Evaluation of serum CA125, HE4 and CA724 and the risk of ovarian malignancy algorithm score in the diagnosis of high-grade serous ovarian cancer.

AIM: To develop a new algorithm for the detection of high-grade serous ovarian cancer (HGSOC). METHODS: Patients diagnosed with HGSOC, borderline ovarian tumours (BOTs) or benign ovarian masses (BOMs) were enrolled between February 2019 and December 2020. Patients with BOTs or BOMs were grouped as non-HGSOC. The cases were divided randomly into a training cohort (two-thirds of cases) and a validation cohort (one-third of cases). Logistic regression was used to find risk factors for HGSOC and to create a new algorithm in the training cohort. Receiver operating characteristic curves were used to compare the diagnostic value of tumour biomarkers. Sensitivity and specificity of tumour markers and the new algorithm were calculated in the training cohort and validation cohort. RESULTS: This study found significant differences in age; BRCA1/2 mutation status; CA125, CA724 and HE4 levels; and Risk of Ovarian Malignancy Algorithm score between the two groups.Logistic regression analysis showed that CA125 and BRCA1/2 were risk factors for HGSOC. A new algorithm combining CA125 and BRCA1/2 increased the specificity of CA125 for diagnosis of HGSOC. The new algorithm had sensitivity of 81.08% and specificity of 93.10% in the training cohort. CONCLUSION: The new algorithm using CA125 and BRCA1/2 helped to distinguish between patients with HGSOC and patients with non-HGSOC.

Workplace psychosocial factors, work organization, and physical exertion as risk factors for low back pain among U.S. workers: Data from the 2015 National Health Interview Survey.

OBJECTIVE: To evaluate the association between workplace psychosocial, organization, and physical risk factors with low back pain (LBP) among U.S. workers. METHODS: 2015 National Health Interview Survey data was analyzed to calculate prevalences and prevalence ratios for LBP across levels of workplace psychosocial and organizational risk factors among 17,464 U.S. adult workers who worked ≥20 hours/week. Results were also stratified by workplace physical exertion. RESULTS: The adjusted prevalences of LBP were significantly elevated for workers reporting high job demand, low job control, work-family imbalance, bullying, job insecurity, working alternate shifts, and physical exertion. Job control and nonstandard shifts were significantly associated with LBP only among those who reported low/no physical exertion. CONCLUSIONS: LBP prevalence was associated with select workplace psychosocial and organization risk factors. Stratification by physical exertion modified multiple associations.

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease.

Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid-gestational age-the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case-control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.

Association between spinal and non-spinal health conditions reported in epidemiological studies: a scoping review protocol.

INTRODUCTION: The increasing prevalence of coexisting health conditions poses a challenge to healthcare providers and healthcare systems. Spinal pain (eg, neck and back pain) and spinal pathologies (eg, osteoporotic fractures and degenerative spinal disease) exist concurrently with other non-spinal health conditions (NSHC). However, the scope of what associations may exist among these co-occurring conditions is unclear. Therefore, this scoping review aims to map the epidemiological literature that reports associations between spine-related pain and pathologies (SPPs) and NSHCs. METHODS AND ANALYSIS: This scoping review will follow the JBI protocol and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. We will systematically search the literature using key words and MeSH terms for SPPs and NSHCs. Terminology/vocabulary for NSHCs will include those for communicable and non-communicable diseases as reported by WHO Global Burden of Disease reports. Five databases will be searched from inception: MEDLINE, EMBASE, APA PsycInfo, Scopus and Web of Science Core Collection. Papers published in English, in peer-reviewed journals, including measures of association between SPPs and NSHCs and using observational epidemiologic study designs will be included. Excluded will be studies of cadaveric, animal or health behaviours; studies with no measures of association and non-observational epidemiologic studies. Results will include the number of studies, the studies that have evaluated the measures of association and the frequency of the studied associations between SPPs and NSHCs. Results will be reported in tables and diagrams. Themes of comorbidities will be synthesised into a descriptive report. ETHICS AND DISSEMINATION: This scoping review was deemed exempt from ethics review. This review will provide a comprehensive overview of the literature that reports associations between SPPs and NSHCs to inform future research initiatives and practices. Results will be disseminated through publication in peer-reviewed journals and research conferences. REGISTRATION DETAILS: https://osf.io/w49u3.

Advances in targeted therapy and immunotherapy for esophageal cancer.

