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1.
Clin Lab ; 70(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38965970

ABSTRACT

BACKGROUND: In this study, we aimed to identify the hub genes responsible for increased vascular endothelial cell permeability. METHODS: We applied the weighted Gene Expression Omnibus (GEO) database to mine dataset GSE178331 and ob-tained the most relevant high-throughput sequenced genes for an increased permeability of vascular endothelial cells due to inflammation. We constructed two weighted gene co-expression network analysis (WGCNA) networks, and the differential expression of high-throughput sequenced genes related to endothelial cell permeability were screened from the GEO database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the differential genes. Their degree values were obtained from the topological properties of protein-protein interaction (PPI) networks of differential genes, and the hub genes associated with an increased endothelial cell permeability were analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting techniques were used to detect the presence of these hub genes in TNF-α induced mRNA and the protein expression in endothelial cells. RESULTS: In total, 1,475 differential genes were mainly enriched in the cell adhesion and TNF-α signaling pathway. With TNF-α inducing an increase in the endothelial cell permeability and significantly increasing mRNA and protein expression levels, we identified three hub genes, namely PTGS2, ICAM1, and SNAI1. There was a significant difference in the high-dose TNF-α group and in the low-dose TNF-α group compared to the control group, in the endothelial cell permeability experiment (p = 0.008 vs. p = 0.02). Measurement of mRNA and protein levels of PTGS2, ICAM1, and SNAI1 by western blotting analysis showed that there was a significant impact on TNF-α and that there was a significant dose-dependent relationship (p < 0.05 vs. p < 0.01). CONCLUSIONS: The three hub genes identified through bioinformatics analyses in the present study may serve as biomarkers of increased vascular endothelial cell permeability. The findings offer valuable insights into the progress and mechanism of vascular endothelial cell permeability.


Subject(s)
Computational Biology , Endothelial Cells , Gene Regulatory Networks , Protein Interaction Maps , Tumor Necrosis Factor-alpha , Humans , Computational Biology/methods , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Endothelial Cells/metabolism , Gene Expression Profiling/methods , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Capillary Permeability , Signal Transduction , Databases, Genetic , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Snail Family Transcription Factors/genetics , Snail Family Transcription Factors/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Gene Ontology
2.
Colloids Surf B Biointerfaces ; 239: 113963, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38759294

ABSTRACT

Among various biomimetic polymer materials, polydimethylsiloxane (PDMS) stands out as an ideal matrix for surface-enhanced Raman scattering (SERS) due to its unique intrinsic Raman signal and tenacity. In order to realize the precise detection of prostate-specific antigen (PSA), we proposed a sandwich-type SERS-active immunostructure composed of PDMS@silver nanoparticles (Ag NPs)@ZIF-67 biomimetic film as the immunosubstrate and gold nanorods (Au NRs) as immunoprobes. Due to the synergistic effect of electromagnetic enhancement facilitated by biomimetic surfaces and chemical enhancement achieved by ZIF-67, this structure enabled an ultrasensitive and selective detection of PSA across a broad range from 10-3 to 10-9 mg/mL. The achieved limit of detection was as low as 3.0 × 10-10 mg/mL. Particularly, the intrinsic Raman signal of PDMS matrix at 2905 cm-1 was employed as a potential internal standard (IS) in the detection, achieving a high coefficient of determination (R2) value of 0.996. This multifunctional SERS substrate-mediated immunoassay holds vast potential for early diagnosis of prostate cancer, offering promising prospects for clinical applications.


