Protein truncating variants in mitochondrial-related nuclear genes and the risk of chronic liver disease.

BACKGROUND: Mitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of liver diseases have not been extensively explored. METHODS: We extracted 60,928 PTVs across 2466 MT-related nucleus genes using whole-exome sequencing data obtained from 442,603 participants in the UK Biobank. We examined their associations with liver dysfunction that represented by the liver-related biomarkers and the risks of chronic liver diseases and liver-related mortality. RESULTS: 96.10% of the total participants carried at least one PTV. We identified 866 PTVs that were positively associated with liver dysfunction at the threshold of P value < 8.21e - 07. The coding genes of these PTVs were mainly enriched in pathways related to lipid, fatty acid, amino acid, and carbohydrate metabolisms. The 866 PTVs were presented in 1.07% (4721) of participants. Compared with participants who did not carry any of the PTVs, the carriers had a 5.33-fold (95% CI 4.15-6.85), 2.82-fold (1.69-4.72), and 4.41-fold (3.04-6.41) increased risk for fibrosis and cirrhosis of liver, liver cancer, and liver disease-related mortality, respectively. These adverse effects were consistent across subgroups based on age, sex, body mass index, smoking status, and presence of hypertension, diabetes, dyslipidemia, and metabolic syndrome. CONCLUSIONS: Our findings revealed a significant impact of PTVs in MT-related genes on liver disease risk, highlighting the importance of these variants in identifying populations at risk of liver diseases and facilitating early clinical interventions.

Genotype, cervical intraepithelial neoplasia, and type-specific cervical intraepithelial neoplasia distributions in hrHPV+ cases referred to colposcopy: A multicenter study of Chinese mainland women.

To investigate age and type-specific prevalences of high-risk human papillomavirus (hrHPV) and cervical intraepithelial neoplasia (CIN) in hrHPV+ women referred to colposcopy. This is a retrospective, multicenter study. Participants were women referred to one of seven colposcopy clinics in China after testing positive for hrHPV. Patient characteristics, hrHPV genotyping, colposcopic impressions, and histological diagnoses were abstracted from electronic records. Main outcomes were age-related type-specific prevalences associated with hrHPV and CIN, and colposcopic accuracy. Among 4419 hrHPV+ women referred to colposcopy, HPV 16, 52, and 58 were the most common genotypes. HPV 16 prevalence was 39.96%, decreasing from 42.57% in the youngest group to 30.81% in the eldest group. CIN3+ prevalence was 15.00% and increased with age. As lesion severity increases, HPV16 prevalence increased while the prevalence of HPV 52 and 58 decreased. No age-based trend was identified with HPV16 prevalence among CIN2+, and HPV16-related CIN2+ was less common in women aged 60 and above (44.26%) compared to those younger than 60 years (59.61%). Colposcopy was 0.73 sensitive at detecting CIN2+ (95% confidence interval[CI]: 0.71, 0.75), with higher sensitivity (0.77) observed in HPV16+ women (95% CI: 0.74, 0.80) compared to HPV16- women (0.68, 95% CI: 0.64, 0.71). Distributions of hrHPV genotypes, CIN, and type-specific CIN in Chinese mainland hrHPV+ women referred to colposcopy were investigated for the first time. Distributions were found to be age-dependent and colposcopic performance appears related to HPV genotypes. These findings could be used to improve the management of women referred to colposcopy.

Assessing colposcopy competencies in medically underserved communities: a multi-center study in China.