ABSTRACT: Esophageal cancer (EC) is one of the most common aggressive malignant tumors in the digestive system with a severe epidemiological situation and poor prognosis. The early diagnostic rate of EC is low, and most EC patients are diagnosed at an advanced stage. Multiple multimodality treatments have gradually evolved into the main treatment for advanced EC, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. And the emergence of targeted therapy and immunotherapy has greatly improved the survival of EC patients. This review highlights the latest advances in targeted therapy and immunotherapy for EC, discusses the efficacy and safety of relevant drugs, summarizes related important clinical trials, and tries to provide references for therapeutic strategy of EC.

Hybrid Additive and Subtractive Manufacturing Method Using Pulsed Arc Plasma.

In this study, a novel hybrid additive and subtractive manufacturing method using pulsed arc plasma (PAP-HASM) was developed to better integrate additive and subtractive processes. The PAP-HASM process is based on the flexible application of pulsed arc plasma. In this PAP-HASM method, wire arc additive manufacturing using pulsed arc plasma (PAP-WAAM) and dry electrical discharge machining (EDM) milling were used as additive and subtractive techniques, respectively; both are thermal machining processes based on pulsed arc plasma, and both are dry machining techniques requiring no working fluids. The PAP-HASM can be easily realized by only changing the pulsed power supply and tool electrodes. A key technological challenge is that the recast layer on the part surface after dry EDM milling may have a detrimental effect on the component fabricated by PAP-HASM. Here, the hybrid manufacturing method developed in this study was validated with commonly used 316L stainless steel. Preliminary experimental results showed that the PAP-HASM specimens exhibited excellent tensile properties, with an ultimate tensile strength of 539 ± 8 MPa and elongation of 46 ± 4%, which were comparable to the PAP-WAAM specimens. The recast layer on the surface after dry EDM milling has no significant detrimental effect on the mechanical properties of the parts fabricated by PAP-HASM. In addition, compared with components fabricated by PAP-WAAM, those fabricated by PAP-HASM showed significantly better surface roughness.

Spinal Pain, Chronic Health Conditions and Health Behaviors: Data from the 2016-2018 National Health Interview Survey.

Spinal pain and chronic health conditions are highly prevalent, burdensome, and costly conditions, both in the United States and globally. Using cross-sectional data from the 2016 through 2018 National Health Interview Survey (n = 26,926), we explored associations between spinal pain and chronic health conditions and investigated the influence that a set of confounders may have on the associations between spinal pain and chronic health conditions. Variance estimation method was used to compute weighted descriptive statistics and measures of associations with multinomial logistic regression models. All four chronic health conditions significantly increased the prevalence odds of spinal pain; cardiovascular conditions by 58%, hypertension by 40%, diabetes by 25% and obesity by 34%, controlling for all the confounders. For all chronic health conditions, tobacco use (45-50%), being insufficiently active (17-20%), sleep problems (180-184%), cognitive impairment (90-100%), and mental health conditions (68-80%) significantly increased the prevalence odds of spinal pain compared to cases without spinal pain. These findings provide evidence to support research on the prevention and treatment of non-musculoskeletal conditions with approaches of spinal pain management.

Bidirectional Comorbid Associations between Back Pain and Major Depression in US Adults.

Low back pain and depression have been globally recognized as key public health problems and they are considered co-morbid conditions. This study explores both cross-sectional and longitudinal comorbid associations between back pain and major depression in the adult population in the United States. We used data from the Midlife in the United States survey (MIDUS), linking MIDUS II and III with a sample size of 2358. Logistic regression and Poisson regression models were used. The cross-sectional analysis showed significant associations between back pain and major depression. The longitudinal analysis indicated that back pain at baseline was prospectively associated with major depression at follow-up (PR 1.96, CI: 1.41, 2.74), controlling for health behavioral and demographic variables. Major depression at baseline was also prospectively associated with back pain at follow-up (PR 1.48, CI: 1.04, 2.13), controlling for a set of related confounders. These findings of a bidirectional comorbid association fill a gap in the current understanding of these comorbid conditions and could have clinical implications for the management and prevention of both depression and low back pain.

Psychosocial risk factors for low back pain in US workers: Data from the 2002-2018 quality of work life survey.

