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Abstract Objective Asprosin, a newly identified adipokine, is pathologically increased in type 2 diabetes. The aim of this study is to see whether serum asprosin concentrations are linked to diabetes mellitus-induced erectile dysfunction (DMED). Methods 90 male patients with type 2 diabetes were included. According to the International Index of Erectile Function (IIEF-5) score, they were classified into two groups: 45 type 2 diabetes patients without erectile dysfunction (DM group) (IIEF-5 > 21),45 patients with diabetes induced erectile dysfunction (DMED group) (IIEF-5 ≤ 21)0.45 healthy male volunteers with normal blood glucose, IIEF-5 score > 21 points, and age matched with the DMED group were included as the control group. Anthropometric and biochemical variables were determined in all participants. Results When compared to the controls, T2DM ( Type 2 Diabetes Mellitus)patients had higher serum asprosin levels. The DMED group had significantly higher serum asprosin than the T2DM groups(p

The crown root system is the most important root component in maize at both the vegetative and reproductive stages. However, the genetic basis of maize crown root traits (CRT) is still unclear, and the relationship between CRT and aboveground agronomic traits in maize is poorly understood. In this study, an association panel including 531 elite maize inbred lines was planted to phenotype the CRT and aboveground agronomic traits in different field environments. We found that root traits were significantly and positively correlated with most aboveground agronomic traits, including flowering time, plant architecture and grain yield. Using a genome-wide association study (GWAS) coupled with resequencing, a total of 115 associated loci and 22 high-confidence candidate genes were identified for CRT. Approximately one-third of the genetic variation in crown root was co-located with 46 QTLs derived from flowering and plant architecture. Furthermore, 103 (89.6%) of 115 crown root loci were located within known domestication- and/or improvement-selective sweeps, suggesting that crown roots might experience indirect selection in maize during domestication and improvement. Furthermore, the expression of Zm00001d036901, a high-confidence candidate gene, may contribute to the phenotypic variation in maize crown roots, and Zm00001d036901 was selected during the domestication and improvement of maize. This study promotes our understanding of the genetic basis of root architecture and provides resources for genomics-enabled improvements in maize root architecture.

Grain filling is the physiological process for determining the obtainment of yield in cereal crops. The grain-filling characteristics of 50 maize brand hybrids released from 1964 to 2014 in China were assayed across multiple environments. We found that the grain-filling duration (54.46%) and rate (43.40%) at the effective grain-filling phase greatly contributed to the final performance parameter of 100-kernel weight (HKW). Meanwhile, along with the significant increase in HKW, the accumulated growing degree days (GDDs) for the actual grain-filling period duration (AFPD) among the selected brand hybrids released from the 1960s to the 2010s in China had a decadal increase of 23.41°C d. However, there was a decadal increase of only 19.76°C d for GDDs of the days from sowing to physiological maturity (DPM), which was also demonstrated by a continuous decrease in the ratio between the days from sowing to silking (DS) and DPM (i.e., from 53.24% in the 1960s to 49.78% in the 2010s). In contrast, there were no significant changes in grain-filling rate along with the release years of the selected hybrids. Moreover, the stability of grain-filling characteristics across environments also significantly increased along with the hybrid release years. We also found that the exotic hybrids showed a longer grain-filling duration at the effective grain-filling phase and more stability of the grain-filling characteristics than those of the Chinese local hybrids. According to the results of this study, it is expected that the relatively longer grain-filling duration, shorter DS, higher grain-filling rate, and steady grain-filling characteristics would contribute to the yield improvement of maize hybrids in the future.

AIM: To investigate the validity of triglyceride glucose(TyG)index to identily diabetic retinopathy(DR)in type 2 diabetic patients. METHODS: A cross-sectional study. A total of 1061 type 2 diabetic patients in Shanghai who underwent health checkup in our hospital in 2021, all the subjects underwent questionnaire survey, physical examination, blood biochemical index detection and fundus examination. According to the fundus photos, they were divided into DR group(275 cases)and no DR group(786 cases). Risk factors for DR were evaluated by univariate and multivariate Logistic regression analyses, receiver operating characteristic(ROC)curve was used to analyse the predicted values of TyG with DR. RESULT: Elevated TyG index was an high risk factor for development of DR in type 2 diabetic patients. After adjusting for multiple confounding factors(gender, age, smoking history, the course of diabetes, glycosylated hemoglobin, systolic blood pressure, diastolic blood pressure, body mass index and serum uric), the OR value of the DR in the TyG index Q4 group relative to the Q1 group was 2.57(95%CI: 1.56-4.05), P

ObjectiveThe objective of this research is to investigate the clinical application value of cerebrospinal fluid (CSF) cytology and circulating tumor DNA (ctDNA) in lung adenocarcinoma (LUAD) meningeal metastasis-meningeal carcinomatosis (MC), and to further explore the possible molecular mechanisms and drug treatment targets of LUAD meningeal metastasis by next-generation sequencing (NGS).MethodsWe retrospectively analyzed LUAD with MC in 52 patients. CSF cytology was carried out using the slide centrifugation precipitation method and May-Grüwald-Giemsa (MGG) staining. Tumor tissue, plasma and CSF ctDNA of some MC patients were detected by NGS.ResultsOf the 52 MC patients, 46 (88.46%) were positive for CSF cytology and 34 (65.38%) were positive for imaging, with statistically significant differences in diagnostic positivity (P < 0.05). In 32 of these patients, CSF cytology, cerebrospinal fluid ctDNA, plasma ctDNA and MRI examination were performed simultaneously, and the positive rates were 84.38, 100, 56.25, and 62.50% respectively, the difference was statistically significant (P < 0.001). Analysis of the NGS profiles of tumor tissues, plasma and CSF of 12 MC patients: the mutated gene with the highest detection rate was epidermal growth factor receptor (EGFR) and the detection rate were 100, 58.33, and 100% respectively in tumor tissues, plasma and CSF, and there were 6 cases of concordance between plasma and tissue EGFR mutation sites, with a concordance rate of 50.00%, and 12 cases of concordance between CSF and tissue EGFR mutation sites, with a concordance rate of 100%. In addition, mutations not found in tissue or plasma were detected in CSF: FH mutation, SETD2 mutation, WT1 mutation, CDKN2A mutation, CDKN2B mutation, and multiple copy number variants (CNV), with the most detected being CDKN2A mutation and MET amplification.ConclusionCSF cytology is more sensitive than traditional imaging in the diagnosis of meningeal carcinomatosis and has significant advantages in the early screening and diagnosis of MC patients. CSF ctDNA can be used as a complementary diagnostic method to negative results of CSF cytology and MRI, and CSF ctDNA can be used as an important method for liquid biopsy of patients with MC, which has important clinical significance in revealing the possible molecular mechanisms and drug treatment targets of meningeal metastasis of LUAD.

