Deep radiomics-based prognostic prediction of oral cancer using optical coherence tomography.

BACKGROUND: This study aims to evaluate the integration of optical coherence tomography (OCT) and peripheral blood immune indicators for predicting oral cancer prognosis by artificial intelligence. METHODS: In this study, we examined patients undergoing radical oral cancer resection and explored inherent relationships among clinical data, OCT images, and peripheral immune indicators for oral cancer prognosis. We firstly built a peripheral blood immune indicator-guided deep learning feature representation method for OCT images, and further integrated a multi-view prognostic radiomics model incorporating feature selection and logistic modeling. Thus, we can assess the prognostic impact of each indicator on oral cancer by quantifying OCT features. RESULTS: We collected 289 oral mucosal samples from 68 patients, yielding 1,445 OCT images. Using our deep radiomics-based prognosis model, it achieved excellent discrimination for oral cancer prognosis with the area under the receiver operating characteristic curve (AUC) of 0.886, identifying systemic immune-inflammation index (SII) as the most informative feature for prognosis prediction. Additionally, the deep learning model also performed excellent results with 85.26% accuracy and 0.86 AUC in classifying the SII risk. CONCLUSIONS: Our study effectively merged OCT imaging with peripheral blood immune indicators to create a deep learning-based model for inflammatory risk prediction in oral cancer. Additionally, we constructed a comprehensive multi-view radiomics model that utilizes deep learning features for accurate prognosis prediction. The study highlighted the significance of the SII as a crucial indicator for evaluating patient outcomes, corroborating our clinical statistical analyses. This integration underscores the potential of combining imaging and blood indicators in clinical decision-making. TRIAL REGISTRATION: The clinical trial associated with this study was prospectively registered in the Chinese Clinical Trial Registry with the trial registration number (TRN) ChiCTR2200064861. The registration was completed on 2021.

Lanthanum chloride exerts therapeutic potential for chronic kidney disease by suppressing nanohydroxyapatite-induced mitophagy and mitochondria-mediated apoptosis.

OBJECTIVE: To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism. METHODS: 1. Patients with CKD stage 2-5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected. RESULTS: 1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride. CONCLUSION: Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively.

Dynamic brain entropy predicts risky decision-making across transdiagnostic dimensions of psychopathology.

OBJECTIVES: Maladaptive risky decision-making is a common pathological behavior among patients with various psychiatric disorders. Brain entropy, which measures the complexity of brain time series signals, provides a novel approach to assessing brain health. Despite its potential, the dynamics of brain entropy have seldom been explored. This study aimed to construct a dynamic model of brain entropy and examine its predictive value for risky decision-making in patients with mental disorders, utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: This study analyzed the rs-fMRI data from a total of 198 subjects, including 48 patients with bipolar disorder (BD), 47 patients with schizophrenia (SZ), 40 patients with adult attention deficit hyperactivity disorder (ADHD), as well as 63 healthy controls (HC). Time series signals were extracted from 264 brain regions based on rs-fMRI. The traditional static entropy and dynamic entropy (coefficient of variation, CV; rate of change, Rate) were constructed, respectively. Support vector regression was employed to predict risky decision-making utilizing leave-one-out cross-validation within each group. RESULTS: Our findings showed that CV achieved the best performances in HC and BD groups (r = -0.58, MAE = 6.43, R2 = 0.32; r = -0.78, MAE = 12.10, R2 = 0.61), while the Rate achieved the best in SZ and ADHD groups (r = -0.69, MAE = 10.20, R2 = 0.47; r = -0.78, MAE = 7.63, R2 = 0.60). For the dynamic entropy, the feature selection threshold rather than the time window length and overlapping ratio influenced predictive performance. CONCLUSIONS: These results suggest that dynamic brain entropy could be a more effective predictor of risky decision-making than traditional static brain entropy. Our findings offer a novel perspective on exploring brain signal complexity and can serve as a reference for interventions targeting risky decision-making behaviors, particularly in individuals with psychiatric diagnoses.

ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure.

