MRI-based radiomic models for the preoperative prediction of extramural venous invasion in rectal cancer: A systematic review and meta-analysis.

AIM: To estimate the diagnostic value of magnetic resonance imaging (MRI)-based radiomic models in detecting the extramural venous invasion (EMVI) of rectal cancer. MATERIALS AND METHODS: Appropriate studies in multiple electronic databases were systematically retrieved. The Quality Assessment of Diagnostic Accuracy Studies 2 and Radiomics Quality Score (RQS) were used to evaluate the eligible studies' methodology quality. Summary accuracy metrics were calculated, and the publication bias was detected using Deek's funnel plot. The sensitivity and meta-regression analysis were performed to investigate the causes of heterogeneity. RESULTS: For the seven eligible studies, which included 1175 patients, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.80 (95 % CI, 0.70-0.88), 0.89 (95 % CI, 0.84-0.92), 7.0 (95 % CI, 4.7, 10.4), 0.22 (95 % CI, 0.14, 0.34), and 32 (95 % CI, 16, 65), respectively. The area under the receiver operating characteristic curve (AUC) was 0.91 (95 % CI, 0.88, 0.93). Moderate heterogeneity was found due to I2 values of 38.63 % and 32.29 % in sensitivity and specificity, respectively. Meta-regression analysis suggested that the patient enrollment, number of patients, segmentation method, and RQS score were the source of the heterogeneity. The head-to-head analysis suggested that radiomics model had a higher sensitivity for detection of EMVI than subjective evaluation by radiologist (0.47 vs. 0.73, p ≤ 0.001). CONCLUSION: Our study suggests that MRI-based radiomic models have good diagnostic value in detecting EMVI for rectal cancer patients. Nevertheless, more prospective and high-quality studies with larger sample sizes are needed in the future to validate these results.

Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults.

Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98-2.27; OR, 2.03; 95% CI, 1.86-2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.

Effect of mydriasis on macular and peripapillary metrics in swept-source optical coherence tomography angiography.

Introduction: The study aimed to evaluate the effect of mydriasis on macular and peripapillary metrics with swept-source optical coherence tomography angiography (SS-OCTA) in healthy subjects. Methods: Thirty-five healthy subjects were included. The macular region was scanned by the 3×3mm mode and 6×6mm mode, and the peripapillary region was scanned by the 4.5×4.5mm mode on both eyes with SS-OCTA before and after mydriasis. Macular and peripapillary metrics, including retinal vessel density (VD) and fundus thickness were measured by the built-in program. Data of the right eye were analyzed. Results: The signal strength of the scans was comparable before and after mydriasis (all P>0.05). There were no significant differences in foveal avascular zone (FAZ) parameters and retinal VD of most sectors in both macular and peripapillary areas (all P>0.05). Choroidal thickness was decreased, outer and whole retinal thickness was increased in most of the macular sectors after mydriasis (all P<0.05). Choroidal thickness was decreased in all the peripapillary sectors, but whole retinal thickness and GCC thickness were increased in some peripapillary sectors after mydriasis (all P<0.05). Conclusions: FAZ parameters and retinal VD in the most macular and peripapillary regions are not affected by mydriasis. The thickness of the choroid is decreased after mydriasis, while the thickness of retinal layers in some sectors may be increased after mydriasis.

Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety.

Purpose: Glaucoma, a leading cause of blindness worldwide, is suspected to exhibit a notable association with psychological disturbances. This study aimed to investigate epidemiological associations and explore shared genetic architecture between glaucoma and mental traits, including depression and anxiety. Methods: Multivariable logistic regression and Cox proportional hazards regression models were employed to investigate longitudinal associations based on UK Biobank. A stepwise approach was used to explore the shared genetic architecture. First, linkage disequilibrium score regression inferred global genetic correlations. Second, MiXeR analysis quantified the number of shared causal variants. Third, specific shared loci were detected through conditional/conjunctional false discovery rate (condFDR/conjFDR) analysis and characterized for biological insights. Finally, two-sample Mendelian randomization (MR) was conducted to investigate bidirectional causal associations. Results: Glaucoma was significantly associated with elevated risks of hospitalized depression (hazard ratio [HR] = 1.54; 95% confidence interval [CI], 1.01-2.34) and anxiety (HR = 2.61; 95% CI, 1.70-4.01) compared to healthy controls. Despite the absence of global genetic correlations, MiXeR analysis revealed 300 variants shared between glaucoma and depression, and 500 variants shared between glaucoma and anxiety. Subsequent condFDR/conjFDR analysis discovered 906 single-nucleotide polymorphisms (SNPs) jointly associated with glaucoma and depression and two associated with glaucoma and anxiety. The MR analysis did not support robust causal associations but indicated the existence of pleiotropic genetic variants influencing both glaucoma and depression. Conclusions: Our study enhances the existing epidemiological evidence and underscores the polygenic overlap between glaucoma and mental traits. This observation suggests a correlation shaped by pleiotropic genetic variants rather than being indicative of direct causal relationships.

