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Tumor-derived circulating cell-free DNA (cfDNA) provides critical clues for cancer early diagnosis, yet it often suffers from low sensitivity. Here, we present a cancer early diagnosis approach using tumor fractions deciphered from circulating cfDNA methylation signatures. We show that the estimated fractions of tumor-derived cfDNA from cancer patients increase significantly as cancer progresses in two independent datasets. Employing the predicted tumor fractions, we establish a Bayesian diagnostic model in which training samples are only derived from late-stage patients and healthy individuals. When validated on early-stage patients and healthy individuals, this model exhibits a sensitivity of 86.1% for cancer early detection and an average accuracy of 76.9% for tumor localization at a specificity of 94.7%. By highlighting the potential of tumor fractions on cancer early diagnosis, our approach can be further applied to cancer screening and tumor progression monitoring. ‘Circulating cell-free DNA can be used to predict cancer, but it is more challenging to assess in early stage cancer. Here, the authors created a diagnostic model using tumor fractions deciphered from circulating cfDNA methylation signatures, which exhibited an 86% sensitivity in detecting early-stage cancer.

We explored the secondary attack rate in different types of contact with persons presymptomatic for coronavirus disease (COVID-19). Close contacts who lived with or had frequent contact with an index case-patient had a higher risk for COVID-19. Our findings provide population-based evidence for transmission from persons with presymptomatic COVID-19 infections.

To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.

Background The global population of adults aged 60 and above surpassed 1 billion in 2020, constituting 13.5% of the global populace. Projections indicate a rise to 2.1 billion by 2050. While Hospital-at-Home (HaH) programs have emerged as a promising alternative to traditional routine hospital care, showing initial benefits in metrics such as lower mortality rates, reduced readmission rates, shorter treatment durations, and improved mental and functional status among older individuals, the robustness and magnitude of these effects relative to conventional hospital settings call for further validation through a comprehensive meta-analysis. Methods A comprehensive literature search was executed during April–June 2023, across PubMed, MEDLINE, Embase, Web of Science, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) to include both RCT and non-RCT HaH studies. Statistical analyses were conducted using Review Manager (version 5.4), with Forest plots and I 2 statistics employed to detect inter-study heterogeneity. For I 2  > 50%, indicative of substantial heterogeneity among the included studies, we employed the random-effects model to account for the variability. For I 2  ≤ 50%, we used the fixed effects model. Subgroup analyses were conducted in patients with different health conditions, including cancer, acute medical conditions, chronic medical conditions, orthopedic issues, and medically complex conditions. Results Fifteen trials were included in this systematic review, including 7 RCTs and 8 non-RCTs. Outcome measures include mortality, readmission rates, treatment duration, functional status (measured by the Barthel index), and mental status (measured by MMSE). Results suggest that early discharge HaH is linked to decreased mortality, albeit supported by low-certainty evidence across 13 studies. It also shortens the length of treatment, corroborated by seven trials. However, its impact on readmission rates and mental status remains inconclusive, supported by nine and two trials respectively. Functional status, gauged by the Barthel index, indicated potential decline with early discharge HaH, according to four trials. Subgroup analyses reveal similar trends. Conclusions While early discharge HaH shows promise in specific metrics like mortality and treatment duration, its utility is ambiguous in the contexts of readmission, mental status, and functional status, necessitating cautious interpretation of findings.

Background China has empowered and continues to empower internet hospitals, which saw an increase in their development due to the pandemic, to fight against COVID-19. The construction and operational models of internet hospitals can be categorized as self-constructed and self-managed models, self-constructed and enterprise-run models, hospital and enterprise joint-owned models, and hosted by a third-party platform. Despite the growing importance of internet hospitals, there have been few systematic summaries of their construction and operational models. The primary purpose of the study was to understand the construction and operational models of internet hospitals in China. Methods Data was collected from 39 internet hospitals and 356 medical staff between September 2020 and April 2021, via internet hospital and hospital staff surveys. T-tests were used to compare the continuous variables, while Chi-square tests were employed to compare the proportions of categorical variables. The self-perception of the internet hospitals’ services was assessed using a 5-point Likert scale on 16 aspects and a root cause analysis was conducted to identify the root causes and influencing factors of current deficiencies experienced by internet hospitals. Results Among the 39 internet hospitals, 22 (56.4%) were self-constructed and self-managed. Compared to other models of Internet hospitals, self-constructed and self-managed hospitals had lower percentages of professionals providing online services ( P  = 0.006), numbers of doctors outside of the entity ( P  = 0.006), numbers of online nurses ( P  = 0.004), and the ratio of online nurses to offline doctors ( P  < 0.001). Of the 16 aspects evaluated with regards to the medical staff’s self-perception of the internet hospital services, the highest scores were given for fee transparency, fee rationality, travel cost capital, patience and responsibility, and consultation behaviors. The root causes included five aspects: human, channels, prices, services, and time. Conclusions While the self-constructed and self-managed model was found to be the most prevalent form of internet hospital in China, the different models of internet hospitals can have an impact on both the quantity and quality of online healthcare services. This study contributes to the existing literature on internet hospitals' construction and operational models, offering additional policy implications for telemedicine management.

