Risk-stratified Approach for Never- and Ever-Smokers in Lung Cancer Screening: A Prospective Cohort Study in China.

Rationale: Over 40% of lung cancer cases occurred in never-smokers in China. However, high-risk never-smokers were precluded from benefiting from lung cancer screening as most screening guidelines did not consider them. Objectives: We sought to develop and validate prediction models for 3-year lung cancer risks for never- and ever-smokers, named the China National Cancer Center Lung Cancer models (China NCC-LCm2021 models). Methods: 425,626 never-smokers and 128,952 ever-smokers from the National Lung Cancer Screening program were used as the training cohort and analyzed using multivariable Cox models. Models were validated in two independent prospective cohorts: one included 369,650 never-smokers and 107,678 ever-smokers (841 and 421 lung cancers), and the other included 286,327 never-smokers and 78,469 ever-smokers (503 and 127 lung cancers). Measurements and Main Results: The areas under the receiver operating characteristic curves in the two validation cohorts were 0.698 and 0.673 for never-smokers and 0.728 and 0.752 for ever-smokers. Our models had higher areas under the receiver operating characteristic curves than other existing models and were well calibrated in the validation cohort. The China NCC-LCm2021 ⩾0.47% threshold was suggested for never-smokers and ⩾0.51% for ever-smokers. Moreover, we provided a range of threshold options with corresponding expected screening outcomes, screening targets, and screening efficiency. Conclusion: The construction of the China NCC-LCm2021 models can accurately reflect individual risk of lung cancer, regardless of smoking status. Our models can significantly increase the feasibility of conducting centralized lung cancer screening programs because we provide justified thresholds to define the high-risk population of lung cancer and threshold options to adapt different configurations of medical resources.

Risk-Adapted Starting Age for Personalized Colorectal Cancer Screening: Validated Evidence From National Population-Based Studies.

BACKGROUND & AIMS: A one-size-fits-all approach to colorectal cancer (CRC) screening that does not account for CRC risk factors is not conducive to personalized screening. On the basis of the principle of equal management of equal risks, we aimed to tailor and validate risk-adapted starting ages of CRC screening for individuals with different CRC risk factors. METHODS: A multi-center community-based population cohort (N = 3,165,088) was used to evaluate the starting age of CRC screening with comprehensive consideration of risk factors. Age-specific 10-year cumulative risk curves were used to determine when individuals at greater risk for CRC reached the same risk level as the 50-year-old general population, which is currently the recommended starting age for CRC screening in China. RESULTS: During the study follow-up period (2013-2021), 4,840 incident CRCs were recorded. Family history of CRC, adverse lifestyle, and comorbidities demonstrated heterogeneous associations with CRC risk (hazard ratios, 1.05-1.55; P < .05). Men and women with CRC family history and at least 2 risk factors reached the standard benchmark risk (0.28%) for screening at the age of 40, 10 years earlier than their peers without risk factors in the general population. Proposed starting ages for CRC screening were validated in an independent community-based population cohort (N = 1,023,367). CONCLUSIONS: We determined a risk-adapted CRC screening starting age for individuals with various CRC risk factors. Earlier, personalized screening based on these findings could allow for scarce health resources to be dedicated to individuals who benefit most.

Gaze-Triggered Communicative Intention Compresses Perceived Temporal Duration.

Eye gaze communicates a person's attentional state and intentions toward objects. Here we demonstrate that this important social signal has the potential to distort time perception of gazed-at objects (N = 70 adults). By using a novel gaze-associated learning paradigm combined with the time-discrimination task, we showed that objects previously associated with others' eye gaze were perceived as significantly shorter in duration than the nonassociated counterparts. The time-compression effect cannot be attributed to general attention allocation because it disappeared when objects were associated with nonsocial attention cues (i.e., arrows). Critically, this effect correlated with observers' autistic traits and vanished when the gazing agent's line of sight was blocked by barriers, reflecting the key role of intention processing triggered by gaze in modulating time perception. Our findings support the existence of a special mechanism tuned to social cues, which can shape our perception of the outer world in time domains.

The prognostic predictive value of the components of the PR interval in hospitalized patients with heart failure.

