Prevalence of the GJB2 IVS1+1G >A mutation in Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2

<p>Abstract</p> <p>Background</p> <p>Mutations in the GJB2 gene are the most common cause of nonsyndromic recessive hearing loss in China. In about 6% of Chinese patients with severe to profound sensorineural hearing impairment, only monoallelic <it>GJB2 </it>mutations known to be either recessive or of unclear pathogenicity have been identified. This paper reports the prevalence of the <it>GJB2 </it>IVS1+1G>A mutation in a population of Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of <it>GJB2</it>.</p> <p>Methods</p> <p>Two hundred and twelve patients, screened from 7133 cases of nonsyndromic hearing loss in China, with monoallelic mutation (mainly frameshift and nonsense mutation) in the coding region of <it>GJB2 </it>were examined for the <it>GJB2 </it>IVS1+1G>A mutation and mutations in the promoter region of this gene. Two hundred and sixty-two nonsyndromic hearing loss patients without <it>GJB2 </it>mutation and 105 controls with normal hearing were also tested for the <it>GJB2 </it>IVS1+1G>A mutation by sequencing.</p> <p>Results</p> <p>Four patients with monoallelic mutation in the coding region of <it>GJB2 </it>were found carrying the <it>GJB2 </it>IVS1+1G>A mutation on the opposite allele. One patient with the <it>GJB2 </it>c.235delC mutation carried one variant, -3175 C>T, in exon 1 of <it>GJB2</it>. Neither <it>GJB2 </it>IVS1+1G>A mutation nor any variant in exon 1 of <it>GJB2 </it>was found in the 262 nonsyndromic hearing loss patients without <it>GJB2 </it>mutation or in the 105 normal hearing controls.</p> <p>Conclusion</p> <p>Testing for the <it>GJB2 </it>IVS 1+1 G to A mutation explained deafness in 1.89% of Chinese <it>GJB2 </it>monoallelic patients, and it should be included in routine testing of patients with <it>GJB2 </it>monoallelic pathogenic mutation.</p

Design and Analysis of Long-Stroke Planar Switched Reluctance Motor for Positioning Applications

This paper presents the design, control, and experimental performance evaluation of a long-stroke planar switched reluctance motor (PSRM) for positioning applications. Based on comprehensive consideration of the electromagnetic and mechanical characteristics of the PSRM, a motor design is first developed to reduce the force ripple and deformation. A control scheme with LuGre friction compensation is then proposed to improve the positioning accuracy of the PSRM. Furthermore, this control scheme is proven to ensure the stable motion of the PSRM system. Additionally, the response speed and steady-state error of the PSRM system with this control scheme are theoretically analyzed. Finally, the experimental results are presented and analyzed. The effectiveness of the precision long-stroke motion of the PSRM and its promise for use in precision positioning applications are verified experimentally

Hepatic arterial infusion chemotherapy versus sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombus: An updated meta-analysis and systematic review

BackgroundSorafenib was the first drug approved for advanced hepatocellular carcinoma (HCC). However, it is limited by poor efficacy for HCC with portal vein tumor thrombus (PVTT). Some studies suggested that hepatic artery infusion chemotherapy (HAIC) could provide survival benefits to patients with advanced HCC with PVTT.AimThe study aimed to compare the efficacy of HAIC versus sorafenib in patients with HCC accompanied by PVTT.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for studies published until September 2022. Statistical analyses were performed using Stata SE 15 software.ResultsEight studies with 672 patients, 403 in the HAIC group and 269 in the sorafenib group, were included in the meta-analysis. The rates of complete response (RR=3.88, 95%CI:1.35-11.16, P=0.01), partial response (RR=3.46, 95%CI:1.94-6.18, P&lt;0.0001), objective response rate (RR=4.21, 95%CI:2.44-7.28, P&lt;0.00001) and disease control rate (RR=1.73, 95%CI:1.28-2.35, P=0.0004) were significantly higher in the HAIC group compared to the sorafenib group, whereas the progressive disease rate (RR=0.57, 95%CI:0.40-0.80, P=0.02) was significantly lower in the former. In contrast, the stable disease rate (RR=1.10, 95%CI (0.69-1.76), P=0.68) was similar in both groups. The overall survival (HR=0.50, 95%CI:0.40-0.63, P&lt;0.05) and progression-free survival (HR=0.49, 95%CI:0.35-0.67, P&lt;0.05) rates were significantly higher in the HAIC group compared to the sorafenib group.ConclusionHAIC has better efficacy against HCC with PVTT than sorafenib and may be considered an alternative to the latter. However, more high-quality randomized control trials and longer follow-ups are needed to verify our findings

