Characterization and trajectories of hematological parameters prior to severe COVID-19 based on a large-scale prospective health checkup cohort in western China: a longitudinal study of 13-year follow-up.

BACKGROUND: The relaxation of the "zero-COVID" policy on Dec. 7, 2022, in China posed a major public health threat recently. Complete blood count test was discovered to have complicated relationships with COVID-19 after the infection, while very few studies could track long-term monitoring of the health status and identify the characterization of hematological parameters prior to COVID-19. METHODS: Based on a 13-year longitudinal prospective health checkup cohort of ~ 480,000 participants in West China Hospital, the largest medical center in western China, we documented 998 participants with a laboratory-confirmed diagnosis of COVID-19 during the 1 month after the policy. We performed a time-to-event analysis to explore the associations of severe COVID-19 patients diagnosed, with 34 different hematological parameters at the baseline level prior to COVID-19, including the whole and the subtypes of white and red blood cells. RESULTS: A total of 998 participants with a positive SARS-CoV-2 test were documented in the cohort, 42 of which were severe cases. For white blood cell-related parameters, a higher level of basophil percentage (HR = 6.164, 95% CI = 2.066-18.393, P = 0.001) and monocyte percentage (HR = 1.283, 95% CI = 1.046-1.573, P = 0.017) were found associated with the severe COVID-19. For lymphocyte-related parameters, a lower level of lymphocyte count (HR = 0.571, 95% CI = 0.341-0.955, P = 0.033), and a higher CD4/CD8 ratio (HR = 2.473, 95% CI = 1.009-6.059, P = 0.048) were found related to the risk of severe COVID-19. We also observed that abnormality of red cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin might also be involved in the development of severe COVID-19. The different trajectory patterns of RDW-SD and white blood cell count, including lymphocyte and neutrophil, prior to the infection were also discovered to have significant associations with the risk of severe COVID-19 (all P < 0.05). CONCLUSIONS: Our findings might help decision-makers and clinicians to classify different risk groups of population due to outbreaks including COVID-19. They could not only optimize the allocation of medical resources, but also help them be more proactive instead of reactive to long COVID-19 or even other outbreaks in the future.

Patients with periodontitis might increase the risk of urologic cancers: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Numerous observational epidemiological studies have reported a bidirectional relationship between periodontitis and urological cancers. However, the causal link between these two phenotypes remains uncertain. This study aimed to examine the bidirectional causal association between periodontitis and four types of urological tumors, specifically kidney cancer (KC), prostate cancer (PC), bladder cancer (BC), and testis cancer (TC). METHODS: Based on large-scale genome-wide association study (GWAS) data, we utilized the two-sample Mendelian randomization (MR) approach to evaluate causal relationships between periodontitis and urological cancers. Several MR methods covering various consistency assumptions were applied in this study, including contamination mixture and Robust Adjusted Profile Score to obtain robust results. Summary-level data of individuals with European ancestry were extracted from the UK Biobank, the Kaiser GERA cohorts, and the FinnGen consortium. RESULTS: Our findings revealed significant positive genetic correlations between periodontitis and kidney cancer (OR 1.287; 95% CI 1.04, 1.594; P = 0.020). We did not find a significant association of periodontitis on prostate cancer, bladder cancer, and testis cancer. In reverse MR, no significant results were observed supporting the effect of urologic cancers on periodontitis (all P > 0.05). CONCLUSION: Our study provides the evidence of a potential causal relationship between periodontitis and kidney cancer. However, large-scale studies are warranted to confirm and elucidate the underlying mechanisms of this association.

Global bibliometric mapping of dental development research for the period 2012-2021.

