PhageScope: a well-annotated bacteriophage database with automatic analyses and visualizations.

Bacteriophages are viruses that infect bacteria or archaea. Understanding the diverse and intricate genomic architectures of phages is essential to study microbial ecosystems and develop phage therapy strategies. However, the existing phage databases are short of meticulous annotations. To this end, we propose PhageScope (https://phagescope.deepomics.org), an online phage database with comprehensive annotations. PhageScope harbors a collection of 873 718 phage sequences from various sources. Applying fifteen state-of-the-art tools to perform systematic annotations and analyses, PhageScope provides annotations on genome completeness, host range, lifestyle information, taxonomy classification, nine types of structural and functional genetic elements, and three types of comparative genomic studies for curated phages. Additionally, PhageScope incorporates automatic analyses and visualizations for curated and customized phages, serving as an efficient platform for phage study.

De novo variants in FRMD5 are associated with developmental delay, intellectual disability, ataxia, and abnormalities of eye movement.

Proteins containing the FERM (four-point-one, ezrin, radixin, and moesin) domain link the plasma membrane with cytoskeletal structures at specific cellular locations and have been implicated in the localization of cell-membrane-associated proteins and/or phosphoinositides. FERM domain-containing protein 5 (FRMD5) localizes at cell adherens junctions and stabilizes cell-cell contacts. To date, variants in FRMD5 have not been associated with a Mendelian disease in OMIM. Here, we describe eight probands with rare heterozygous missense variants in FRMD5 who present with developmental delay, intellectual disability, ataxia, seizures, and abnormalities of eye movement. The variants are de novo in all for whom parental testing was available (six out of eight probands), and human genetic datasets suggest that FRMD5 is intolerant to loss of function (LoF). We found that the fly ortholog of FRMD5, CG5022 (dFrmd), is expressed in the larval and adult central nervous systems where it is present in neurons but not in glia. dFrmd LoF mutant flies are viable but are extremely sensitive to heat shock, which induces severe seizures. The mutants also exhibit defective responses to light. The human FRMD5 reference (Ref) cDNA rescues the fly dFrmd LoF phenotypes. In contrast, all the FRMD5 variants tested in this study (c.340T>C, c.1051A>G, c.1053C>G, c.1054T>C, c.1045A>C, and c.1637A>G) behave as partial LoF variants. In addition, our results indicate that two variants that were tested have dominant-negative effects. In summary, the evidence supports that the observed variants in FRMD5 cause neurological symptoms in humans.

Quantitative annotations of T-Cell repertoire specificity.

The specificity of a T-cell receptor (TCR) repertoire determines personalized immune capacity. Existing methods have modeled the qualitative aspects of TCR specificity, while the quantitative aspects remained unaddressed. We developed a package, TCRanno, to quantify the specificity of TCR repertoires. We created deep-learning-based, epitope-aware vector embeddings to infer individual TCR specificity. Then we aggregated clonotype frequencies of TCRs to obtain a quantitative profile of repertoire specificity at epitope, antigen and organism levels. Applying TCRanno to 4195 TCR repertoires revealed quantitative changes in repertoire specificity upon infections, autoimmunity and cancers. Specifically, TCRanno found cytomegalovirus-specific TCRs in seronegative healthy individuals, supporting the possibility of abortive infections. TCRanno discovered age-accumulated fraction of severe acute respiratory syndrome coronavirus 2 specific TCRs in pre-pandemic samples, which may explain the aggressive symptoms and age-related severity of coronavirus disease 2019. TCRanno also identified the encounter of Hepatitis B antigens as a potential trigger of systemic lupus erythematosus. TCRanno annotations showed capability in distinguishing TCR repertoires of healthy and cancers including melanoma, lung and breast cancers. TCRanno also demonstrated usefulness to single-cell TCRseq+gene expression data analyses by isolating T-cells with the specificity of interest.

