An antagonistic pleiotropic gene regulates the reproduction and longevity tradeoff.

The antagonistic pleiotropy theory of aging proposes that genes enhancing fitness in early life limit the lifespan, but the molecular evidence remains underexplored. By profiling translatome changes in Caenorhabditis elegans during starvation recovery, we find that an open reading frame (ORF) trl-1 "hidden" within an annotated pseudogene significantly translates upon refeeding. trl-1 mutant animals increase brood sizes but shorten the lifespan and specifically impair germline deficiency­induced longevity. The loss of trl-1 abnormally up-regulates the translation of vitellogenin that produces copious yolk to provision eggs, whereas vitellogenin overexpression is known to reduce the lifespan. We show that the TRL-1 protein undergoes liquid­liquid phase separation (LLPS), through which TRL-1 granules recruit vitellogenin messenger RNA and inhibit its translation. These results indicate that trl-1 functions as an antagonistic pleiotropic gene to regulate the reproduction­longevity tradeoff by optimizing nutrient production for the next generation.

DYF-5/MAK-dependent phosphorylation promotes ciliary tubulin unloading.

Cilia are microtubule-based organelles that power cell motility and regulate sensation and signaling, and abnormal ciliary structure and function cause various ciliopathies. Cilium formation and maintenance requires intraflagellar transport (IFT), during which the kinesin-2 family motor proteins ferry IFT particles carrying axonemal precursors such as tubulins into cilia. Tubulin dimers are loaded to IFT machinery through an interaction between tubulin and the IFT-74/81 module; however, little is known of how tubulins are unloaded when arriving at the ciliary tip. Here, we show that the ciliary kinase DYF-5/MAK phosphorylates multiple sites within the tubulin-binding module of IFT-74, reducing the tubulin-binding affinity of IFT-74/81 approximately sixfold. Ablation or constitutive activation of IFT-74 phosphorylation abnormally elongates or shortens sensory cilia in Caenorhabditis elegans neurons. We propose that DYF-5/MAK-dependent phosphorylation plays a fundamental role in ciliogenesis by regulating tubulin unloading.

Ciliogenesis requires sphingolipid-dependent membrane and axoneme interaction.

Cilium formation and regeneration requires new protein synthesis, but the underlying cytosolic translational reprogramming remains largely unknown. Using ribosome footprinting, we performed global translatome profiling during cilia regeneration in Chlamydomonas and uncovered that flagellar genes undergo an early transcriptional activation but late translational repression. This pattern guided our identification of sphingolipid metabolism enzymes, including serine palmitoyltransferase (SPT), as essential regulators for ciliogenesis. Cryo-electron tomography showed that ceramide loss abnormally increased the membrane-axoneme distance and generated bulged cilia. We found that ceramides interact with intraflagellar transport (IFT) particle proteins that IFT motors transport along axoneme microtubules (MTs), suggesting that ceramide-IFT particle-IFT motor-MT interactions connect the ciliary membrane with the axoneme to form rod-shaped cilia. SPT-deficient vertebrate cells were defective in ciliogenesis, and SPT mutations from patients with hereditary sensory neuropathy disrupted cilia, which could be restored by sphingolipid supplementation. These results reveal a conserved role of sphingolipid in cilium formation and link compromised sphingolipid production with ciliopathies.

Deciphering prognostic indicators in AQP4-IgG-seropositive neuromyelitis optica spectrum disorder: An integrative review of demographic and laboratory factors.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a group of inflammatory diseases affecting the central nervous system, characterized by optic neuritis and myelitis. The complex nature of NMOSD and varied patient response necessitates personalized treatment and efficient patient stratification strategies. OBJECTIVE: To provide a comprehensive review of recent advances in clinical and biomarker research related to aquaporin-4 (AQP4)-immunoglobulin G (IgG)-seropositive NMOSD prognosis and identify key areas for future research. METHODS: A comprehensive review and synthesis of recent literature were conducted, focusing on demographic factors and laboratory investigations. RESULTS: Demographic factors, such as age, ethnicity, and sex, influence NMOSD prognosis. Key biomarkers for NMOSD prognosis include homocysteine, antinuclear antibodies, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, thyroid hormone levels, neurofilament light chain levels, and serum glial fibrillary acidic protein might also predict NMOSD attack prognosis. CONCLUSION: Further investigation is required to understand sex-related disparities and biomarker inconsistencies. Identification and understanding of these factors can aid in the development of personalized therapeutic strategies, thereby improving outcomes for NMOSD patients. Future studies should focus on unifying research design for consistent results.