A gadoxetic acid-enhanced MRI-based model using LI-RADS v2018 features for preoperatively predicting Ki-67 expression in hepatocellular carcinoma.

PURPOSE: To construct a gadoxetic acid-enhanced MRI (EOB-MRI) -based multivariable model to predict Ki-67 expression levels in hepatocellular carcinoma (HCC) using LI-RADS v2018 imaging features. METHODS: A total of 121 patients with HCC who underwent EOB-MRI were enrolled in this study. The patients were divided into three groups according to Ki-67 cut-offs: Ki-67 ≥ 20% (n = 86) vs. Ki-67 < 20% (n = 35); Ki-67 ≥ 30% (n = 73) vs. Ki-67 < 30% (n = 48); Ki-67 ≥ 50% (n = 45) vs. Ki-67 < 50% (n = 76). MRI features were analyzed to be associated with high Ki-67 expression using logistic regression to construct multivariable models. The performance characteristic of the models for the prediction of high Ki-67 expression was assessed using receiver operating characteristic curves. RESULTS: The presence of mosaic architecture (p = 0.045), the presence of infiltrative appearance (p = 0.039), and the absence of targetoid hepatobiliary phase (HBP, p = 0.035) were independent differential factors for the prediction of high Ki-67 status (≥ 50% vs. < 50%) in HCC patients, while no features could predict high Ki-67 status with thresholds of 20% (≥ 20% vs. < 20%) and 30% (≥ 30% vs. < 30%) (p > 0.05). Four models were constructed including model A (mosaic architecture and infiltrated appearance), model B (mosaic architecture and targetoid HBP), model C (infiltrated appearance and targetoid HBP), and model D (mosaic architecture, infiltrated appearance and targetoid HBP). The model D yielded better diagnostic performance than the model C (0.776 vs. 0.669, p = 0.002), but a comparable AUC than model A (0.776 vs. 0.781, p = 0.855) and model B (0.776 vs. 0.746, p = 0.076). CONCLUSIONS: Mosaic architecture, infiltrated appearance and targetoid HBP were sensitive imaging features for predicting Ki-67 index ≥ 50% and EOB-MRI model based on LI-RADS v2018 features may be an effective imaging approach for the risk stratification of patients with HCC before surgery.

Fermentation of waste water from agar processing with Bacillus subtilis by metabolomic analysis.

Fungal infection has become a major threat to crop loss and affects food safety. The waste water from agar processing industries extraction has a number of active substances, which could be further transformed by microorganisms to synthesize antifungal active substances. In this study, Bacillus subtilis was used to ferment the waste water from agar processing industries extraction to analyze the antifungal activity of the fermentation broth on Alternaria alternata and Alternaria spp. Results showed that 25% of the fermentation broth was the most effective in inhibited A. alternata and Alternaria spp., with fungal inhibition rates of 99.9% and 96.1%, respectively, and a minimum inhibitory concentration (MIC) was 0.156 µg/mL. Metabolomic analysis showed that flavonoid polyphenols such as coniferyl aldehyde, glycycoumarin, glycitin, and procyanidin A1 may enhance the inhibitory activity against the two pathogenic fungal strains. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that polyphenols involved in the biosynthesis pathways of isoflavonoid and phenylpropanoid were upregulated after fermentation. The laser confocal microscopy analyses and cell conductivity showed that the cytoplasm of fungi treated with fermentation broth was destroyed. This study provides a research basis for the development of new natural antifungal agents and rational use of seaweed agar waste. KEY POINTS: • Bacillus subtilis fermented waste water has antifungal activity • Bacillus subtilis could transform active substances in waste water • Waste water is a potential raw material for producing antifungal agents.