BACKGROUND: Colposcopy plays an essential role in diagnosing cervical lesions and directing biopsy; however, there are few studies of the capabilities of colposcopists in medically underserved communities in China. This study aims to fill this gap by assessing colposcopists' competencies in medically underserved communities of China. METHODS: Colposcopists in medically underserved communities across China were considered eligible to participate. Assessments involved presenting participants with 20 cases, each consisting of several images and various indications. Participants were asked to determine transformation zone (TZ) type, colposcopic diagnoses and to decide whether biopsy was necessary. Participants are categorized according to the number of colposcopic examinations, i.e., above or below 50 per annum. RESULTS: There were 214 participants in this study. TZ determination accuracy was 0.47 (95% CI 0.45,0.49). Accuracy for colposcopic diagnosis was 0.53 (95% CI 0.51,0.55). Decision to perform biopsies was 0.73 accurate (95% CI 0.71,0.74). Participants had 0.61 (95% CI 0.59,0.64) sensitivity and a 0.80 (95% CI 0.79,0.82) specificity for detecting high-grade lesions. Colposcopists who performed more than 50 cases were more accurate than those performed fewer across all indicators, with a higher sensitivity (0.66 vs. 0.57, p = 0.001) for detecting high-grade lesions. CONCLUSIONS: In medically underserved communities of China, colposcopists appear to perform poorly at TZ identification, colposcopic diagnosis, and when deciding to biopsy. Colposcopists who undertake more than 50 colposcopies each year performed better than those who perform fewer. Therefore, colposcopic practice does improve through case exposure although there is an urgent need for further pre-professional and clinical training.

Hollow-core terahertz Bragg waveguide based on a helical support structure.

A helical structural support scheme is proposed to mechanically support dielectric layers in a hollow-core terahertz Bragg waveguide by means of an axially rotating wrap-around strip structure. The helical-strip supported waveguide samples are fabricated using 3D printing technology, and the waveguide samples are experimentally tested using a terahertz time-domain spectroscopy system. The results show that choosing a suitable helix period can obtain loss characteristics close to those of an ideal Bragg waveguide, with a low transmission loss of less than 0.097 dB/m in the range of 0.57-0.58 THz.

Knowledge, Attitude, and Uptake of Human Papillomavirus (HPV) Vaccination among Chinese Female Adults: A National Cross-sectional Web-Based Survey Based on a Large E-commerce Platform.

BACKGROUND: Human papillomavirus (HPV) vaccination is a promising step toward cervical cancer elimination. This study was conducted to investigate the knowledge, attitude, and HPV vaccine uptake among female adults in mainland China based on a large e-commerce platform. METHODS: We conducted a cross-sectional online survey of female adults between March 4 to April 20, 2022. The survey consisted of sociodemographic information, related knowledge, vaccination uptake, and attitudes toward vaccination. We included women aged 18-45 years in the final analysis. Logistic regressions were conducted to explore influencing factors associated with related knowledge, HPV vaccination uptake, and willingness to be vaccinated. RESULTS: In total, 3,572 female adults (34 years, IQR 30-39) were included in the analysis. The majority of the participants were highly educated (78.7%) with a high monthly family income (79.0%). The median HPV knowledge score was 8.25 out of 11. More than 75% of respondents were unvaccinated, while 95.8% of unvaccinated female adults are willing to be vaccinated. Variables such as age, insurance, vaccination history, and whether one had heard of the HPV vaccine influence HPV vaccination practice (all p-values < 0.05). The main barriers to vaccination were vaccine inaccessibility and the high cost of the vaccine. CONCLUSION: The findings of our study highlight a moderate knowledge level, poor vaccination rate, and strong willingness to be vaccinated among Chinese female adults who were better educated and wealthier. Targeted health education and practical support should be provided in the future, to reduce gaps between vaccine uptake and vaccine acceptance.

Quantitative Label-Free SERS Detection of Trace Fentanyl in Biofluids with a Freestanding Hydrophobic Plasmonic Paper Biosensor.

The prevalence of fentanyl abuse raises global public health concerns with an unprecedented surge in overdose deaths. Rapid identification and quantification of fentanyl in biofluids is of paramount importance to combat fentanyl abuse for law enforcement agencies and promptly treat patients for medical professionals. Herein, a freestanding surface-enhanced Raman spectroscopy (SERS) biosensor with excellent condensing enrichment capability, termed FrEnSERS biosensor, is reported for quantitative label-free detection of trace fentanyl in biofluids. This biosensor comprises a reduced graphene oxide membrane decorated with high-density hydrophobic Au nanostars. A combination of the high SERS enhancement and the focusing effect for analyte enrichment of the hydrophobic surface accounts for the remarkable SERS performance of the FrEnSERS biosensor. We demonstrate that the FrEnSERS biosensor achieves the sensitive and quantitative detection of fentanyl in both serum and urine over a wide dynamic range spanning more than 4 orders of magnitude, with a limit of detection of 0.47 ng/mL for serum samples and 0.73 ng/mL for urine samples. Our biosensor is sensitive, cost-effective, and reliable for rapid quantitative analysis of fentanyl in biofluids with great promise for forensic analysis and clinical diagnosis.

