.

Conclusion

SLC7A11 is likely an important factor in the prognosis of HNSCC. SLC7A11 expression can be predicted effectively and reliably by radiomics models based on enhanced CT.
Association study reveals a susceptibility locus with male pattern baldness in the Han Chinese population
Authors: Li Yang , Huang He , Liang Bo , Xiao Feng-Li , Zhou Fu-Sheng , Zheng Xiao-Dong , Yang Sen , Zhang Xue-Jun
Published: September 2024

Introduction

Male pattern baldness (MPB), also known as androgenetic alopecia, represents the most prevalent form of progressive hair loss in humans. It is characterized by a distinctive pattern of hair loss progression from the scalp; however, its underlying mechanism remains elusive and is influenced by hereditary, immune, and environmental factors. Genome-wide association studies (GWASs) have uncovered numerous risk genes/loci among European individuals with MPB. However, the validation of these susceptibility genes/loci within Han Chinese men remains largely unexplored. The aim of this study was to investigate whether the 71 susceptibility loci identified in a recent GWAS among European men also confer risk for MPB in Chinese men.

Methods

Forty-seven single nucleotide polymorphisms (SNPs) previously reported in GWASs of MPB were selected and genotyped in independent individuals comprising 499 Han Chinese cases and 1,489 controls using the Sequenom MassArray system. After stringent quality control measures, 25 SNPs were subjected to statistical analyses. Cochran–Armitage trend test was used to evaluate the association between SNPs and disease susceptibility. To address multiple tests, Bonferroni correction was conducted, setting the threshold for statistical significance at a p-value <2 × 10−3 (0.05/25).

Results

The rs13405699 SNP located at 2q31.1 exhibited a significant association with MPB in Han Chinese men (p = 4.84 × 10−5, OR = 1.37, 95% CI: 1.18–1.59). Moreover, the difference in rs13405699 genotype distribution between MPB cases and controls was statistically significant (p = 7.00 × 10−5). Genotype-based association analysis suggested that the recessive model provided the best fit for the rs13405699 polymorphism.

Conclusion

This study represents the first confirmation of the association between the rs13405699 SNP at 2q31.1 and MPB within the Han Chinese population, thereby enhancing our understanding of the genetic underpinnings of MPB.
The role of pyroptosis in the occurrence and development of pregnancy-related diseases
Authors: Li Jiahui , Wang Min , Zhou Haiyan , Jin Zhong , Yin Haonan , Yang Shuli
Published: September 2024

Pyroptosis is a form of programmed cell death that is crucial in the development of various diseases, including autoimmune diseases, atherosclerotic diseases, cancer, and pregnancy complications. In recent years, it has gained significant attention in national and international research due to its association with inflammatory immune overactivation and its involvement in pregnancy complications such as miscarriage and preeclampsia (PE). The mechanisms discussed include the canonical pyroptosis pathway of gasdermin activation and pore formation (caspase-1-dependent pyroptosis) and the non-canonical pyroptosis pathway (cysteoaspartic enzymes other than caspase-1). These pathways work on various cellular and factorial levels to influence normal pregnancy. This review aims to summarize and analyze the pyroptosis pathways associated with abnormal pregnancies and pregnancy complications. The objective is to enhance pregnancy outcomes by identifying various targets to prevent the onset of pyroptosis.
Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation
Authors: Shaikh Ahmad , Gangaplara Arunakumar , Kone Abdoul , Almengo Katherine , Kabore Mariama D. , Ali Mohamed A.E. , Xu Xin , Saxena Ankit , Lopez-Ocasio Maria , McCoy J. Philip , Fitzhugh Courtney D.
Published: September 2024

Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4+ T cells, CD8+ T cells, natural killer cells, IFN-γ and TNF-α producing CD4+ T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios+, IL-10-producing CD4+ T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1+Gal-1+ cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.
Differential modulation of mutant CALR and JAK2 V617F-driven oncogenesis by HLA genotype in myeloproliferative neoplasms
Authors: Shivarov Velizar , Tsvetkova Gergana , Micheva Ilina , Hadjiev Evgueniy , Petrova Jasmina , Ivanova Anela , Madjarova Galia , Ivanova Milena
Published: September 2024

