Comparative Genomics Reveals Insights into the Divergent Evolution of Astigmatic Mites and Household Pest Adaptations.

Highly diversified astigmatic mites comprise many medically important human household pests such as house dust mites causing ∼1-2% of all allergic diseases globally; however, their evolutionary origin and diverse lifestyles including reversible parasitism have not been illustrated at the genomic level, which hampers allergy prevention and our exploration of these household pests. Using six high-quality assembled and annotated genomes, this study not only refuted the monophyly of mites and ticks, but also thoroughly explored the divergence of Acariformes and the diversification of astigmatic mites. In monophyletic Acariformes, Prostigmata known as notorious plant pests first evolved, and then rapidly evolving Astigmata diverged from soil oribatid mites. Within astigmatic mites, a wide range of gene families rapidly expanded via tandem gene duplications, including ionotropic glutamate receptors, triacylglycerol lipases, serine proteases and UDP glucuronosyltransferases. Gene diversification after tandem duplications provides many genetic resources for adaptation to sensing environmental signals, digestion, and detoxification in rapidly changing household environments. Many gene decay events only occurred in the skin-burrowing parasitic mite Sarcoptes scabiei. Throughout the evolution of Acariformes, massive horizontal gene transfer events occurred in gene families such as UDP glucuronosyltransferases and several important fungal cell wall lytic enzymes, which enable detoxification and digestive functions and provide perfect drug targets for pest control. This comparative study sheds light on the divergent evolution and quick adaptation to human household environments of astigmatic mites and provides insights into the genetic adaptations and even control of human household pests.

Genome assembly and annotation of Periplaneta americana reveal a comprehensive cockroach allergen profile.

BACKGROUND: One of the most common cockroach types in urban areas, the American cockroach (Periplaneta americana), has been reported to impose an increased risk of allergies and asthma. Limited groups of allergens (Per a 1-13) have been identified in this species due to the lack of genome-related information. METHODS: To expand the allergen profile of P. americana, genomic, transcriptomic, and proteomic approaches were applied. With the support of a high-quality genome assembled using nanopore, Illumina, and Hi-C sequencing techniques, potential allergens were identified based on protein homology. Then, using enzyme-linked immunosorbent assay, selected allergens were tested in Thai patients allergic to P. americana. RESULTS: A chromosomal-level genome of P. americana (3.06 Gb) has been assembled with 94.6% BUSCO completeness, and its contiguity has been significantly improved (N50 = 151 Mb). A comprehensive allergen profile has been characterized, with seven novel groups of allergens, including enolase (Per a 14), cytochrome C (Per a 15), cofilin (Per a 16), alpha-tubulin (Per a 17), cyclophilin (Per a 18), porin3 (Per a 19), and peroxiredoxin-6 (Per a 20), showing IgE sensitivity in enzyme-linked immunosorbent assay. A new isoallergen of tropomyosin (Per a 7.02) and multiple potential isoallergens of Per a 5 were revealed using bioinformatics and proteomic approaches. Additionally, comparative analysis of P. americana with the closely related Blattodea species revealed the possibility of cross-reaction. CONCLUSION: The high-quality genome and proteome of P. americana are beneficial in studying cockroach allergens at the molecular level. Seven novel allergen groups and one isoallergen in Per a 7 were identified.

Sex-specific incidence of hepatitis B virus flares among Bcr-Abl tyrosine kinase inhibitor users in Taiwan.

BACKGROUND: The use of Bcr-Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr-Abl TKI users, to estimate sex-specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr-Abl TKI. METHODS: Bcr-Abl TKI users with chronic HBV infection were identified from Taiwan's National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case-control analysis was used to evaluate the cumulative effect of Bcr-Abl TKI use on HBV flare. RESULTS: Among 415 patients with chronic HBV infection treated with Bcr-Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr-Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person-years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr-Abl TKI on HBV flare was not observed. CONCLUSION: Approximately 10% of HBV carriers who used Bcr-Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia.

The impact of obesity in cognitive and memory dysfunction in obstructive sleep apnea syndrome.