Subject(s)
Dimethylpolysiloxanes , Metal Nanoparticles , Prostate-Specific Antigen , Silver , Spectrum Analysis, Raman , Silver/chemistry , Spectrum Analysis, Raman/methods , Immunoassay/methods , Prostate-Specific Antigen/analysis , Metal Nanoparticles/chemistry , Dimethylpolysiloxanes/chemistry , Humans , Gold/chemistry , Biomimetic Materials/chemistry , Surface Properties , Limit of Detection , Nanotubes/chemistry , Male , Particle Size , Imidazoles , Zeolites
3.
Front Biosci (Landmark Ed) ; 29(5): 178, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38812302

ABSTRACT

The Warburg effect, also called aerobic glycolysis, refers to tumor cells that metabolize glucose through glycolysis even in the presence of oxygen. This rapid breakdown of glucose fuels the fast development, growth, and migration of tumor cells. Lactate, the final product of aerobic glycolysis, contributes to an acidic environment within the tumor, promoting the formation of an immunosuppressive microenvironment and accelerating tumor progression by impeding anti-tumor immunity. Numerous studies have confirmed the critical role of aerobic glycolysis in the occurrence and development of hepatocellular carcinoma by influencing tumor cells proliferation, invasion, metastasis, apoptosis, immune escape, angiogenesis, and more. Clinical trials have shown that inhibitors of rate-limiting enzymes in the glycolysis pathway can enhance the effectiveness of sorafenib, a targeted drug for hepatocellular carcinoma, by reducing drug resistance. Additionally, active components of traditional Chinese medicine and specific compound prescriptions are gaining attention for their potential to target and regulate aerobic glycolysis in hepatocellular carcinoma. Therefore, inhibiting the aerobic glycolysis pathway holds promise as a therapeutic strategy for treating liver tumors. This manuscript aims to review the role, research directions, and clinical studies of aerobic glycolysis in hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Warburg Effect, Oncologic , Humans , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Glycolysis , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Animals
4.
Geriatr Nurs ; 57: 224-231, 2024.
Article in English | MEDLINE | ID: mdl-38696880

ABSTRACT

The factors that affect resident satisfaction with emerging residential integrated care for older people in China have been unclear due to a lack of validated instruments. Based on psychometric assessment procedures, we developed a new scale for older resident satisfaction with residential integrated care (SORSRIC). The scale was developed using a two-step process and a sample of 16 Chinese institutions and 333 residents. Exploratory and confirmatory factor analysis was used to evaluate reliability and validity. Principal component analysis and maximum variance methods were used to orthogonally rotate the items to extract seven factors. These were: resident expectations, perceived quality (physical care), perceived quality (mental care), perceived value, resident satisfaction, resident complaints, and resident loyalty. The CR value of each dimension of the pre-tested, formal scale was greater than 0.80, and the AVE value was greater than 0.50. This 24-item instrument showed good reliability and structural validity and can be applied to improve the experience and outcomes for older people in residential care.


Subject(s)
Psychometrics , Humans , China , Male , Female , Aged , Reproducibility of Results , Surveys and Questionnaires , Patient Satisfaction , Aged, 80 and over
5.
Opt Express ; 32(6): 9837-9846, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38571208

ABSTRACT

Obstruction is inevitable and will significantly impact the actual output performance of photovoltaic modules, even jeopardize their operational safety. We introduced a layer of bubbles into photovoltaic glass. These bubbles can alter the path of incident light, while the internal reflection at the glass/air interface enables the redirected light rays to have longer lateral propagation distance, circumventing the obstructions. The optimized photovoltaic glass with a bubble diameter of 1.8 mm and a surface density of 16 cm-2 enables the light intensity underneath a 6.6 × 6.6 cm2 obstruction to reach 21.83% of the incident light intensity. This enhancement permits a partial shading of the photovoltaic module, increasing its output power by ∼20.8% and decreasing the reverse bias voltage on the shaded cell by ∼1.4 V.

6.
Adv Sci (Weinh) ; 11(23): e2402509, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38590132

ABSTRACT

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.


