Effect and mechanism of Hashimoto thyroiditis on female infertility: A clinical trial, bioinformatics analysis, and experiments-based study.

Diagnosing Hashimoto thyroiditis (HT) relies on thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) titers. The influence of these antibodies on female infertility remains a subject of debate. This study aims to explore the effect and mechanism of HT on female infertility. First, a single-center cross-sectional study was conducted to investigate whether TgAb and TPOAb are the key factors leading to female infertility. Second, bioinformatic analysis was performed to investigate the potential target molecules and pathways. Third, in vivo experiments were performed to explore the effects of elevated TgAb levels on embryo implantation in a mouse model of autoimmune thyroiditis (AIT). Four hundred and five infertile women and 155 healthy controls were enrolled in the cross-sectional study. Results indicated that the TPOAb titer was associated with female infertility, while the TgAb titer showed no significant association. The increased levels of TgAb and TPOAb are not significantly correlated with anti-Mullerian hormone. Bioinformatic analysis indicated that the common target molecules for HT and female infertility include interleukin (IL)-6, IL-10, matrix metalloproteinase 9, and tumor necrosis factor, suggesting potential regulation through multiple signaling pathways such as HIF-1, VEGF, MAPK, and Th17 cell differentiation. A certain dose of porcine thyroglobulin can successfully establish a mouse model of AIT. In this mouse model, embryo implantation and ovarian reserve remain unaffected by elevated TgAb levels. In conclusion, the serum TPOAb titer was associated with infertility due to female factors but the TgAb titer showed no significant association. A simple increase in serum TgAb titer does not affect embryo implantation and ovarian reserve in the AIT model.

Reprogramming the future: Capitalizing on in vitro embryo culture by advancing stem cell technologies in the fight against rare genetic disorders.

Capitalizing on breakthroughs in reproductive genetics, the utilization of in vitro embryo culture and stem cell technologies heralds a transformative era in addressing global challenges posed by rare genetic diseases. These cutting-edge practices illuminate the intricacies of early human development, elucidate the mechanisms behind rare diseases, and guide the development of potential therapies. Balancing this remarkable innovation with necessary ethical considerations, these technologies have the potential to revolutionize the trajectory of rare genetic disorders, transforming the landscape of diagnosis, treatment, and genetic counseling while offering renewed hope for affected individuals and families worldwide.

Association of CHAT Gene Polymorphism rs3793790 and rs2177370 with Donepezil Response and the Risk of Alzheimer's Disease Continuum.

Background: Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer's disease continuum (ADC). Objective: This study focused on the associations between two single nucleotide polymorphisms (SNPs) (rs3793790 and rs2177370) located in the CHAT gene and donepezil response in ADC patients, and further evaluated the associations between the two SNPs and ADC. Material and Methods: According to 2018 National Institute on Aging and Alzheimer's Association (NIA-AA) standard, amyloid ß-protein positive (Aß+) and negative (Aß-) patients were recruited according to the Aß-PET/CT standard. rs3793790 and rs2177370 were genotyped in buccal swab samples by using the MassARRAY system. We used the Mini Mental State Examination (MMSE) in Chinese version, caregiver evaluation, and prescribing behavior to assess therapeutic response during the 9-month period. Using logistic regression models, we analyzed the relationship between the two SNPs and donepezil response in 58 Aß+ patients treated with donepezil alone at the initial diagnosis of ADC. We also explored a probable link between the two SNPs and ADC in 147 Aß+ and 73 Aß- patients using a logistic regression analysis. Results: The chance of donepezil response was higher in patients with the G allele of rs3793790 and/or the A allele of rs2177370 than in those without (odds ratio (OR) 6.83, 95% confidence interval (CI): 1.64-28.49). Additionally, the rs3793790 variant was not associated with ADC, whereas the A allele in rs2177370 increased 1.51-fold the ADC risk (OR 2.51, 95% CI: 1.28-4.95). Conclusion: The genetic variants of rs3793790 and rs2177370 were associated with the donepezil response, and rs2177370 may have a moderate relationship with the risk of ADC.

