Identification and Construction of a Disulfidptosis-Mediated Diagnostic Model and Associated Immune Microenvironment of Osteoarthritis from the Perspective of PPPM.

Background: Osteoarthritis (OA) is a major cause of human disability. Despite receiving treatment, patients with the middle and late stage of OA have poor survival outcomes. Therefore, within the framework of predictive, preventive, and personalized medicine (PPPM/3PM), early personalized diagnosis of OA is particularly prominent. PPPM aims to accurately identify disease by integrating multiple omic techniques; however, the efficiency of currently available methods and biomarkers in predicting and diagnosing OA should be improved. Disulfidptosis, a novel programmed cell death mechanism and appeared in particular metabolic status, plays a mysterious characteristic in the occurrence and development of OA, which warrants further investigation. Methods: In this study, we integrated three public datasets from the Gene Expression Omnibus (GEO) database, including 26 OA samples and 20 normal samples. Via a series of bioinformatic analysis and machine learning, we identified the diagnostic biomarkers and several subtypes of OA. Moreover, the expression of these biomarkers were verified in our in-house cohort and the single cell dataset. Results: Three significant regulators of disulfidptosis (NCKAP1, OXSM, and SLC3A2) were identified through differential expression analysis and machine learning. And a nomogram constructed based on these three regulators exhibited ideal efficiency in predicting early- and late-stage OA. Furthermore, based on the expression of three regulators, we identified two disulfidptosis-related subtypes of OA with different infiltration of immune cells and personalized expression level of immune checkpoints. Notably, the expression of the three regulators was demonstrated in a single-cell RNA profile and verified in the synovial tissue in our in-house cohort including 6 OA patients and 6 normal people. Finally, an efficient disulfidptosis-mediated diagnostic model was constructed for OA, with the AUC value of 97.6923% in the training set and 93.3333% and 100% in two validation sets. Conclusion: Overall, with regard to PPPM, this study provided novel insights into the role of disulfidptosis regulators in the personalized diagnosis and treatment of OA.

Redox properties of Mn(III)porphyrins in hyaluronan oxidative degradation: Single electron transfer mechanism.

Cationic Mn(III)-meso-tetraarylporphyrin derivatives, substituted in para position with different size alkyl chains, were investigated to function as antioxidants in free-radical degradation of high-molar-mass hyaluronan by the methods of rotational viscometry and oximetry. The results of rotational viscometry showed that MnTM-4-PyP5+, MnTE-4-PyP5+, MnTPr-4-PyP5+, MnTPen-4-PyP5+ and MnTHep-4-PyP5+ showed high efficiency in decomposing H2O2, and reducing of peroxidized hyaluronan. When using oxygen electrode, MnTE-4-PyP5+, MnTPr-4-PyP5+, MnTPen-4-PyP5+, and MnTHep-4-PyP5+ applied to function as protective antioxidants in hyaluronan degradation, the uptake of dissolved oxygen from the reaction milieu was rapid, followed by continual increase in oxygen concentration up to the end of the measurement. However, when especially MnTE-4-PyP5+, MnTPr-4-PyP5+, and MnTPen-4-PyP5+ were examined as hyaluronan chain-breaking antioxidants, after short-term dissolved oxygen uptake, almost no increase in oxygen concentration was shown.

Discovering Subgroups of Children With High Mortality in Urban Guinea-Bissau: Exploratory and Validation Cohort Study.

