Effect of osmotic dehydration combined with vacuum freeze-drying treatment on characteristic aroma components of peach slices.

Hot air drying (HD), vacuum freeze drying (FD), and pilot-scale freeze drying (PSFD) are extensively used to prepare peach slices. However, the aroma of hot air drying and vacuum freeze-drying is yet to be addressed. In this study, HS-SPME-GC-MS was used to characterize and quantify the volatile compounds in peach slices. First, 33, 36, and 46 volatile compounds were identified and quantified in the HD, FD, and PSFD groups, respectively. PSFD is preferable to HD and FD in terms of the volatile compound types, content, and aroma profiles. PSFD was selected for subsequent permeation and dehydration experiments. The key aroma compounds with an OAV ≥ 1 were found in the PSFD30 group. GC-O analysis was conducted on the PSFD30 group, leading to the preliminary identification of 2-methylbutanal, pentanal, hexanal, 2-hexenal, phenylacetaldehyde, ethyl acetate, 2-methylbutyl acetate, ethyl lactate, linalool, methyl heptenone, and γ-octalactone as distinctive aromas in dried peach slices.

Neoadjuvant chemotherapy may be the best neoadjuvant therapy modality for non-metastatic pancreatic cancer: a population based study.

Objective: Currently, there are no studies showing which neoadjuvant therapy modality can provide better prognosis for patients after pancreatic cancer surgery. This study explores the optimal neoadjuvant therapy model by comparing the survival differences between patients with non-metastatic pancreatic cancer (cT1-4N0-1M0) who received neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NARCT). Methods: We retrospectively analyzed the clinical data of 723 patients with cT1-4N0-1M0 pancreatic cancer who received neoadjuvant therapy before surgery from the Surveillance, Epidemiology, and End Results (SEER) database. After propensity score matching (PSM), we compared the effects of NACT and NARCT on overall survival (OS) and cancer-specific survival (CSS) in patients with non-metastatic pancreatic cancer, and then performed subgroup analyze. Finally, we used univariate and multivariate Cox regression analysis to explore potential risk factors for OS and CSS in patients with non-metastatic pancreatic cancer treated with preoperative neoadjuvant therapy. Result: Before PSM, mOS (30.0 months VS 26.0 months, P=0.122) and mCSS (30.0 months VS 26.0 months, P=0.117) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, but this was not statistically significant (P>0.05). After PSM, mOS (30.0 months VS 25.0 months, P=0.032) and mCSS (33.0 months VS 26.0 months, P=0.028) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, and this difference was statistically significant (P<0.05). Multivariate Cox regression analysis results showed that age, lymph node positivity, and NARCT were independent adverse prognostic factors for OS and CSS in patients with non-metastatic pancreatic cancer. Conclusion: The study results show that compared with NARCT, NACT is the best preoperative neoadjuvant therapy mode for patients with non-metastatic pancreatic cancer. This result still needs to be confirmed by more prospective randomized controlled trials.

Pro-inflammatory enzyme inhibition of lipoxygenases by flavonoid rich extract from Artemisia vulgaris.

The peroxyl radicals generated by the activity of lipoxygenases (LOX) are mediators to trigger inflammatory diseases. Therefore, it is important to investigate potent LOX inhibitor for modulating the occurrence and resolving inflammatory processes. Artemisa vulgaris, is a herbal plant that is known for flavonoids, potentially inhibiting lipid peroxidation and scavenging radicals. The objectives of the present study were to obtain flavonoids rich extract from A. vulgaris, and determine the inhibitory mode of the extract against LOX. The flavonoids rich extract was optimized in an ultrasound assisted extraction using ionic liquids as extraction solvent. The results found that the optimum conditions; ratio of solid-to-liquid (1:10) and 30 min of extraction time could produce the high yield (10.14 %) and flavonoid content (5.30 mg QE/g). The LOX activity was demonstrated to follow a mixed mode of inhibition in the presence of the flavonoid rich extract as an inhibitor. The Michaelis-Menten constant (Km) was increased from 0.283 µM to 0.435 µM, whereas the maximum velocity was reduced from 0.22 µM/min to 0.058 µM/min in the inhibition. The flavonoids rich extract is likely to be a natural potent non-competitive inhibitor which may bind to free LOX or substrate-bound LOX.