Alterations of outer retinal reflectivity in diabetic patients without clinically detectable retinopathy.

PURPOSE: This study aimed to investigate alterations of outer retinal reflectivity on spectral-domain optical coherence tomography (OCT) in diabetic patients without clinically detectable retinopathy (NDR). METHODS: In this retrospective study, 64 NDR patients and 71 controls were included. Relative reflectivity (RR) of the ellipsoid zone (EZ), photoreceptor outer segment (OS) and inner segment (IS), and outer nuclear layer (ONL) at the foveola and at 500 µm, 1000 µm, and 2000 µm nasal (N), temporal (T), superior (S), and inferior (I) to the foveola was measured by cross-line OCT and ImageJ. Retinal vessel densities (VD) in fovea, parafovea, and perifovea areas were detected by OCT angiography (OCTA). RESULTS: EZ RR in most retinal locations was significantly lower in NDR eyes compared to controls (all P < 0.05), except the foveola. Compared with controls, NDR eyes also displayed lower RR at N2000, T2000, S1000, and I1000 of OS, at S500 and I500 of IS, and at I500 of ONL (all P < 0.05). Negative correlations could be observed between retinal RR and diabetes duration, HbA1c, and best-corrected visual acuity (BCVA) (r = - 0.303 to - 0.452). Compared to controls, EZ, OS, and IS RR of the NDR eyes showed lower correlation coefficients with whole image SCP and DCP VD of parafovea and perifovea regions. CONCLUSION: Outer retinal reflectivity, along with the coefficients between retinal reflectivity and VD, is reduced in NDR patients and is correlated with diabetes duration, HbA1c, and BCVA. The reduction of outer retinal reflectivity may be a potential biomarker of early retinal alterations in diabetic patients.

Development and Validation of a Deep Learning and Radiomics Combined Model for Differentiating Complicated From Uncomplicated Acute Appendicitis.

RATIONALE AND OBJECTIVES: This study aimed to develop and validate a deep learning and radiomics combined model for differentiating complicated from uncomplicated acute appendicitis (AA). MATERIALS AND METHODS: This retrospective multicenter study included 1165 adult AA patients (training cohort, 700 patients; validation cohort, 465 patients) with available abdominal pelvic computed tomography (CT) images. The reference standard for complicated/uncomplicated AA was the surgery and pathology records. We developed our combined model with CatBoost based on the selected clinical characteristics, CT visual features, deep learning features, and radiomics features. We externally validated our combined model and compared its performance with that of the conventional combined model, the deep learning radiomics (DLR) model, and the radiologist's visual diagnosis using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of our combined model in distinguishing complicated from uncomplicated AA was 0.816 (95% confidence interval [CI]: 0.785-0.844). In the validation cohort, our combined model showed robust performance across the data from three centers, with AUCs of 0.836 (95% CI: 0.785-0.879), 0.793 (95% CI: 0.695-0.872), and 0.723 (95% CI: 0.632-0.802). In the total validation cohort, our combined model (AUC = 0.799) performed better than the conventional combined model, DLR model, and radiologist's visual diagnosis (AUC = 0.723, 0.755, and 0.679, respectively; all P < 0.05). Decision curve analysis showed that our combined model provided greater net benefit in predicting complicated AA than the other three models. CONCLUSION: Our combined model allows the accurate differentiation of complicated and uncomplicated AA.

Effect of Mild Therapeutic Hypothermia Combined with Stereotactic Aspiration on Patients with Severe Cerebral Hemorrhage.