BACKGROUND: The decline in global child mortality is an important public health achievement, yet child mortality remains disproportionally high in many low-income countries like Guinea-Bissau. The persisting high mortality rates necessitate targeted research to identify vulnerable subgroups of children and formulate effective interventions. OBJECTIVE: This study aimed to discover subgroups of children at an elevated risk of mortality in the urban setting of Bissau, Guinea-Bissau, West Africa. By identifying these groups, we intend to provide a foundation for developing targeted health interventions and inform public health policy. METHODS: We used data from the health and demographic surveillance site, Bandim Health Project, covering 2003 to 2019. We identified baseline variables recorded before children reached the age of 6 weeks. The focus was on determining factors consistently linked with increased mortality up to the age of 3 years. Our multifaceted methodological approach incorporated spatial analysis for visualizing geographical variations in mortality risk, causally adjusted regression analysis to single out specific risk factors, and machine learning techniques for identifying clusters of multifactorial risk factors. To ensure robustness and validity, we divided the data set temporally, assessing the persistence of identified subgroups over different periods. The reassessment of mortality risk used the targeted maximum likelihood estimation (TMLE) method to achieve more robust causal modeling. RESULTS: We analyzed data from 21,005 children. The mortality risk (6 weeks to 3 years of age) was 5.2% (95% CI 4.8%-5.6%) for children born between 2003 and 2011, and 2.9% (95% CI 2.5%-3.3%) for children born between 2012 and 2016. Our findings revealed 3 distinct high-risk subgroups with notably higher mortality rates, children residing in a specific urban area (adjusted mortality risk difference of 3.4%, 95% CI 0.3%-6.5%), children born to mothers with no prenatal consultations (adjusted mortality risk difference of 5.8%, 95% CI 2.6%-8.9%), and children from polygamous families born during the dry season (adjusted mortality risk difference of 1.7%, 95% CI 0.4%-2.9%). These subgroups, though small, showed a consistent pattern of higher mortality risk over time. Common social and economic factors were linked to a larger share of the total child deaths. CONCLUSIONS: The study's results underscore the need for targeted interventions to address the specific risks faced by these identified high-risk subgroups. These interventions should be designed to work to complement broader public health strategies, creating a comprehensive approach to reducing child mortality. We suggest future research that focuses on developing, testing, and comparing targeted intervention strategies unraveling the proposed hypotheses found in this study. The ultimate aim is to optimize health outcomes for all children in high-mortality settings, leveraging a strategic mix of targeted and general health interventions to address the varied needs of different child subgroups.

Cryptococcosis and Cryptococcal Meningitis: A Narrative Review and the Up-to-Date Management Approach.

Cryptococcosis is a fungal infectious disease that enormously impacts human health worldwide. Cryptococcal meningitis is the most severe disease caused by the fungus Cryptococcus, and can lead to death, if left untreated. Many patients develop resistance and progress to death even after treatment. It requires a prolonged treatment course in people with AIDS. This narrative review provides an evidence-based summary of the current treatment modalities and future trial options, including newer ones, namely, 18B7, T-2307, VT-1598, AR12, manogepix, and miltefosine. This review also evaluated the management and empiric treatment of cryptococcus meningitis. The disease can easily evade diagnosis with subacute presentation. Despite the severity of the disease, treatment options for cryptococcosis remain limited, and more research is needed.

The mediating effect of perceived stress on the relationship between big five personality traits and suboptimal health status in Chinese population: a nationwide survey in the framework of predictive, preventive, and personalized medicine.