It has been demonstrated previously that human leukocyte antigen class I (HLA-I) and class II (HLA-II) alleles may modulate JAK2 V617F and CALR mutation (CALRmut)-associated oncogenesis in myeloproliferative neoplasms (MPNs). However, the role of immunogenetic factors in MPNs remains underexplored. We aimed to investigate the potential involvement of HLA genes in CALRmut+ MPNs. High-resolution genotyping of HLA-I and -II loci was conducted in 42 CALRmut+ and 158 JAK2 V617F+ MPN patients and 1,083 healthy controls. A global analysis of the diversity of HLA-I genotypes revealed no significant differences between CALRmut+ patients and controls. However, one HLA-I allele (C*06:02) showed an inverse correlation with presence of CALR mutation. A meta-analysis across independent cohorts and healthy individuals from the 1000 Genomes Project confirmed an inverse correlation between the presentation capabilities of the HLA-I loci for JAK2 V617F and CALRmut-derived peptides in both patients and healthy individuals. scRNA-Seq analysis revealed low expression of TAP1 and CIITA genes in CALRmut+ hematopoietic stem and progenitor cells. In conclusion, the HLA-I genotype differentially restricts JAK2 V617F and CALRmut-driven oncogenesis potentially explaining the mutual exclusivity of the two mutations and differences in their presentation latency. These findings have practical implications for the development of neoantigen-based vaccines in MPNs.
Metabolic mediators: microbial-derived metabolites as key regulators of anti-tumor immunity, immunotherapy, and chemotherapy
Authors: Lu Shan , Wang Chunling , Ma Jingru , Wang Yichao
Published: September 2024

The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs’ remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.
Varicella-zoster virus recapitulates its immune evasive behaviour in matured hiPSC-derived neurospheroids
Authors: Govaerts Jonas , Van Breedam Elise , De Beuckeleer Sarah , Goethals Charlotte , D’Incal Claudio Peter , Di Stefano Julia , Van Calster Siebe , Buyle-Huybrecht Tamariche , Boeren Marlies , De Reu Hans , Paludan Søren R. , Thiry Marc , Lebrun Marielle , Sadzot-Delvaux Catherine , Motaln Helena , Rogelj Boris , Van Weyenbergh Johan , De Vos Winnok H. , Vanden Berghe Wim , Ogunjimi Benson , Delputte Peter , Ponsaerts Peter
Published: September 2024

Varicella-zoster virus (VZV) encephalitis and meningitis are potential central nervous system (CNS) complications following primary VZV infection or reactivation. With Type-I interferon (IFN) signalling being an important first line cellular defence mechanism against VZV infection by the peripheral tissues, we here investigated the triggering of innate immune responses in a human neural-like environment. For this, we established and characterised 5-month matured hiPSC-derived neurospheroids (NSPHs) containing neurons and astrocytes. Subsequently, NSPHs were infected with reporter strains of VZV (VZVeGFP-ORF23) or Sendai virus (SeVeGFP), with the latter serving as an immune-activating positive control. Live cell and immunocytochemical analyses demonstrated VZVeGFP-ORF23 infection throughout the NSPHs, while SeVeGFP infection was limited to the outer NSPH border. Next, NanoString digital transcriptomics revealed that SeVeGFP-infected NSPHs activated a clear Type-I IFN response, while this was not the case in VZVeGFP-ORF23-infected NSPHs. Moreover, the latter displayed a strong suppression of genes related to IFN signalling and antigen presentation, as further demonstrated by suppression of IL-6 and CXCL10 production, failure to upregulate Type-I IFN activated anti-viral proteins (Mx1, IFIT2 and ISG15), as well as reduced expression of CD74, a key-protein in the MHC class II antigen presentation pathway. Finally, even though VZVeGFP-ORF23-infection seems to be immunologically ignored in NSPHs, its presence does result in the formation of stress granules upon long-term infection, as well as disruption of cellular integrity within the infected NSPHs. Concluding, in this study we demonstrate that 5-month matured hiPSC-derived NSPHs display functional innate immune reactivity towards SeV infection, and have the capacity to recapitulate the strong immune evasive behaviour towards VZV.
Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes
Authors: Kakabadse Dimitri , Chen Dawei , Fishman Sigal , Weinstein-Marom Hadas , Davies Joanne , Wen Li , Gross Gideon , Wong F. Susan
Published: September 2024

Introduction

In this study, we report a novel therapeutic approach redirecting antigen-specific CD4+ T cells recognizing a hybrid insulin peptide (BDC2.5 T cell receptor (TCR) transgenic CD4+ T cells) to attract and suppress islet-specific CD8+ T cells T cells in the non-obese diabetic (NOD) mouse model, and prevent the development of autoimmune diabetes.