Clinical Impact of Operating Room Nursing Pathways on Hospitalization Duration and Consciousness Status in Patients Undergoing Emergency Craniocerebral Injury Surgery.

Background: Craniocerebral injuries carry high disability and mortality rates. In clinical practice, timely determination of the condition and immediate rescue interventions are crucial for patients with emergency craniocerebral injuries. Nurses play a pivotal role in providing proactive nursing services to save patients' lives. Objective: This study aims to examine the practical implications of implementing operating room nursing pathways in the care of patients undergoing emergency craniocerebral injury surgery. Design: A randomized controlled study was conducted. Setting: The study was conducted at the Department of Operating Room at Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine. Participants: A total of 80 patients undergoing emergency craniocerebral injury surgery in our hospital from August 2020 to August 2022 were included. They were randomly divided into control and observation groups through a lottery, with 40 cases in each. Interventions: The control group received conventional nursing, while the observation group received operating room nursing pathways. Primary Outcome Measures: (1) Surgical preparation time, surgical time, and hospitalization time; (2) Pupil scores; (3) Brain injury grading; and (4) Nursing satisfaction score. Results: The observation group exhibited a significant decrease in surgical preparation time and hospitalization time compared to the control group (P < .05). After the intervention, severe craniocerebral injury pupil scores in the observation group showed improvement compared to the control group (P < .05). The total satisfaction rate in the observation group (92.5%) was higher than that in the control group (80.0%) (P = .012). Conclusions: The application of operating room nursing pathways in patients undergoing emergency craniocerebral injury surgery can lead to a shortened length of stay, substantial improvement in patients' consciousness status, and high satisfaction rates from both patients and their family members. This intervention holds significant clinical value and merits further promotion.

Are Physical Sunscreens Safe for Marine Life? A Study on a Coral-Zooxanthellae Symbiotic System.

Limited toxic and ecological studies were focused on physical sunscreen that is considered to have "safer performance", in which nanosize zinc oxide (nZnO) and nanosize titanium dioxide (nTiO2) generally are added as ultraviolet filters. Herein, the common button coral Zoanthus sp. was newly used to assess the toxic effects and underlying mechanisms of physical sunscreen. Results showed that physical sunscreen induced severe growth inhibition effects and largely compelled the symbiotic zooxanthellae, indicating that their symbiotic systems were threatened and, also, that neural and photosynthesis functions were influenced. Zn2+ toxicity and bioaccumulation were identified as the main toxic mechanisms, and nTiO2 particles released from physical sunscreen also displayed limited bioattachment and toxicity. Oxidative stress, determined by increased reactive oxygen species, superoxide dismutase, and malondialdehyde content, was indicated as another important toxic mechanism. Furthermore, when Zoanthus sp. was restored, the inhibited individual coral could be largely recovered after a short (3 d) exposure time; however, a longer exposure time damaged the coral irretrievably, which revealed the latent environmental risks of physical sunscreen. This study investigated the toxic effect of physical sunscreen on Zoanthus sp. in a relatively comprehensive manner, thus providing new insights into the toxic response of sunscreen on marine organisms.

Development and Psychometric Properties of a Scale Measuring Barriers to Perioperative Hypothermia Prevention for Anesthesiologists and Nurses.