BACKGROUND: Dental development is a complex long-term biological process, significant attention should be paid to the dental development and health of this critical time window in childhood for the oral health of the whole life cycle. AIM: This study aimed to conduct bibliometric studies on the scientific outputs of global dental development research by the CiteSpace software. DESIGN: The global scientific outputs about dental development between January 1, 2012, and December 31, 2021, retrieved from Web of Science Core Collection, CiteSpace, and Microsoft Excel were applied for this bibliometric study. RESULTS: A total of 3746 reviews and articles were obtained from the Web of Science core database for exploring the basic publication characteristics, hotspots, and frontiers of this research field. The results showed that dental development is gaining more researcher's attention over time. In terms of countries, the USA and China were the major contributors to this research area. At the institutional level, Sichuan University ranked first. Meanwhile, international cooperation across regions was quite active. The Journal of Dental Research has exerted a broad and far-reaching influence on dental development research in both publications and citations. James P Simmer, Jungwook Kim, Charles E Smith, and Jan CC Hu are among the most influential scholars in this field. Finally, the future hotspots were proposed, covering three directions: dental analysis, tooth development, and post-translational phosphorylation of histones. CONCLUSION: In the past decade, the field of dental development has developed rapidly, and the cooperation between scholars, institutions, and researchers has become increasingly close.

Effectiveness and safety of knotless barbed sutures in cosmetic surgery: A systematic review and meta-analysis.

BACKGROUND: The barbed suture, which can eliminate knot tying and accelerate the placement of sutures, is an innovative type of suture, whereas the benefits of cosmetic surgeries (CS) are controversial. This study aimed to comprehensively evaluate the effectiveness and safety of barbed sutures in CS. METHOD: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched for English studies comparing the use of barbed with conventional sutures in CS up to October 2020. The updated Cochrane risk-of-bias tool (ROB2.0) and Newcastle-Ottawa Scale (NOS) were utilized to evaluate the risk of bias. Subgroup analysis was performed according to study designs and barbed suture types. RESULTS: A total of 14 studies, including 5 randomized controlled trials and 9 cohort studies, were included (risk of bias: moderate to low), representing 2259 patients. The barbed suture was identified to reduce suture time (mean difference [MD]=-6.18, 95% confidence interval [CI]: -8.75 to -3.60, P < 0.00001) and operative time (MD=-10.80, 95% CI: -20.83 to -0.76, P = 0.03) without increasing the hospital stays and total postoperative complications (most were Clavien I and IIIa). No significant difference was detected for incisional infection, delayed wound healing, and hematoma; however, increasing incidence of wound dehiscence (odds ratio [OR]=1.60, 95% CI: 1.09-2.34, P = 0.02) and suture extrusion (OR=3.97, 95%CI: 1.96-8.04, P = 0.0001) were found, particularly in the unidirectional barbed suture subgroup. Barbed sutures might also help CS advance and reduce seroma formation. CONCLUSION: The barbed suture was effective in CS; however, its safety needs to be cautiously interpreted as it might be related to more wound dehiscence and suture extrusion despite similar total postoperative complications with conventional sutures. This study might provide important references for decision-makers and clinicians, though further evidence of randomized design, larger sample size, longer follow-up, and standardized rating approaches are warranted.

The landscape of endodontic education research area: A bibliometric analysis.

OBJECTIVES: Educational research is essential for rationalizing curriculum design, improving evaluation systems, and updating teaching content. This bibliometric study aimed at analyzing the characteristics of publications relevant to endodontic education, thus forming a comprehensive scope of this research area. METHODS: The search was conducted in the Web of Science Core Collection database in May 2022. Knowledge units of the included publications, such as year of publication, journal, country/institution/author, keywords, and highly cited articles/references, were analyzed. RESULTS: The United States ranked first in the number of articles with a total of 17 articles. The majority of included articles were published in Journal of Dental Education (n = 25), International Endodontic Journal (n = 21), and European Journal of Dental Education (n = 14). The top 3 most frequent keywords were Endodontics, Education, and Root canal treatment. The main topic in endodontic education were curriculum, preclinical education, educational technology, and continuing education. CONCLUSION: Forming a full scope of the endodontic research area, this bibliomertic analysis can help mine the hot topic, predict the frontiers in the field and provide the data necessary to determine the direction of research, rationalize resource allocation, and formulate policy.

A Bibliometric Analysis of Studies on Root Caries.