BACKGROUND: Examining workplace psychosocial risk factors for back pain becomes increasingly important because of the changing nature of work and rising healthcare costs. Some psychosocial risk factors for back pain, such as work and family imbalance, exposure to a hostile work environment, and job insecurity, are understudied for the working population in the United States. METHODS: Data used in this study came from the Quality of Work Life Survey (QWL), a supplementary module of the General Social Survey conducted in the United States. Data from the 2002, 2006, 2010, 2014, and 2018 QWL surveys were used in these analyses, giving a total sample size of 6661. Five domains of workplace psychosocial risk factors for back pain were examined, including job strain, low social support, work-family imbalance, exposure to a hostile work environment (harassment and discrimination), and job insecurity. The adjusted odds ratio (aOR) of each psychosocial risk factor for back pain with 95% confidence intervals (CI) was estimated using a multivariable logistic regression model after controlling for job physical factors, occupation, and demographic and socioeconomic characteristics. RESULTS: Significant associations were found between back pain and several psychosocial factors including job strain (aOR 1.19; CI 1.00,1.41), work-family imbalance (aOR,1.42; CI 1.22,1.64), harassment (aOR 1.40; CI 1.15,1.71), and discrimination (aOR 1.20 CI 1.00,1.44). CONCLUSION: This study contributes to the understanding of the relationship between a variety of workplace psychosocial factors and back pain. Our findings suggest directions in future longitudinal research to examine emerging workplace psychosocial factors for back pain.

Working Conditions and Wellbeing among Prison Nurses during the COVID-19 Pandemic in Comparison to Community Nurses.

The psychological health and work challenges of nurses working in prisons during the COVID-19 pandemic are understudied. We evaluated the work and wellbeing characteristics of a California prison nurse group, with a comparison to those of a community nurse group. From May to November 2020, an online survey measured psychosocial and organizational work factors, sleep habits, psychological characteristics, COVID-19 impacts, and pre-pandemic recall among 62 prison nurses and 47 community nurses. Prison nurses had significantly longer work hours (54.73 ± 14.52, p < 0.0001), higher pandemic-related work demands, and less sleep hours (5.36 ± 1.30, p < 0.0001) than community nurses. Community nurses had significantly higher pandemic-related fear levels (work infection: p = 0.0115, general: p = 0.0025) and lower perceived personal protective equipment (PPE) supply (p = 0.0103). Between pre-pandemic and pandemic periods, both groups had significantly increased night shift assignments and decreased sleep hours, but the prison group had increased work hours. Although not statistically significant, both groups had high occupational stress and prevalence of post-traumatic stress symptoms. Our results indicate that prison nurses experienced work and wellbeing challenges during the pandemic. Future research and practice ought to address nurses' workload, PPE, and psychological resources in correctional facilities and healthcare organizations.

Erratum: Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis: Erratum.

[This corrects the article DOI: 10.7150/thno.44419.].

Retraction Notice to: Exosome miR-155 Derived from Gastric Carcinoma Promotes Angiogenesis by Targeting the c-MYB/VEGF Axis of Endothelial Cells.

[This retracts the article DOI: 10.1016/j.omtn.2020.01.024.].

Correlation between vaginal microbiota and different progression stages of cervical cancer.

The process from high-risk human papillomavirus (HR-HPV) infection to cervical cancer is a continuous and long-term process, but the pathogenesis of the whole process is not completely clear. Here, 59 Chinese women were engaged in this study, and divided into five groups: normal healthy group, HR-HPV infections group, low-grade intraepithelial neoplasia (LSIL) group, high-SIL(HSIL) group, and cervical cancer group. With the occurrence of HR-HPV infection and the development of cervical lesions, the diversity of vaginal microbiota species was increased, and the relative abundance of Lactobacillus (L.), the dominant bacteria in maintaining vaginal microecological balance, was decreased gradually. In contrast, the abundance of Actinobacteria in the four disease groups was significantly higher than that in normal group. Furthermore L. iners may be related to the serious progression of cervical cancer. After analyzing the whole process, we found that Gardnerella(G.), Atopobium(A.) and Dialister(D.) have important effects on both persistent HR-HPV infection and the pathogenesis of cervical cancer. In addition, PICRUSt2 and KEGG results showed that the KEGG pathways enriched by the predicted genes of vaginal microbiota in cancer group included metabolic diseases, endocrine system and immune systems when compared with that in normal group. These findings may provide insights into the pathogenesis of cervical cancer, and help to improve the early detection and prevention of cervical precancerous lesions.

lncRNA-encoded pep-AP attenuates the pentose phosphate pathway and sensitizes colorectal cancer cells to Oxaliplatin.