TIMEDB: tumor immune micro-environment cell composition database with automatic analysis and interactive visualization.

Deciphering the cell-type composition in the tumor immune microenvironment (TIME) can significantly increase the efficacy of cancer treatment and improve the prognosis of cancer. Such a task has benefited from microarrays and RNA sequencing technologies, which have been widely adopted in cancer studies, resulting in extensive expression profiles with clinical phenotypes across multiple cancers. Current state-of-the-art tools can infer cell-type composition from bulk expression profiles, providing the possibility of investigating the inter-heterogeneity and intra-heterogeneity of TIME across cancer types. Much can be gained from these tools in conjunction with a well-curated database of TIME cell-type composition data, accompanied by the corresponding clinical information. However, currently available databases fall short in data volume, multi-platform dataset integration, and tool integration. In this work, we introduce TIMEDB (https://timedb.deepomics.org), an online database for human tumor immune microenvironment cell-type composition estimated from bulk expression profiles. TIMEDB stores manually curated expression profiles, cell-type composition profiles, and the corresponding clinical information of a total of 39,706 samples from 546 datasets across 43 cancer types. TIMEDB comes readily equipped with online tools for automatic analysis and interactive visualization, and aims to serve the community as a convenient tool for investigating the human tumor microenvironment.

The promising role of tumor-associated macrophages in the treatment of cancer.

Macrophages are important components of the immune system. Mature macrophages can be recruited to tumor microenvironment that affect tumor cell proliferation, invasion and metastasis, extracellular matrix remodeling, immune suppression, as well as chemotherapy resistance. Classically activated type I macrophages (M1) exhibited marked tumor killing and phagocytosis. Therefore, using macrophages for adoptive cell therapy has attracted attention and become one of the most effective strategies for cancer treatment. Through cytokines and/or chemokines, macrophage can inhibit myeloid cells recruitment, and activate anti-tumor and immune killing functions. Applying macrophages for anti-tumor delivery is one of the most promising approaches for cancer therapy. This review article introduces the role of macrophages in tumor development and drug resistance, and the possible clinical application of targeting macrophages for overcoming drug resistance and enhancing cancer therapeutics, as well as its challenges.

Mid-infrared auto-correction on-chip waveguide gas sensor based on 2f/1f wavelength modulation spectroscopy.

Compared to the most commonly used on-chip direct absorption spectroscopy (DAS) gas detection technique, the second harmonic (2f) based on-chip wavelength modulation spectroscopy (WMS) proposed by our group has the faculty to suppress noise and improve performance, but the accuracy of 2f WMS is easily affected by optical power variation. A mid-infrared auto-correction on-chip gas sensor based on 2f/1f WMS was proposed for decreasing the influence of the variation of optical power. The limit of detection of methane (CH4) obtained by a chalcogenide waveguide with a length of 10 mm is 0.031%. Compared with the 2f WMS, the maximum relative concentration error of the auto-correction on-chip gas sensor was decreased by ∼5.6 times. The measurement error is ≤2% in a temperature variation range of 30°C. This auto-correction sensor without a complicated manual calibration is helpful to the high accuracy measurement for on-chip integrated gas sensing.

HPV16-miRNAs exert oncogenic effects through enhancers in human cervical cancer.

BACKGROUND: Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear. METHODS: Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration. RESULTS: HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells. CONCLUSIONS: Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer.

Fine mapping and candidate gene analysis of qSRC3 controlling the silk color in maize (Zea mays L.).