Methods

Purified BDC2.5 CD4+ T cells were induced to differentiate into regulatory T cells (Tregs). The Tregs were then electroporated with mRNA encoding chimeric human β2 microglobulin (hβ2m) covalently linked to insulin B chain amino acids 15-23 (designated INS-eTreg) or islet-specific glucose-6-phosphatase related protein (IGRP) peptide 206-214 (designated IGRP-eTreg). Immunoregulatory functions of these engineered regulatory T cells (eTregs) were tested by in vitro assays and in vivo co-transfer experiments with β-cell-antigen-specific CD8+ T cells in NOD.Scid mice or by adoptive transfer into young, pre-diabetic NOD mice.

Results

These eTregs were phenotyped by flow cytometry, and shown to have high expression of FoxP3, as well as other markers of Treg function, including IL-10. They suppressed polyclonal CD4+ T cells and antigen-specific CD8+ T cells (recognizing insulin or IGRP), decreasing proliferation and increasing exhaustion and regulatory markers in vitro. In vivo, eTregs reduced diabetes development in co-transfer experiments with pathogenic antigen-specific CD8+ T cells (INS-CD8+ or IGRP-CD8+ cells) into NOD.Scid mice. Finally, when the eTreg were injected into young NOD mice, they reduced insulitis and prevented spontaneous diabetes in the recipient mice.

Conclusion

Our results suggest a novel therapeutic strategy to protect NOD mice by targeting antigen-specific cytotoxic CD8+ T cells, using redirected antigen-specific CD4+ Treg cells, to suppress autoimmune diabetes. This may suggest an innovative therapy for protection of people at risk of development of type 1 diabetes.
Beyond counting calls: estimating detection probability for Antarctic blue whales reveals biological trends in seasonal calling
Authors: de Castro Franciele R. , Harris Danielle V. , Buchan Susannah J. , Balcazar Naysa , Miller Brian S.
Published: September 2024

We explore the utility of estimating the density of calls of baleen whales for better understanding acoustic trends over time. We consider as a case study stereotyped ‘song’ calls of Antarctic blue whales (Balaenoptera musculus intermedia) on their Antarctic feeding grounds over the course of a year-long, continuous recording from 2014. The recording was made in the Southern Ocean from a deep-water autonomous hydrophone moored near the seafloor in the Eastern Indian sector of the Antarctic. We estimated call density seasonally via a Monte-Carlo simulation based on the passive sonar equation, and compared our estimates to seasonal estimates of detection rate, which are commonly reported in acoustic studies of Antarctic blue whales. The resulting seasonal call densities at our Antarctic site were strongly influenced by seasonally varying noise levels, which in turn yielded seasonal differences in detection range. Incorporating the seasonal estimates of detection area into our analysis revealed a pattern of call densities in accord with historic (non-acoustic) knowledge of Antarctic blue whale seasonal distribution and migrations, a pattern that differed from seasonal detection rates. Furthermore, our methods for estimating call densities produced results that were more statistically robust for comparison across sites and time and more meaningful for interpretation of biological trends compared to detection rates alone. These advantages came at the cost of a more complex analysis that accounts for the large variability in detection range of different sounds that occur in Antarctic waters, and also accounts for the performance and biases introduced by automated algorithms to detect sounds. Despite the additional analytical complexities, broader usage of call densities, instead of detection rates, has the potential to yield a standardized, statistically robust, biologically informative, global investigation of acoustic trends in baleen whale sounds recorded on single hydrophones, especially in the remote and difficult to access Antarctic.
Cross-talk between macrophages and gut microbiota in inflammatory bowel disease: a dynamic interplay influencing pathogenesis and therapy
Authors: Ning Shiyang , Zhang Zhe , Zhou Chuan , Wang Binbin , Liu Zhanju , Feng Baisui
Published: September 2024