PI-NLOS: polarized infrared non-line-of-sight imaging.

Passive non-line-of-sight (NLOS) imaging is a promising technique to enhance visual perception for the occluded object hidden behind the wall. Here we present a data-driven NLOS imaging framework by using polarization cue and long-wavelength infrared (LWIR) images. We design a dual-channel input deep neural network to fuse the intensity features from polarized LWIR images and contour features from polarization degree images for NLOS scene reconstruction. To train the model, we create a polarized LWIR NLOS dataset which contains over ten thousand images. The paper demonstrates the passive NLOS imaging experiment in which the hidden people is approximate 6 meters away from the relay wall. It is an exciting finding that even the range is further than that in the prior works. The quantitative evaluation metric of PSNR and SSIM show that our method as an advance over state-of-the-art in passive NLOS imaging.

Enhancing colposcopy training using a widely accessible digital education tool in China.

BACKGROUND: Colposcopy is a cornerstone of cervical cancer prevention; however, there is a global shortage of colposcopists. It is challenging to train a sufficient number of colposcopists through in-person methods, which hinders our ability to adequately diagnose and manage positive cases. A digital platform is needed to make colposcopy training more efficient, scalable, and sustainable; however, current online training programs are generally based on didactic curricula that do not incorporate image analysis training. In addition, long-term assessments of online training are not readily available. Therefore, innovative digital training and an assessment of its effectiveness are needed. OBJECTIVE: This study aimed to evaluate the short- and long-term effects of DECO (an online Digital Education Tool for Colposcopy) on trainees' colposcopy competencies and confidence. STUDY DESIGN: DECO can be used both on laptops and smartphones and comprises 4 training modules (image interpretation; terminology learning; video teaching; and collection of guidelines and typical cases) and 2 test modules. DECO was tested through a pre-post study between September and November 2022. Participants were recruited in China, and DECO training lasted 12 days. Trainees initially learned basic theory before completing training using 200 image-based cases. Pretest, posttest, and follow-up testing included 20 distinct image-based questions, and was conducted on Days 0, 13, and 60. Primary outcomes were competence and confidence scores. Secondary measures were response distributions for colposcopic diagnoses, biopsies, and DECO training satisfaction. Multilevel modeling was used to determine improvement from baseline to posttraining and follow-up for the outcomes of interest. RESULTS: Among 402 participants recruited, 96.8% (n=389) completed pretesting, 84.1% (n=338) posttesting, and 75.1% (n=302) follow-up testing. Colposcopic competence and confidence increased across this study. Diagnostic scores improved on average from 55.3 (53.7-56.9) to 70.4 (68.9-71.9). The diagnostic accuracy for normal/benign lesions, low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions or worse increased by 16.9%, 13.1%, and 16.9%, respectively. Mean confidence scores increased from 48.1 (45.6-50.6) to 56.2 (54.5-57.9). These improvements remained evident 2 months after training. Trainees were also satisfied with DECO overall. Most found DECO to be scientific (82.5%), easy to use (75.2%), and clinically useful (98.4%), and would recommend it to colleagues (93.2%). CONCLUSION: DECO is a useful, acceptable digital education tool that improves colposcopy competencies and confidence. DECO could make colposcopy training more efficient, scalable, and sustainable because there are no geographic or time limitations. Therefore, DECO could be used to alleviate the shortage of trained colposcopists around the world.

Development and validation of the systemic lupus erythematous scale amongst the system of quality of life instruments for chronic diseases QLICD-SLE (V2.0).