OBJECTIVE: Previous reports on the epidemiology, influencing factors, and the prognostic value of the components of PR interval in hospitalized heart failure patients were limited. METHODS: This study retrospectively enrolled 1182 patients hospitalized with heart failure from 2014 to 2017. Multiple linear regression analysis was used to explore the association between the components of PR interval and the baseline parameters. The primary outcome was all-cause death or heart transplantation. Multivariable-adjusted Cox proportional hazard regression models were constructed to explore the predictive value of the components of PR interval for the primary outcome. RESULTS: In multiple linear regression analysis, higher height (for every 10 cm increase in height: regression coefficient 4.83, P < 0.001) as well as larger atrial and ventricular size were associated with larger P wave duration but not with PR segment. The primary outcome occurred in 310 patients after an average follow-up of 2.39 years. Cox regression analyses revealed that the increase in PR segment was an independent predictor of the primary outcome (every 10 ms increase: hazard ratio 1.041, 95% confidence interval [CI] 1.010-1.083, P = 0.023), whereas the P wave duration did not show significant correlation. When adding the PR segment to an initial prognostic prediction model, the likelihood ratio test and categorical net reclassification index (NRI) showed a significant improvement, but the increase in C-index was not significant. In subgroup analysis, increased PR segment was an independent predictor of the primary endpoint in patients taller than 170 cm (each 10 ms increase: hazard ratio 1.153, 95% CI 1.085-1.225, P < 0.001) but not the shorter group (P for interaction = 0.006). CONCLUSIONS: In hospitalized patients with heart failure, longer PR segment was an independent predictor of the composite endpoint of all-cause death and heart transplantation, especially in the taller group, but it had limited significance in improving the prognostic risk stratification of this population.

Internal Social Attention: Gaze Cues Stored in Working Memory Trigger Involuntary Attentional Orienting.

Previous research has shown that social cues, including eye gaze, can readily guide our focus of attention-a phenomenon referred to as social attention. Here, we demonstrated that internally maintained social cues in working memory (WM) can produce an analogous attentional effect (N = 57). Using the delayed-match-to-sample paradigm combined with the dot-probe task, we found that holding irrelevant gaze cues in WM can induce attentional orienting in college-age adults. Importantly, this WM-induced attention effect could not be explained simply by the perceptual-attentional process, because the identical gaze cues that were only passively viewed and not memorized in WM could not trigger attentional orienting beyond the typical time window of social attention. Furthermore, nonsocial cues (i.e., arrows) held in WM failed to elicit the attentional-orienting effect. These findings provide new evidence for the conceptualization of WM as internally directed attention and highlight the uniqueness of social attention compared with nonsocial attention.

Cost-effectiveness of risk-stratified endoscopic screening for esophageal cancer in high-risk areas of China: a modeling study.

BACKGROUND AND AIMS: Risk-stratified endoscopic screening (RSES) has been suggested to improve screening efficiency. We aimed to assess the cost-effectiveness of RSES and identify the optimal risk-score thresholds for once in a lifetime esophageal cancer (EC) screening in high-risk areas of China. METHODS: From a healthcare system perspective, a Markov model was constructed to compare the cost-effectiveness of 13 RSES strategies (under different score thresholds for EC risk), universal endoscopic screening strategy, and no screening. Six cohorts of 100,000 participants with different screening ages (40-65 years) were followed up to age 77 years. The incremental cost-effectiveness ratio (ICER), that is, incremental costs per quality-adjusted life-year (QALY) gained, was the primary outcome. RESULTS: Compared with no screening, as the score threshold was lowered, additionally gained QALYs increased, with 49 to 172 QALYs and 329 to 1147 QALYs gained from screening performed at 40 and 65 years, respectively. RSES in all age scenarios had ICERs less than the gross domestic product (GDP) per capita, and 11 RSES strategies with score thresholds of 3 to 13 had lower ICERs than universal endoscopic screening. At a willingness-to-pay threshold of the GDP per capita (U.S.$10,276/QALY), RSES at score thresholds of 8 or 9 and universal endoscopic screening were the most cost-effective strategies at ages <55 and ≥55 years, respectively. CONCLUSIONS: RSES is cost-effective, and score thresholds of 8 or 9 should be considered for screening ages <55 years. For individuals aged ≥55 years, universal endoscopic screening is the optimal strategy.