Photodynamic antibacterial research on hypericin-loaded PEGylated mesoporous silica delivery system.

In this study, a novel drug delivery system (MSN-PEG-Hypericin) was successfully fabricated using tetraethyl orthosilicate and 3-aminopropyltriethoxysilane as raw materials, and the PEGylation of the prepared aminated mesoporous silica and grafting of hypericin onto the carrier were further conducted to obtain MSN-PEG-Hypericin. The successful preparation of MSN-PEG-Hypericin was characterized by several physical-chemical techniques. Furthermore, the MSN-PEG-Hypericin system increased the ability of hypericin to generate reactive oxygen species (ROS) in vitro. The cytotoxicity assay and hemolysis analysis showed that MSN-PEG-Hypericin had good biocompatibility. For antibacterial studies, the irradiation time and incubation time of photodynamic therapy (PDT) for S. aureus and E. coli were respectively 8 min and 8 h, and the concentrations of hypericin were 2.5 and 5 µg/mL. The result of triphenyl tetrazolium chloride assay indicated that MSN-PEG-Hypericin had stronger photodynamic antibacterial activity than free hypericin, and S. aureus was more sensitive to PDT than E. coli, which was related to their cell structural differences. The antibacterial mechanism study indicated that the generated ROS could destroy the bacterial structures and cause bacterial death due to the leakage of the contents. The MSN-PEG-Hypericin system prepared in this study had potential application prospects in the antibacterial field.

Patient satisfaction with nursing care in infertility patients: A questionnaire survey.

Infertility remains a persistent global reproductive health challenge, with causative factors encompassing abnormalities in both the male and female reproductive systems. Typically, female partners seek initial consultations for infertility concerns, often within the context of routine annual well-woman check-ups. Nurses providing preventive care play a crucial role, conducting initial diagnostic assessments, and addressing certain causes of infertility. Patient satisfaction serves as a vital indicator of care quality. Identifying factors contributing to patient satisfaction with nursing services is crucial, yet research in this area has been limited. This study aimed to compare infertility patients' assessments of nurse quality and satisfaction with hospital services. The findings could offer valuable insights for healthcare providers, hospitals, and policymakers, guiding improvements in nursing care delivery and enhancing patient satisfaction in China's infertility treatment sector. By understanding patients' perspectives and experiences, healthcare providers can make necessary adjustments to improve care quality and patient outcomes. The sample included 1200 patients, and data collection utilized a self-assessment questionnaire, with percentages employed for analysis. Nurses are integral to caring for infertility patients during visits and conducting research to advance fertility care practices.

A multifunctional protein-based hydrogel with Au nanozyme-mediated self generation of H2S for diabetic wound healing.

Diabetics usually suffer from chronic impaired wound healing due to facile infection, excessive inflammation, diabetic neuropathy, and peripheral vascular disease. Hence, the development of effective diabetic wound therapy remains a critical clinical challenge. Hydrogen sulfide (H2S) regulates inflammation, oxidative stress, and angiogenesis, suggesting a potential role in promoting diabetic wound healing. Herein, we propose a first example of fabricating an antibiotic-free antibacterial protein hydrogel with self-generation of H2S gas (H2S-Hydrogel) for diabetic wound healing by simply mixing bovine serum albumin­gold nanoclusters (BSA-AuNCs) with Bis[tetrakis(hydroxymethyl)phosphonium] sulfate (THPS) at room temperature within a few minutes. In this process, the amino group in BAS and the aldehyde group in THPS are crossed together by Mannich reaction. At the same time, tris(hydroxymethyl) phosphorus (trivalent phosphorus) from THPS hydrolysis could reduce disulfide bonds in BSA to sulfhydryl groups, and then the sulfhydryl group generates H2S gas under the catalysis of BSA-AuNCs. THPS in H2S-Hydrogel can destroy bacterial biofilms, while H2S can inhibit oxidative stress, promote proliferation and migration of epidermal/endothelial cells, increase angiogenesis, and thus significantly increase wound closure. It would open a new perspective on the development of effective diabetic wound dressing.