Subject(s)
Biomarkers, Tumor , Extracellular Vesicles , Histones , Prostatic Neoplasms , Proteomics , Humans , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Male , Proteomics/methods , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/urine , Extracellular Vesicles/metabolism , Histones/metabolism , Risk Assessment/methods , Middle Aged , Aged , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Laminin
7.
BMJ Open ; 14(4): e076107, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38604638

ABSTRACT

OBJECTIVES: Clinical practice guideline (CPG) developers conduct systematic summaries of research evidence, providing them great capacity and ability to identify research priorities. We systematically analysed the reporting form and content of research priorities in CPGs related to knee osteoarthritis (KOA) to provide a valuable reference for guideline developers and clinicians. DESIGN: A methodological literature analysis was done and the characteristics of the reporting form and the content of the research priorities identified in KOA CPGs were summarised. DATA SOURCES: Six databases (PubMed, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang and Chinese Biomedical Literature Database) were searched for CPGs published from 1 January 2017 to 4 December 2022. The official websites of 40 authoritative orthopaedic societies, rheumatology societies and guideline development organisations were additionally searched. ELIGIBILITY CRITERIA: We included all KOA CPGs published in English or Chinese from 1 January 2017 that included at least one recommendation for KOA. We excluded duplicate publications, older versions of CPGs as well as guidance documents for guideline development. DATA EXTRACTION AND SYNTHESIS: Reviewers worked in pairs and independently screened and extracted the data. Descriptive statistics were used, and absolute frequencies and proportions of related items were calculated. RESULTS: 187 research priorities reported in 41 KOA CPGs were identified. 24 CPGs reported research priorities, of which 17 (41.5%) presented overall research priorities for the entire guideline rather than for specific recommendations. 110 (58.8%) research priorities were put forward due to lack of evidence. Meanwhile, more than 70% of the research priorities reflected the P (population) and I (intervention) structural elements, with 135 (72.2%) and 146 (78.1%), respectively. More than half of the research priorities (118, 63.8%) revolved around evaluating the efficacy of interventions. Research priorities primarily focused on physical activity (32, 17.3%), physical therapy (30, 16.2%), surgical therapy (27, 14.6%) and pharmacological treatment (26, 14.1%). CONCLUSIONS: Research priorities reported in KOA CPGs mainly focused on evaluating non-pharmacological interventions. There exists considerable room for improvement for a comprehensive and standardised generation and reporting of research priorities in KOA CPGs.


Subject(s)
Orthopedics , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/therapy , Publications , Research , Practice Guidelines as Topic
8.
Eur J Pharm Biopharm ; 199: 114281, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38599299

ABSTRACT

Nattokinase (NK) is a thrombolytic enzyme extracted from natto, which can be used to prevent and treat blood clots. However, it is sensitive to the environment, especially the acidic environment of human stomach acid, and its effect of oral ingestion is minimal. This study aims to increase NK's oral and storage stability by embedding NK in microcapsules prepared with chitosan (CS) and γ-polyglutamic acid (γ-PGA). The paper prepared a double-layer NK oral delivery system by layer self-assembly and characterized its stability and in vitro simulated digestion. According to the research results, the bilayer putamen structure has a protective effect on NK, which not only maintains high activity in various environments (such as acid-base, high temperature) and long-term storage (60 days), but also effectively protects the loaded NK from being destroyed in gastric fluid and achieves its slow release. This work has proved the feasibility of the design of bilayer putamen structure in oral administration and has good fibrolytic activity. Therefore, the novel CS/γ-PGA microcapsules are expected to be used in nutraceutical delivery systems.


