Sound source direction-of-arrival estimation method for microphone array based on ultra-weak fiber Bragg grating distributed acoustic sensor.

A sound source direction-of-arrival (DOA) estimation method for microphone array based on ultra-weak fiber Bragg grating (UW-FBG) distributed acoustic sensor is proposed. The principle of acoustic signal demodulation is introduced, the sound pressure sensitivity and frequency response range of a single UW-FBG microphone are analyzed, and a series linear array with three UW-FBG microphones is designed. Combined with convolutional recurrent neural networks, the DOA estimation method is developed. Log-Mel spectral features and SCOT/PHAT joint weighting generalized cross correlation features are used for DOA estimation. The corresponding system is established and experimentally verified. Results show that the measured sound pressure sensitivity of the UW-FBG microphone is in the range of 0.1032-3.306 rad/Pa within the frequency range of 1000-3000 Hz, and the peak sound pressure sensitivity is about 3.306 rad/Pa. The estimated mean error of 2D DOA estimation is about 2.85°, and the error of 3D DOA estimation is about 5.465°. This method has good application prospects in distributed sound source localization.

Assessing thyroid cancer risk using polygenic risk scores.

Genome-wide association studies (GWASs) have identified at least 10 single-nucleotide polymorphisms (SNPs) associated with papillary thyroid cancer (PTC) risk. Most of these SNPs are common variants with small to moderate effect sizes. Here we assessed the combined genetic effects of these variants on PTC risk by using summarized GWAS results to build polygenic risk score (PRS) models in three PTC study groups from Ohio (1,544 patients and 1,593 controls), Iceland (723 patients and 129,556 controls), and the United Kingdom (534 patients and 407,945 controls). A PRS based on the 10 established PTC SNPs showed a stronger predictive power compared with the clinical factors model, with a minimum increase of area under the receiver-operating curve of 5.4 percentage points (P ≤ 1.0 × 10-9). Adding an extended PRS based on 592,475 common variants did not significantly improve the prediction power compared with the 10-SNP model, suggesting that most of the remaining undiscovered genetic risk in thyroid cancer is due to rare, moderate- to high-penetrance variants rather than to common low-penetrance variants. Based on the 10-SNP PRS, individuals in the top decile group of PRSs have a close to sevenfold greater risk (95% CI, 5.4-8.8) compared with the bottom decile group. In conclusion, PRSs based on a small number of common germline variants emphasize the importance of heritable low-penetrance markers in PTC.

Comparison of the effects of contrast-enhanced ultrasound and conventional ultrasound-guided radiofrequency ablation on benign thyroid nodules.

Objective: To compare the effect of contrast-enhanced ultrasound (CEUS) and conventional ultrasound-guided radiofrequency ablation (RFA) on benign thyroid nodules (BTNs). Methods: In this retrospective observational study, the data of 72 patients with BTNs who received RFA treatment in The Fourth Affiliated Hospital of Zhejiang University School of Medicine from January 2020 to December 2021 were retrospectively reviewed and selected. The records showed that 34 patients received RFA under the guidance of conventional ultrasound (conventional ultrasound group) and 38 patients received RFA under the guidance of CEUS (CEUS group). The effect of treatment, complications and recurrence of the two groups were compared and analyzed. Results: There was a smaller volume of thyroid nodules in the two groups immediately post-operation. The incidence of complications was lower in the CEUS group (5.26%) compared to the conventional ultrasound group (23.53%) (P<0.05). The recurrence rate at 6-months (0.00% vs 11.76%) and 12- months (2.63% vs 20.59%) post-operation was lower in the CEUS group compared to the conventional ultrasound group (P<0.05). Conclusions: Compared with conventional ultrasound, CEUS-guided RFA is effective in treating BTNs, with smaller postoperative nodule volume, reduced occurrence of surgical complications, and reduced recurrence rate of thyroid nodules.

Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium.

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.