This study aimed to investigate the effects of mild therapeutic hypothermia combined with stereotactic aspiration of spontaneous intracerebral hematoma on neurological function, inflammatory markers, cerebral hematoma, and cerebral edema in patients with severe cerebral hemorrhage. The clinical data of 86 patients with severe cerebral hemorrhage treated at our hospital between March 2020 and January 2022 were retrospectively analyzed. The patients were grouped according to their treatment plans: the control group consisted of 40 patients who underwent stereotactic aspiration of the spontaneous intracerebral hematoma, whereas the study group consisted of 46 patients who received adjuvant mild therapeutic hypothermia in addition to the aforementioned treatment. Clinical efficacy, neurological function (NIHSS score), daily living ability (BI score), cerebral hematoma, cerebral edema, cerebral hemodynamics (PI, RI, Vm, Vd), inflammatory markers (IL-6, IL-8, TNF-α, hs-CRP), oxidative stress indicators (SOD, MDA, 8-iso-PGF2α), serum-related factors (MMP-9, ICAM-1, ET-1, NO), and prognosis were compared between the groups. The total efficacy rate in the study group (95.65%) was significantly higher than that in the control group (77.50%) (P < 0.05). Post-treatment NIHSS scores, intracranial hematoma volume, perihematoma edema volume, cerebral edema volume, RI, serum IL-6, IL-8, TNF-α, hs-CRP, MDA, and 8-iso-PGF2α levels were significantly lower in both groups, with the study group showing even greater reductions. The BI score and PI, Vm, Vd, SOD, and NO levels were significantly higher in the study group (P < 0.05). At the 6-month follow-up, the prognosis of patients in the intervention group was significantly better than that of patients in the control group (P < 0.05). The combination of mild therapeutic hypothermia with stereotactic aspiration of a spontaneous intracerebral hematoma has demonstrated efficacy in the treatment of severe cerebral hemorrhage. This approach effectively reduces cerebral hematoma and edema, improves daily living ability, alleviates neurological deficits, regulates cerebral hemodynamics, suppresses inflammatory responses and oxidative stress, modulates serum-related factor levels, and enhances patient prognosis.

Cataract, glaucoma, and diabetic retinopathy are independent risk factors affecting falls in the older adult with eye diseases.

OBJECTIVES: Falls are the leading cause of injury-related hospitalization in older adult, presenting a significant public health concern. To examine the specific eye diseases for risk factors of falls in the older adult. METHODS: A total of 775 older adults admitted to tertiary care hospitals were divided into a fall or non-fall group based on a questionnaire. Logistic regression analysis was used to identify factors associated with falls. RESULTS: With 208 falls, 775 participants were recruited. The major associated factors of falls were older age (Odds ratios [OR]: 1.05), female (OR: 1.91), cardiovascular diseases (OR: 1.65), more outdoor activities (OR: 2.81), cataract (OR: 1.65), glaucoma (OR: 1.63), diabetic retinopathy (OR: 2.72). CONCLUSIONS: Our study demonstrates that cataract, glaucoma, and diabetic retinopathy in the older adult with eye diseases are independent risk factors of falls, which may shed light on the prevention of falls in the older adult with eye diseases.

Determinants of incident atherosclerotic cardiovascular disease events among individuals with type 2 diabetic microvascular complications in the UK: a prospective cohort study.

OBJECTIVE: To evaluate the association of atherosclerotic cardiovascular disease (ASCVD) risk factors with incident ASCVD events among type 2 diabetes (T2D) individuals with microvascular complications. METHODS: We included T2D participants with only microvascular complications from the UK Biobank cohort at baseline (2006-2010). Multivariable-adjusted Cox proportional hazards models were used to study the association between ASCVD risk factors with adjudicated incident ASCVD in T2D participants with only microvascular complications. A restricted cubic spline approach was employed to evaluate potential nonlinear associations between ASCVD risk factors and ASCVD. RESULTS: We studied 4,129 T2D individuals with microvascular complications at baseline. Over a median follow-up of 11.7 years, a total of 1,180 cases of incident ASCVD were documented, of which 1,040 were CHD, 100 were stroke, and 40 were both CHD and stroke events. After multivariable-adjustment, high-density lipoprotein cholesterol (HDL-C) level was linearly associated with a decreased risk of incident ASCVD [hazard ratio (HR): 0.49, 95% Confidence interval (CI): 0.32-0.75, Plinear = 0.011] and each 10 nmol/L increase of lipoprotein(a) [Lp(a)] level (HR: 1.02, 95% CI: 1.00-1.04, Plinear = 0.012) was linearly associated with an increased risk of incident ASCVD in T2D participants with only microvascular complications. CONCLUSION: HDL-C levels and Lp(a) levels (per 10 nmol/L) showed an independent linear relation with ASCVD risk among T2D individuals with only microvascular complications at long-term follow-up.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank.

