GCN2 in Viral Defence and the Subversive Tactics Employed by Viruses.

The recent SARS-CoV-2 pandemic and associated COVID19 disease illustrates the important role of viral defence mechanisms in ensuring survival and recovery of the host or patient. Viruses absolutely depend on the host's protein synthesis machinery to replicate, meaning that impeding translation is a powerful way to counteract viruses. One major approach used by cells to obstruct protein synthesis is to phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α). Mammals possess four different eIF2α-kinases: PKR, HRI, PEK/PERK, and GCN2. While PKR is currently considered the principal eIF2α-kinase involved in viral defence, the other eIF2α-kinases have also been found to play significant roles. Unsurprisingly, viruses have developed mechanisms to counteract the actions of eIF2α-kinases, or even to exploit them to their benefit. While some of these virulence factors are specific to one eIF2α-kinase, such as GCN2, others target all eIF2α-kinases. This review critically evaluates the current knowledge of viral mechanisms targeting the eIF2α-kinase GCN2. A detailed and in-depth understanding of the molecular mechanisms by which viruses evade host defence mechanisms will help to inform the development of powerful anti-viral measures.

[Analysis of factors affecting the prognosis of patients with pancreatic cancer patients with obstructive jaundice].

Objective: Objective To analyze the relationship between the survival outcomes of pancreatic cancer patients with obstructive jaundice and various clinical and pathological factors. Methods: A case series study was conducted, where clinical data from pancreatic cancer patients with obstructive jaundice, who were admitted to the Cancer Hospital of Tianjin Medical University between March 2022 and May 2023, were retrospectively gathered. Factors potentially affecting patient prognosis were initially analyzed using univariate analysis, followed by multivariate analysis using the Cox regression model for selected factors. A P-value of less than 0.05 was deemed statistically significant. Results: The study included 104 patients, comprising 69 males and 35 females, with a median age of 62 years (ranging from 38 to 85 years). Of these, 76 patients (73.1%) were followed until death, with a median survival time of 8.9 (6.2,11.5) months. The number of deaths versus surviving cases at 6 and 12 months were 20/75 and 64/14, respectively, resulting in estimated survival rates of 79.6% and 22.8%. Univariate analysis identified factors such as weight loss, primary site, TNM stage, liver metastasis, number of organs with tumor, stage at which jaundice appeared, CA19-9 levels, albumin levels, and D-dimer levels as significant in influencing prognosis (all P<0.05). Multivariate analysis revealed TNM stage, number of organs with tumor, method of jaundice treatment, albumin levels, and D-dimer levels as independent prognostic factors (all P<0.05). Conclusion: In pancreatic cancer patients presenting with obstructive jaundice, close monitoring of weight loss, primary site, TNM stage, liver metastasis, number of organs with tumor, the timing of jaundice occurrence, method of jaundice treatment, CA19-9, albumin, and D-dimer levels is crucial, as these factors may significantly impact the patient's survival and prognosis.

[Spatial-temporal distribution characteristics of etiologically positive pulmonary tuberculosis in Jiangsu Province from 2011 to 2021].

