HiCervix: An Extensive Hierarchical Dataset and Benchmark for Cervical Cytology Classification.

Cervical cytology is a critical screening strategy for early detection of pre-cancerous and cancerous cervical lesions. The challenge lies in accurately classifying various cervical cytology cell types. Existing automated cervical cytology methods are primarily trained on databases covering a narrow range of coarse-grained cell types, which fail to provide a comprehensive and detailed performance analysis that accurately represents real-world cytopathology conditions. To overcome these limitations, we introduce HiCervix, the most extensive, multi-center cervical cytology dataset currently available to the public. HiCervix includes 40,229 cervical cells from 4,496 whole slide images, categorized into 29 annotated classes. These classes are organized within a three-level hierarchical tree to capture fine-grained subtype information. To exploit the semantic correlation inherent in this hierarchical tree, we propose HierSwin, a hierarchical vision transformer-based classification network. HierSwin serves as a benchmark for detailed feature learning in both coarse-level and fine-level cervical cancer classification tasks. In our comprehensive experiments, HierSwin demonstrated remarkable performance, achieving 92.08% accuracy for coarse-level classification and 82.93% accuracy averaged across all three levels. When compared to board-certified cytopathologists, HierSwin achieved high classification performance (0.8293 versus 0.7359 averaged accuracy), highlighting its potential for clinical applications. This newly released HiCervix dataset, along with our benchmark HierSwin method, is poised to make a substantial impact on the advancement of deep learning algorithms for rapid cervical cancer screening and greatly improve cancer prevention and patient outcomes in real-world clinical settings.

Retracted: Ultra-processed food consumption and risk of dementia and Alzheimer's disease: Long-term results from the Framingham Offspring Study

Retraction: Wang, K, Tang, W, Hao, X, Zhao, J. Ultra-processed food consumption and risk of dementia and Alzheimer's disease: Long-term results from the Framingham Offspring Study. Alzheimer's Dement. 2023; 1­11. https://doi.org/10.1002/alz.13351. The above article, published online on 03 July 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor-in-Chief Dr. Donna M. Wilcock, the Alzheimer's Association and Wiley Periodicals LLC. The retraction has been agreed as the authors did not have the appropriate approvals in place from the National Heart, Lung and Blood Institute (NHLBI) for use of the data in this article. This contravenes the journal's policy on data use and the journal is issuing this retraction as a result.

High consumption of whole grain foods decreases the risk of dementia and Alzheimer's disease: Framingham Offspring Cohort.

AIMS: To examine the longitudinal associations between total and individual whole grain (WG) food intake and the risk of all-cause dementia and Alzheimer's disease (AD) dementia. METHODS: This study included 2958 subjects (mean age at baseline was 61 ± 9 years) from the Framingham Offspring Cohort. Standardized interviews, physician examinations, and laboratory tests were collected approximately every 4 years, and the Food Frequency Questionnaire (FFQ) was conducted in cycle 5. Proportional hazards models and cubic spline regression examined associations between WG foods and all-cause dementia and AD dementia. RESULTS: Over an average of 12.6 years of follow-up, there were 322 dementia cases, of which 247 were AD dementia. After multivariate and dietary adjustments, individuals with the highest category for total WG food consumption had a lower risk of all-cause dementia [HR 0.66, 95% confidence interval (CI) 0.51-0.81] and AD dementia (HR 0.60, 95% CI 0.46-0.78) than individuals with the lowest category. The results remained comparable in different subgroups stratifying for age, sex, education, body mass index, and smoking status without significant interaction. Moreover, these inverse associations were seen for most individual WG foods except popcorn. A nonlinear dose-response association was shown between total WG intake and all-cause dementia and AD dementia, where the rate reduction slightly plateaued at more than one and two servings/day, respectively. CONCLUSIONS: Higher consumption of total and several common individual WG foods was strongly associated with a lower risk of all-cause dementia and AD dementia.

Elevated Myoglobin in Patients With Primary Aldosteronism: A Cross-Sectional Study.

