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Simple Summary: Atrial fibrillation (AF), the most prevalent sustained dysrhythmia, is accountable for substantial mortality and morbidity. Accumulating convincing evidence highlights the predominant roles of heritable components in the initiation and maintenance of AF. Here, through pan-genomic genotyping with genetic markers followed by a genetic linkage study in an AF family, a novel AF-causing locus was located at human chromosome 7p14.2–p14.3. An exome-wide sequence assay unveiled that, at the defined locus, the mutation in TBX20, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another AF family uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were found in 600 control persons. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. These findings strongly indicate that TBX20 is a new AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the individually tailored treatment of AF. Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via whole-genome genotyping with genetic markers and a linkage assay in a family suffering from AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89 cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. An exome-wide sequencing assay unveiled that, at the defined locus, the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another family suffering from AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the allele-specific treatment of AF patients. [ABSTRACT FROM AUTHOR]

Rapid and robust detection assays for Salmonella Enteritidis (SE) in shell eggs are essential to enable a quick testing turnaround time (TAT) at the earliest checkpoint and to ensure effective food safety control. Real-time polymerase chain reaction (qPCR) assays provide a workaround for the protracted lead times associated with conventional Salmonella diagnostic testing. However, DNA-based analysis cannot reliably discriminate between signals from viable and dead bacteria. We developed a strategy based on an SE qPCR assay that can be integrated into system testing to accelerate the detection of viable SE in egg-enriched cultures and verify the yielded SE isolates. The specificity of the assay was evaluated against 89 Salmonella strains, and SE was accurately identified in every instance. To define the indicator for a viable bacteria readout, viable or heat-inactivated SE were spiked into shell egg contents to generate post-enriched, artificially contaminated cultures to establish the quantification cycle (Cq) for viable SE. Our study has demonstrated that this technique could potentially be applied to accurately identify viable SE during the screening stage of naturally contaminated shell eggs following enrichment to provide an early alert, and that it consistently identified the serotypes of SE isolates in a shorter time than conventional testing. [ABSTRACT FROM AUTHOR]

Simple Summary: Congenital heart disease is associated with substantial mortality and morbidity as well as socioeconomic burden, and increasing research underscores the genetic basis for it. In this study, a genome-wide genotyping with microsatellite markers followed by linkage analysis was performed in a Chinese family suffering congenital heart disease and arrhythmias, and a novel genetic locus linked to the disease was located on chromosome 17q21.31-q21.33. Sequencing assays of the candidate genes at the locus revealed a novel heterozygous mutation in the GJC1 gene coding for Cx45, NM_005497.4:c.550A>G;p.R184G, which was in co-segregation with the disease in the whole family and was not detected in 516 control individuals. Electrophysiological analyses showed that the mutation significantly diminished the coupling conductance in homomeric cell pairs (R184G/R184G) and in cell pairs expressing R184G/Cx45 or R184G/Cx43, in a dominant-negative mode. Fluorescent dye uptake experiments demonstrated no apparent change of the R184G mutation on the Cx45 hemichannels. These findings define a new genetic locus for congenital heart disease and arrhythmias on chromosome 17q21.31-q21.33 and indicate GJC1 as a new gene predisposing to the disease. As the most prevalent type of birth malformation, congenital heart disease (CHD) gives rise to substantial mortality and morbidity as well as a socioeconomic burden. Although aggregating investigations highlight the genetic basis for CHD, the genetic determinants underpinning CHD remain largely obscure. In this research, a Chinese family suffering from autosomal dominant CHD (atrial septal defect) and arrhythmias was enrolled. A genome-wide genotyping with microsatellite markers followed by linkage assay as well as sequencing analysis was conducted. The functional effects of the discovered genetic mutation were characterized by dual patch-clamp electrophysiological recordings in N2A cells and propidium iodide uptake assays in HeLa cells. As a result, a novel genetic locus for CHD and arrhythmias was located on chromosome 17q21.31-q21.33, a 4.82-cM (5.12 Mb) region between two markers of D17S1861 and D17S1795. Sequencing assays of the genes at the mapped locus unveiled a novel heterozygous mutation in the GJC1 gene coding for connexin 45 (Cx45), NM_005497.4:c.550A>G;p.R184G, which was in co-segregation with the disease in the whole family and was not observed in 516 unrelated healthy individuals or gnomAD. Electrophysiological analyses revealed that the mutation significantly diminished the coupling conductance in homomeric cell pairs (R184G/R184G) and in cell pairs expressing either R184G/Cx45 or R184G/Cx43. Propidium iodide uptake experiments demonstrated that the Cx45 R184G mutation did not increase the Cx45 hemichannel function. This investigation locates a new genetic locus linked to CHD and arrhythmias on chromosome 17q21.31-q21.33 and indicates GJC1 as a novel gene predisposing to CHD and arrhythmias, implying clinical implications for prognostic risk assessment and personalized management of patients affected with CHD and arrhythmias. [ABSTRACT FROM AUTHOR]