Effect of sodium-glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis.

BACKGROUND: Although the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established. METHODS: We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A-B or stage C HF population and HF types. RESULTS: Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I2 = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A-B HF patients. SGLT2i showed benefits in the E/e' ratio (MD - 0.45, 95% CI - 0.88 to - 0.03, p = 0.04; I2 = 0%), plasma NT-proBNP level (SMD - 0.09, 95% CI - 0.16 to - 0.03, p = 0.004; I2 = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p  = 0.01; I2 = 0%) in the overall population. CONCLUSION: The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.

Associations between female lung cancer risk and sex steroid hormones: a systematic review and meta-analysis of the worldwide epidemiological evidence on endogenous and exogenous sex steroid hormones.

BACKGROUND: Published findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women. METHODS: The PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed. RESULTS: Forty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87-0.98) and exogenous (OR: 0.86, 95% CI: 0.80-0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86-0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78-0.99) than in smoking women (OR: 0.98, 95% CI: 0.77-1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74-0.96). CONCLUSIONS: Our meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.

Heritability of reflexive social attention triggered by eye gaze and walking direction: common and unique genetic underpinnings.

BACKGROUND: Social attention ability is crucial for human adaptive social behaviors and interpersonal communications, and the malfunction of which has been implicated in autism spectrum disorder (ASD), a highly genetic neurodevelopmental disorder marked by striking social deficits. METHODS: Using a classical twin design, the current study investigated the genetic contribution to individual variation in social and non-social attention abilities, and further probed their potential genetic linkage. Moreover, individual autistic traits were further measured in an independent group of non-twin participants to examine the hypothetical link between the core social attention ability and ASD. RESULTS: We found reliable genetic influences on the social attentional effects induced by two distinct cues (eye gaze and walking direction), with 91% of their covariance accounted for by common genetic effects. However, no evidence of heritability or shared genetic effects was observed for the attentional effect directed by a non-social cue (i.e. arrow direction) and its correlation with the social attention ability. Remarkably, one's autistic traits could well predict his/her heritable core social attention ability extracted from the conventional social attentional effect. CONCLUSIONS: These findings together suggest that human social attention ability is supported by unique genetic mechanisms that can be shared across different social, but not non-social, processing. Moreover, they also encourage the identification of 'social attention genes' and highlight the critical role of the core human social attention ability in seeking the endophenotypes of social cognitive disorders including ASD.

Cross-modal social attention triggered by biological motion cues.

Previous research has demonstrated that biological motion (BM) cues can induce reflexive attentional orienting. This BM-triggered social attention has hitherto only been investigated within visual modality. It remains unknown whether and to what extent social attention induced by BM cues can occur across different sensory modalities. By introducing auditory stimuli to a modified central cueing paradigm, we showed that observers responded significantly faster to auditory targets presented in the walking direction of BM than in the opposite direction, reflecting the notion that BM cues can trigger cross-modal social attention. This effect was not due to the viewpoint effect of the global configuration and could be extended to local BM cues without any global configuration. Critically, such cross-modal social attention was sensitive to the orientation of BM cues and completely disappeared when critical biological characteristics were removed. Our findings, taken together, support the existence of a special multimodal attention mechanism tuned to life motion signals and shed new light on the unique and cross-modal nature of social attention.

Establishment of a detection assay for DNA endonuclease activity and its application in the screening and prognosis of malignant lymphoma.

BACKGROUND: Endonucleases play critical roles in maintaining genomic stability and regulating cell growth. The purpose of this study was to evaluate detection of endonuclease activity as an indicator in the early diagnosis and prognosis of lymphoma. RESULTS: The method of endonuclease activity determination was successfully established and applied to compare cancer patient and control cohorts. Endonuclease activities of cancer tissues were significantly higher than those of adjacent control tissues (P < 0.001). We next investigated endonuclease activity in peripheral blood of enrolled patients and the controls, which were also significantly higher in patients than in controls (P = 0.015). Additionally, endonuclease activities were elevated in the metastasis subgroup compared with the non-metastasis subgroup(P = 0.038), whereas no significant difference was found between age(≤ 56y, > 56y) and gender (P = 0.736 > 0.05 and P = 0.635 > 0.05, respectively). Although there was no significant difference between control group with the non-metastatic cancer patients (P = 0.800 > 0.05), endonuclease activities were lower in the control group compared with the non-metastatic cancer patients with lymphoma (P = 0.033). The progression-free survival probability of patients with elevated R ratios(R ratio ≥ 1.4) was significantly lower than that of patients with lower R ratios (R ratio < 1.4). CONCLUSIONS: An assay was established to detect the endonuclease activity,which might be useful for the prognosis of cancers, especially lymphoma.

