The African Sacred Ibis Threskiornis aethiopicus is an invasive bird species in Taiwan and has expanded its distribution range rapidly over the past three decades. There is limited information ...available on the invasion process of African Sacred Ibises in Taiwan and its genetic consequences. We investigated whether genetic factors reflected the expansion of African Sacred Ibises and determined the extent to which two behaviour‐associated genes may have facilitated invasion. The dopamine receptor gene (DRD4) and the serotonin transporter gene (SERT) have both been found to be associated with novel‐seeking and bold behaviour in birds. We hypothesized that: (1) selection on temperament traits may determine the polymorphisms in these two genes and (2) the likelihood of dispersal of African Sacred Ibis populations can be explained by the intraspecific variation at these two genes. To detect the signals of population expansion and natural selection, we compared intra‐population variation and inter‐population differentiation of DRD4 and SERT with those of a mitochondrial gene (COX1) and an additional intron. We recovered contrasting patterns of nucleotide variation between the mitochondrial and nuclear genes with no single nucleotide polymorphisms detected in COX1 compared with allelic polymorphism in DRD4 and SERT. Populations showed decreasing genetic diversity at DRD4 as their distance to the initial invasive locality increased, consistent with a rapid expansion from one founder population. However, we found little evidence of selection on DRD4 or SERT, suggesting that these behaviour‐related genes are unlikely to have played a significant role in the successful invasion of the African Sacred Ibises in Taiwan. We detected high levels of genetic variation at these two behaviour‐related genes despite the effects of inbreeding in these invasive birds.
Persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) under current antiviral therapy is a major barrier to eradication of chronic hepatitis B (CHB). Curing CHB will require ...novel strategies for specific disruption of cccDNA. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is a newly developed tool for site-specific cleavage of DNA targets directed by a synthetic guide RNA (gRNA) base-paired to the target DNA sequence. To examine whether this system can cleave HBV genomes, we designed eight gRNAs against HBV of genotype A. With the HBV-specific gRNAs, the CRISPR/Cas9 system significantly reduced the production of HBV core and surface proteins in Huh-7 cells transfected with an HBV-expression vector. Among eight screened gRNAs, two effective ones were identified. Interestingly, one gRNA targeting the conserved HBV sequence acted against different genotypes. Using a hydrodynamics-HBV persistence mouse model, we further demonstrated that this system could cleave the intrahepatic HBV genome-containing plasmid and facilitate its clearance in vivo, resulting in reduction of serum surface antigen levels. These data suggest that the CRISPR/Cas9 system could disrupt the HBV-expressing templates both in vitro and in vivo, indicating its potential in eradicating persistent HBV infection.
We tested the association between two intronic polymorphisms (CTG18.1 and rs613872) in TCF4 and Fuchs' endothelial corneal dystrophy (FECD), and analyzed their segregation patterns in families.
We ...recruited 120 unrelated Caucasian subjects with FECD and 100 controls. Available family members of probands were recruited. Genotyping of the single nucleotide polymorphism (SNP) rs613872 was performed using Sanger sequencing or real-time allelic discrimination assay. The trinucleotide repeat polymorphism, CTG18.1, was genotyped using a combination of short tandem repeat assay and triplet repeat primed PCR assay. The cytosine-thymine-guanine (CTG) repeat length of ≥40 was classified as an expanded CTG18.1 allele. Association of the two loci with FECD was evaluated. Segregation in 29 families was examined.
The two polymorphisms are in linkage disequilibrium (r(2) = 0.65 in cases and 0.31 in controls). Significant associations were found between FECD and rs613872 (P = 3.1 × 10(-17)), expanded CTG18.1 allele (P = 6.5 × 10(-25)), and their haplotypes (P = 5.9 × 10(-19)). The odds ratio (OR) of each copy of the rs613872 G allele for FECD was estimated to be 9.5 (95% confidence interval CI, 5.1-17.5). The OR of each copy of the CTG18.1 expanded allele was estimated to be 32.3 (95% CI, 13.4-77.6). The expanded CTG 18.1 allele cosegregated with the trait in 52% (15/29) of families with complete penetrance and 10% (3/29) with incomplete penetrance.
We report, to our knowledge, the first independent replication of the expanded CTG 18.1 allele conferring significant risk for FECD (>30-fold increase). The expanded allele cosegregates with the trait with complete penetrance in a majority of families, but we also document cases of incomplete penetrance.
Loss of smell or taste are early symptoms of COVID-19. Given the high asymptomatic rate of COVID-19, as well as unreliable temperature checking and contact history taking, it is important to ...understand the role of olfactory and gustatory dysfunction (OGD) in the diagnosis of COVID-19. The aim of this study is to determine how initial symptoms of OGD can be used to screen patients for COVID-19 laboratory testing.
We followed recommendations from the Preferred Reporting Items for Systemic Reviews and Meta-analysis (PRISMA) statement to conduct this systematic review study. We used OGD-related key words to search for literature published between January 1, 2020 and September 30, 2020 on Pubmed, Ovid Medline databases. We estimated the prevalence of OGD and compared it with that of other OGD-related symptoms. The weighted summary proportion under the fixed and random effects model was assessed using MedCalc statistical software. Whenever there was heterogeneity, a random effects model was selected. Publication bias was assessed by funnel plot asymmetry and Egger's regression test.