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a group of chronic immune-mediated gastrointestinal disorders. The etiology of IBD is multifactorial, involving genetic susceptibility, environmental factors, and a complex interplay between the gut microbiota and the host’s immune system. Intestinal resident macrophages play an important role in the pathogenesis and progress of IBD, as well as in maintaining intestinal homeostasis and facilitating tissue repair. This review delves into the intricate relationship between intestinal macrophages and gut microbiota, highlighting their pivotal roles in IBD pathogenesis. We discuss the impact of macrophage dysregulation and the consequent polarization of different phenotypes on intestinal inflammation. Furthermore, we explore the compositional and functional alterations in gut microbiota associated with IBD, including the emerging significance of fungal and viral components. This review also examines the effects of current therapeutic strategies, such as 5-aminosalicylic acid (5-ASA), antibiotics, steroids, immunomodulators, and biologics, on gut microbiota and macrophage function. We underscore the potential of fecal microbiota transplantation (FMT) and probiotics as innovative approaches to modulate the gut microbiome in IBD. The aim is to provide insights into the development of novel therapies targeting the gut microbiota and macrophages to improve IBD management.
The unique chemical and microbiological signatures of an array of bottled drinking water
Authors: Nadreen Yasmeen M. , Vrouwenvelder Johannes S. , Saikaly Pascal E. , Gonzalez-Gil Graciela
Published: September 2024

The bottled drinking water market has seen significant growth and diversification, yet the selection criteria lack scientific basis, as all must adhere to stringent health standards. Prior studies predominantly focused on chemical quality, with limited assessments of microbial quality using methods prone to underestimation. Moreover, insufficient research explores the impact of packaging materials and temperatures optimal for mesophilic growth on microbial quality. To understand the unique characteristics and justify the distinction among different types of bottled waters, a comprehensive analysis encompassing both chemical and microbiological aspects is imperative. Addressing these gaps, our study examines 19 diverse bottled water brands comprising purified, mineral, artesian, and sparkling water types from Saudi Arabia and abroad. Our findings reveal distinct chemical compositions among bottled waters, with notable variations across types. Flow cytometry analysis reveals significant differences in bacterial content among water types, with natural mineral waters having the highest concentrations and treated purified waters the lowest. Bacterial content in plastic-bottled mineral water suggests it may be higher than in glass-bottled water. Flow cytometry fingerprints highlight separate microbial communities for purified and mineral waters. Additionally, temperatures favorable for mesophilic growth reveal varying microbial responses among different types of bottled waters. Some variation is also observed in mineral water bottled in plastic versus glass, suggesting potential differences that warrant further investigation. 16S rRNA gene sequencing identifies unique microbial taxa among different mineral waters. Overall, our study underscores that all bottled waters meet health regulations. Furthermore, the combined chemical and microbial profiles may serve as authenticity indicators for distinct bottled water types. This study can serve as a basis for future research on the environmental impact of bottled water transportation, suggesting that locally produced water may offer a more sustainable option.
Association of sleep quality with cognitive dysfunction in middle-aged and elderly adults: a cross-sectional study in China
Authors: Jiang Mengyang , Liu Yang , Wang Xin , Liu Yuhe , Deng Xuan , Zhang Xiaoyu , Wang Baoguo
Published: September 2024

Objectives

Sleep is an indispensable part of human health, which can help us to restore physical strength, enhance immunity and maintain nervous system stability. The relationship between sleep quality and cognitive dysfunction is unclear, especially at the community population level. This study aims to explore the association between sleep quality and cognitive dysfunction.

Methods

A total of 5,224 community residents were enrolled in this cross-sectional study. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Sleep quality was assessed by the multidimensional sleep questionnaire. Multivariate logistic regression was used to analyze the association between sleep quality and cognitive dysfunction. The adjusted models took into account relevant demographic, clinical, and sleep variables.