RCAN1 Mutation and Functional Characterization in Children with Sporadic Congenital Heart Disease.

Congenital heart disease (CHD) is the most frequent birth defect. RCAN1 (regulator of calcineurin 1) contributes to CHD in Down syndrome. However, whether RCAN1 is also associated with nonsyndromic CHD remains unclear. This study sequenced the exons and flanking region of RCAN1 in 128 sporadic CHD patients and 150 normal controls. We identified six novel heterozygous mutations in CHD patients. Functional assay showed that the g.482G>T could obviously raise the promoter activity of RCAN1.4 in vitro; However, we failed to detect the expression of RCAN1 in the right auricle, which made it confused to evaluate the pathogenicity of this mutation. In addition, we demonstrated that c.290T>C and g.1056+58C>A had no effect on the alternative splicing of RCAN1. The *196C>T, *790G>A, and *1278C>G did not influence the translation of RCAN1 post transcription. In conclusion, a novel mutation of g.482G>T in RCAN1 may be related to CHD by causing overexpression of RCAN1.4.

COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level.

The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27. SOC cells with COPS5 depletion were arrested in G1/G0-phase and exhibited a reduced proliferation ability and an increased cytoplasmic p27 expression. Whereas, the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3. Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC.

[Effect of three kinds of drinking water on learning and memory and hippocampal neurotransmitter of mice].

OBJECTIVE: To explore the effect of three kinds of drinking water on learning and memory and hippocampal neurotransmitter of mice. METHODS: Water quality parameters, including total dissolved solid( TDS), total hardness, oxygen consumed( OC), sodium, potassium, calcium, magnesium and metasilicic acid, were measured for pure water, tap water and natural mineral water. A total of 60 ICR mice( half male and half female) were randomly divided into three groups and fed with pure water( control group), tap water and mineral water for 90 days. After learning-memory abilities were detected with Morris water maze and passive avoidance test, mice were killed and hippocampi were removed immediately to measure contents of acetylcholine( Ach), nitric oxide( NO), glutamic acid( Glu) and gamma-aminobutyric acid( GABA) and activities of acetylcholinesterase( ACh E), choline acetyltransferase( Ch AT) and total nitric oxide synthase( T-NOS). RESULTS: Water quality parameters were higher in tap water and natural mineral water than in pure water. On the first day of place navigation test, the escape latency of tap water group [( 69. 15 ± 50. 87) s]was obviously shorter than that of pure water group [( 86. 07 ± 44. 03) s]( P < 0. 05), and mice in tap water group chose effect strategies( 51. 25%) more frequently compared to control mice( 30%)( P <0. 05). In the probe trial, the swimming time of the targeted quadrant was significantly longer in tap water group [( 28. 44 ± 10. 17) s] or mineral water group [( 28. 81 ±12. 43) s] than in pure water group [( 19. 84 ± 9. 59) s ]( P < 0. 05). In passive avoidance test, the training latency and testing latency were significantly longer in tap water group [( 60. 27 ± 57. 84) and( 209. 54 ± 121. 41) s] or mineral water group[( 58. 12 ± 42. 52) and( 271. 40 ± 90. 44) s]than in pure water group [( 10. 99 ± 9. 40)and( 72. 77 ± 67. 51) s ]( P < 0. 05), as the frequency of electric shock and the percentage of animals showing errors in tap water group [( 0. 90 ± 0. 88) times and 50%]or mineral water group [( 0. 10 ± 0. 32) times and 20%]were obviously less than those in pure water group [( 5. 00 ± 4. 62) times and 90% ]( P < 0. 05). Compared with pure water group [( 8. 53 ± 2. 12) µg / mg prot and( 0. 94 ± 0. 49) U / mg prot], a significant increase of Ach concentration and a significant decrease of ACh E activity were observed in tap water group [( 11. 18 ± 3. 46) µg / mg prot and( 0. 41 ± 0. 21) U / mg prot]or mineral water group [( 12. 91 ± 3. 91) µg / mg prot and( 0. 54 ± 0. 28) U / mg prot]( P < 0. 05). CONCLUSION: Compared with pure water, long-term drinking tap water or mineral water is more beneficial to learning and memory of mice, and it may be associated with a higher content of hippocampal Ach.