OBJECTIVE: The present study is aimed to develop and validate a quality of life scale for systemic lupus erythematosus (SLE) patients with Chinese cultural background, QLICD-SLE (V2.0). METHODS: The QLICD-SLE (V2.0) was developed using a systematic approach that involved focus groups, nominal discussions, and pilot testing. A total of 428 SLE patients participated in the scale's assessment. Validity was examined through qualitative analysis, item domain correlation, multidimensional scaling, and factor analysis. Reliability was assessed using Pearson's correlation and Cronbach's alpha coefficients. To evaluate responsiveness, paired T-tests were conducted to compare pre- and post-treatment measurements with the standardised response mean (SRM) being calculated. RESULTS: Correlation and factor analyses demonstrated strong construct validity. When using SF-36 as criteria, the correlation between various domains of QLICD-SLE and SF-36 ranged from 0.55 to 0.70. Test-retest correlation coefficients exceeded 0.71, and Cronbach's alpha coefficients for both measurements in each domain were greater than or equal to 0.75. T-test results showed that both the overall score and most facet scores within each domain showed statistically significant changes after treatment (P < 0.05), indicating reasonable responsiveness. CONCLUSION: The QLICD-SLE (V2.0) appears to be a valid and reliable instrument for assessing the quality of life in patients with SLE.

Knowledge, willingness, uptake and barriers of cervical cancer screening services among Chinese adult females: a national cross-sectional survey based on a large e-commerce platform.

BACKGROUND: Improving the coverage rate of cervical cancer screening is a challenge mission for cervical cancer elimination. This study attempted to assess the knowledge, willingness, and uptake of cervical cancer screening services among Chinese females and determined associated factors. METHODS: This is a cross-sectional online survey conducted in China from March to April 2022. Information on demographic characteristics, knowledge, willingness, and uptake of cervical cancer screening was collected through a large e-commerce platform. Women aged 18-65 were included in the analysis. Logistic regression analysis was employed to detect the possible factors associated with knowledge, willingness, and screening participation. RESULTS: A total of 4518 women (37.83 ± 9.14 years) were included in the final analysis, of whom 87.16% (n = 3938) lived in urban areas. About 93.40% (n = 4220) of the respondents reported hearing of cervical cancer screening. The median score of knowledge about cervical cancer was 16 out of 26. Over 84% (n = 3799) of the respondents were willing to receive regular cervical cancer screening. Nearly 40% (n = 1785) had never received cervical cancer screening. Among the screened women, 21.26% (n = 581), 35.24% (n = 1151), and 42.37% (n = 1158) were screened through a national cervical cancer screening program, employee physical examination, and self-paid physical examination, respectively. Knowledge was positively associated with willingness and screening participation. Age, marital status, occupation, monthly household income, and HPV vaccination history could influence screening participation (all p < 0.05). CONCLUSIONS: Though women had high-level awareness and strong participation willingness in cervical cancer screening, the overall screening coverage among Chinese women was still low. Besides, the knowledge about cervical cancer was still limited. Comprehensive health education should be enhanced by utilizing social media platforms and medical workers. It is also important to promote national free cervical cancer screening with high-performance screening methods.

Cascaded terahertz hollow-core Bragg waveguide: numerical design and experimental demonstration.

A THz hollow-core Bragg waveguide with discontinuous support bridges in both radial and axial directions is proposed. The influence of the support bridges on the transmission loss of the waveguide is demonstrated numerically. The proposed waveguide shows confinement loss two orders of magnitude lower than that of the Bragg waveguide with conventional support bridges. A waveguide sample is fabricated by 3D printing technology, and the experimental results show that the transmission loss is in agreement with that of the simulation results. It is also demonstrated that the transmission loss of the fabricated waveguide is mainly determined by the large absorption loss of the waveguide material used in the experiment.

Unassisted Clinicians Versus Deep Learning-Assisted Clinicians in Image-Based Cancer Diagnostics: Systematic Review With Meta-analysis.

