Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

[Analysis of clinical features and genetic variant in a child with Cowden syndrome 1].

OBJECTIVE: To explore the genetic etiology of a child with Cowden syndrome 1 (CS1). METHODS: A child who had visited the Ningbo Women and Children's Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c.781C>T (p.Q261*) variant of the PTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The c.781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

The role of IL-36 and 37 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management.

Progress of Research on Conductive Hydrogels in Flexible Wearable Sensors.

Conductive hydrogels, characterized by their excellent conductivity and flexibility, have attracted widespread attention and research in the field of flexible wearable sensors. This paper reviews the application progress, related challenges, and future prospects of conductive hydrogels in flexible wearable sensors. Initially, the basic properties and classifications of conductive hydrogels are introduced. Subsequently, this paper discusses in detail the specific applications of conductive hydrogels in different sensor applications, such as motion detection, medical diagnostics, electronic skin, and human-computer interactions. Finally, the application prospects and challenges are summarized. Overall, the exceptional performance and multifunctionality of conductive hydrogels make them one of the most important materials for future wearable technologies. However, further research and innovation are needed to overcome the challenges faced and to realize the wider application of conductive hydrogels in flexible sensors.

Nanopore sequencing of infectious fluid is a promising supplement for gold-standard culture in real-world clinical scenario.

Introduction: Infectious diseases are major causes of morbidity and mortality worldwide, necessitating the rapid identification and accurate diagnosis of pathogens. While unbiased metagenomic next-generation sequencing (mNGS) has been extensively utilized in clinical pathogen identification and scientific microbiome detection, there is limited research about the application of nanopore platform-based mNGS in the diagnostic performance of various infectious fluid samples. Methods: In this study, we collected 297 suspected infectious fluids from 10 clinical centers and detected them with conventional microbiology culture and nanopore platform-based mNGS. The objective was to assess detective and diagnostic performance of nanopore-sequencing technology (NST) in real-world scenarios. Results: Combined with gold-standard culture and clinical adjudication, nanopore sequencing demonstrated nearly 100% positive predictive agreements in microbial-colonized sites, such as the respiratory and urinary tracts. For samples collected from initially sterile body sites, the detected microorganisms were highly suspected pathogens, and the negative predictive agreements were relatively higher than those in the microbial-colonized sites, particularly with 100% in abscess and 95.7% in cerebrospinal fluid. Furthermore, consistent performance was also observed in the identification of antimicrobial resistance genes and drug susceptibility testing of pathogenic strains of Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii. Discussion: Rapid NST is a promising clinical tool to supplement gold-standard culture, and it has the potential improve patient prognosis and facilitate clinical treatment of infectious diseases.

Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases.

The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID-19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.

[Clinical phenotype and genetic analysis of a fetus with Cardiac valvular dysplasia type 1].

OBJECTIVE: To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1). METHODS: A CVDP1 fetus identified at the Ningbo Women and Children's Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing. RESULTS: The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c.2977C>T (p.R993*) and c.1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP4), whilst the c.1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The c.2977C>T (p.R993*) and c.1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.

Physicochemical properties and solution conformation of polysaccharides from Toona sinensis (A. Juss) Roem leaves.

In this study, two polysaccharide fractions (TSP-1 and TSP-2) were isolated from Toona sinensis leaves. The physicochemical properties and solution conformations of TSP-1 and TSP-2 were investigated. DSC and TG results showed that TSP-1 and TSP-2 had thermal stability. The intrinsic viscosities of TSP-1 and TSP-2 solutions were 11.42 and 6.13 mL/g, respectively. Rheological results showed that the viscosities of TSP-1 and TSP-2 solutions were affected by polysaccharide concentration, Ca2+ and extreme pH. Furthermore, TSP-1 exhibited a weak gel behavior at the concentrations of 0.5 %-2.0 %, while TSP-2 showed a weak gel behavior at the concentration of 2 %. HPSEC-MALLS analysis revealed that the Rg values of TSP-1 and TSP-2 were 96.8 nm and 56.2 nm, respectively. Conformation analysis indicated that TSP-1 behaved as a sphere, while TSP-2 behaved like a rigid rod. These results suggest that TSP-1 and TSP-2 can be used as additives in food, pharmaceutical and cosmetic industries.

Reciprocal Links Between Friendship Quality and Peer Victimization Among Middle Adolescents.

There is a robust association between friendship quality and victimization in adolescence; yet, it remains unclear whether friendship quality may be linked causally with different forms of victimization in middle adolescence. To fill this gap, this study examines the bidirectional associations of friendship quality and relational/verbal victimization with data collected at two time points, 6 months apart, in a sample of 671 middle Chinese adolescents (Mage = 15.63, SDage = 0.73, 49% males). Cross-lagged panel analyses revealed a two-way relationship between friendship quality and victimization, which existed in both verbal and relational victimization. Multi-group panel analyses observed that the cross-lagged associations between friendship quality and relational/verbal victimization were only found for males, but not for females. This result suggests that adolescent males' victimization is both affected by and a predictor of friendship quality, with implications for youth prevention programs.