While maintaining information over a delay of time, working memory (WM) also allows individuals to prepare the mnemonic contents for prospective utilisation. However, it remains unclear whether the expectation of the time of WM test could modulate neural responses during the retention interval of WM and subsequent performance. Here, we investigated whether temporal expectations based on the variability of delay duration can modulate 9–13 Hz alpha oscillations during WM retention and whether the expectation-induced alpha activity was associated with WM performance. Participants performed a retro-cueing WM task with magnetoencephalography (MEG) (Experiment 1) and a standard WM task with electroencephalography (EEG) (Experiment 2). The expectation of the timing of the WM test was manipulated by the temporal structure of the tasks with small or large variability in the delay durations. We showed that alpha oscillations during retention interval and WM performance varied with duration variability in both of the MEG and EEG experiments. The novel finding was greater alpha-power attenuation over the left frontal and parietal regions during WM retention when the duration variability was small and the test onset was predictable, compared to when the duration variability was large and the test onset was less predictable. Importantly, we observed a positive relationship in variability difference between the response benefit and alpha-power attenuation in the left posterior parietal regions at both MEG-source and EEG-electrode levels. Finally, we confirmed the behavioural benefit when a condition with a fixed delay-duration was included in a behavioural experiment (Experiment 3). When conjoined, the delay duration enables individuals to anticipate when the relevant information would be put to work, and alpha oscillations track the anticipatory states during WM maintenance.

Drought is one of the most important abiotic stresses affecting maize growth and development and therefore resulting in yield loss. Thus it is essential to understand molecular mechanisms of drought stress responses in maize for drought tolerance improvement. The root plays a critical role in plants sensing water deficit. In the present study, two maize inbred lines, H082183, a drought-tolerant line, and Lv28, a drought-sensitive line, were grown in the field and treated with different water conditions (moderate drought, severe drought, and well-watered conditions) during vegetative stage. The transcriptomes of their roots were investigated by RNA sequencing. There were 1 428 and 512 drought-responsive genes (DRGs) in Lv28, 688 and 3 363 DRGs in H082183 under moderate drought and severe drought, respectively. A total of 31 Gene Ontology (GO) terms were significantly over-represented in the two lines, 13 of which were enriched only in the DRGs of H082183. Based on results of Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, “plant hormone signal transduction” and “starch and sucrose metabolism” were enriched in both of the two lines, while “phenylpropanoid biosynthesis” was only enriched in H082183. Further analysis revealed the different expression patterns of genes related to abscisic acid (ABA) signal pathway, trehalose biosynthesis, reactive oxygen scavenging, and transcription factors might contribute to drought tolerance in maize. Our results contribute to illustrating drought-responsive molecular mechanisms and providing gene resources for maize drought improvement.

Drought stress affects the growth and productivity of crop plants including sorghum. To study the molecular basis of drought tolerance in sorghum, we conducted the transcriptomic profiling of sorghum leaves and roots under drought stress using RNA-Seq method. A total of 510, 559, and 3 687 differentially expressed genes (DEGs) in leaves, 3 368, 5 093, and 4 635 DEGs in roots responding to mild drought, severe drought, and re-watering treatments were identified, respectively. Among them, 190 common DEGs in leaves and 1 644 common DEGs in roots were responsive to mild drought, severe drought, and re-watering environment. Gene Ontology (GO) enrichment analysis revealed that the GO categories related to drought tolerance include terms related to response to stimulus especially response to water deprivation, abscisic acid stimulus, and reactive oxygen species. The major transcription factor genes responsive to drought stress include heat stress transcription factor (HSF), ethylene-responsive transcription factor (ERF), Petunia NAM, Arabidopsis ATAF1/2 and CUC2 (NAC), WRKY transcription factor (WRKY), homeodomain leucine zipper transcription factor (HD-ZIP), basic helix-loop-helix transcription factor (bHLH), and V-myb myeloblastosis viral oncogene homolog transcription facotr (MYB). Functional protein genes for heat shock protein (HSPs), late-embryogenesis-abundant protein (LEAs), chaperones, aquaporins, and expansins might play important roles in sorghum drought tolerance. Moreover, the genomic regions enriched with HSP, expansin, and aquaporin genes responsive to drought stress could be used as powerful targets for improvement of drought tolerance in sorghum and other cereals. Overall, our results provide a genome-wide analysis of DEGs in sorghum leaves and roots under mild drought, severe drought, and re-watering environments. This study contributes to a better understanding of the molecular basis of drought tolerance of sorghum and can be useful for crop improvement.

The aim of this study was to investigate whether clinic, cumulative, and 24h ambulatory systolic blood pressure (SBP) was associated with chronic kidney damage, defind as estimated glomerular filtration rate (eGFR) .05). Cumulative SBP exposure seems inferior to other measurement in indentifying chronic kidney damage, including decreased GFR and microalbuminuria.

