Enhancing the fairness of AI prediction models by Quasi-Pareto improvement among heterogeneous thyroid nodule population.

Artificial Intelligence (AI) models for medical diagnosis often face challenges of generalizability and fairness. We highlighted the algorithmic unfairness in a large thyroid ultrasound dataset with significant diagnostic performance disparities across subgroups linked causally to sample size imbalances. To address this, we introduced the Quasi-Pareto Improvement (QPI) approach and a deep learning implementation (QP-Net) combining multi-task learning and domain adaptation to improve model performance among disadvantaged subgroups without compromising overall population performance. On the thyroid ultrasound dataset, our method significantly mitigated the area under curve (AUC) disparity for three less-prevalent subgroups by 0.213, 0.112, and 0.173 while maintaining the AUC for dominant subgroups; we also further confirmed the generalizability of our approach on two public datasets: the ISIC2019 skin disease dataset and the CheXpert chest radiograph dataset. Here we show the QPI approach to be widely applicable in promoting AI for equitable healthcare outcomes.

Predicting axillary metastasis in breast cancer using lymphatic contrast-enhanced ultrasound-guided fine-needle aspiration of one lymph node.

OBJECTIVES: Fine-needle aspiration (FNA) is a microinvasive method to diagnose lymph nodes. This study aims to determine the capability of lymphatic contrast-enhanced ultrasound (LCEUS)-guided FNA in predicting the axillary metastasis with the target of one lymph node (LN) in patients with breast cancer. METHODS: LCEUS was prospectively performed in 105 patients with breast cancer. The most suspicious LN was targeted based on the characters of LCEUS. FNA was performed in the LN, followed by localization using a guide wire. The detection of lymph cells and/or tumour cells was recognized as a puncture success. Cytologic diagnosis was compared with histologic diagnosis of wire-marked LN for diagnosing accuracy and compared with histologic diagnosis of axillary LNs for predicting accuracy. RESULTS: LCEUS-guided FNA was performed in all 105 female patients who underwent axillary dissection. The puncture success rates were 74.3%, 91.4%, and 97.1% for three sequential groups (P = .010). In diagnosing LN metastasis, the sensitivity, specificity, and accuracy values of LCEUS-guided FNA were 89.7%, 100%, and 95.7%, respectively. In predicting axillary metastasis, the sensitivity, specificity, and accuracy values of LCEUS-guided FNA were 81.4%, 100%, and 91.3%, respectively. CONCLUSIONS: The microinvasive LCEUS-guided FNA of one lymph node can be an accurate method and may help predict axillary metastasis in patients with breast cancer. ADVANCES IN KNOWLEDGE: This study presented that LCEUS combined with FNA would be practical in clinic. The characters of LCEUS could indicate the suspicious LNs and promote the accuracy in predicting axillary metastasis.

Fecal Immunochemical Testing and the Risk of Advanced Colorectal Neoplasia: A Difference-In-Difference Analysis.

PURPOSE: To evaluate the effectiveness of fecal immunochemical testing (FIT) in colorectal cancer screening. METHODS: We conducted a prospective cohort study among 5,598 participants age 40-74 years between 2012 and 2020 in Tianjin, China. Inverse probability weighting was adopted to adjust for potential imbalanced factors between groups. A Cox proportional hazards model was used to estimate the weighted associations between FIT screening and advanced colorectal neoplasia. A difference-in-difference (DID) model was adopted to compare the incidence rates of advanced colorectal neoplasia between groups. RESULTS: In DID analysis, the rate of incidence was reduced by 0.34 cases per person-years in the screening group as compared with the historical FIT screening group (rate ratio [RR], 0.08 [95% CI, 0.07 to 0.10]) and by 0.06 cases per person-years in the non-FIT screening group as compared with the historical non-FIT screening group (RR, 0.37 [95% CI, 0.29 to 0.48]; P < .001 for both comparisons), with a relative reduction of 0.28. Similar benefit effect from FIT screening was observed in sex and age subgroups. CONCLUSION: FIT screening was associated with a reduction in incidence density from advanced colorectal neoplasia.

