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1.
PLoS Negl Trop Dis ; 18(7): e0012239, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38959212

ABSTRACT

BACKGROUND: Dengue virus (DENV) infection, a common mosquito-borne disease, has been linked to several mental disorders like depression and anxiety. However, the temporal risk of these disorders after DENV infection is not well studied. METHODS: This population-based cohort study encompassed 45,334 recently lab-confirmed dengue patients in Taiwan spanning 2002 to 2015, matched at a 1:5 ratio with non-dengue individuals based on age, gender, and residence (n = 226,670). Employing subdistribution hazard regression analysis, we assessed the immediate (<3 months), intermediate (3-12 months), and prolonged (>12 months) risks of anxiety disorders, depressive disorders, and sleep disorders post DENV infection. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure. RESULTS: A significant increase in depressive disorder risk across all timeframes post-infection was observed (<3 months [aSHR 1.90, 95% CI 1.20-2.99], 3-12 months [aSHR 1.68, 95% CI 1.32-2.14], and >12 months [aSHR 1.14, 95% CI 1.03-1.25]). Sleep disorder risk was higher only during 3-12 months (aSHR 1.55, 95% CI 1.18-2.04). No elevated anxiety disorder risk was found. Subgroup analysis of hospitalized dengue patients showed increased risk of anxiety disorders within 3 months (aSHR 2.14, 95% CI 1.19-3.85) and persistent risk of depressive disorders across all periods. Hospitalized dengue patients also had elevated sleep disorder risk within the first year. CONCLUSION: Dengue patients exhibited significantly elevated risks of depressive disorders in both the short and long term. However, dengue's impact on sleep disorders and anxiety seems to be short-lived. Further research is essential to elucidate the underlying mechanisms.


Subject(s)
Anxiety Disorders , Dengue , Depressive Disorder , Sleep Wake Disorders , Humans , Dengue/epidemiology , Dengue/complications , Male , Female , Taiwan/epidemiology , Sleep Wake Disorders/epidemiology , Adult , Anxiety Disorders/epidemiology , Cohort Studies , Young Adult , Middle Aged , Adolescent , Depressive Disorder/epidemiology , Risk Factors , Child , Aged , Child, Preschool
2.
IEEE Trans Biomed Eng ; PP2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968024

ABSTRACT

OBJECTIVE: Brain dynamic effective connectivity (dEC), characterizes the information transmission patterns between brain regions that change over time, which provides insight into the biological mechanism underlying brain development. However, most existing methods predominantly capture fixed or temporally invariant EC, leaving dEC largely unexplored. METHODS: Herein we propose a deep dynamic causal learning model specifically designed to capture dEC. It includes a dynamic causal learner to detect time-varying causal relationships from spatio-temporal data, and a dynamic causal discriminator to validate these findings by comparing original and reconstructed data. RESULTS: Our model outperforms established baselines in the accuracy of identifying dynamic causalities when tested on the simulated data. When applied to the Philadelphia Neurodevelopmental Cohort, the model uncovers distinct patterns in dEC networks across different age groups. Specifically, the evolution process of brain dEC networks in young adults is more stable than in children, and significant differences in information transfer patterns exist between them. CONCLUSION: This study highlights the brain's developmental trajectory, where networks transition from undifferentiated to specialized structures with age, in accordance with the improvement of an individual's cognitive and information processing capability. SIGNIFICANCE: The proposed model consists of the identification and verification of dynamic causality, utilizing the spatio-temporal fusing information from fMRI. As a result, it can accurately detect dEC and characterize its evolution over age.

3.
Adv Sci (Weinh) ; : e2404628, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981022

ABSTRACT

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%-80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c-Myc, further promoting the stability of c-Myc via deacetylation-mediated inhibition of K48-linked ubiquitylation. Stably expressed c-Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p-AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD-L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c-Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

4.
Hum Brain Mapp ; 45(10): e26774, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38949599

ABSTRACT

Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.