Objective: To analyze the spatial-temporal distribution of etiologically positive pulmonary tuberculosis (PTB) at the county (city, district) unit in Jiangsu Province from 2011 to 2021 to provide evidence for the implementation and adjustment of prevention and control strategies of PTB in Jiangsu Province. Methods: The registration data of etiologically positive PTB patients in Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System in the China Information System of Disease Control and Prevention. Data on the permanent population were from the statistical yearbook of each county (city, district) in Jiangsu Province. Geoda 1.18.0 software was used to analyze the global and local spatial autocorrelation and explore the spatial clustering. SaTScan 10.1 software was used to analyze the spatial-temporal clusters, and ArcGIS 10.7 software was used to visualize the spatial-temporal clusters. Results: A total of 128 240 etiological positive PTB cases were registered in Jiangsu Province from 2011 to 2021, with an average annual registration rate of 13.99/100 000. The registration rate showed an overall upward trend (trend χ2=63.49, P<0.001) after 2017, and the etiologically positive rate showed an overall upward trend (trend χ2=3 710.86, P<0.001). The annual Moran's I values ranged from 0.107 to 0.343, which showed a spatial clustering distribution. The results of local spatial autocorrelation analysis showed that there were "high-high" clustering areas in Jiangsu Province each year, showing a dynamic distribution, and most of the areas were distributed in the central and southern regions of Jiangsu Province, with the largest number (7) in 2015 and the smallest number (1) in 2011. A total of 4 spatial-temporal clustering areas were explored by spatial-temporal scanning analysis (all P<0.001), among which the first-level clustering area covered 3 counties (cities, districts), namely Changshu, Taicang, and Xiangcheng District of Suzhou, and the clustering time was from 2011 to 2015. The secondary clustering areas covered 24 counties (cities, districts), mainly covering Jiangsu's central and northern regions, such as Huai'an, Suqian, and Yancheng. The third-level clustering areas covered 26 counties (cities, districts); the fourth-level clustering area was the Gaochun District of Nanjing, with the clustering period from 2017 to 2021. Conclusions: From 2011 to 2021, the etiologically positive PTB registration rate at the county (city, district) level in Jiangsu Province had obvious spatial-temporal clustering characteristics. The clustering areas included the northern areas with relatively backward economies and the southern areas with better economic development. Multiple measures should be taken to prevent and control PTB according to the specific situation in different regions.

[Epidemic characteristics and trend analysis of major injuries deaths among children and adolescents in Jiangsu Province from 2012 to 2021].

Objective: To understand the situation and epidemic characteristics of injury deaths among children aged 5 to 24 years in Jiangsu Province from 2012 to 2021 and the trend of annual changes. Methods: The main injury mortality data of children and adolescents was collected, and the crude and standardized mortality rates of road traffic accidents, drowning, suicide, and accidental falls among children and adolescents over a decade and the annual average percentage of change (AAPC) were calculated. The main injury mortality characteristics and trends of children and adolescents of different age groups and genders were analyzed. Results: The total number of injury deaths among 5 to 24 adolescents in Jiangsu Province was 16 052, with a standardized mortality rate of 9.58/100 000. There was no significant trend in the overall standardized mortality rate of injuries (AAPC=-3.450%, P=0.055). The standardized mortality rate of road traffic injuries among children and adolescents showed a decreasing trend over the past decade, with statistical significance (AAPC=-9.406%, P<0.001). The standardized suicide mortality rate showed an upward trend over the past decade, with statistical significance (AAPC=9.000%, P=0.001). The overall injury mortality rate showed an upward trend with age. Suicide rates in males and females were on the rise and both have statistical significance (AAPC=9.420% and AAPC=9.607%, both P<0.05). The standardized mortality rates of female traffic accidents, drowning, and male traffic accidents showed a decreasing trend and were statistically significant (AAPC for female traffic accidents=-7.364%, AAPC for female drowning=-5.352%, and AAPC for male traffic accidents=-10.242%, all P<0.05). The standardized mortality rate of urban and rural traffic accidents showed a decreasing trend and was statistically significant(AAPC=-7.899% and AAPC=-9.421%, both P<0.001). The standardized suicide mortality rate showed an upward trend and statistical significance (AAPC=11.009% and AAPC=7.528%, both P<0.05). Conclusions: The overall injury situation of children and adolescents in Jiangsu Province improved in the past decade from 2012 to 2021, but the suicide mortality rate was on the rise. It is necessary to focus on the mental health issues of this age group and to strengthen the prevention and control of suicide among children and adolescents, in Jiangsu.

Enteropathy and intestinal malabsorption in patients treated with antihypertensive drugs. A retrospective cohort study.

OBJECTIVES: To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea. METHODS: In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021. RESULTS: Of the 44,775 patients, 51 (0.11%) were observed to have enteropathy or intestinal malabsorption. Compared with the ACEI group, the adjusted odds ratios (ORs) for enteropathy and intestinal malabsorption were OR=1.313 (95% confidence interval [CI]: [0.188-6.798], p=0.893) for olmesartan, OR=0.915 (95% CI: [0.525-1.595], p=0.754) for the other ARBs, OR=0.928 (95% CI: [0.200-4.307]; p=0.924) for the CCB, and OR=0.663 (95% CI: [0.151-2.906]; p=0.586) for the BBs group. These findings were adjusted for factors such as age, gender, duration of antihypertensive medication, and comorbidities. CONCLUSION: In a retrospective cohort study of patients on antihypertensive medications, no significant difference was found in the incidence of enteropathy or intestinal malabsorption when ACEI was compared to olmesartan, other ARBs, CCB, and BBs.