Recent advances with large-scale pre-trained language models (e.g., BERT) have brought significant potential to natural language processing. However, the large model size hinders their use in IoT and edge devices. Several studies have utilized task-specific knowledge distillation to compress the pre-trained language models. However, to reduce the number of layers in a large model, a sound strategy for distilling knowledge to a student model with fewer layers than the teacher model is lacking. In this work, we present Layer-wise Adaptive Distillation (LAD), a task-specific distillation framework that can be used to reduce the model size of BERT. We design an iterative aggregation mechanism with multiple gate blocks in LAD to adaptively distill layer-wise internal knowledge from the teacher model to the student model. The proposed method enables an effective knowledge transfer process for a student model, without skipping any teacher layers. The experimental results show that both the six-layer and four-layer LAD student models outperform previous task-specific distillation approaches during GLUE tasks. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM), characterized by left ventricular or biventricular enlargement with systolic dysfunction, is the most common type of cardiac muscle disease. It is a major cause of congestive heart failure and the most frequent indication for heart transplantation. Aggregating evidence has convincingly demonstrated that DCM has an underlying genetic basis, though the genetic defects responsible for DCM in a larger proportion of cases remain elusive, motivating the ongoing research for new DCM-causative genes. In the current investigation, a multigenerational family affected with autosomal-dominant DCM was recruited from the Chinese Han population. By whole-exome sequencing and Sanger sequencing analyses of the DNAs from the family members, a new BMP10 variation, NM_014482.3:c.166C > T;p.(Gln56*), was discovered and verified to be in co-segregation with the DCM phenotype in the entire family. The heterozygous BMP10 variant was not detected in 268 healthy volunteers enrolled as control subjects. The functional measurement via dual-luciferase reporter assay revealed that Gln56*-mutant BMP10 lost the ability to transactivate its target genes NKX2.5 and TBX20, two genes that had been causally linked to DCM. The findings strongly indicate BMP10 as a new gene contributing to DCM in humans and support BMP10 haploinsufficiency as an alternative pathogenic mechanism underpinning DCM, implying potential implications for the early genetic diagnosis and precision prophylaxis of DCM. [ABSTRACT FROM AUTHOR]

The identification of microorganisms using single-temperatures pyrolysis gas chromatography (ST-PyGC) has limitations, for example, the risk of missing characteristic peaks that are essential to the chemotaxonomic interpretation. In this paper, we proposed a new multi-temperature PyGC (MT-PyGC) method as an alternative to ST-PyGC, without sacrificing its speed and quality. Six bacteria (three Gram-positive and three Gram-negative), one micro-fungus and one archaeon, representing microorganisms from different domains, were analyzed by MT-PyGC. It is found that MT pyrograms cover a more complete range of characteristic peaks than ST. Coupling with thermogravimetric analysis, chemotaxonomic information extracted from pyrograms by MT-PyGC have the potential for the differentiation of microorganisms from environments including deep subterranean reservoirs and biomass conversion/biofuel production. [ABSTRACT FROM AUTHOR]