Subject(s)
Magnetoencephalography , Memory, Short-Term , Testosterone , Humans , Male , Memory, Short-Term/physiology , Female , Adolescent , Child , Brain/physiology , Saliva/chemistry , Saliva/metabolism , Brain Mapping , Sex Characteristics
6.
Front Cell Infect Microbiol ; 14: 1364545, 2024.
Article in English | MEDLINE | ID: mdl-38868299

ABSTRACT

Introduction: Gestational diabetes mellitus (GDM) is a form of gestational diabetes mellitus characterized by insulin resistance and abnormal function of pancreatic beta cells. In recent years, genomic association studies have revealed risk and susceptibility genes associated with genetic susceptibility to GDM. However, genetic predisposition cannot explain the rising global incidence of GDM, which may be related to the increased influence of environmental factors, especially the gut microbiome. Studies have shown that gut microbiota is closely related to the occurrence and development of GDM. This paper reviews the relationship between gut microbiota and the pathological mechanism of GDM, in order to better understand the role of gut microbiota in GDM, and to provide a theoretical basis for clinical application of gut microbiota in the treatment of related diseases. Methods: The current research results on the interaction between GDM and gut microbiota were collected and analyzed through literature review. Keywords such as "GDM", "gut microbiota" and "insulin resistance" were used for literature search, and the methodology, findings and potential impact on the pathophysiology of GDM were systematically evaluated. Results: It was found that the composition and diversity of gut microbiota were significantly associated with the occurrence and development of GDM. Specifically, the abundance of certain gut bacteria is associated with an increased risk of GDM, while other changes in the microbiome may be associated with improved insulin sensitivity. In addition, alterations in the gut microbiota may affect blood glucose control through a variety of mechanisms, including the production of short-chain fatty acids, activation of inflammatory pathways, and metabolism of the B vitamin group. Discussion: The results of this paper highlight the importance of gut microbiota in the pathogenesis of GDM. The regulation of the gut microbiota may provide new directions for the treatment of GDM, including improving insulin sensitivity and blood sugar control through the use of probiotics and prebiotics. However, more research is needed to confirm the generality and exact mechanisms of these findings and to explore potential clinical applications of the gut microbiota in the management of gestational diabetes. In addition, future studies should consider the interaction between environmental and genetic factors and how together they affect the risk of GDM.


Subject(s)
Diabetes, Gestational , Gastrointestinal Microbiome , Insulin Resistance , Diabetes, Gestational/microbiology , Humans , Pregnancy , Female , Probiotics , Bacteria/classification , Bacteria/genetics
7.
ACS Omega ; 9(23): 24998-25013, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38882067

ABSTRACT

The focus of exploration geochemistry is an accurate interpretation of geochemical data and the precise extraction of anomaly information related to mineralization from complex geological information. However, geochemical data are component data and exhibit a closure effect. Thus, traditional statistical methods cannot adequately reveal and identify the distribution of deep-seated anomaly information. This paper focuses on the Sidaowanzi area in Inner Mongolia and uses multivariate component data analysis methods to process 1:50 000 soil geochemical data. Using the Exploratory Data Analysis (EDA) method, the spatial distribution and internal structure characteristics of raw, logarithmic, and isometric logarithmic ratio (ILR) transformed data were compared and, coupled with robust principal component analysis (RPCA) and elemental component biplots, the association between element combinations and mineralization indicated by these three types of data was revealed. The S-A method was used to decompose composite anomalies of the ILR transformed RPCA score data to extract the characteristics of elemental combination anomalies and background distribution, and the Fry analysis method was utilized to analyze the dominant mineralization direction within the area. The results show that (1) data transformed using the ILR eliminated the influence of the closure effect, making the data more uniform on a spatial scale and exhibiting characteristics of an approximately normal distribution. (2) The S-A method was further used to decompose the composite anomaly of the PC1 and PC2 principal component combinations. The screened-out anomaly and background fields can essentially reflect the ore-causing anomalies dominated by Au and Cu-Mo mineralization. Moreover, the extracted anomalies and background information closely align with known mineral deposits (prospects) and can effectively identify weakly retarded geochemical anomaly information. (3) Fry analysis based on geochemical anomalies indicates that the dominant mineralization directions, by an assemblage dominated by Au and Cu-Mo, predominantly occur in the NE, NW, and proximate EW orientations. The combined application of the aforementioned three methods for the quantitative analysis of geochemical data aims to explore a transferable methodological system, providing new insights and approaches for further prediction of mineralization potential.