Abstract: The germplasm resources for the S-type male sterility is rich in maize and it is resistant to Bipolaris maydis race T and CI, but the commercial application of S-type cytoplasmic male sterility (CMS-S) in maize hybrid industry is greatly compromised because of its common fertility instability. Currently, the existence of multiple minor effect loci in specific nuclear genetic backgrounds was considered as the molecular mechanism for this phenomenon. In the present study, we evaluated the fertility segregation of the different populations with the fertility instable material FIL-H in two environments of Beijing and Hainan, China. Our results indicated that the fertility instability of FIL-H was regulated by multiple genes, and the expression of these genes was sensitive to environmental factors. Using RNA sequencing (RNA-seq) technology, transcriptomes of the sterile plants and partially fertile plants resulted from the backcross of FIL-H×Jing 724 in Hainan were analyzed and 2 108 genes with different expression were identified, including 1 951 up-regulated and 157 down-regulated genes. The cluster analysis indicated that these differentially expressed genes (DEGs) might play roles in many biological processes, such as the energy production and conversion, carbohydrate metabolism and signal transduction. In addition, the pathway of the starch and sucrose metabolism was emphatically investigated to reveal the DEGs during the process of starch biosynthesis between sterile and partially fertile plants, which were related to the key catalytic enzymes, such as ADP-G pyrophosphorylase, starch synthase and starch branching enzyme. The up-regulation of these genes in the partially fertile plant may promote the starch accumulation in its pollen. Our data provide the important theoretical basis for the further exploration of the molecular mechanism for the fertility instability in CMS-S maize.

The effects of air–sea coupling over the tropical Indian Ocean (TIO) on the eastward propagating boreal winter intraseasonal oscillation (MJO) are investigated by comparing a fully coupled and a partially decoupled Indian Ocean experiment using the SINTEX-F coupled model. Air–sea coupling over the TIO significantly enhances the intensity of the eastward propagations of the MJO along the 5°–10°S zonal areas. The zonal asymmetry of the SST anomaly (SSTA) is responsible for the enhanced eastward propagation. A positive SSTA appears to the east of the MJO convection, which results in the boundary layer moisture convergence and positively feeds back to the MJO convection. In addition, the air–sea interaction effect on the eastward propagation of the MJO is related to the interannual variations of the TIO. Air–sea coupling enhances (reduces) the eastward-propagating spectrum during the negative Indian Ocean dipole mode and positive Indian Ocean basin mode. Such phase dependence is attributed to the role of the background mean westerly in affecting the wind–evaporation–SST feedback. Air–sea coupling (decoupling) enhances (reduces) the zonal asymmetry of the low-level specific humidity, and thus the eastward propagation spectrum of the MJO.

Aims and Objectives: To detect the protein expression level of Cx43, smad4 and PCNA in normal and gastric carcinoma tissue by immuno-histochemistry, western blotting and RT-PCR method. We intend to reveal the relationship between their expression in occurrence and development. Simultaneously through analyzing experimental data we have obtained the correlation among them. Materials and Methods: Immuno-histochemistry and western blotting were adopted to detect the expression of Cx43, smad4 and PCNA protein in normal and carcinomatous gastric tissue, expression levels mRNA of Cx43, smad4 and PCNA were detected by RT-PCR in normal and carcinomatous gastric tissue. Experimental data were analyzed by combining clinical pathology data using statistical approach. Results: The expression levels of Cx43, and smad4 in carcinomatous gastric tissue were lower than they were in normal gastric tissue. The expression level of PCNA in carcinomatous gastric tissue was higher than that in normal gastric tissue. The expression levels of Cx43, Smad4 and PCNA in groups of age and gender is not significant. The expression of Cx43, Smad4 and PCNA in different clinicopathologic features of carcinomatous gastric tissue including degrees of pathological differentiation, lymph node metastasis condition, depth of tumor invasion and TNM stages is statistically significant. With the progression of gastric carcinoma, the expression levels of Cx43 and Smad4 were decreased, conversely PCNA showed a high expression level. Based on the analysis Cx43 negatively correlated with PCNA, Cx43 positively correlated with Smad4, Smad4 negatively correlated with PCNA. Conclusions: The protein and mRNA expressions of Cx43, smad4 and PCNA were significant differences between normal gastric tissue and gastric carcinoma, also were concerned with differentiation degree, lymph node metastasis, TNM stages and depth of invasion, while not significant with age and gender. This suggests that they may play an important role in occurrence and development of gastric carcinoma, but also may have some interaction.

Background and Objectives: Microtubules, the main components of spindles in the mitotic phase, can provide the suitable conditions for unlimited proliferation of tumor cells. Cytoskeleton microtubule-associated-Tau accelerates the progress of malignant tumor through microtubules. Currently, the expression of Cytoskeleton microtubule-associated-Tau in gastric cancer and the relationship between clinical pathological factors research has not yet been reported, so the report aims to elucidate the features of Cytoskeleton microtubule-associated-Tau expression in normal gastric tissue and gastric carcinoma tissue.Materials and Methods: The expressions of Cytoskeleton microtubule-associated protein-Tau protein and Cytoskeleton microtubule-associated protein-Tau mRNA were investigated in 60 cases of gastric carcinoma (cases) and 10 cases of normal gastric tissues (controls). Immunohistochemistry and RT-PCR were respectively used to detect the expression of Cytoskeleton microtubule-associated protein-Tau protein and Tau mRNA in the normal and carcinomatous gastric tissues.Results: The expressions of both cytoskeleton microtubule-associated protein-Tau protein and Tau mRNA in the carcinomatous gastric tissue were higher than in the normal gastric tissue (P). Likewise, both biomarkers were expressed significantly lower in the well-differentiated and moderately-differentiated gastric carcinoma was than in the poorly-differentiated one (P). Moreover, their expressions in the gastric carcinoma without lymph node metastasis was lower than in the gastric carcinoma with lymph node metastasis (P).Conclusion: The expressions of Cytoskeleton microtubule-associated-protein, Tau-protein and Cytoskeleton microtubule-associated-protein, Tau-mRNA were significantly different between the normal gastric tissue and the gastric carcinoma tissue, and were correlated with the degree differentiation and lymph node status.JCMS Nepal. 2015;11(3):6-11.