Variants in LRRC34 reveal distinct mechanisms for predisposition to papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) demonstrates high heritability and a low somatic mutation burden relative to other cancers. Therefore, the genetic risk predisposing to PTC is likely due to a combination of low penetrance variants. A recent genome-wide association study revealed the association of PTC with a missense variant, rs6793295, at 3q26 in a gene called Leucine Repeat Rich Containing 34 (LRRC34). METHODS: We report the mechanisms of PTC risk at 3q26 using a combination of overexpression, mass spectroscopy, knockdown, transcriptome profiling, migration assays and genetic analysis. RESULTS: We observed differential binding of wild-type and missense LRRC34 to RANBP1. Overexpression of missense LRRC34 reduced RanGTP levels and increased apoptosis. We also identified a second linkage disequilibrium (LD) block upstream of LRRC34 containing regulatory variants with allele-specific expression. Transcriptome profiling of LRRC34 knockdown cells showed changes in genes involved with cellular movement. LRRC34 knockdown reduced the migration of thyroid cancer cell lines. Lastly, we assessed the relative contribution of PTC risk from each locus using haplotype analysis. CONCLUSIONS: Our study demonstrates two separate mechanisms, one in G protein signalling and the other in transcriptional control, dictating PTC risk at 3q26 using both biochemical and genetic techniques.

Deformation detection of a double-clamped beam according to ultra-weak fiber Bragg grating.

Metal beam strain detection may offer valuable insight into health monitoring for large-scale steel structures. This research presents, to the best of our knowledge, the first implementation of ultra-weak fiber Bragg gratings for the deformation detection of a double-clamped beam because of their higher multiplexing and denser detection points compared to fiber Bragg gratings. The measured values are entirely consistent with those determined by strain gauges applied for reference and demonstrate that the strain of each sensing point increases linearly with the load at the middle of the beam. The errors of different loads at different load points between inversion maximum deflection and measured displacement are less than 9.59%.

Pilot study of a customized nanotextile wet garment treatment on moderate and severe atopic dermatitis: A randomized clinical trial.

BACKGROUND: Atopic dermatitis (AD) is a common dermatosis. The cornerstone of eczema management is to repair and maintain skin barrier and hydration, as well as to reduce inflammation. Wet wrap therapy (WWT) is a widely used adjunct to achieve this. The conventional material used for WWT is viscose, which presents drawbacks including discomfort, high cost, and poor durability. Here, we explore the possibility of using customized nanotextile (nanopolyester) for WWT, hoping to prove that this material is non-inferior to viscose in clinical effectiveness and patient acceptance. METHODS: Patients aged 0-18 years with moderate to severe eczema were randomized to receive either viscose (Tubifast™) or nanotextile for WWT. Patients were instructed to apply WWT daily overnight for 2 weeks. Patients' disease severity score (IGA, SCORAD) and quality of life (QoL) score (IDQOL/CDLQI) were measured on day 0, 7, and 14 of treatment. Patient survey was conducted to collect patients' feedback about garment use. RESULTS: Fifty-three children aged 7 months to 17 years were recruited (27 in Tubifast™ and 26 in nanotextile group). Patients in both groups showed significant improvement in disease severity and QoL from baseline (P < .001), and such improvement was similar in both groups. However, nanotextile garment was significantly more comfortable (2.73/10 vs 5.12/10, P = .001), easier to wear (2.78/10 vs 5.24/10, P = .003), and cooler (2.43/10 vs 3.96/10, P = .033) from patients' feedback. CONCLUSION: This study demonstrates that nanomaterial is as effective as conventional viscose in WWT, while superior in patient acceptability. Nanotextile for WWT has good potential in eczema management, especially in patients with suboptimal response to topicals alone.

MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus.