Isolated non-immune mediated second-degree atrioventricular block in fetus: natural history and predictive factors for spontaneous recovery.

OBJECTIVES: To uncover the clinical course of fetal isolated non-immune mediated second-degree AVB and determine the factors associated with the spontaneous recovery for fetal non-immune second-degree atrioventricular block (AVB). METHODS: A total of 20 fetuses with isolated, non-immune mediated second-degree AVB were prospectively recruited between 2014 and 2022. These fetuses were divided into the spontaneous recovery group (n=12) and the non-spontaneous recovery group (n=8). Maternal and fetal basic characteristics, intrauterine and postnatal outcomes were compared between groups. RESULTS: Twelve fetuses restored 1:1 atrioventricular conduction in utero and did not recur during the postnatal follow-up period. The residual eight fetuses maintained as second-degree AVB and six of them were aborted due to parental request in utero. Of the two live children with second-degree AVB, one of them progressed to complete AVB at the latest follow up at the age of 34 months, but without any symptoms, heart enlargement or dysfunction. The residual one progressed to complete AVB and was finally diagnosed with type 2 long-QT syndrome. Fetuses in the spontaneous recovery group presented with earlier gestational age at diagnosis (20.0[17.0-26.0] vs. 24.5[18.0-35.0] weeks, p=0.004) and higher atrial rate (147[130-160] vs 138.00[125.00-149.00] bpm, p=0.006) in comparison with the non-spontaneous recovery group. A cut-off value of 22.5 weeks of gestational age and 144 bpm of atrial rate at diagnosis could predict the failure of spontaneous recovery, with sensitivities of 87.5%, 75%, and specificities of 92.0%, 87.5%, respectively. CONCLUSIONS: The outcome of fetal non-immune second-degree AVB was favorable. Earlier gestational age at diagnosis and higher atrial rate were related to spontaneous reversion for isolated non-immune-mediated second-degree AVB. However, prenatal gene test should be performed for those with persistent AVB to exclude the heritable disorders including LQTS. These findings may provide important references for clinical management and prenatal counseling. This article is protected by copyright. All rights reserved.

Improving Communication with Family Members during a Global Pandemic: Effect on Patient Experience.

OBJECTIVES: Communication with patients and their families/caregivers to facilitate informed decision making is an integral part of patient/family-centered care. Due to the high coronavirus disease 2019 (COVID-19) infection rates and limited personal protective equipment, healthcare systems were forced to restrict patient visitors, limit patient-provider interactions, and implement other changes in treatment protocols that disturbed traditional communications and risked eroding patient/family-centered care and adversely affected patient satisfaction. This article focuses on changes in patient experience in two dedicated COVID-19 units of an academic medical center located in the US South as a result of the enhanced communication process implemented specifically during the COVID-19 pandemic. METHODS: This retrospective quality improvement project used data from Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, fielded between January 1, 2021 and August 31, 2021, to understand the role of a proactive communication initiative in patient satisfaction. RESULTS: Our results show that HCAHPS scores for hospital unit hospital unit 4 (HSP4) in all categories increased over time, with the greatest improvements seen in the responsiveness of staff and care transition; however, HCAHPS scores for hospital unit HSP3 remained stable, with a small increase in responsiveness of staff. CONCLUSIONS: Our findings suggest that communication is a critical factor in patient satisfaction, demonstrating the efficacy of a swift and innovative initiative to improve communication with family/caregivers, which may have been linked to better patient experiences. Developing communication strategies is crucial for enhancing patient satisfaction.

Improving chilling tolerance of peanut seedlings by enhancing antioxidant-modulated ROS scavenging ability, alleviating photosynthetic inhibition, and mobilizing nutrient absorption.