Oxaliplatin (L-OHP) is a standard treatment for colorectal cancer (CRC), but chemoresistance is a considerable challenge. L-OHP shows dose-dependent toxicity, and potential approaches that sensitize cancer cells to L-OHP could reduce the dosage. With the development of translatomics, it was found that some lncRNAs encode short peptides. Here, we use ribosome footprint profiling combined with lncRNA-Seq to screen 12 lncRNAs with coding potential, of which lnc-AP encodes the short peptide pep-AP, for their role in L-OHP resistance. Co-IP and LC-MS/MS data show that the TALDO1 protein interacts with pep-AP and that pep-AP suppresses the expression of TALDO1. The pep-AP/TALDO1 pathway attenuates the pentose phosphate pathway (PPP), reducing NADPH/NADP+ and glutathione (GSH) levels and causing ROS accumulation and apoptosis, which sensitizes CRC cells to L-OHP in vitro and in vivo. pep-AP thus might become a potential anticancer peptide for future treatments of L-OHP-resistant CRC.

Chemotoxicity-induced exosomal lncFERO regulates ferroptosis and stemness in gastric cancer stem cells.

Cancer stem cells (CSCs) are an important cause of tumor recurrence and drug resistance. As a new type of cell death that relies on iron ions and is strictly regulated by intracellular and extracellular signals, the role of ferroptosis in tumor stem cells deserves extensive attention. Mass spectrum was applied to screen for ferroptosis-related proteins in gastric cancer (GC). Sphere-formation assay was used to estimate the stemness of gastric cancer stem cells (GCSCs). Exosomal lnc-ENDOG-1:1 (lncFERO) was isolated by ultracentrifugation. Ferroptosis was induced by erastin and was assessed by detecting lipid ROS, mitochondrial membrane potential, and cell death. Furthermore, a series of functional in vitro and in vivo experiments were conducted to evaluate the effects of lncFERO on regulating ferroptosis and chemosensitivity in GCSCs. Here, we showed that stearoyl-CoA-desaturase (SCD1) played a key role in regulating lipid metabolism and ferroptosis in GCSCs. Importantly, exosomal lncFERO (exo-lncFERO) derived from GC cells was demonstrated to promote SCD1 expression by directly interacting with SCD1 mRNA and recruiting heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which resulted in the dysregulation of PUFA levels and the suppression of ferroptosis in GCSCs. Moreover, we found that hnRNPA1 was also involved in lncFERO packing into exosomes in GC cells, and both in vitro and in vivo data suggested that chemotoxicity induced lncFERO secretion from GC cells by upregulating hnRNPA1 expression, leading to enhanced stemness and acquired chemo-resistance. All these data suggest that GC cells derived exo-lncFERO controls GCSC tumorigenic properties through suppressing ferroptosis, and targeting exo-lncFERO/hnRNPA1/SCD1 axis combined with chemotherapy could be a promising CSC-based strategy for the treatment of GC.

Gastric cancer derived exosomes mediate the delivery of circRNA to promote angiogenesis by targeting miR-29a/VEGF axis in endothelial cells.

Accumulating evidence has been found that circular RNA (circRNA) plays a critical role in the initiation and development of various diseases by modulating gene expression in the cytoplasm. However, the role of circ_0044366 (termed circ29) in gastric cancer (GC) has yet to be elusive. We detected that exosomal circ29 was confirmed to be highly expressed in GC and can significantly impair the proliferation, migration, tube formation of HUVEC by exosomal communication. Interestingly, this effect could be blocked by the effect of miR-29a. In brief, we confirmed that circ29, as a sponge of miR-29a, plays a responsible role in the occurrence and development of GC by regulating the VEGF pathway. Therefore, it may be used as a potential target for the treatment of GC.

Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis.

Hypoxia is one of the important properties of solid tumor. However, oxygen supply within tumors is generally heterogeneous according to the distance from the nearest blood vessel. The discrepancy of metastatic potential exists between hypoxic cancer cells and relatively normoxic cancer cells. But the molecular mechanism remains poorly understood. Methods: Differential expression of circRNAs in plasma exosomes of CRC patients and normal subjects was performed by screening. Exosomes were isolated by ultra-centrifugation and RNA expressions were determined by RT-qPCR. The migratory capacity of cells was performed by high intension imaging, wound healing assay and transwell chamber migration assay. Results: Circ-133 is enriched in the plasma exosomes of CRC patients and increased with the disease progression. Exosomal circ-133 derived from hypoxic cells delivered into normoxic cells and promoted cancer metastasis by acting on miR-133a/GEF-H1/RhoA axis. Meanwhile, animal experiments revealed that knockdown of circ-133 can inhibit tumor metastasis. Circ-133 is expected to be a new biomarker for monitoring tumor progression and might be a novel therapeutic target. Conclusions: Hypoxia-derived exosomal circ-133 transported into normaxic cancer cells and promoted cell migration via miR-133a/GEF-H1/RhoA axis. This study reveals a potential mechanism for that the intra-tumor heterogeneity of oxygen promote cancer progression.