Efficacy of ceftazidime-avibactam in the treatment of carbapenem-resistant Klebsiella pneumoniae infections: Focus on solid organ transplantation recipients.

INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a new option to treat KPC- and OXA-48 carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. However, clinical evidence is limited regarding its use in treating CRKP infections, especially in solid organ transplantation (SOT) recipients. In this study, we assessed the efficacy of CAZ-AVI in treating CRKP infections in both the general population and the SOT recipients in comparison with other antibiotic regimens. METHODS: This is a single-centre retrospective cohort study of patients admitted between January 1, 2018 and June 30, 2021 with the diagnosis of CRKP infections receiving either CAZ-AVI or other regimens ≥ 72 hours and clinical outcomes were analysed. RESULTS: Of 200 patients with CRKP infections, 67 received CAZ-AVI, 133 received other regimens, and 50 were SOT recipients. In the SOT cohort, 30 patients received CAZ-AVI, and 20 received other regimens. The overall 30-day mortality was 38% in the SOT cohort. Compared with patients receiving other regimens, CAZ-AVI therapy resulted in lower 30-day mortality (23.3% vs. 60%, P = 0.014) and 90-day mortality (35.7% vs. 86.7%, P = 0.003), higher clinical cure (93.3% vs. 40%, P < 0.001) and microbiological clearance. Similar promising results of CAZ-AVI were also shown in the whole population cohort. Moreover, clinical outcomes of SOT recipients receiving CAZ-AVI were not inferior to those without SOT. CONCLUSIONS: CAZ-AVI therapy was associated with better clinical outcomes in CRKP infections in both the general population and SOT recipients. Considering the limitations of the present study, well-conducted RCTs are still warranted to confirm these findings.

Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients.

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.

The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study.

Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, we used a method based on genetic principles-Mendelian randomization (MR) analysis to test whether there is a causal relationship between alcohol consumption and EC. MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates. An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41-0.79, P < 0.001]. Subgroup analysis of EC revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (EEC) (OR = 0.56, 95% CI 0.38-0.83, P = 0.004) but not for non-endometrioid endometrial cancer (NEC) (OR = 1.36, 95% CI 0.40-4.66, P = 0.626). The MR-Egger regression and weighted median method yielded consistent causal effects with the IVW method. The consistent results of sensitivity analyses indicated the reliability of our causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels. This MR study suggests that genetically predicted alcohol consumption is a protective factor for EC, particularly for EEC, and this protective effect may be mediated through the reduction of HCG and IGF1.

Slow-wave sleep and REM sleep without atonia predict motor progression in Parkinson's disease.

BACKGROUND: Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated. METHODS: We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson's Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects models. RESULTS: Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P < 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that low SWE (HR = 1.739, 95% CI = 1.038-2.914; P = 0.036; FDR-P = 0.036) and high tonic RWA (HR = 0.575, 95% CI = 0.343-0.963; P = 0.032; FDR-P = 0.036) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P < 0.001; FDR-P < 0.001) while higher tonic RWA density was associated with faster rate of rigidity progression (P = 0.006; FDR-P = 0.024) using linear mixed-effects models. CONCLUSIONS: These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.

The association between plasma GPNMB and Parkinson's disease and multiple system atrophy.