Background: The effects of psychological factors on suboptimal health status (SHS) have been widely described; however, mechanisms behind the complex relationships among the Big Five personality traits and SHS are unclear. Identifying people with specific traits who are susceptible to SHS will help improve life quality and reduce the chronic disease burden under the framework of predictive, preventive, and personalized medicine (PPPM / 3PM). This study investigated the relationships among personality traits and SHS. It also explored whether perceived stress plays a mediating role in SHS development. Method: A nationwide cross-sectional survey based on multistage random sampling was conducted in 148 cities in China between June 20 and August 31, 2022. Personality traits, perceived stress, and SHS were evaluated using the Big Five Inventory-10 (BFI-10), the 4-item Perceived Stress Scale (PSS-4), and the Short-Form Suboptimal Health Status Questionnaire (SHSQ-SF), respectively. Pearson's correlation analysis was employed to examine the associations between personality traits, perceived stress, and SHS. Structural equation modeling (SEM) was used to discern the mediating role of perceived stress in the relationships among personality traits and SHS. Result: A total of 22,897 participants were enrolled in this study, among whom the prevalence of SHS was 52.9%. SHS was negatively correlated with three trait dimensions (i.e., extraversion, agreeableness, and conscientiousness) but positively correlated with neuroticism. Meanwhile, stress was negatively correlated with extraversion, agreeableness, conscientiousness, and openness, whereas it was positively correlated with neuroticism. The SEM results showed that, when adjusting for covariates (i.e., gender, age, BMI, educational level, current residence, marital status, and occupational status), higher agreeableness (ß = - 0.049, P < 0.001) and conscientiousness (ß = - 0.103, P < 0.001) led to lower SHS prevalence, higher neuroticism (ß = 0.130, P < 0.001), and openness (ß = 0.026, P < 0.001) caused SHS to be more prevalent. Perceived stress played a partial mediating role in the relationships among personality traits and SHS, respectively, contributing 41.3%, 35.9%, and 32.5% to the total effects of agreeableness, conscientiousness, and neuroticism on SHS. Additionally, the mediating impact of stress was significant even though extraversion had no direct effect on SHS. Conclusion: This study revealed a high prevalence of SHS in Chinese residents. Personality traits significantly influenced SHS rates, which perceived stress tended to mediate. From a PPPM perspective, early screening and targeted intervention for people with neuroticism (as well as stress alleviation) might contribute to health enhancement and chronic disease prevention. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00349-x.

Clinically relevant stratification of lung squamous carcinoma patients based on ubiquitinated proteasome genes for 3P medical approach.

Relevance: The proteasome is a crucial mechanism that regulates protein fate and eliminates misfolded proteins, playing a significant role in cellular processes. In the context of lung cancer, the proteasome's regulatory function is closely associated with the disease's pathophysiology, revealing multiple connections within the cell. Therefore, studying proteasome inhibitors as a means to identify potential pathways in carcinogenesis and metastatic progression is crucial in in-depth insight into its molecular mechanism and discovery of new therapeutic target to improve its therapy, and establishing effective biomarkers for patient stratification, predictive diagnosis, prognostic assessment, and personalized treatment for lung squamous carcinoma in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine). Methods: This study identified differentially expressed proteasome genes (DEPGs) in lung squamous carcinoma (LUSC) and developed a gene signature validated through Kaplan-Meier analysis and ROC curves. The study used WGCNA analysis to identify proteasome co-expression gene modules and their interactions with the immune system. NMF analysis delineated distinct LUSC subtypes based on proteasome gene expression patterns, while ssGSEA analysis quantified immune gene-set abundance and classified immune subtypes within LUSC samples. Furthermore, the study examined correlations between clinicopathological attributes, immune checkpoints, immune scores, immune cell composition, and mutation status across different risk score groups, NMF clusters, and immunity clusters. Results: This study utilized DEPGs to develop an eleven-proteasome gene-signature prognostic model for LUSC, which divided samples into high-risk and low-risk groups with significant overall survival differences. NMF analysis identified six distinct LUSC clusters associated with overall survival. Additionally, ssGSEA analysis classified LUSC samples into four immune subtypes based on the abundance of immune cell infiltration with clinical relevance. A total of 145 DEGs were identified between high-risk and low-risk score groups, which had significant biological effects. Moreover, PSMD11 was found to promote LUSC progression by depending on the ubiquitin-proteasome system for degradation. Conclusions: Ubiquitinated proteasome genes were effective in developing a prognostic model for LUSC patients. The study emphasized the critical role of proteasomes in LUSC processes, such as drug sensitivity, immune microenvironment, and mutation status. These data will contribute to the clinically relevant stratification of LUSC patients for personalized 3P medical approach. Further, we also recommend the application of the ubiquitinated proteasome system in multi-level diagnostics including multi-omics, liquid biopsy, prediction and targeted prevention of chronic inflammation and metastatic disease, and mitochondrial health-related biomarkers, for LUSC 3PM practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00352-w.

Perceptions and Attitudes Toward Community Medicine Among Medical Students: A Systematic Review.