Association between use of antihypertensive drugs and the risk of cancer: a population-based cohort study in Shanghai.

BACKGROUND: Previously studies shown a potential risk of antihypertensive medicines in relation to cancer susceptibility, which creating significant debate in the scientific community and public concern. We sought to investigate the relationship between antihypertensive medicines and cancer risk, by drug type and class. METHODS: We conducted a population-based cohort study and enrolled patients diagnosed with hypertension from community healthcare centers in Changning District, Shanghai, China. Antihypertensive drug administration were classified as five common antihypertensive drugs. The main outcomes were incidence of total cancer and by major cancer type. RESULTS: Between January 2013 and December 2017, a total of 101,370 hypertensive patients were enrolled in this cohort. During a mean follow-up of 5.1 (SD 1.3) years, 4970 cancer cases were newly diagnosed in the cohort. CCBs were the most frequently used antihypertensives which were associated with a moderately increased risk of total cancer (hazard ratio, HR = 1.11, 95% CI: 1.05-1.18). The second commonly used drug ARBs were also associated with increased risk of total cancer (HR = 1.10, 95%CI: 1.03-1.17) as well as lung and thyroid cancers (HR = 1.21, 95%CI: 1.05-1.39; HR = 1.62 95%CI: 1.18-2.21, respectively). No significant association was found between cancer and other antihypertensives. Hypertensive patients who use more than one class of antihypertensives drugs had a higher risk of total cancer (HR: 1.22, 95%CI: 1.10-1.35 for two classes; HR: 1.22, 95%CI: 1.03-1.45 for three or more classes), and a possible dose-response relationship was suggested (P for trend < 0.001). The risk of thyroid cancer was higher in hypertensive patients prescribed with three or more antihypertensive classes. CONCLUSIONS: Use of ARBs or CCBs may be associated with an increased risk of total cancer. Taking more than one class of antihypertensives drugs appeared to have a higher risk for total cancer.

Automated diagnosis and management of follicular thyroid nodules based on the devised small-dataset interpretable foreground optimization network deep learning: a multicenter diagnostic study.

BACKGROUND: Currently, follicular thyroid carcinoma (FTC) has a relatively low incidence with a lack of effective preoperative diagnostic means. To reduce the need for invasive diagnostic procedures and to address information deficiencies inherent in a small dataset, we utilized interpretable foreground optimization network deep learning to develop a reliable preoperative FTC detection system. METHODS: In this study, a deep learning model (FThyNet) was established using preoperative ultrasound images. Data on patients in the training and internal validation cohort ( n =432) were obtained from Ruijin Hospital, China. Data on patients in the external validation cohort ( n =71) were obtained from four other clinical centers. We evaluated the predictive performance of FThyNet and its ability to generalize across multiple external centers and compared the results yielded with assessments from physicians directly predicting FTC outcomes. In addition, the influence of texture information around the nodule edge on the prediction results was evaluated. RESULTS: FThyNet had a consistently high accuracy in predicting FTC with an area under the receiver operating characteristic curve (AUC) of 89.0% [95% CI 87.0-90.9]. Particularly, the AUC for grossly invasive FTC reached 90.3%, which was significantly higher than that of the radiologists (56.1% [95% CI 51.8-60.3]). The parametric visualization study found that those nodules with blurred edges and relatively distorted surrounding textures were more likely to have FTC. Furthermore, edge texture information played an important role in FTC prediction with an AUC of 68.3% [95% CI 61.5-75.5], and highly invasive malignancies had the highest texture complexity. CONCLUSION: FThyNet could effectively predict FTC, provide explanations consistent with pathological knowledge, and improve clinical understanding of the disease.

Human understandable thyroid ultrasound imaging AI report system - A bridge between AI and clinicians.