KEY MESSAGE: Fine mapping of the maize QTL qSRC3, responsible for red silk, uncovered the candidate gene ZmMYB20, which encodes an R2R3-MYB transcription factor, has light-sensitive expression, and putatively regulates genes expression associated with anthocyanin biosynthesis. Colorless silk is a key characteristic contributing to the visual quality of fresh corn intended for market distribution. Nonetheless, the identification of Mendelian trait loci and associated genes that control silk color has been scarce. In this study, a F2 population arising from the hybridization of the single-segment substitution line qSRC3MT1 with red silk, carrying an introgressed allele from teosinte (Zea mays ssp. mexicana), and the recurrent maize inbred line Mo17, characterized by light green silk, was utilized for fine mapping. We found that the red silk trait is controlled by a semi-dominant genetic locus known as qSRC3, and its expression is susceptible to light-mediated inhibition. Moreover, qSRC3 explained 68.78% of the phenotypic variance and was delimited to a 133.2 kb region, which includes three genes. Subsequent expression analyses revealed that ZmMYB20 (Zm00001d039700), which encodes an R2R3-MYB transcription factor, was the key candidate gene within qSRC3. Yeast one-hybrid and dual-luciferase reporter assays provided evidence that ZmMYB20 suppresses the expression of two crucial anthocyanin biosynthesis genes, namely ZmF3H and ZmUFGT, by directly binding to their respective promoter regions. Our findings underscore the significance of light-inhibited ZmMYB20 in orchestrating the spatial and temporal regulation of anthocyanin biosynthesis. These results advance the production of colorless silk in fresh corn, responding to the misconception that fresh corn with withered colored silk is not fresh and providing valuable genetic resources for the improvement of sweet and waxy maize.

Development of in vitro microfluidic models to study endothelial responses to pulsatility with different mechanical circulatory support devices.

Continuous-flow ventricular assist devices (CFVAD) and counterpulsation devices (CPD) are used to treat heart failure (HF). CFVAD can diminish pulsatility, but pulsatile modes have been implemented to increase vascular pulsatility. The effects of CFVAD in a pulsatile mode and CPD support on the function of endothelial cells (ECs) are yet to be investigated. In this study, two in vitro microfluidic models for culturing ECs are proposed to reproduce blood pressure (BP) and wall shear stress (WSS) on the arterial endothelium while using these medical devices. The layout and parameters of the two microfluidic systems were optimized based on the principle of hemodynamic similarity to efficiently simulate physiological conditions. Moreover, the unique design of the double-pump and double afterload systems could successfully reproduce the working mode of CPDs in an in vitro microfluidic system. The performance of the two systems was verified by numerical simulations and in vitro experiments. BP and WSS under HF, CFVAD in pulsatile modes, and CPD were reproduced accurately in the systems, and these induced signals improved the expression of Ca2+, NO, and reactive oxygen species in ECs, proving that CPD may be effective in normalizing endothelial function and replacing CFVAD to a certain extent to treat non-severe HF. This method offers an important tool for the study of cell mechanobiology and a key experimental basis for exploring the potential value of mechanical circulatory support devices in reducing adverse events and improving outcomes in the treatment of HF in the future.

Genetically predicted biomarkers of iron homeostasis and risk of non-ischemic cardiomyopathy: A mendelian randomization study.

BACKGROUND AND AIMS: Both iron overload and iron deficiency have been associated with cardiovascular diseases in observational studies. Previous Mendelian Randomization (MR) studies discovered a protective effect of higher iron status on coronary atrial disease, while a neutral effect on all-cause heart failure. Using two-sample MR, we evaluated how genetically predicted systemic iron status affects the risk of non-ischemic cardiomyopathy and different phenotypes. METHODS AND RESULTS: Two-sample MR analyses were performed to estimate the causal effect of four biomarkers of systemic iron status on diagnosed cardiomyopathy and its subtypes in 242,607 participants from the FinnGen research project. The level of transferrin saturation was significantly associated with an increased risk of cardiomyopathy (OR, 1.17; 95% CI, 1.13-1.38) when using nine separately selected genetic instruments. An increase in genetically determined serum iron (odds ratio [OR] per standard deviation [SD], 1.25; 95% confidence interval [CI], 1.13-1.38) and ferritin (OR, 1.49; 95% CI, 1.02-2.18) were associated with an increased risk of cardiomyopathy. Total iron binding capacity, a marker of reduced iron status, was inversely linked with cardiomyopathy (OR, 0.80; 95% CI, 0.65-0.98). The risk effect of iron status was more evident in hypertrophic cardiomyopathy and related heart failure. CONCLUSIONS: These analyses support the causal effect of increased systemic iron status on a higher risk of non-ischemic cardiomyopathy. A screening test for cardiomyopathy should be considered in patients with evidence of iron overload. Future study is needed for exploring the mechanism of these causal variants on cardiomyopathy.