8.
Heliyon ; 10(11): e31746, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38828287

ABSTRACT

Initial indications propose that repetitive transcranial magnetic stimulation (rTMS) could mitigate clinical manifestations in patients with autism spectrum disorder (ASD). Nevertheless, the precise mechanisms responsible for these therapeutic and behavioral outcomes remain elusive. We examined alterations in effective connectivity induced by rTMS using concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) in children with ASD. TMS-EEG data were acquired from 12 children diagnosed with ASD both before and following rTMS treatment. The rTMS intervention regimen included delivering 5-s trains at a frequency of 15 Hz, with 10-min intervals between trains, targeting the left parietal lobe. This was conducted on each consecutive weekday over 3 weeks, totaling 15 sessions. The dynamic EEG network analysis revealed that following the rTMS intervention, long-range feedback connections within the brains of ASD patients were strengthened (e.g., frontal to parietal regions, frontal to occipital regions, and frontal to posterior temporal regions), and short-range connections were weakened (e.g., between the bilateral occipital regions, and between the occipital and posterior temporal regions). In alignment with alterations in network connectivity, there was a corresponding amelioration in fundamental ASD symptoms, as assessed through clinical scales post-treatment. According to our findings, people with ASD may have increased long-range frontal-posterior feedback connection on application of rTMS to the parietal lobe.

9.
Cogn Neurodyn ; 18(3): 893-906, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38826664

ABSTRACT

Mental subtraction, involving numerical processing and operation, requires a complex interplay among several brain regions. Diverse studies have utilized scalp electroencephalograph, electrocorticogram, or functional magnetic resonance imaging to resolve the structure pattern and functional activity during subtraction operation. However, a high resolution of the spatial-temporal understanding of the neural mechanisms involved in mental subtraction is unavailable. Thus, this study obtained intracranial stereoelectroencephalography recordings from 20 patients with pharmacologically resistant epilepsy. Specifically, two sample-delayed mismatch paradigms of numeric comparison and subtracting results comparison were used to help reveal the time frame of mental subtraction. The brain sub-regions were chronologically screened using the stereoelectroencephalography recording for mental subtraction. The results indicated that the anterior cortex, containing the frontal, insular, and parahippocampous, worked for preparing for mental subtraction; moreover, the posterior cortex, such as parietal, occipital, limbic, and temporal regions, cooperated during subtraction. Especially, the gamma band activities in core regions within the parietal-cingulate-temporal cortices mediated the critical mental subtraction. Overall, this research is the first to describe the spatiotemporal activities underlying mental subtraction in the human brain. It provides a comprehensive insight into the cognitive control activity underlying mental arithmetic. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09937-z.

10.
Brain Res Bull ; 215: 111018, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38908759

ABSTRACT

PURPOSE: To explore the utility of high frequency oscillations (HFO) and long-range temporal correlations (LRTCs) in preoperative assessment of epilepsy. METHODS: MEG ripples were detected in 59 drug-resistant epilepsy patients, comprising 5 with parietal lobe epilepsy (PLE), 21 with frontal lobe epilepsy (FLE), 14 with lateral temporal lobe epilepsy (LTLE), and 19 with mesial temporal lobe epilepsy (MTLE) to identify the epileptogenic zone (EZ). The results were compared with clinical MEG reports and resection area. Subsequently, LRTCs were quantified at the source-level by detrended fluctuation analysis (DFA) and life/waiting -time at 5 bands for 90 cerebral cortex regions. The brain regions with larger DFA exponents and standardized life-waiting biomarkers were compared with the resection results. RESULTS: Compared to MEG sensor-level data, ripple sources were more frequently localized within the resection area. Moreover, source-level analysis revealed a higher proportion of DFA exponents and life-waiting biomarkers with relatively higher rankings, primarily distributed within the resection area (p<0.01). Moreover, these two LRCT indices across five distinct frequency bands correlated with EZ. CONCLUSION: HFO and source-level LRTCs are correlated with EZ. Integrating HFO and LRTCs may be an effective approach for presurgical evaluation of epilepsy.