Subject(s)
Chitosan , Drug Stability , Fibrinolytic Agents , Polyglutamic Acid , Subtilisins , Chitosan/chemistry , Polyglutamic Acid/chemistry , Polyglutamic Acid/analogs & derivatives , Subtilisins/metabolism , Subtilisins/chemistry , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/pharmacology , Administration, Oral , Humans , Digestion/drug effects , Capsules , Drug Delivery Systems/methods , Drug Compounding/methods , Drug Liberation , Drug Carriers/chemistry
9.
PLoS One ; 19(3): e0300841, 2024.
Article in English | MEDLINE | ID: mdl-38517858

ABSTRACT

OBJECTIVES: To compared the presentation of research priorities in the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) clinical practice guidelines (CPGs) developed under the guidance of the GRADE working group or its two co-chair, and the Chinese CPGs. METHODS: This was a methodological empirical analysis. We searched PubMed, Embase, and four Chinese databases (Wanfang, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure and Chinese Biomedical Literature Database) and retrieved nine Chinese guideline databases or Society websites as well as GRADE Pro websites. We included all eligible GRADE CPGs and a random sample of double number of Chinese CPGs, published 2018 to 2022. The reviewers independently screened and extracted the data, and we summarized and analyzed the reporting on the research priorities in the CPGs. RESULTS: Of the 135 eligible CPGs (45 GRADE CPGs and 90 Chinese CPGs), 668, 138 research priorities were identified respectively. More than 70% of the research priorities in GRADE CPGs and Chinese CPGs had population and intervention (PI) structure. 99 (14.8%) of GRADE CPG research priorities had PIC structures, compared with only 4(2.9%) in Chinese. And 28.4% (190) GRADE CPG research priorities reflected comparisons between PICO elements, approximately double those in Chinese. The types of research priorities among GRADE CPGs and Chinese CPGs were mostly focused on the efficacy of interventions, and the type of comparative effectiveness in the GRADE research priorities was double those in Chinese. CONCLUSIONS: There was still considerable room for improvement in the developing and reporting of research priorities in Chinese CPGs. Key PICO elements were inadequately presented, with more attention on intervention efficacy and insufficient consideration given to values, preferences, health equity, and feasibility. Identifying and reporting of research priorities deserves greater effort in the future.


Subject(s)
Publications , Research Design , Humans , China , Databases, Factual
10.
BMC Geriatr ; 24(1): 243, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468239

ABSTRACT

BACKGROUND: With the growing challenge of an aging population, emerging technologies are increasingly being integrated into the production, organization, and delivery of aged care services. Geographic Information System (GIS), a computer-based tool for spatial information analysis and processing, has made significant strides in the allocation of care recources and service delivery for older adults, a notably vulnerable group. Despite its growing importance, cross-disciplinary literature reviews on this theme are scare. This scoping review was conducted to encapsulate the advancements and discern the future trajectory of GIS applications in aged care services. METHODS: A comprehensive search across nine databases yielded 5941 articles. Adhering to specific inclusion and exclusion criteria, 61 articles were selected for a detailed analysis. RESULTS: The 61 articles span from 2003 to 2022, with a notable increase in publications since 2018, comprising 41 articles (67% of the total) published between 2018-2022. Developed countries contributed 66% of the papers, with 45% focusing on accessibility issues. In the domain of aged care services, GIS has been predominantly utilized for model construction, mapping, and site selection, with a growing emphasis on addressing the unique needs of different subgroups of older adults. CONCLUSION: The past two decades have seen substantial growth in the application of GIS in aged care services, reflecting its increasing importance in this field. This scoping review not only charts the historical development of GIS applications in aged care services but also underscores the need for innovative research approaches. Future directions should emphasize the integration of GIS with diverse methodologies to address the heterogeneous needs of older adults and improve the overall delivery of aged care services. Such advancements in GIS applications have the potential to significantly enhance the efficiency, accessibility, and quality of care for the aging population.