VoiceFixer: A Unified Framework for High-Fidelity Speech Restoration

Speech restoration aims to remove distortions in speech signals. Prior methods mainly focus on a single type of distortion, such as speech denoising or dereverberation. However, speech signals can be degraded by several different distortions simultaneously in the real world. It is thus important to extend speech restoration models to deal with multiple distortions. In this paper, we introduce VoiceFixer, a unified framework for high-fidelity speech restoration. VoiceFixer restores speech from multiple distortions (e.g., noise, reverberation, and clipping) and can expand degraded speech (e.g., noisy speech) with a low bandwidth to 44.1 kHz full-bandwidth high-fidelity speech. We design VoiceFixer based on (1) an analysis stage that predicts intermediate-level features from the degraded speech, and (2) a synthesis stage that generates waveform using a neural vocoder. Both objective and subjective evaluations show that VoiceFixer is effective on severely degraded speech, such as real-world historical speech recordings. Samples of VoiceFixer are available at https://haoheliu.github.io/voicefixer.Comment: Submitted to INTERSPEECH 202

Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis

<p>Abstract</p> <p>Background</p> <p>The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of <it>GJB2 </it>gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried <it>GJB2 </it>mutations. The <it>SLC26A4 </it>gene mutations and relevant phenotype are analyzed in this study.</p> <p>Methods</p> <p>One hundred and thirty-five deaf patients were included. The coding exons of <it>SLC26A4 </it>gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic <it>GJB2 </it>mutations or one patient carrying a known <it>GJB2 </it>dominant mutation as well as one patient with <it>mtDNA </it>1555A>G mutation. All patients with <it>SLC26A4 </it>mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays.</p> <p>Results</p> <p>Twenty-six patients (19.26%, 26/135) were found carrying <it>SLC26A4 </it>mutation. Among them, 17 patients with bi-allelic <it>SLC26A4 </it>mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one <it>SLC26A4 </it>mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43) of all <it>SLC26A4 </it>mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed.</p> <p>Conclusion</p> <p>In Inner Mongolia, China, mutations in <it>SLC26A4 </it>gene account for about 12.6% (17/135) of the patients with hearing loss. Together with <it>GJB2 </it>(23/135), <it>SLC26A4 </it>are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects <it>SLC26A4 </it>mutations prior to the temporal bone CT scan to find EVA and inner ear malformation patients. This model has a unique advantage in epidemiologic study of large deaf population.</p

Early-Life Exposure to Polycyclic Aromatic Hydrocarbons and ADHD Behavior Problems

Importance Polycyclic aromatic hydrocarbons are widespread urban air pollutants from combustion of fossil fuel and other organic material shown previously to be neurotoxic. Objective In a prospective cohort study, we evaluated the relationship between Attention Deficit Hyperactivity Disorder behavior problems and prenatal polycyclic aromatic hydrocarbon exposure, adjusting for postnatal exposure. Materials and Methods Children of nonsmoking African-American and Dominican women in New York City were followed from in utero to 9 years. Prenatal polycyclic aromatic hydrocarbon exposure was estimated by levels of polycyclic aromatic hydrocarbon- DNA adducts in maternal and cord blood collected at delivery. Postnatal exposure was estimated by the concentration of urinary polycyclic aromatic hydrocarbon metabolites at ages 3 or 5. Attention Deficit Hyperactivity Disorder behavior problems were assessed using the Child Behavior Checklist and the Conners Parent Rating Scale- Revised. Results High prenatal adduct exposure, measured by elevated maternal adducts was significantly associated with all Conners Parent Rating Scale-Revised subscales when the raw scores were analyzed continuously (N = 233). After dichotomizing at the threshold for moderately to markedly atypical symptoms, high maternal adducts were significantly associated with the Conners Parent Rating Scale-Revised DSM-IV Inattentive (OR = 5.06, 95% CI [1.43, 17.93]) and DSM-IV Total (OR = 3.37, 95% CI [1.10, 10.34]) subscales. High maternal adducts were positivity associated with the DSM-oriented Attention Deficit/Hyperactivity Problems scale on the Child Behavior Checklist, albeit not significant. In the smaller sample with cord adducts, the associations between outcomes and high cord adduct exposure were not statistically significant (N = 162). Conclusion The results suggest that exposure to polycyclic aromatic hydrocarbons encountered in New York City air may play a role in childhood Attention Deficit Hyperactivity Disorder behavior problems