Objectives: Primary aldosteronism (PA) is characterized by the autonomous excessive production of aldosterone in the adrenal cortex. Aldosterone is associated with damages to heart muscle and skeletal muscle. The purpose of this study was to evaluate serum levels of muscle injury markers and their associated factors in patients with primary aldosteronism. Methods: We retrospectively enrolled subjects with PA and essential hypertension (EH) who had completed testing for serum high sensitivity troponin T (hs-TnT), creatine kinase isoenzyme MB (CK-MB) and myoglobin from the database of the Chongqing Primary Aldosteronism Study (CONPASS). Univariate and multivariate linear regression analyses were performed to analyze the influencing factors of myocardial injury markers. Results: In total, 278 patients with PA and 445 patients with EH were enrolled in this study. Compared with EH patients, serum concentrations of hs-TnT [7.0 (4.0-12.0) vs. 6.0 (3.0-11.0) ng/L; p=0.005] and myoglobin [24.2 (21.0-38.1) vs. 21.8 (21.0-31.9) µg/L; p=0.023] were significantly higher among PA patients, while no significant difference of CK-MB was found between two groups [1.4 (1.0-2.0) vs. 1.3 (0.9-1.9) µg/L; p=0.154]. Univariate linear regression analysis showed that myoglobin was negatively correlated with serum potassium (ß=-0.31; p<0.01) and positively correlated with plasma aldosterone concentration (ß=0.40; p<0.01) in the PA group, while no significant correlation was found between hs-TnT and biochemical parameters. After adjusting for multiple confounders, myoglobin was negatively correlated with serum potassium (ß=-0.15; p<0.05) and positively correlated with plasma aldosterone concentration (ß=0.34; p<0.01) in the PA group. Conclusions: The serum level of myoglobin was significantly increased in PA patients, and myoglobin was independently correlated with plasma aldosterone concentration.

Heightened Cardiovascular Risk in Hypertension Associated With Renin-Independent Aldosteronism Versus Renin-Dependent Aldosteronism: A Collaborative Study.

Background While both renin-dependent and renin-independent aldosterone secretion contribute to aldosteronism, their relative associations with cardiovascular disease (CVD) risk has not been investigated. Methods and Results A total of 2909 participants from the FOS (Framingham Offspring Study) with baseline, serum aldosterone concentration, and plasma renin concentration who attended the sixth examination cycle and were followed up until 2014 and who were free of CVD were included. We further recruited 2612 hypertensive participants from the CONPASS (Chongqing Primary Aldosteronism Study). Captopril challenge test was performed to confirm renin-dependent or -independent aldosteronism in CONPASS. Among 1433 hypertensive subjects of FOS, when compared with those with serum aldosterone concentration <10 ng dL-1 (normal aldosterone), participants who had serum aldosterone concentration ≥10 ng dL-1 and plasma renin concentration ≤15 mIU L-1 (identified as renin-independent aldosteronism) showed a higher risk of CVD (hazard ratio, 1.40 [95% CI, 1.08-1.82]), while those who had serum aldosterone concentration ≥10 ng dL-1 and plasma renin concentration >15 mIU L-1 (identified as renin-dependent aldosteronism) showed an unchanged CVD risk. In CONPASS, renin-independent aldosteronism carried a significantly higher risk of CVD than normal aldosterone (odds ratio, 2.57 [95% CI, 1.13-5.86]), while the CVD risk remained unchanged in renin-dependent aldosteronism. Elevation of the urinary potassium-to-sodium excretion ratio, reflective of mineralocorticoid receptor activity, was only observed in participants with renin-independent aldosteronism. Conclusions Among patients with hypertension, renin-independent aldosteronism is more closely associated with CVD risk than renin-dependent aldosteronism.

Association between widespread pain and dementia, Alzheimer's disease and stroke: a cohort study from the Framingham Heart Study.