PURPOSE: To develop a scale that measures barriers to perioperative hypothermia prevention (BPHP) as perceived by anesthesiologists and nurses. DESIGN: A methodological and prospective psychometric study. METHODS: Based on the theoretical domains framework, the item pool was created through a literature review, qualitative interviews, and expert consultation. The scale was pretested with a sample of 154 key stakeholders in perioperative temperature management and then field tested with 416 anesthesiologists and nurses working at three hospitals in Southeast China. Item analysis, and reliability and validity analysis were performed. FINDINGS: The average content validity index was 0.94. According to exploratory factor analysis, seven factors were obtained that could explain 70.283% of the total variance. Confirmatory factor analysis showed excellent or acceptable goodness-of-fit indices. The reliability analysis demonstrated that the scale had high internal consistency and temporal stability, with Cronbach's α, split-half coefficient and test-retest values of 0.926, 0.878 and 0.835, respectively. CONCLUSIONS: The BPHP scale meets the psychometric criteria for reliability and validity and promises to be a useful quality measure for IPH management during the perioperative period. Further investigations on educational or resource needs and the development of an optimal perioperative hypothermia prevention protocol to narrow the gap between research evidence and clinical practice should be performed.

Construction of machine learning tools to predict threatened miscarriage in the first trimester based on AEA, progesterone and ß-hCG in China: a multicentre, observational, case-control study.

BACKGROUND: Endocannabinoid anandamide (AEA), progesterone (P4) and ß-human chorionic gonadotrophin (ß-hCG) are associated with the threatened miscarriage in the early stage. However, no study has investigated whether combing these three hormones could predict threatened miscarriage. Thus, we aim to establish machine learning models utilizing these three hormones to predict threatened miscarriage risk. METHODS: This is a multicentre, observational, case-control study involving 215 pregnant women. We recruited 119 normal pregnant women and 96 threatened miscarriage pregnant women including 58 women with ongoing pregnancy and 38 women with inevitable miscarriage. P4 and ß-hCG levels were detected by chemiluminescence immunoassay assay. The level of AEA was tested by ultra-high-performance liquid chromatography-tandem mass spectrometry. Six predictive machine learning models were established and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), accuracy and precision. RESULTS: The median concentration of AEA was significantly lower in the healthy pregnant women group than that in the threatened miscarriage group, while the median concentration of P4 was significantly higher in the normal pregnancy group than that in the threatened miscarriage group. Only the median level of P4 was significantly lower in the inevitable miscarriage group than that in the ongoing pregnancy group. Moreover, AEA is strongly positively correlated with threatened miscarriage, while P4 is negatively correlated with both threatened miscarriage and inevitable miscarriage. Interestingly, AEA and P4 are negatively correlated with each other. Among six models, logistic regression (LR), support vector machine (SVM) and multilayer perceptron (MLP) models obtained the AUC values of 0.75, 0.70 and 0.70, respectively; and their accuracy and precision were all above 0.60. Among these three models, the LR model showed the highest accuracy (0.65) and precision (0.70) to predict threatened miscarriage. CONCLUSIONS: The LR model showed the highest overall predictive power, thus machine learning combined with the level of AEA, P4 and ß-hCG might be a new approach to predict the threatened miscarriage risk in the near feature.

Study on illness perceptions of Chinese rural-dwelling adults with hypertension: A descriptive study.

OBJECTIVE: The aim of this study was to describe the levels of illness perception and identify interrelations among the variables of illness perception, demographic, and health-related characteristics in a sample of rural Chinese adults with hypertension (HTN). DESIGN: This is a cross-sectional descriptive study using descriptive and correlation analysis. SAMPLE: It included 163 people diagnosed with HTN for at least 3 years who lived in two rural villages in Zhejiang Province of mainland China during 2014-2015. MEASUREMENTS: Illness perception was measured by the Chinese Illness Perception Questionnaire-Revised. Demographic and illness characteristics were collected by the researcher. Weight, height, and blood pressure (BP) were, respectively, measured by calibrated scale and digital sphygmomanometers. RESULTS: The findings showed that the BP control rate was 28.80% in the village. The highest average item score found in timeline (3.98 ± 0.76) and control (3.29 ± 0.67) subscales indicated that rural Chinese adults believe in the chronicity and controllability of HTN. Negative illness representation presented the lowest mean item score (2.64) suggesting that the participants neither perceive symptom variation of the illness nor their illness as serious. Interrelations existed among the illness perception variables with variation from that in other previous study. The cause of HTN was attributed to balance factors, psychological factors, risk factors, and cultural factors in sequence. Age, education, body mass index, and household annual income were correlated with illness perception. CONCLUSION: These findings suggested that misconceptions about HTN perception existed among rural adults in the villages. Comprehensive health education program is needed to increase rural adults' knowledge and management of HTN.