Artificial intelligence (AI) enables accurate diagnosis of thyroid cancer; however, the lack of explanation limits its application. In this study, we collected 10,021 ultrasound images from 8,079 patients across four independent institutions to develop and validate a human understandable AI report system named TiNet for thyroid cancer prediction. TiNet can extract thyroid nodule features such as texture, margin, echogenicity, shape, and location using a deep learning method conforming to the clinical diagnosis standard. Moreover, it offers excellent prediction performance (AUC 0.88) and provides quantitative explanations for the predictions. We conducted a reverse cognitive test in which clinicians matched the correct ultrasound images according to TiNet and clinical reports. The results indicated that TiNet reports (87.1% accuracy) were significantly easier to understand than clinical reports (81.6% accuracy; p < 0.001). TiNet can serve as a bridge between AI-based diagnosis and clinicians, enhancing human-AI cooperative medical decision-making.

Mitochondrial transfer from bone mesenchymal stem cells protects against tendinopathy both in vitro and in vivo.

BACKGROUND: Although mesenchymal stem cells (MSCs) have been effective in tendinopathy, the mechanisms by which MSCs promote tendon healing have not been fully elucidated. In this study, we tested the hypothesis that MSCs transfer mitochondria to injured tenocytes in vitro and in vivo to protect against Achilles tendinopathy (AT). METHODS: Bone marrow MSCs and H2O2-injured tenocytes were co-cultured, and mitochondrial transfer was visualized by MitoTracker dye staining. Mitochondrial function, including mitochondrial membrane potential, oxygen consumption rate, and adenosine triphosphate content, was quantified in sorted tenocytes. Tenocyte proliferation, apoptosis, oxidative stress, and inflammation were analyzed. Furthermore, a collagenase type I-induced rat AT model was used to detect mitochondrial transfer in tissues and evaluate Achilles tendon healing. RESULTS: MSCs successfully donated healthy mitochondria to in vitro and in vivo damaged tenocytes. Interestingly, mitochondrial transfer was almost completely blocked by co-treatment with cytochalasin B. Transfer of MSC-derived mitochondria decreased apoptosis, promoted proliferation, and restored mitochondrial function in H2O2-induced tenocytes. A decrease in reactive oxygen species and pro-inflammatory cytokine levels (interleukin-6 and -1ß) was observed. In vivo, mitochondrial transfer from MSCs improved the expression of tendon-specific markers (scleraxis, tenascin C, and tenomodulin) and decreased the infiltration of inflammatory cells into the tendon. In addition, the fibers of the tendon tissue were neatly arranged and the structure of the tendon was remodeled. Inhibition of mitochondrial transfer by cytochalasin B abrogated the therapeutic efficacy of MSCs in tenocytes and tendon tissues. CONCLUSIONS: MSCs rescued distressed tenocytes from apoptosis by transferring mitochondria. This provides evidence that mitochondrial transfer is one mechanism by which MSCs exert their therapeutic effects on damaged tenocytes.

Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma.

Germline or somatic loss-of-function mutations of fumarate hydratase (FH) predispose patients to an aggressive form of renal cell carcinoma (RCC). Since other than tumor resection there is no effective therapy for metastatic FH-deficient RCC, an accurate method for early diagnosis is needed. Although MRI or CT scans are offered, they cannot differentiate FH-deficient tumors from other RCCs. Therefore, finding noninvasive plasma biomarkers suitable for rapid diagnosis, screening, and surveillance would improve clinical outcomes. Taking advantage of the robust metabolic rewiring that occurs in FH-deficient cells, we performed plasma metabolomics analysis and identified 2 tumor-derived metabolites, succinyl-adenosine and succinic-cysteine, as excellent plasma biomarkers for early diagnosis. These 2 molecules reliably reflected the FH mutation status and tumor mass. We further identified the enzymatic cooperativity by which these biomarkers are produced within the tumor microenvironment. Longitudinal monitoring of patients demonstrated that these circulating biomarkers can be used for reporting on treatment efficacy and identifying recurrent or metastatic tumors.

Integrated gene profiling of fine-needle aspiration sample improves lymph node metastasis risk stratification for thyroid cancer.