Aneuploidy, the presence of a chromosomal anomaly, is a major cause of spontaneous abortions and recurrent pregnancy loss in humans. However, the underlying molecular mechanisms still remain poorly understood. Here, we report that ARHGAP26, a putative tumor suppressor gene, is a newly identified regulator of oocyte quality to maintain mitochondrial integrity and chromosome euploidy, thus ensuring normal embryonic development and fertility. Taking advantage of knockout mouse model, we revealed that genetic ablation of Arhgap26 caused the oocyte death at GV stage due to the mitochondrial dysfunction-induced ROS accumulation. Lack of Arhgap26 also impaired both in vitro and in vivo maturation of survived oocytes which results in maturation arrest and aneuploidy, and consequently leading to early embryonic development defects and subfertility. These observations were further verified by transcriptome analysis. Mechanistically, we discovered that Arhgap26 interacted with Cofilin1 to maintain the mitochondrial integrity by regulating Drp1 dynamics, and restoration of Arhgap26 protein level recovered the quality of Arhgap26-null oocytes. Importantly, we found an ARHGAP26 mutation in a patient with history of recurrent miscarriage by chromosomal microarray analysis. Altogether, our findings uncover a novel function of ARHGAP26 in the oocyte quality control and prevention of aneuploidy and provide a potential treatment strategy for infertile women caused by ARHGAP26 mutation.

ChatGPT-based meta-analysis for evaluating the temporal and spatial characteristics of deoxynivalenol contamination in Chinese wheat.

Deoxynivalenol (DON) is a major source of mycotoxins in wheat. However, there is a lack of systematic reporting of the overall contamination status in China, hindering comprehensive assessments. In this study, we utilized a meta-analysis approach based on ChatGPT to systematically analyze DON contamination in wheat-growing regions in China, as reported in the literature from 2010 to 2021. By optimizing the query processes and refining the methodology keywords using ChatGPT, efficient screening, data identification, and literature extraction were achieved for the first time during the meta-analysis data acquisition phase. The matching rates for the screening and extraction of 1091 articles were 100 % and 95.4 %, respectively, resulting in a 20.5-fold work efficiency increase compared to that by manual operations. Meta-subgroup analysis by province and year revealed significant spatiotemporal heterogeneity in DON contamination in the wheat-growing regions of China. Furthermore, the relationship between climate factors and DON levels in wheat was investigated to illustrate the spatial and temporal heterogeneity of DON in Chinese wheat. The results showed that DON concentrations were mainly influenced by relative humidity and precipitation during the wheat-growing season. This novel ChatGPT-assisted meta-analysis approach provides valuable insights and offers a promising method for efficient meta-analyses in other fields.

Identification of bile acids in snake bile by hydrogen/deuterium exchange mass spectrometry and quantitative structure-retention relationship analysis.

Natural bile acids, a class of steroids with a valeric acid side chain at the C-17 position, present significant challenges in separation and analysis due to structural similarities, isomerism, and large polarity differences. Therefore, advanced analytical methods are essential for the accurate identification and quantification of bile acids. This study conducted a comprehensive qualitative analysis of bile acids by integrating liquid chromatography-tandem mass spectrometry (LC-MS/MS), hydrogen-deuterium exchange tandem mass spectrometry (HDX-MS/MS), and quantitative structure-retention relationship (QSRR) methods. Firstly, LC-MS/MS conditions were optimized to enhance chromatographic separation and improve the reliability of characteristic fragment ions. MS/MS fragmentation rules for bile acids were derived from the mass spectral data of bile acid standards and validated through HDX-MS/MS experiments. Secondly, potential bile acids in snake bile were identified based on these validated fragmentation rules, and a QSRR model was established to predict the retention times of the proposed structures. Thirdly, HDX-MS/MS was applied to assist in identifying bile acid isomers. Finally, a total of 150 bile acids, including 11 free bile acids (free BA), 5 glyco-bile acids (GBA) and 134 tauro-bile acids (TBA), were detected in snake bile. Thirteen bile acids were accurately characterized by comparing their retention time and MS/MS spectra with standards. Forty-nine bile acids were reasonably annotated using the QSRR model and HDX-MS/MS. This study is notable for being the first to utilize the QSRR and HDX-MS/MS techniques for the annotation of bile acids in snake bile, providing a robust framework for the structural elucidation of these compounds.

High-risk factors for massive haemorrhage in medical abortion patients with missed miscarriage.