PURPOSE: Major risk factors of atherosclerotic cardiovascular disease (ASCVD) and mortality have been well-established in the general population. Our study is aimed at assessing longitudinal relationships between ASCVD risk factors and incident ASCVD events or all-cause mortality in patients with age-related macular degeneration (AMD). METHODS: Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors with adjudicated incident ASCVD events and all-cause mortality outcomes followed until 2021. A restricted cubic spline approach was utilized to assess nonlinear associations between potential cardiovascular risk factors and ASCVD or mortality. RESULTS: We identified 3508 eligible patients [mean (SD) age = 61.45 (6.43) years; 37.76% males] with AMD at baseline. During a median follow-up year of 12, there were 110 cases of ASCVD events and 186 cases of all-cause mortality. After multivariable adjustment, each 10 U/L increase of serum gamma-glutamyl transferase level was linearly associated with incident ASCVD [hazard ratio (HR) = 1.03, 95% CI = 1.00-1.07, Pnonlinear = 0.85)] in AMD. A history of chronic kidney disease (HR = 1.94, 95% CI = 1.09-3.46) and lower vitamin D [HR = 0.98, 95% CI = 0.97-0.99, per nanomoles per liter (nmol/L)] were significantly associated with all-cause mortality in patients with AMD, with the association between vitamin D and all-cause mortality presenting a U shape (Pnonlinear = 0.02). In contrast, risk factors significantly associated with ASCVD and all-cause mortality in healthy controls differed from patients with AMD. CONCLUSIONS: Our findings demonstrate risk factors associated with ASCVD events and all-cause mortality among individuals with AMD differed from healthy controls and suggest the long-term management of risk factors in patients with AMD.

Deep learning-based diagnosis of osteoblastic bone metastases and bone islands in computed tomograph images: a multicenter diagnostic study.

OBJECTIVE: To develop and validate a deep learning (DL) model based on CT for differentiating bone islands and osteoblastic bone metastases. MATERIALS AND METHODS: The patients with sclerosing bone lesions (SBLs) were retrospectively included in three hospitals. The images from site 1 were randomly assigned to the training (70%) and intrinsic verification (10%) datasets for developing the two-dimensional (2D) DL model (single-slice input) and "2.5-dimensional" (2.5D) DL model (three-slice input) and to the internal validation dataset (20%) for evaluating the performance of both models. The diagnostic performance was evaluated using the internal validation set from site 1 and additional external validation datasets from site 2 and site 3. And statistically analyze the performance of 2D and 2.5D DL models. RESULTS: In total, 1918 SBLs in 728 patients in site 1, 122 SBLs in 71 patients in site 2, and 71 SBLs in 47 patients in site 3 were used to develop and test the 2D and 2.5D DL models. The best performance was obtained using the 2.5D DL model, which achieved an AUC of 0.996 (95% confidence interval [CI], 0.995-0.996), 0.958 (95% CI, 0.958-0.960), and 0.952 (95% CI, 0.951-0.953) and accuracies of 0.950, 0.902, and 0.863 for the internal validation set, the external validation set from site 2 and site 3, respectively. CONCLUSION: A DL model based on a three-slice CT image input (2.5D DL model) can improve the prediction of osteoblastic bone metastases, which can facilitate clinical decision-making. KEY POINTS: • This study investigated the value of deep learning models in identifying bone islands and osteoblastic bone metastases. • Three-slice CT image input (2.5D DL model) outweighed the 2D model in the classification of sclerosing bone lesions. • The 2.5D deep learning model showed excellent performance using the internal (AUC, 0.996) and two external (AUC, 0.958; AUC, 0.952) validation sets.

Deep learning-based artificial intelligence model for classification of vertebral compression fractures: A multicenter diagnostic study.

Objective: To develop and validate an artificial intelligence diagnostic system based on X-ray imaging data for diagnosing vertebral compression fractures (VCFs). Methods: In total, 1904 patients who underwent X-ray at four independent hospitals were retrospectively (n=1847) and prospectively (n=57) enrolled. The participants were separated into a development cohort, a prospective test cohort and three external test cohorts. The proposed model used a transfer learning method based on the ResNet-18 architecture. The diagnostic performance of the model was evaluated using receiver operating characteristic curve (ROC) analysis and validated using a prospective validation set and three external sets. The performance of the model was compared with three degrees of musculoskeletal expertise: expert, competent, and trainee. Results: The diagnostic accuracy for identifying compression fractures was 0.850 in the testing set, 0.829 in the prospective set, and ranged from 0.757 to 0.832 in the three external validation sets. In the human and deep learning (DL) collaboration dataset, the area under the ROC curves(AUCs) in acute, chronic, and pathological compression fractures were as follows: 0.780, 0.809, 0.734 for the DL model; 0.573, 0.618, 0.541 for the trainee radiologist; 0.701, 0.782, 0.665 for the competent radiologist; 0.707,0.732, 0.667 for the expert radiologist; 0.722, 0.744, 0.610 for the DL and trainee; 0.767, 0.779, 0.729 for the DL and competent; 0.801, 0.825, 0.751 for the DL and expert radiologist. Conclusions: Our study offers a high-accuracy multi-class deep learning model which could assist community-based hospitals in improving the diagnostic accuracy of VCFs.