BACKGROUND: Lymph node metastasis risk stratification is crucial for the surgical decision-making of thyroid cancer. This study investigated whether the integrated gene profiling (combining expression, SNV, fusion) of Fine-Needle Aspiration (FNA) samples can improve the prediction of lymph node metastasis in patients with papillary thyroid cancer. METHODS: In this retrospective cohort study, patients with papillary thyroid cancer who went through thyroidectomy and central lymph node dissection were included. Multi-omics data of FNA samples were assessed by an integrated array. To predict lymph node metastasis, we built models using gene expressions or mutations (SNV and fusion) only and an Integrated Risk Stratification (IRS) model combining genetic and clinical information. Blinded histopathology served as the reference standard. ROC curve and decision curve analysis was applied to evaluate the predictive models. RESULTS: One hundred and thirty two patients with pathologically confirmed papillary thyroid cancer were included between 2016-2017. The IRS model demonstrated greater performance [AUC = 0.87 (0.80-0.94)] than either expression classifier [AUC = 0.67 (0.61-0.74)], mutation classifier [AUC = 0.61 (0.55-0.67)] or TIRADS score [AUC = 0.68 (0.62-0.74)] with statistical significance (p < 0.001), and the IRS model had similar predictive performance in large nodule [>1 cm, AUC = 0.88 (0.79-0.97)] and small nodule [≤1 cm, AUC = 0.84 (0.74-0.93)] subgroups. The genetic risk factor showed independent predictive value (OR = 10.3, 95% CI:1.1-105.3) of lymph node metastasis in addition to the preoperative clinical information, including TIRADS grade, age, and nodule size. CONCLUSION: The integrated gene profiling of FNA samples and the IRS model developed by the machine-learning method significantly improve the risk stratification of thyroid cancer, thus helping make wise decisions and reducing unnecessary extensive surgeries.

Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. METHODS: We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. RESULTS: In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. CONCLUSIONS: Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.

N6 -methyladenosine-modified circRNA RERE modulates osteoarthritis by regulating ß-catenin ubiquitination and degradation.

OBJECTIVES: N6 -methyladenosine (m6A) is one of the most abundant internal RNA modifications. We investigated the role of m6A-modified circRERE in osteoarthritis (OA) and its mechanism. MATERIALS AND METHODS: CircRERE and IRF2BPL were screened by microarrays. The role of m6A-modification in circRERE was examined by methylated RNA precipitation and morpholino oligo (MOs) treatment. The axis of circRERE/miR-195-5p/IRF2BPL/ß-catenin was determined using flow cytometry, western blotting and immunofluorescence in human chondrocytes (HCs) and corroborated using a mouse model of destabilization of medial meniscus (DMM) with intra-articular (IA) injection of adeno-associated viruses (AAV). RESULTS: CircRERE was decreased in OA cartilage and chondrocytes compared with control. CircRERE downregulation was likely attributed to its increased m6A modification prone to endoribonucleolytic cleavage by YTHDF2-HRSP12-RNase P/MRP in OA chondrocytes. MOs transfection targeting HRSP12 binding motifs in circRERE partially reversed decreased circRERE expression and increased apoptosis in HCs treated with IL-1ß for 6 h. CircRERE exerted chondroprotective effects by targeting miR-195-5p/IRF2BPL, thus regulating the ubiquitination and degradation of ß-catenin. CircRere (mouse homologue) overexpression by IA-injection of AAV-circRere into mice attenuated the severity of DMM-induced OA, whereas AAV-miR-195a-5p or AAV-sh-Irf2bpl reduced the protective effects. The detrimental effects of AAV-sh-Irf2bpl on DMM-induced OA were substantially counteracted by ICG-001, an inhibitor of ß-catenin. CONCLUSIONS: Our study is a proof-of-concept demonstration for targeting m6A-modified circRERE and its target miR-195-5p/IRF2BPL/ß-catenin as potential therapeutic strategies for OA treatment.

Evaluation of whole axillary status with lymphatic contrast-enhanced ultrasound in patients with breast cancer.

