Shared genetic architecture between autoimmune disorders and B-cell acute lymphoblastic leukemia: insights from large-scale genome-wide cross-trait analysis.

BACKGROUND: To study the shared genetic structure between autoimmune diseases and B-cell acute lymphoblastic leukemia (B-ALL) and identify the shared risk loci and genes and genetic mechanisms involved. METHODS: Based on large-scale genome-wide association study (GWAS) summary-level data sets, we observed genetic overlaps between autoimmune diseases and B-ALL, and cross-trait pleiotropic analysis was performed to detect shared pleiotropic loci and genes. A series of functional annotation and tissue-specific analysis were performed to determine the influence of pleiotropic genes. The heritability enrichment analysis was used to detect crucial immune cells and tissues. Finally, bidirectional Mendelian randomization (MR) methods were utilized to investigate the casual associations. RESULTS: Our research highlighted shared genetic mechanisms between seven autoimmune disorders and B-ALL. A total of 73 pleiotropic loci were identified at the genome-wide significance level (P < 5 × 10-8), 16 of which had strong evidence of colocalization. We demonstrated that several loci have been previously reported (e.g., 17q21) and discovered some novel loci (e.g., 10p12, 5p13). Further gene-level identified 194 unique pleiotropic genes, for example IKZF1, GATA3, IKZF3, GSDMB, and ORMDL3. Pathway analysis determined the key role of cellular response to cytokine stimulus, B cell activation, and JAK-STAT signaling pathways. SNP-level and gene-level tissue enrichment suggested that crucial role pleiotropic mechanisms involved in the spleen, whole blood, and EBV-transformed lymphocytes. Also, hyprcoloc and stratified LD score regression analyses revealed that B cells at different developmental stages may be involved in mechanisms shared between two different diseases. Finally, two-sample MR analysis determined causal effects of asthma and rheumatoid arthritis on B-ALL. CONCLUSIONS: Our research proved shared genetic architecture between autoimmune disorders and B-ALL and shed light on the potential mechanism that might involve in.

Genomic analysis of penicillin-binding proteins and recombination events in an emerging amoxicillin- and meropenem-resistant PMEN3 (Spain9V-3, ST156) variant in Taiwan and comparison with global descendants of this lineage.

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain9V-3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a, pbp2b, and pbp2x alleles into the ß-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance. A clonal shift with a highly ß-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain9V-3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance.

Investigation of carbapenem-resistant Klebsiella pneumoniae in Taiwan revealed strains co-harbouring blaNDM and blaOXA-48-like and a novel plasmid co-carrying blaNDM-1 and blaOXA-181.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is related to the transmission of carbapenemase genes. Strains carrying more than one carbapenemase with a broadened spectrum of antibiotic resistance have been detected, which is concerning. Although blaKPC-encoding ST11-KL47/KL64 strains are dominant, other clones are emerging. This study investigated 137 CRKP from patients' blood samples in Taiwan. Polymerase chain reaction (PCR) was used to identify carbapenemase genes and capsular (KL) types. Most strains (56%, 77/137) possessed blaKPC alone; however, 12% (17/137) carried blaNDM+blaOXA-48-like and these strains showed high resistance to imipenem and meropenem. Strains carrying blaNDM+blaOXA-48-like predominantly belonged to KL51 (n=15), followed by KL64 (n=1) and KL47 (n=1). Whole-genome sequencing of one KL51 strain indicated that blaNDM-4 and blaOXA-181 are carried on two different plasmids. PCR was performed using specific primers located in these plasmids, and all blaNDM+blaOXA-48-like-encoding strains except the KL64 strain were considered to carry the two abovementioned plasmids. Genome analysis for the KL64 strain revealed that blaNDM-1 and blaOXA-181 are encoded in one plasmid. Notably, the KL51 blaOXA-181 plasmid shared high sequence similarity with the KL64 blaNDM-1+blaOXA-181 plasmid, except the KL64 plasmid comprised a 15,040-bp insertion encoding blaNDM-1. The data revealed KL51 as a predominant KL type carrying blaNDM-4+blaOXA-181, and identified a novel plasmid carrying blaNDM-1+blaOXA-181, highlighting the spread of specific plasmids and clones of CRKP in Taiwan.