BACKGROUND AND OBJECTIVE: Chronic pain may be an early indicator of cognitive decline, but previous studies have not systematically examined the population-level associations between widespread pain and adverse cognitive outcomes and stroke. This study was designed to determine the association between widespread pain, a common subtype of chronic pain, and subsequent dementia, Alzheimer's disease dementia and stroke. METHODS: This retrospective cohort study used data from the US community-based Framingham Heart Study. Pain status was assessed at a single time point between 1990 and 1994. Widespread pain was determined based on the Framingham Heart Study pain homunculus. Dementia follow-up occurred across a median of 10 years (IQR, 6-13 years) for persons who were dementia free at baseline. Proportional hazard models examined associations between widespread pain and incident dementia, Alzheimer's disease dementia and stroke. RESULTS: A total of 347 (14.1%) subjects fulfilled the criteria for widespread pain, whereas 2117 (85.9%) subjects did not. Of 188 cases of incident all-cause dementia, 128 were Alzheimer's disease dementia. In addition, 139 patients suffered stroke during the follow-up period. After multivariate adjustment including age and sex, widespread pain was associated with 43% increase in all-cause dementia risk (HR: 1.43; 95% CI 1.06 to 1.92), 47% increase in Alzheimer's disease dementia risk (HR: 1.47; 95% CI 1.13 to 2.20) and 29% increase in stroke risk (HR: 1.29; 95% CI 1.08 to 2.54). Comparable results were shown in the subgroup of individuals over 65 years old. CONCLUSION: Widespread pain was associated with an increased incidence of all-cause dementia, Alzheimer's disease dementia and stroke. TRIAL REGISTRATION NUMBER: NCT00005121.

Cardiovascular events and all-cause mortality in surgically or medically treated primary aldosteronism: A Meta-analysis.

OBJECTIVES: To compare the effect of surgical or medical treatment on the risk of cardiovascular diseases (CVD) and all-cause mortality in patients with established primary aldosteronism (PA). METHODS: We searched PUBMED, MEDLINE and Cochrane Library for the meta-analysis. We included patients who were diagnosed with PA following guideline-supported protocols and received surgery or mineralocorticoid receptor antagonist (MRA)-based medical treatment, and age-sex matched patients with treated essential hypertension (EH). Primary endpoints were CVD incidence and all-cause mortality. RESULTS: Compared with EH, patients with treated PA had a higher risk of CVD [odds ratio (OR) 1.79; 95% confidence interval (CI) 1.39-2.31]. This elevated risk was only observed in patients with medically treated PA [OR 2.11; 95%CI 1.88-2.38] but not in those with surgically treated PA. The risk of all-cause mortality was significantly lower in patients with treated PA [OR 0.86; 95% CI 0.77-0.95] compared to EH. The reduced risk was only observed in patients with surgically treated PA [OR 0.47; 95% CI 0.34-0.66], but not in those with medically treated PA. CONCLUSIONS: Patients with medically treated PA have a higher risk of CVD compared to patients with EH. Surgical treatment of PA reduces the risk of CVD and all-cause mortality in patients with PA.

Nomogram-Based Preoperative Score for Predicting Clinical Outcome in Unilateral Primary Aldosteronism.

CONTEXT: More than half of patients diagnosed with unilateral primary aldosteronism (UPA) suffer from persisting hypertension after unilateral adrenalectomy. OBJECTIVE: The objective of this work is to develop and validate a nomogram-based preoperative score (NBPS) to predict clinical outcomes after unilateral adrenalectomy for UPA. DESIGN AND SETTING: The NBPS was developed in an Asian cohort by incorporating predictors independently associated with remission of hypertension after unilateral adrenalectomy for UPA and validated in a Caucasian cohort. PARTICIPANTS: Participants comprised patients with UPA achieving complete biochemical success after unilateral adrenalectomy. MAIN OUTCOME MEASURE: Measurements included the predictive performance of the NBPS compared with 2 previously developed outcome prediction scores: aldosteronoma resolution score (ARS) and primary aldosteronism surgical outcome (PASO) score. RESULTS: Ninety-seven of 150 (64.7%) patients achieved complete clinical success after unilateral adrenalectomy in the training cohort and 57 out of 165 (34.5%) in the validation cohort. A nomogram was established incorporating sex, duration of hypertension, aldosterone-to-renin ratio, and target organ damage. The nomogram showed good C indices and calibration curves both in Asian and Caucasian cohorts. The area under the receiver operating characteristic curve (AUC) of the NBPS for predicting hypertension remission in the training cohort was 0.853 (0.786-0.905), which was superior to the ARS (0.745 [0.667-0.812], P = .019) and PASO score (0.747 [0.670-0.815], P = .012). The AUC of the NBPS in the validation cohort was 0.830 (0.764-0.884), which was higher than the ARS (0.745 [95% CI, 0.672-0.810], P = .045), but not significantly different from the PASO score (0.825 [95% CI, 0.758-0.880], P = .911). CONCLUSION: The NBPS is useful in predicting clinical outcome for UPA patients, especially in the Asian population.