Subject(s)
Geographic Information Systems , Population Groups , Humans , Aged
11.
J Colloid Interface Sci ; 661: 366-373, 2024 May.
Article in English | MEDLINE | ID: mdl-38306746

ABSTRACT

Hydrogels, recognized for their biocompatibility, are extensively employed in the realm of wearable devices. Nevertheless, their application is often constrained by their low mechanical robustness, rendering them susceptible to damage during operation. The restoration of their load-bearing and sensory functionalities post-damage represents a captivating yet underexplored domain. Conventional repair techniques, reliant on hydrogen bonding or van der Waals forces, falter in the face of hydrogels' high water content. In this study, a novel composite adhesive gel (SGG), integrating sodium alginate, guar gum, and graphene oxide, was engineered to mend impaired hydrogels. Furthermore, an optimized repair approach, utilizing a cross-shaped sectional (CSS) enhancement strategy, was devised to reinstate the hydrogels' load and sensory capabilities. Investigations revealed that the SGG adhesive infiltrated the hydrogel, establishing an intermediary gel stratum, subsequently solidifying to mend the material through topological adhesion. This process reestablished the continuity of the polymer network and the aqueous phase within the hydrogel. Following the application of the CSS augmentation method, the peak tensile strain of the remediated hydrogel exceeded 200 %, with the uppermost observable adhesive energy touching 2526 J/m2. In addition, the ability to respond to strain was significantly rejuvenated, suggesting an effective methodology for the rehabilitation of wearable technology.


Subject(s)
Alginates , Hydrogels , Physical Phenomena , Hydrogen Bonding , Polymers , Electric Conductivity
13.
BMC Complement Med Ther ; 24(1): 19, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178118

ABSTRACT

BACKGROUND: The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs. METHODS: This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018-2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs. RESULTS: Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation. CONCLUSIONS: The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized.


Subject(s)
Integrative Medicine , Medicine, Chinese Traditional , China , Databases, Factual
14.
Health Commun ; : 1-15, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37919837

ABSTRACT

The internet has revolutionized how we live, providing unprecedented convenience and up-to-date information. Consequently, an increasing number of individuals are turning to the internet for health-related information, despite research suggesting a correlation between this behavior and health anxiety. Therefore, drawing on cognitive - behavioral theory, we explore the link between online health information seeking and health anxiety via a systematic review and meta-analysis of cross-sectional studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis, we ran searches in multiple databases, including PubMed, Web of Science, Embase, Elsevier/Science Direct, Cochrane Database, China National Knowledge Infrastructure, VIP Chinese Database, and Wanfang Data. Our searches identified 16 studies eligible for review, involving 4,920 participants across seven countries. The random-effects meta-analysis revealed a significant positive correlation between online health information seeking and health anxiety (r = 0.28, 95% confidence interval [0.16, 0.41], p < .0001), despite considerable heterogeneity. Furthermore, meta-regression analysis demonstrated that the identity characteristics of the sample, female percentage, sample size, and country all contributed to the heterogeneity across studies. Overall, this meta-analysis provides support for the association between online health information seeking and health anxiety, and helps to elucidate the cognitive - behavioral theory underpinning this phenomenon.

15.
Chem Commun (Camb) ; 60(1): 59-62, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-37987536

ABSTRACT

We investigate the dynamic degradation behaviors of a nickel-copper-molybdenum hydrogen evolution catalyst in a liquid and solid polymer electrolyte to figure out its endurance in a renewable energy-driven electrolyzer. A cathode current protection approach is proposed to achieve a durable electrolyzer during intermittent operation.