11.
Plant Commun ; : 100999, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38853433

ABSTRACT

Grain weight, a key determinant of yield in rice (Oryza sativa L.), is governed primarily by genetic factors, whereas grain chalkiness, a detriment to grain quality, is intertwined with environmental factors such as mineral nutrients. Nitrogen (N) is recognized for its impact on grain chalkiness, yet the underlying molecular mechanisms remain elusive. This study revealed the pivotal role of rice NODULE INCEPTION-LIKE PROTEIN 3 (OsNLP3) in simultaneously regulating grain weight and grain chalkiness. Our investigation showed that the loss of OsNLP3 leads to a reduction in both grain weight and dimension, in contrast to the enhancement observed with OsNLP3 overexpression. OsNLP3 directly suppresses the expression of OsCEP6.1 and OsNF-YA8, which were identified as negative regulators associated with grain weight. Consequently, two novel regulatory modules, OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8, were identified as key players in grain weight regulation. Notably, the OsNLP3-OsNF-YA8 module not only augments grain weight but also mitigates grain chalkiness in response to N. This research clarifies the molecular mechanisms orchestrating grain weight through the OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8 modules, underscoring the pivotal role of the OsNLP3-OsNF-YA8 module in alleviating grain chalkiness. These findings offer potential targets for concurrently enhancing rice yield and quality.

13.
Endocrine ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849645

ABSTRACT

PURPOSE: No study has comprehensively assessed the relationship of metabolic factors including insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia with the development of carotid plaque. Therefore, we constructed metabolic scores based on the above metabolic factors and examined its association with carotid plaque in young and older Chinese adults. METHODS: This study included 17,396 participants who underwent carotid ultrasound examinations, including 14,173 young adults (<65 years) and 3,223 older adults (≥65 years). Individual metabolic score was calculated using triglyceride-glucose (TyG) index, mean arterial pressure (MAP), uric acid, and total cholesterol (TC). Logistic regression models were conducted to examine the role of metabolic score and its components in the prevalence of carotid plaque. The nonlinear relationship was examined using restricted cubic spline regression. Meanwhile, subgroup, interaction, and sensitivity analyses were conducted. RESULTS: The multivariate logistic regression analysis showed that TyG (OR: 1.088; 95%CI: 1.046-1.132), MAP (OR: 1.121; 95%CI: 1.077-1.168), TC (OR: 1.137; 95%CI: 1.094-1.182) and metabolic score (OR: 1.064; 95%CI: 1.046-1.082) were associated with carotid plaque prevalence in young adults rather than older adults. The nonlinear association was not observed for metabolic scores and carotid plaque. Subgroup analyses showed significant associations between metabolic scores and carotid plaque prevalence in men, women, normal-weight, and overweight young adults. No interaction of metabolic score with sex and BMI were observed. CONCLUSIONS: The results support that control of TyG, MAP, TC, and metabolic scores is a key point in preventing the prevalence of carotid plaque in the young adults.

14.
Arch Gerontol Geriatr ; 126: 105525, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38896974

ABSTRACT

OBJECTIVE: Genetic risks can accelerate ageing, yet better quality sleep may slow down it. We thus examined the interaction and combined effects of genetic predisposition and sleep quality on the risk of accelerate aging. METHODS: This study included 407,027 participants from the UK Biobank. Sleep index of each participant was retrieved from the following seven sleep behaviors: snoring, chronotype, daytime sleepiness, sleep duration, insomnia, nap and difficulties in getting up. The biological age (PhenoAge) were estimated by corresponding algorithms based on clinical traits, and their residual discrepancies with chronological age were defined as the age accelerations (PhenoAgeaccel). We explored the interaction and combined effects of genetic risk and sleep quality on accelerated ageing by constructing a linear model. RESULTS: Compared with participants in low sleep quality group, those in medium and high sleep quality group decreased 0.727 (95%CI, 0.653 to 0.801) and 1.056 (95%CI, 0.982 to 1.130) years of PhenoAgeaccel, respectively. Compared with participants in low genetic risk group, those in medium and high genetic risk group increased 0.833 (95%CI, 0.792 to 0.874) and 1.543 (95%CI, 1.494 to 1.592) years of PhenoAgeaccel, respectively. There was interaction between the genetic risk and sleep quality (P-interaction<0.001). For combined effect, compared to the group with high sleep quality and lower genetic risk, people with low sleep quality and high genetic risk had 2.747 (95%CI, 2.602 to 2.892) years higher PhenoAgeaccel. CONCLUSION: Our findings elucidate that better sleep quality could lessen accelerated biological ageing especially among population with high genetic risk.