Development and Validation of Criteria for Sparing Confirmatory Tests in Diagnosing Primary Aldosteronism.

CONTEXT: The Endocrine Society Guidelines for the diagnosis of primary aldosteronism (PA) suggest that confirmatory tests (CFT) are not required when the following criteria are met: plasma aldosterone concentration (PAC) is >20 ng/dL, plasma renin is below detection levels, and hypokalemia is present. The evidence for the applicability of the guideline criteria is limited. OBJECTIVE: To develop and validate optimized criteria for sparing CFT in the diagnosis of PA. DESIGN AND SETTING: The optimized criteria were developed in a Chinese cohort using the captopril challenge test, verified by saline infusion test (SIT) and fludrocortisone suppression test (FST), and validated in an Australian cohort. PARTICIPANTS: Hypertensive patients who completed PA screening and CFT. MAIN OUTCOME MEASURE: Diagnostic value of the optimized criteria. RESULTS: In the development cohort (518 PA and 266 non-PA), hypokalemia, PAC, and plasma renin concentration (PRC) were selected as diagnostic indicators by multivariate logistic analyses. The combination of PAC >20 ng/dL plus PRC <2.5 µIU/mL plus hypokalemia had much higher sensitivity than the guideline criteria (0.36 vs 0.11). The optimized criteria remained superior when the SIT or FST were used as CFT. Non-PA patients were not misdiagnosed by either criteria, but the percentage of patients in whom CFT could be spared was higher with the optimized criteria. In the validation cohort (125 PA and 81 non-PA), the sensitivity of the optimized criteria was also significantly higher (0.12 vs 0.02). CONCLUSIONS: Hypertensive patients with PAC >20 ng/dL, PRC <2.5 µIU/mL, plus hypokalemia can be confidently diagnosed with PA without confirmatory tests.

RELATIONSHIP BETWEEN THE ENVIRONMENTAL ENDOCRINE DISRUPTOR BISPHENOL A AND DYSLIPIDEMIA: A FIVE-YEAR PROSPECTIVE STUDY.

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia. Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL <40 mg/dL). Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Multivariable linear and logistic regression models were used. Data from baseline and follow-up were used for cross-sectional and longitudinal analyses, respectively. Results: In the cross-sectional analysis, compared to subjects in the low BPA tertile, those in the high BPA tertile showed a higher level of LDL cholesterol (108.1 ± 24.4 mg/dL versus 119.5 ± 26.9 mg/dL; P<.05) and a lower level of HDL cholesterol (46.2 ± 11.7 mg/dL versus 39.5 ± 7.5 mg/dL; P<.05). In multivariable linear regression models, Z-transformed BPA was positively associated with LDL cholesterol (ß= 0.13, P = .002) and negatively associated with HDL cholesterol (ß= -0.28; P<.001). After cross-sectionally adjusting for confounders, subjects in higher BPA exposure was associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, in subjects without low-HDL-cholesterolemia at baseline, each SD increment in baseline BPA was associated with a higher incidence of low-HDL-cholesterolemia after adjustment for confounders (odds ratio [95% confidence interval; CI] 2.76, 95% CI 1.21, 6.29). Conclusion: Cross-sectionally, higher BPA exposure is associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, baseline BPA is an independent predictor of the 5-year incidence of low-HDL-cholesterolemia. Abbreviations: BMI = body mass index; BPA = bisphenol A; CI = confidence interval; CVD = cardiovascular disease; EIMDS = environment, inflammation and metabolic diseases study; HDL = high density lipoprotein; LDL = low density lipoprotein; OR = odds ratio; PPAR = peroxisome proliferator-activated receptor; SBP = systolic blood pressure; TG = triglyceride; Z-BPA = Z-transformed bisphenol A.