Mood assessments of family caregivers of patients with severe brain injury in China.

OBJECTIVES: Long-term care of severe brain injury patients places a significant mental burden on family caregivers, yet few studies have reported the situation in China. We aimed to describe the mood states of family caregivers of patients with severe brain injury and examine the influencing factors that affect caregivers' moods. METHODS: Cross-sectional survey was used to assess the mood profiles of Chinese family caregivers between February 2019 and February 2020. Demographic data of caregivers and patients, the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7) were used to assess the level of depressive and anxiety symptoms. The quality of life score was also assessed by a visual analog scale, and the Coma Recovery Scale-Revised was used to assess the patient's consciousness. RESULT: One hundred and one patients with severe brain injury (57 unresponsive wakefulness syndrome, UWS) between the age of 14 and 70 and their main family caregivers were enrolled in the study. Most caregivers displayed depressive (n = 62) and anxiety symptoms (n = 65), with 17 and 20 of these family caregivers reporting (moderately) severe depressive symptom and severe anxiety symptom, respectively. The caregiver's depressive symptom level significantly decreased as the patient's injury lasted longer (r = - 0.208, P = 0.037). Moreover, the age of the patient negatively related to the levels of depressive (r = - 0.310, P = 0.002) and anxiety symptoms (r = - 0.289, P = 0.003) in caregivers. There was a significant positive correlation between anxiety and depressive symptoms scores in family caregivers (r = 0.838, P < 0.001). The higher the level of anxiety (r = - 0.273, P = 0.006) and depressive symptoms (r = - 0.265, P = 0.007), the worse the quality of life. CONCLUSION: Many family caregivers of patients with severe brain injury experience various levels of anxiety and depressive symptoms in China. Tailor-made psychological help seems imperative. Researchers and doctors can provide information about patient's conditions to assist family members in discussing rehabilitation options for patients in different states of consciousness will help to ease anxiety of family caregivers.

Altered brain activity and cognitive impairment in patients with psoriasis.

BACKGROUND: Patients with psoriasis may have cognitive impairment. However, there is limited information regarding intrinsic brain activity and cognitive function in patients with psoriasis. OBJECTIVES: This study aim to assess alterations of intrinsic brain activity and its association with cognitive function in patients with psoriasis. METHODS: A total of 222 patients with psoriasis aged 18-70 years and 144 age and gender-matched healthy controls (HCs) were enrolled into this study. All subjects underwent brain resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological testing. The rs-fMRI data were analysed for both intrinsic brain activity as indicated by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC). Correlative analysis of brain activity with cognitive assessment was performed. RESULTS: Compared with the HCs, patients with psoriasis had worse cognitive performance in the Trail Making Test, Digit Span Test and Stroop Color-Word Test (p < 0.05). Patients with psoriasis showed decreased ALFF in the left superior frontal gyrus, the left medial superior frontal gyrus and the right precuneus gyrus; as well as enhanced ALFF in the left paracentral lobule (pFWE < 0.05). Significant correlations were noted between the altered ALFF in the four brain regions and cognitive assessment (p < 0.05). Moreover, patients with psoriasis had increased FC between the four brain regions with altered ALFF (seeds) and the left prefrontal gyrus, the left anterior cingulate gyrus, left superior parietal lobule and default mode network (DMN) regions such as the right precuneus gyrus, left inferior parietal lobule, right angular gyrus and bilateral inferior temporal gyrus (pFWE < 0.05). CONCLUSIONS: Patients with psoriasis had altered brain activity and connectivity in the key brain areas within the DMN-prefrontal circuit. These brain changes may be the underlying neural correlates for cognitive functioning in patients with psoriasis.