Yishen Huatan Huoxue decoction and quercetin ameliorate decidualization dysfunction in polycystic ovary syndrome: A comprehensive investigation combining clinical trial and experimental studies.

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.

Bu-Shen-Ning-Xin decoction inhibits macrophage activation to ameliorate premature ovarian insufficiency-related osteoimmune disorder via FSH/FSHR pathway.

Limited studies are associated with premature ovarian insufficiency (POI)-related osteoimmune disorder currently. Bu-Shen-Ning-Xin decoction (BSNXD) displayed a favorable role in treating postmenopausal osteoporosis. However, its impact on the POI-related osteoimmune disorder remains unclear. The study primarily utilized animal experiments and network pharmacology to investigate the effects and underlying mechanisms of BSNXD on the POI-related osteoimmune disorder. First, a 4-vinylcyclohexene dioxide (VCD)-induced POI murine model was conducted to explore the therapeutical action of BSNXD. Second, we analyzed the active compounds of BSNXD and predicted their potential mechanisms for POI-related osteoimmune disorder via network pharmacology, further confirmed by molecular biology experiments. The results demonstrated that VCD exposure led to elevated follicle-stimulating hormone (FSH) levels, a 50% reduction in the primordial follicles, bone microstructure changes, and macrophage activation, indicating an osteoimmune disorder. BSNXD inhibited macrophage activation and osteoclast differentiation but did not affect serum FSH and estradiol levels in the VCD-induced POI model. Network pharmacology predicted the potential mechanisms of BSNXD against the POI-related osteoimmune disorder involving tumor necrosis factor α and MAPK signaling pathways, highlighting BSNXD regulated inflammation, hormone, and osteoclast differentiation. Further experiments identified BSNXD treatment suppressed macrophage activation via downregulating FSH receptor (FSHR) expression and inhibiting the phosphorylation of ERK and CCAAT enhancer binding proteins ß. In conclusion, BSNXD regulated POI-related osteoimmune disorder by suppressing the FSH/FSHR pathway to reduce macrophage activation and further inhibiting osteoclastogenesis.

Degradation kinetics of vitamins in different enteral feeding formulas during storage at different temperatures.

Vitamin degradation may be affected differently by various food matrices. In this study, the kinetics of vitamin A, B1, and C degradation were directly compared in two types of enteral feeding formulas (EFFs) with different energy densities over a nine-month storage period at 4, 25, and 30 °C. The content of vitamins A, B1, and C was measured in the initial and stored formulas. The results justified the finding that the content of these vitamins was gradually decreased with storage time or temperature increases during the period. At each temperature during storage, the degradation of vitamins A, B1, and C followed first-order kinetics, and the rate constants calculated indicated the degradation of vitamins was temperature-dependent. The EFF-B exhibited a higher activation energy for vitamin degradation than that in the EFF-A, and the activation energy indicated an inverse relationship with the fat content of EFFs. The outcomes might provide a reference for the development and application of EEFs.

Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies.

Background: Emerging evidence suggests the potential relationship between vitamin D deficiency and risk of cognitive impairment or dementia. To what extent the excess risk of dementia conferred by vitamin D deficiency is less clear. Objective: We summarized the current evidence from several aspects and further quantified these associations. Methods: We collected relevant prospective cohort studies by searching PubMed, Embase and Cochrane up to July 2023. The pooled relative risks (RR) were evaluated by random-effects models. Dose-response analyses were conducted by the method of two-stage generalized least squares regression. Results: Of 9,267 identified literatures, 23 were eligible for inclusion in the meta-analyses, among which 9 and 4 literatures were included in the dose-response analyses for the risk of dementia and Alzheimer's disease (AD). Vitamin D deficiency exhibited a 1.42 times risk for dementia (95% confidence interval (CI) = 1.21-1.65) and a 1.57-fold excess risk for AD (95% CI = 1.15-2.14). And vitamin D deficiency was associated with 34% elevated risk with cognitive impairment (95% CI = 1.19-1.52). Additionally, vitamin D was non-linearly related to the risk of dementia (pnonlinearity = 0.0000) and AD (pnonlinearity = 0.0042). The approximate 77.5-100 nmol/L 25-hydroxyvitamin D [25(OH)D] was optimal for reducing dementia risk. And the AD risk seemed to be decreased when the 25(OH)D level >40.1 nmol/L. Conclusions: Vitamin D deficiency was a risk factor for dementia, AD, and cognitive impairment. The nonlinear relationships may further provide the optimum dose of 25(OH)D for dementia prevention.