Life motion signals bias the perception of apparent motion direction.

Walking direction conveyed by biological motion (BM) cues, which humans are highly sensitive to since birth, can elicit involuntary shifts of attention to enhance the detection of static targets. Here, we demonstrated that such intrinsic sensitivity to walking direction could also modulate the direction perception of simultaneously presented dynamic stimuli. We showed that the perceived direction of apparent motion was biased towards the walking direction even though observers had been informed in advance that the walking direction of BM did not predict the apparent motion direction. In particular, rightward BM cues had an advantage over leftward BM cues in altering the perception of motion direction. Intriguingly, this perceptual bias disappeared when BM cues were shown inverted, or when the critical biological characteristics were removed from the cues. Critically, both the perceptual direction bias and the rightward advantage persisted even when only local BM cues were presented without any global configuration. Furthermore, the rightward advantage was found to be specific to social cues (i.e., BM), as it vanished when non-social cues (i.e., arrows) were utilized. Taken together, these findings support the existence of a specific processing mechanism for life motion signals and shed new light on their influences in a dynamic environment.

Radiomics-Based Machine Learning Classification Strategy for Characterization of Hepatocellular Carcinoma on Contrast-Enhanced Ultrasound in High-Risk Patients with LI-RADS Category M Nodules.

Objective Accurate differentiation within the LI-RADS category M (LR-M) between hepatocellular carcinoma (HCC) and non-HCC malignancies (mainly intrahepatic cholangiocarcinoma [CCA] and combined hepatocellular and cholangiocarcinoma [cHCC-CCA]) is an area of active investigation. We aimed to use radiomics-based machine learning classification strategy for differentiating HCC from CCA and cHCC-CCA on contrast-enhanced ultrasound (CEUS) images in high-risk patients with LR-M nodules. Methods A total of 159 high-risk patients with LR-M nodules (69 HCC and 90 CCA/cHCC-CCA) who underwent CEUS within 1 month before pathologic confirmation from January 2006 to December 2019 were retrospectively included (111 patients for training set and 48 for test set). The training set was used to build models, while the test set was used to compare models. For each observation, six CEUS images captured at predetermined time points (T1, peak enhancement after contrast injection; T2, 30 seconds; T3, 45 seconds; T4, 60 seconds; T5, 1-2 minutes; and T6, 2-3 minutes) were collected for tumor segmentation and selection of radiomics features, which included seven types of features: first-order statistics, shape (2D), gray-level co-occurrence matrix, gray-level size zone matrix, gray-level run length matrix, neighboring gray tone difference matrix, and gray-level dependence matrix. Clinical data and key radiomics features were employed to develop the clinical model, radiomics signature (RS), and combined RS-clinical (RS-C) model. The RS and RS-C model were built using the machine learning framework. The diagnostic performance of these three models was calculated and compared. Results Alpha-fetoprotein (AFP), CA19-9, enhancement pattern, and time of washout were included as independent factors for clinical model (all p < 0.05). Both the RS and RS-C model performed better than the clinical model in the test set (area under the curve [AUC] of 0.698 [0.571-0.812] for clinical model, 0.903 [0.830-0.970] for RS, and 0.912 [0.838-0.977] for the RS-C model; both p < 0.05). Conclusions Radiomics-based machine learning classifiers may be competent for differentiating HCC from CCA and cHCC-CCA in high-risk patients with LR-M nodules.

Understanding Gaps in the Hypertension and Diabetes Care Cascade: Systematic Scoping Review.