Effects of supplemental Glycyrrhiza polysaccharide on growth performance and intestinal health in weaned piglets.

In this study, we investigated the effects of supplemental Glycyrrhiza polysaccharide (GCP) on growth performance and intestinal health of weaned piglets. Ninety piglets weaned at 28 days of age were randomly allocated to three groups with five replicates per treatment. Piglets were fed the following diets for 28 days: (1) CON (control group), basal diet; (2) G500, CON + 500 mg/kg GCP; (3) G1000, CON + 1000 mg/kg GCP. The results showed that supplementation with 1000 mg/kg GCP increased the average daily gain (ADG) and decreased the feed-to-gain ratio (F/G) (P < 0.05). Serum diamine oxidase (DAO) and D-lactic acid (DL-A) levels were lower in the G1000 group (P < 0.05). Dietary GCP 1000 mg/kg improved mucosal trypsin activity in the duodenum, jejunum and ileum and increased lipase and amylase activity in the jejunum (P < 0.05). Moreover, in the G1000 group, ZO-1, claudin 1 and occludin levels were increased in the jejunum mucosa, whereas interleukin-1ß (IL-1ß) and IL-6 levels were decreased (P < 0.05). The 16S rRNA gene analysis indicated that dietary 1000 mg/kg GCP altered the jejunal microbial community, with increased relative abundances of beneficial bacteria. In conclusion, dietary GCP 1000 mg/kg can improve growth performance, digestive enzyme activity, intestinal immunity, barrier function and microbial community in weaned piglets.

Perception of diagnosis by family caregivers in severe brain injury patients in China.

OBJECTIVES: Surrogate decision-making by family caregivers for patients with severe brain injury is influenced by the availability and understanding of relevant information and expectations for future rehabilitation. We aimed to compare the consistency of family caregivers' perceptions with clinical diagnoses and to inform their expectation of prognosis in the future. METHODS: The Coma Recovery Scale-Revised was used to assess the diagnosis of inpatients with severe brain injury between February 2019 and February 2020. A main family caregiver was included per patient. The family caregiver's perception of the patient's consciousness and expectations of future recovery were collected through questionnaires and compared consistently with the clinical diagnosis. RESULTS: The final sample included 101 main family caregivers of patients (57 UWS, unresponsive wakefulness syndrome, 37 MCS, minimally conscious state, 7 EMCS, emergence from MCS) with severe brain injury. Only 57 family caregivers correctly assessed the level of consciousness as indicated by the CRS-R, showing weak consistency (Kappa = 0.217, P = 0.002). Family caregivers' demographic characteristics and CRS-R diagnosis influenced the consistency between perception and clinical diagnosis. Family caregivers who provided hands-on care to patients showed higher levels of consistent perception (AOR = 12.24, 95% CI = 2.06-73.00, P = 0.006). Compared to UWS, the family caregivers of MCS patients were more likely to have a correct perception (OR = 7.68, 95% CI = 1.34-44.06). Family caregivers had positive expectations for patients' recovery in terms of both communication and returning to normal life. CONCLUSION: Nearly half of family caregivers have inadequate understanding of their relative's level of consciousness, and most of them report overly optimistic expectations that do not align with clinical diagnosis. Providing more medical information to family caregivers to support their surrogate decision-making process is essential.

Alteration of prefrontal cortex and its associations with emotional and cognitive dysfunctions in adolescent borderline personality disorder.