OBJECTIVES: This study aims to evaluate the whole axillary status of patients with breast cancer by lymphatic contrast-enhanced ultrasound (LCEUS). METHODS: LCEUS was applied for 169 patients with suspected breast cancer. Abnormal patterns in lymphatic channels, sentinel lymph nodes (SLNs), and non-enhanced but abnormal lymph nodes were investigated. The signs of distorted, attenuated, netted, or interrupted lymphatic channels, defective-filling or no-filling SLNs, and the appearance of non-enhanced but abnormal lymph nodes were designated as features of axillary metastasis. A positive outcome was given when any of the abnormal patterns was found in the LCEUS. The diagnostic efficiencies were calculated to differentiate the axillary lymphatic status using LCEUS for the whole axilla, compared with conventional ultrasound (US) and LCEUS for SLNs. RESULTS: The LCEUS procedure was successfully performed for 157 breast cancer patients with axillary dissection. Compared to normal axillae, abnormal patterns had a significantly higher frequency in metastatic axillae (p = 0.000). Using conventional US to evaluate the whole axillae, the diagnostic sensitivity, specificity, and accuracy were 69.1%, 71.9%, and 70.7%, respectively. When LCEUS was used for SLN evaluation to predict the whole axilla, the diagnostic sensitivity, specificity, and accuracy were 66.2%, 89.9%, and 79.6%, respectively. When LCEUS was used as the whole axillary evaluation method, the diagnostic sensitivity, specificity, and accuracy were 76.5%, 86.5%, and 82.2%, respectively. CONCLUSION: LCEUS can be an accurate method to observe the whole axillae in breast cancer patients. Lymphatic channels, SLNs, and non-enhanced but abnormal lymph nodes constitute the LCEUS for whole axillary evaluation. KEY POINTS: • LCEUS can be an accurate method to observe the whole axillae in breast cancer patients. • Three aspects in the LCEUS for whole axillary evaluation are the lymphatic channels, sentinel lymph nodes (SLNs), and non-enhanced but abnormal lymph nodes. • Signs of distorted, attenuated, netted, or interrupted lymphatic channels, defective-filling or no-filling SLNs, and the appearance of non-enhanced but abnormal lymph nodes were considered as features of axillary metastasis.

Development and evaluation of cancer differentiation analysis technology: a novel biophysics-based cancer screening method.

BACKGROUND: Routine health checkup is an essential strategy for monitoring population health and maintaining healthy workforces. However, there was a lack of cancer screening tests among routine health checkups due to high costs and unreliable methods. METHODS: We conducted a two-stage study to evaluate the value of a blood test, Cancer Differentiation Analysis (CDATM), which is developed to differentiate the blood samples of healthy individuals from those of cancer patients through measuring and analyzing multiple biophysical properties. RESULTS: The first stage of a cross-sectional study included 75,942 healthy individuals in routine health checkup, and the second stage of a prospective population-based cohort included 1,957 healthy community members. Forty-eight and ten cancer cases were identified among cross-sectional study and prospective population-based cohort, respectively. Using a pre-determined cutoff, we found that the CDA™ test could differentiate blood samples between healthy and cancer individuals with >93% specificity and >55% sensitivity in both studies. CONCLUSIONS: With high specificity and moderate sensitivity of CDA™ test, our study indicates that we can analyze biophysical properties in the blood to rapidly and reliably screen healthy individuals from cancer patients in a health checkup setting where most individuals are healthy or with average risk of cancer.

Associations of osteoclastogenesis and nerve growth in subchondral bone marrow lesions with clinical symptoms in knee osteoarthritis.