BACKGROUND: Recently, the incidence of missed miscarriage has gradually increased, and medical abortion is a common method to terminate a pregnancy. In the process of medical abortion, massive vaginal bleeding takes place, leading to emergency surgical haemostasis. Emergency surgery may produce infection and organ damage. Our study aimed to investigate the high-risk factors for massive haemorrhage during a medical abortion. METHODS: A total of 1062 missed miscarriage patients who underwent medical abortion participated in this retrospective study. According to the amount of bleeding, the patients were divided into a massive haemorrhage group and a control group. By comparing the general conditions of the two groups, such as fertility history, uterine surgery history, uterine fibroids, etc., the high-risk factors for massive haemorrhage during medical abortion were identified. RESULTS: Relative to the control group, the massive haemorrhage group exhibited a higher proportion of patients with a previous artificial abortion (51.9% vs. 38.1%, P = 0.001). Additionally, the massive haemorrhage group had a lower percentage of first-time pregnant women (32.1% vs. 40.4%) and a higher proportion of women with shorter pregnancy intervals (44.9% vs. 33.1%, P = 0.03). Furthermore, there were notable differences between the two groups regarding maximum fibroid size, the duration of amenorrhea, and gestational week (P < 0.05). CONCLUSION: In this study, we determined that a history of artificial abortion and an amenorrhea duration of > 11 weeks represented high-risk factors for massive vaginal bleeding during medical abortion in missed miscarriage patients.

Oat anthranilamides regulates high-fat diet-induced intestinal inflammation by the TLR4/NF-κb signalling pathway and gut microbiota.

Oat anthranilamides have demonstrated antioxidant and anti-inflammatory effects; however, the precise mechanism of action remains unclear. This study investigated the impact of oat anthranilamide B (AVN B) on high-fat diet (HFD)-induced intestinal inflammation in mice and its underlying mechanisms. The results indicated that AVN B supplementation mitigated weight gain and reduced inflammatory and oxidative stress markers in serum, liver, and intestines. It improved intestinal barrier dysfunction by upregulating the expression levels of Occludin and MUC2 while simultaneously reducing intestinal inflammation by inhibiting the TLR4/NF-κB signalling pathway. Additionally, AVN B treatment improved gut microbiota composition. It increased the abundance of beneficial flora and the production of short-chain fatty acids (SCFAs), especially propionate and butyrate, associated with reduced production of pro-inflammatory factors and enhanced intestinal protection. The findings provide scientific evidence for the potential of AVN B as an anti-inflammatory agent.

Oat AVN B reduces body weight gain and inflammation levels in HFD-fed miceAVN B protects the intestinal barrier and inhibits intestinal inflammationAVN B inhibits TLR4/NF-κB signalling pathway in the ileum of HFD-induced miceAVN B improves gut microbial imbalance in HFD-induced miceAVN B increases butyrate and propionic acid by promoting SCFA-producing bacteria.

Exploring the causal association between epigenetic clocks and menopause age: insights from a bidirectional Mendelian randomization study.

Background: Evidence suggests a connection between DNA methylation (DNAm) aging and reproductive aging. However, the causal relationship between DNAm and age at menopause remains uncertain. Methods: Employing established DNAm epigenetic clocks, such as DNAm Hannum age acceleration (Hannum), Intrinsic epigenetic age acceleration (IEAA), DNAm-estimated granulocyte proportions (Gran), DNAm GrimAge acceleration (GrimAgeAccel), DNAm PhenoAge acceleration (PhenoAgeAccel), and DNAm-estimated plasminogen activator inhibitor-1 levels (DNAmPAIadjAge), a bidirectional Mendelian randomization (MR) study was carried out to explore the potential causality between DNAm and menopausal age. The primary analytical method used was the inverse variance weighted (IVW) estimation model, supplemented by various other estimation techniques. Results: DNAm aging acceleration or deceleration, as indicated by Hannum, IEAA, Gran, GrimAgeAccel, PhenoAgeAccel, and DNAmPAIadjAge, did not exhibit a statistically significant causal effect on menopausal age according to forward MR analysis. However, there was a suggestive positive causal association between age at menopause and Gran (Beta = 0.0010; 95% confidence interval (CI): 0.0004, 0.0020) in reverse MR analysis. Conclusion: The observed increase in granulocyte DNAm levels in relation to menopausal age could potentially serve as a valuable indicator for evaluating the physiological status at the onset of menopause.

Acoustic Controllable Spatiotemporal Cell Micro-oscillation for Noninvasive Intracellular Drug Delivery.