MFA-UNet: a vessel segmentation method based on multi-scale feature fusion and attention module.

Introduction: The accurate segmentation of retinal vessels is of utmost importance in the diagnosis of retinal diseases. However, the complex vessel structure often leads to poor segmentation performance, particularly in the case of microvessels. Methods: To address this issue, we propose a vessel segmentation method composed of preprocessing and a multi-scale feature attention network (MFA-UNet). The preprocessing stage involves the application of gamma correction and contrast-limited adaptive histogram equalization to enhance image intensity and vessel contrast. The MFA-UNet incorporates the Multi-scale Fusion Self-Attention Module(MSAM) that adjusts multi-scale features and establishes global dependencies, enabling the network to better preserve microvascular structures. Furthermore, the multi-branch decoding module based on deep supervision (MBDM) replaces the original output layer to achieve targeted segmentation of macrovessels and microvessels. Additionally, a parallel attention mechanism is embedded into the decoder to better exploit multi-scale features in skip paths. Results: The proposed MFA-UNet yields competitive performance, with dice scores of 82.79/83.51/84.17/78.60/81.75/84.04 and accuracies of 95.71/96.4/96.71/96.81/96.32/97.10 on the DRIVE, STARE, CHASEDB1, HRF, IOSTAR and FIVES datasets, respectively. Discussion: It is expected to provide reliable segmentation results in clinical diagnosis.

Highly sensitive temperature and refractive index sensor based on no-core fiber cascaded with a balloon-shaped bent single-mode fiber.

A highly sensitive temperature and refractive index (RI) sensor based on no-core fiber (NCF) cascaded with a balloon-shaped bent single-mode fiber (BSBSF) is proposed and demonstrated. The NCF can excite higher-order modes which will be concentrated and transmitted into the BSBSF due to the characteristic of self-imaging effect. The BSBSF has an excellent temperature performance due to the high thermo-optical coefficient and thermal expansion coefficient of the polymer coating. The NCF and BSBSF are both conducive to the excitation of higher-order modes, which induces the sensitivity of the sensor with an efficiency improvement. The experimental results show that the maximum temperature sensitivity is -3.19n m/ ∘ C in the range of 22°C-83°C, which is the highest temperature sensitivity in the cascaded BSBSF structure to our best knowledge. In addition, the maximum RI sensitivity is 232.16 nm/RIU when the RI changes from 1.3234 to 1.3512. Compared with other cascaded BSBSF structures, this sensor has a higher temperature sensitivity and can be applicated in the prospects of food, biology, and environmental monitoring.

Changes in the symptom clusters of elderly patients with lung cancer over the course of postoperative rehabilitation and their correlation with frailty and quality of life: A longitudinal study.

OBJECTIVE: To explore changes in the symptom clusters of perioperatively elderly patients with lung cancer at different time points (i.e., the day of admission [T0]), 2-4 days after surgery [T1], 1 month after discharge [T2] and 3 months after discharge [T3]) and to analyze correlations between cluster severity, frailty and quality of life (QOL). METHODS: A longitudinal study was conducted from August 2020 to June 2021 among elderly lung cancer patients undergoing surgery at hospitals in Jiangsu Province. Data were collected using the Chinese Tilburg Frailty Indicator, the MD Anderson Symptom Inventory and the Quality of Life-Core scale. RESULTS: According to exploratory factor analysis, a total of 5 symptom clusters were found and three of them (the global mental function symptom cluster, the special mental function symptom cluster and the respiratory function symptom cluster) were persistent. The incidence of the top four symptoms varied at different time points. The severity of symptom clusters at different time points was positively correlated with frailty and negatively correlated with QOL. CONCLUSIONS: The findings may serve as a reference for medical staff to implement symptom management in elderly lung cancer patients after surgery. Frailty may be an important variable affecting the severity of symptom clusters and the QOL of patients.

Rational Design of Multifunctional Hydrogels for Wound Repair.

The intricate microenvironment at the wound site, coupled with the multi-phase nature of the healing process, pose significant challenges to the development of wound repair treatments. In recent years, applying the distinctive benefits of hydrogels to the development of wound repair strategies has yielded some promising results. Multifunctional hydrogels, by meeting the different requirements of wound healing stages, have greatly improved the healing effectiveness of chronic wounds, offering immense potential in wound repair applications. This review summarized the recent research and applications of multifunctional hydrogels in wound repair. The focus was placed on the research progress of diverse multifunctional hydrogels, and their mechanisms of action at different stages of wound repair were discussed in detail. Through a comprehensive analysis, we found that multifunctional hydrogels play an indispensable role in the process of wound repair by providing a moist environment, controlling inflammation, promoting angiogenesis, and effectively preventing infection. However, further implementation of multifunctional hydrogel-based therapeutic strategies also faces various challenges, such as the contradiction between the complexity of multifunctionality and the simplicity required for clinical translation and application. In the future, we should work to address these challenges, further optimize the design and preparation of multifunctional hydrogels, enhance their effectiveness in wound repair, and promote their widespread application in clinical practice.