Au nanozyme-based multifunctional hydrogel for inflammation visible monitoring and treatment.

Chronic inflammation can delay wound healing, eventually leading to tissue necrosis and even cancer. Developing real-time intelligent inflammation monitoring and treatment to achieve effective wound management is important to promote wound healing. In this study, a smart multifunctional hydrogel (Hydrogel@Au NCs&DG) was proposed to monitor and treat the wound inflammation. It was prepared by mixing 3-carboxy-phenylboronic acid modified chitosan (CS-cPBA), ß-glycerophosphate (ß-GP), albumin-protected gold nanoclusters (BSA-Au NCs), and dipotassium glycyrrhizinate (DG) about 10 s. In this hydrogel, CS-cPBA and ß-GP are crosslinked together by boric acid ester bond and hydrogen bond to form the main hydrogel network, endowing the hydrogel with self-healing and injectable properties to adapt irregular wounds. Importantly, the as-prepared hydrogel with good biocompatibility and excellent adhesion property could directly determine the H2O2 to monitor the wound microenvironment by visible fluorescence change of BSA-Au NCs and then guide the frequency of dressing change to eliminate inflammation. The results demonstrated that the as-prepared smart hydrogel could be expected to serve as an intelligent wound dressing to promote inflammation-infected wound healing.

Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial.

Importance: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases. Objectives: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study. Design, Setting, and Participants: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. Interventions: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. Main Outcomes and Measures: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). Results: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. Conclusions and Relevance: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. Trial Registration: ClinicalTrials.gov Identifier: NCT04812509.

Fluorescence and colorimetric dual-mode multienzyme cascade nanoplatform based on CuNCs/FeMn-ZIF-8/PCN for detection of sarcosine.

It is critical to develop a highly efficient and sensitive method for detecting the biomarker sarcosine (SA) of prostate cancer due to its importance for men's health. In our work, a fluorescence (FL) and colorimetric dual-mode multienzyme cascade nanoplatform for SA detection was designed and constructed. CuNCs/FeMn-ZIF-8/PCN nanocomposites with high FL properties and peroxidase-like activity were successfully prepared by encapsulating copper nanoclusters (CuNCs) into FeMn-ZIF-8 and then loaded onto P-doped graphitic carbon nitride (PCN). Furthermore, the nanocomposites served as carriers for the immobilization of sarcosine oxidase (SOX) to construct a high-efficiency dual-mode multienzyme cascade nanoplatform CuNCs/SOX@FeMn-ZIF-8/PCN for the detection of SA. The intermediate H2O2 generated in the cascade caused the FL quenching of nanocomposites and the discoloration of 3,3',5,5'-tetramethylbenzidin. The linear ranges for SA detection in the dual-mode system were 1-100 µM (FL) and 1-200 µM (colorimetric), with detection limits of 0.34 and 0.59 µM, respectively. This nanoplatform exhibited notable repeatability, specificity, and stability, making it suitable for detecting sarcosine in real human urine samples. Therefore, this dual-mode multienzyme cascade nanoplatform would have a potential applicative prospect for detecting SA and other biomarkers in real clinical samples.

A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004).