15.
Dev Cogn Neurosci ; 67: 101385, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38713999

ABSTRACT

INTRODUCTION: The human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan. Developmental studies of the cerebellar anatomy and function are scant. We examine age-dependent MRI morphometry of the anterior cerebellar vermis, lobules I-V and posterior neocortical lobules VI-VII and their relationship to sensorimotor and cognitive functions. METHODS: Typically developing children (TDC; n=38; age 9-15) and healthy adults (HAC; n=31; 18-40) participated in high-resolution MRI. Rigorous anatomically informed morphometry of the vermis lobules I-V and VI-VII and total brain volume (TBV) employed manual segmentation computer-assisted FreeSurfer Image Analysis Program [http://surfer.nmr.mgh.harvard.edu]. The neuropsychological scores (WASI-II) were normalized and related to volumes of anterior, posterior vermis, and TBV. RESULTS: TBVs were age independent. Volumes of I-V and VI-VII were significantly reduced in TDC. The ratio of VI-VII to I-V (∼60%) was stable across age-groups; I-V correlated with visual-spatial-motor skills; VI-VII with verbal, visual-abstract and FSIQ. CONCLUSIONS: In TDC neither anterior I-V nor posterior VI-VII vermis attained adult volumes. The "inverted U" developmental trajectory of gray matter peaking in adolescence does not explain this finding. The hypothesis of protracted development of oligodendrocyte/myelination is suggested as a contributor to TDC's lower cerebellar vermis volumes.


Subject(s)
Cerebellar Vermis , Cognition , Magnetic Resonance Imaging , Humans , Adolescent , Child , Female , Male , Magnetic Resonance Imaging/methods , Cognition/physiology , Adult , Young Adult , Cerebellar Vermis/diagnostic imaging , Cerebellum/diagnostic imaging , Cerebellum/anatomy & histology
16.
Front Endocrinol (Lausanne) ; 15: 1371220, 2024.
Article in English | MEDLINE | ID: mdl-38737551

ABSTRACT

Background and objective: Aberrant epigenetic regulation and increased oxidative stress in the placenta play a significant role in placental pathophysiology and fetal programming in preeclampsia, a hypertensive disorder in human pregnancy. The purpose of the study is to investigate if hypermethylation of histone H3K9 occurs in placental trophoblasts from preeclampsia. Methods: Trophoblasts were isolated and cultured from 14 placentas, 7 from normotensive pregnant women and 7 from preeclamptic pregnancies. Methylated H3K9 expression and antioxidant superoxide dismutase expression were determined by Western blot. We also examined consequences of oxidative stress and the downstream effects of histone methyltransferase inhibition on H3K9 expression associated with antioxidant CuZn-SOD and Mn-SOD expression in placental trophoblasts. Results: We found that expression of mono-, di-, and tri-methylation of histone H3 lysine 9 (H3K9me1, H3K9me2 and H3K9me3) was significantly increased, p<0.01, which correlated with downregulation of antioxidant superoxide dismutase CuZn-SOD and Mn-SOD expression, in trophoblasts from preeclamptic placentas compared to those from uncomplicated control placentas. We further demonstrated hypoxia could promote histone H3K9 methylation in placental trophoblasts, and hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression was reversible when hypoxic condition was removed. In addition, we also uncovered that inhibition of methyltransferase not only prevented hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression, but also abolished hypoxia-induced downregulation of CuZn-SOD and Mn-SOD expression in placental trophoblasts. Conclusions: These findings are noteworthy and provide further evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in placental trophoblasts in preeclampsia. Moreover, CuZn-SOD and Mn-SOD expression/activity are possibly H3K9 methylation-dependent in placental trophoblasts, which further suggest that oxidative stress and aberrant histone modification have significant impact on placental trophoblasts/fetal programming in preeclampsia.