This study aimed to review the current state of the root caries field, explore the current hot topic, and anticipate future research frontiers. The Web of Science Core Collections was searched to acquire publications that were relevant to root caries from 1992 to 2021. After retrieval and manual screening, the co-occurrence and co-operation analysis of keywords and countries/institutions/authors were performed through CiteSpace and VOSviewer based on two periods (1992-2006 and 2007-2021). From 1992 to 2021, 451 unique publications were selected. The USA, which has been the center of international cooperation, has produced the most publications in the research area in 1992-2021. Journal of Dental Research and Caries Research are the main counterpart journals in the field of root caries. The University of London is the institution with the highest number of publications in the analyzed 30 years. "Demineralization," "remineralization," "aged," "dentin," and "fluoride" have been commonly used as keywords throughout the past 30 years. More studies from different aspects have been published in the field of root caries in recent years (2007-2021). The findings of this study provide a full picture of the last 30 years in this research area; hopefully, they also provide essential information for researchers and policymakers to make decisions.

Mutation-associated transcripts reconstruct the prognostic features of oral tongue squamous cell carcinoma.

Tongue squamous cell carcinoma is highly malignant and has a poor prognosis. In this study, we aimed to combine whole-genome sequencing, whole-genome methylation, and whole-transcriptome analyses to understand the molecular mechanisms of tongue squamous cell carcinoma better. Oral tongue squamous cell carcinoma and adjacent normal tissues from five patients with tongue squamous cell carcinoma were included as five paired samples. After multi-omics sequencing, differentially methylated intervals, methylated loop sites, methylated promoters, and transcripts were screened for variation in all paired samples. Correlations were analyzed to determine biological processes in tongue squamous cell carcinoma. We found five mutated methylation promoters that were significantly associated with mRNA and lncRNA expression levels. Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade, which is associated with cancer progression and the development of drug resistance during treatment. The prognostic signature models constructed based on WDR81 and HNRNPH1 and combined clinical phenotype-gene prognostic signature models showed high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings. We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs. Collectively, changes in transcript levels affect the prognosis of tongue squamous cell carcinoma patients.

DNA Methylation Architecture Provides Insight into the Pathogenesis of Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: Numerous studies suggested methylation modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted DNA methylation architecture on the pathological process of UTUC. We aimed to better understand the pathogenesis of UTUC and provide precision medicine references when managing UTUC patients. METHODS: PubMed, Cochrane Library, EMBASE, and Scopus were searched for UTUC until December 31, 2020. Methodological quality assessment was conducted according to NIH recommendations. Meta-analysis was conducted to assess the prognostic effect of methylated genes. Kaplan-Meier survival analyses were performed to validate methylated genes and cytosine-phosphate-guanine (CpG) sites. RESULTS: Eleven studies (3619 patients) were eligible to investigate 12 methylated genes and 10 CpGs. The quality of all the studies was fair to good. Meta-analysis found the pooled effect of eligible methylated genes had a low risk of tumor recurrence (HR = 0·67; 95% CI: 0·51-0·87; P = ·003), but a high risk of tumor progression (HR = 1·60; 95% CI: 1·17-2·18; P = ·003) and cancer-specific mortality (HR = 1·35; 95% CI: 1·06-1·72; P = ·01). For individual methylation status of GDF15, HSPA2, RASSF1A, TMEFF2, and VIM, the pooled effect of each gene was found pleiotropic on both diagnosis and prognosis. Survival analysis suggested higher methylation of SPARCL1 had a better disease-specific survival (P = ·048). CONCLUSION: We combined meta-analysis and Kaplan-Meier survival analysis using the most updated evidence on the methylation of UTUC. Candidate biomarkers with essential diagnosis and prognosis function might provide precision medicine references for personalized therapies.

Core outcomes were rarely reported overall in systematic reviews on acupuncture for osteoarthritis: a cross-sectional meta-epidemiological study.