Combining immunotherapy with chemotherapy can provide improved survival in advanced squamous non-small-cell lung cancer (NSCLC) patients without targetable gene alterations. 537 previously untreated patients with stage IIIB/IIIC or IV squamous NSCLC without targetable gene alterations were enrolled and randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo, both in combination with nab-paclitaxel and carboplatin, intravenously in 3-week cycles. The primary endpoint of progression-free survival (PFS) was met at the first interim analysis. At the second interim analysis, PFS benefit was maintained in serplulimab-chemotherapy group (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.42-0.67). At the final analysis, serplulimab-chemotherapy significantly improved median OS compared to placebo-chemotherapy (HR 0.73, 95% CI 0.58-0.93; p = 0.010). Grade ≥3 serplulimab or placebo-related adverse events occurred in 126 (35.2%) and 58 (32.4%) patients, respectively. Our results demonstrate that adding serplulimab to chemotherapy significantly improves survival in advanced squamous NSCLC patients, with manageable safety.

An ultrasensitive unlabeled electrochemical immunosensor for the detection of cardiac troponin I based on Pt/Au-B,S,N-rGO as the signal amplification platform.

In this study, an ultrasensitive unlabeled electrochemical immunosensor for the detection of cardiac troponin I (cTnI) was developed based on Pt/Au modified B,S,N co-doped reduced graphene oxide (Pt/Au-B,S,N-rGO) as a signal amplification platform. First-principles calculations were employed to analyze the electron density of states of Pt/Au-B,S,N-rGO, revealing an increase in the electron density of the graphene oxide (GO) states. Furthermore, scanning electron microscopy (SEM), X-ray photoelectron diffraction spectroscopy (XPS), and electrochemical detection were used to successfully construct and analyze Pt/Au-B,S,N-rGO. The results showed that B,S,N-rGO exhibited good electrochemical activity, and the Au/Pt NPs demonstrated excellent catalytic properties, which provided a strong foundation for achieving high-sensitivity detection. Moreover, the constructed unlabeled electrochemical immunosensor had an ideal linear range (0.1 pg/mL∼50 ng/mL) and detection limit (0.082 pg/mL). In human serum detection, the results of this immunosensor were essentially similar to the ELISA results for the same samples, which suggested that the immunosensor had a promising clinical application prospect for the detection of cTnI.

ldi-miR396-LdPMaT1 enhances reactive oxygen species scavenging capacity and promotes drought tolerance in Lilium distichum Nakai autotetraploids.

Drought is a key environmental stress that inhibits plant growth, development, yield and quality. Whole-genome replication is an effective method for breeding drought resistant cultivars. Here, we evaluated the tolerance of Lilium distichum Nakai diploids (2n = 2× = 24) and artificially induced autotetraploids (2n = 4× = 48) to drought simulated by polyethylene glycol (PEG) stress. Autotetraploids showed stronger drought tolerance than diploids, and high-throughput sequencing during PEG stress identified five differentially expressed miRNAs. Transcriptome analysis revealed significantly different reactive oxygen species (ROS)-scavenger expression levels between diploids and autotetraploids, which increased the drought tolerance of autotetraploids. Specifically, we identified ldi-miR396b and its only target gene (LdPMaT1) for further study based on its expression level and ROS-scavenging ability in response to drought stress (DS). Autotetraploids showed higher expression of LdPMaT1 and significantly downregulated expression of ldi-miR396b under DS compared with diploids. Through a short tandem target mimic (STTM) in transgenic lilies, functional studies revealed that miR396b silencing promotes LdPMaT1 expression and the DS response. Under PEG stress, STTM393 transgenic lines showed improved drought resistance mediated by lowered MDA content but exhibited high antioxidant enzyme activity, consistent with the autotetraploid results. Collectively, these findings suggest that ldi-miR396b-LdPMaT1 potentially enhances ROS-scavenging ability, which contributes to improved stress adaptation in autotetraploid lilies.

Nickel-Catalyzed Regioselectivity-Switchable Hydroheteroarylation of Vinylarenes with Electron-Rich Heteroarenes.