Intracellular cargo delivery is crucial for drug evaluation, nanomedicine development, and gene therapy, in which high efficiency while maintaining cell viability is needed for downstream analysis. Here, an acoustic-mediated precise drug delivering mechanism is proposed by directly modulating cell micro-oscillation mode and membrane permeability. Through phase shifting keying-based spatiotemporal acoustic tweezers, controllable oscillating cell arrays can be achieved in shaking potentials. At the same time, continually oscillating radiation force and fluid shear stress exerted on cells effectively disturbs cellular membrane mobility and enhances permeability, thereby facilitating nanodrug entrance. In experiments, cell oscillation is tunable in frequency (10-2 to 102 Hz), shaking direction, amplitude (0 to quarter acoustic wavelength), and speed. Doxorubicin is actively delivered across cellular membranes and accumulates in inner cells, with a concentration more than 8 times that of the control group. Moreover, there is no obvious compromise in cell activity during oscillation, exhibiting excellent biocompatibility. This "dancing acoustic waves" scheme introduces a new dimension of cell manipulation in both space and time domains and an effective drug delivering strategy, offering advantages of flexibility, gentleness, and high throughput. It may advance related fields like nanobiological research, drug and nanomedicine development, and medical treatment.

Spatio-temporal characteristics and multi-scale risk identification of pollution load based on sensitivity analysis in small watersheds located in Tuojiang River Basin, China.

High-quality development of water resources supports high-quality socio-economic development. High-quality development connects high-quality life, and clarifying the key management contents of small watersheds plays an important role in building ecologically clean small watersheds and promoting regional production and life. Previous research on pollution loads has focused on examining the impact of various external drivers on pollution loads but still lacks research on the impact of changes in pollution sources themselves on pollution loads. In this study, sensitivity analysis was used to determine the impact of changes from different sources on the total pollution loads, which can recognize the critical pollution sources. We first employed the pollutant discharge coefficient method to quantify non-point source pollution loads in the small watershed in the upstream Tuojiang River basin from 2010 to 2021. Then, combination sensitivity analysis with Getis-Ord Gi* was used to identify the critical sources and their crucial areas at the global, districts (counties), and towns (streets) scales, respectively. The results indicate: (1) The pollution loads of COD, NH3-N, TN, and TP all show a decreasing trend, reducing by 18.3%, 16.2%, 18.6%, and 28.1% from 2010 to 2021, respectively; (2) Livestock and poultry breeding pollution source is the most critical source for majority areas across watershed; (3) High-risk areas are mainly concentrated in Jingyang district and its subordinate towns (streets). There is a trend of low-pollution risk areas transitioning to high-pollution risk areas, with high-risk areas predominantly concentrated in the southeast and exhibiting a noticeable phenomenon of pollution load spilling around. This study can promote other similar small watersheds, holding significant importance for non-point source pollution control in small watersheds.

Water quality assessment and its pollution source analysis from spatial and temporal perspectives in small watershed of Sichuan Province, China.

Rapid socio-economic development has led to many water environmental issues in small watersheds such as non-compliance with water quality standards, complex pollution sources, and difficulties in water environment management. To achieve a quantitative evaluation of water quality, identify pollution sources, and implement refined management in small watersheds, this study collected monthly seven water quality indexes of four monitoring points from 2010 to 2023, and ten water quality indexes of 23 sampling points in the Shiting River and Mianyuan River which are tributaries of the Tuojiang River Basin. Then, water quality evaluation and pollution source analysis were conducted from both temporal and spatial perspectives using the Water Quality Index (WQI) method, the Absolute Principal Component Scores/Multiple Linear Regression (APCS-MLR) method, and the Positive Matrix Factorization (PMF) receptor modeling technique. The results indicated that except for total nitrogen (TN), the concentrations of other water quality indexes exhibited a decreasing trend, and all were divided into two obvious stages before and after 2016. Furthermore, the proportion of water quality grade of Good and above increased from 73.96 to 84.94% from 2010-2015 to 2016-2023, and the water quality grade of Good and above from upstream to downstream dropped from 100 to 23.33%. From the temporal scale, four and five pollution sources were identified in the first and second stages, respectively. The distinct TN pollutant is mainly affected by agricultural non-point sources (NPS), whose impact is enhanced from 17.76 to 78.31%. Total phosphorus (TP) was affected by the phosphorus chemical industry, whose contribution gradually weakened from 50.8 to 24.9%. From a spatial perspective, four and five pollution sources were identified in the upstream and downstream, respectively. Therefore, even though there are some limitations due to the data availability of water monitory and hydrology data, the proposed research framework of this study can be applied to the water environmental management of other similar watersheds.

Contribution assessment and accumulation prediction of heavy metals in wheat grain in a smelting-affected area using machine learning methods.