OBJECTIVE: Obstructive sleep apnea (OSA), a sleep disorder, results in decreased daytime alertness and neurocognitive dysfunction. Obesity is considered a major risk factor for the development and progression of OSA and the resulting cognitive dysfunction. However, the effect of obesity on neurocognitive dysfunction in OSA has been rarely investigated. METHODS: Eighty-three patients with moderate to severe OSA syndrome were recruited in our study. After matching for education, age, and body mass index (BMI), 40 patients were enrolled into our study with matched obese (BMI ≧ 30) and non-obese (BMI < 30) groups. All enrolled patients completed a polysomnographic study, sleepiness questionnaires, and attention, cognitive, and memory function tests. RESULTS: Compared to obese OSA patients, non-obese OSA patients had shorter reaction times in the psychomotor vigilance task but not the Flanker or Stroop cognitive tasks. Additionally, obese OSA patients had a reduced capacity for working memory relative to non-obese OSA patients. CONCLUSIONS: Obesity had a significant effect on OSA patients in our study, including delayed reaction times in the psychomotor vigilance task and a decrease in working memory.

Borderline personality disorder is associated with an increased risk of sexually transmitted infections: A nationwide population-based cohort study in Taiwan.

BACKGROUND: Several features of borderline personality disorder (BPD) are likely to be associated with sexual health problems, such as unstable attachment, unstable sexual identity and sexual impulsivity. Since the issue of sex is not openly discussed in Taiwanese society, sexual health needs, including screening and prevention of sexually transmitted infections (STI), are often neglected in this population. OBJECTIVE: The study aims to determine whether BPD is associated with an increased risk of subsequent STI in Taiwan. METHODS: Overall 669 patients with BPD and 2676 controls matched by gender and age were enrolled between 2000 and 2012 and followed until the end of 2013 using Taiwan's National Health Insurance Research Database. During the follow-up period, participants who developed STI (human immunodeficiency virus, syphilis, genital warts, gonorrhoea, chlamydia and trichomoniasis) were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the STI incidence rate between patients with BPD and unaffected controls. RESULTS: Patients with BPD were predisposed to developing STI (HR: 4.17, 95% CI 1.62 to 10.8) after adjusting for demographic data and psychiatric comorbidities. The stratification analysis revealed a similar risk trend with BPD and subsequent STI in each gender and age group and was significant in the subgroups of male (HR: 11.3, 95% CI 2.97 to 42.7) and those aged 18-34 years (HR: 4.85, 95% CI 1.71 to 13.7). Also, the comorbidity stratification analysis revealed that, when the effect of comorbidities was excluded, patients with pure BPD significantly exhibited the risk association for subsequent STI after adjusting for all variables (HR: 4.24, 95% CI 1.25 to 14.4). CONCLUSION: Given the greater potential of BPD to be associated with an increased risk of STI, there should be direct implications for the development of targeted prevention interventions in Taiwan's mental health clinics.

Value of early evaluation of treatment response using 18F-FDG PET/CT parameters and the Epstein-Barr virus DNA load for prediction of outcome in patients with primary nasopharyngeal carcinoma.

PURPOSE: To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) using 18F-FDG PET-derived parameters and the Epstein-Barr virus (EBV) DNA titre in outcome prediction in patients with primary nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with primary NPC were prospectively enrolled. All patients underwent 18F-FDG PET/CT before and during CCRT. The plasma EBV DNA titre was measured along with the PET/CT-derived parameters. Changes in EBV DNA titre and PET/CT-derived parameters during CCRT were analysed in relation to response to treatment, recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of >0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p < 0.001 versus p = 0.175). CONCLUSION: Early evaluation of response to CCRT using 18F-FDG PET-derived parameters and the EBV DNA titre can predict outcome in patients with primary NPC. A combination of interim PET parameters and the EBV DNA titre enables better stratification of patients into subgroups with different survival rates.

Systemic autoimmune diseases are associated with an increased risk of obsessive-compulsive disorder: a nationwide population-based cohort study.

PURPOSE: Studies suggested autoimmunity plays a role in the etiology of obsessive-compulsive disorder (OCD). The purpose of this study was to determine if a history of systemic autoimmune diseases (SADs) is associated with an increased risk of subsequent onset of OCD. METHODS: Patients with or without SADs were identified in the Taiwan National Health Insurance Program. The SADs cohort consisted of 63,165, while the comparison cohort consisted of 315,825 patients. The incidence rates of OCD with a maximum follow-up period of 10 years between patients with and without SADs were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: The major finding was the discovery of a higher incidence of subsequent OCD among patients with SADs (HR: 1.85; 95% CI 1.41-2.43) after adjusted for other demographic characteristics. Specifically, the risk of OCD was observed to be significant increase in systemic lupus erythematosus (1.65, 1.07-2.54) dermatomyositis (3.25, 1.04-10.17), and Sjögren's syndrome (2.38, 1.53-3.72). Also, this study revealed some potential risk factors for developing OCD, including younger age (less than or equal to 50-year-old) and some comorbidities (alcohol use disorder, liver cirrhosis, and malignancies). Conversely, this study found that steroid use was a potential protective factor for the development of OCD. CONCLUSIONS: This study confirms that SADs are associated with higher incidence of OCD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Risk of obstructive sleep apnea in patients with bipolar disorder: A nationwide population-based cohort study in Taiwan.