Subject(s)
Histones , Oxidative Stress , Placenta , Pre-Eclampsia , Trophoblasts , Humans , Female , Pre-Eclampsia/metabolism , Pre-Eclampsia/genetics , Pre-Eclampsia/pathology , Pregnancy , Trophoblasts/metabolism , Histones/metabolism , Adult , Placenta/metabolism , Methylation , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , DNA Methylation , Cells, Cultured , Lysine/metabolism
17.
J Glob Antimicrob Resist ; 38: 83-89, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38719186

ABSTRACT

OBJECTIVES: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. METHODS: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. RESULTS: In total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. CONCLUSIONS: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment.

18.
Arab J Gastroenterol ; 25(2): 194-204, 2024 May.
Article in English | MEDLINE | ID: mdl-38705811

ABSTRACT

BACKGROUND AND STUDY AIMS: Immunotherapy has emerged as a hot topic in cancer treatment in recent years and has also shown potential in the treatment of Helicobacter pylori-associated gastric cancer. However, there is still a need to identify potential immunotherapy targets. MATERIAL AND METHODS: We used the GSE116312 dataset of Helicobacter pylori-associated gastric cancer to identify differentially expressed genes, which were then overlapped with immune genes from the ImmPort database. The identified immune genes were used to classify gastric cancer samples and evaluate the relationship between classification and tumor mutations, as well as immune infiltration. An immune gene-based prognostic model was constructed, and the expression levels of the genes involved in constructing the model were explored in the tumor immune microenvironment. RESULTS: We successfully identified 60 immune genes and classified gastric cancer samples into two subtypes, which showed differences in prognosis, tumor mutations, immune checkpoint expression, and immune cell infiltration. Subsequently, we constructed an immune prognostic model consisting of THBS1 and PDGFD, which showed significant associations with macrophages and fibroblasts. CONCLUSION: We identified abnormal expression of THBS1 and PDGFD in cancer-associated fibroblasts (CAFs) within the tumor immune microenvironment, suggesting their potential as therapeutic targets.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Platelet-Derived Growth Factor , Stomach Neoplasms , Thrombospondin 1 , Tumor Microenvironment , Stomach Neoplasms/microbiology , Stomach Neoplasms/immunology , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Humans , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Helicobacter pylori/immunology , Helicobacter pylori/genetics , Helicobacter Infections/immunology , Helicobacter Infections/complications , Thrombospondin 1/genetics , Prognosis , Platelet-Derived Growth Factor/genetics , Platelet-Derived Growth Factor/metabolism , Cancer-Associated Fibroblasts/immunology , Cancer-Associated Fibroblasts/metabolism , Mutation , Lymphokines
19.
ArXiv ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38800653

ABSTRACT

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

20.
Anal Methods ; 16(23): 3766-3773, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38818642

ABSTRACT

5-Hydroxymethylfurfural (5-HMF) is a heterocyclic compound with six carbons commonly found in heat-treated carbohydrate-rich foods. 5-HMF exceeding the specified limit is cytotoxic to the human body, and will be converted into carcinogenic substances (5-sulfoxide methyl furfural) after long-term accumulation in the body. Therefore, it is highly necessary to develop a sensitive and accurate detection method for 5-HMF in the field of food safety. In this study, a photoelectric sensing method was developed for the highly sensitive detection of 5-HMF using hollow TiO2 nanospheres successfully synthesized by template, sol-gel and lye etching methods. The structure and composition of the materials were studied by XRD, XPS, SEM and TEM. The electrochemical and photoelectrochemical properties of an h-TiO2 electrode probe based on indium tin oxide (ITO) slides were investigated. The results indicated that the linear relationship of 5-HMF is good in the concentration range of 10-11-10-7 M, and the detection limit of 5-HMF is 0.001 nM. Moreover, the PEC sensor shows high accuracy in the detection of actual samples.

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