Peanut production is threatened by climate change. Damage to seedlings from low temperatures in early spring can limit yield. Plant adaptations to chilling stress remain unclear in peanut seedlings. It is essential to understand how peanut acquires chilling tolerance. We evaluated effects of chilling stress on growth and recovery of peanut seedlings. We compared and analysed biological characteristics, antioxidants, photosynthesis, biochemical and physiological responses, and nutrient absorption at varying levels of chilling. Compared with chilling-sensitive FH18, the reduced impact of chilling stress on chilling-tolerant NH5 was associated with reduced ROS accumulation, higher ascorbate peroxidase activity and soluble sugar content, lower soluble protein content, and smaller reductions in nutrient content during stress. After removal of chilling stress, FH18 had significant accumulation of O2 •- and H2O2, which decreased photosynthesis, nutrient absorption, and transport. ROS-scavenging reduced damage from chilling stress, allowed remobilization of nutrients, improved chilling tolerance, and restored plant functioning after chilling stress removal. These findings provide a reference for targeted research on peanut seedling tolerance to chilling and lay the foundation for bioinformatics-based research on peanut chilling tolerance mechanisms.

[A prospective study on association between sleep duration and the risk of chronic obstructive pulmonary disease in adults in Suzhou].

Objective: To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou. Methods: The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio (HR) values and their 95%CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results: The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD (HR=1.42, 95%CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers (HR=2.49, 95%CI: 1.35-4.59, interaction P<0.001). Conclusion: Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Expression of chicken epidermal growth factor (cEGF) in Escherichia coli regulates the microflora structure of the duodenum to improve growth performance and intestinal morphogenesis in broilers.

1. A study used gene synthesis to obtain the functional domains of chicken epidermal growth factor (cEGF) and examined their impact on broiler growth performance, small intestinal morphology, digestive enzyme activities in the intestinal contents and the structure of duodenal microflora.2. The pET-32a-cEGF recombinant expression vector was constructed. The specific band at 26 KDa was shown by SDS-PAGE analysis and WB results. The purified protein content was shown to be 1687 µg/ml by assay.3. A total of 180 healthy, one-day-old Arbor Acres male, white-feathered broilers were randomly divided into three dietary treatment groups (six replicate pens, 10 birds per replicate): A control diet (ND); cEGF diet (cEGF), control supplemented with 250 mg/kg cEGF and the control diet (CD) supplemented with 250 mg/kg chlortetracycline.4. The results showed that feeding the cEGF and CD diet reduced FCR of broilers aged 1-21 d, average daily feed intake (ADFI) at 22-42 d, and the FCR in the whole period (1-42 d; p < 0.05). Compared with the ND group, the cEGF diet increased duodenal α-amylase and alkaline phosphatase activities in the 1-21 d, duodenal lipase, alkaline phosphatase, and ileal alkaline phosphatase activities in the post-period and increased villus height in the duodenum and ileum (p < 0.05). In addition, the ACE and Chao1 index for the birds fed cEGF were higher than the ND group (p < 0.05). At the phyla level, Firmicutes and Proteobacteria were dominant in all groups. At the genus level, the dominant genus was Lactobacillus. The LEfSe analysis showed that the cEGF group was enriched by 11 species including Brevibacillus, Eisenbergiella, Cloacibacterium, Butyricoccus spp.5. The addition of 250 mg/kg cEGF to the diet can increase growth performance by improving intestinal development and digestive enzyme activity, which may be related to the duodenal intestinal microflora. Therefore, cEGF is an effective alternative to antibiotics in broiler farming.

[Epidemic trends and prevention and control of seasonal influenza in China after the COVID-19 pandemic].

During the COVID-19 pandemic, a series of non-pharmaceutical interventions, which were implemented to curb the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significantly modified the seasonal pattern of influenza. The intensity of influenza activity markedly decreased and B/Yamagata lineage was no longer detected. As the national influenza sentinel surveillance data shown, clear seasonal patterns were observed for influenza between 2012-2019, annually with an average of 14.57% of specimens tested positive for influenza virus. However, the seasonal pattern of influenza was disrupted after the outbreak of COVID-19. In the 2020-2021 season, influenza demonstrated an extremely low activity (yearly positivity rate<1.0%), followed by a resurgence of winter peak in the 2021-2022 season. Following the downgrade of management of COVID-19 to Class B in China in December 26, 2022, social activities gradually resumed, leading to the rebound of influenza activity with an out-of-season ciculation. After COVID-19 pademic, other respiratory infectious diseases caused by SARS-CoV-2, respiratory syncytial virus, and mycoplasma pneumonia were alternatively or concurrently circulated with influenza. The prevention and control of influenza and other respiratory infectious diseases emphasizes a multi-disease prevention strategy, including long-term and continuous monitoring the epidemic trends in influenza virus and SARS-CoV-2, promoting influenza and COVID-19 vaccination among key populations, and strengthening the knowledge and public awareness of prevention and control for respiratory infectious diseases, etc.