AIMS: Parkinson's disease (PD), as the second most common neurodegenerative disorder, often presents diagnostic challenges in differentiation from other forms of Parkinsonism. Recent studies have reported an association between plasma glycoprotein nonmetastatic melanoma protein B (pGPNMB) and PD. METHODS: A retrospective study was conducted, comprising 401 PD patients, 111 multiple system atrophy (MSA) patients, 13 progressive supranuclear palsy (PSP) patients and 461 healthy controls from the Chinese Han population, with an assessment of pGPNMB levels. RESULTS: The study revealed that pGPNMB concentrations were significantly lower in PD and MSA patients compared to controls (area under the receiver operating characteristics curve (AUC) 0.62 and 0.74, respectively, P < 0.0001 for both), but no difference was found in PSP patients compared to controls (P > 0.05). Interestingly, the level of pGPNMB was significantly higher in PD patients than in MSA patients (AUC = 0.63, P < 0.0001). Furthermore, the study explored the association between pGPNMB levels and disease severity in PD and MSA patients, revealing a positive correlation in PD patients but not in MSA patients with both disease severity and cognitive impairment. CONCLUSION: This study successfully replicated prior findings, demonstrating an association between pGPNMB levels and disease severity, and also identified a correlation with cognitive impairment in PD patients of the Chinese Han population. Additionally, this study is the first to identify a significant difference in pGPNMB levels between MSA, PD, and normal controls. The data provide new evidence supporting the potential role of pGPNMB in the diagnosis and differential diagnosis of Parkinsonism.

Effects of heavy metals and metalloids on the biodegradation of organic contaminants.

Heavy metals and metalloids (HMMs) inhibit the biodegradation of organic pollutants. The degree of inhibition depends not only on the concentration and bioavailability of HMMs but also on additional factors, such as environmental variables (e.g., inorganic components, organic matter, pH, and redox potential), the nature of the metals, and microbial species. Based on the degradation pattern and metal concentrations causing half biodegradation rate reductions (RC50s), the inhibition of biodegradation was: Hg2+, As2O3 > Cu2+, Cd2+, Pb2+, Cr3+ > Ni2+, Co2+ > Mn2+, Zn2+ > Fe3+. Four patterns were observed: inhibition increases with increasing metal concentration; low concentrations stimulate, while high concentrations inhibit; high concentrations inhibit less; and mild inhibition remains constant. In addition, metal ion mixtures have more complex inhibitory effects on the degradation of organic pollutants, which may be greater than, similar to, or less than that of individual HMMs. Finally, the inhibitory mechanism of HMMs on biodegradation is reviewed. HMMs generally have little impact on the biodegradation pathway of organic pollutants for bacterial strains. However, when pollutants are biodegraded by the community, HMMs may activate microbial populations harbouring different transformation pathways. HMMs can affect the biodegradation efficiency of organic pollutants by changing the surface properties of microbes, interfering with degradative enzymes, and interacting with general metabolism.

LRRK2 G2019S promotes astrocytic inflammation induced by oligomeric α-synuclein through NF-κB pathway.

Parkinson's disease (PD) is characterized by the irreversible loss of dopaminergic neurons and the accumulation of α-synuclein in Lewy bodies. The oligomeric α-synuclein (O-αS) is the most toxic form of α-synuclein species, and it has been reported to be a robust inflammatory mediator. Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are also genetically linked to PD and neuroinflammation. However, how O-αS and LRRK2 interact in glial cells remains unclear. Here, we reported that LRRK2 G2019S mutation, which is one of the most frequent causes of familial PD, enhanced the effects of O-αS on astrocytes both in vivo and in vitro. Meanwhile, inhibition of LRRK2 kinase activity could relieve the inflammatory effects of both LRRK2 G2019S and O-αS. We also demonstrated that nuclear factor κB (NF-κB) pathway might be involved in the neuroinflammatory responses. These findings revealed that inhibition of LRRK2 kinase activity may be a viable strategy for suppressing neuroinflammation in PD.

Application of Real-Time Sound Touch Elastography for Evaluating Chronic Kidney Disease of Transplanted Kidneys.