Application of capsaicin as a potential new therapeutic drug in human cancers.

WHAT IS KNOWN AND OBJECTIVE: Capsaicin, the major active ingredient of chili pepper, may play a "dual role" in tumourigenesis, acting as a carcinogen or as a cancer preventive agent. The aim of this study was to investigate the anticancer mechanisms of capsaicin and the effects of capsaicin on traditional chemotherapeutic drugs and radiotherapy in various cancer types and the potential for clinical application in cancer therapy. METHODS: We conducted extensive literature searches through PubMed to collect representative studies of capsaicin in different cancer types. These studies investigated the anticancer molecular mechanisms of capsaicin. We then searched for the effects of capsaicin on traditional chemotherapeutic drugs or radiotherapy. Finally, in terms of clinical application, we searched for the advances of capsaicin-loaded nanoparticles in malignant tumours. RESULTS AND DISCUSSION: In most studies, capsaicin is a potential anti-tumour compound and the anti-cancer mechanisms are mainly related to anti-proliferation, induction of apoptosis and autophagy, anti-angiogenesis and anti-metastasis. It is worth noting that the biological functions of capsaicin are greatly affected by its concentration and the effective concentration in different malignant tumours varies considerably. Furthermore, capsaicin can affect the anti-cancer activity of conventional chemotherapeutic drugs or radiation therapy and more and more capsaicin-loaded nanoparticles have been developed to prolong the drug retention of capsaicin in the blood circulation and allow active targeting of specific cancer cells to enhance its accurate delivery and targeting specificity, suggesting that capsaicin may be used as a potential chemopreventive or a new auxiliary therapeutic drug for cancer. However, there is still a need for well-controlled studies to assess the safety and efficacy of capsaicin, and further preclinical and clinical trials are needed to elucidate its anti-tumour effects when combined with other standard drugs or radiotherapy. WHAT IS NEW AND CONCLUSION: Capsaicin exhibits strong anti-cancer properties in various cancer types. The combination of capsaicin with conventional chemotherapy drugs or radiotherapy can improve the sensitivity, reduce the side effects and enhance the tolerance of patients to cancer treatment. The development of capsaicin-loaded nanoparticles may provide a very promising approach to chemotherapy for malignant tumours.

Emergence Delirium in Elderly Patients as a Potential Predictor of Subsequent Postoperative Delirium: A Descriptive Correlational Study.

PURPOSE: This study aimed to investigate the incidence of emergence delirium (ED) in elderly patients under general anesthesia and to determine the correlation between ED and delirium at five subsequent postoperative days. DESIGN: This research is a descriptive correlational study. METHODS: A total of 168 aged patients undergoing elective general anesthesia were recruited from a comprehensive tertiary teaching hospital with 2,400 beds in Southern China from April 2018 to September 2018. The Nursing Delirium Screening Scale was used to assess delirium at 30 and 60 minutes after extubation or on discharge from the postanesthesia care unit. Patients were assessed for delirium at postoperative days one through five using the same method. Patients' demographic information, including cognitive function, were collected. FINDINGS: Among the 168 aged patients, 58 suffered from ED (34.5%), including the 79.3% for the 46 patients who experienced postoperative delirium (POD). A positive correlation existed between ED and POD (χ2 = 111.744; P < .01). Logistic regression analysis included seven variables: age, preoperative Mini-Mental State Examination score, underlying diseases, American Society of Anesthesiologists grade, surgery duration, postoperative complications, and the presence of ED. Age and ED were concluded to be independent predictive factors of POD. CONCLUSIONS: ED in the first hour after tracheal tube removal is a predictor of delirium at five subsequent postoperative days. Accurate and timely assessment of recovery period can effectively guide the treatment and rehabilitation of POD and maximize prevention of adverse consequences.