Aims and Objectives: To provide theoretical basis for the gastric carcinoma pathogenesis and the clinical targeted therapy. Materials and Methods: We detected the expression of Tau protein and Tau mRNA in 60 cases of gastric carcinoma tissues (observation group) and 10 cases of normal gastric tissues (control group). Immunohistochemisty was adopted to detect the expression of Tau protein in normal and carcinomatous gastric tissue. Tau mRNA was detected by RT-PCR in normal and carcinomatous gastric tissue. To analyse the experimental data combined clinical pathology with statistics. Results: The expression of Tau protein in carcinomatous gastric tissue was higher than that in normal gastric tissue (P

Background and Objective: The role of (Human Papilloma Virus) HPV in cancer of certain anatomical location, such as cervix, has been widely recognized. The present study was conducted to explore the association between HPV 16-E6 protein and esophageal squamous cell carcinoma. Methods: SP immunohistochemical method was used to examine the expression of HPV 16-E6 in 50 cases of esophageal squamous cell carcinoma, 10 cases of normal esophageal squamous cell and 10 cases of adjacent tissue. Results: The expression of HPV 16-E6 was significantly higher in esophageal carcinoma than in normal esophageal mucosa and in adjacent tissue. The expressions of HPV 16-E6 had significant correlation with invasive depth (P0.05). Conclusion: HPV 16-E6 can promote the growth and metastasis of esophageal squamous cell carcinoma and can be a prognostic factor of esophageal squamous cell carcinoma.DOI: http://dx.doi.org/10.3126/jcmsn.v10i4.12970 JCMS Nepal 2014; 10(4):1-5

AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy (PDR), an advanced stage of diabetic retinopathy (DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy. METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR (NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I Test, and corneal fluorescein staining. The non-invasive tear film break-up time (NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy. RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls (P< 0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls (P < 0.001). Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover, significant decrease in the corneal epithelial density and morphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients. CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores, and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.

Background: To detect the Protein expression level of Cx43, Smad4 and PCNA in normal and gastric carcinoma tissue by immunohistochemistry, western blotting and RT-PCR method.Materials and Methods: Immunohistochemistry and western blotting were adopted to detect the expression and expression level of Cx43, Smad4 and PCNA protein in normal and carcinomatous gastric tissue. Experimental data were analyzed by combining clinical pathology data using statistical tools.Results: The expression levels of Cx43 and Smad4 in carcinomatous gastric tissue were lower than they were in normal gastric tissue. The expression level of PCNA in carcinomatous gastric tissue was higher than that in normal gastric tissue. The expression levels of Cx43, Smad4 and PCNA in groups of age and gender is not significant. The expression of Cx43, Smad4 and PCNA in different clinic pathologic features of carcinomatous gastric tissue which includes degrees of pathological differentiation, lymph node metastasis condition, depth of tumor invasion and TNM stages is statistically significant. With the progression of gastric carcinoma, the expression levels of Cx43 and Smad4 were decreased, conversely PCNA showed a high expression level.Conclusion: The protein and mRNA expressions of Cx43, Smad4 and PCNA were significantly different between normal gastric tissue and gastric carcinoma and also were concerned with degree of differentiation, lymph node metastasis, TNM stages and depth of invasion, though not significant with age and gender. This suggests that they may play an important role in occurrence and development of gastric carcinoma, but also may have some interaction.Journal of Pathology of Nepal (2015) Vol. 5, 696-704

Background?Gastrointestinal cancer is the most common malignant tumor in China. This research aims to explore the association between HPV16-E6 protein and esophageal squamous cell carcinoma.Materials and Methods: SP immunohistochemical method was used to examine the expression of HPV 16-E6 in 50 cases of esophageal squamous cell carcinoma, 10 cases of normal esophageal squamous cell and 10 cases of adjacent tissue.Results: The expressions of HPV 16-E6 was significantly higher in esophageal carcinoma than in normal esophageal mucosa and in adjacent tissue. The expressions of HPV 16-E6 had correlation with invasive depth (P0.05).Conclusion: HPV 16-E6 can promote the growth and metastasis of esophageal squamous cell carcinoma and can be a prognostic factor of esophageal squamous cell carcinoma.Journal of Pathology of Nepal (2015) Vol. 5, 752-755

In this study, in order to obtain a novel biomaterials surface which possesses the functions of an anticoagulant, inhibiting smooth muscle proliferation and pro-endothelialisation simultaneously, a micro-patterned titanium dioxide (TiO(2))-nanotubes (P-TiO(2)-nanotubes) thin film was prepared on titanium (Ti) surface by photolithography combining with anodising method. The authors found that the P-TiO(2)-nanotubes could reduce platelet attachment and conformational change of fibrinogen (FGN) as well as promoting endothelial cells (ECs) growth compared with the TiO(2)-nanotubes. Notably, P-TiO(2)-nanotubes could significantly reduce smooth muscle cells (SMCs) proliferation compared with TiO(2)-nanotubes and TiO(2), and the ECs and SMCs cultured on the P-TiO(2)-nanotubes thin film were elongated, which was suggested to be beneficial for maintaining the cell function. Therefore it is suggested that the P-TiO(2)-nanotubes thin film can contribute more to biocompatible functions of regulating and coordinating the behaviour of platelets, ECs and SMCs.