Community medicine is yet to become a popular discipline as a choice for postgraduation and career among medical students in India. Our objective is to find the proportion of students opting for community medicine as a choice for a career. We also aim to find out the perceptions and attitudes of medical students about the subject of community medicine. Our inclusion criteria encompassed studies of any design, written or translated into the English language, and published from their inception up to the last date of our search, which was 15th August 2023. Our comprehensive search covered prominent databases, including PubMed, Scopus, and Embase, as well as an extensive screening of the first 10 pages of Google Scholar and Google. The risk of bias in the studies was evaluated by using the quality assessment tools recommended by the Joanna Briggs Institute critical appraisal tool for prevalence studies. In the initial search, 2069 articles were identified, with 1109 duplicates removed. The remaining 960 articles underwent title and abstract screening, leading to the exclusion of 931 articles. After applying eligibility criteria and reviewing the full text of 29 articles, seven studies were excluded. Ultimately, 22 studies were deemed eligible for inclusion in the systematic review. Among the total of 5106 students, 1032 students expressed a willingness to choose community medicine as their career. The pooled estimate, derived through a random effects model, was 0.21, with a 95% CI of 0.14 to 0.27. Studies conducted in India revealed a willingness of 0.23 (95% CI: 0.13- 0.33), whereas studies conducted outside India reported a lower proportion of 0.17 (0.14-0.24). When considering the year of study, a combined willingness of 0.02 (95% CI: 0.00-0.03) was observed among first and second-year students, contrasting with a higher proportion of 0.18 (95% CI: 0.04-0.32) among third-year students. Fourth-year students and interns demonstrated a willingness of 0.03 (95% CI: 0.00-0.06). The factors for disliking the subject included the perceived absence of clinical engagements, concerns about financial rewards, limited prospects for recognition and fame, etc. By actively engaging in the solution of these challenges, medical educators and policymakers can contribute to the vitalization of community medicine as a coveted and attractive specialty.

Identification and Fungicide Screening of Fungal Species Associated with Walnut Anthracnose in Shaanxi and Liaoning Provinces, China.

Walnut is cultivated around the world for its precious woody nut and edible oil. Recently, walnut infected by Colletotrichum spp. resulted in a great yield and quality loss. In August and September 2014, walnut fruits with anthracnose were sampled from two commercial orchards in Shaanxi and Liaoning provinces, and five representative isolates were used in this study. To identify the pathogen properly, four genes per region (internal transcribed spacer, glyceraldehyde-3-phosphate dehydrogenase, actin, and chitin synthase) were sequenced and used in phylogenetic studies. Based on multilocus phylogenetic analysis, five isolates clustered with Colletotrichum fioriniae, including its ex-type, with 100% bootstrap support. The results of multilocus phylogenetic analyses, morphology, and pathogenicity confirmed that C. fioriniae was one of the walnut anthracnose pathogens in China. All 13 fungicides tested inhibited mycelial growth and spore germination. Flusilazole, fluazinam, prochloraz, and pyraclostrobin showed the strongest suppressive effects on the mycelial growth than the others, the average EC50 values ranged from 0.09 to 0.40 µg/ml, and there was not any significant difference (P < 0.05). Pyraclostrobin, thiram, and azoxystrobin were the most effective fungicides on spore germination (P < 0.05), and the EC50 values ranged from 0.01 to 0.44 µg/ml. Pyraclostrobin, azoxystrobin, fluazinam, flusilazole, mancozeb, thiram, and prochloraz exhibited a good control effect on walnut anthracnose caused by C. fioriniae, and preventive activities were greater than curative activities. Pyraclostrobin at 250 a.i. µg/ml and fluazinam at 500 a.i. µg/ml provided the highest preventive and curative efficacy, and the values ranged from 81.3 to 82.2% and from 72.9 to 73.6%, respectively. As a consequence, mancozeb and thiram could be used at the preinfection stage, and pyraclostrobin, azoxystrobin, flusilazole, fluazinam, and prochloraz could be used at the early stage for effective prevention and control of walnut anthracnose caused by C. fioriniae. The results will provide more significant instructions for controlling the disease effectively in northern China.