Current status and influencing factors of barriers to enteral feeding of critically ill patients: A multicenter study.

AIMS AND OBJECTIVES: To investigate the barriers in administering enteral feeding to critically ill patients from the nursing perspective. Our objectives are to provide tailored interventions for addressing identified barriers and propose an optimal enteral nutrition (EN) practice in intensive care unit (ICU). BACKGROUND: Despite the availability of numerous verified clinical practice guidelines focusing on enteral feeding of critically ill patients, a wide gap remains between the guideline recommendations and actual nutrition performances. Underfeeding is also a global problem. Therefore, to further understand the reasons of the systemic iatrogenic underfeeding in ICUs, several potential issues are investigated. DESIGN: This research is a cross-sectional descriptive study. METHODS: A total of 808 nurses were recruited from 10 comprehensive hospitals from different districts in China. The nursing staff demographic, the unit's EN management information and the Chinese version of barriers to enteral feeding critically ill patients questionnaire were the parameters used to collect data via WeChat app. Moreover, the collected data were analysed by descriptive and correlative statistical analysis methods. RESULTS: Results obtained by multiple linear regression showed that frequency of EN-related training, full-time ICU nutritionist, hospital level, specific protocols for enteral feeding and position were significantly influencing the enteral feeding of ICU patients. CONCLUSIONS: Enteral feeding barriers of ICU patients are at a moderate level and are influenced by multiple aspects. Hence, hospital departments should strengthen standardisation and systematic EN training, provide ICU full-time nutritionists and distribute medical resources and personnel rationally. Moreover, construction of a localised feeding process and exerting subjective initiative of clinical nurses from an evidence-based guideline are important. Multifaceted tailored interventions should be implemented to address these barriers. RELEVANCE TO CLINICAL PRACTICE: The findings of this study can be used to inform future intervention and guidelines aimed at addressing these barriers systematically and improving adherence to critical care nutrition guidelines for the provision of enteral nutrition.

Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia.

Patients with schizophrenia do not usually achieve remission state even after adequate antipsychotics treatment. Previous studies found significant difference in white matter integrity between patients with good outcomes and those with poor outcomes, but difference is still unclear at individual tract level. This study aimed to use a systematic approach to identify the tracts that were associated with remission state in patients with schizophrenia. We evaluated 91 patients with schizophrenia (remitted, 50; nonremitted, 41) and 50 healthy controls through diffusion spectrum imaging. White matter tract integrity was assessed through an automatic tract-specific analysis method to determine the mean generalized fractional anisotropy (GFA) values of the 76 white matter tract bundles in each participant. Analysis of covariance among the 3 groups revealed 12 tracts that were significantly different in GFA values. Post-hoc analysis showed that compared with the healthy controls, the nonremission group had reduced integrity in all 12 tracts, whereas the remission group had reduced integrity in only 4 tracts. Comparison between the remission and nonremission groups revealed 4 tracts with significant difference (i.e., the right fornix, bilateral uncinate fasciculi, and callosal fibers connecting the temporal poles) even after adjusting age, sex, education year, illness duration, and medication dose. Furthermore, all the 4 tracts were correlated with negative symptoms scores of the positive and negative syndrome scale. In conclusion, our study identified the tracts that were associated with remission state of schizophrenia. These tracts might be a potential prognostic marker for the symptomatic remission in patients with schizophrenia.

Correction to: CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma.

[This corrects the article DOI: 10.1186/s12935-017-0473-z.].