Neuroendocrine tumors of the esophagus are derived from thediffuse neuroendocrine system in the gastrointestinal tract. Neuroendocrine tumors in the esophagus can be distinguished from othermesenchymal tumors by immunostaining for synaptophysin and chromogranin-A. Both carcinoid of the esophagus and adenocarcinoma ofthe esophagus are malignant tumors and considered to have a specifi cmolecular pathogenesis. This paper presents a rare case diagnosed ascarcinoid of the esophagus concomitant with an adenocarcinoma ofthe esophagus, a review of the literature is also presented here.

Background: Early assessment and management of cerebral edema and hematoma following aneurysmal subarachnoid hemorrhage (a-SAH) can significantly impact clinical cognitive outcomes. However, current clinical practices lack predictive models to identify early structural brain abnormalities affecting cognition. To address this gap, the authors propose the development of a predictive model termed the a-SAH Early Brain Edema/Hematoma Compression Neural (Structural Brain) Networks Score System (SEBE-HCNNSS). Methods: In this study, 202 consecutive patients with spontaneous a-SAH underwent initial computed tomography (CT) or MRI scans within 24 h of ictus with follow-up 2 months after discharge. Using logistic regression analysis (univariate and multivariate), the authors evaluated the association of clinically relevant factors and various traditional scale ratings with cognitive impairment (CI). Risk factors with the highest area under the curve (AUC) values were included in the multivariate analysis and least absolute shrinkage and selection operator (LASSO) analysis or Cox regression analysis. Results: A total of 177 patients were enrolled in the study, and 43 patients were classified with a high SEBE-HCNNSS grade (3-5). After a mean follow-up of 2 months, 121 individuals (68.36%) with a-SAH and three control subjects developed incident CI. The CT interobserver reliability of the SEBE-HCNNSS scale was high, with a Kappa value of 1. Furthermore, ROC analysis identified the SEBEHCNNSS scale (OR 3.322, 95% CI: 2.312-7.237, P=0.00025) as an independent predictor of edema, CI, and unfavorable prognosis. These results were also replicated in a validation cohort. Conclusion: Overall, the SEBE-HCNNSS scale represents a simple assessment tool with promising predictive value for CI and clinical outcomes post-a-SAH. Our findings indicate its practical utility as a prognostic instrument for risk evaluation after a-SAH, potentially facilitating early intervention and treatment. [ABSTRACT FROM AUTHOR]

Purpose: Osteoporosis is characterized by low bone mineral density (BMD) and high risk of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. This study was to identify PBM-expressed proteins significant for osteoporosis in Chinese Han elderly population (>65 years), and focused on two phenotypes of osteoporosis: low BMD and OF. Methods: Label-free quantitative proteomics was employed to profile PBM proteome and to identify differentially expressed proteins (DEPs) between OF (N=27) vs. non-fractured (NF, N=24) subjects and between low BMD (N=12) vs. high BMD (N=12) subjects in women. Western blotting (WB) was conducted to validate differential expression, and ELISA to evaluate translational value for secretory protein of interest. Results: We discovered 59 DEPs with fold change (FC)>1.3 (P<1×10-5), and validated the significant upregulation of pyruvate kinase isozyme 2 (PKM2) with osteoporosis (P<0.001). PKM2 protein upregulation with OF was replicated with PBM in men (P=0.04). Plasma PKM2 protein level was significantly elevated with OF in an independent sample (N=100, FC=1.68, P=0.01). Pursuant functional assays showed that extracellular PKM2 protein supplement not only promoted monocyte trans-endothelial migration, growth, and osteoclast differentiation (marker gene expression), but also inhibited osteoblast growth, differentiation (ALP gene expression), and activity. Conclusion: The above findings suggest that PKM2 protein is a novel osteoporosis-associated functional protein in Chinese Han elderly population. It may serve as a risk biomarker and drug target for osteoporosis. [ABSTRACT FROM AUTHOR]

Objectives: This study used the Disability-Adjusted Life Years (DALYs) to quantify the long-term trends for four cancers (oral cancer, colorectal cancer, breast cancer, and cervical cancer) that have undergone cancer screening in Taiwan. Methods: DALYs were calculated as the sum of Years of Life Lost (YLL) due to premature mortality and Years Lived with Disability (YLD). YLLs were determined using cancer-specific mortality data from the Health Promotion Administration (HPA), Ministry of Health and Welfare, based on age-specific life expectancy. YLDs were estimated by combining the incidence rates of the cancers, average disability durations, and disability weights, with data sourced from the Taiwan Cancer Registry. Results were expressed as DALYs per 100,000 population. Results: The disease burden has significantly increased over the past 12 years. Oral cancer rose from 263 to 368 DALYs per 100,000 population (40 % increase), colorectal cancer from 343 to 563 DALYs (64 % increase), and breast cancer from 446 to 782 DALYs (75 % increase), while the burden of cervical cancer decreased from 168 to 147 DALYs per 100,000 population from 2010 to 2017, showing a 13 % reduction. At the cancer stages, the impact of YLDs was mostly at cancer stage IV (oral cancer), cancer stage 0 (colorectal and cervical cancer), and stage I (breast cancer). Conclusion: Oral cancer increased by 40 %, colorectal cancer by 64 %, and breast cancer by 75 % from 2005 to 2017, while cervical cancer decreased by 13 % between 2010 and 2017. YLD contributions were highest in stage IV for oral cancer, stage 0 for colorectal and cervical cancers, and stage I for breast cancer. The highest DALYs consistently occurred in the 50–69 age group across all cancer types, highlighting the significant burden on middle-aged populations.