Singapore launched a population-based organised mammography screening (MAM) programme in 2002. However, uptake is low. A better understanding of breast cancer (BC) risk factors has generated interest in shifting from a one-size-fits-all to a risk-based screening approach. However, public acceptability of the change is lacking. Focus group discussions (FGD) were conducted with 54 women (median age 37.5 years) with no BC history. Eight online sessions were transcribed, coded, and thematically analysed. Additionally, we surveyed 993 participants in a risk-based MAM study on how they felt in anticipation of receiving their risk profiles. Attitudes towards MAM (e.g., fear, low perceived risk) have remained unchanged for ~25 years. However, FGD participants reported that they would be more likely to attend routine mammography after having their BC risks assessed, despite uncertainty and concerns about risk-based screening. This insight was reinforced by the survey participants reporting more positive than negative feelings before receiving their risk reports. There is enthusiasm in knowing personal disease risk but concerns about the level of support for individuals learning they are at higher risk for breast cancer. Our results support the empowering of Singaporean women with personal health information to improve MAM uptake. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is the most frequent kind of birth deformity in human beings and the leading cause of neonatal mortality worldwide. Although genetic etiologies encompassing aneuploidy, copy number variations, and mutations in over 100 genes have been uncovered to be involved in the pathogenesis of CHD, the genetic components predisposing to CHD in most cases remain unclear. We recruited a family with CHD from the Chinese Han population in the present investigation. Through whole-exome sequencing analysis of selected family members, a new SOX18 variation, namely NM_018419.3:c.349A>T; p.(Lys117*), was identified and confirmed to co-segregate with the CHD phenotype in the entire family by Sanger sequencing analysis. The heterozygous variant was absent from the 384 healthy volunteers enlisted as control individuals. Functional exploration via luciferase reporter analysis in cultivated HeLa cells revealed that Lys117*-mutant SOX18 lost transactivation on its target genes NR2F2 and GATA4, two genes responsible for CHD. Moreover, the genetic variation terminated the synergistic activation between SOX18 and NKX2.5, another gene accountable for CHD. The findings strongly indicate SOX18 as a novel gene contributing to CHD, which helps address challenges in the clinical genetic diagnosis and prenatal prophylaxis of CHD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the protective effects of ganoderic acids (GA) from Ganoderma lucidum against liver injury and intestinal microbial disorder in mice with excessive alcohol intake. Results showed GA supplement significantly inhibited the abnormal elevation of the liver index, serum lipid parameters, aspartate aminotransferase and alanine aminotransferase in mice exposed to alcohol intake, and also significantly protected the excessive lipid accumulation and pathological changes. Alcohol-induced oxidative stress in the liver was significantly ameliorated by GA intervention through reducing the levels of maleic dialdehyde and lactate dehydrogenase and increasing the levels of glutathione, catalase, superoxide dismutase and alcohol dehydrogenase. Intestinal microbiota profiling demonstrated GA intervention modulated the composition of intestinal microflora by increasing the levels of Lactobacillus, Faecalibaculum, Romboutsia, Bifidobacterium and decreasing the Helicobacter level. Furthermore, liver metabolomic profiling suggested GA intervention had a remarkable regulatory effect on liver metabolism with excessive alcohol consumption. Moreover, GA intervention regulated mRNA levels of alcohol metabolism, fatty lipid metabolism, oxidative stress, bile acid biosynthesis and metabolism-related genes in the liver. Conclusively, these findings demonstrate GA intervention can significantly relieve alcoholic liver injury and it is hopeful to become a new functional food ingredient for the prevention of alcoholic liver injury. [ABSTRACT FROM AUTHOR]

The advancement of the Internet has changed people's ways of expressing and sharing their views with the world. Moreover, user-generated content has become a primary guide for customer purchasing decisions. Therefore, motivated by commercial interest, some sellers have started manipulating Internet ratings by writing false positive reviews to encourage the sale of their goods and writing false negative reviews to discredit competitors. These reviews are generally referred to as deceptive reviews. Deceptive reviews mislead customers in purchasing goods that are inconsistent with online information and thus obstruct fair competition among businesses. To protect the right of consumers and sellers, an effective method is required to automate the detection of misleading reviews. Previously developed methods of translating text into feature vectors usually fail to interpret polysemous words, which leads to such functions being obstructed. By using dynamic feature vectors, the present study developed several misleading review-detection models for the Chinese language. The developed models were then compared with the standard detection-efficiency models. The deceptive reviews collected from various online forums in Taiwan by previous studies were used to test the models. The results showed that the models proposed in this study can achieve 0.92 in terms of precision, 0.91 in terms of recall, and 0.91 in terms of F1-score. The improvement rate of our proposal is higher than 20%. Accordingly, we prove that our proposal demonstrated improved performance in detecting misleading reviews, and the models based on dynamic feature vectors were capable of more accurately capturing semantic terms than the conventional models based on the static feature vectors, thereby enhancing effectiveness. [ABSTRACT FROM AUTHOR]