AIM: Previous studies have found a high prevalence of risk factors for obstructive sleep apnea (OSA) in patients with bipolar disorder (BD). This study aimed to determine whether BD patients are associated with an increased risk of incident OSA. METHODS: Using the National Health Insurance Research Database of Taiwan, 3650 BD patients and 18 250 non-BD controls matched by sex and age were enrolled between 2000 and 2010 and followed until the end of 2013. Patients who developed OSA confirmed by a polysomnographic examination during the follow-up period were identified. Cox regression analysis was performed to examine the risk of OSA between BD patients and comparative controls. RESULTS: BD patients were prone to developing OSA in the crude analysis (hazard ratio [HR]: 1.63, 95% confidence interval [CI]: 1.07-2.49). After adjusting for demographics and comorbidities, the HR declined and was only marginally significant (HR: 1.54, 95%CI: 0.99-2.37). The stratification analysis by sex revealed that the risk trend with BD and subsequent OSA was mainly contributed by male BD patients (HR: 1.72, 95%CI: 1.02-2.91) and female BD patients weakened the overall association. Additionally, this study found that older age, higher income, living in urbanized areas, and some metabolic comorbidities were potential risk factors for developing OSA. CONCLUSION: This study shows that male BD patients are associated with an increased risk of OSA, which has direct implications for the development of targeted prevention interventions or the implementation of a screening algorithm for OSA to reduce its negative health impact.

Differential impact of CX3CL1 on lung cancer prognosis in smokers and non-smokers.

CX3CL1 is a unique chemokine, expressed in both soluble and membrane bound forms, which mediates different biological activities. Recent studies have revealed the potential of CX3CL1 signaling pathway as a target for the treatment of inflammation and cancer. The correlation between expression of CX3CL1 and prognosis of patients varies among cancers. In this study, based on CX3CL1 immunohistochemistry in non-small cell lung cancer, CX3CL1 levels were positively associated with cancer stage (Pearson chi-square, P = 0.048) and lymph node status (P = 0.033). Interestingly, survival effects of CX3CL1 were only observed in patients with smoking history and adenocarcinoma (AD, log rank, P = 0.027), but not in patients with squamous cell carcinoma (SQ). The median survival time of patients with smoking history and low level CX3CL1 expressing AD was 1538 days, while that of patients with smoking history and high level CX3CL1 expressing AD was 396 days. Cox regression models showed adverse effects of high CX3CL1 levels only in AD patients with smoking history (hazard ratio = 3.01, p = 0.034), but not in AD patients without smoking history or in SQ patients with smoking history. The results of this study suggest that CX3CL1 plays different roles in lung tumorigenesis in smokers and non-smokers, and different CX3CL1-based therapeutic strategies are needed depending on patient smoking status and tumor type. Furthermore, high level of CX3CL1 expression enhances nodal metastasis by activating JNK & MMP2/MMP9 activity in lung cancer cells.

Bipolar Disorder Is Associated With an Increased Risk of Sexually Transmitted Infections: A Nationwide Population-based Cohort Study.

BACKGROUND: Previous studies have suggested that sexually transmitted infections (STI) tend to increase in patients with bipolar disorder during a manic or hypomanic episode. However, in the long-term course of this disease, it is unclear whether patients with bipolar disorder have a higher risk of incident STI. METHODS: Using the National Health Insurance Research Database of Taiwan, 3721 patients with bipolar disorder and 14,884 controls without bipolar disorder matched by gender and age were enrolled between 2000 and 2010 and followed up until the end of 2013. Participants who developed any STI (human immunodeficiency virus [HIV], syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis) during the follow-up period were identified. Cox regression analysis was performed to examine the risk of STI between patients with bipolar disorder and comparative controls. RESULTS: Patients with bipolar disorder were prone to develop STI (hazard ratio [HR], 1.67, 95% confidence interval [95% CI], 1.27-2.18) especially for HIV (HR, 3.59; 95% CI, 1.16-11.08) and syphilis (HR, 2.26; 95% CI, 1.06-4.85). In addition, this study found that the incidence of STI was higher among women than men (HR, 1.83; 95% CI, 1.41-2.39). CONCLUSIONS: This study shows that bipolar disorder is associated with an increased risk of developing STI, which has direct implications for the development of targeted prevention interventions or regular sexual health screening in mental health clinics to reduce the disproportionate burden of HIV and other STI in patients with bipolar disorder.