ABSTRACT Background Cancer is a leading cause of death globally, with significant variations in incidence and mortality rates among different cancer types and regions. In Taiwan, breast cancer (BC), cervical cancer (CxCa), colorectal cancer (CRC), and oral cancer (OC) are prevalent and have prompted government‐led screening programs to mitigate their impact. This study aims to assess the burden of these cancers at the county scale using disability‐adjusted life years (DALYs) as a metric, focusing on the years 2010, 2015, 2018, 2019, and 2020. Methods Data on cancer incidence, mortality, disability weights, and treatment outcomes were sourced from the Taiwan HPA, Ministry of Health and Welfare, and Taiwan Cancer Registry. Years of life lost (YLLs) and years lived with disability (YLDs) were calculated for each cancer, considering age, stage, and treatment. The correlation between cancer screening rates and disease burden also conducted. Results The analysis highlights significant trends in cancer mortality, incidence, and disease burden in Taiwan from 2010 to 2020. BC and CRC showed rising ASMR and DALYs rates, while CxCa experienced consistent declines. OC had a fluctuating pattern, particularly in eastern regions. YLLs contributed significantly to DALYs for all cancers, emphasizing premature mortality's role in the disease burden. Screening rates, particularly for BC and CxCa, correlated with changes in burden, with BC rates increasing and CxCa decreasing, reflecting the impact of preventive measures on cancer outcomes. Conclusions The findings underscore the importance of targeted interventions and evidence‐informed resource allocation to address regional differences in cancer burden in Taiwan.

Background The Menstrual Distress Questionnaire (MDQ) is a commonly used questionnaire that assesses various symptoms and distress associated with the menstrual cycle in women. However, the questionnaire has not been completely translated into Chinese with rigorous reliability and validity testing.Methods This study translated the Menstrual Distress Questionnaire Form Cycle (MDQC) from English into Chinese: MDQCC in two stages. First, it was translated forward and backward using Jones’ model; second, to test the validity and reliability, 210 Chinese-speaking women were recruited through online announcements and posters posted between June 2019 and May 2020. Expert validity, construct validity, convergent validity, and factorial validity were determined using content validity index (CVI), intraclass correlation coefficient (ICC), composite reliability (CR), and exploratory factor analysis, respectively. For concurrent criterion validity, MDQCC score was compared with three existing pain scales. Reliability was evaluated using internal consistency across items and two-week test-retest reliability over time.Results The CVI for content validity was .92. Item-CVI for expert validities among the 46 items ranged from .50 − 1; scale-CVI for the eight subscales, from .87 − 1; ICC, from .650 − .897; and CRs, from .303 − .881. Pearson correlation coefficients between MDQCC and short-form McGill pain questionnaire, present pain intensity, and visual analog scale scores were .640, .519, and .575, respectively. Cronbach’s α for internal consistency was satisfactory (.932). ICC for test-retest reliability was .852 for the entire MDQCC.Conclusion MDQCC was valid and reliable for Mandarin Chinese-speaking women. It can be used to evaluate female psychiatric symptoms related to the menstrual cycle in future work.

Abstract Background The fruit of Phyllanthus emblica L., a traditional medicine in China and India, is used to treat diabetes mellitus. Its water extract (WEPE) has demonstrated hypoglycemic effects in diabetic rats, but its mechanisms on glucose utilization and insulin resistance in skeletal muscle remain unclear. Therefore, this study aims to investigate the effects and underlying mechanisms of WEPE on glucose utilization and insulin resistance using C2C12 myotubes. Methods Effects of WEPE on glucose uptake, GLUT4 translocation, and AMPK and AKT phosphorylation were investigated in C2C12 myotubes and palmitate-treated myotubes. An AMPK inhibitor and siRNA were used to explore the mechanisms of WEPE. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay, and protein expression and GLUT4 translocation were assessed via western blotting. Results In normal myotubes, WEPE significantly stimulated glucose uptake and GLUT4 translocation to the plasma membrane at concentrations of 125 and 250 µg/mL. This was accompanied by an increase in the phosphorylation of AMPK and its downstream targets. However, both compound C and AMPK siRNA blocked the WEPE-induced GLUT4 translocation and glucose uptake. Moreover, pretreatment with STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, inhibited WEPE-induced AMPK phosphorylation and attenuated the WEPE-stimulated glucose uptake and GLUT4 translocation. In myotubes treated with palmitate, WEPE prevented palmitate-induced insulin resistance by enhancing insulin-mediated glucose uptake and AKT phosphorylation. It also restored the insulin-mediated translocation of GLUT4 from cytoplasm to membrane. However, these effects of WEPE on glucose uptake and GLUT4 translocation were blocked by pretreatment with compound C. Conclusions WEPE significantly stimulated basal glucose uptake though CaMKKβ/AMPK pathway and markedly ameliorated palmitate-induced insulin resistance by activating the AMPK pathway in C2C12 myotubes.

Convolutional neural networks typically employ convolutional layers for feature extraction and pooling layers for dimensionality reduction. However, conventional pooling methods often lead to a loss of critical feature information, particularly in images with diverse content, such as vehicle images. This study proposes a novel approach to address these problems: a convolutional neural network with type-2 fuzzy-based pooling (CNN-T2FP). This innovative pooling method utilizes type-2 fuzzy membership functions to effectively manage local imprecision in feature maps. Compared with type-1 fuzzy pooling, which only addresses uncertainty to a certain extent, type-2 fuzzy pooling exhibits improved adaptability to different image contents. The experimental results of this study revealed that the CNN-T2FP achieved average accuracies of 92.14% and 93.34% on two datasets, surpassing the performance of existing pooling techniques. In addition, t-distributed stochastic neighbor embedding plots and feature visualization maps further highlighted the potential of type-2 fuzzy-based pooling to overcome the limitations of conventional pooling methods and enhance the performance of convolutional neural networks in image analysis tasks.