The neurobiological mechanism of borderline personality disorder (BPD) in adolescents remains unclear. The study aimed to assess the alterations in neural activity within prefrontal cortex in adolescents with BPD and investigate the relationship of prefrontal activity with emotional regulation and cognitive function. This study enrolled 50 adolescents aged 12-17 years with BPD and 21 gender and age-matched healthy control (HC) participants. Study assessment for each participant included a brain resting-state functional MRI (rs-fMRI), clinical assessment questionnaires such as Borderline Personality Features Scale (BPFS), Difficulties in Emotion Regulation Scale (DERS), Ottawa Self-Injury Inventory and Childhood Trauma Questionnaire (CTQ) and cognitive testing with Stroop Color-Word Test (SCWT). Fractional amplitude of low-frequency fluctuations (fALFF) and seed-based functional connectivity (FC) were obtained from rs-fMRI analysis. Correlation analysis was also performed to evaluate the associations of the neuroimaging metrics such as fALFF and FC with clinical assessment questionnaire and cognitive testing scores. Adolescents with BPD showed increased fALFF values in the right inferior frontal gyrus and decreased activity in the left middle frontal gyrus as compared to the HC group (p < 0.05, cluster size ≥ 100, FWE correction). In adolescents with BPD, increased fALFF in the right inferior frontal gyrus was related to the BPFS (emotional dysregulation), DERS-F (lacking of emotional regulation strategies) and Ottawa Self-Injury Inventory-4 C scores (internal emotional regulation function of self-injurious behavior). The reduced fALFF in the left middle frontal gyrus was associated with the SCWT-A (reading characters) and the SCWT-B (reading color) scores. Additionally, the fALFF values in the left middle frontal gyrus and the right inferior frontal gyrus were related to the CTQ-D (emotional neglect) (p < 0.05). The left middle frontal gyrus exhibited increased FC with the right hippocampus, left inferior temporal gyrus and right inferior frontal gyrus (voxel p < 0.001, cluster p < 0.05, FWE correction). The increased FC between the left middle frontal gyrus and the right hippocampus was related to the SCWT-C (cognitive flexibility) score. We observed diverging changes in intrinsic brain activity in prefrontal cortex, and neural compensatory changes to maintain function in adolescents with BPD. In addition, decreased neural function was closely associated with emotional dysregulation, while increased neural function as indicated by brain activity and FC was associated with cognitive dysfunction. These results indicated that alterations of intrinsic brain activity may be one of the underlying neurobiological markers for clinical symptoms in adolescents with BPD.

Dynamical vaccination behavior with risk perception and vaccination rewards.

Vaccination is the most effective way to control the epidemic spreading. However, the probability of people getting vaccinated changes with the epidemic situation due to personal psychology. Facing various risks, some people are reluctant to vaccinate and even prefer herd immunity. To encourage people to get vaccinated, many countries set up reward mechanisms. In this paper, we propose a disease transmission model combining vaccination behaviors based on the SIR (Susceptible-Infected-Recovered) model and introduce three vaccination mechanisms. We analyze the impact of the infection rate and the recovery rate on the total cost and the epidemic prevalence. Numerical simulations fit with our intuitive feelings. Then, we study the impact of vaccination rewards on the total social cost. We find that when vaccination rewards offset vaccination costs, both the total cost and the epidemic prevalence reach the lowest levels. Finally, this paper suggests that encouraging people to get vaccinated at the beginning of an epidemic has the best effect.

Outbreak of Septoria leaf spot caused by Sphaerulina musiva on Populus × euramericana in China.