OBJECTIVE: To identify a comprehensive list of outcomes and explore the reporting rate of core outcome sets (COS) and related factors in systematic reviews (SRs) of acupuncture for osteoarthritis (OA). STUDY DESIGN AND SETTING: Databases were searched for the relative SRs. Descriptive statistics were calculated as frequencies and percentages. Binary logistic regression was used to explore the factors affecting the reporting rate of COS. RESULTS: We included 59 SRs. Outcome measures reported in the SRs were classified into 11 domains and 67 unique outcomes. No SR completely reported COS. In COS released in 2016, 75% of outcomes (6/8) were only reported by ⩽5% SRs. In COS released in 2019, the reporting rate was very low (from 0% to 17%) for 73.3% of outcomes (11/15). SRs published in the most recent 5 years had a significantly greater possibility of reporting COS (odds ratio (OR) = 4.74, 95% confidence interval (CI) = 1.33 to 16.88, p = 0.016). CONCLUSION: Core outcomes were rarely reported in systematic reviews of acupuncture for OA, with considerable heterogeneity in the use of outcomes. The publication of COS in the COMET (Core Outcome Measures in Effectiveness Trials) database may help promote the reporting of COS. We encourage systematic reviewers to use relevant COS.

Senescence-associated secretory phenotype and its impact on oral immune homeostasis.

The senescence-associated secretory phenotype (SASP), which accumulates over the course of normal aging and in age-related diseases, is a crucial driver of chronic inflammation and aging phenotypes. It is also responsible for the pathogenesis of multiple oral diseases. However, the pathogenic mechanism underlying SASP has not yet been fully elucidated. Here, relevant articles on SASP published over the last five years (2017-2022) were retrieved and used for bibliometric analysis, for the first time, to examine SASP composition. More than half of the relevant articles focus on various cytokines (27.5%), growth factors (20.9%), and proteases (20.9%). In addition, lipid metabolites (13.1%) and extracellular vesicles (6.5%) have received increasing attention over the past five years, and have been recognized as novel SASP categories. Based on this, we summarize the evidences demonstrating that SASP plays a pleiotropic role in oral immunity and propose a four-step hypothetical framework for the progression of SASP-related oral pathology-1) oral SASP development, 2) SASP-related oral pathological alterations, 3) pathological changes leading to oral immune homeostasis disruption, and 4) SASP-mediated immune dysregulation escalating oral disease. By targeting specific SASP factors, potential therapies can be developed to treat oral and age-related diseases.

Integrative analysis of gut microbiota and fecal metabolites in metabolic associated fatty liver disease patients.

Objective: Metabolic associated fatty liver disease (MAFLD) affects nearly a quarter of the world's population. Our study aimed to characterize the gut microbiome and overall changes in the fecal and serum metabolomes in MAFLD patients. Methods: Thirty-two patients diagnosed with MAFLD and 30 healthy individuals (control group, CG) were included in this study, the basic clinical characteristics and laboratory test results including routine biochemistry, etc. were recorded for all, and their serum and fecal samples were collected. A portion of the fecal samples was subjected to 16S rDNA sequencing, and the other portion of the fecal samples and serum samples were subjected to non-targeted metabolomic detection based on liquid chromatography-mass spectrometry (LC-MS). Statistical analysis of clinical data was performed using SPSS software package version 25.0 (SPSS Inc., Chicago, IL, United States). The analysis of 16S rDNA sequencing results was mainly performed by R software (V. 2.15.3), and the metabolomics data analysis was mainly performed by CD 3.1 software. Two-tailed p value < 0.05 was considered statistically significant. Results: The 16S sequencing data suggested that the species richness and diversity of MAFLD patients were reduced compared with controls. At the phylum level, the relative abundance of Bacteroidota, Pseudomonadota, and Fusobacteriota increased and Bacillota decreased in MAFLD patients. At the genus level, the relative abundances of Prevotella, Bacteroides, Escherichia-Shigella, etc. increased. 2,770 metabolites were detected in stool samples and 1,245 metabolites were detected in serum samples. The proportion of differential lipid metabolites in serum (49%) was higher than that in feces (21%). There were 22 differential metabolites shared in feces and serum. And the association analysis indicated that LPC 18:0 was positively correlated with Christensenellaceae_R-7_group, Oscillospiraceae_UCG-002; neohesperidin was also positively correlated with Peptoniphilus, Phycicoccus, and Stomatobaculum. Conclusion: Microbial sequencing data suggested decreased species richness and diversity and altered ß-diversity in feces. Metabolomic analysis identified overall changes in fecal and serum metabolites dominated by lipid molecules. And the association analysis with gut microbes provided potentially pivotal gut microbiota-metabolite combinations in MAFLD patients, which might provide new clues for further research on the disease mechanism and the development of new diagnostic markers and treatments.