CBFA2T2 is associated with a cancer stem cell state in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80-90% of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. METHODS: OncoLnc was used as a tool for interactively exploring survival correlations. Gene manipulation and expression analysis were carried out using siRNA, RT-PCR and Western blotting. Wound healing and invasion assays were used for phenotypical characterization. Aldefluor assay and FACS sorting Sphere culture were used to determine the "stemness" of CSCs. Co-Immunoprecipitation (Co-IP) was used to examine the interaction between OCT4 and CBFA2T2. Student's t-test and Chi square test was used to analyze statistical significance. RESULTS: CBFA2T2 expression can significantly predict the survival of RCC patients. Knocking-down of CBFA2T2 can inhibit cell migration and invasion in RCC cells in vitro, and reduce ALDHhigh CSCs populations. CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines. CONCLUSIONS: Our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of "stemness" through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

nbCNV: a multi-constrained optimization model for discovering copy number variants in single-cell sequencing data.

BACKGROUND: Variations in DNA copy number have an important contribution to the development of several diseases, including autism, schizophrenia and cancer. Single-cell sequencing technology allows the dissection of genomic heterogeneity at the single-cell level, thereby providing important evolutionary information about cancer cells. In contrast to traditional bulk sequencing, single-cell sequencing requires the amplification of the whole genome of a single cell to accumulate enough samples for sequencing. However, the amplification process inevitably introduces amplification bias, resulting in an over-dispersing portion of the sequencing data. Recent study has manifested that the over-dispersed portion of the single-cell sequencing data could be well modelled by negative binomial distributions. RESULTS: We developed a read-depth based method, nbCNV to detect the copy number variants (CNVs). The nbCNV method uses two constraints-sparsity and smoothness to fit the CNV patterns under the assumption that the read signals are negatively binomially distributed. The problem of CNV detection was formulated as a quadratic optimization problem, and was solved by an efficient numerical solution based on the classical alternating direction minimization method. CONCLUSIONS: Extensive experiments to compare nbCNV with existing benchmark models were conducted on both simulated data and empirical single-cell sequencing data. The results of those experiments demonstrate that nbCNV achieves superior performance and high robustness for the detection of CNVs in single-cell sequencing data.

Attenuation of 40S ribosomal subunit abundance differentially affects host and HCV translation and suppresses HCV replication.

For Hepatitis C virus (HCV), initiation of translation is cap-independently mediated by its internal ribosome entry site (IRES). Unlike other IRES-containing viruses that shut off host cap-dependent translation, translation of HCV coexists with that of the host. How HCV IRES-mediated translation is regulated in the infected cells remains unclear. Here, we show that the intracellular level of 40S ribosomal subunit plays a key role in facilitating HCV translation over host translation. In a loss-of-function screen, we identified small subunit ribosomal protein 6 (RPS6) as an indispensable host factor for HCV propagation. Knockdown of RPS6 selectively repressed HCV IRES-mediated translation, but not general translation. Such preferential suppression of HCV translation correlated well with the reduction of the abundance of 40S ribosomal subunit following knockdown of RPS6 or other RPS genes. In contrast, reduction of the amount of ribosomal proteins of the 60S subunit did not produce similar effects. Among the components of general translation machineries, only knockdowns of RPS genes caused inhibitory effects on HCV translation, pointing out the unique role of 40S subunit abundance in HCV translation. This work demonstrates an unconventional notion that the translation initiation of HCV and host possess different susceptibility toward reduction of 40S ribosomal subunit, and provides a model of selective modulation of IRES-mediated translation through manipulating the level of 40S subunit.

High mobility group box 1 promotes endometriosis under hypoxia by regulating inflammation and autophagy in vitro and in vivo.

