Chemoresistance in acute myeloid leukemia: An alternative single-cell RNA sequencing approach.

Our previous study demonstrated that myc, mitochondrial oxidative phosphorylation, mTOR, and stemness are independently responsible for chemoresistance in acute myeloid leukemia (AML) cells. This study aimed to identify potential mechanisms of chemoresistance of the "7 + 3" induction in AML by using a single-cell RNA sequencing (scRNA-seq) approach. In the present study, 13 untreated patients with de novo AML were enrolled and stratified into two groups: complete remission (CR; n = 8) and non-CR (n = 5). Single-cell RNA sequencing was used to analyze genetic profiles of 28,950 AML cells from these patients; results were validated using a previously published bulk RNA-seq dataset. Our study results showed chemoresistant AML cells had premature accumulation during early hematopoiesis. Hematopoietic stem cell-like cells from the non-CR group expressed more leukemic stem cell markers (CD9, CD82, IL3RA, and IL1RAP) than those from the CR group. Chemoresistant progenitor cells had impaired myeloid differentiation owing to early arrest of hematopoiesis. Notably, AML cells analyzed by scRNA-seq and bulk RNA-seq harbored a comparable myeloid lineage cell fraction, which internally validated our results. Using the TCGA database, our analysis demonstrated that patients with AML with higher expression of chemoresistant genetic markers (IL3RA and IL1RAP) had a worse overall survival (p < 0.01 for IL3RA; p < 0.05 for IL1RAP). In conclusion, AML cells responsive and resistant to the "7 + 3" induction were derived from a diverse cancerous hematopoietic stem cell population, as indicated by the specific genetic biomarkers obtained using scRNA-seq approach. Furthermore, arrest of hematopoiesis was shown to occur earlier in chemoresistant AML cells, furthering the current understanding of chemoresistance in AML.

AGR2 expression as a predictive biomarker for therapy response in esophageal squamous cell carcinoma.

Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we aimed to identify for tumor therapy response a biomarker based on RNA sequencing. We collected endoscopic biopsies of 32 ESCC patients, who were divided according to nCRT response, into two groups: the complete response group (n = 13) and the non-complete response group (n = 19). RNA-sequencing data showed that 464 genes were differentially expressed. Increased in non-complete response group, 4 genes increased expressions were AGR2 (anterior gradient 2), GADD45B (growth arrest and DNA damage inducible beta), PPP1R15A (protein phosphatase 1 regulatory subunit 15A) and LRG1 (leucine rich alpha-2-glycoprotein 1). The areas under the curve (AUC) of the AGR2 gene was 0.671 according to read counts of RNA-seq and therapy response of nCRT. In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy.

Quality of life and symptom distress after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/ HIPEC) for peritoneal surface malignancy can effectively control the disease, however it is also associated with adverse effects which may affect quality of life (QoL). AIM: To investigate early perioperative QoL after CRS/HIPEC, which has not been discussed in Taiwan. METHODS: This single institution, observational cohort study enrolled patients who received CRS/HIPEC. We assessed QoL using the Taiwanese version of the MD Anderson Symptom Inventory (MDASI-T) and European Organization Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Participants completed the questionnaires before CRS/HIPEC (S1), at the first outpatient follow-up (S2), and 3 mo after CRS/HIPEC (S3). RESULTS: Fifty-eight patients were analyzed. There was no significant perioperative difference in global health status. Significant changes in physical and role functioning scores decreased at S2, and fatigue and pain scores increased at S2 but returned to baseline at S3. Multiple regression analysis showed that age and performance status were significantly correlated with QoL. In the MDASI-T questionnaire, distress/feeling upset and lack of appetite had the highest scores at S1, compared to fatigue and distress/feeling upset at S2, and fatigue and lack of appetite at S3. The leading interference items were working at S1 and S2 and activity at S3. MDASI-T scores were significantly negatively correlated with the EORTC QLQ-C30 results. CONCLUSION: QoL and symptom severity improved or returned to baseline in most categories within 3 mo after CRS/HIPEC. Our findings can help with preoperative consultation and perioperative care.