EBD: an eye biomarker database.

MOTIVATION: Many ophthalmic disease biomarkers have been identified through comprehensive multiomics profiling, and hold significant potential in advancing the diagnosis, prognosis, and management of diseases. Meanwhile, the eye itself serves as a natural biomarker for several systemic diseases including neurological, renal, and cardiovascular systems. We aimed to collect and standardize this eye biomarkers information and construct the eye biomarker database (EBD) to provide ophthalmologists with a platform to search, analyze, and download these eye biomarker data. RESULTS: In this study, we present the EBD , a world-first online compilation comprising 889 biomarkers for 26 ocular diseases and 939 eye biomarkers for 181 systemic diseases. The EBD also includes the information of 78 "nonbiomarkers"-the objects that have been proven cannot be biomarkers. Biological function and network analysis were conducted for these ocular disease biomarkers, and several hub pathways and common network topology characteristics were newly identified, which may promote future ocular disease biomarker discovery and characterizes the landscape of biomarkers for eye diseases at the pathway and network level. The EBD is expected to yield broader utility among developmental biologists and clinical scientists in and outside of the eye field by assisting in the identification of biomarkers linked to eye disorders and related systemic diseases. AVAILABILITY AND IMPLEMENTATION: EBD is available at http://www.eyeseeworld.com/ebd/index.html.

Novel insights into impacts of the "7.20" extreme rainstorm event on water supply security of Henan Province, China: Levels and health risks of tap water disinfection by-products.

Spatial distributions, levels, and comprehensive assessments of post-flood tap water disinfection by-products (DBPs) were first studied in Henan Province after the "7.20" Extreme Rainstorm Event in 2021. DBPs levels and health risks in tap water were higher in areas flooded (waterlogged) by storm or upstream flood discharge (WA) and rainstorm-affected areas (RA) compared with other areas (OA), suggesting that extreme rainstorm and flooding events may somehow exacerbate DBPs contamination of tap water through disinfection. WA sites were characterized as contamination hotspots. The results revealed high haloacetic acids (HAAs) levels in WA (Avg: 57.79 µg·L-1) and RA (Avg: 32.63 µg·L-1) sites. Compared with normal period, DBPs-caused cancer risk increased by 3 times, exceeding the negligible risk level. Cancer risk came primarily from the ingestion of trihalomethanes (THMs) (>80%), children were the sensitive group. Those between 30 and 69 showed approximately 1.7 times higher disability-adjusted life yearsper person-yearthan other age groups. Apart from regulated DBPs, bromochloracetic acid (BCAA) and dibromoacetonitrile (DBAN) appear to be the main toxicity contributors in these samples. Our results provide a scientific basis for preventing and controlling health risks from tap water DBPs and for assessing the social benefits and burdens of emergency disinfection.

Differential regulation of phosphorylation, structure, and stability of circadian clock protein FRQ isoforms.

