An Algorithmic Framework for Computing Validation Performance Bounds by Using Suboptimal Models

Practical model building processes are often time-consuming because many different models must be trained and validated. In this paper, we introduce a novel algorithm that can be used for computing the lower and the upper bounds of model validation errors without actually training the model itself. A key idea behind our algorithm is using a side information available from a suboptimal model. If a reasonably good suboptimal model is available, our algorithm can compute lower and upper bounds of many useful quantities for making inferences on the unknown target model. We demonstrate the advantage of our algorithm in the context of model selection for regularized learning problems

Site‐specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136246/1/mc22577.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136246/2/mc22577_am.pd

Development of 11 polymorphic microsatellite markers for Xylocarpus granatum (Meliaceae) using next-generation sequencing technology

Human impacts have seriously damaged mangroves, and conservation of mangroves will require information on local and regional population genetic structures. Here, we report the development and polymorphism of eleven novel microsatellite markers, developed using next- generation sequencing on 56 samples of widespread man- grove species Xylocarpus granatum (Meliaceae) from nine populations across the Indo-West Pacific region. All loci were found to be polymorphic, with the number of alleles per locus ranging from four to 19. In a population from Sabah (Malaysia), the mean observed and expected heterozygosity per locus was 0.59 and 0.58, respectively. No null allele, significant linkage disequilibrium or deviation from Hardy–Weinberg equilibrium was detected among all loci. The eleven markers developed can be valuable tools to conservation genetics of this species across its distributional range

Update on Findings about Sudden Sensorineural Hearing Loss and Insight into Its Pathogenesis

Sudden sensorineural hearing loss (SSNHL) is routinely encountered and is one of the most common emergent diseases in otolaryngology clinics. However, the etiology of SSNHL remains unclear. Due to the inaccessibility of the living human inner ear for biopsy, studies investigating the etiology of SSNHL have been performed by analyzing data obtained from examinations using peripheral blood or imaging. We updated the findings obtained from serological, magnetic resonance imaging, genetic, and viral examinations to reveal the etiology of SSNHL. Regarding viral examination, we focused on sensorineural hearing loss associated with coronavirus disease (COVID-19) because the number of correlated reports has been increasing after the outbreak. The updated findings revealed the following three possible mechanisms underlying the development of SSNHL: thrombosis and resulting vascular obstruction in the cochlea, asymptomatic viral infection and resulting damage to the cochlea, and cochlear inflammation and resulting damage to the cochlea. Thrombosis and viral infection are predominant, and cochlear inflammation can be secondarily induced through viral infection or even thrombosis. The findings about sensorineural hearing loss associated with COVID-19 supported the possibility that asymptomatic viral infection is one of the etiologies of SSNHL, and the virus can infect inner ear tissues and directly damage them

G Protein-Coupled Receptor Genes, PTGDR1, PTGDR2, and PTGIR, Are Candidate Epigenetic Biomarkers and Predictors for Treated Patients with HPV-Associated Oropharyngeal Cancer

Differences in the biology of human papillomavirus (HPV)-associated oropharyngeal cancers (OPCs) and HPV-negative OPCs may have implications in patient management. Early detection is imperative to reduce HPV-associated OPC mortality. Circulating tumor DNA (ctDNA) can potentially serve as a biomarker for monitoring clinically relevant cancer-related genetic and epigenetic modifications. We analyzed the methylation status of 24 G protein-coupled receptor (GPCR) genes in verification (85 OPC primary samples) and validation (8 OPC ctDNA samples) studies using quantitative methylation-specific polymerase chain reaction (Q-MSP). The Q-MSP-based verification study with 85 OPC primary samples revealed the GPCR genes that were significantly associated with recurrence in high methylation groups (≥14 methylated genes) with OPC and HPV-associated OPC (p < 0.001). In the Kaplan–Meier estimate and multivariate Cox proportional hazard analyses, 13 GPCR genes were significantly related to increased recurrence in the methylation group. Furthermore, the validation study on ctDNA showed that three of these genes (Prostaglandin D2 receptor 1: PTGDR1, Prostaglandin D2 receptor 2: PTGDR2, and Prostaglandin I2 Receptor: PTGIR) had a prediction performance as emerging biomarkers. We characterized the relationship between the methylation status of GPCR genes and outcomes in HPV-associated OPC. Our results highlight the potential utility of ctDNA methylation-based detection for the clinical management of HPV-associated OPC

Relationship between Rate of Force Development of Tongue Pressure and Physical Performance