Lipid Droplets in Lung Cancers Are Crucial for the Cell Growth and Starvation Survival.

For rapid and unlimited cell growth and proliferation, cancer cells require large quantities of nutrients. Many metabolic pathways and nutrient uptake systems are frequently reprogrammed and upregulated to meet the demand from cancer cells, including the demand for lipids. The lipids for most adult normal cells are mainly acquired from the circulatory system. Whether different cancer cells adopt identical mechanisms to ensure sufficient lipid supply, and whether the lipid demand and supply meet each other, remains unclear, and was investigated in lung cancer cells. Results showed that, despite frequent upregulation in de novo lipogenesis and the lipid transporter system, different lung cancer cells adopt different proteins to acquire sufficient lipids, and the lipid supply frequently exceeds the demand, as significant amounts of lipids stored in the lipid droplets could be found within lung cancer cells. Lipid droplet surface protein, PLIN3, was found frequently overexpressed since the early stage in lung cancer tissues. Although the expression is not significantly associated with a specific gender, age, histology type, disease stage, and smoking habit, the frequently elevated expression of PLIN3 protein indicates the importance of lipid droplets for lung cancer. These lipid droplets are not only for nutrient storage, but are also crucial for tumor growth and proliferation, as well as survival in starvation. These results suggest that manipulation of lipid droplet formation or TG storage in lung cancer cells could potentially decrease the progression of lung cancer. Further exploration of lipid biology in lung cancer could help design novel treatment strategies.

Identification of a novel norketamine precursor from seized powders: 2-(2-chlorophenyl)-2-nitrocyclohexanone.

The identification of new psychoactive substances (NPSs) and their precursors is crucial to understand trends in NPSs so that they can be regulated before they pose a serious threat to human health. In this case, 24 bags containing approximately 600 kg of yellow powder were seized; the smugglers had been monitored for 3 years by the officers of Taiwan's Ministry of Justice Investigation Bureau. A handheld Raman analyzer yielded a positive result for N-boc norketamine; thus, the seized powder was sent to this laboratory for confirmation through gas chromatography-mass spectrometry, liquid chromatographyhigh-resolution mass spectrometry, proton nuclear magnetic resonance (1H NMR), carbon-13 nuclear magnetic resonance (13C NMR), two-dimensional correlation NMR measurements (2D_COSY), heteronuclear single-quantum correlation NMR measurements (2D_HSQC), and single-crystal X-ray diffraction. This thermolabile powder was subsequently identified as 2-(2-chlorophenyl)- 2-nitrocyclohexanone (2-CPNCH), which can be employed as a precursor for the synthesis of norketamine and is available commercially. Norketamine has similar pharmacological effects to ketamine and phencyclidine but is not regulated in many countries. In this case report, mass fragments, 1H NMR, 13C NMR, 2D_COSY, and 2D_HSQC data of 2-CPNCH are presented; moreover, how criminals exploit the loopholes in the law for conducting unauthorized drug manufacturing is discussed.

Assessment of total and regional bone mineral density using bioelectrical impedance vector analysis in elderly population.

This study aimed to investigate the relationship between bone mineral density (BMD) and height-adjusted resistance (R/H), reactance (Xc/H) and phase angle (PhA). A total of 61 male and 64 female subjects aged over 60 years were recruited from middle Taiwan. The R and Xc were measured using Bodystat Quadscan 4000 at a frequency of 50 kHz. BMD at the whole body, L2-L4 spine, and dual femur neck (DFN), denoted as BMDTotal, BMDL2-L4, and BMDDFN, were calculated using a Hologic DXA scanner. The R-Xc graph was used to assess vector shift among different levels of BMD. BMD was positively correlated with Xc/H and negatively correlated with R/H (p < 0.001). The General Linear Model (GLM) regression results were as follows: BMDTotal = 1.473-0.002 R/H + 0.007 Xc/H, r = 0.684; BMDL2-L4 = 1.526-0.002 R/H + 0.012 Xc/H, r = 0.655; BMDDFN = 1.304-0.002 R/H + Xc/H, r = 0.680; p < 0.0001. Distribution of vector in the R-Xc graph was significantly different for different levels of BMDTotal, BMDL2-L4 and BMDDFN. R/H and Xc/H were correlated with BMD in the elderly. The linear combination of R/H and Xc/H can effectively predict the BMD of the whole body, spine and proximal femur, indicating that BIVA may be used in clinical and home-use monitoring tool for screening BMD in the elderly in the future.