We report the first example of a regioselectivity switch in the hydroheteroarylation of vinylarenes with electron-rich heteroarenes, including benzofurans, benzothiophenes, and indoles, using an expedient ligand-controlled strategy. In the presence of NaOtBu, Ni(IMesMe)[P(OEt)3]Br2 yields C2-alkylated heteroarenes with high branched selectivity, whereas the use of Ni(IPr*OMe)[P(OEt)3]Br2 favors the formation of the corresponding linear products. This robust method also provides easy access to a range of C2-alkylated electron-rich heteroarenes without employing directing groups.

Integrating somatic mutation profiles with structural deep clustering network for metabolic stratification in pancreatic cancer: a comprehensive analysis of prognostic and genomic landscapes.

Pancreatic cancer is a globally recognized highly aggressive malignancy, posing a significant threat to human health and characterized by pronounced heterogeneity. In recent years, researchers have uncovered that the development and progression of cancer are often attributed to the accumulation of somatic mutations within cells. However, cancer somatic mutation data exhibit characteristics such as high dimensionality and sparsity, which pose new challenges in utilizing these data effectively. In this study, we propagated the discrete somatic mutation data of pancreatic cancer through a network propagation model based on protein-protein interaction networks. This resulted in smoothed somatic mutation profile data that incorporate protein network information. Based on this smoothed mutation profile data, we obtained the activity levels of different metabolic pathways in pancreatic cancer patients. Subsequently, using the activity levels of various metabolic pathways in cancer patients, we employed a deep clustering algorithm to establish biologically and clinically relevant metabolic subtypes of pancreatic cancer. Our study holds scientific significance in classifying pancreatic cancer based on somatic mutation data and may provide a crucial theoretical basis for the diagnosis and immunotherapy of pancreatic cancer patients.

Free Water MR Imaging of White Matter Microstructural Changes is a Sensitive Marker of Amyloid Positivity in Alzheimer's Disease.

BACKGROUND: Extracellular free water (FW) resulting from white matter degeneration limits the sensitivity of diffusion tensor imaging (DTI) in predicting Alzheimer's disease (AD). PURPOSE: To evaluate the sensitivity of FW-DTI in detecting white matter microstructural changes in AD. To validate the effectiveness of FW-DTI indices to predict amyloid-beta (Aß) positivity in mild cognitive impairment (MCI) subtypes. STUDY TYPE: Retrospective. POPULATION: Thirty-eight Aß-negative cognitively healthy (CH) controls (68.74 ± 8.28 years old, 55% female), 15 Aß-negative MCI patients (MCI-n) (68.87 ± 8.83 years old, 60% female), 29 Aß-positive MCI patients (MCI-p) (73.03 ± 7.05 years old, 52% female), and 29 Aß-positive AD patients (72.93 ± 9.11 years old, 55% female). FIELD STRENGTH/SEQUENCE: 3.0T; DTI, T1 -weighted, T2 -weighted, T2 star-weighted angiography, and Aß PET (18 F-florbetaben or 11 C-PIB). ASSESSMENT: FW-corrected and standard diffusion indices were analyzed using trace-based spatial statistics. Area under the curve (AUC) in distinguishing MCI subtypes were compared using support vector machine (SVM). STATISTICAL TESTS: Chi-squared test, one-way analysis of covariance, general linear regression analyses, nonparametric permutation tests, partial Pearson's correlation, receiver operating characteristic curve analysis, and linear SVM. A P value <0.05 was considered statistically significant. RESULTS: Compared with CH/MCI-n/MCI-p, AD showed significant change in tissue compartment indices of FW-DTI. No difference was found in the FW index among pair-wise group comparisons (the minimum FWE-corrected P = 0.114). There was a significant association between FW-DTI indices and memory and visuospatial function. The SVM classifier with tissue radial diffusivity as an input feature had the best classification performance of MCI subtypes (AUC = 0.91), and the classifying accuracy of FW-DTI was all over 89.89%. DATA CONCLUSION: FW-DTI indices prove to be potential biomarkers of AD. The classification of MCI subtypes based on SVM and FW-DTI indices has good accuracy and could help early diagnosis. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.