[Analysis of the experience and procedural complications of trans-radial access versus trans-femoral access for hepatic arterial perfusion chemotherapy in patients with advanced hepatic malignancies:a retrospective study].

Objective: To analyze the differences between trans-radial access (TRA) and trans-femoral access (TFA) in hepatic arterial perfusion chemotherapy (HAIC) in terms of patient experience, postoperative complications, and patient preferences; explore whether TRA in HAIC is associated with better patient experience and compliance; and determine whether it is safer than TFA. Methods: The study was a retrospective cohort study of patients with advanced hepatocellular carcinoma and liver metastases from colorectal cancer treated with HAIC. We enrolled a total of 91 patients with advanced liver malignancies treated with HAIC from November 2022 to May 2023 in the Department of Interventional Therapy and Hepatobiliary Medicine at Tianjin Medical University Cancer Hospital. The patients were divided into three groups: group TRA (n=20, receiving TRA HAIC only), group TFA (n=33, receiving TFA HAIC only), and crossover group [n=19, receiving TFA HAIC (Cross-TFA group) first, followed by TRA HAIC (Cross-TRA group)]. Meanwhile, to facilitate the expression of partial results, all patients receiving TRA HAIC were defined as the TRA-HAIC group (n=39, TRA+Cross-TRA group), and all patients receiving TFA HAIC were defined as the TFA-HAIC group (n=52, TFA+Cross-TFA group). The primary research index was the Quality of Life (QOL) visualization scale score. The secondary research index included approach-related and catheter-related adverse events, duration of surgery, and mean length of patient stay. We used various statistical methods such as Mann-Whitney U test, t-test, Chi-square test, Fisher's exact test, univariate logistic regression analysis, and multi-factor analysis. Results: TRA patients had significantly lower QOL scores than TFA patients (all P<0.001). The QOL scores of the Cross-TRA group were significantly lower than those of the Cross-TFA group (pain at the puncture site Z=-3.24, P=0.001, others P<0.001). The QOL scores of the Cross-TRA group were compared with those of the TRA group, which showed that the scores of the Cross-TRA group in overall discomfort (Z=-3.07,P=0.002), postoperative toilet difficulty (Z=-2.12, P=0.034), and walking difficulty (Z=-2.58, P=0.010) were significantly lower than those of the TRA group. Satisfaction scores were significantly higher in the Cross-TRA group than in the Cross-TFA group (Z=-3.78, P<0.001), and patients were more likely to receive TRA HAIC as the next procedure (χ2=30.42, P<0.001). In terms of mean length of stay, patients receiving TRA HAIC had a significantly lower mean length of stay than those receiving TFA HAIC (50.1±3.2 h vs. 58.4±6.4 h, t=7.98, P<0.001). The incidence of radial artery occlusion (RAO) as an approach-related adverse event was 15.4% (6/39) in the TRA-HAIC group, which was significantly higher than that in the TFA-HAIC group (15.4% vs. 0, χ2=8.56, P=0.005). Notably, multifactorial analysis of RAO-related factors showed that intraoperative enoxaparin use and patency of radial artery flow during pressure were significantly associated with a reduced risk of postoperative RAO (P=0.037 for enoxaparin use and P=0.049 for pressure). Conclusions: With respect to procedure approach, TRA was significantly better than TFA in terms of patient satisfaction and mean length of stay. Through further process optimization and prevention of adverse reactions, the incidence of adverse reactions can be maintained at a relatively low level, so that patients can benefit from TRA in future operations in terms of cost-effectiveness and medical efficiency.

Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Beyond Vision: A View from Eye to Alzheimer's Disease and Dementia.