Leveraging advances in immunopathology and artificial intelligence to analyze in vitro tumor models in composition and space.

Cancer is the leading cause of death worldwide. Unfortunately, efforts to understand this disease are confounded by the complex, heterogenous tumor microenvironment (TME). Better understanding of the TME could lead to novel diagnostic, prognostic, and therapeutic discoveries. One way to achieve this involves in vitro tumor models that recapitulate the in vivo TME composition and spatial arrangement. Here, we review the potential of harnessing in vitro tumor models and artificial intelligence to delineate the TME. This includes (i) identification of novel features, (ii) investigation of higher-order relationships, and (iii) analysis and interpretation of multiomics data in a (iv) holistic, objective, reproducible, and efficient manner, which surpasses previous methods of TME analysis. We also discuss limitations of this approach, namely inadequate datasets, indeterminate biological correlations, ethical concerns, and logistical constraints; finally, we speculate on future avenues of research that could overcome these limitations, ultimately translating to improved clinical outcomes.

Prediction of Nonalcoholic Fatty Liver Disease by Anthropometric Indices and Bioelectrical Impedance Analysis in Children.

Background: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in children and is associated with obesity. Objectives: To test whether addition of bioelectrical impedance analysis (BIA) parameters to BMI and anthropometric indices improves the prediction performance of NAFLD than BMI z score (BAZ) alone. Methods: This cross-sectional study recruited 933 children 6-12 years of age for anthropometric measure, BIA, and liver ultrasound. Prediction models of the BAZ, anthropometric, and BIA sets were built in children with obesity using machine learning algorithms. Results: Prevalences of NAFLD were 44.4% (59/133) and 20% (12/60) in boys and girls with obesity, respectively. In both sexes, BAZ set performed worst; adding anthropometric indices into the model improved the model performance, whereas BIA parameters were the best approach for predicting NAFLD. The best result in boys achieved had an accuracy of 75.9% and area under receiver operating characteristic curve of 0.854. In girls, the best result achieved had an F-measure score of 0.615, Matthews correlation coefficient of 0.512, and area under precision-recalled curve of 0.697. Conclusion: BIA is a simple and highly precise tool that yields better NAFLD prediction model than anthropometric indices, and much better performance than BAZ. This study suggests BIA as a potential predictor for pediatric NAFLD.

Adding Value of MRI over CT in Predicting Peritoneal Cancer Index and Completeness of Cytoreduction.

BACKGROUND: This study aimed to investigate the adding value of MRI over CT for preoperative cytoreductive surgery with hyperthermic intraperitoneal chemotherapies (CRS/HIPEC). METHODS: Imaging and intraoperative peritoneal cancer index (PCI) were calculated in 62 patients with peritoneal metastasis. Predictive models for the completeness of cytoreductive score using PCI data were established using decision tree algorithms. RESULTS: In gastric cancer patients, a large discrepancy and poor agreement was appreciated between CT and surgical PCI, and a nonsignificant difference was noted between MRI and surgical PCI. In colon cancer patients, a better agreement and higher correlation with a smaller error was observed in PCI score using MRI than in that using CT. However, the addition of MRI to CT was limited for appendiceal and ovarian cancer patients. For predicting incomplete cytoreduction, CT models yielded inadequate accuracy while MRI models were more accurate with fair discrimination ability. CONCLUSIONS: CT was suitable for estimating PCI and surgery outcome in appendiceal and ovarian cancer patients, while further MRI in addition to CT was recommended for colon and gastric cancer patients. However, for classifying patients with peritoneal carcinomatosis into complete and incomplete cytoreduction, MRI was more effective than CT.

