HBCR_DMR: A Hybrid Method Based on Beta-Binomial Bayesian Hierarchical Model and Combination of Ranking Method to Detect Differential Methylation Regions in Bisulfite Sequencing Data.

DNA methylation is a key epigenetic modification involved in gene regulation, contributing to both physiological and pathological conditions. For a more profound comprehension, it is essential to conduct a precise comparison of DNA methylation patterns between sample groups that represent distinct statuses. Analysis of differentially methylated regions (DMRs) using computational approaches can help uncover the precise relationships between these phenomena. This paper describes a hybrid model that combines the beta-binomial Bayesian hierarchical model with a combination of ranking methods known as HBCR_DMR. During the initial phase, we model the actual methylation proportions of the CpG sites (CpGs) within the replicates. This modeling is achieved through beta-binomial distribution, with parameters set by a group mean and a dispersion parameter. During the second stage, we establish the selection of distinguishing CpG sites based on their methylation status, employing multiple ranking techniques. Finally, we combine the ranking lists of differentially methylated CpG sites through a voting system. Our analyses, encompassing simulations and real data, reveal outstanding performance metrics, including a sensitivity of 0.72, specificity of 0.89, and an F1 score of 0.76, yielding an overall accuracy of 0.82 and an AUC of 0.94. These findings underscore HBCR_DMR's robust capacity to distinguish methylated regions, confirming its utility as a valuable tool for DNA methylation analysis.

Comparative Study of the Effect of Experience on Auditory Processing Abilities in Voice Therapists and Other Speech-Language Pathologist in Auditory Perceptual Judgment of Voice.

OBJECTIVE: This study aimed to compare the effect of experience on central auditory processing skills in voice therapists and other Speech-Language Pathologists in the auditory perceptual evaluation of voice. STUDY DESIGN: This research is a descriptive-analytical cross-sectional observational study. METHODS: Our study population includes three groups; first-year speech-language pathology students who have not undergone any training or education in the evaluation of auditory samples (group 1; n = 10), Speech-Language Pathologists who do not have any activity in the field of voice disorders (group 2; n = 10), and therapists who have at least 2 years of experience in auditory-perceptual judgment (group 3; n = 10). Initially, the participants underwent a basic audiological evaluation (Pure Tone Audiometry, Speech Recognition Threshold, Speech Discrimination Score, tympanometry, and acoustic reflex) to assess peripheral hearing. In the next step, the auditory processing skills of the participants were evaluated with the Buffalo model (staggered spondaic word (SSW) test, phonemic synthesis test (PST), speech in noise (SPN) test). In the third step, four recorded voice samples of patients with voice disorders and healthy individuals were randomly selected for auditory perceptual judgment. These samples were the same for all participants. All the voices were previously subjected to auditory perceptual analysis by two Speech-Language Pathologist who had at least 6 years of experience in the evaluation and treatment of voice disorders; the voices were played for participants to assess auditory perception using the grade, roughness, breathiness, asthenia, strain (GRBAS) scale. RESULTS: All subjects had normal hearing and auditory processing abilities but there were some differences among the groups in processing skills. A difference was found in the SSW-qualifier and SPN-R components between the three groups. The third group had significant differences with the other two groups in the evaluation of auditory perception in the components of R, B, and S (from the GRBAS scale) in voice number one, and the components of G, R, and A in voice number three. In voice number two, there was a correlation between the SSW order effect component and the G component, as well as between the PST component and the A component. In voice number three, there was a correlation between the SPN-L component and the G component, and between the SSW condition, SSW qualifier, and SSW All errors components with the S component. In voice number four, there was a correlation between the SSW-RC, SSW-LC, SSW condition, SSW competing, and SSW order effect components with the A component. Lastly, there was a correlation between the SSW order effect and SSW type A components with the R component in voice number three in group three. CONCLUSION: The results of the present study indicate that experience has an impact on auditory processing skills and the participants of the third group, who had more experience in the evaluation of voice disorders obtained better scores than the other two groups in the auditory processing skills. Additionally, the level of experience is related to the accuracy of auditory perceptual judgment of voice. The participants of the third group performed better than the other two groups, and the performance of the first and second groups was almost the same.