[Prevalence of metabolic syndrome and its family factors for children and adolescents in Chongqing City in 2014].

OBJECTIVE: To study the prevalence and family factors on metabolic syndrome( MS) in children and adolescents for Chongqing City. METHODS: Multi-stage cluster sampling was used to recruit 1309 children and adolescents between 10 and 17 years old for physical examination( height, weight, waist circumference and blood pressure), blood biochemical examination( fasting plasma glucose, triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol)and questionnaire for family factors( breast feeding, delivery mode, birth weight, education of parents, height and weight of parents, family history of hypertension and diabetes, and so on). MS was diagnosed by the definition of metabolic syndrome and prophylaxis and treatment proposal in Chinese children and adolescents. RESULTS: The prevalence of MS on children and adolescents in Chongqing city was 5. 5%, and among normal weight, overweight, and obese groups were 0. 6%, 13. 8% and 41. 2%, respectively. Univariate analysis showed BMI of father( χ~2= 8. 237, P = 0. 016), BMI of mother( χ~2= 8. 978, P = 0. 011), occupation of father( χ~2= 7. 742, P = 0. 021), occupation of mother( χ~2= 6. 578, P = 0. 037) and family history of hypertension( χ~2=7. 684, P = 0. 006) were associated with MS. Logistic regression analysis showed father's overweight( OR = 1. 956, 95% CI 1. 176-3. 254), mother's obesity( OR = 2. 934, 95%CI 1. 230-6. 999) and family history of hypertension( OR = 1. 867, 95% CI 1. 139-3. 059) were risk factors for MS. CONCLUSION: The detection rate of MS on children and adolescents in Chongqing city is higher, and the mainly risk family factors are father's overweight, mother's obesity and family history of hypertension.

[Correlation of pubertal timing, obesity, and body composition of children and adolescents in Chongqing City].

OBJECTIVE: To investigate the correlation of pubertal timing, obesity, and body composition in children and adolescents in Chongqing city, China, and the difference in physical development and body fat among male and female students during puberty. METHODS: By a purposive sampling method, 1447 primary and junior high school students( 7- 17 years old) from two 9- year coherent-style schools in the Jiulongpo district( Chongqing City) were selected as research subjects. Height, weight, waist circumference, and skinfold thickness of the subjects were measured. In addition, breastdevelopment and age at first menstruation among female students and testicular volume and pubic hair development among male students were investigated. RESULTS: The average age at stage Ⅱ breast development for female students was 9. 78 years, while the average age at first menstruation was 12. 32 years. The average age at stage Ⅱ testicular development for male students was 11. 50 years, while the average age at stage Ⅱ pubic hair development was 12. 62 years. The incidence of overweight in female students from the group with early pubertal timing( 18. 8%) was found to be significantly higher than that of students from the group with normal pubertal timing( 7. 7%)( χ~2= 8. 881, P = 0. 005), while the incidence of obesity in the group with early pubertal timing( 18. 7%) was found to be significantly higher than that of the group with normal pubertal timing( 1. 5%)( χ~2=40. 653, P < 0. 001). Spearman rank correlation analysis showed that early pubertal timing in female students was positively correlated with their weight( r = 0. 324, P <0. 001). The incidence of overweight in male students from the group with early pubertal timing( 17. 9%) was found to be significantly higher than that of the group with normal pubertal timing( 8. 3%)( χ~2= 5. 134, P = 0. 047). Spearman rank correlation analysis also showed a positive correlation between early pubertal timing in male students and their weight( r =0. 103, P =0. 030). All body composition indices of female students revealed the same pattern. Body composition indices of the group with early pubertal timing were greater than that of the group with normal pubertal timing, and body composition indices of the group with normal pubertal timing were greater than that of the group with late pubertal timing. The differences were statistically significant( P < 0. 001). The lean body mass index of male students from the group with early pubertal timing( 46. 718 ± 1. 186) was greater than that of the group with normal pubertal timing( 42. 114 ± 0. 437), and the lean body mass index of the group with normal pubertal timing was greater than that of the group with late pubertal timing( 37. 899 ± 0. 944). The differences were statistically significant( F =14. 870, P < 0. 001). CONCLUSION: Overweight, obesity, and body composition of female students in Chongqing city, China, correlate with early pubertal timing, while overweight and lean body mass of male students correlate with early pubertal timing.