Abstract The associations between people with severe mental illnesses (SMI) and the risks of stroke, suicide, and death remain unclear. We examined healthcare service usage among adults with and without SMI and explored the risk of stroke, suicide, and death. We divided 18–80-year-old adults with SMI into catastrophic and non-catastrophic illness groups. These groups were subjected to a 1:5:5 propensity score matching with people without SMI. Data on demographic characteristics, economic factors, environmental factors, comorbid conditions, self-injury behavior, the number of outpatients and ED visits, and hospitalization were collected. The primary outcomes were risks of stroke, suicide, and death. We included 19,570 people with catastrophic SMI, 97,850 with non-catastrophic SMI, and 97,850 controls. Patients with SMI, especially those with catastrophic illnesses, had higher stroke risk, suicide, and death than those without SMI. People with SMI used health services more frequently than those without SMI. Patients with a history of hospitalization or ED access had a higher risk of stroke, suicide, and death. Our data indicate that special attention should be given to patients with SMI, particularly those with a history of healthcare service utilization, such as through more extended hospital stays with high-intensity interventions.

Successful production of metallic selective laser melting components requires a quality assurance process that can effectively and nondestructively assess internal defects. Ultrasound testing has emerged as a valuable modality for defect identification as well as the characterization of microstructural and material properties. In this study, a comprehensive quality assessment approach was developed, leveraging quantitative ultrasound parameters, images, and image texture analysis. The evaluation focused on Inconel 718 selective laser melting components manufactured using diverse combinations of process parameters. The investigation involved examining the correlation between ultrasound parameters, image texture features, and the overall quality of the fabricated components. To validate the findings obtained through ultrasound testing, micro-computed tomography was employed. The experimental results provided evidence that the ultrasound parameters and image texture features successfully detected nonhomogeneous microstructures present within the selective laser melting components. Notably, the speed of sound and attenuation exhibited a positive correlation of 0.64 and 0.74, respectively, with porosity, indicating their potential as indicators of porosity. Furthermore, image texture features such as entropy, contrast, and homogeneity demonstrated high correlations ( $R^{2}\gt 0.7$ ) with the quality of the components. Consequently, these identified features hold promising potential for aiding in the selection of optimal process parameters and the prediction of porosity in future research.

Abstract Ovarian cancer (OC) represents one of the most detrimental gynecological malignancies. RNA‐binding protein eukaryotic translation initiation factor 4A isoform 3 (EIF4A3) is well‐regarded as a definitive oncogene that contributes to the development of multiple malignant tumors. This study sought to elucidate the molecular mechanism of EIF4A3 in OC growth and aerobic glycolysis by regulation of pyruvate dehydrogenase kinase 4 (PDK4) mRNA stability. We determined the EIF4A3 and PDK4 expression levels in OC cell lines and normal ovarian epithelial cells, and subsequently evaluated the cell viability and colony formation by cell counting kit‐8 and colony formation assays. The degree of cell aerobic glycolysis was evaluated by measurements of lactic acid production, glucose intake, adenosine triphosphate level, extracellular oxygen consumption, and protein levels of pyruvate kinase isozymes M2 and hexokinase‐2. Afterwards, we verified the binding of EIF4A3 and PDK4 mRNA via RNA immunoprecipitation, and determined the mRNA stability after actinomycin D treatment. Finally, a series of rescue experiments was performed with pcDNA3.1‐PDK4. EIF4A3 and PDK4 were upregulated in OC cells. Silencing EIF4A3 obstructed cell proliferation and aerobic glycolysis, while the same was annulled by EIF4A3 overexpression. Mechanically, EIF4A3 could bind to PDK4 mRNA to stabilize its mRNA and upregulate its protein levels. PDK4 overexpression inverted the inhibitory role of silencing EIF4A3 in proliferation and aerobic glycolysis. Overall, our findings highlighted that EIF4A3 induced OC progression by stabilizing PDK4 mRNA.

The successful production of metallic workpieces through selective laser melting requires a quality assurance process that can effectively and nondestructively assess internal defects. Ultrasound testing is a nondestructive testing modality that can be used to identify defects and characterize the microstructure and properties of a material. Moreover, developments in computer vision techniques have led to the increased use of neural networks (NNs) in quality assurance processes. Therefore, a novel multiscale convolutional fuzzy NN (MCFNN) that uses ultrasound images as input data was developed in this study to automatically evaluate Inconel 718 workpieces fabricated through selective laser melting under various combinations of process parameters. The average accuracy, precision, recall, F1 score, and number of required parameters for the developed MCFNN were comparable to those of state-of-the-art models. Moreover, several concatenation methods, multiscale fusion strategies, and fuzzy inference systems were implemented in the developed MCFNN for performance comparison. Subsequently, the workpieces were examined through microcomputed tomography to verify the results obtained using ultrasound images. The experimental results indicated that among the compared models, the MCFNN achieved the highest average accuracy (91.44% ± 4.73%), precision (92.74% ± 3.79%), recall (91.44% ± 4.73%), and F1 score (91.35% ± 4.82%) and required the fewest parameters (107,138). The experimental results demonstrate that the developed MCFNN has high potential for implementation in the embedded devices of portable ultrasound scanning systems.