Neurospora crassa is an important model organism for circadian clock research. The Neurospora core circadian component FRQ protein has two isoforms, large FRQ (l-FRQ) and small FRQ (s-FRQ), of which l-FRQ bears an additional N-terminal 99-amino acid fragment. However, how the FRQ isoforms operate differentially in regulating the circadian clock remains elusive. Here, we show l-FRQ and s-FRQ play different roles in regulating the circadian negative feedback loop. Compared to s-FRQ, l-FRQ is less stable and undergoes hypophosphorylation and faster degradation. The phosphorylation of the C-terminal l-FRQ 794-aa fragment was markedly higher than that of s-FRQ, suggesting the l-FRQ N-terminal 99-aa region may regulate the phosphorylation of the entire FRQ protein. Quantitative label-free LC/MS analysis identified several peptides that were differentially phosphorylated between l-FRQ and s-FRQ, which were distributed in FRQ in an interlaced fashion. Furthermore, we identified two novel phosphorylation sites, S765 and T781; mutations S765A and T781A showed no significant effects on conidiation rhythmicity, although T781 conferred FRQ stability. These findings demonstrate that FRQ isoforms play differential roles in the circadian negative feedback loop and undergo different regulations of phosphorylation, structure, and stability. The l-FRQ N-terminal 99-aa region plays an important role in regulating the phosphorylation, stability, conformation, and function of the FRQ protein. As the FRQ circadian clock counterparts in other species also have isoforms or paralogues, these findings will also further our understanding of the underlying regulatory mechanisms of the circadian clock in other organisms based on the high conservation of circadian clocks in eukaryotes.

Signet ring cell-like diffuse large B-cell lymphoma involving the breast: a case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) with signet ring cell components is extremely rare. Here, we present a case of DLBCL with signet ring cell components involving the breast, which can be easily confused with invasive lobular carcinoma of the breast or metastatic signet ring cell carcinoma of gastrointestinal origin. CASE PRESENTATION: A 66-year-old woman presented with a painless mass in her left breast. Enhanced magnetic resonance imaging (MRI) of the breast revealed a 42 × 29 × 28 mm mass in the left breast. Histological examination revealed a diffuse or scattered arrangement of round cells mixed with signet ring-like cells. Immunohistochemically, the neoplastic cells were positive for PAX-5, CD79a, CD20, Bcl-6, and MUM-1 but and negative for cytokeratin, ER, PR, E-cadherin, and P120. The Ki-67 proliferation index was approximately 70%. Fluorescence in situ hybridisation (FISH) demonstrated non-rearrangement of Bcl-2, Bcl-6, and c-MYC genes. Immunohistochemistry and FISH examination confirmed the diagnosis of DLBCL. Subsequently, immunofluorescence showed both IgM and IgG deposits in the signet ring-like lymphocytes. After confirming the diagnosis, the patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy in a specialist hospital and achieved partial remission; however, she unfortunately died of secondary pneumocystis pneumonia infection 3 months later. CONCLUSION: Malignant lymphoma with signet ring cell morphology is quite uncommon, and this variant can be a diagnostic pitfall. We emphasise that pathologists should consider lymphoma in the differential diagnosis of malignant breast tumours.

The associations and mediators between visual disabilities and anxiety disorders in middle-aged and older adults: A population-based study.

Visual disabilities significantly impact an individual's mental health. Little is known about the prospective relationship between visual disabilities and anxiety disorders and the underlying effects of modifiable risk factors. Our analysis was based on 117,252 participants from the U.K. Biobank, with baseline data collected between 2006 and 2010. Habitual visual acuity was measured by a standardized logarithmic chart, and ocular disorders reported using questionnaires were collected at baseline. Incident hospitalized anxiety recorded using longitudinal linkage with hospital inpatient data, lifetime anxiety disorder, and current anxiety symptoms assessed by a comprehensive online mental health questionnaire were identified over a 10-year follow-up. After adjustments for confounding factors, one-line worse visual acuity (0.1 logarithm of the minimum angle of resolution [logMAR]) was associated with an increased risk of incident hospitalized anxiety (HR = 1.05, 95% CI = 1.01-1.08), lifetime anxiety disorder (OR = 1.07, 95% CI [1.01-1.12]), and current anxiety scores (ß = 0.028, 95% CI [0.002-0.054]). Besides poorer visual acuity, the longitudinal analysis also supported that each ocular disorder (including cataracts, glaucoma, macular degeneration, and diabetes-related eye disease) was significantly associated with at least two anxiety outcomes. Mediation analyses highlighted that subsequent onsets of eye diseases, especially cataracts, and lower socioeconomic status (SES) partly mediated the association between poorer visual acuity and anxiety disorders. This study demonstrates an overall association between visual disabilities and anxiety disorders in middle-aged and older adults. In particular, early interventions involving treatments for visual disabilities and effective psychological counseling services sensitive to socioeconomic status may help prevent anxiety in those living with poor vision. (PsycInfo Database Record (c) 2023 APA, all rights reserved).