Protective Effects of MDG-1, a Polysaccharide from Ophiopogon japonicus on Diabetic Nephropathy in Diabetic KKAy Mice.

Ophiopogon japonicus is a traditional Chinese medicine that might be effective for treating type 2 diabetes. Recent research confirmed that MDG-1, a polysaccharide from O. japonicas, activates the PI3K/Akt signaling pathway and improves insulin sensitivity in a diabetic KKAy mouse model, but little is known about its effects on diabetic nephropathy. In this study, KKAy mice were orally administered distilled water (control group), MDG-1, or rosiglitazone for 12 weeks. Blood glucose levels were tested every two weeks for the fed mice. At 6 and 12 weeks, blood samples were collected for biochemical examination. At the end of the experiment, all kidney tissues were collected for histological examination and western blot analysis. Results show that MDG-1 (300 mg/kg) significantly decreased the levels of blood glucose, triglycerides, blood urine nitrogen and albumin, and significantly inhibited the expression of transforming growth factor-beta 1 and connective tissue growth factor. Moreover, MDG-1 could alleviate glomerular mesangial expansion and tubulointerstitial fibrosis in the diabetic mice, as confirmed by histopathological examination. These data indicated that MDG-1 ameliorates renal disease in diabetic mice by reducing hyperglycemia, hyperinsulinemia, and hyperlipidemia, and by inhibiting intracellular signaling pathways.

Clinical Characteristics and In-Hospital Prognosis of Infective Endocarditis in Two Eastern Counties of Taiwan.

BACKGROUND: Infective endocarditis (IE) is a common and potentially serious disease. Although it is an illness that affects populations around the world, narrower descriptions of this disease as it impacts specific regions are uncommon. We analyzed the clinical characteristics of IE patients from two eastern counties in Taiwan and studied the relationship between the isolated pathogens and clinical outcomes in these patients. METHODS: This is a retrospective chart review study which enrolled patients who received services between January 2007 and December 2010. Subsequent to chart review, IE was confirmed in a total of 55 patients by the modified Duke criteria. RESULTS: Of these patients, 17 (31%) had previous traumatic open skin wounds. Pre-existing cardiac abnormalities were found in 47 (85%) patients, 28 of whom had valvular abnormalities. Staphylococcus aureus was isolated from the blood as the leading pathogen in 25 (45%) patients (including 23 methicillin-sensitive and 2 methicillin-resistant). Septic emboli and shock occurred in 27 (49%) of 55 patients; surgery was performed on 11 (20%) of those patients, and 4 (36%) of them died post-operatively. The total in-hospital mortality rate was 40% (n = 22). Staphylococcus aureus infection was associated with significantly higher complication and mortality rate than non-Staphylococcus aureus infection (59% vs. 41% and 64% vs. 36%, respectively; p < 0.05). In addition, patients with complications had a very high mortality rate (81.5%). CONCLUSIONS: We found that Staphylococcus aureus was the most common pathogen of IE in Eastern Taiwan, and was associated with higher rates of morbidities and mortality. KEY WORDS: Infective endocarditis; Septic shock; Staphylococcus aureus; Systemic embolization.

Recent strategies for triplet-state emission regulation toward non-lead organic-inorganic metal halides.

Organic-inorganic metal halides (OIMHs) have strengthened the development of triplet-state emission materials due to their excellent luminescence performance. Due to the inherent toxicity of lead (Pb) significantly limiting its further advancement, numerous studies have been conducted to regulate triplet-state emission of non-Pb OIMHs, and several feasible strategies have been proposed. However, most of the non-Pb OIMHs reported have a relatively short lifetime or a low luminescence efficiency, not in favor of their application. In this review, we provide a summary of recent reports on the regulation of triplet-state emissions in non-Pb OIMHs to provide benefits for the design of innovative luminescent materials. Our focus is primarily on exploring the internal and external factors that influence the triplet-state emission. Starting from the luminescence mechanism, the current strategies for regulating triplet-state emissions are summarized. Moreover, by manipulating these strategies, it becomes feasible to achieve triplet-state emissions that span a range of colors from blue to red, and even extend into the near-infrared spectrum with high luminescence efficiency, while also increasing their lifetimes. This review not only provides fresh insights into the advancement of triplet-state emissions in OIMHs but also integrates experimental and theoretical perspectives to illuminate the trajectory of future research endeavors.