[CiteSpace-Based Analysis of Hot Research Topics and Frontiers of Preclinical Dentistry Education].

Objective: To analyze the hot research topics and frontiers of preclinical dentistry education with bibliometric methods. Methods: We launched searches in the Web of Science Core Collection database to find relevant literature on preclinical dentistry education, with the time frame of the searches limited between the creation of the database and January 1, 2022. After data extraction, we used the CiteSpace software to conduct visualized analysis of a number of factors, including the number of publications, countries, institutions, authors, keywords, etc. Results: A total of 322 articles and reviews were included in the study, and the annual publication volume showed a trend of steady growth in the past decade. With 98 papers, the United States had the most number of published papers. The United States and the United Kingdom were important countries in the national cooperation network. There were 10 institutions that published more than 5 articles. The total number of authors of the papers covered in the study was as many as 410. One author published 4 articles and was the most published author among them. The hot research topics of preclinical dentistry education included computer-assisted instruction, instructional methodology, clinical skills and 3D printing. Moreover, computer-assisted instruction was the new hot issue of the past decade. Besides, technology, restoration, clinic skills and communication skills were identified as novel research frontiers. Conclusion: Visualized analysis of the research literature generates an intuitive understanding of hot research topics and frontiers of preclinical dentistry education, which provides references for future studies.

Network architecture of non-coding RNAs provides insights into the pathogenesis of upper tract urothelial carcinoma.

Numerous studies suggested that non-coding RNA modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted the architecture of non-coding RNA on the pathological process of UTUC. We aimed to better understand the pathogenesis of UTUC and provide precision medicine references of non-coding RNA when managing UTUC patients. PubMed, Cochrane Library, Embase, and Scopus were searched for UTUC until December 31, 2020. Methodological quality assessment was conducted according to NIH recommendations. Enrichment analyses and network analyses were conducted to explore the interactions of miRNA with genes and other non-coding RNAs. Survival analyses were performed to validate the novel genes. A total of 12 pairs of UTUC tumors and adjacent normal tissues were also included to validate the gene expressions regulated by miRNAs from the miRNA-gene network. Thirteen studies with 945 patients were eligible, investigating 106 miRNAs mutations. The quality of all the studies was fair to good. Most miRNAs were enriched in tissue/organs, diseases, and specific anti-cancer drugs (false discovery rate <0.05). Other non-coding RNAs, i.e.,: miR-34a, DLGAP1-AS1, USP39, and RNA5SP479, were highlighted by network analyses to have potential in the pathogenesis of UTUC. Top hub genes in the miRNA-gene network, namely ZNF460, NUFIP2, and E2F3, were all validated by survival analysis(P < 0.05). Using own cohort data, the differential expression analyses identified 368 overlapped significant genes, including above 3 hub genes (false discovery rate <0.05). Novel biomarkers identified in our studies might play essential roles in UTUC, from the perspectives of the molecule, tissue/organ, diagnosis, treatment, and prognosis. Candidate biomarkers could be significant references for personalized and target therapies.

A search of only four key databases would identify most randomized controlled trials of acupuncture: A meta-epidemiological study.