Analyzing aberrant DNA methylation in colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients.

Colorectal cancer (CRC) involves epigenetic alterations. Irregular gene-methylation alteration causes and advances CRC tumor growth. Detecting differentially methylated genes (DMGs) in CRC and patient survival time paves the way to early cancer detection and prognosis. However, CRC data including survival times are heterogeneous. Almost all studies tend to ignore the heterogeneity of DMG effects on survival. To this end, we utilized a sparse estimation method in the finite mixture of accelerated failure time (AFT) regression models to capture such heterogeneity. We analyzed a dataset of CRC and normal colon tissues and identified 3406 DMGs. Analysis of overlapped DMGs with several Gene Expression Omnibus datasets led to 917 hypo- and 654 hyper-methylated DMGs. CRC pathways were revealed via gene ontology enrichment. Hub genes were selected based on Protein-Protein-Interaction network including SEMA7A, GATA4, LHX2, SOST, and CTLA4, regulating the Wnt signaling pathway. The relationship between identified DMGs/hub genes and patient survival time uncovered a two-component mixture of AFT regression model. The genes NMNAT2, ZFP42, NPAS2, MYLK3, NUDT13, KIRREL3, and FKBP6 and hub genes SOST, NFATC1, and TLE4 were associated with survival time in the most aggressive form of the disease that can serve as potential diagnostic targets for early CRC detection.

The trend of top five types of poisonings in hospitalized patients based on ICD-10 in the northeast of Iran during 2012-2018: A cross-sectional study.

Background and Aims: Poisoning remains a major health issue in developing countries with high morbidity and mortality rates; also it is one of the most common causes of admission to hospitals. This study aimed to investigate the trend of the top five types of poisonings in hospitalized patients according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) in Imam Reza hospital, Mashhad, Iran. Methods: This was a cross-sectional study performed from March 20, 2012, until September 22, 2018. We collected data from all patients hospitalized for poisoning admitted to the poisoning center at Imam Reza hospital in northeast Iran. ICD-10 was adopted to categorize all types of poisonings (T36-T65). The results obtained were analyzed by SPSS 16. Results: Thirty-four thousand eight hundred and ten cases were included. The mean age of the patients was 29.64 ± 14.69 years, of them, 50.7% were males. Benzodiazepine poisoning (T42.4) has the highest frequency among other subcategories and it was more common among females (60.5%). Opium poisoning (T40.0) has the highest mortality rate (5.4%) among other subcategories that is more common in males (72.0%). The mortality associated with narcotics was the highest frequency (2.7%). Suicide (83.6%) was the most common cause of poisoning. Most poisonings occurred in summer (27.4%). Conclusion: These findings could help health care managers and policymakers develop prevention and educational programs to reduce these poisonings and limit people's easy access to drugs and substances.

Effect of cherry consumption on blood pressure: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The present systematic review and meta-analysis aimed to summarize the findings of randomized controlled trials (RCTs) evaluating the effect of tart and sweet cherries on systolic and diastolic blood pressure (SBP and DBP). METHODS: PubMed, Scopus, Embase, and Web of Science were searched to acquire the RCTs up to December 2020. RESULTS: Seven RCTs comprising 201 participants were included. The meta-analysis showed that cherry supplementation does not lead to a significant decrease in SBP or DBP. CONCLUSIONS: Incorporating cherries into the diet has no significant effect on blood pressure.

Higher Viral Load of Polyomavirus Type BK but not JC among Renal Transplant Recipients in Comparison to Donors.