Whole genomic analysis reveals atypical non-homologous off-target large structural variants induced by CRISPR-Cas9-mediated genome editing.

CRISPR-Cas9 genome editing has promising therapeutic potential for genetic diseases and cancers, but safety could be a concern. Here we use whole genomic analysis by 10x linked-read sequencing and optical genome mapping to interrogate the genome integrity after editing and in comparison to four parental cell lines. In addition to the previously reported large structural variants at on-target sites, we identify heretofore unexpected large chromosomal deletions (91.2 and 136 Kb) at atypical non-homologous off-target sites without sequence similarity to the sgRNA in two edited lines. The observed large structural variants induced by CRISPR-Cas9 editing in dividing cells may result in pathogenic consequences and thus limit the usefulness of the CRISPR-Cas9 editing system for disease modeling and gene therapy. In this work, our whole genomic analysis may provide a valuable strategy to ensure genome integrity after genomic editing to minimize the risk of unintended effects in research and clinical applications.

Advances in graft-versus-host disease prevention strategies: latest updates from the 2022 ASH annual meeting.

This review summarizes the significant advancements in prophylaxis against graft-versus-host disease (GvHD) presented at the 2022 ASH Annual Meeting. The use of innovative agents and regimens, along with the conventional prophylactic approach of combining post-transplant cyclophosphamide and anti-thymocyte globulin, were discussed. The innovative agents and regimens highlighted in this review include abatacept, the first FDA-approved drug for acute GvHD prophylaxis; RGI-2001, which promotes the expansion of regulatory T cells; and cell therapies such as Orca-T and Orca-Q. These advancements provide promising strategies and options for GvHD prevention, offering hope for improved post-transplant patient outcomes in terms of survival rates.

Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75 years and older.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity. RESULTS: Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers. CONCLUSIONS: The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.

Integrated Multiplex Sensing Clear Aligner for In Situ Monitoring of Dental Enamel Demineralization.

Clear aligners have become one of the most important tools in orthodontic treatment. However, over a lengthy period of orthodontic treatment, enamel demineralization or even dental caries could be susceptible for occurrence. Therefore, early diagnosis of enamel demineralization has been widely investigated. Nevertheless, for reasons including bulky monitoring equipment and complexity of operation, few techniques reported to date possessed clinical utility. The combination of flexible electronics and electrochemical sensing technology presented a promising strategy. Herein, an integrated multiplex sensing clear aligner (IMSCA) system, including a clear aligner with a multiplex sensor array patch, was developed for in situ monitoring of Ca2+, pH, and PO43- in the oral environment to provide a foundation for early diagnosis of enamel demineralization. The IMSCA exhibited a broad linear response range, great selectivity, temporal stability, reproducibility, and biological safety. Results of enamel demineralization simulating experiments and human permanent tooth demineralization experiments validate the capability of the IMSCA to indicate the occurrence of enamel demineralization. All results ultimately point to the promising clinical utility of the IMSCA, which facilitates the quantitative characterization of enamel demineralization in complex oral environments. This study provides a novel strategy in the early diagnosis of enamel demineralization.

Association of Body Mass Index (BMI) with Lip Morphology Characteristics: A Cross-Sectional Study Based on Chinese Population.

BACKGROUND: Lip morphology is essential in diagnosis and treatment of orthodontics and orthognathic surgery to ensure facial aesthetics. Body mass index (BMI) has proved to have influence on facial soft tissue thickness, but its relationship with lip morphology is unclear. This study aimed to evaluate the association between BMI and lip morphology characteristics (LMCs) and thus provide information for personalized treatment. METHODS: A cross-sectional study consisted of 1185 patients from 1 January 2010 to 31 December 2020 was conducted. Confounders of demography, dental features, skeletal parameters and LMCs were adjusted by multivariable linear regression to identify the association between BMI and LMCs. Group differences were evaluated with two-samples t-test and one-way ANOVA test. Mediation analysis was used for indirect effects assessment. RESULTS: After adjusting for confounders, BMI is independently associated with upper lip length (0.039, [0.002-0.075]), soft pogonion thickness (0.120, [0.073-0.168]), inferior sulcus depth (0.040, [0.018-0.063]), lower lip length (0.208, [0.139-0.276]), and curve fitting revealed non-linearity to BMI in obese patients. Mediation analysis found BMI was associated with superior sulcus depth and basic upper lip thickness through upper lip length. CONCLUSIONS: BMI is positively associated with LMCs, except for nasolabial angle as negatively, while obese patients reverse or weaken these associations.