Due to the diverse controlling factors and their uneven spatial distribution, especially atmospheric deposition from smelters, assessing and predicting the accumulation of heavy metals (HM) in crops across smelting-affected areas becomes challenging. In this study, integrating HM influx from atmospheric deposition, a boosted regression tree model with an average R2 > 0.8 was obtained to predict accumulation of Pb, As, and Cd in wheat grain across a smelting region. The atmospheric deposition serves as the dominant factor influencing the accumulation of Pb (28.2 %) and As (31.2 %) in wheat grain, but shows a weak influence on Cd accumulation (12.1 %). The contents of available HM in soil affect HM accumulation in wheat grain more significantly than their total contents in soil with relative importance rates of Pb (14.4 % > 8.2 %), As (30.9 % > 4.0 %), and Cd (55.0 % > 16.9 %), respectively. Marginal effect analysis illustrates that HM accumulation in wheat grain begins to intensify when Pb content in atmospheric dust reaches 5140 mg/kg and available Cd content in soil exceeds 1.15 mg/kg. The path analysis rationalizes the cascading effects of distances from study sites to smelting factories on HM accumulation in wheat grain via negatively influencing atmospheric HM deposition. The study provides data support and a theoretical basis for the sustainable development of non-ferrous metal smelting industry, as well as for the restoration and risk management of HM-contaminated soils.

The therapeutic value of ipsilateral supraclavicular lymphadenectomy in locally advanced breast cancer: A review.

The treatment of isolated ipsilateral supraclavicular lymph node metastasis for locally advanced breast cancer has always been a controversial issue for breast surgeons. However, with the further understanding of the metastasis and treatment of breast cancer, it is now considered to be a locally advanced disease, and there is a new debate on the treatment of isolated ipsilateral supraclavicular lymph node metastasis. The author reviewed the relevant literature and briefly discussed the clinical significance of supraclavicular lymph node resection in patients with locally advanced breast cancer presenting with isolated ipsilateral supraclavicular lymph node metastasis.

Ecological security assessment of Yunnan Province, China in the context of Production-Living-Ecological space division.

With the rapid development of population, society and economy, human activities have caused serious adverse impacts on the environment, ecosystems and landscape patterns over the long term. In order to address the series of impacts of human activities on the environment, territorial space and resource use, the study of Production-Living-Ecological Space (PLES) and ecological security have all become academic frontiers in the field of sustainable development. In this study, we applied multi-source data and GIS technology to construct an ecological security evaluation model based on the results of PLES delineation and the Pressure-State-Response (PSR) framework, and carried out the three-period PLES ecological security evaluation for 2000, 2010 and 2020 at the county and grid scales in Yunnan Province. The PLES pattern in Yunnan Province is dominated by ecological space, which accounts for 75%, followed by 23% of production space, with ecological space shrinking from 2000 to 2020. Ecological security in ecological space and living space shows an improving trend from 2000 to 2020. The ecological security of production space improved in 2010 compared to 2000 but then showed a decreasing trend in 2020. Ecological security in ecological space shows that north-western and southern Yunnan is safer than central Yunnan, while ecological security in living space is safer in central Yunnan, and ecological security in production space is better in southern Yunnan than in northern Yunnan. Comparison with related research results shows that the ecological security evaluation results of PLES in Yunnan Province in this study are scientific and reasonable. The ecological security evaluation model of PLES constructed in this study solves the problem of complex and incomplete ecological security evaluation indexes in the past, and the results of the study are more refined and precise, which provides new ideas for the study of regional ecological security.

Exploring the gut microbiota's crucial role in acute pancreatitis and the novel therapeutic potential of derived extracellular vesicles.

During acute pancreatitis, intestinal permeability increases due to intestinal motility dysfunction, microcirculatory disorders, and ischemia-reperfusion injury, and disturbances in the intestinal flora make bacterial translocation easier, which consequently leads to local or systemic complications such as pancreatic and peripancreatic necrotic infections, acute lung injury, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Therefore, adjusting intestinal ecosystem balance may be a promising approach to control local and systemic complications of acute pancreatitis. In this paper, we reviewed the causes and manifestations of intestinal flora disorders during acute pancreatitis and their complications, focused on the reduction of acute pancreatitis and its complications by adjusting the intestinal microbial balance, and innovatively proposed the treatment of acute pancreatitis and its complications by gut microbiota-derived extracellular vesicles.

Comparative analysis of chloroplast genome and evolutionary history of Hemerocallis.