Results

A total of 3,106 participants were enrolled in this study, of whom 463 (15%) had cognitive dysfunction. Total sleep duration, staying up, sleep latency, number of awakenings, and history of sleep medications were associated with cognitive dysfunction in unadjusted models, and these effects were consistent after adjustment. First, those who slept 6–7.9 h per day (OR = 0.57, 95% CI 0.40 to 0.80, p = 0.001) had a lower risk for cognitive dysfunction compared to those who slept less than 6 h per day. Second, participants who stayed up more than 10 times over the 3 months (OR = 1.90, 95% CI 1.20 to 3.00, p = 0.006) were more likely to suffer cognitive dysfunction than those who never stayed up. Third, we also found that participants with sleep latencies of 16–30 min were less likely to experience cognitive dysfunction than those with sleep latencies of less than 16 min after adjusting confounders (OR = 0.33, 95% CI 0.23 to 0.47, p < 0.001). Fourth, participants who woke up once (OR = 1.65, 95% CI 1.19 to 2.30, p = 0.003) and three or more times (OR = 2.34, 95% CI 1.25 to 4.36, p = 0.008) after falling asleep had a higher risk than those who did not wake up at night. Last, participants taking sleep medication (OR = 2.97, 95% CI 1.19 to 7.45, p = 0.020) were more vulnerable to cognitive dysfunction, relative to participants without taking any medications.

Conclusion

Our results suggest that after adjustment for potential confounding variables, poor sleep quality is associated with cognitive dysfunction.
Quantitative reliability assessment of brain MRI volumetric measurements in type II GM1 gangliosidosis patients
Authors: Zoppo Christopher , Kolstad Josephine , Johnston Jean , D'Souza Precilla , Kühn Anna Luisa , Vardar Zeynep , Peker Ahmet , Lindsay Clifford , Rentiya Zubir S. , King Robert , Gray-Edwards Heather , Vachha Behroze , Acosta Maria T. , Tifft Cynthia J. , Shazeeb Mohammed Salman
Published: September 2024

Purpose

GM1-gangliosidosis (GM1) leads to extensive neurodegenerative changes and atrophy that precludes the use of automated MRI segmentation techniques for generating brain volumetrics. We developed a standardized segmentation protocol for brain MRIs of patients with type II GM1 and then assessed the inter- and intra-rater reliability of this methodology. The volumetric data may be used as a biomarker of disease burden and progression, and standardized methodology may support research into the natural history of the disease which is currently lacking in the literature.

Approach

Twenty-five brain MRIs were included in this study from 22 type II GM1 patients of which 8 were late-infantile subtype and 14 were juvenile subtype. The following structures were segmented by two rating teams on a slice-by-slice basis: whole brain, ventricles, cerebellum, lentiform nucleus, thalamus, corpus callosum, and caudate nucleus. The inter- and intra-rater reliability of the segmentation method was assessed with an intraclass correlation coefficient as well as Sorensen-Dice and Jaccard coefficients.

Results

Based on the Sorensen-Dice and Jaccard coefficients, the inter- and intra-rater reliability of the segmentation method was significantly better for the juvenile patients compared to late-infantile (p < 0.01). In addition, the agreement between the two rater teams and within themselves can be considered good with all p-values < 0.05.

Conclusions

The standardized segmentation approach described here has good inter- and intra-rater reliability and may provide greater accuracy and reproducibility for neuromorphological studies in this group of patients and help to further expand our understanding of the natural history of this disease.
Case report: Combination therapy with selinexor, decitabine and half-dose CAG regimen for relapsed elderly acute myeloid leukemia
Authors: Zhang Xueya , Sun Yuqi , Zhong Jinfa
Published: September 2024

The treatment of elderly patients diagnosed with acute myeloid leukemia (AML) poses significant challenges. Currently, one promising strategy in therapeutic interventions for geriatric individuals revolves around the utilization of small molecule targeted drugs either independently or in conjunction with demethylating agents. In this report, we present the successful attainment of complete remission in an elderly female patient with relapsed AML, the patient underwent treatment with a combination of Selinexor, decitabine, and a half-dose CAG regimen for two cycles. Subsequently, the patient has sustained this remission through consolidation therapy involving a medium dose of Ara-c. This therapeutic regimen has demonstrated favorable outcomes in the management of relapsed AML in elderly individuals. Furthermore, the adverse reactions were manageable. In order to devise an efficacious treatment regimen for elderly patients suffering from relapsed and refractory acute myeloid leukemia, it is imperative to incorporate a larger cohort of cases for clinical investigation.
A nomogram with Nottingham prognostic index for predicting locoregional recurrence in breast cancer patients
Authors: Zheng Jianqing , Zeng Bingwei , Huang Bifen , Wu Min , Xiao Lihua , Li Jiancheng
Published: September 2024

Background

The Nottingham prognostic index (NPI) has been shown to negatively impact survival in breast cancer (BC). However, its ability to predict the locoregional recurrence (LRR) of BC remains still unclear. This study aims to determine whether a higher NPI serves as a significant predictor of LRR in BC.