Abstract Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40–59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756–0.797; validation AUC 0.766, 0.741–0.790). The validation cohort was stratified as low-risk (score 0–8), intermediate-risk (score 9–13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

Abstract Background Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients. Method This is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix. Results The cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p

Abstract Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known to protect tumour cells from ferroptosis upon cysteine starvation through transamination. However, whether amino acids‐produced metabolites participate in ferroptosis independent of the cysteine pathway is largely unknown. Here, the authors show that the tryptophan metabolites serotonin (5‐HT) and 3‐hydroxyanthranilic acid (3‐HA) remarkably facilitate tumour cells to escape from ferroptosis distinct from cysteine‐mediated ferroptosis inhibition. Mechanistically, both 5‐HT and 3‐HA act as potent radical trapping antioxidants (RTA) to eliminate lipid peroxidation, thereby inhibiting ferroptotic cell death. Monoamine oxidase A (MAOA) markedly abrogates the protective effect of 5‐HT via degrading 5‐HT. Deficiency of MAOA renders cancer cells resistant to ferroptosis upon 5‐HT treatment. Kynureninase (KYNU), which is essential for 3‐HA production, confers cells resistant to ferroptotic cell death, whereas 3‐hydroxyanthranilate 3,4‐dioxygenase (HAAO) significantly blocks 3‐HA mediated ferroptosis inhibition by consuming 3‐HA. In addition, the expression level of HAAO is positively correlated with lipid peroxidation and clinical outcome. Together, the findings demonstrate that tryptophan metabolism works as a new anti‐ferroptotic pathway to promote tumour growth, and targeting this pathway will be a promising therapeutic approach for cancer treatment.

ObjectiveTo investigate the short-term effect of music therapy combined with binaural frequency difference therapy on patients with consciousness disorder.Materials and methodsNinety patients with definite diagnosis of disorders of consciousness (DOC) were selected. These patients were randomly divided into control group, experiment 1 group and experiment 2 group, with 30 patients in each group. The control group was treated with routine clinical treatment and rehabilitation. In experiment 1 group, music therapy was added to the control group. In experimental group 2, music therapy combined with binaural α frequency difference therapy was added to the control group. All patients were assessed before and after 30 treatments. The assessment items included Glasgow Coma Scale (GCS), Coma Recovery Scale revised (CRS-R), electroencephalogram (EEG), upper somatosensory evoked potential (USEP), and brainstem auditory evoked potential (BAEP).ResultsBefore treatment, there were no significant differences in GCS score, CRS-R score, USEP, BAEP, and EEG scores among the three groups (P > 0.05). After 30 times of treatment, GCS score, CRS-R score, USEP, BAEP, and EEG scores in 3 groups were significantly higher than those before treatment (P < 0.05), and experimental group 2 >experimental group 1 >control group (P < 0.05). And the consciousness rate of experimental group 2 was better than experimental group 1, experimental group 1 was better than the control group and the difference was statistically significant (P < 0.05).ConclusionMusic therapy combined with binaural α frequency difference therapy is more effective in stimulating DOC patients.

Abstract Background Alisol A 24-acetate (AA-24-a), one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., exhibits multiple biological activities including hypolipidemic activity. However, its effect on lipid metabolism in adipocytes remains unclear. The present study aimed to clarify the effect of AA-24-a on adipocyte lipolysis and to determine its potential mechanism of action using 3 T3-L1 cells. Methods We assayed the release of glycerol into culture medium of 3 T3-L1 cells under treatment with AA-24-a. Protein and mRNA expression and phosphorylation levels of the main lipases and kinases involved in lipolysis regulation were determined by quantitative polymerase chain reaction and western blotting. Specific inhibitors of protein kinase A (PKA; H89) and extracellular signal-regulated kinase (ERK; PD98059), which are key enzymes in relevant signaling pathways, were used to examine their roles in AA-24-a-stimulated lipolysis. Results AA-24-a significantly stimulated neutral lipolysis in fully differentiated adipocytes. To determine the underlying mechanism, we assessed the changes in mRNA and protein levels of key lipolysis-related genes in the presence or absence of H89 and PD98059. Both inhibitors reduced AA-24-a-induced lipolysis. Moreover, pretreatment with H89 attenuated AA-24-a-induced phosphorylation of hormone-sensitive lipase at Ser660, while pretreatment with PD98059 attenuated AA-24-a-induced downregulation of peroxisome proliferator-activated receptor-γ and perilipin A. Conclusions Our results indicate that AA-24-a promoted neutral lipolysis in 3 T3-L1 adipocytes by activating PKA-mediated phosphorylation of hormone-sensitive lipase and ERK- mediated downregulation of expression of perilipin A.

BackgroundStudies comparing mental disorder risks between women with breast cancer and cervical cancer are lacking. This study compared risks of developing anxiety and depression between women with breast cancer (BC cohort) and women with cervical cancer (CC cohort) using insurance claims data of Taiwan.MethodsFrom the 2000 to 2016 data, we identified a BC cohort and BC controls (N = 96,862) and a CC cohort and CC controls (N = 26,703), matched by propensity scores. Incident mental disorders and the Cox method estimated the related cancer cohort to control cohort hazard ratios (HRs), and 95% confidence intervals (CIs) were estimated by the end of 2016.ResultsCompared to the CC cohort, the BC cohort had slightly higher incident anxiety (15.9 versus 15.5 per 1,000 person-years) and depression (6.92 vs. 6.28 per 1,000 person-years). These mental disorders were higher in respective cancer cohorts than controls. The BC cohort to BC control adjusted HRs of anxiety and depression were 1.29 (95% CI = 1.25–1.33) and 1.78 (95% CI = 1.69–1.87), respectively. The corresponding adjusted HRs for the CC cohort were 1.12 (95% CI = 1.06–1.18) and 1.29 (95% CI = 1.18–1.41). The combined incidence rates of both disorders were 1.4-fold greater in the BC cohort than in BC controls (22.8 vs. 15.8 per 1,000 person-years), and 1.2-fold greater in the CC cohort than in the CC controls (21.7 vs. 18.3 per 1,000 person-years).ConclusionWomen with breast cancer or cervical cancer are at an elevated likelihood of developing anxiety and depression disorders. These incident disorders are slightly higher in those with breast cancer.