With the aging of the global population, the health care burden of Alzheimer's disease (AD) and dementia is considered to increase dramatically in the coming decades. Given the insufficiency of effective interventions for AD and dementia, clinical research on identifying potentially modifiable risk factors and early diagnostic biomarkers becomes a public health priority. Currently, extracerebral manifestations with a large proportion of ocular involvement are usually recognized to precede the symptoms of AD and dementia. Growing epidemiologic evidence also suggests that eye disorders, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy, and so on, are closely associated with and even have a higher incidence of AD and dementia. The eye, as an extension of the central nervous system, therefore has the potential to provide a feasible approach to detecting structural and functional abnormalities of the brain. Numerous new imaging modalities are developed and give novel insights into the detection of several neurodegenerative, vascular, neuropathological, and other ocular abnormalities of AD and dementia in scientific research and clinical application. This review provides an overview of the epidemiologic associations between eye disorders and AD or dementia and summarizes the recent advances in ocular examinations and techniques employed for the detection of AD and dementia. With more brain-and-eye interconnections being identified, the eye is becoming a noninvasive and easily accessible window for the early diagnosis and prevention of AD and dementia.

Comparative Transcriptomic Analysis of the Flavor Production Mechanism in Yogurt by Traditional Starter Strains.

Synergistic fermentation of milk by Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus is one of the key factors that determines the quality of yogurt. In this study, the mechanism whereby yogurt flavor compounds are produced by mixture of S. thermophilus SIT-20.S and L. delbrueckii ssp. bulgaricus SIT-17.B were investigated by examining these strains' flavor production, growth, and gene transcription. The results showed that yogurt produced by a 10:1 mixture of the aforementioned strains had the highest abundance of acetoin, whereas yogurt produced by a 1:1 mixture had the highest abundance of diacetyl and acetaldehyde. In addition, the growth of S. thermophilus SIT-20.S was enhanced in the 10:1 mixture. Transcriptomic analysis revealed differentially expressed genes in the flavor-compound-related pathways of S. thermophilus SIT-20.S and L. delbrueckii ssp. bulgaricus SIT-17.B in yogurts produced by 10:1 and 1:1 mixture compared with those produced by either strain alone. Mixed fermentations regulated the expression of genes related to glycolysis, resulting in an increase of pyruvate, which is an important precursor for diacetyl and acetoin synthesis. The gene encoding the acetoin reductase (SIT-20S_orf01454) was decreased in S. thermophilus SIT-20.S, which ensured the accumulation of acetoin. Besides, gene encoding the acetaldehyde dehydrogenase (SIT-20S_orf00949) was upregulated in S. thermophilus SIT-20.S, and the expression of alcohol dehydrogenase (SIT-20S_orf01479; SIT-17B_orf00943) was downregulated in both strains, maintaining the abundance of acetaldehyde. In addition, the gene encoding the NADH oxidase (SIT-17B_orf00860) in L. delbrueckii ssp. bulgaricus SIT-17.B were upregulated, which promoted the accumulation of diacetyl and acetoin. In conclusion, we characterized the mechanism by which S. thermophilus and L. delbrueckii ssp. bulgaricus synergistically generated yogurt flavor compounds during their production of yogurt and highlighted the importance of appropriate proportions of fermentation starters for improving the flavor of yogurts.

[Mitigating metal artifacts from cobalt-chromium alloy crowns in cone-beam CT images through deep learning techniques].

Objective: To develop and evaluate metal artifact removal systems (MARS) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images. Methods: A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05). Results: Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0, 1.5, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively (F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively (F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 (F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 (F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 (F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 (F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARS. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions: Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

Prognostic value of cardiac magnetic resonance imaging feature tracking technology in patients with light chain amyloidosis.