Methods

In total, 238 patients with BC were included in this analysis, and relevant clinicopathological features were collected. Correlation analysis was performed between NPI scores and clinicopathological characteristics. The optimal nomogram model was determined by Akaike information criterion. The accuracy of the model’s predictions was evaluated using receiver operating characteristic curves (ROC curves), calibration curves and goodness of fit tests. The clinical application value was assessed through decision curve analysis.

Results

Six significant variables were identified, including age, body mass index (BMI), TNM stage, NPI, vascular invasion, perineural invasion (P<0.05). Two prediction models, namely a TNM-stage-based model and an NPI-based model, were constructed. The area under the curve (AUC) for the TNM-stage- and NPI-based models were 0.843 (0.785,0.901) and 0.830 (0.766,0.893) in training set and 0.649 (0.520,0.778) and 0.728 (0.610,0.846) in validation set, respectively. Both models exhibited good calibration and goodness of fit. The F-measures were 0.761vs 0.756 and 0.556 vs 0.696, respectively. Clinical decision curve analysis showed that both models provided clinical benefits in evaluating risk judgments based on the nomogram model.

Conclusions

a higher NPI is an independent risk factor for predicting LRR in BC. The nomogram model based on NPI demonstrates good discrimination and calibration, offering potential clinical benefits. Therefore, it merits widespread adoption and application.
Assessing microvascular invasion in HBV-related hepatocellular carcinoma: an online interactive nomogram integrating inflammatory markers, radiomics, and convolutional neural networks
Authors: Zhong Yun , Chen Lingfeng , Ding Fadian , Ou Wenshi , Zhang Xiang , Weng Shangeng
Published: September 2024

Objective

The early recurrence of hepatocellular carcinoma (HCC) correlates with decreased overall survival. Microvascular invasion (MVI) stands out as a prominent hazard influencing post-resection survival status and metastasis in patients with HBV-related HCC. The study focused on developing a web-based nomogram for preoperative prediction of MVI in HBV-HCC.

Materials and methods

173 HBV-HCC patients from 2017 to 2022 with complete preoperative clinical data and Gadopentetate dimeglumine-enhanced magnetic resonance images were randomly divided into two groups for the purpose of model training and validation, using a ratio of 7:3. MRI signatures were extracted by pyradiomics and the deep neural network, 3D ResNet. Clinical factors, blood-cell-inflammation markers, and MRI signatures selected by LASSO were incorporated into the predictive nomogram. The evaluation of the predictive accuracy involved assessing the area under the receiver operating characteristic (ROC) curve (AUC), the concordance index (C-index), along with analyses of calibration and decision curves.

Results

Inflammation marker, neutrophil-to-lymphocyte ratio (NLR), was positively correlated with independent MRI radiomics risk factors for MVI. The performance of prediction model combined serum AFP, AST, NLR, 15 radiomics features and 7 deep features was better than clinical and radiomics models. The combined model achieved C-index values of 0.926 and 0.917, with AUCs of 0.911 and 0.907, respectively.

Conclusion

NLR showed a positive correlation with MRI radiomics and deep learning features. The nomogram, incorporating NLR and MRI features, accurately predicted individualized MVI risk preoperatively.
Advanced CNN models in gastric cancer diagnosis: enhancing endoscopic image analysis with deep transfer learning
Authors: Bhardwaj Priya , Kim SeongKi , Koul Apeksha , Kumar Yogesh , Changela Ankur , Shafi Jana , Ijaz Muhammad Fazal
Published: September 2024

Introduction

The rapid advancement of science and technology has significantly expanded the capabilities of artificial intelligence, enhancing diagnostic accuracy for gastric cancer.