Electrochemical Phenyl-Carbonyl Coupling Reaction of Aromatic Aldehydes or Ketones.

An electrochemical phenyl-carbonyl coupling reaction of aromatic aldehydes or ketones to synthesize 4-(hydroxy(phenyl)methyl)benzaldehyde derivatives has been developed. The method shows high chemoselectivity, broad functional group compatibility, atom economy, and environmental benignity and has good potential applicability.

Influenza vaccination rates among healthcare workers: a systematic review and meta-analysis investigating influencing factors.

Introduction: Healthcare workers risk of exposure to the influenza virus in their work, is a high-risk group for flu infections. Thus WHO recommends prioritizing flu vaccination for them-an approach adopted by >40 countries and/or regions worldwide. Methods: Cross-sectional studies on influenza vaccination rates among healthcare workers were collected from PubMed, EMBASE, CNKI, and CBM databases from inception to February 26, 2023. Influenza vaccination rates and relevant data for multiple logistic regression analysis, such as odds ratios (OR) and 95% confidence intervals (CI), were extracted. Results: A total of 92 studies comprising 125 vaccination data points from 26 countries were included in the analysis. The meta-analysis revealed that the overall vaccination rate among healthcare workers was 41.7%. Further analysis indicated that the vaccination rate was 46.9% or 35.6% in low income or high income countries. Vaccination rates in the Americas, the Middle East, Oceania, Europe, Asia, and Africa were 67.1, 51.3, 48.7, 42.5, 28.5, and 6.5%, respectively. Influencing factors were age, length of service, education, department, occupation, awareness of the risk of influenza, and/or vaccines. Conclusion: The global influenza vaccination rate among healthcare workers is low, and comprehensive measures are needed to promote influenza vaccination among this population. Systematic review registration: www.inplysy.com, identifier: 202350051.

[Clinical and genetic analysis of a rare fetus with Protein C deficiency due to compound heterozygous variants of PROC gene].

OBJECTIVE: To explore the genetic etiology for a fetus with hydrocephalus and intraventricular hemorrhage. METHODS: Trio whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing of the fetus and its parents. RESULTS: The fetus was found to harbor c.818G>A (p.W273X) and c.833T>C (p.L278P) compound heterozygous variants of the PROC gene, which were respectively inherited from its mother and father. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PVS1_Strong+PM2_Supporting+PP4; PM2_Supporting+PM3+PP1+PP3+PP4). CONCLUSION: The fetus was diagnosed with Protein C deficiency due to the c.818G>A (p.W273X) and c.833T>C (p.L278P) compound heterozygous variants of the PROC gene. Above finding has enriched the spectrum of PROC gene variants and enabled genetic counseling and prenatal diagnosis for the family.

Regioselective Cycloaddition of Alkenes with tert-butyl Nitrite: A Cascade Approach to the Formation of Δ2-Isoxazolines.

A route for cycloaddition reaction of alkenes and tert-butyl nitrite to synthesize Δ2-isoxazolines has been developed. The overall process involves the formation of multiple chemical bonds without the use of a catalyst. This methodology features mild reaction conditions and good functional group tolerance, providing a direct approach for the preparation of isoxazolines.

Protective role of resilience on the associations between childhood maltreatment and internalising and externalising problems.

Different types of childhood maltreatment have negative effects on individual mental and behavioural outcomes. However, most of previous studies investigated their effects separately. Little is known about the effects of co-occurring maltreatment profiles on adolescents' developmental outcomes and the potential protective factor. The current study sought to identify distinct profiles of childhood maltreatment and examine the effects of profiles of childhood maltreatment on internalising and externalising problems and the protective role of resilience based on two-wave longitudinal data, which was collected from a sample of 670 Chinese adolescents (Mage  = 15.50, SDage  = 0.75, 48.4% boys). Four profiles of childhood maltreatment, that is, No maltreatment (67.9%), High neglect (23.0%), High abuse and neglect/Low sexual abuse (5.0%), and Multi-maltreatment (4.1%), were identified. Adolescents in High neglect, High abuse and neglect/Low sexual abuse, and Multi-maltreatment profiles were more likely to report internalising and externalising problems. Further, significant moderating effects of resilience only emerged for the association between the High neglect profile and internalising problems, such that high levels of resilience may weaken the association between the High neglect profile and internalising problems. Our findings revealed the importance and utility of identifying maltreatment profiles to tailor treatment based on specific maltreatment experiences. Resilience-oriented intervention could be considered for Chinese adolescents who have experienced high neglect.