Ionomer Membranes Produced from Hexaarylbenzene-Based Partially Fluorinated Poly(arylene ether) Blends for Proton Exchange Membrane Fuel Cells.

In this study, a series of high molecular weight ionomers of hexaarylbenzene- and fluorene-based poly(arylene ether)s were synthesized conveniently through condensation and post-sulfonation modification. The use a of blending method might increase the stacking density of chains and affect the formation both of interchain and intrachain proton transfer clusters. Multiscale phase separation caused by the dissolution and compatibility differences of blend ionomer in high-boiling-point solvents was examined through analysis and simulations. The blend membranes produced in this study exhibited a high proton conductivity of 206.4 mS cm−1 at 80 °C (increased from 182.6 mS cm−1 for precursor membranes), excellent thermal resistance (decomposition temperature > 200 °C), and suitable mechanical properties with a tensile strength of 73.8−77.4 MPa. As a proton exchange membrane for fuel cell applications, it exhibits an excellent power efficiency of approximately 1.3 W cm−2. Thus, the ionomer membranes have strong potential for use in proton exchange membrane fuel cells and other electrochemical applications.

Unprecedented outbreak of respiratory syncytial virus in Taiwan associated with ON1 variant emergence between 2010 and 2020.

An outbreak of respiratory syncytial virus (RSV) has been observed in Taiwan since August 2020. We reviewed a central laboratory-based surveillance network established over 20 years by Taiwan Centres for Disease Control for respiratory viral pathogens between 2010 and 2020.A retrospective study of children <5 years old hospitalized with RSV infection at Chang Gung Memorial Hospital between 2018 and 2020 was conducted, and samples positive for RSV-A were sequenced. Clinical data were obtained and stratified by genotype and year.Data from 2020 showed an approximately 4-fold surge in RSV cases compared to 2010 in Taiwan, surpassing previous years during which ON1 was prevalent. Phylogenetic analysis of G protein showed that novel ON1 variants were clustered separately from those of 2018 and 2019 seasons and ON1 reference strains. The variant G protein carried six amino acid changes that emerged gradually in 2019; high consistency was observed in 2020. A unique substitution, E257K, was observed in 2020 exclusively. The F protein of the variant carried T12I and H514N substitutions, which weren't at antigenic sites. In terms of multivariate analysis, age (OR: 0.97; 95% CI: 0.94-0.99; p = 0.02) and 2020 ON1 variant (OR:2.52; 95% CI:1.13-5.63; p = 0.025) were independently associated with oxygen saturation <94% during hospitalization.The 2020 ON1 variant didn't show higher replication or virulence compared with those in 2018 in our study. The unprecedented 2020 RSV epidemic may attribute to antigenic changes and lack of interferon-stimulated immunity induced by seasonal circulating virus under non-pharmaceutical intervention.

Exploring the association between capsular types, sequence types, and carbapenemase genes in Acinetobacter baumannii.

Acinetobacter baumannii is the main cause of nosocomial infections, which are increasingly difficult to treat due to the emergence of carbapenem resistance. This study focused on major carbapenemase genes and explored the association between carbapenemase genes, sequence types (ST types), and capsular types (K types). A total of 98 carbapenem-resistant A. baumannii (CRAB) strains were collected from two hospitals, the Chang Gung Memorial Hospital-Lin Kou branch (LCGMH) in northern Taiwan and the CGMH-Kaohsiung branch (KCGMH) in southern Taiwan, from 2015 to 2017. Major carbapenemase genes of class A, B, and D ß-lactamases were detected by polymerase chain reaction. All strains except 1 were positive for blaOXA-51-like, 76 strains (77.6%) carried blaOXA-23-like, and 25 strains (25.5%) carried blaOXA-24-like. The regional distribution showed that blaOXA-23-like was more common than blaOXA-24-like in both hospitals (85.3% and 60% in LCGMH and KCGMH, respectively); however, the percentage of blaOXA-24-like was much higher in KCGMH (46.7%) than in LCGMH (16.2%). Oxford multilocus sequence typing and global optimal eBURST analysis were conducted for 59 strains. The results of this study showed the association between blaOXA gene patterns, ST types, and K types and demonstrated that four major K types, KL2, KL10, KL22, and KL52, which were associated with specific ST types, were mainly clustered into clonal complexes CC208 and CC549 (a unique clonal complex found in Taiwan). These findings provide important information for monitoring the epidemiology and dissemination of this pathogen.