Rosmarinic acid against cognitive impairment via RACK1/HIF-1α regulated microglial polarization in sepsis-surviving mice.

Microglial polarization modulation has been considered the potential therapeutic strategy for relieving cognitive impairment in sepsis survivors. Rosmarinic acid (RA), a water-soluble polyphenolic natural compound, processes a strong protective effect on various types of neurological disorders including Parkinson's disease, depression, and anxiety. However, its role and potential molecular mechanisms in sepsis-associated cognitive impairment remain unclear. To investigate the preventive and therapeutic effect of RA on sepsis-associated cognitive impairment and elucidate the potential mechanism of RA on regulating microglial polarization, we established a CLP-induced cognitive impairment model in mice and a lipopolysaccharide-induced microglia polarization cell model in BV-2. RACK1 siRNA was designed to identify the potential molecular mechanism of RACK1 on microglial polarization. The preventive and therapeutic effect of RA on cognitive impairment followed by PET-CT and behavioral tests including open-field test and tail suspension test. RACK1/HIF-1α pathway and microglial morphology in the hippocampus or BV-2 cells were measured. The results showed that RA significantly ameliorated the CLP-induced depressive and anxiety-like behaviors and promoted whole-brain glucose uptake in mice. Moreover, RA markedly improved CLP-induced hippocampal neuron loss and microglial activation by inhibiting microglial M1 polarization. Furthermore, experiments showed RACK1 was involved in the regulation of LPS-induced microglial M1 polarization via HIF-1α, and RA suppressed lipopolysaccharide or sepsis-associated microglial M1 polarization via RACK1/HIF-1α pathway (rescued the decrease of RACK1 and increase of HIF-1α). Taken together, RA could be a potential preventive and therapeutic medication in improving cognitive impairment through RACK1/HIF-1α pathway-regulated microglial polarization.

Lesson learned from COVID-19 pandemic for the future of food industry.

With WHO announcing COVID-19 no longer as a public health emergency of international concern (PHEIC) on May 5, 2023, coupled with the fact that the majority of the countries of the world have dropped strict city lockdown or border closure, this perhaps signals the end of the COVID-19 crisis caused by the SARS-CoV-2 virus. However, the COVID-19 pandemic has resulted in far-reaching effects affecting nearly every aspect of our lives and society. Notably, the food industry including agriculture, food manufacturers, food logistics, distributors and retailers have all felt the profound impact and had experienced significant stress during the pandemic. Therefore, it is essential to retrospect the lessons that can be learned from this pandemic for the food industry. This short review aims to address the food safety issues related to the COVID-19 pandemic by focusing on its foodborne transmission potential, innovations of virus detection strategies suitable for food industry; development of phathogenicaidal methods and devices to inactivate SARS-CoV-2 virus (particularly in industrial scale); and the set-up of related food regulations and guidelines as preventive and control measures for preventing the spread of SARS-CoV-2 virus through the food supply chain during the pandemic. This article may provide useful references for the food industry to minimize the food safety impact of COVID-19 (as well as other respiratory virus) and allows them to better prepare for similar future challenges.

Development and validation of a short-form suboptimal health status questionnaire.