A simple and rapid ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) coupled with a one-step liquid-liquid extraction method has been developed and validated for the simultaneous determination of two flavonoids (chrysin, tectochrysin) from Alpinia oxyphylla fruits extract in rat plasma. Plasma samples were extracted with diethyl ether and separated on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) using gradient elution consisting of 0.1% formic acid in water (A) and methanol (B). The multiple reaction monitoring (MRM) mode with electrospray ionization in the positive ion mode was used for detection. The linear range was 0.1 ng/mL to 50 ng/mL for chrysin and tectochrysin, respectively. The accuracy (relative error, RE%) ranged from −8.8% to 7.5% and the intra-day and inter-day precision were within 15% and had a mean extraction recovery rate of 80.3% to 86.7%. The validated method was applied to a comparative pharmacokinetic study after oral administration of Alpinia oxyphylla fruit ethanol extract between normal rats and dementia rats. The area under the curve (AUC) and peak plasma concentration (Cmax) of the two constituents were remarkably increased in dementia rats than in normal rats. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) represents the most common type of clinical cardiac arrhythmia and substantially increases the risks of cerebral stroke, heart failure and death. Accumulating evidence has convincingly demonstrated the strong genetic basis of AF, and an increasing number of pathogenic variations in over 50 genes have been causally linked to AF. Nevertheless, AF is of pronounced genetic heterogeneity, and the genetic determinants underpinning AF in most patients remain obscure. In the current investigation, a Chinese pedigree with AF as well as ventricular arrhythmias and hypertrophic cardiomyopathy was recruited. Whole exome sequencing and bioinformatic analysis of the available family members were conducted, and a novel heterozygous variation in the KLF15 gene (encoding Krüppel-like factor 15, a transcription factor critical for cardiac electrophysiology and structural remodeling), NM_014079.4: c.685A>T; p.(Lys229*), was identified. The variation was verified by Sanger sequencing and segregated with autosomal dominant AF in the family with complete penetrance. The variation was absent from 300 unrelated healthy subjects used as controls. In functional assays using a dual-luciferase assay system, mutant KLF15 showed neither transcriptional activation of the KChIP2 promoter nor transcriptional inhibition of the CTGF promoter, alone or in the presence of TGFB1, a key player in the pathogenesis of arrhythmias and cardiomyopathies. The findings indicate KLF15 as a new causative gene responsible for AF as well as ventricular arrhythmias and hypertrophic cardiomyopathy, and they provide novel insight into the molecular mechanisms underlying cardiac arrhythmias and hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

The administration of A/B exams usually involves the use of items. Issues arise when the pre-establishment of a question bank is necessary and the inconsistency in the knowledge points to be tested (in the two exams) reduces the exams 'fairness'. These are critical for a large multi-teacher course wherein the teachers are changed such that the course and examination content are altered every few years. However, a fair test with randomly participating students should still be a guaranteed subject with no item pool. Through data-driven decision-making, this study collected data related to a term test for a compulsory general course for empirical assessments, pre-processed the data and used item response theory to statistically estimate the difficulty, discrimination and lower asymptotic for each item in the two exam papers. Binary goal programing was finally used to analyze and balance the fairness of A/B exams without an item pool. As a result, pairs of associated questions in the two exam papers were optimized in terms of their overall balance in three dimensions (as the goals) through the paired exchanges of items. These exam papers guarantee their consistency (in the tested knowledge points) and also ensure the fairness of the term test (a key psychological factor that motivates continued studies). Such an application is novel as the teacher(s) did not have a pre-set question bank and could formulate the fairest strategy for the A/B exam papers. The model can be employed to address similar teaching practice issues. [ABSTRACT FROM AUTHOR]