Curriculum setting and students' feedback of pre-clinical training in different dental schools in China-A national-wide survey.

INTRODUCTION: Adequate time and effective training facilities are essential for undergraduate dental students participating in pre-clinical dental practice to ensure them providing safe treatment for patients in the future. The study aimed to explore the current status of pre-clinical dental training in China in relation to the curriculum setting and students' feedback of pre-clinical training in different dental schools and thus provide information for further standardise curricula. MATERIALS AND METHOD: An online questionnaire was distributed electronically to undergraduates in 44 Chinese dental schools of different levels according to China Discipline Ranking (CDR). The questionnaire collected information in relation to the training hour and student to facility ratio of four main dental courses (cariology and endodontics, periodontology, prosthodontics and oral surgery), as well as the application and effect of virtual reality (VR) simulator in pre-clinical dental practice in different schools. Students' feedback was also collected. RESULTS: A total of 565 valid questionnaires were recruited. Results of this cross-sectional survey show that training hour of periodontology course was the lowest, and oral surgery course showed most prominent shortage of facilities. The application of VR simulator amongst schools is uneven. Students from A and A+ level schools showed higher satisfaction with their pre-clinical courses and reported a more positive attitude towards the use of VR simulator than other students. (p < .05). CONCLUSION: Pre-clinical dental training in China remained imperfect in insufficient training time, training facility and students did not have access to standard pre-clinical training and quality assurance. VR technique has potential values in pre-clinical dental practice in China.

Global Genome Diversity and Recombination in Mycoplasma pneumoniae.

Genomic changes in Mycoplasma pneumoniae caused by adaptation to environmental or ecologic pressures are poorly understood. We collected M. pneumoniae from children who had confirmed pneumonia in Taiwan during 2017-2020. We used whole-genome sequencing to compare these isolates with a worldwide collection of current and historical clinical strains for characterizing population structures. A phylogenetic tree for 284 strains showed that all sequenced strains consisted of 5 clades: T1-1 (sequence type [ST]1), T1-2 (mainly ST3), T1-3 (ST17), T2-1 (mainly ST2), and T2-2 (mainly ST14). We identified a putative recombination block containing 6 genes (MPN366‒371). Macrolide resistance involving 23S rRNA mutations was detected for each clade. Clonal expansion of macrolide resistance occurred mostly within subtype 1 strains, of which clade T1-2 showed the highest recombination rate and genome diversity. Functional characterization of recombined regions provided clarification of the biologic role of these recombination events in the evolution of M. pneumoniae.

Molecular detection of respiratory pathogens in community-acquired pneumonia involving adults.

BACKGROUND: Community-acquired pneumonia (CAP) causes substantial morbidity and mortality in adults worldwide. The etiology of CAP often remains uncertain, and therapy is empirical. Thus, there is still room for improvement in the diagnosis of pneumonia. METHODS: Adults aged >20 years who presented at the outpatient or emergency departments of Linkou and Keelung Chang Gung Memorial Hospital with CAP were prospectively included between November 2016 and December 2018. We collected respiratory specimens for culture and molecular testing and calculated the incidence rates of CAP according to pathogens. RESULTS: Of 212 hospitalized adult patients with CAP, 69.3% were male, and the median age of the patients was 67.8 years. Bacterial pathogens were detected in 106 (50%) patients, viruses in 77 (36.3%), and fungal pathogens in 1 patient (0.5%). The overall detection rate (culture and molecular testing method) was 70.7% (n = 150). Traditional microbial culture yielded positive results in 36.7% (n = 78), molecular testing in 61.3% (n = 130). The most common pathogens were influenza (16.1%), followed by Klebsiella pneumoniae (14.1%), Pseudomonas aeruginosa (13.6%), human rhinovirus (11.8%), and Streptococcus pneumoniae (9.9%). Multiple pathogen co-infections accounted for 28.7% (n = 61), of which co-infection with K. pneumoniae and human rhinovirus comprised the largest proportion. CONCLUSIONS: Molecular diagnostic testing could detect 23.6% more pathogens than traditional culture techniques. However, despite the current diagnostic tests, there is still the possibility that no pathogen was detected.