BACKGROUND/OBJECTIVE: Subchondral bone marrow lesions (BMLs) are common magnetic resonance imaging (MRI) features in joints affected by osteoarthritis (OA), however, their clinical impacts and mechanisms remain controversial. Thus, we aimed to investigate subchondral BMLs in knee OA patients who underwent total knee arthroplasty (TKA), then evaluate the associations of osteoclastogenesis and nerve growth in subchondral BMLs with clinical symptoms. METHODS: Total 70 patients with primary symptomatic knee OA were involved, then separated into three groups based on MRI (without BMLs group, n â€‹= â€‹14; BMLs without cyst group, n â€‹= â€‹37; BMLs with cyst group, n â€‹= â€‹19). Volume of BMLs and cyst-like lesions was calculated via the OsiriX system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to assess clinical symptoms. Histology and immunohistochemistry were deployed to assess subchondral osteoclastogenesis and nerve distribution. Pearson's correlation coefficient was used to evaluate the associations between volume of BMLs and joint symptoms, and to assess the associations of osteoclastogenesis and nerve growth in subchondral BMLs with joint symptoms. RESULTS: In BMLs combined with cyst group, patients exhibited increased osteoclastogenesis and nerve distribution in subchondral bone, as shown by increased expression of tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5). Volume of subchondral cyst-like component was associated with joint pain (p â€‹< â€‹0.05). Subchondral osteoclastogenesis and nerve distribution were positively associated with joint pain in BMLs with cyst group (p â€‹< â€‹0.05). CONCLUSION: The subchondral cyst-like lesion was an independent factor for inducing pain in OA patients; osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for this joint pain. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our results indicated that the increased osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for the pain of OA joints. These findings may provide valuable basis for the treatment of OA.

The Design and Rationale of a Multicentre Randomised Controlled Trial Comparing Transperineal Percutaneous Laser Ablation With Transurethral Resection of the Prostate for Treating Benign Prostatic Hyperplasia.

Background: Transurethral resection of the prostate (TURP) is regarded as the "gold standard" for the treatment of benign prostatic hyperplasia (BPH) in elderly men. However, ~15% of patients who had undergone TURP had intraoperative and postoperative complications, such as bleeding, urinary incontinence and urethral stricture. Transperineal percutaneous laser ablation (TPLA) is a method that places the optical fibre directly into the prostate with the guidance of ultrasound imaging, and the percutaneous transperineal approach is performed distal to the urethra and rectum to protect these structures and reduce urethral or postoperative infection. Several studies on TPLA for BPH treatment have been reported recently; however, high-quality randomised controlled trial (RCT) to evaluate its efficacy, safety, and long-term follow up remain absent. Methods: This study is a multicentre, open-label RCT to assess the efficacy and safety of TPLA vs. TURP to treat BPH. We hypothesise that the TPLA has non-inferior efficacy to TURP in the International Prostate Symptom Score (IPSS) at 3 months changing from the baseline and lower incidence of post-surgery complications. One hundred and fourteen patients with BPH will be recruited at 19 sites and randomly assigned at 1:1 to TPLA or TURP groups. The patients will be followed up at 1, 3, 6, 12, and 24 months after the procedure. Discussion: The study will be the first multicentre clinical trial including 16 participating centres in China, Italy, Switzerland, and Poland with relatively large sample size 114. By comprehensively compare the safety and efficacy of TPLA with TURP in patients with BPH, especially concerning the improvement of lower urinary tract symptoms (LUTS) and complication incidence, the study will help to illustrate the clinical value of TPLA and provide a beneficial alternative treatment for BPH patients. Clinical Trial Registration: The study has been registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn), identifier [ChiCTR1900022739].

Increasing Gap Between Thyroid Cancer Incidence and Mortality in Urban Shanghai, China: An Analysis Spanning 43 Years.

OBJECTIVE: To examine the secular trends of thyroid cancer incidence and mortality and to estimate the proportion of thyroid cancer cases potentially attributable to overdiagnosis. METHODS: Data on thyroid cancer cases from 1973 to 2015 were obtained from the Shanghai Cancer Registry. The average annual percent change (AAPC) was evaluated using the joinpoint regression analysis. The age, period, and birth cohort effects were assessed using an age-period-cohort model. The overdiagnosis of thyroid cancer cases was estimated based on the difference between observed and expected incidences using the rates of Nordic countries as reference. RESULTS: From 1973 to 2015, the number of thyroid cancer cases was 23 117, and 75% of the patients were women. The age-standardized rates were seven- to eightfold higher from 2013 to 2015 than from 1973 to 1977. Compared with relatively stable mortality, thyroid cancer incidence was dramatically increased from 2002 to 2015 in both sexes, with significant trends (men: AAPC = 21.84%, 95% CI: 18.77%-24.98%, P < .001; women: AAPC = 18.55%, 95% CI: 16.49%-20.64%, P < .001). The proportion of overdiagnosis has gradually increased over time, rising from 68% between 2003 and 2007 to more than 90% between 2013 and 2015. This increasing trend appeared to be similar between men and women. CONCLUSION: An increasing gap between thyroid cancer incidence and mortality was observed in Shanghai, and overdiagnosis has contributed substantially to the rise of incidence, which calls for an urgent update on the practice of thyroid examination.

Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer.

BACKGROUND: Lung cancer is the tumor with the highest morbidity and mortality, and has become a global public health problem. The incidence of lung cancer in men has declined in some countries and regions, while the incidence of lung cancer in women has been slowly increasing. Therefore, the aim is to explore whether estrogen-related genes are associated with the incidence and prognosis of lung cancer. METHODS: We obtained all estrogen receptor genes and estrogen signaling pathway genes in The Cancer Genome Atlas (TCGA), and then compared the expression of each gene in tumor tissues and adjacent normal tissues for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) separately. Survival analysis was performed of the differentially expressed genes in LUAD and LUSC patients separately. The diagnostic and prognostic values of the candidate genes were validated in the Gene Expression Omnibus (GEO) datasets. RESULTS: We found 5 estrogen receptor genes and 66 estrogen pathway genes in TCGA. A total of 50 genes were differently expressed between tumor tissues and adjacent normal tissues and 6 of the 50 genes were related to the prognosis of LUAD in TCGA. 56 genes were differently expressed between tumor tissues and adjacent normal tissues and none of the 56 genes was related to the prognosis of LUSC in TCGA. GEO datasets validated that the 6 genes (SHC1, FKBP4, NRAS, PRKCD, KRAS, ADCY9) had different expression between tumor tissues and adjacent normal tissues in LUAD, and 3 genes (FKBP4, KRAS, ADCY9) were related to the prognosis of LUAD. CONCLUSIONS: The expressions of FKBP4 and ADCY9 are related to the pathogenesis and prognosis of LUAD. FKBP4 and ADCY9 may serve as biomarkers in LUAD screening and prognosis prediction in clinical settings.

Values of liquid biopsy in early detection of cancer: results from meta-analysis.

BACKGROUND: There is tremendous interest in the development of liquid biopsy techniques, but the potential role of liquid biopsy for the early detection of cancer has not yet been elucidated. We aim to explore the performance of liquid biopsy in the early diagnosis of cancer. METHODS: A systematic review was conducted of liquid biopsy in cancer early detection. Meta-regression was carried out to explore the source of heterogeneity and publication bias was also evaluated. RESULTS: Overall, there were six types of biomarkers and 17 studies focusing on liquid biopsy in the early detection of cancer, 7 studies in ctDNA, 5 studies in cfDNA, 2 studies in CTC, and the other three studies used circulating nucleosome, microRNA, and multiple biomarkers, respectively. Pooled sensitivity and specificity of liquid biopsy in cancer early detection was 0.76 (95%CI:0.67-0.83) and 0.92 (95%CI:0.86-0.96) and the area under the SROC curve was 0.91 (95%CI:0.88-0.93). CONCLUSIONS: The current evidence shows that liquid biopsy has relatively low sensitivity and high specificity in cancer early detection. Among all these biomarkers, cfDNA may have potentially promising value in cancer early detection, thereby supporting further study of cancer early detection. STUDY REGISTRATION: The study is registered at PROSPERO (Identifier number: CRD42020137205).

Effects of atmospheric particulate matter pollution on sleep disorders and sleep duration: a cross-sectional study in the UK biobank.