BACKGROUND: If chronic allograft nephropathy can be detected early and treated, the long-term survival rate of the transplanted kidney may be effectively improved. PURPOSE: To compare the application value of real-time sound touch elastography (STE), strain elastography, and color Doppler flow imaging in evaluating chronic kidney disease of transplanted kidneys. MATERIALS AND METHODS: A total of 101 patients with renal transplantation were divided into a normal group (serum creatinine <134 mol/L, 58 patients) and a chronic allograft nephropathy group after renal transplantation over 6 months (serum creatinine >134 mol/L, 43 patients). The maximum elastic modulus (Emax) was determined, and receiver operator characteristics were used to compare the diagnostic efficacy of STE ultrasound. RESULTS: Emean, Emax, B/A (the strain rate of the internal oblique muscle tissue/ the strain rate of the central renal cortex) of cortical standard strain ratio in strain elastography, and resistance index (RI) between normal and chronic allograft nephropathy groups have statistical significance (P < .05). Emax is superior to B/A and arcuate artery RI in the chronic cortex in the diagnosis of renal dysfunction, and the area under the receiver operator characteristics curve is 0.88. The estimated glomerular filtration rate was negatively correlated with renal cortex Emax, B/A, and arcuate artery RI, among which Emax was the strongest (r = - 0.713, P < .001). The renal cortical Emax cut-off was 30.95 kPa, the sensitivity was 92%, the specificity was 88%, and the accuracy was 88%. CONCLUSION: The STE technique to evaluate chronic renal dysfunction after renal transplantation is more sensitive than traditional strain-type elastography and hemodynamic parameters, with renal function decline, renal cortex Emax, renal cortical B/A, and arcuate artery RI gradually increased, and renal cortex Emax was particularly obvious.

The effect of early oral nutritional supplements on improving nutritional outcomes and radiation-induced oral mucositis for nasopharyngeal carcinoma patients undergoing concurrent chemoradiotherapy.

BACKGROUND: To explore the value of early oral nutritional supplements (ONS) in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT). METHODS: Patients with newly diagnosed II-IVA stage NPC were analyzed and divided into Early and Routine ONS groups according to whether they received early ONS at the beginning of CCRT. Changes in nutritional indicators, incidence of treatment-related toxicity, radiation interruption, and completion of CCRT were compared. RESULTS: In total, 161 patients with NPC were analyzed, including 72 in the Early ONS group and 89 in the Routine ONS group. Multivariate analysis showed that early ONS was an independent protective factor for concurrent chemotherapy ≥2 cycles, and a protective factor against ≥grade 3 radiation-induced oral mucositis (RIOM) and weight loss >5%. In stage III-IVA patients, early ONS was beneficial in decreasing the risk of severe malnutrition. CONCLUSIONS: Early ONS can improve nutritional outcomes, reduce RIOM, and enhance treatment adherence.

Overlapping Epstein-Barr virus encephalitis and autoimmune glial fibrillary acidic protein astrocytopathy.

We describe three cases of overlapping Epstein-Barr virus (EBV) Encephalitis and Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A). The three cases all presented with initial symptoms of fever, headache, coma, and posture tremor of the upper limbs, then followed by limb weakness and dysuria. All of the three cases were on ventilators. Case 1 and 2 improved dramatically after intravenous methylprednisoloneand immunoglobulin treatment. However, case 3 presented dyspneic, and died from gastrointestinal hemorrhage. The GFAP-A triggered by EBV intracranial infection could initially masquerade as EBV encephalitis only, and the detection of GFAP antibody is essential for differentiation.

Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice.

CONTEXT: Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. OBJECTIVE: This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. MATERIALS AND METHODS: Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings. RESULTS: Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1ß and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1ß, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment. DISCUSSION AND CONCLUSION: Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1ß, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.

A systematic analysis of genotype-phenotype associations with PLA2G6.

BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) can be categorized into infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), neurodegeneration with brain iron accumulation (NBIA), and early-onset parkinsonism (EOP). OBJECTIVES: To determine the genotype-phenotype association in PLAN. METHODS: "PLA2G6" or "PARK14" or "phospholipase A2 group VI" or "iPLA2ß" were searched across MEDLINE from June 23, 1997, to March 1, 2023. A total of 391 patients were identified, and 340 patients of them were finally included in the assessment. RESULTS: The loss of function (LOF) mutation ratios were significantly different (p < 0.001), highest in INAD, followed by NBIA, aNAD, and EOP. Four ensemble scores (i.e., BayesDel, VARITY, ClinPred, and MetaRNN) were assessed to predict the deleteriousness of missense mutations and demonstrated significant differences (p < 0.001). Binary logistic regression analyses demonstrated that LOF mutations were independently associated with brain iron accumulation (p = 0.006) and ataxia (p = 0.025). CONCLUSIONS: LOF or more deleterious missense mutations are more likely to promote the development of serious phenotype of PLAN, and LOF mutations are independently associated with brain iron accumulation and ataxia.

Evaluating Biological Properties of Stingless Bee Propolis.

The aim of the present study was to determine the content of phenolics, flavonoids and tannins, as well as the biological functions of propolis extracts from the stingless bee (Heterotrigona itama). The raw propolis was extracted via maceration with ultrasonic pretreatment in 100% water and 20% ethanol. The yield of ethanolic propolis extracts was about 1% higher than its aqueous counterpart. The colorimetric assays showed that the ethanolic propolis extract had about two times higher phenolics (17.043 mg GAE/g) and tannins (5.411 mg GAE/g), and four times higher flavonoids (0.83 mg QE/g). The higher phenolic content had enhanced the antiradical and antibacterial capacities of the ethanolic extract. The propolis extracts significantly exhibited higher antibacterial activity against gram-positive bacteria (Staphylococcus aureus) than gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). However, aqueous extract was found to have a higher anticancer property based on the viability of lung cancer cells. No cytotoxic effect was observed on normal lung cells as the cell viability was maintained >50%, even the concentration of propolis extracts were increased up to 800 µg/mL. Different chemical compositions of propolis extract would show different bioactivities depending upon the individual applications. The high content of phenolics suggests that the propolis extract could be a natural source of bioactive ingredients for the development of innovative and functional foods.

Development and acceptability validation of a deep learning-based tool for whole-prostate segmentation on multiparametric MRI: a multicenter study.

Background: Accurate whole prostate segmentation on magnetic resonance imaging (MRI) is important in the management of prostatic diseases. In this multicenter study, we aimed to develop and evaluate a clinically applicable deep learning-based tool for automatic whole prostate segmentation on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI). Methods: In this retrospective study, 3-dimensional (3D) U-Net-based models in the segmentation tool were trained with 223 patients who underwent prostate MRI and subsequent biopsy from 1 hospital and validated in 1 internal testing cohort (n=95) and 3 external testing cohorts: PROSTATEx Challenge for T2WI and DWI (n=141), Tongji Hospital (n=30), and Beijing Hospital for T2WI (n=29). Patients from the latter 2 centers were diagnosed with advanced prostate cancer. The DWI model was further fine-tuned to compensate for the scanner variety in external testing. A quantitative evaluation, including Dice similarity coefficients (DSCs), 95% Hausdorff distance (95HD), and average boundary distance (ABD), and a qualitative analysis were used to evaluate the clinical usefulness. Results: The segmentation tool showed good performance in the testing cohorts on T2WI (DSC: 0.922 for internal testing and 0.897-0.947 for external testing) and DWI (DSC: 0.914 for internal testing and 0.815 for external testing with fine-tuning). The fine-tuning process significantly improved the DWI model's performance in the external testing dataset (DSC: 0.275 vs. 0.815; P<0.01). Across all testing cohorts, the 95HD was <8 mm, and the ABD was <3 mm. The DSCs in the prostate midgland (T2WI: 0.949-0.976; DWI: 0.843-0.942) were significantly higher than those in the apex (T2WI: 0.833-0.926; DWI: 0.755-0.821) and base (T2WI: 0.851-0.922; DWI: 0.810-0.929) (all P values <0.01). The qualitative analysis showed that 98.6% of T2WI and 72.3% of DWI autosegmentation results in the external testing cohort were clinically acceptable. Conclusions: The 3D U-Net-based segmentation tool can automatically segment the prostate on T2WI with good and robust performance, especially in the prostate midgland. Segmentation on DWI was feasible, but fine-tuning might be needed for different scanners.

Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague-Dawley rats via the P38 MAPK signaling pathway.

Background: Periodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process. Methods: We established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-α, IL-1ß, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), ß-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation. Results: We demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-α, IL-1ß, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes. Conclusion: Our findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment.

Development and clinical utility analysis of a prostate zonal segmentation model on T2-weighted imaging: a multicenter study.

OBJECTIVES: To automatically segment prostate central gland (CG) and peripheral zone (PZ) on T2-weighted imaging using deep learning and assess the model's clinical utility by comparing it with a radiologist annotation and analyzing relevant influencing factors, especially the prostate zonal volume. METHODS: A 3D U-Net-based model was trained with 223 patients from one institution and tested using one internal testing group (n = 93) and two external testing datasets, including one public dataset (ETDpub, n = 141) and one private dataset from two centers (ETDpri, n = 59). The Dice similarity coefficients (DSCs), 95th Hausdorff distance (95HD), and average boundary distance (ABD) were calculated to evaluate the model's performance and further compared with a junior radiologist's performance in ETDpub. To investigate factors influencing the model performance, patients' clinical characteristics, prostate morphology, and image parameters in ETDpri were collected and analyzed using beta regression. RESULTS: The DSCs in the internal testing group, ETDpub, and ETDpri were 0.909, 0.889, and 0.869 for CG, and 0.844, 0.755, and 0.764 for PZ, respectively. The mean 95HD and ABD were less than 7.0 and 1.3 for both zones. The U-Net model outperformed the junior radiologist, having a higher DSC (0.769 vs. 0.706) and higher intraclass correlation coefficient for volume estimation in PZ (0.836 vs. 0.668). CG volume and Magnetic Resonance (MR) vendor were significant influencing factors for CG and PZ segmentation. CONCLUSIONS: The 3D U-Net model showed good performance for CG and PZ auto-segmentation in all the testing groups and outperformed the junior radiologist for PZ segmentation. The model performance was susceptible to prostate morphology and MR scanner parameters.

The Oral Microbiome as Mediator between Oral Hygiene and Its Impact on Nasopharyngeal Carcinoma.

Oral hygiene and the alteration of the oral microbiome have been linked to nasopharyngeal carcinoma (NPC). This study aimed to investigate whether the oral microbiome plays a mediating role in the relationship between oral hygiene and NPC, and identify differential microbial taxonomies that potentially mediated this association. We conducted a case-control study that involved 218 NPC patients and 192 healthy controls. The 16S rRNA gene sequencing of the V4 region was performed to evaluate the composition of the oral microbiome. Mediation analysis was applied to explore the relationship among oral hygiene, the oral microbiome and NPC. We found that dental fillings and poor oral hygiene score were associated with increased risks of NPC (OR = 2.51 (1.52-4.25) and OR = 1.54 (1.02-2.33)). Mediation analysis indicated that dental fillings increased the risk of NPC by altering the abundance of Erysipelotrichales, Erysipelotrichaceae, Solobacterium and Leptotrichia wadei. In addition, Leptotrichia wadei also mediated the association between oral hygiene score and the risk of NPC. Our study confirmed that poor oral hygiene increased the risk of NPC, which was partly mediated by the oral microbiome. These findings might help us to understand the potential mechanism of oral hygiene influencing the risk of NPC via the microbiome.