In June 2023, severe leaf spots were noted in Populus × euramericana cv 'Nanlin95' plantations located in the Nanjing Baguazhou Wetland Park (32°09'16.97″N, 118°48'16.74″E) of Jiangsu Province and Populus × canadensis cv 'Sacrau 79' and Populus × canadensis cv 'Guariento' in the Liyuan Village in Nanyang City (32°53'43.70″N, 112°17'29.12″E) of Henan Province, respectively. The disease incidence in both locations could reach 97.9% (556 out of 568 trees) and 98.9% (2409 out of 2436 trees), respectively. The initial symptoms appear as numerous small and circular spots (1.59 to 3.18 mm in diameter) with gray or tan centers and dark-brown margins on the leaves. As the spots age, they sometimes enlarge, often coalesce, and may extend down the petioles. Diseased leaves and petioles were both surface sterilized with 75% ethanol for 30 seconds. With the aid of a hand lens, pycnidia (brown to black, spherical in profile, 90 to 250 µm diam) were easily picked out in the center of the spots and subsequently transferred into 1 mL sterilized water for preparing the spore suspension plated on KV8 medium amended with 100 mg/liter streptomycin sulfate and 50 mg/liter chloramphenicol. After 12 days of incubation, 86 single-spore isolates were obtained and identified as typical Septoria-like fungi according to morphological features, including slow-growing, gray or black colonies with pink mucilaginous matrix and hyaline, straight or curved conidia (size = 25 to 59 × 3.5 to 4 µm; septa = 1 to 6). Species identification was further validated by PCR amplification and sequencing of the internal transcribed spacer (ITS) region with ITS1/ITS4 primer pairs. Multiple sequence alignments with ClustalW revealed that the obtained ITS sequences of 86 isolates were 100% identical to each other. A BLAST search in GenBank indicated that the selfsame sequences of two representative isolates (isolate BGZ11 of Jiangsu Province, accession no. OR660379; isolate KZB22 of Henan Province, accession no. OR711499) shared 99.8% identity (494 of 495 bp) and 100% identity (504 of 504 bp) with related sequences of Sphaerulina musiva (Peck) Quaedvlieg, Verkley, and Crous (syn. = Septoria musiva Peck) in GenBank (MN275187; KF251619), respectively. Furthermore, we used a S. musiva-specific PCR assay (Abraham et al. 2018) on symptomatic leaf samples collected from the plantation. Each sample consisted of 20 cut-out leaf spots per leaf. Eight of the 10 samples were positive for S. musiva DNA. To confirm pathogenicity, six sterile tissue culture of poplar plants (Populus trichocarpa and Populus × euramericana cv 'Nanlin895') were respectively transplanted into pots and grown in a greenhouse for a week and for a month with an 18-h photoperiod augmented with sodium lamps and a 20°C (day)/16°C (night) temperature regime. Inoculations were conducted by spraying the plants with conidia suspension (106 conidia/mL) (LeBoldus et al. 2010). Control plants were sprayed with distilled water. Leaf spots were developed on the inoculated P. trichocarpa leaves at one week and P. × euramericana cv 'Nanlin895' leaves at 10 days after inoculation while no symptoms were observed on the control plants. The fungus S. musiva was successfully reisolated from all symptomatic leaves fulfilling Koch's postulates. Sphaerulina musiva only causes an endemic leaf spot disease on its natural North American host Populus. deltoides (Feau et al. 2010; Ostry 1987). However, on susceptible Populus species (e.g., P. balsamifera, P. trichocarpa, P. maximowiczii) and hybrids, S. musiva causes not only leaf spots but also severely damaging stem and branch cankers (Jeger et al. 2018; LeBoldus et al. 2009; Sondreli et al. 2020). To our knowledge, this is the first report of S. musiva causing leaf spots on poplar in China. Large-scale timber imports (e.g., cut branches, isolated bark, wood with and without bark) potentially lead to anthropogenic-facilitated transport of this pathogen. This outbreak of Septoria leaf spot underscores the potential threat of this pathogen to P. × euramericana in China, where it is widely planted as a keystone forestry species.

Scar Hypertrophy Causing Nasal Obstruction Reconstruction.