A locus on chromosome 9q22 harbors a SNP (rs965513) firmly associated with risk of papillary thyroid carcinoma (PTC). The locus also comprises the forkhead box E1 (FOXE1) gene, which is implicated in thyroid development, and a long noncoding RNA (lncRNA) gene, papillary thyroid cancer susceptibility candidate 2 (PTCSC2). How these might interact is not known. Here we report that PTCSC2 binds myosin-9 (MYH9). In a bidirectional promoter shared by FOXE1 and PTCSC2, MYH9 inhibits the promoter activity in both directions. This inhibition can be reversed by PTCSC2, which acts as a suppressor. RNA knockdown of FOXE1 in primary thyroid cells profoundly interferes with the p53 pathway. We propose that the interaction between the lncRNA, its binding protein MYH9, and the coding gene FOXE1 underlies the predisposition to PTC triggered by rs965513.

Fine mapping of 14q13 reveals novel variants associated with different histological subtypes of papillary thyroid carcinoma.

The first two genome wide association studies (GWAS) of papillary thyroid carcinoma (PTC) detected five variants associated with PTC. Two of them (rs944289 and rs116909374) are located at 14q13 making that locus an important target of research into the genetic predisposition to PTC. We aimed at uncovering other variants at 14q13 associated with PTC independently from the GWAS variants. We performed next generation sequencing of the 14q13 region and analyzed the allele frequencies of single nucleotide polymorphisms (SNPs) in n = 90 PTC cases vs. n = 379 EUR controls from the 1,000 Genome Project. The variants associated with PTC were validated in an Ohio cohort of n = 1,216 PTC cases and n = 1,416 controls. Next, we analyzed the association between SNPs and expression of nearby genes and clinical parameters. We showed that rs368187 was associated with PTC (OR = 1.31, p = 2.20 × 10-6 ). Rs1632250, Rs1863347 and rs1755787 showed association with classical PTC (cPTC) (n = 891; OR = 1.24, 2.22 × 10-3 , OR = 1.31, p = 2.15 × 10-4 and OR = 1.24, p = 2.06 × 10-3 , respectively) while variant rs28397092 showed association with follicular variant (n = 243; OR = 1.51, p = 1.36 × 10-3 ). Rs1863347 was associated with suppression of PTCSC3 in unaffected thyroid tissue (p = 0.026). Rs1632250, rs1863347 and rs1755787 showed association with multifocality (OR = 1.85, p = 0.001, OR = 1.98, p = 0.001 and OR = 1.76, p = 0.003 respectively) and N stage (OR = 1.79, p = 0.014, OR = 1.73, p = 0.023 and OR = 1.81, p = 0.013, respectively) in microPTC (n = 328) while rs368187 was associated with M stage (OR = 0.56, p = 0.034) in cPTC. Our results disclose multiple variants associated with PTC and clinical features in the 14q13 superlocus. We suggest that translational genotype/phenotype studies should take into account not only somatic mutations but also germline variants.

The role of SMAD3 in the genetic predisposition to papillary thyroid carcinoma.

PURPOSE: To identify and characterize the functional variants, regulatory gene networks, and potential binding targets of SMAD3 in the 15q22 thyroid cancer risk locus. METHODS: We performed linkage disequilibrium (LD) and haplotype analyses to fine map the 15q22 locus. Luciferase reporter assays were applied to evaluate the regulatory effects of the candidate variants. Knockdown by small interfering RNA, microarray analysis, chromatin immunoprecipitation (ChIP) and quantitative real-time polymerase chain reaction assays were performed to reveal the regulatory gene network and identify its binding targets. RESULTS: We report a 25.6-kb haplotype within SMAD3 containing numerous single-nucleotide polymorphisms (SNPs) in high LD. SNPs rs17293632 and rs4562997 were identified as functional variants of SMAD3 by luciferase assays within the LD region. These variants regulate SMAD3 transcription in an allele-specific manner through enhancer elements in introns of SMAD3. Knockdown of SMAD3 in thyroid cancer cell lines revealed its regulatory gene network including two upregulated genes, SPRY4 and SPRY4-IT1. Sequence analysis and ChIP assays validated the actual binding of SMAD3 protein to multiple SMAD binding element sites in the region upstream of SPRY4. CONCLUSION: Our data provide a functional annotation of the 15q22 thyroid cancer risk locus.