Effects of Laser Acupuncture Therapy for Patients With Inadequate Recovery From Bell's Palsy: Preliminary Results From Randomized, Double-Blind, Sham-Controlled Study.

Introduction: Inadequate recovery from Bell's palsy exists in a third of patients and results in physical and social impairments. The controversial nature of existing medical treatment options means that novel, alternative approaches are needed. In basic and clinical studies, low-level laser therapy (LLLT) has proven successful in regenerating peripheral nerves. Laser acupuncture therapy (LAT) is a rapidly growing treatment modality; however, its effectiveness for treating chronic Bell's palsy is unknown. The feasibility of this innovative approach is the focus of this pilot study. Methods: A two-armed, parallel, randomized, investigator-subject-assessor-blinded, sham-controlled pilot study was conducted, and 17 eligible subjects were randomly allocated to either LAT (n=8) or sham LAT (n=9). The LAT group received three treatments each week for six weeks (18 sessions), while the sham LAT group received the same procedure but with a sham laser device. The change from baseline to week 6 in the social subscale of the Facial Disability Index (FDI) was the primary outcome. Secondary outcomes were changes in the House-Brackmann facial paralysis scale (HB), the Sunnybrook facial grading system (SB) and a stiffness scale at weeks 3 and 6. Results: A significant difference was shown in the HB score (P=0.0438) between baseline and week 3 and borderline significance was observed in both SB and stiffness scores from baseline to week 6 (P=0.0598 and P=0.0980 respectively). There was no significant difference in the FDI score between baseline and week 6. Conclusion: To the best of our knowledge, this clinical trial is the first such investigation on this topic. Our findings suggest that using LAT may have clinical effects on long-term complications of Bell's palsy and justify further large-scale studies.

Acupuncture Decreased the Risk of Coronary Heart Disease in Patients with Osteoarthritis in Taiwan: A Nationwide Matched Cohort Study.

Objectives: Patients with osteoarthritis (OA) are more likely to develop coronary heart disease (CHD) than the general population. Acupuncture is commonly used in OA patients; however, the therapeutic effect of acupuncture on the risk of CHD in patients with OA and the association between OA patients and their risk to develop CHD in Taiwan are unknown. We investigated the risk of CHD according to acupuncture use in OA patients and compared it with the general population. Design: Records obtained from Taiwan's National Health Insurance Research Database identified 84,773 patients with OA, which were compared with 727,359 patients without OA diagnosis. Five thousand forty-six of those who met study inclusion criteria had 1:1 frequency matching and were categorized as OA-acupuncture cohort (n = 1682), OA nonacupuncture cohort (n = 1682), and non-OA cohort (n = 1682). Cox proportional hazards regression analysis determined the risk of CHD, which was defined as the study main outcome. Therapeutic effects of acupuncture and medical expenditure were also analyzed. Results: OA nonacupuncture cohort had 3.04 higher risk to develop CHD compared with OA-acupuncture cohort (95% confidence interval [CI], 2.54-3.63, p < 0.001) and non-OA cohort had 1.88 higher risk to develop CHD compared with OA-acupuncture cohort (95% CI, 1.52-2.32, p < 0.001). In subgroup analyses, OA patients treated with both acupuncture and oral steroids were at significantly lower risk of CHD compared with those who used neither (adjusted hazard ratio 0.34; 95% CI, 0.22-0.53), and OA patients treated with acupuncture had the lowest medical expenditure in a follow-up time of 6 months, and 3 and 5 years. Conclusion: This is the first large-scale investigation in Taiwan that shows the association between OA and CHD and the beneficial effects of acupuncture in OA patients, and their associated risk to develop CHD. Our results may provide valuable information for health policy decision making. Further randomized controlled trials are needed to confirm these observational findings.