Background: Suboptimal health status (SHS) is a reversible, borderline state between optimal health and disease. Although this condition's definition is widely understood, related questionnaires must be developed to identify individuals with SHS in various populations relative to predictive, preventive, and personalized medicine (PPPM/3PM). This study presents a short-form suboptimal health status questionnaire (SHSQ-SF) that appears to possess sufficient reliability and validity to assess SHS in large-scale populations. Methods: A total of 6183 participants enrolled from Southern China constituted a training set, while 4113 participants from Northern China constituted an external validation set. The SHSQ-SF includes nine key items from the Suboptimal Health Status Questionnaire-25 (SHSQ-25), an instrument that has been applied to Africans, Asians, and Caucasians. Item analysis and reliability and validity tests were carried out to validate the SHSQ-SF. The receiver operating characteristic (ROC) curve was used to identify an optimal cutoff value for SHS diagnosis, by which the area under the curve (AUC) and 95% confidence interval (CI) were determined. Results: Cronbach's α coefficient for the training dataset was 0.902; the split-half reliability was 0.863. The Kaiser-Meyer-Olkin (KMO) value was 0.880, and Bartlett's test of sphericity was significant (χ2 = 32,929.680, p < 0.05). Both Kaiser's criteria (eigenvalues > 1) and the scree plot revealed one factor explaining 57.008% of the total variance. Standardized factor loadings for the confirmatory factor analysis (CFA) indices ranged between 0.58 and 0.74, with χ2/dƒ = 4.972, GFI = 0.996, CFI = 0.996, RFI = 0.989, and RMSEA = 0.031. The AUC was equal to 0.985 (95% CI: 0.983-0.988) for the training dataset. A cutoff value (≥ 11) was then identified for SHS diagnosis. The SHSQ-SF showed good discriminatory power for the external validation dataset (AUC = 0.975, 95% CI: 0.971-0.979) with a sensitivity of 96.2% and a specificity of 87.4%. Conclusions: We developed a short form of the SHS questionnaire that demonstrated sound reliability and validity when assessing SHS in Chinese residents. From a PPPM/3PM perspective, the SHSQ-SF is recommended for the rapid screening of individuals with SHS in large-scale populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00339-z.

Blueprint designing and validation for competency-based curriculum for theory assessment in community medicine.

Background: Blueprint provides a base for assessment by assigning proportionate weightage to various content areas and helps the paper setter to construct a uniform and valid assessment. This study aimed to design and validate a blueprint for theory in Community Medicine as per the new curriculum for Medical Undergraduates in India. Methods: Blueprint in community medicine was designed by assigning impact score (I) and frequency score (F) for the competencies. Blueprint was validated using the Content Validity Index (CVI), and inter-rater agreement for subject experts using Fleiss' kappa statistics was calculated. Feedback from faculty and students was obtained afterward to assess the postimplementation response. Results: Blueprint was designed by an expert group where impact score and frequency score were assigned to 146 competencies in the theory of Community Medicine. In Delphi survey I, 63.2% of subject experts responded, while in Delphi survey II, a response rate of 58.3% was achieved. Value of the Fleiss' Kappa test for an inter-rater agreement was 0.68, i.e. "substantial agreement," while CVI among the raters came out to be 0.86, i.e. overall valid assessment. Feedback of faculty (n = 11) suggested that the blueprint was helpful and standardized the paper setting, whereas feedback from students (n = 138) depicted that it helped in preparing for exams, and they would recommend it to other students. Conclusion: Validated blueprint by consensus of subject experts has impact score and frequency score along with topic-wise distribution of marks for the convenience of faculty and its utility is well proven among learners too.

Community Medicine in Ayushman Bharat Digital Mission: The Hidden Cornerstone.

Background: India has launched Ayushman Bharat Digital Mission (ABDM), to provide an integrated digital health infrastructure. The success of digital health systems lies in their ability to achieve universal healthcare and incorporate all levels of disease prevention. The objective of this study was to develop an expert consensus on how Community Medicine (Preventive and Social Medicine) can be integrated into ABDM. Methods: A total of 17 and 15 participants, who were Community Medicine professionals with more than 10 years experience in the Public Health Sector and/or Medical Education in various parts of India, participated in round 1 and 2 of this Delphi study respectively. The study explored three domains: 1. Advantages and challenges of ABDM, and possible solutions; 2. Intersectoral convergence in Unified Health Interface (UHI) and 3. Way ahead in medical education and research. Results: Participants envisaged improved accessibility, affordability, and quality of care due to ABDM. However, awareness generation, reaching out to marginalized populations, human resource constraints, financial sustainability, and data security issues were anticipated challenges. The study identified plausible solutions addressing six broad challenges of ABDM and classified them based on the priority of implementation. Participants listed out nine key roles of Community Medicine professionals in digital health. The Study identified about 95 stakeholders who play direct and indirect roles in public health and can be connected to the general public through the Unified Health Interface of ABDM. Further, the study explored the future of medical education and research in the digital era. Conclusion: The Study contributes to broadening the scope of India's digital health mission, with elements of Community Medicine in its cornerstone.

Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells.

Significant limitations of the reactive medical approach in breast cancer management are clearly reflected by alarming statistics recorded worldwide. According to the WHO updates, breast malignancies become the leading cancer type. Further, the portion of premenopausal breast cancer cases is permanently increasing and demonstrates particularly aggressive patterns and poor outcomes exemplified by young patients with triple-negative breast cancer that lacks targeted therapy. Accumulating studies suggest the crucial role of stem cells in tumour biology, high metastatic activity, and therapy resistance of aggressive breast cancer. Therefore, targeting breast cancer stem cells is a promising treatment approach in secondary and tertiary breast cancer care. To this end, naturally occurring substances demonstrate high potential to target cancer stem cells which, however, require in-depth analysis to identify effective anti-cancer agents for cost-effective breast cancer management. The current article highlights the properties of flavonoids particularly relevant for targeting breast cancer stem cells to mitigate therapy resistance. The proposed approach is conformed with the principles of 3P medicine by applying predictive diagnostics, patient stratification and treatments tailored to the individualised patient profile. Expected impacts are very high, namely, to overcome limitations of reactive medical services improving individual outcomes and the healthcare economy in breast cancer management. Relevant clinical applications are exemplified in the paper.

A cysteine-rich secretory protein involves in phytohormone melatonin mediated plant resistance to CGMMV.

BACKGROUND: Melatonin is considered to be a polyfunctional master regulator in animals and higher plants. Exogenous melatonin inhibits plant infection by multiple diseases; however, the role of melatonin in Cucumber green mottle mosaic virus (CGMMV) infection remains unknown. RESULTS: In this study, we demonstrated that exogenous melatonin treatment can effectively control CGMMV infection. The greatest control effect was achieved by 3 days of root irrigation at a melatonin concentration of 50 µM. Exogenous melatonin showed preventive and therapeutic effects against CGMMV infection at early stage in tobacco and cucumber. We utilized RNA sequencing technology to compare the expression profiles of mock-inoculated, CGMMV-infected, and melatonin+CGMMV-infected tobacco leaves. Defense-related gene CRISP1 was specifically upregulated in response to melatonin, but not to salicylic acid (SA). Silencing CRISP1 enhanced the preventive effects of melatonin on CGMMV infection, but had no effect on CGMMV infection. We also found exogenous melatonin has preventive effects against another Tobamovirus, Pepper mild mottle virus (PMMoV) infection. CONCLUSIONS: Together, these results indicate that exogenous melatonin controls two Tobamovirus infections and inhibition of CRISP1 enhanced melatonin control effects against CGMMV infection, which may lead to the development of a novel melatonin treatment for Tobamovirus control.

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications-risks and mitigation.

Proliferative diabetic retinopathy (PDR) the sequel of diabetic retinopathy (DR), a frequent complication of diabetes mellitus (DM), is the leading cause of blindness in the working-age population. The current screening process for the DR risk is not sufficiently effective such that often the disease is undetected until irreversible damage occurs. Diabetes-associated small vessel disease and neuroretinal changes create a vicious cycle resulting in the conversion of DR into PDR with characteristic ocular attributes including excessive mitochondrial and retinal cell damage, chronic inflammation, neovascularisation, and reduced visual field. PDR is considered an independent predictor of other severe diabetic complications such as ischemic stroke. A "domino effect" is highly characteristic for the cascading DM complications in which DR is an early indicator of impaired molecular and visual signaling. Mitochondrial health control is clinically relevant in DR management, and multi-omic tear fluid analysis can be instrumental for DR prognosis and PDR prediction. Altered metabolic pathways and bioenergetics, microvascular deficits and small vessel disease, chronic inflammation, and excessive tissue remodelling are in focus of this article as evidence-based targets for a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary DR care management.

Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms.