In the assessment of skeletal muscle strength, rate of force development (RFD) is clinically identified as a functional index that reflects the effects of aging, but there are few reports on RFD of the tongue. The purpose of this study was to examine the relationship between RFD of tongue pressure (RFD-TP) and oral and whole-body physical performance in older adults, and to clarify its characteristics. We enrolled adults aged ≥65 years with pathological occlusal contact in premolar and molar regions of teeth in the Tamba-Sasayama area, Japan, from 2017 to 2018. Maximum tongue pressure (MTP) and the speed to reach the maximum tongue pressure (RFD-TP) were evaluated as measures of tongue function. Oral functions related to objective measures of tongue function, such as repetitive saliva swallowing test, oral diadochokinesis, and physical status or performance, such as mini mental state examination, body mass index, skeletal mass index, knee extension force, one-leg standing time, grip strength, walking speed, timed up-and-go test, and five-time chair stand speed was evaluated. No significant correlation was found between MTP and age, but RFD-TP had a significant negative correlation with age. Neither RFD-TP nor MTP showed a significant correlation with oral function. RFD-TP was associated with physical performance, such as knee extension force and one-leg standing time. RFD-TP is more sensitive to aging than MTP. In addition, RFD-TP is related to physical performance and may be useful for the early detection of frailty

Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer

Loss of heterozygosity (LOH) on chromosome 18q23 is associated with significantly decreased survival in head and neck cancer. In agreement with such tumor suppressive roles, the loss of function of genes located in this region can be achieved through LOH and promotor hypermethylation. In this study, the methylation status of promoters of 18q23 genes in 243 head and neck cancer patients was assessed by quantitative methylation-specific PCR. Promoter methylation was then compared to various clinical characteristics and patient survival. GALR1 and SALL3 promoter methylation correlated with reduced disease-free survival (log-rank test, p = 0.018 and p = 0.013, respectively). Furthermore, based on multivariate Cox proportional hazards analysis, these methylation events were associated with poor disease-free survival, with hazard ratios of 1.600 (95% confidence interval: CI, 1.027–2.493; p = 0.038) and 1.911 (95% CI, 1.155–3.162; p = 0.012), respectively. By comparison, GALR1 and SALL3 methylation were not prognostic for overall survival in The Cancer Genome Atlas (TCGA) cohort. Our findings suggest that the methylation status of 18q23 genes could serve as important biomarkers for the prediction of clinical outcomes in well-annotated head and neck squamous cell carcinoma cohorts. GALR1 and SALL3 methylation could thus help to facilitate risk stratification for individualized treatment

Efficacy and safety of repeated endoscopic radial incision and cutting procedure for benign esophageal stricture

Background: Radial incision and cutting (RIC) is indicated for refractory benign esophageal strictures after curative treatment for esophageal cancer and has shown favorable short-term outcomes. However, re-stricture after RIC may occur in the long term, and RIC is performed repeatedly in such cases, but the efficacy and safety of repeated RIC are unclear. Therefore, we aimed to demonstrate the efficacy and safety of the repeated RIC for refractory benign esophageal strictures after surgical and non-surgical treatment. Methods: Between April 2008 and September 2019, we enrolled patients who were treated with the first RIC for benign esophageal strictures. The RIC was indicated for the refractory stricture and repeatedly performed for re-refractory esophageal stricture after RIC. We retrospectively evaluated the 6-month refractory stricture-free rate, and adverse events in the first RIC and repeated RICs. Results: Forty-six patients (39 men, 7 women; median age, 71 years, range 49–85) were included. RIC was performed once in 24 patients (non-repeated RIC group) and two or more times in 22 patients (repeated RIC group). In all patients, the 6-month refractory stricture-free rate after the first RIC were 42.3%. In the repeated RIC group, the 6-month refractory stricture-free rate after the first and repeated RICs were 18.2% vs 18.2%, respectively. No adverse events were noted. Conclusions: The repeated RIC could not be a curative treatment, but can be effective in the short-term and safe, even for patients with refractory benign esophageal stricture after the first RIC

Associations between Abdominal Trunk Muscle Weakness and Future Osteoporotic Vertebral Fracture in Middle-Aged and Older Adult Women: A Three-Year Prospective Longitudinal Cohort Study

Potential risk factors associated with future osteoporotic vertebral fracture (OVF) were prospectively investigated in middle-aged and older adult women. We enrolled 197 female patients aged ≥50 years who were scheduled to undergo surgery for lower-extremity degenerative diseases. Patient anthropometric and muscle strength measurements, a bone mineral density measurement of the lumbar spine (L-BMD), and full-spine standing radiographs to examine the presence of old OVFs and spinopelvic sagittal parameters were obtained preoperatively. We evaluated 141 patients who underwent full-spine standing radiographs three years postoperatively to identify new OVFs. We excluded 54 patients who did not undergo a second radiographic examination and 2 with new traumatic OVFs. Univariate and multivariate analyses were performed to identify risk factors associated with new non-traumatic OVF occurrence. Ten (7.1%) patients developed new non-traumatic OVFs during the study period (fracture group). The fracture group had less abdominal trunk muscle strength, lower L-BMD, smaller sacral slopes, and larger pelvic tilt than the non-fracture group. The fracture group showed a higher prevalence of old OVFs preoperatively than the non-fracture group. Abdominal trunk muscle weakness, low L-BMD, and the presence of old OVFs were identified as significant risk factors for OVF occurrence. In middle-aged or older adult women, abdominal trunk muscle weakness, low L-BMD, and old OVFs were associated with future OVF