Sex-specific effects of aging on humoral immune responses to repeated influenza vaccination in older adults.

Older adults (≥65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeated vaccination and levels of pre-existing humoral immunity to influenza, we evaluated pre- and post-vaccination strain-specific hemagglutination inhibition (HAI) titers in adults over 75 years of age who received a high-dose influenza vaccine in at least four out of six influenza seasons. Pre-vaccination titers, rather than host factors and repeated vaccination were significantly associated with post-vaccination HAI titer outcomes, and displayed an age-by-sex interaction. Pre-vaccination titers to H1N1 remained constant with age. Titers to H3N2 and influenza B viruses decreased substantially with age in males, whereas titers in females remained constant with age. Our findings highlight the importance of pre-existing immunity in this highly vaccinated older adult population and suggest that older males are particularly vulnerable to reduced pre-existing humoral immunity to influenza.

An Outbreak of tet(X6)-Carrying Tigecycline-Resistant Acinetobacter baumannii Isolates with a New Capsular Type at a Hospital in Taiwan.

Dissemination of multidrug-resistant, particularly tigecycline-resistant, Acinetobacter baumannii is of critical importance, as tigecycline is considered a last-line antibiotic. Acquisition of tet(X), a tigecycline-inactivating enzyme mostly found in strains of animal origin, imparts tigecycline resistance to A. baumannii. Herein, we investigated the presence of tet(X) variants among 228 tigecycline-non-susceptible A. baumannii isolates from patients at a Taiwanese hospital via polymerase chain reaction using a newly designed universal primer pair. Seven strains (3%) carrying tet(X)-like genes were subjected to whole genome sequencing, revealing high DNA identity. Phylogenetic analysis based on the PFGE profile clustered the seven strains in a clade, which were thus considered outbreak strains. These strains, which were found to co-harbor the chromosome-encoded tet(X6) and the plasmid-encoded blaOXA-72 genes, showed a distinct genotype with an uncommon sequence type (Oxford ST793/Pasteur ST723) and a new capsular type (KL129). In conclusion, we identified an outbreak clone co-carrying tet(X6) and blaOXA-72 among a group of clinical A. baumannii isolates in Taiwan. To the best of our knowledge, this is the first description of tet(X6) in humans and the first report of a tet(X)-like gene in Taiwan. These findings identify the risk for the spread of tet(X6)-carrying tigecycline- and carbapenem-resistant A. baumannii in human healthcare settings.

U-Net combined with multi-scale attention mechanism for liver segmentation in CT images.

BACKGROUND: The liver is an important organ that undertakes the metabolic function of the human body. Liver cancer has become one of the cancers with the highest mortality. In clinic, it is an important work to extract the liver region accurately before the diagnosis and treatment of liver lesions. However, manual liver segmentation is a time-consuming and boring process. Not only that, but the segmentation results usually varies from person to person due to different work experience. In order to assist in clinical automatic liver segmentation, this paper proposes a U-shaped network with multi-scale attention mechanism for liver organ segmentation in CT images, which is called MSA-UNet. Our method makes a new design of U-Net encoder, decoder, skip connection, and context transition structure. These structures greatly enhance the feature extraction ability of encoder and the efficiency of decoder to recover spatial location information. We have designed many experiments on publicly available datasets to show the effectiveness of MSA-UNet. Compared with some other advanced segmentation methods, MSA-UNet finally achieved the best segmentation effect, reaching 98.00% dice similarity coefficient (DSC) and 96.08% intersection over union (IOU).

Association of Upper Lip Morphology Characteristics with Sagittal and Vertical Skeletal Patterns: A Cross Sectional Study.