Objective: Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM). Methods: This study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms. Results: PheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc ('ntreeA') was associated with both AAA (ß = -0.36, P = 6.75e-10) and ICA (ß = -0.11, P = 5.51e-06). In addition, the mean angles between each artery branch ('curveangle_mean_a') were commonly associated with 4 MFS genes (FBN1: ß = -0.10, P = 1.63e-12; COL16A1: ß = -0.07, P = 3.14e-09; LOC105373592: ß = -0.06, P = 1.89e-05; C8orf81/LOC441376: ß = 0.07, P = 1.02e-05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780-0.838], which was similar to the clinical risk model (0.806 [0.778-0.834]) but higher than the baseline model (0.739 [0.733-0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727-0.869) for the aneurysm-RVF model, 0.795 (0.718-0.871) for the clinical risk model and 0.719 (0.620-0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5-48.8], P = 1.02e-05). Conclusion: We identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00315-7.

The Pathology of Primary Familial Brain Calcification: Implications for Treatment.

Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC. In this review, considering mechanistic studies of these genes at the cellular level and in animals, we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients. Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics, provides a summary of the known composition of brain calcification, and identifies some potential therapeutic targets for PFBC.

Exploring COVID-19 transmission patterns and key factors during epidemics caused by three major strains in Asia.

The COVID-19 epidemic has lasted for more than two years since the outbreak in late 2019. An urgent and challenging question is how to systematically evaluate epidemic developments in different countries, during different periods, and to determine which measures that could be implemented are key for successful epidemic prevention. In this study, SBD distance-based K-shape clustering and hierarchical clustering methods were used to analyse epidemics in Asian countries. For the hierarchical clustering, epidemic time series were divided into three periods (epidemics induced by the Original/Alpha, Delta and Omicron variants separately). Standard deviations, the Hurst index, mortality rates, peak value of confirmed cases per capita, average growth rates, and the control efficiency of each period were used to characterize the epidemics. In addition, the total numbers of cases in the different countries were analysed by correlation and regression in relation to 15 variables that could have impacts on COVID-19. Finally, some suggestions on prevention and control measures for each category of country are given. We found that the total numbers of cases per million of a population, total deaths per million and mortality rates were highly correlated with the proportion of people aged over 65 years, the prevalence of multiple diseases, and the national GDP. We also found significant associations between case numbers and vaccination rates, health expenditures, and stringency of control measures. Vaccinations have played a positive role in COVID-19, with a gradual decline in mortality rates in later periods, and are still playing protective roles against the Delta and Omicron strains. The stringency of control measures taken by a government is not an indicator of the appropriateness of a country's response to the outbreak, and a higher index does not necessarily mean more effective measures; a combination of factors such as national vaccination rates, the country's economic foundation and the availability of medical equipment is also needed. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Construction and effectiveness evaluation of surgical complication monitoring mode based on medical record homepage data / 中华医院管理杂志

Objective:To explore the establishment of a surgical complication monitoring mode based on data on the medical record homepage, and analyze its impact on the trend of changes in surgical complication incidence.Methods:A monitoring mode of surgical complication was developed based on the " structure-process-results" framework by using surgical complication rates derived from performance appraisal for a tertiary general hospital in Guangzhou. The number of surgical complications and the number of discharged surgical patients was collected from the hospital from January 2019 to June 2022 through the home page collection system for performance appraisal of national tertiary public hospitals. Descriptive analysis was used to analyze the incidence of surgical complications, and Joinpoint regression was used to analyze the trend of changes in the incidence of surgical complications. Monthly percentage change ( MPC) and average monthly percentage change ( AMPC) were calculated. Results:Since the hospital began implementing the surgical complication monitoring mode in May 2021, the incidence of surgical complications had decreased from 2.55% in June 2021 to 0.82% in June 2022, with an MPC of -5.58% ( P=0.024), which was better than the changes from January 2019 to May 2021 ( MPC=0.18%, P=0.755). Conclusions:The surgical complication monitoring mode constructed by the hospital can effectively reduce the incidence of surgical complications, providing reference for optimizing hospital′s medical quality management process and decision-making mode.