Risk factors of acute renal impairment after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Acute renal impairment (ARI) is a major complication after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for cancer patients with peritoneal metastases. This study aimed to investigate the incidence and identify the risk factors of post-HIPEC creatinine increased. METHODS: From April 2015 to December 2019, demographic and perioperative data of 169 patients undergoing CRS/HIPEC with a preoperative creatinine level <1.5 mg/dL were retrospectively reviewed. Renal impairment was defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. The risk factors of creatinine increased were analyzed using univariate and multiple logistic regression analyses. RESULTS: Among the 169 enrolled patients, 21 (12.4%) had postoperative creatinine increased (ARI group) and 148 (87.6%) did not (non-ARI group). Significantly more of the ARI group received a cisplatin HIPEC regimen than the non-ARI group (71.4 vs. 37.8%, p = 0.004). Multiple logistic regression analysis revealed that the patients who received a cisplatin HIPEC regimen (adjusted odds ratio [AOR] = 11.38, p < 0.001) and peritoneal dialysis solution as HIPEC perfusate (AOR = 7.07, p = 0.002) were more likely to develop post-HIPEC creatinine increased. CONCLUSIONS: Identifying the risk factors of post-HIPEC creatinine increased can help to improve patient selection, a dose of HIPEC regimens modification and perioperative care. We also identified the detrimental renal effect of peritoneal dialysis solution as HIPEC perfusate. More prospective studies are warranted to confirm these findings.

Prediction and discrimination of skeletal muscle function by bioelectrical impedance vector analysis using a standing impedance analyzer in healthy Taiwanese adults.

BACKGROUND: Bioelectrical impedance vector analysis (BIVA) has been used for prediction of muscle performance. However, little is known about BIVA in Asian adults, and even less is known about using standing BIVA devices. Standing impedance analyzer allows quicker and more convenient way to gather data than conventional supine analyzer and is more suitable for clinical practice. This study aimed to investigate the relations between muscle function and BIVA parameters measured with a standing impedance analyzer in healthy Taiwanese adults. METHODS: A total of 406 healthy subjects (age 34.5 ± 17.3 years, body mass index 24.1 ± 4.1 kg/m2) were recruited for BIVA and handgrip strength (HGS) measurements. Impedance parameters, including resistance (R) and reactance (Xc), were measured and normalized to body size by dividing by height (H). The resulting phase angle (PhA) was calculated. HGS in the dominant, left, and right hands were referred to as HGSDH, HGSLH, and HGSRH, respectively. All subjects were divided into 5 grades according to HGS. RESULTS: Muscle strength in the dominant, right, and left arms was correlated with variables in the order of sex, weight, age, height, Xc/H, and R/H (all, p < 0.001). Using all 6 variables, the determination coefficients were 0.792, 0.782, and 0.745, respectively, whereas the standard errors of estimates were 56.89, 58.01, and 56.67 N for HGSDH, HGSLH, and HGSRH, respectively. HGS was positively correlated with PhA, and negatively correlated with Xc/H and R/H. CONCLUSIONS: BIVA parameters measured with a standing impedance analyzer and anthropometric variables can predict and discriminate muscle function with good performance in healthy Asian adults.

A 16-Year Study on Incidence and Progression of Diseased Sphenoethmoidal (Onodi) Cell.

Traumatic operative injury of the optic nerve in an endoscopic sinus surgery may cause immediate or delayed blindness. It should be cautioned when operating in a sphenoethmoidal cell, or known as Onodi cell, with contact or bulge of the optic canal. It remains unclear how frequent progression to visual loss occurs and how long it progresses to visual loss because of a diseased sphenoethmoidal cell. Research to discuss these questions is expected to help decision making to treat diseased sphenoethmoidal cells. From July 2001 to June 2017, 216 patients received conservative endoscopic sinus surgery without opening a diseased sphenoethmoidal cell. We used their computed tomography images of paranasal sinuses to identify diseased sphenoethmoidal cells that could be associated with progression to visual loss. Among the 216 patients, 52.3% had at least one sphenoethmoidal cell, and 14.8% developed at least one diseased sphenoethmoidal cell. One patient developed acute visual loss 4412 days after the first computed tomography. Our results show that over half of the patients have a sphenoethmoidal cell but suggest a rare incidence of a diseased sphenoethmoidal cell progressing to visual loss during the follow-up period.