Disentangling the effects of vapor pressure deficit on northern terrestrial vegetation productivity

The impact of atmospheric vapor pressure deficit (VPD) on plant photosynthesis has long been acknowledged, but large interactions with air temperature (T) and soil moisture (SM) still hinder a complete understanding of the influence of VPD on vegetation production across various climate zones. Here, we found a diverging response of productivity to VPD in the Northern Hemisphere by excluding interactive effects of VPD with T and SM. The interactions between VPD and T/SM not only offset the potential positive impact of warming on vegetation productivity but also amplifies the negative effect of soil drying. Notably, for high-latitude ecosystems, there occurs a pronounced shift in vegetation productivity\u27s response to VPD during the growing season when VPD surpasses a threshold of 3.5 to 4.0 hectopascals. These results yield previously unknown insights into the role of VPD in terrestrial ecosystems and enhance our comprehension of the terrestrial carbon cycle\u27s response to global warming

Contrasting fate of western Third Pole's water resources under 21st century climate change

Seasonal melting of glaciers and snow from the western Third Pole (TP) plays important role in sustaining water supplies downstream. However, the future water availability of the region, and even today’s runoff regime, are both hotly debated and inadequately quantified. Here, we characterize the contemporary flow regimes and systematically assess the future evolution of total water availability, seasonal shifts, and dry and wet discharge extremes in four most meltwater-dominated basins in the western TP, by using a process-based, well-established glacier-hydrology model, well-constrained historical reference climate data, and the ensemble of 22 global climate models with an advanced statistical downscaling and bias correction technique. We show that these basins face sharply diverging water futures under 21st century climate change. In RCP scenarios 4.5 and 8.5, increased precipitation and glacier runoff in the Upper Indus and Yarkant basins more than compensate for decreased winter snow accumulation, boosting annual and summer water availability through the end of the century. In contrast, the Amu and Syr Darya basins will become more reliant on rainfall runoff as glacier ice and seasonal snow decline. Syr Darya summer river-flows, already low, will fall by 16–30% by end-of-century, and striking increases in peak flood discharge (by >60%), drought duration (by >1 month) and drought intensity (by factor 4.6) will compound the considerable water-sharing challenges on this major transboundary river

Comparative Genomics Unravels the Functional Roles of Co-occurring Acidophilic Bacteria in Bioleaching Heaps

The spatial-temporal distribution of populations in various econiches is thought to be potentially related to individual differences in the utilization of nutrients or other resources, but their functional roles in the microbial communities remain elusive. We compared differentiation in gene repertoire and metabolic profiles, with a focus on the potential functional traits of three commonly recognized members (Acidithiobacillus caldus, Leptospirillum ferriphilum, and Sulfobacillus thermosulfidooxidans) in bioleaching heaps. Comparative genomics revealed that intra-species divergence might be driven by horizontal gene transfer. These co-occurring bacteria shared a few homologous genes, which significantly suggested the genomic differences between these organisms. Notably, relatively more genes assigned to the Clusters of Orthologous Groups category [G] (carbohydrate transport and metabolism) were identified in Sulfobacillus thermosulfidooxidans compared to the two other species, which probably indicated their mixotrophic capabilities that assimilate both organic and inorganic forms of carbon. Further inspection revealed distinctive metabolic capabilities involving carbon assimilation, nitrogen uptake, and iron-sulfur cycling, providing robust evidence for functional differences with respect to nutrient utilization. Therefore, we proposed that the mutual compensation of functionalities among these co-occurring organisms might provide a selective advantage for efficiently utilizing the limited resources in their habitats. Furthermore, it might be favorable to chemoautotrophs' lifestyles to form mutualistic interactions with these heterotrophic and/or mixotrophic acidophiles, whereby the latter could degrade organic compounds to effectively detoxify the environments. Collectively, the findings shed light on the genetic traits and potential metabolic activities of these organisms, and enable us to make some inferences about genomic and functional differences that might allow them to co-exist