16.
Nat Protoc ; 18(10): 2975-2997, 2023 10.
Article in English | MEDLINE | ID: mdl-37670036

ABSTRACT

Structural DNA nanotechnology can be programmed into complex designer structures with molecular precision for directing a wide range of inorganic and biological materials. However, the use of DNA-templated approaches for the fabrication and performance requirements of ultra-scaled semiconductor electronics is limited by its assembly disorder and destructive interface composition. In this protocol, using carbon nanotubes (CNTs) as model semiconductors, we provide a stepwise process to build ultra-scaled, high-performance field-effect transistors (FETs) from micron-scale three-dimensional DNA templates. We apply the approach to assemble CNT arrays with uniform pitches scaled between 24.1 and 10.4 nm with yields of more than 95%, which exceeds the resolution limits of conventional lithography. To achieve highly clean CNT interfaces, we detail a rinsing-after-fixing step to remove residual DNA template and salt contaminations present around the contact and the channel regions, without modifying the alignment of the CNT arrays. The DNA-templated CNT FETs display both high on-state current (4-15 µA per CNT) and small subthreshold swing (60-100 mV per decade), which are superior to previous examples of biotemplated electronics and match the performance metrics of high-performance, silicon-based electronics. The scalable assembly of defect-free three-dimensional DNA templates requires 1 week and the CNT arrays can be synthesized within half a day. The interface engineering requires 1-2 d, while the fabrication of high-performance FET and logic gate circuits requires 2-4 d. The structural and performance characterizations of molecular-precise DNA self-assembly and high-performance electronics requires 1-2 d. The protocol is suited for users with expertise in DNA nanotechnology and semiconductor electronics.


Subject(s)
Nanotubes, Carbon , Transistors, Electronic , Nanotubes, Carbon/chemistry , Semiconductors , DNA , Electronics
17.
bioRxiv ; 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37693607

ABSTRACT

Copy number losses (deletions) are a major contributor to the etiology of severe genetic disorders. Although haploinsufficient genes play a critical role in deletion pathogenicity, current methods for deletion pathogenicity prediction fail to integrate multiple lines of evidence for haploinsufficiency at the gene level, limiting their power to pinpoint deleterious deletions associated with genetic disorders. Here we introduce DosaCNV, a deep multiple-instance learning framework that, for the first time, models deletion pathogenicity jointly with gene haploinsufficiency. By integrating over 30 gene-level features potentially predictive of haploinsufficiency, DosaCNV shows unmatched performance in prioritizing pathogenic deletions associated with a broad spectrum of genetic disorders. Furthermore, DosaCNV outperforms existing methods in predicting gene haploinsufficiency even though it is not trained on known haploinsufficient genes. Finally, DosaCNV leverages a state-of-the-art technique to quantify the contributions of individual gene-level features to haploinsufficiency, allowing for human-understandable explanations of model predictions. Altogether, DosaCNV is a powerful computational tool for both fundamental and translational research.

18.
Brain Res ; 1819: 148543, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37611887

ABSTRACT

Intermittent exotropia (IXT) is characterizedby an intermittent outward deviation of the eyes. Yet, the neural substrates associated with IXT are not fully understood. This study investigated brain structure and spontaneous functional activity changes in children with IXT. All participants underwent detailed ophthalmological examinations and multimodal magnetic resonance imaging (MRI) scanning. During functional scanning, binocular visual stimuli were presented to subjects to determine brain areas involved in visual and oculomotor processing. Regions of interest(ROI) were subsequently selected based on functional activation to investigate brain structural and spontaneous functional differences between IXT children and healthy controls (HCs) using small volume correction (SVC). Reduced gray matter density (GMD) was found in the right frontal eye field (FEF) and bilateral inferior parietal lobe (IPL) in IXT children compared with HCs. Besides, reduced fractional amplitude of low-frequency fluctuations (fALFF) values were observed in the left lingual gyrus, right inferior occipital gyrus (IOG), bilateral IPL, and bilateral cerebellum in the IXT children compared to the HCs. IXT children with worse eye position control ability exhibited lower GMD and fALFF values in these areas. Finally, resting state functional connectivity (RSFC) was reduced in frontoparietal oculomotor processing areas in IXT children compared to HCs. In addition, increased cortical thickness was found in the right visual areas and bilateral IPL. These results showed that IXT-related structural and functional brain abnormalities occurred in childhood and may be related to underlying neuropathological mechanisms.