BACKGROUND: Hypertension and diabetes are global health challenges requiring effective management to mitigate their considerable burden. The successful management of hypertension and diabetes requires the completion of a sequence of stages, which are collectively termed the care cascade. OBJECTIVE: This scoping review aimed to describe the characteristics of studies on the hypertension and diabetes care cascade and identify potential interventions as well as factors that impact each stage of the care cascade. METHODS: The method of this scoping review has been guided by the framework by Arksey and O'Malley. We systematically searched MEDLINE, Embase, and Web of Science using terms pertinent to hypertension, diabetes, and specific stages of the care cascade. Articles published after 2011 were considered, and we included all studies that described the completion of at least one stage of the care cascade of hypertension and diabetes. Study selection was independently performed by 2 paired authors. Descriptive statistics were used to elucidate key patterns and trends. Inductive content analysis was performed to generate themes regarding the barriers and facilitators for improving the care cascade in hypertension and diabetes management. RESULTS: A total of 128 studies were included, with 42.2% (54/128) conducted in high-income countries. Of them, 47 (36.7%) focused on hypertension care, 63 (49.2%) focused on diabetes care, and only 18 (14.1%) reported on the care of both diseases. The majority (96/128, 75.0%) were observational in design. Cascade stages documented in the literature were awareness, screening, diagnosis, linkage to care, treatment, adherence to medication, and control. Most studies focused on the stages of treatment and control, while a relative paucity of studies examined the stages before treatment initiation (76/128, 59.4% vs 52/128, 40.6%). There was a wide spectrum of interventions aimed at enhancing the hypertension and diabetes care cascade. The analysis unveiled a multitude of individual-level and system-level factors influencing the successful completion of cascade sequences in both high-income and low- and middle-income settings. CONCLUSIONS: This review offers a comprehensive understanding of hypertension and diabetes management, emphasizing the pivotal factors that impact each stage of care. Future research should focus on upstream cascade stages and context-specific interventions to optimize patient retention and care outcomes.

Modified American College of Radiology Thyroid Imaging Reporting and Data System and Modified Artificial Intelligence Thyroid Imaging Reporting and Data System for Thyroid Nodules: A Multicenter Retrospective Study.

Background: Risk stratification systems for thyroid nodules are limited by low specificity. The fine-needle aspiration (FNA) biopsy size thresholds and stratification criteria are based on evidence from the literature and expert consensus. Our aims were to investigate the optimal FNA biopsy size thresholds in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and artificial intelligence (AI) TI-RADS and to revise the stratification criteria in AI TI-RADS. Methods: A total of 2596 thyroid nodules (in 2511 patients) on ultrasound examination with definite pathological diagnoses were retrospectively identified from January 2017 to September 2021 in 6 participating Chinese hospitals. The modified criteria for ACR TI-RADS were as follows: (1) no FNA for TR3; (2) FNA threshold for TR4 increased to 2.5 cm. The modified criteria for AI TI-RADS were as follows: (1) 6-point nodules upgraded to TR5; (2) no FNA for TR3; (3) FNA threshold for TR4 increased to 2.5 cm. The diagnostic performance and the unnecessary FNA rate (UFR) of modified versions were compared with the original ACR TI-RADS. Results: Compared with the original ACR TI-RADS, the modified ACR (mACR) TI-RADS yielded higher specificity (73% vs. 46%), accuracy (74% vs. 51%), area under the receiver operating characteristic curve (AUC; 0.80 vs. 0.70), and lower UFR (25% vs. 48%; all p < 0.001), although the sensitivity was slightly decreased (87% vs. 93%, p = 0.057). Compared with the original ACR TI-RADS, the modified AI (mAI) TI-RADS yielded higher specificity (73% vs. 46%), accuracy (75% vs. 51%), AUC (0.81 vs. 0.70), and lower UFR (24% vs. 48%; all p < 0.001), although the sensitivity tended to be slightly decreased (89% vs. 93%, p = 0.13). There was no significant difference between the mACR TI-RADS and mAI TI-RADS in the diagnostic performance and UFR (all p > 0.05). Conclusions: The revised FNA thresholds and the stratification criteria of the mACR TI-RADS and mAI TI-RADS may be associated with improvements in specificity and accuracy, without significantly sacrificing sensitivity for malignancy detection.