Added values of DXA-derived visceral adipose tissue to discriminate cardiometabolic risks in pre-pubertal children.

BACKGROUND: The new generation of dual energy X-ray absorptiometry (DXA) scanners provide visceral adipose tissue (VAT) estimates by applying different algorithms to the conventional DXA-derived fat parameters such as total fat, trunk fat and android fat for the same image data. OBJECTIVE: This cross-sectional study aimed to investigate whether VAT estimates from Hologic scanners are better predictors of VAT than conventional DXA parameters in pre-pubertal children, and to explore the discrimination ability of these VAT methods for cardiometabolic risks. METHODS: Healthy pre-pubertal children aged 7-10 years were recruited for basic anthropometric, DXA and magnetic resonance imaging (MRI) measurements. Laboratory tests included lipid profile, glycaemic tests and blood pressure. RESULTS: All VAT methods had acceptable to excellent performance for the diagnosis of dyslipidaemia (area under the curve [AUC] = 0.753-0.837) and hypertensive risk (AUC = 0.710-0.821) in boys, but suboptimal performance for these risks in girls, except for VAT by MRI in the diagnosis of dyslipidaemia. In both sexes, all VAT methods had no or poor discrimination ability for diabetes risk. CONCLUSIONS: DXA-derived VAT estimates are very highly correlated with standard methods but has equivalent discrimination abilities compared to the existing DXA-derived fat estimates.

Age-Specific Breast Density Changes in Taiwanese Women: A Cross-Sectional Study.

Breast density is a risk factor for breast cancer. This study explored distribution of mammographic density quantitatively and qualitatively in a wide age range of Taiwanese women. Subjects with negative and benign mammographic findings were included. According to the Breast Imaging Reporting and Data System, the proportion of extremely dense breasts declined from 58.0% in women < 30 years to 1.9% in women > 74 years. More than 80% of mammograms in women < 55 years old were classified as extremely or heterogeneously dense, while the proportion of dense breasts was still high in women aged 60-64 years (59.3%). The absolute dense area of the breast declined from 35.8% in women < 30 years to 18.5% in women > 74 years. The correlation between breast density and age was significant, with and without controlling for the effect of body composition (p < 0.001), implying that the relationship between breast density and age was not wholly related to body composition. In conclusion, the higher breast density in Taiwanese women aged 60-64 years was comparable to that of Western women aged 40-44 years in the literature. This suggests that breast cancer screening using mammography may be more challenging for Asian women than for Western women of the same age.

Performance of Bioelectrical Impedance Analysis in the Estimation of Bone Mineral Content in Healthy Children Aged 6-12 Years.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a widely available tool which provides mineral estimate. However, BIA is not currently recognized as a bone mineral measuring method. This study aimed to explore the ability of BIA to predict bone mineral content (BMC) in children, using dual-energy X-ray absorptiometry as a gold standard. METHODS: Healthy children aged 6-12 years (n = 176) were recruited for BIA and dual-energy X-ray absorptiometry measurements. Predictive models were generated using basic indices (age, height, weight, waist circumference, hip circumference, etc.) and BIA parameters (minerals, fat mass, and fat free mass). RESULTS: The root-mean-square deviation and R2 for the total BMC predictive model were 0.089 kg and 0.926, respectively using height and weight as predictors whereas 0.113 kg and 0.886, respectively using minerals by BIA. The root-mean-square deviation and R2 for the subtotal BMC predictive model were 0.080 kg and 0.935, respectively using height and weight as predictors whereas 0.098 kg and 0.906, respectively using minerals by BIA. The best predictive models included basic indices and BIA parameters as predictors, but they had only slightly better performance over simple models. CONCLUSIONS: Mineral content by BIA was good predictor of total and subtotal BMC in healthy children but with similar overall model performance compared to basic indices. More complex models combined all the predictive variables gave better prediction power, but of little improvement to these simple models. The BIA instrument does not appear to be useful in estimating BMC in healthy children as basic indices are more widely available measures but provide comparable performance. Future studies are needed to determine the clinical usefulness of the more complex prediction model in children with disease or children in other subgroups.