Low syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China. An open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing. Compared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested). Chinese Clinical Trial Registry: ChiCTR1900022409.

Background Men who have sex with men (MSM) are at high risk for human immunodeficiency virus (HIV) infection in China. Correct and consistent condom use is one of the most effective strategies for preventing the spread of HIV. This study developed a modified Information-Motivation-Behavioral Skills (IMB) model to predict condom use behavior among Chinese MSM. Methods A cross-sectional study was conducted to collect data using self-administered electronic questionnaire. Participants were recruited from HIV Voluntary Counseling and Testing clinics in six district Centers for Disease Control and Prevention in Guangzhou and two community-based HIV service centers (Lingnan Partners and Zhitong Charity) from May to September 2017. Structural equation modeling was performed to develop the modified IMB model with extended multilevel factors. Results Among the 976 MSM included, 52.05% had engaged in anal intercourse with a condom every time. The final modified IMB model fitted the data more ideally than the conventional model. The final modified IMB model revealed that behavioral skills positively contributed directly to condom use ( β  = 0.385, p  < 0.001) and partially mediated the associations between information ( β  = 0.106, p  = 0.005) and motivation ( β  = 0.390, p  < 0.001) and condom use. Regarding the extended multilevel factors, education, income, receiving HIV prevention services, sexual partner seeking behavior, depression, intimate partner violence, and child sexual abuse had indirect impacts on condom use that were mediated by information, motivation, and/or behavioral skills ( p  < 0.05). All paths from the latent variable to the corresponding observed variables were statistically significant ( p  < 0.001). Conclusion The modified IMB model with extended multilevel factors could serve as a theoretical framework for behavioral interventions for condom use among Chinese MSM. Further prospective studies are needed to examine the predictive power of the modified IMB model.

Aflatoxin B 1 (AFB 1 ) contamination in foods is an important health challenge for low-and middle-income countries in subtropical regions. AFB 1 has been detected in a variety of foodsin Guangzhou, while the risk of dietary exposure is unknown. This study aimed to assess the probabilistic risk of dietary exposure to AFB 1 contamination in food stuffs in Guangzhou by using margin of exposure (MOE) and quantitative liver cancer risk approaches. A total of1854 AFB 1 -contaminated foodstuffs were sampled in supermarkets, agricultural markets, retail shops, and family workshops from 11 districts of Guangzhou, and AFB 1 content was determined by HPLC-fluorescence detector. In total, 9.9% (184/1854) of the test samples had AFB 1 concentrations above the limit of detection. Home-made peanut oil had the highest AFB 1 concentration, with a mean value of 38.74 ± 47.45 μg kg −1 . The average MOE levels of Guangzhou residents ranged from 100 to 1000. The risk of liver cancer was 0.0264 cancers (100,000 population year) −1 . The health risks of suburban people were higher than those of urban people, and home-made peanut oil was the main contributorto dietary exposure to AFB 1 among suburban residents in Guangzhou. The production of home-made peanut oil should be supervised to reduce the risk of AFB 1 exposure.

Current preoperative assessment methods for C2 pedicle screw placement face challenges including low consistency, operational complexity, and high skill demands. This study aimed to develop and validate a deep learning model for rapid and accurate assessment of C2 pedicle screw placement feasibility. We developed C2-Net, an automated deep learning pipeline incorporating an image segmentation module for delineating C2 pedicles in CT images and a screw placement probability assessment module. The model's performance was evaluated using 3D-printed manually placed screws as ground truth and compared with surgeons of different experience levels. On the test set, C2-Net achieved an accuracy of 89.4%, sensitivity of 90.0%, and specificity of 89.0%. The model demonstrated performance comparable to senior surgeons and numerically superior to junior surgeons, with higher consistency in diagnostic metrics. Attention maps generated by the model provided visual interpretation of the decision-making process. The predicted probabilities demonstrated capability in differentiating structural variations of C2 pedicles. C2-Net shows high accuracy and efficiency in assessing C2 pedicle screw placement, outperforming junior surgeons. With its ability to provide rapid, consistent evaluations and visual interpretations, C2-Net demonstrates potential as a valuable assistive tool for clinical decision-making in spinal surgery. Trial Registration: ChiCTR2500101655.