BACKGROUND: A number of publications have demonstrated that deep learning (DL) algorithms matched or outperformed clinicians in image-based cancer diagnostics, but these algorithms are frequently considered as opponents rather than partners. Despite the clinicians-in-the-loop DL approach having great potential, no study has systematically quantified the diagnostic accuracy of clinicians with and without the assistance of DL in image-based cancer identification. OBJECTIVE: We systematically quantified the diagnostic accuracy of clinicians with and without the assistance of DL in image-based cancer identification. METHODS: PubMed, Embase, IEEEXplore, and the Cochrane Library were searched for studies published between January 1, 2012, and December 7, 2021. Any type of study design was permitted that focused on comparing unassisted clinicians and DL-assisted clinicians in cancer identification using medical imaging. Studies using medical waveform-data graphics material and those investigating image segmentation rather than classification were excluded. Studies providing binary diagnostic accuracy data and contingency tables were included for further meta-analysis. Two subgroups were defined and analyzed, including cancer type and imaging modality. RESULTS: In total, 9796 studies were identified, of which 48 were deemed eligible for systematic review. Twenty-five of these studies made comparisons between unassisted clinicians and DL-assisted clinicians and provided sufficient data for statistical synthesis. We found a pooled sensitivity of 83% (95% CI 80%-86%) for unassisted clinicians and 88% (95% CI 86%-90%) for DL-assisted clinicians. Pooled specificity was 86% (95% CI 83%-88%) for unassisted clinicians and 88% (95% CI 85%-90%) for DL-assisted clinicians. The pooled sensitivity and specificity values for DL-assisted clinicians were higher than for unassisted clinicians, at ratios of 1.07 (95% CI 1.05-1.09) and 1.03 (95% CI 1.02-1.05), respectively. Similar diagnostic performance by DL-assisted clinicians was also observed across the predefined subgroups. CONCLUSIONS: The diagnostic performance of DL-assisted clinicians appears better than unassisted clinicians in image-based cancer identification. However, caution should be exercised, because the evidence provided in the reviewed studies does not cover all the minutiae involved in real-world clinical practice. Combining qualitative insights from clinical practice with data-science approaches may improve DL-assisted practice, although further research is required. TRIAL REGISTRATION: PROSPERO CRD42021281372; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=281372.

Correction: Unassisted Clinicians Versus Deep Learning-Assisted Clinicians in Image-Based Cancer Diagnostics: Systematic Review With Meta-analysis.

[This corrects the article DOI: 10.2196/43832.].

Reactivity and Recyclability of Ligand-Protected Metal Cluster Catalysts for CO2 Transformation.

It remains a significant challenge to construct an integrated catalyst that combines advantages of homogeneous and heterogeneous catalysis with clarified mechanism and high performance. Here we show atomically precise CuAg cluster catalysts for CO2 capture and utilization, where two functional units are combined into the clusters: metal and ligand. Due to atomic resolution on total and local structures of such catalysts to be achieved, which disentangles heterogeneous imprecise systems and permits tracing the reaction processes via experiments coupled with theory, site-specific catalysis induced by metal-ligand synergy can be accurately elucidated. The CuAg cluster catalysts exhibit excellent reactivity and recyclability to forge the C-N bonding from CO2 formylation with secondary amines that can make the cluster catalysts more unique compared with typically homogeneous complexes.

Efficient mode converters and filters using asymmetrical directional couplers with subwavelength gratings.

Mode-division multiplexing (MDM) is a promising solution to improve data transmission capacity for future optical interconnect networks. Mode converters and mode filters play a key role in on-chip MDM systems. Here, we propose and experimentally demonstrate a device, enabling mode conversion and filtering simultaneously, which is composed of asymmetrical directional couplers with subwavelength gratings, in a small footprint of 14.7 µm × 1.42 µm. The device can realize optical mode conversion between the first-order transverse electric (TE) mode and the fundamental TE mode, and can also filter the fundamental TE mode efficiently. The conversion efficiency is over 95%, with a broad 1 dB bandwidth over 80 nm and a high mode extinction ratio of >29 dB. As a mode filter, strong mode elimination of >30 dB is achieved.

Wnt signalling in oral and maxillofacial diseases.