A total of 25 articles (evidence level III:5; IV:20) were identified and reviewed. Data synthesis of 19 articles revealed that the pooled prevalence of olfactory dysfunction in COVID-19 is 53.56% (range 5.6-100%, 95% CI 40.25-66.61%). The pooled prevalence of gustatory dysfunction in COVID-19 is 43.93% (range 1.5-85.18%, 95% CI 28.72-59.74%), just behind fever (62.22%, range 18.18-95.83%, 95% CI 54.82-69.33%), cough (64.74%, range 38.89-87.5%, 95% CI 57.97-71.22%), and fatigue (56.74%, range 6.25-93.62%, 95% CI 32.53-79.35%). The prevalence of gustatory dysfunction in subgroup with objective evaluation is lower than those without (9.91% vs. 49.21%, relive risk 2.82, p<0.001).
Our updated systematic review attests that OGD is an important early symptom of COVID-19 infection. Screening for OGD should be further emphasized to prioritize patients for laboratory test.
This paper presents an innovative grasping system for pick-and-place applications, capable of handling a wide range of objects with varying characteristics, including size, shape, weight, rigidity, ...and fragility. The system uses a four-finger design to incorporate multiple grasping modes, including inner gripping, outer gripping, suction, and pinch-gripping. The paper details the development of a soft actuator system that drives a Watt’s Type I link chain for mechanical compliance and passive safety. Additionally, an end-to-end grasping policymaker using depth vision is proposed to determine the optimal grasping mode and finger trajectory. Results from experiments demonstrate the system’s versatility and state-of-the-art performance.
Background
To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1−2N0M0 oral cavity squamous ...cell carcinoma (OCSCC).
Methods
Between 2011 and 2019, we analyzed data for 13,542 cT1−2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well‐balanced study groups (initial surgery, n = 580; definitive RT, n = 145).
Results
Before PS matching, the 5‐year disease‐specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5‐year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5‐year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5‐year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001.
Conclusions
In Taiwanese patients with cT1−2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.
Patients with cT1−2N0M0 oral cavity cancer who underwent initial surgery demonstrated significantly improved disease‐specific and overall survival rates compared to those who received primary definitive radiotherapy (≥6600 cGy), even after propensity score matching. Subgroup analyses further revealed that survival outcomes remained significantly better for the positive margin subgroup compared to the radiotherapy group, irrespective of whether they received concurrent chemotherapy.
Background
The current NCCN guidelines recommend considering elective neck dissection (END) for early‐stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. ...However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria.
Methods
We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO).
Results
Patients who underwent END had better 5‐year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease‐specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate‐to‐poor tumor differentiation as independent risk factors for 5‐year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low‐risk subgroup (DOI <5 mm plus well‐differentiated tumor), an intermediate‐risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high‐risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5‐year survival outcomes (neck control/DSS/OS) for the low‐risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%).
Conclusions
By implementing risk stratification within the NO group, we found that 26% (251/979) of low‐risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account.
Most human traits are influenced by the interplay between genetic and environmental factors. Many statistical methods have been proposed to screen for gene-environment interaction (GxE) in the post ...genome-wide association study era. However, most of the existing methods assume a linear interaction between genetic and environmental factors toward phenotypic variations, which diminishes statistical power in the case of nonlinear GxE. In this paper, we present a flexible statistical procedure to detect GxE regardless of whether the underlying relationship is linear or not. By modeling the joint genetic and GxE effects as a varying-coefficient function of the environmental factor, the proposed model is able to capture dynamic trajectories of GxE. We employ a likelihood ratio test with a fast Monte Carlo algorithm for hypothesis testing. Simulations were conducted to evaluate validity and power of the proposed model in various settings. Real data analysis was performed to illustrate its power, in particular, in the case of nonlinear GxE.
Identifications of novel genetic signals conferring susceptibility to human complex diseases is pivotal to the disease diagnosis, prevention, and treatment. Genetic association study is a powerful ...tool to discover candidate genetic signals that contribute to diseases, through statistical tests for correlation between the disease status and genetic variations in study samples. In such studies with a case-control design, a standard practice is to perform the Cochran-Armitage (CA) trend test under an additive genetic model, which suffers from power loss when the model assumption is wrong. The Jonckheere-Terpstra (JT) trend test is an alternative method to evaluate association in a nonparametric way. This study compares the power of the JT trend test and the CA trend test in various scenarios, including different sample sizes (200-2000), minor allele frequencies (0.05-0.4), and underlying modes of inheritance (dominant genetic model to recessive genetic model). By simulation and real data analysis, it is shown that in general the JT trend test has higher, similar, and lower power than the CA trend test when the underlying mode of inheritance is dominant, additive, and recessive, respectively; when the sample size is small and the minor allele frequency is low, the JT trend test outperforms the CA trend test across the spectrum of genetic models. In sum, the JT trend test is a valuable alternative to the CA trend test under certain circumstances with higher statistical power, which could lead to better detection of genetic signals to human diseases and finer dissection of their genetic architecture.
The reaction mechanism of lithium-ion batteries is directly affect system safety and performance. Understanding the actual battery status through model simulation has become an important issue in ...battery management systems. This research proposes a non-destructive parameter identification method that uses whale optimization algorithm with unique global searching to identify the parameters of the electrochemical model and analyze the sensitivity of important parameters in the battery model. First, we establish an experimental platform and conduct four conditions, including 1C, 0.5C, 2C and one driving cycle. Moreover, 1C charge and discharge are taken as the benchmark for the parameter identification. After obtaining the key parameters of the battery, the battery performance prediction is carried out for the remaining three types. The terminal voltage of 0.5C, 2C and the road driving prediction errors are less than 15.45 mV, and the battery SOC errors are less than 1.21%. The results of parameter sensitivity studies show that the electrode-related parameters for the migration of lithium ions are the key to calculating the accuracy of the performance, and the porosity of the electrode has the greatest influence. The accurate parameter identification and the sensitivity provide a future methodology to design a proper battery model for battery management systems.
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