Circulating TNF receptors 1 and 2 predict progression of diabetic kidney disease: A meta-analysis.

BACKGROUND: We conducted a meta-analysis to investigate the association of circulating tumor necrosis factor-1 (TNFR-1) and TNFR-2 with diabetic kidney disease (DKD) progression, which is the first-ever quantitative analysis of these associations thus far. Whether TNFRs were better than albumin-creatinine ratio (ACR) in predicting DKD progression was also explored. METHODS: A systematic search of the PubMed, EMBASE, and Cochrane Library databases up to 1 February 2018, was conducted. The main outcome was DKD progression, which was defined as eGFR decline, macroalbuminuria, or incidence of DKD-related events. Eligible studies were included for pooled analysis using either fixed-effects or random-effects models to incorporate between-study variation by different measurement standards. Publication bias was evaluated using Egger's test. RESULTS: The meta-analysis included 6526 participants from 11 cohorts with circulating TNFR-1 measurements and 5385 participants from 10 prospective studies with circulating TNFR-2 measurements. Compared with the lowest level category, diabetic patients with the highest TNFR-1 or TNFR-2 level category exhibited a higher risk of DKD progression (RR 2.51, 95% CI [1.92-3.27] for TNFR-1; 3.23 [1.99-5.26] for TNFR-2). The risk of DKD progression was also increased with the per unit increment of TNFR-1 or TNFR-2 (1.68 [1.43-1.97] for TNFR-1; 1.69 [1.31-2.17] for TNFR-2). Although existing studies did not support a direct comparison between ACR and TNFRs, it was undeniable that TNFRs could improve the predictive value in DKD progression. CONCLUSIONS: Circulating TNFR-1 and TNFR-2 are reliable predictors of DKD progression. Whether TNFRs are better than ACR at predicting DKD progression needs to be further investigated.

Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on All-Cause Mortality and Renal Outcomes in Patients with Diabetes and Albuminuria: a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) could benefit patients with diabetes and albuminuria remains controversial. A systematic review and meta-analysis were conducted to answer this question by comparing ACE inhibitors or ARB with placebo among these patients. METHODS: In this meta-analysis, electronic data sources (Medline, the Cochrane Collaboration, and EMBASE) were searched. Randomized controlled trials (RCTs) comparing ACE inhibitors or ARB with placebo in subjects with diabetes and albuminuria (defined as urinary albumin-to-creatinine ratio, UACR≥30mg/g Cr) were included. Outcomes parameters were all-cause mortality, end stage renal disease (ESRD), doubling of serum creatinine levels, and cardiovascular events (CV). RESULTS: Twenty-six RCTs (including 20 for ACE inhibitors and 6 for ARB) were included, comprising 10378 participants with diabetes and albuminuria. Compared to placebo, treatment with ACE inhibitors or ARBs did not reduce all-cause mortality or CV. For renal outcomes, ARBs significantly reduced the risk of ESRD by 23% (odds ratio 0.77, 95%CI 0.65-0.92), while ACE inhibitors were not associated with a decreased risk of ESRD (0.69, 0.43-1.10). Both ACE inhibitors and ARBs reduced the risk of doubling of the serum creatinine level (0.60, 0.39-0.91 for ACE inhibitors; 0.75, 0.64-0.88 for ARBs), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results. CONCLUSION: In patients with diabetes and albuminuria, ARBs reduced risks of ESRD and doubling of the serum creatinine level. ACE inhibitors and ARBs failed to reduce all-cause mortality and CV. Based on the renoprotective effects, ARBs may be preferred for diabetic patients with albuminuria.