Wnts include more than 19 types of secreted glycoproteins that are involved in a wide range of pathological processes in oral and maxillofacial diseases. The transmission of Wnt signalling from the extracellular matrix into the nucleus includes canonical pathways and noncanonical pathways, which play an important role in tooth development, alveolar bone regeneration, and related diseases. In recent years, with the in-depth study of Wnt signalling in oral and maxillofacial-related diseases, many new conclusions and perspectives have been reached, and there are also some controversies. This article aims to summarise the roles of Wnt signalling in various oral diseases, including periodontitis, dental pulp disease, jaw disease, cleft palate, and abnormal tooth development, to provide researchers with a better and more comprehensive understanding of Wnts in oral and maxillofacial diseases.

Phenethoxy Derivatives with Anti-inflammatory Activities from the Betelnut Endophytic Trichoderma asperellum G10.

Eight new phenethoxy derivatives, trichoasperellins A-H (1-8), were isolated from the endophytic fungus Trichoderma asperellum G10 isolated from the medicinal plant Areca catechu L. The structures of these compounds were elucidated from spectroscopic data, J-based configurational analysis, and Mosher's methods. Compounds 1-4 and 6-8 bear one or two multioxidized C7 moieties with the same carbon skeleton. The carbon skeletons of compounds 6-8 are new, all containing three moieties connected via two acetal carbons similar to those of disaccharide glycosides. Compound 4 inhibited nitric oxide production with an IC50 value of 48.3 µM, comparable to that of the positive control indomethacin (IC50, 42.3 µM).

Bidirectional Drive with Inhibited Hysteresis for Piezoelectric Actuators.

Piezoelectric actuators with a flexible displacement amplification structure are widely used in the fields of precision driving and positioning. The displacement curve of conventional piezoelectric actuators is asymmetrical and non-linear, which leads to large non-linear errors and reduced positioning accuracy of these piezoelectric actuators. In this paper, a bidirectional active drive piezoelectric actuator is proposed, which suppresses the hysteresis phenomenon to a certain extent and reduces the non-linear error. Based on the deformation theory of the beam, a theoretical model of the rhombus mechanism was established, and the key parameters affecting the drive performance were analyzed. Then, the static and dynamic characteristics of series piezoelectric actuators were analyzed by the finite element method. A prototype was manufactured and the output performance was tested. The results show that the actuator can achieve a bidirectional symmetric output of amplification displacement, with a maximum value of 91.45 µm and a resolution of 35 nm. In addition, compared with the hysteresis loop of the piezoelectric stack, the nonlinear error is reduced by 62.94%.

Coping and post-traumatic stress disorder symptoms among Chinese youth in the peak and remission periods of COVID-19.

The COVID-19 pandemic has exposed emergent vulnerability to adolescents' mental health. This longitudinal study investigated the association between coping at the peak of the COVID outbreak (T1) and Post-Traumatic Stress Disorder (PTSD) symptoms concurrently, and at the remission periods of COVID in China three months (T2) and six months (T3) later in a sample of 6th to 12th-grade students (N = 782). The results showed that forward-focus coping was negatively associated with PTSD symptoms across all three timepoints and predicted reduced risk for more PTSD symptoms at T2, and trauma-focus coping was positively associated with PTSD symptoms across all three timepoints and predicted higher risk of PTSD symptoms both at T2 and T3. There was an interaction effect of trauma-focus coping and T1 symptoms on later symptoms (T3) - trauma-focus coping was more detrimental for those who had more initial symptoms. The results showed the beneficial effects of future-oriented coping and harmful effects of trauma-focus coping for Chinese youth during the epidemic. Clinical implications of the results were discussed.

Two new indole-diterpenoids from the marine-derived fungus Penicillium sp. KFD28.

Two new compounds named epipaxilline (1) and penerpene J (2) were isolated from the marine-derived fungus Penicillium sp. KFD28. Their structures including absolute configurations were determined on the basis of spectroscopic methods and ECD analysis. Compounds 1 and 2 showed inhibitory activities against PTP1B with IC50 values of 31.5 and 9.5 µM, respectively, and compound 2 also showed inhibitory activities against TCPTP with IC50 value of 14.7 µM.