Little research has been conducted to assess which specific databases should be searched when performing a systematic review (SR) on acupuncture. The current study aimed to identify key databases and the optimal database combination to retrieve randomized controlled trials (RCTs) on acupuncture for inclusion in SRs. A systematic search for SRs in the field of acupuncture was conducted in order to identify target databases and RCTs were extracted from the SRs that had searched all target databases. The proportions of SRs that had achieved 100%, 95%, or 90% recall of RCTs and the total recall of RCTs in various combinations of target databases were calculated. Sensitivity analysis was performed on those SRs that included 10 or more RCTs. CNKI, WanFang, VIP, PubMed, CENTRAL and Embase were regarded as target databases. A total of 4349 acupuncture RCTs were extracted from 286 SRs. Searching all six target databases retrieved 99.3% of all RCTs while 99.1% were recalled by searching the combination of CNKI, WanFang, PubMed and CENTRAL. There were no significant differences on total recall of RCTs (p = 0.549) or in the proportion of SRs with 90% recall of RCTs (97.2% vs. 97.6%; p = 0.794) between searching the above four and the full six target databases. Most results were similar in the sensitivity analysis. The combined retrieval power of CNKI, WanFang, PubMed and CENTRAL was considered an efficient choice to retrieve acupuncture RCTs included in SRs.

Is the CyberKnife© radiosurgery system effective and safe for patients? An umbrella review of the evidence.

Background: The CyberKnife© system combines real-time image guidance and a dynamic tracking system to implement frameless radiotherapy. This umbrella review is aimed to evaluate the effectiveness and safety of CyberKnife. Methods: A comprehensive search of health technology assessments and systematic reviews was performed among the Embase, PubMed and other grey databases until July 2020. Treatment outcomes were extracted, and the quality of included studies were assessed using AMSTAR-2. Results: Nineteen studies were eligible. CyberKnife not only had a wide range of applications, long overall survival and great local control, but also had a limited toxicity and good cost-effectiveness compared with other radiotherapy equipment. Conclusion: Despite the relatively low quality of the evidence, our findings can still provide a decision reference for policymakers.

An umbrella review on the effectiveness and safety of the CyberKnife^© system was performed by comprehensively searching for all related publications. The CyberKnife system had excellent effect on treatment of cancer and some noncancer diseases, with limited toxicity. Additionally, it was a cost-effective treatment compared with other types of radiotherapy. Despite the relatively low quality of the included evidence, our findings can still provide a comprehensive decision reference for policymakers of patients, government and hospitals.

Hemostatic Agent May Improve Perioperative Outcomes in Partial Nephrectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Hemostatic agents (HAs) are used to achieve hemostasis and prevent postoperative complications in multiple surgeries, but the role of HAs is ambiguous during partial nephrectomy (PN), so this study aimed to assess the role of HAs in PN. METHODS: PubMed, Embase, CENTRAL and ClinicalTrials.gov were searched for randomized controlled trials and cohort studies regarding the comparison of HA use alone and standard suturing during PN on January 17, 2020. RevMan 5.3 was used to conduct meta-analysis. Sensitivity analyses and subgroup analyses were performed based on surgical procedures and HA types. RESULTS: Six studies involving 1,066 patients were included. The quality of studies was moderate to high. There were significant reductions in warm ischemia time (mean difference [MD] = -6.30 min, 95% confidence interval [CI] -7.70 to -4.90, p < 0.00001), operative time (MD = -19.81 min, 95% CI -27.54 to -12.08, p < 0.00001), and estimated blood loss (MD = -108.62 mL, 95% CI -177.27 to -39.9, p = 0.002) in the HA group, and HA use alone did not increase postoperative complications. The results were similar in the subgroup analyses and sensitivity analyses. CONCLUSION: HA may be an effective and safe surgical material in PN, which can improve postoperative outcomes. High-quality and randomly designed studies are needed to validate the applicability.

Characteristic and Early Discontinuation of Obsessive-Compulsive Disorder Trials Registered on ClinicalTrials.gov.