BACKGROUND: Sleep disorder prevalence exhibited a six-fold relative increase from 2000 to 2010 in the United States. Sleep problems could increase the risk of stroke, cardiovascular disease, diabetes and cancer. Objective short sleep duration is associated with increased mortality. Obesity, smoking and sex differences could influence sleep disorders and sleep duration. The health effects of atmospheric particulate matter (PM) pollution are of great concern. However, a large general population-based study with abundant demographic and lifestyle information is needed to confirm the effect of PM pollution on sleep disorders and sleep duration. METHODS: Information on PM air pollution, demographics and other related factors was obtained from the UK Biobank. Subjects' characteristics were described as the means and 95% confidence intervals (95% CIs) for continuous variables and counts (percentages) for categorical variables. In the case-control study of sleep disorders, univariate analysis, single-pollutant models and a four-pollutant model with logistic regression were performed to estimate the odds ratio (OR) of the risk factors. For sleep duration, univariate analysis, single-pollutant models and a four-pollutant model with linear regressions were carried out to assess the effect of the factors. Sensitivity analysis was performed by data imputation and study population change. RESULTS: There were 5976 cases and 97,160 controls included in the case-control study of sleep disorders. For sleep duration analysis, most of the participants had environmental PM data, and 457,358 participants were selected. The single-pollutant models showed that the OR of PM2.5 for sleep disorders was 2.39 (95% CI: 1.64-3.48) for every 10 µg/m3 increase. PM2.5 and PM10 reduced sleep duration by 0.14 (95% CI: 0.10-0.18) and 0.12 (95% CI: 0.10-0.14) hours for every 10 µg/m3 increase, respectively. Four-pollutant models showed that the OR of PM2.5 for sleep disorders was 4.42 (95% CI: 2.36-8.26) for every 10 µg/m3 increase. PM10 appeared to reduce sleep duration by 0.09 (95% CI: 0.06-0.12) hours for every 10 µg/m3 increase. The main results showed good robustness after sensitivity analysis. CONCLUSIONS: PM2.5 was a risk factor for sleep disorders. PM2.5 and PM10 reduced sleep duration. A reduction in particulate matter exposure may decrease the risk of sleep disorders and improve sleep duration.

Different subchondral trabecular bone microstructure and biomechanical properties between developmental dysplasia of the hip and primary osteoarthritis.

OBJECTIVE: Developmental dysplasia of the hip (DDH) is recognized as a frequent cause of secondary osteoarthritis (OA). The purpose in this study was to compare structural and biomechanical properties of subchondral trabecular bone â€‹and its relationship with cartilage damage between patients with DDH and patients with primary hip OA. METHODS: Forty-three femoral head specimens obtained from patients who underwent total hip arthroplasty [DDH, n â€‹= â€‹17; primary OA, n â€‹= â€‹16; and normal control (NC), n â€‹= â€‹10] were scanned by microcomputed tomography and analyzed by individual trabecula segmentation to obtain the microstructural types of subchondral trabecular bone. The biomechanical properties were analyzed by micro-finite element analysis, and cartilage damage was evaluated by histology. The linear regression analysis was used to indicate the association between microstructures, biomechanical property, and articular cartilage. RESULTS: The DDH group showed the lowest total bone volume fractions (BV/TV) and plate BV/TV in the three groups (p â€‹< â€‹0.05). There were also different discrepancies between the three groups in plate/rod trabecular number, plate/rod trabecular thickness, trabecular plate surface area/trabecular rod length, and junction density with different modes (plate-plate, rod-rod, and plate-rod junction density). The micro-finite element analysis, histology, and linear regression revealed that the subchondral trabecular bone in the DDH group had inferior biomechanical properties â€‹and cartilage damage of patients with DDH was more serious with different subchondral trabecular bone microstructures. CONCLUSION: Our findings detected deteriorating subchondral trabecular bone microstructures in patients with DDH. The mass and type of subchondral trabecular bone play a key role in mechanical properties in DDH, which might be related to cartilage damage. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our findings suggested that changes of subchondral trabecular bone play a critical role â€‹in DDH progression and that the improvement on subchondral trabecular bone may be a sensitive and promising way in treatment of DDH.