Reconstructive surgery plays a crucial role in addressing congenital defects, posttraumatic deformities, and related conditions, providing transformative solutions for patients. Its primary goal is to restore or enhance damaged tissue structures, improving both functionality and appearance, and empowering individuals to lead fulfilling lives. Take, for example, a female patient who experienced a nasal infection after a cat bite. Despite initial treatment, she developed severe scar contractures and excessive scar tissue within her nostrils, significantly impacting her quality of life. Seeking assistance, she consulted the authors' plastic and reconstructive surgery team. By utilizing various flap techniques, the authors embarked on the intricate journey of reconstructing her nasal framework, ultimately restoring both form and function.

Toward Reliable Symptom Coding in Electronic Health Records for Symptom Assessment and Research: Identification and Categorization of International Classification of Diseases, Ninth Revision, Clinical Modification Symptom Codes.

To date, symptom documentation has mostly relied on clinical notes in electronic health records or patient-reported outcomes using disease-specific symptom inventories. To provide a common and precise language for symptom recording, assessment, and research, a comprehensive list of symptom codes is needed. The International Classification of Diseases, Ninth Revision or its clinical modification (International Classification of Diseases, Ninth Revision, Clinical Modification) has a range of codes designated for symptoms, but it does not contain codes for all possible symptoms, and not all codes in that range are symptom related. This study aimed to identify and categorize the first list of International Classification of Diseases, Ninth Revision, Clinical Modification symptom codes for a general population and demonstrate their use to characterize symptoms of patients with type 2 diabetes mellitus in the Cerner database. A list of potential symptom codes was automatically extracted from the Unified Medical Language System Metathesaurus. Two clinical experts in symptom science and diabetes manually reviewed this list to identify and categorize codes as symptoms. A total of 1888 International Classification of Diseases, Ninth Revision, Clinical Modification symptom codes were identified and categorized into 65 categories. The symptom characterization using the newly obtained symptom codes and categories was found to be more reasonable than that using the previous symptom codes and categories on the same Cerner diabetes cohort.

Risk Factors for Incontinence-Associated Dermatitis in Critically Ill Patients with Incontinence: A Systematic Review and Meta-analysis.

PURPOSE: This systematic review analyzed evidence related to risk factors for Incontinence Associated Dermatitis (IAD) in critically ill incontinent patients. METHOD: Systematic review and meta-analysis. SEARCH STRATEGY: Eight databases, including PubMed, Embase, CINAHL, Cochrane Library, and Web of Science, were searched for studies published in the English language. The China National Knowledge Infrastructure, WanFang Data, and Chinese Scientific Journal Database were also searched for studies evaluating risk of IAD in critically ill incontinent patients published in the Chinese language. FINDINGS: Twenty-four studies with moderate-to-high methodological quality were included. Significant risk factors for developing IAD were being older [odds ratio (OR) = 1.06, 95% confidence interval (CI): 1.02-1.10, P = .007], fever (OR = 2.57, 95% CI: 1.87-3.57, P < .00001), diagnosed with consciousness disorder (OR = 5.70, 95% CI: 2.28-14.22, P = .0002), having higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR = 1.71, 95% CI: 1.25-2.35, P = .0009), lower Braden score (OR = 0.73, 95% CI: 0.56-0.96, P = .02), lower oxygen saturation (OR = 2.76, 95% CI: 1.52-5.00, P = .0008), double incontinence (OR = 4.10, 95% CI: 2.34-7.17, P < .00001), liquid stool (OR = 6.55, 95% CI: 4.12-10.41, P < .00001), frequent incontinence (OR = 1.21, 95% CI: 1.03-1.43, P = .02), and higher perineal assessment tool (PAT) score (OR = 3.18, 95% CI: 1.76-5.76, P = .0001). IMPLICATIONS: Findings of this systematic review and meta-analysis suggest that healthcare providers should consider risk factors such as older age, fever, consciousness disorder, higher APACHE II score, lower Braden score and double incontinence matter when developing strategies for the prevention and management of IAD in critically ill incontinent patients.