Methods

This research aims to utilize endoscopic images to identify various gastric disorders using an advanced Convolutional Neural Network (CNN) model. The Kvasir dataset, comprising images of normal Z-line, normal pylorus, ulcerative colitis, stool, and polyps, was used. Images were pre-processed and graphically analyzed to understand pixel intensity patterns, followed by feature extraction using adaptive thresholding and contour analysis for morphological values. Five deep transfer learning models—NASNetMobile, EfficientNetB5, EfficientNetB6, InceptionV3, DenseNet169—and a hybrid model combining EfficientNetB6 and DenseNet169 were evaluated using various performance metrics.

Results & discussion

For the complete images of gastric cancer, EfficientNetB6 computed the top performance with 99.88% accuracy on a loss of 0.049. Additionally, InceptionV3 achieved the highest testing accuracy of 97.94% for detecting normal pylorus, while EfficientNetB6 excelled in detecting ulcerative colitis and normal Z-line with accuracies of 98.8% and 97.85%, respectively. EfficientNetB5 performed best for polyps and stool with accuracies of 98.40% and 96.86%, respectively.The study demonstrates that deep transfer learning techniques can effectively predict and classify different types of gastric cancer at early stages, aiding experts in diagnosis and detection.
Roles of small peptides encoded by non-coding RNAs in tumor invasion and migration
Authors: Liu Jie , Chang Xiyue , Manji Laeeqa , Xu Zhijie , Xiao Wan’an
Published: September 2024

Non-coding RNAs (ncRNAs), which are usually considered not to encode proteins, are widely involved in important activities including signal transduction and cell proliferation. However, recent studies have shown that small peptides encoded by ncRNAs (SPENs) have important roles in the development of malignant tumors. Some SPENs participate in the regulation of skeleton reorganization, intercellular adhesion, signaling and other processes of tumor cells, with effects on the invasive and migratory abilities of the cells. Therefore, SPENs have potential applications as therapeutic targets and biomarkers of malignant tumors. Invasion and migration of malignant tumor cells are the main reasons for poor prognosis of cancer patients and represent the most challenging aspects of treatment of malignant tumors. Currently, the main treatments for tumors include surgery, radiotherapy, targeted drug therapy. Surgery, however, is reserved for early stages of cancer and carries risks and costs. Radiotherapy and targeted therapy have serious side effects. This review describes the mechanisms of SPENs and their roles in tumor invasion and migration, with the aim of providing new targets for tumor diagnosis and treatment.
HER2-targeted therapies for HER2-positive early-stage breast cancer: present and future
Authors: Xu Luying , Xie Yuxin , Gou Qiheng , Cai Rui , Bao Rong , Huang Yucheng , Tang Ruisi
Published: September 2024

Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%–30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody–drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.
Rooted in therapeutics: comprehensive analyses of Cannabis sativa root extracts reveals potent antioxidant, anti-inflammatory, and bactericidal properties
Authors: Gagné Valérie , Merindol Natacha , Boucher Raphaël , Boucher Nathalie , Desgagné-Penix Isabel
Published: September 2024

Following the legalization of recreational Cannabis in Canada in 2018, the associated waste, including Cannabis roots, has significantly increased. Cannabis roots, comprising 30%–50% of the total plant, are often discarded despite their historical use in Ayurvedic medicine for treating inflammatory and infectious disorders. This study evaluates the phytochemical and therapeutic properties of Cannabis root extracts from a high tetrahydrocannabinolic acid, low cannabidiolic acid cultivar (variety Alien Gorilla Glue). We performed ultra high-performance liquid chromatography coupled with mass spectrometry (UPLC-QTOF-MS) to identify the chemical components of the Cannabis roots. Extracts using water, ethanol and acid-base solvents were tested for antioxidant activity through free radical scavenging, metal chelation, and lipoperoxidation inhibition assays. Mitochondrial membrane protection was assessed using flow cytometry with the MitoPerOx probe in THP-1 monocytic leukemia cells. Anti-inflammatory potential was evaluated by measuring interleukin-6 levels in lipopolysaccharide-stimulated THP-1 cells. Bactericidal/fungicidal efficacy against Escherichia coli, Staphylococcus aureus, and Candida albicans was determined using the p-iodonitrophenyltetrazolium assay. Additionally, we investigated the anticholinesterase activity of Cannabis root extracts, given the potential role of plant alkaloids in inhibiting cholinesterase, an enzyme targeted in Alzheimer’s disease treatments. UPLC-QTOF-MS analysis suggested the presence of several phenolic compounds, cannabinoids, terpenoids, amino acids, and nitrogen-containing compounds. Our results indicated significant antioxidant, bactericidal, and anticholinesterase properties of Cannabis root extracts from both soil and hydroponic cultivation. Extracts showed strong antioxidant activity across multiple assays, protected mitochondrial membrane in THP-1 cells, and exhibited anti-inflammatory and bactericidal/fungicidal efficacy. Notably, soil-cultivated roots displayed superior anti-inflammatory effects. These findings demonstrate the remarkable antioxidant, anti-inflammatory, and anti-microbial activities of Cannabis roots, supporting their traditional uses and challenging their perception as mere waste. This study highlights the therapeutic potential of Cannabis roots extracts and suggests avenues for further research and application.
High-precision HD spectroscopy near 1.53 μm
Authors: Gotti Riccardo , Wójtewicz Szymon , Marangoni Marco , Gatti Davide , Lamperti Marco
Published: September 2024