BACKGROUND: Endometriosis is a chronic disease. Our previous study identified a positive correlation between high mobility group box 1 (HMGB1) and endometriosis, and HMGB1 and inflammation. However, the precise roles of HMGB1 in endometriosis are not fully elucidated. METHODS: We overexpressed HMGB1 in human endometrial stromal cells (HESCs). The expression of pro-inflammatory cytokines and autophagy-related markers were detected by Western blot and ELISA. We generated HMGB1 deficient mice and established the murine model of endometriosis. The development of endometriosis was evaluated. The expression of cytokines and markers of autophagy in implant lesions and mouse endometrial stromal cells was measured. RESULTS: Overexpression of HMGB1 in HESCs promoted the pro-inflammatory cytokines production and expression of autophagy-related markers. HMGB1 deficient mice had less implant lesions, decreased inflammatory cytokines level and down-regulated autophagy-related markers in implant lesions and mouse endometrial stromal cells. CONCLUSION: HMGB1 promotes endometriosis by regulating inflammation and autophagy.

Prediction models for amputation after diabetic foot: systematic review and critical appraisal.

BACKGROUND: Numerous studies have developed or validated prediction models aimed at estimating the likelihood of amputation in diabetic foot (DF) patients. However, the quality and applicability of these models in clinical practice and future research remain uncertain. This study conducts a systematic review and assessment of the risk of bias and applicability of amputation prediction models among individuals with DF. METHODS: A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, EBSCO CINAHL Plus, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedical Literature Database (CBM), and Weipu (VIP) from their inception to December 24, 2023. Two investigators independently screened the literature and extracted data using the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies. The Prediction Model Risk of Bias Assessment Tool (PROBAST) checklist was employed to evaluate both the risk of bias and applicability. RESULTS: A total of 20 studies were included in this analysis, comprising 17 development studies and three validation studies, encompassing 20 prediction models and 11 classification systems. The incidence of amputation in patients with DF ranged from 5.9 to 58.5%. Machine learning-based methods were employed in more than half of the studies. The reported area under the curve (AUC) varied from 0.560 to 0.939. Independent predictors consistently identified by multivariate models included age, gender, HbA1c, hemoglobin, white blood cell count, low-density lipoprotein cholesterol, diabetes duration, and Wagner's Classification. All studies were found to exhibit a high risk of bias, primarily attributed to inadequate handling of outcome events and missing data, lack of model performance assessment, and overfitting. CONCLUSIONS: The assessment using PROBAST revealed a notable risk of bias in the existing prediction models for amputation in patients with DF. It is imperative for future studies to concentrate on enhancing the robustness of current prediction models or constructing new models with stringent methodologies.

Causal associations between modifiable risk factors and isolated REM sleep behavior disorder: a mendelian randomization study.

Objectives: This Mendelian randomization (MR) study identified modifiable risk factors for isolated rapid eye movement sleep behavior disorder (iRBD). Methods: Genome-wide association study (GWAS) datasets for 29 modifiable risk factors for iRBD in discovery and replication stages were used. GWAS data for iRBD cases were obtained from the International RBD Study Group. The inverse variance weighted (IVW) method was primarily employed to explore causality, with supplementary analyses used to verify the robustness of IVW findings. Co-localization analysis further substantiated causal associations identified via MR. Genetic correlations between mental illness and iRBD were identified using trait covariance, linkage disequilibrium score regression, and co-localization analyses. Results: Our study revealed causal associations between sun exposure-related factors and iRBD. Utilizing sun protection (odds ratio [OR] = 0.31 [0.14, 0.69], p = 0.004), ease of sunburn (OR = 0.70 [0.57, 0.87], p = 0.001), childhood sunburn occasions (OR = 0.58 [0.39, 0.87], p = 0.008), and phototoxic dermatitis (OR = 0.78 [0.66, 0.92], p = 0.003) decreased iRBD risk. Conversely, a deep skin color increased risk (OR = 1.42 [1.04, 1.93], p = 0.026). Smoking, alcohol consumption, low education levels, and mental illness were not risk factors for iRBD. Anxiety disorders and iRBD were genetically correlated. Conclusion: Our study does not corroborate previous findings that identified smoking, alcohol use, low education, and mental illness as risk factors for iRBD. Moreover, we found that excessive sun exposure elevates iRBD risk. These findings offer new insights for screening high-risk populations and devising preventive measures.