BACKGROUND & OBJECTIVE: Polyomaviruses types BK and JC and Cytomegalovirus (CMV) have been shown to be related to kidney transplantation complications. This study aimed to assess the prevalence of these viruses in patients receiving kidney transplantation. METHODS: This cross-sectional study was performed on 40 kidney transplant recipients and 44 donors. Urine samples were used for the extraction of viral DNA. The prevalence of JC and BK viruses and their viral loads were determined by real-time polymerase chain reaction. RESULTS: JC and BK viruses were identified in 31% and 92.3% of all subjects, respectively. The frequency of JC and BK cases was not statistically different between the recipient and donor groups (P>0.05). All patients in the donor group and 96.8% of the recipients were positive for CMV IgG antibody. The mean viral load of BK in donors and recipients was 4.5×1010 and 3.3×1011 copies, respectively. The mean viral load of JC was 8.6×107 copies in donors and 2.9×108 copies in recipients. The distribution of BKV was significantly higher in recipients than donors (P=0.001), while no difference was observed between the two studied groups for JCV. CONCLUSION: This study showed a relatively high prevalence of BK and JC viruria in both renal transplant donors and recipients. The viral load for BKV, but not JCV, was higher in recipients than in donors.

Which Psychological and Electrodiagnostic Factors Are Associated With Limb Disability in Patients With Carpal Tunnel Syndrome?

BACKGROUND: It has been observed that patients with carpal tunnel syndrome (CTS) who also experience emotional distress, depression, or anxiety report more severe symptoms. As patients' own perspectives about their health increasingly are guiding treatment decisions, it seems important to study the simultaneous association of psychological distress and neuropathology with hand disability in patients who have CTS, as this may help prioritize and sequence management steps. QUESTIONS/PURPOSES: What are the relationships among validated scores for (1) depression, (2) anxiety, (3) pain catastrophizing, and (4) nerve electrodiagnostic severity with measures of hand disability in patients with confirmed CTS? METHODS: Between 2017 and 2019, we evaluated 116 patients for CTS in a referral urban hospital in Mashhad, Iran. Of those, we considered 85% (99) as potentially eligible by considering the following Electromyography-Nerve Conduction Study (EMG-NCS) diagnostic criteria: sensory latency ≥ 3.5 Ms, median-ulnar latency difference ≥ 0.5 Ms, motor latency ≥ 4.2 Ms, and abnormal EMG findings in the opponens pollicis muscle (neurogenic motor unit action potentials, positive sharp waves, or fibrillation). A further 13% (15 of 116) were excluded because of nonidiopathic CTS and prior surgery, and another 12% (14 of 116) were lost because of incomplete datasets, leaving 60% (70 of 116) for final inclusion in this cross-sectional study. In all, 89% of patients were women with total mean age of 47 years. We measured depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) questionnaire (scored from 0 to 21, with a minimum clinically important difference [MCID] of 1.7 points), and we evaluated patients' state of mind regarding pain using the Pain Catastrophizing Scale (PCS) (scored from 0 to 52). Higher scores on these questionnaires represent more distress and pain catastrophizing. Hand disability was assessed with Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire outcomes (scored from 0 [no disability] to 100 [most severe disability]; MCID of 15 points), Likert pain score (from 0 to 10), and grip/pinch dynamometry results. Correlational analyses were conducted once among HADS and PCS scores and again among EMG-NCS indices with pain and disability variables to answer our first, third, and fourth questions, respectively. Regression analysis was performed to assess the percentage of variance in QuickDASH and pain severity, which could be explained by psychological and electrodiagnostic factors. We did not include grip and pinch in our multivariable model (regression analysis) as dependent variables because they did not correlate with any of psychological or EMG-NCS variables (all p values > 0.1). Significance was set at p < 0.05. RESULTS: Correlational analysis showed that the scores of all three psychological questionnaires correlated with the QuickDASH score (r = 0.50, 0.42, and 0.53 for HADS-A, HADS-D, and PCS, respectively; p < 0.001 for all three), while EMG-NCS parameters had no correlation with QuickDASH and pain scores. We also found that 37% of the variance in QuickDASH score can be explained by HADS and PCS scores (r2 = 0.37; p < 0.001). CONCLUSION: Evaluation and treatment of psychological distress before deciding on elective surgery for CTS is important because patient-reported disability-often used as a factor in surgical decision-making-is substantially correlated with emotional distress. Future prospective, controlled studies on this topic are recommended; ideally, these should evaluate psychological interventions specifically to ascertain whether they improve patients' ratings of hand disability. LEVEL OF EVIDENCE: Level III, prognostic study.