AIM: To undertake a meta-analysis of the prognostic value of cardiac magnetic resonance imaging feature tracking (CMR-FT) in patients with light-chain cardiac amyloidosis (LCA). MATERIALS AND METHODS: A systematic search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. All analyses were conducted using RevMan 5.3 software. RESULTS: Eight studies were included with 663 patients. For the left ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired global circumferential (GCS), radial (GRS) and longitudinal (GLS) strain in survivors of LCA (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.09-1.25; 0.95, 0.93-0.96; 1.12, 1.05-1.20, all p<0.001). For ejection fraction (EF) and mass index, surviving patients had higher EFs and mass index (OR 0.96, 95% CI 0.96-0.97; 1.01, 1.01-1.02). For the right ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired GLS and GRS in survivors of LCA (OR 1.11, 95% CI 1.08-1.15; 0.93, 0.90-0.96, all p<0.001). Surviving patients had higher EFs (OR 0.97, 95% CI 0.96-0.98, p<0.001). Upon removing the studies one by one, there was no significant change in the results of the study. Both analyses showed no apparent publication deviation on funnel plots. CONCLUSION: Parameters derived from CMR-FT technology are promising new predictors for LCA, and are easily available and reliable. Patients with poor myocardial deformability are at highest risk of death.

The analgesic effect of transversalis fascia plane block after caesarean section under spinal anaesthesia with intrathecal morphine: a randomised controlled trial.

We aimed to test whether bilateral injection of bupivacaine 0.25% in the transversalis fascia plane reduced 24 h opioid dose after singleton caesarean section, under spinal anaesthesia with intrathecal morphine, compared with saline 0.9% injectate. We allocated randomly 52 women to bilateral injection of 20 ml saline 0.9% on arrival in the post-anaesthesia care unit and 54 women to bilateral injection of 20 ml bupivacaine 0.25% (with adrenaline 2.5 µg.ml-1 ). Mean (SD) cumulative morphine equivalent opioid dose 24 h after saline injection was 32.3 (28.3) mg and 18.7 (20.2) mg after bupivacaine injection, a mean (95%CI) difference of 13.7 (4.1-23.2) mg (p = 0.006). Median (IQR [range]) time to first postoperative opioid dose was 3.0 (1.5-10.3 [0.0-57.4]) h after saline 0.9% and 8.2 (2.7-29.6 [0.2-55.4]) h after bupivacaine 0.25% (p = 0.054). Transversalis fascia plane with bupivacaine 0.25% with adrenaline reduced postoperative pain at rest during 48 h (0-10-point scale) by a mean (95%CI) of 0.9 (0.2-1.6) points (p = 0.013) and on movement by 1.2 (0.4-2.1) points (p = 0.004). We conclude that transversalis fascia plane bupivacaine 0.25% with adrenaline reduces pain and opioid dose after caesarean section compared with saline 0.9%.

[10-Methacryloyloxydecyl dihydrogen phosphate in resin-to-zirconia bonding durability: a systematic review and meta-analysis].

Objective: To systematically assess the durability of the 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) pretreated resin-to-zirconia bonding and conducted a meta-analysis to provide clinical guidance on zirconia bonding strategies. Methods: A comprehensive search was conducted on PubMed, Scopus, Web of Science, CNKI, and Wanfang database to identify relevant studies on the resin-to-zirconia bonding after surface pretreatment with 10-MDP. Strict inclusion and exclusion criteria were applied to select appropriate literature and extract essential information and data. The included studies were categorized based on aging methods (water storage, thermocycling, or both), 10-MDP application methods (within primer, adhesive, resin cement, or both), and additional surface treatments (alumina sandblasting, tribochemical silica coating, acid etching, laser etching, and plasma treatment) and were analyzed by Review Manager 5.4. The evaluation indicator was the bonding strength of zirconia after surface pretreatment with 10-MDP. Results: A total of 72 studies were included in the systematic review, with 68 studies eligible for the meta-analysis. The bonding strength of zirconia decreased significantly after aging [P<0.001; mean difference (MD): 5.58; 95%CI: 5.11-6.05]. No significant differences in bonding strength of zirconia were observed after aging when employing various application methods of 10-MDP (all P>0.05). The bonding strength of zirconia was significantly enhanced after aging when 10-MDP was applied in conjunction with additional surface treatments, as compared to the application of 10-MDP alone (P<0.001; MD: 10.17; 95%CI: 8.20-12.14). Conclusions: The bonding strength of zirconia pretreated with 10-MDP exhibited a reduction after undergoing water storage or thermocycling. The application of 10-MDP with additional surface treatments enhanced the bonding strength of zirconia after aging, while the application methods of 10-MDP did not exert an influence.