In this study, we report highly precise and accurate measurements of the P(5), P(6), and O(3) transitions of the 2–0 band of HD occurring at approximately 1.5 μm. HD spectra were acquired in the pressure range of 100–900 Torr using a cavity ring-down spectrometer linked to an optical frequency comb. The line-shape analysis was performed using the Hartmann–Tran profile in the so-called β-corrected version. For the P(5) transition, we improved the accuracy of previous line center frequency determinations by more than two orders of magnitude. Moreover, for the P(5) and P(6) line centers, the total standard uncertainty is below 3 MHz, similar to those provided by quantum electrodynamics predictions, making them useful for direct comparisons that might foster future improvements of the theoretical model.
Effect of gamma irradiation on proliferation and growth of friable embryogenic callus and in vitro nodal cuttings of ugandan cassava genotypes
Authors: Apio Hellen B. , Elegba Wilfred , Nunekpeku Wonder , Otu Solomon Ayeboafo , Baguma Julius Karubanga , Alicai Titus , Danso Kenneth Ellis , Bimpong Isaac Kofi , Ogwok Emmanuel
Published: September 2024

Cassava (Manihot esculenta Crantz) production and productivity in Africa is affected by two viral diseases; cassava mosaic disease (CMD) and cassava brown streak disease (CBSD). Induced mutagenesis of totipotent/embryogenic tissues or in vitro plant material can lead to the generation of CMD and/or CBSD tolerant mutants. To massively produce non-chimeric plants timely and with less labor, totipotent cells or tissues are a pre-requisite. This study aimed to determine the effect of gamma radiation on the proliferation and growth of friable embryogenic callus (FEC) and in vitro nodal cuttings respectively. To obtain FEC, 2-6 mm sized leaf lobes of nine cassava genotypes were plated on Murashige and Skoog (MS) basal media supplemented with varying levels (37, 50, 70, 100) μM of picloram for production of organized embryogenic structures (OES). The OES of five cassava genotypes (Alado, CV-60444, NASE 3, NASE 13 and TME 204) were crushed and plated in Gresshoff and Doy (GD) basal media in combination with the amino acid tyrosine in varying concentrations for FEC production. FEC from five cassava genotypes and in vitro nodal cuttings of nine genotypes were irradiated using five different gamma doses (0, 5, 10, 15, 20 and 25 Gy) at a dose rate of 81Gy/hr. The lethal dose (LD)50 was determined using the number of roots produced and flow cytometry was done to determine the ploidy status of plants. The highest production of OES was noted in Alado across varying picloram concentrations, while TME 204 obtained the highest amount of FEC. The irradiated FEC gradually died and by 28 days post irradiation, FEC from all five cassava genotypes were lost. Conversely, the irradiated in vitro nodal cuttings survived and some produced roots, while others produced callus. The LD50 based on number of roots varied from genotype to genotype, but plants remained diploid post-irradiation. Accordingly, the effect of gamma irradiation on Ugandan cassava genotypes (UCGs) was genotype-dependent. This information is foundational for the use of in vitro tissues as target material for cassava mutation breeding.