Correlation between the incidence and severity of Bell's palsy and seasonal variations in Taiwan.

OBJECTIVE: To investigate possible correlations between the incidence and severity of Bell's palsy and seasonal variations in Taiwan. METHODS: We studied data on the incidence of Bell's palsy over a 3-year period in Taiwan. The electroneurographic quotient was used as an index for the severity of nerve involvement. A higher electroneurographic quotient indicates less severe disease. RESULTS: Data were collected from 775 patients. We analyzed the data using the chi-square goodness-of-fit test, and the results showed that seasonality was significantly associated with the incidence of Bell's palsy among men, with the incidence increasing during the cold months (p = 0.012). A significant association was evident between age and incidence, with a higher incidence among patients aged 50 years or younger (p = 0.027). By contrast, no significant relationship was found between seasonality and either female sex or older age. No statistical association was found between the degree of nerve involvement and season of onset in patients with Bell's palsy. CONCLUSION: Bell's palsy increased among men and among younger patients during the cold seasons in Taiwan. No association emerged between the severity of Bell's palsy and the season of onset.

Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma.

OBJECTIVE: We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma. METHODS: We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models. RESULTS: Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively). CONCLUSION: The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.

Dissecting the effects of METTL3 on alternative splicing in prostate cancer.

Although the role of METTL3 has been extensively studied in many cancers, its role in isoform switching in prostate cancer (PCa) has been poorly explored. To investigate its role, we applied standard RNA-sequencing and long-read direct RNA-sequencing from Oxford Nanopore to examine how METTL3 affects alternative splicing (AS) in two PCa cell lines. By dissecting genome-wide METTL3-regulated AS events, we noted that two PCa cell lines (representing two different PCa subtypes, androgen-sensitive or resistant) behave differently in exon skipping and intron retention events following METTL3 depletion, suggesting AS heterogeneity in PCa. Moreover, we revealed that METTL3-regulated AS is dependent on N6-methyladenosine (m6A) and distinct splicing factors. Analysis of the AS landscape also revealed cell type specific AS signatures for some genes (e.g., MKNK2) involved in key functions in PCa tumorigenesis. Finally, we also validated the clinical relevance of MKNK2 AS events in PCa patients and pointed to the possible regulatory mechanism related to m6A in the exon14a/b region and SRSF1. Overall, we characterize the role of METTL3 in regulating PCa-associated AS programs, expand the role of METTL3 in tumorigenesis, and suggest that MKNK2 AS events may serve as a new potential prognostic biomarker.

Mutational signatures representative transcriptomic perturbations in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary malignancy with increasing incidence and poor prognosis. Heterogeneity originating from genomic instability is one of the critical reasons of poor outcomes. However, the studies of underlying mechanisms and pathways affected by mutations are still not intelligible. Currently, integrative molecular-level studies using multiomics approaches enable comprehensive analysis for cancers, which is pivotal for personalized therapy and mortality reduction. In this study, genomic and transcriptomic data of HCC are obtained from The Cancer Genome Atlas (TCGA) to investigate the affected coding and non-coding RNAs, as well as their regulatory network due to certain mutational signatures of HCC. Different types of RNAs have their specific enriched biological functions in mutational signature-specific HCCs, upregulated coding RNAs are predominantly associated with lipid metabolism-related pathways, and downregulated coding RNAs are enriched in axonogenesis for tumor microenvironment generation. Additionally, differentially expressed miRNAs are inclined to concentrate in cancer-related signaling pathways. Some of these RNAs also serve as prognostic factors that help predict the survival outcome of HCCs with certain mutational signatures. Furthermore, deregulation of competing endogenous RNA (ceRNA) regulatory network is identified, which suggests a potential therapy via interference of miRNA activity for mutational signature-specific HCC. This study proposes a projection approach to reduce therapeutic complexity from genomic mutations to transcriptomic alterations. Through this method, we identify genes and pathways critical for mutational signature-specific HCC and further discover a series of prognostic markers indicating patient survival outcome.