Molecular profiling of thymoma with myasthenia gravis: Risk factors of developing myasthenia gravis in thymoma patients.

OBJECTIVE: Thymoma is a rare epithelial tumor arising from the thymus in the anterior mediastinum. Nearly 50% of patients with thymoma develop myasthenia gravis, which is an indication of a poor long-term prognosis. Here, we identified specific and effective molecular markers for predicting in the development of myasthenia gravis patients with thymoma. MATERIAL AND METHODS: We investigated molecular profiling based on RNA-sequencing (RNA-seq) for myasthenia gravis development in patients with thymoma. RNA was extracted from 34 patients with thymoma, 16 of whom had myasthenic and 18 of whom did not, and transcriptome profiles were analyzed through next-generation sequencing. RESULTS: We discovered 140 differential expressed genes associated with myasthenia gravis in thymoma patients. The four genes, hypoxia-inducible factor 3 alpha (HIF3A), insulin-like growth factor-binding protein 1, pyruvate dehydrogenase kinase, and Krüppel-like factor 15 were differentially expressed in patients with thymoma who has myasthenia gravis and were validated by quantitative polymerase chain reaction. HIF3A expression was significantly higher in patients with myasthenia gravis than in those without. CONCLUSION: HIF3A is aberrantly expressed in patient with thymoma who has myasthenia gravis and may be involved in the development of myasthenia gravis in thymoma patient.

Does a spinal implant alter dual energy X-ray absorptiometry body composition measurements?

BACKGROUND: Most manufacturer manuals do not verify the use of dual energy X-ray absorptiometry for body composition analysis in subjects with a metal implant. This study aimed to quantify the effects of a spinal implant on body composition, and to determine whether unadjusted lean mass estimates are valid for patients with a spinal implant. METHODS: A total of 30 healthy subjects were recruited. Three consecutive scans were performed for each participant, one with and two without extraneous spinal implant, without repositioning between scans. Lean, fat and bone estimates in the total body, trunk and limb were measured. RESULTS: Precision errors for all total and regional body compositions were within the recommended ranges. Bone masses in the trunk and total body were significantly increased with spinal implant, and the increases exceeded the least significant change. For total and regional lean and fat estimates, the measurements between subjects with and without metal implants were in substantial to almost perfect agreement and the differences were not significant and did not exceed the least significant change. CONCLUSIONS: Spinal metal artifacts significantly increased the total body and trunk bone mass but the differences in lean- and fat-related estimates at total and regional body levels and all estimates in the extremity remained within the clinical acceptable range. Thus, a spinal implant may not compromise screening of patients for fat and lean masses using dual energy X-ray absorptiometry. Application of image reconstruction or a filtering algorithm may help reduce the effect of metallic artifacts and further study is needed.

Major Mental Illness as a Risk Factor for Incarceration.

OBJECTIVE: Individuals with serious mental illness are overrepresented in correctional populations. However, little is known about the representation of persons with serious mental illness at earlier stages in the criminal justice process. This research sought to measure the prevalence of arrestees in New York State who were treated for a major mental illness in the year before their arrest and to assess whether these individuals had a disproportionate rate of incarceration. METHODS: Approximately 600,000 individuals arrested in New York State between January 1, 2010, and December 31, 2013, were matched against public mental health records to identify defendants diagnosed as having a major mental illness in the 12 months before their arrest. RESULTS: Between 4% and 6% of the arrestees were diagnosed as having a major mental illness during a mental health service visit in the 12 months prior to their arrest. A major mental illness diagnosis was associated with more than a 50% increase in the odds of a jail sentence for misdemeanor arrestees, after the analyses controlled for the other case characteristics. Conversely, it was unrelated to the likelihood of a prison sentence given a felony arrest, but it did moderate the effect of other case characteristics within the group of arrestees with felonies. CONCLUSIONS: Differential adjudication of misdemeanor arrestees with a major mental illness diagnosis appears to contribute to their overrepresentation within the jail population. The role that poverty and pretrial incarceration may play in this relationship was not explored in this research and should be the subject of future investigation.