Temperament and character traits in substance use disorder in Iran: a case control study.

BACKGROUND: Patients with Substance use disorder have distinct personality traits, they were high score in novelty seeking (NS) and sensation seeking and lower in Self-directedness and higher in Self-transcendence, so we aim to investigate the relationships of temperament and characteristics with related some variables such as substance of choice. DESIGN AND SETTING: A case-control study enrolling 70 Substance use disorder patients and 70 controls was conducted at Mashhad University of medical sciences. METHODS: Using a case-control design, a group of 70 Substance use disorder patients and 70 controls was conducted at Mashhad university of medical sciences. All participation completed the 240 questions of Temperament and Character Inventory-Revised (TCI-R). Multivariate analysis of covariance (MANCOVA) was employed to compare the relationship between temperament and character traits and patterns of substance use. RESULTS: The scores of reward dependence, persistence, self-directedness, cooperativeness, and self-transcendence were significantly lower in the case group compared to healthy individuals (P < 0.05). In contrast, the score of novel seeking was significantly higher in the case group (P < 0.05). On the other hand, harm avoidance was not significantly different between the two studied groups (P = 0.637). CONCLUSIONS: Higher NS in patients with substance use disorder is common and different traits, and temperaments would choose different substance combinations.

Latissimus Dorsi Musculocutaneous Flap Inset Innovation in Breast Reconstruction.

BACKGROUND: Breast reconstruction is distinct among plastic surgery techniques. This study analysed the results of breast reconstruction with the Latissimus dorsi (LD) myocutaneous flap as a strategy for better coverage and positioning of the implant. METHODS: Twenty patients who underwent surgery between September 2013 and September 2016 were enrolled. Fourteen patients underwent reconstruction with LD and tissue expander (TE) exchanged later with implant. Six patients were reconstructed with LD and implant. The complications, problems, and aesthetic improvement associated with the use of implants placed under LD muscle were assessed. RESULTS: 0ne case required an expander removal because of deflation of TE, also one case had seroma formation due to recurrence of breast cancer and also one case had seroma in donor site. No asymmetry was detected in the inframammary fold (IMF) position between reconstructed and normal regions. After the procedure, 80% of the patients reported that their expectations were met, 95% reported no functional limitations, and 5% reported mild limitations that ameliorated with physiotherapy. The placement of implants (prostheses or expanders) under the muscle with using the LD muscle flap to cover the implant improved the breast contour by softening the inframammary crease and positioning the implants in the upper and medial quadrants of the new breasts. CONCLUSION: Breast reconstruction using silicone implants and the LD muscle flap can have excellent outcomes with low rates of complications. Placing the implant under a layer of muscle improved the harmony of the upper quadrants during breast reconstruction.

Surgical management of early and late esophageal perforation.

INTRODUCTION: Esophageal perforation is a rare and life-threating problem with a 10%-40% mortality rate. Early diagnosis and treatment are important for prevention of complications. Strategies for treatment of esophageal perforation have been controversial for many years, especially in cases of late presentation. METHODS: We prospectively studied 27 patients (12 male, 17 female, mean age 42.7 ± 17.8 years) who presented with esophageal perforation from 1996 to 2015, and evaluated the results of surgical treatment. The patients were divided into 3 groups according to time of presentation: early (<24 h), intermediate (24-72 h), and late (>72 h). We also considered the etiology and site of esophageal perforation, complications, and mortality. RESULTS: Surgery was performed in 5 patients in the early group, 7 in the moderate group, and 15 in the late group. Primary repair was carried out in 5 cases, primary repair and reinforcement with a flap in 10, esophageal resection and reconstruction in 8, and a T-tube stent was used in 4. Four patients developed a fistula postoperatively, and there was one death due to respiratory failure. No relationship was found between complications and the cause of perforation, time of presentation, or type of treatment. CONCLUSION: In patients without sepsis, primary repair can be an option even in those presenting late after esophageal perforation, with an acceptable result.