Objective: This study aimed to analyze the characteristics and reasons of early discontinuation of obsessive-compulsive disorder (OCD) trials registered on ClinicalTrials.gov. Methods: OCD trials and relevant publications were searched on ClinicalTrials.gov and PubMed, respectively. The characteristics and details regarding the timely publication of trials were recorded. Cox regression analysis was used to explore factors associated with the early discontinuation of OCD trials. Results: The analysis included 298 OCD therapy trials. Most investigations recruited <100 patients and were more likely to involve adults. Of all OCD studies identified, 67.8% were randomized and 61.4% were blind (single- or double-blind). Universities and hospitals were recorded as the two primary locations in the majority of trials. A total of 155 trials (52%) were completed; however, only 29% of those were published. Of the published trials, >70% were published at least 1 year after completion. Behavioral therapy trials were the most common type of major treatment-aimed OCD trials (39%), followed by drug trials (35.1%) and device/procedure trials (24.7%). The univariate Cox regression analysis indicated that drug trials [hazard ratio (HR) = 2.56, 95% confidence interval (CI): 1.21-5.43], absence of collaborators (HR = 3.87, 95% CI: 1.62-9.26), and sponsorship by industry (HR = 3.97, 95% CI: 1.49-10.53) were risk factors for early discontinuation of OCD trials. Further multivariate Cox regression showed that drug trials (HR = 3.93, 95% CI: 1.71-9.08) and absence of collaborators (HR = 5.17, 95% CI: 1.97-13.54) were independent risk factors for early trial discontinuation of OCD trials. The sensitivity analysis confirmed these results. Non-drug trials (OR = 3.32, 95% CI: 1.21-9.11), absence of collaborators (OR = 3.25, 95% CI: 1.10-9.60), and non-blinded trials (OR = 5.23, 95% CI: 1.05-26.2) were independent risk factors for unreported results in registry. Conclusion: The diagnosis and prevention of OCD are rarely investigated in trials. Underreporting and delayed reporting remain major problems. The type of intervention and participation of collaborators are associated with early discontinuation of OCD trials.

Deep Collocative Learning for Immunofixation Electrophoresis Image Analysis.

Immunofixation Electrophoresis (IFE) analysis is of great importance to the diagnosis of Multiple Myeloma, which is among the top-9 cancer killers in the United States, but has rarely been studied in the context of deep learning. Two possible reasons are: 1) the recognition of IFE patterns is dependent on the co-location of bands that forms a binary relation, different from the unary relation (visual features to label) that deep learning is good at modeling; 2) deep classification models may perform with high accuracy for IFE recognition but is not able to provide firm evidence (where the co-location patterns are) for its predictions, rendering difficulty for technicians to validate the results. We propose to address these issues with collocative learning, in which a collocative tensor has been constructed to transform the binary relations into unary relations that are compatible with conventional deep networks, and a location-label-free method that utilizes the Grad-CAM saliency map for evidence backtracking has been proposed for accurate localization. In addition, we have proposed Coached Attention Gates that can regulate the inference of the learning to be more consistent with human logic and thus support the evidence backtracking. The experimental results show that the proposed method has obtained a performance gain over its base model ResNet18 by 741.30% in IoU and also outperformed popular deep networks of DenseNet, CBAM, and Inception-v3.

The crystal structure of Atg18 reveals a new binding site for Atg2 in Saccharomyces cerevisiae.

Macroautophagy (hereafter referred to as autophagy) is a highly conserved catabolic eukaryotic pathway that is critical for stress responses and homeostasis. Atg18, one of the core proteins involved in autophagy, belongs to the PROPPIN family and is composed of seven WD40 repeats. Together with Atg2, Atg18 participates in the elongation of phagophores and the recycling of Atg9 in yeast. Despite extensive studies on the PROPPIN family, the structure of Atg18 from Saccharomyces cerevisiae has not been determined. Here, we report the structure of ScAtg18 at a resolution of 2.8 Å. Based on bioinformatics and structural analysis, we found that the 7AB loop of ScAtg18 is extended in Atg18, in comparison to other members of the PROPPIN family. Genetic analysis revealed that the 7AB loop of ScAtg18 is required for autophagy. Biochemical and biophysical experiments indicated that the 7AB loop of ScAtg18 is critical for interaction with ScAtg2 and the recruitment of ScAtg2 to the autophagy-initiating site. Collectively, our results show that the 7AB loop of ScAtg18 is a new binding site for Atg2 and is of functional importance to autophagy.