Members of the genus Hemerocallis have significant value as ornamental, edible, and medicinal plants, particularly in China, where they have been utilized for thousands of years as both a vegetable and Traditional Chinese Medicine. Hemerocallis species exhibit strict control over flowering time, with individuals flowering either diurnally or nocturnally. However, our understanding of the evolutionary history of this genus, especially concerning important horticultural traits, remains limited. In this study, sequencing and assembly efforts were conducted on 73 samples within the Hemerocallis genus. All accessions were classified into two distinct groups based on their diurnal (daylilies) or nocturnal (nightlilies) flowering habits. Comparative analysis of the chloroplast genomes from these two groups identified fifteen variant hotspot regions, including fourteen SNPs and one deletion, which hold promise for the development of molecular markers for interspecific identification. Phylogenetic trees, generated through both maximum-likelihood and Bayesian inference methods using 76 shared protein-coding sequences, revealed that diurnal flowering evolved prior to nocturnal flowering. The divergence between the two groups is estimated to have occurred approximately 0.82 MYA (95% CI: 0.35-1.45 MYA). The ancestral state of Hemerocallis is hypothesized to have featured diurnal flowering with orange yellow petals. This study marks the first reconstruction of the evolutionary history and ancestral state of the genus Hemerocallis. The findings contribute significantly to our understanding of the adaptation and speciation history within the genus.

The gap between statistical and clinical significance: time to pay attention to clinical relevance in patient-reported outcome measures of insomnia.

BACKGROUND: Appropriately defining and using the minimal important change (MIC) and the minimal clinically important difference (MCID) are crucial for determining whether the results are clinically significant. The aim of this study is to survey the status of randomized controlled trials (RCTs) for insomnia interventions to assess the inclusion and interpretation of MIC/MCID values. METHODS: We conducted a cross-sectional study to survey the status of RCTs for insomnia interventions to assess the inclusion and appropriate interpretation of MIC/MCID values. A literature search was conducted by searching the main sleep medicine journals indexed in PubMed, the Excerpta Medica Database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify a broad range of search terms. We included RCTs with no restriction on the intervention. The included studies used the Insomnia Severity Index (ISI) or the Pittsburgh Sleep Quality Index (PSQI) questionnaire as the outcome measures. RESULTS: 81 eligible studies were identified, and more than one-third of the included studies used MIC/MCID (n = 31, 38.3%). Among them, 21 studies with ISI as the outcome used MIC defined as a relative decrease ranging from 3 to 8 points. The most frequently used MIC value was a 6-point decrease (n = 7), followed by 8-point (n = 6) and 7-point decrease (n = 4), a 4 to 5-points decrease (n = 3), and a 30% reduction from baseline; 6 studies used MCID values, ranging from 2.8 to 4 points. The most frequently used MCID value was a 4-point decrease in the ISI (n = 4). 4 studies with PSQI as the outcome used a 3-point change as the MIC (n = 2) and a 2.5 to 2.7-point difference as MCID (n = 2). 4 non-inferiority design studies considered interval estimation when drawing clinically significant conclusions in their MCID usage. CONCLUSIONS: The lack of consistent MIC/MCID interpretation and usage in outcome measures for insomnia highlights the urgent need for further efforts to address this issue and improve reporting practices.

An Exploration of Shared Risk Factors for Coronary Artery Disease and Cancer from 109 Traits: The Evidence from Two-Sample Mendelian Randomization Studies.

Background: Although observational studies have reported several common biomarkers related to coronary artery disease (CAD) and cancer, there is a shortage of traditional epidemiological data to establish causative linkages. Thus, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis to systematically investigate the causal associations of 109 traits with both CAD and cancer to identify their shared risk and protective factors. Methods: The genetic association datasets pertaining to exposure and outcomes were reviewed using the most recent and public genome-wide association studies (GWAS). Inverse variance weighting (IVW), weighted median (WM), and MR-Egger strategies were implemented for the MR analyses. The heterogeneity and pleiotropy were measured utilizing leave-one-out sensitivity testing, MR-PRESSO outlier detection, and Cochran's Q test. Results: The IVW analyses revealed that genetic-predicted mean sphered cell volume (MSCV) is a protective factor for CAD, and weight is a risk factor. MSCV and weight also show similar effects on cancer. Furthermore, our study also identified a set of risk and protective factors unique to CAD and cancer, such as telomere length. Conclusions: Our Mendelian randomization study sheds light on shared and unique risk and protective factors for CAD and cancer, offering valuable insights that could guide future research and the development of personalized strategies for preventing and treating these two significant health issues.