Subject(s)
Exotropia , Humans , Child , Exotropia/pathology , Brain , Cerebellum/pathology , Parietal Lobe , Gray Matter , Magnetic Resonance Imaging/methods
19.
Hum Brain Mapp ; 44(15): 5002-5012, 2023 10 15.
Article in English | MEDLINE | ID: mdl-37539805

ABSTRACT

To explore the functional changes of the frontal eye field (FEF) and relevant brain regions and its role in the pathogenesis of intermittent exotropia (IXT) children via functional magnetic resonance imaging (fMRI). Twenty-four IXT children (mean age, 11.83 ± 1.93 years) and 28 normal control (NC) subjects (mean age, 11.11 ± 1.50 years) were recruited. During fMRI scans, the IXT children and NCs were provided with static visual stimuli (to evoke sensory fusion) and dynamic visual stimuli (to evoke motor fusion and vergence eye movements) with binocular disparity. Brain activation in the relevant brain regions and clinical characteristics were evaluated. Group differences of brain activation and brain-behavior correlations were investigated. For dynamic and static visual disparity relative to no visual disparity, reduced brain activation in the right FEF and right inferior occipital gyrus (IOG), and increased brain activation in the left middle temporal gyrus complex (MT+) were found in the IXT children compared with NCs. Significant positive correlations between the fusional vergence amplitude and the brain activation values were found in the right FEF, right IPL, and left cerebellum in the NC group. Positive correlations between brain activation values and Newcastle Control Scores (NCS) were found in the left MT+ in the IXT group. For dynamic visual disparity relative to static visual disparity, reduced brain activation in the right middle occipital gyrus, left cerebellum, and bilateral IPL was found in the IXT children compared with NCs. Significant positive correlations between brain activation values and the fusional vergence amplitude were found in the right FEF and right cerebellum in the NC group. Negative correlations between brain activation values and NCS were found in the right middle occipital gyrus, right cerebellum, left IPL, and right FEF in the IXT group. These results suggest that the reduced brain activation in the right FEF, left IPL, and cerebellum may play an important role in the pathogenesis of IXT by influencing fusional vergence function. While the increased brain activation in the left MT+ may compensate for this dysfunction in IXT children.


Subject(s)
Exotropia , Frontal Lobe , Exotropia/diagnostic imaging , Exotropia/physiopathology , Humans , Child , Adolescent , Magnetic Resonance Imaging , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Brain Mapping
20.
Front Public Health ; 11: 1109981, 2023.
Article in English | MEDLINE | ID: mdl-37427265

ABSTRACT

Background: Home-and community-based integrated care has been developing rapidly in China in recent years. However, empirical research on the demand from older people is insufficient. Most studies have failed to identify or differentiate the heterogeneity of older people, resulting in poor understanding of their needs and fragmentation of services. This study seeks to identify latent classes of demand for home-and community-based integrated care among older Chinese adults and the predictors that differentiate these demands. Methods: From January to March 2021, a questionnaire was administered to older people (aged ≥60 years) in community-based service centers for older people in six districts of Changsha City, Hunan Province. Participants were selected through purposive and incidental sampling. Latent profile analysis was used to categorize older people's demand for home-and community-based integrated care. By extending Andersen's behavioral model of health service use, and running multinomial logistic regression analyses, we explored which factors influenced the latent classes of demand. Results: A total of 382 older people were included in the analyses: 64.4% were women and 33.5% were aged 80-89. The demand from older people for home-and community-based integrated care was classified into four latent classes: high health and social interaction demand (30% - 115/382); high comprehensive demand (23% - 88/382); high care service demand (26% - 100/382), and high social participation and low care demand (21% - 79/382). Taking this last class as the reference group, the other three latent classes differed significantly in the factors of predisposition, enabling, need, and perception of aging. Conclusion: The demand from older people for home-and community-based integrated care is multifaceted and heterogeneous. Services for older people should be designed with different sub-models of integrated care.


Subject(s)
Delivery of Health Care, Integrated , East Asian People , Humans , Adult , Female , Middle Aged , Aged , Male , Aging , China , Surveys and Questionnaires
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