BACKGROUND: Upper lip morphology is essential in diagnosis and treatment of orthodontics and orthognathic surgery. This study is aimed to evaluate the association between upper lip characteristics (ULCs) and skeletal patterns (SPs). METHODS: 2079 patients were involved and grouped by sagittal and vertical. Class I, II, and III were identified by ANB angle, while normodivergent, hyperdivergent, and hypodivergent were identified by Facial Height Index and Sum of Angles. ULCs were evaluated by superior sulcus depth, nasolabial angle, upper lip length, basic upper lip thickness, and upper lip thickness. Confounders including demography, malocclusion, upper incisors, and upper lips were adjusted by multivariate linear regression to identify the association between ULCs and SPs. Group differences were evaluated with analysis of variance and Chi-square test. RESULTS: The mean value of ULCs and prevalence of SPs were explored in the Western China population. ULCs were significantly different in various sagittal, vertical, and combined SPs. Superior sulcus depth was negatively related to Class II, and positively related to Class III and the hypodivergent pattern after adjusted by confounders. CONCLUSIONS: ULCs significantly varied among different SPs, while only superior sulcus depth was independently associated with SPs, indicating superior sulcus depth is the only ULC that might be significantly corrected by intervention of skeletal growth.

Novel Portable Sensing System with Integrated Multifunctionality for Accurate Detection of Salivary Uric Acid.

Uric acid, as the terminal product of purine metabolism in the body, is an important marker of many diseases. Uric acid is abundant in saliva, offering the possibility of its non-invasive detection. However, it is sensitive to interference in saliva by a variety of factors. A reliable method of processing saliva is centrifugation (CF), but the cost and size of equipment limit its use in everyday life. In this study, a novel portable salivary-sensing system (PSSS) with integrated suction filtration (SF) and temperature insulation was proposed to obtain more accurate salivary uric acid levels through a simple procedure. The PSSS includes a saliva container, a high-sensitive uric acid sensor (UAS), an accompanying printed circuit board (PCB), and a mobile application. The responses produced by the UAS presents excellent linearity (4.6 µA/mM with R2 = 0.9964), selectivity, reproducibility, and stability for the detection of low levels of uric acid. The difference in detection values between the UAS and the commercial sensor is only ~4%. The primary feature of the saliva container is the processing of saliva by SF instead of CF. Samples from CF and SF showed no significant differences regarding uric acid levels, and both exhibited approximately 50% deviation from the untreated samples, while the difference in uric acid levels between the samples after SF and after applying both treatments was ~10%. Besides, insulation of the saliva container can partially eliminate sources of error induced by the environment during uric acid level testing. The PSSS provides a novel strategy for the immediate detection of specific markers in saliva. We believe that the PSSS has promising potential for future application in the rapid saliva testing.

Bacterial factors required for Streptococcus pneumoniae coinfection with influenza A virus.

BACKGROUND: Streptococcus pneumoniae is a common cause of post-influenza secondary bacterial infection, which results in excessive morbidity and mortality. Although 13-valent pneumococcal conjugate vaccine (PCV13) vaccination programs have decreased the incidence of pneumococcal pneumonia, PCV13 failed to prevent serotype 3 pneumococcal disease as effectively as other vaccine serotypes. We aimed to investigate the mechanisms underlying the co-pathogenesis of influenza virus and serotype 3 pneumococci. METHODS: We carried out a genome-wide screening of a serotype 3 S. pneumoniae transposon insertion mutant library in a mouse model of coinfection with influenza A virus (IAV) to identify the bacterial factors required for this synergism. RESULTS: Direct, high-throughput sequencing of transposon insertion sites identified 24 genes required for both coinfection and bacterial infection alone. Targeted deletion of the putative aminotransferase (PA) gene decreased bacterial growth, which was restored by supplementation with methionine. The bacterial burden in a coinfection with the PA gene deletion mutant and IAV in the lung was lower than that in a coinfection with wild-type pneumococcus and IAV, but was significantly higher than that in an infection with the PA gene deletion mutant alone. These data suggest that IAV infection alters host metabolism to benefit pneumococcal fitness and confer higher susceptibility to pneumococcal infection. We further demonstrated that bacterial growth was increased by supplementation with methionine or IAV-infected mouse lung homogenates. CONCLUSIONS: The data indicates that modulation of host metabolism during IAV infection may serve as a potential therapeutic intervention against secondary bacterial infections caused by serotype 3 pneumococci during IAV outbreaks in the future.