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Abstract Purpose To evaluate the effectiveness and safety of a method for repairing an eroded Ahmed glaucoma valve (AGV) tube using two short scleral tunnels made in tandem with a 22G needle instead of covering the eroded tube with another scleral graft. Methods From May 12, 2015, to July 27, 2019, we retrospectively reviewed eight patients at Ningbo Aier Eye Hospital who developed AGV tube erosion secondary to necrosis of their overlying conjunctiva and scleral grafts. This defect was repaired in all the patients using the double short tandem scleral tunnel technique, which involved the creation of double short tandem scleral tunnels made by a 22G needle. Two parallel-to-limbus scleral incisions were made 3 mm and 6 mm from the limbus first, then a curved 22G needle was inserted between the two scleral cuts to make one scleral tunnel, the other scleral tunnel was completed during the first surgery, inserted the tube into the two tunnels. The mean length of time between the AGV placement and the first erosion was 12.25 ± 6.36 months (3–24 months). The mean age of the patients was 65.50 ± 11.70 years (49–78 years). Results The surgical outcome was assessed in terms of the tectonic integrity of the conjunctiva over the follow-up period (12 months). There was no AGV tube erosion, scleral thinning, or ocular infection after a mean of 41.25 ± 26.54 months of follow-up in all eight patients. Conclusion AGV tube erosion following shunt surgery can be successfully managed using the improved double short tandem scleral tunnel technique.

Abstract Background Ripeness is a phenotype that significantly impacts the quality of fruits, constituting a crucial factor in the cultivation and harvesting processes. Manual detection methods and experimental analysis, however, are inefficient and costly. Results In this study, we propose a lightweight and efficient melon ripeness detection method, MRD-YOLO, based on an improved object detection algorithm. The method combines a lightweight backbone network, MobileNetV3, a design paradigm Slim-neck, and a Coordinate Attention mechanism. Additionally, we have created a large-scale melon dataset sourced from a greenhouse based on ripeness. This dataset contains common complexities encountered in the field environment, such as occlusions, overlapping, and varying light intensities. MRD-YOLO achieves a mean Average Precision of 97.4% on this dataset, achieving accurate and reliable melon ripeness detection. Moreover, the method demands only 4.8 G FLOPs and 2.06 M parameters, representing 58.5% and 68.4% of the baseline YOLOv8n model, respectively. It comprehensively outperforms existing methods in terms of balanced accuracy and computational efficiency. Furthermore, it maintains real-time inference capability in GPU environments and demonstrates exceptional inference speed in CPU environments. The lightweight design of MRD-YOLO is anticipated to be deployed in various resource constrained mobile and edge devices, such as picking robots. Particularly noteworthy is its performance when tested on two melon datasets obtained from the Roboflow platform, achieving a mean Average Precision of 85.9%. This underscores its excellent generalization ability on untrained data. Conclusions This study presents an efficient method for melon ripeness detection, and the dataset utilized in this study, alongside the detection method, will provide a valuable reference for ripeness detection across various types of fruits.

The phyllospheric microbial composition of tobacco plants is influenced by multiple factors. Disease severity level is one of the main influencing factors. This study was designed to understand the microbial community in tobacco wildfire disease with different disease severity levels. Tobacco leaves at disease severity level of 1, 5, 7, and 9 (L1, L5, L7, and L9) were collected; both healthy and diseased leaf tissues for each level were collected. The community structure and diversity in tobacco leaves with different disease severity levels were compared using high-throughput technique and Biolog Eco. The results showed that in all healthy and diseased tobacco leaves, the most dominant bacterial phylum was Proteobacteria with a high prevalence of genus Pseudomonas; the relative abundance of Pseudomonas was most found at B9 diseased samples. Ascomycota represents the most prominent fungal phylum, with Blastobotrys as the predominant genus. In bacterial communities, the Alpha diversity of healthy samples was higher than that of diseased samples. In fungal community, the difference in Alpha diversity between healthy and diseased was not significant. LEfSe analysis showed that the most enriched bacterial biomarker was unclassified_Gammaproteobacteria in diseased samples; unclassified_Alcaligenaceae were the most enrich bacterial biomarker in healthy samples. FUNGuild analysis showed that saprotroph was the dominated mode in health and lower diseased samples, The abundance of pathotroph–saprotroph and pathotroph–saprotroph–symbiotroph increases at high disease levels. PICRUSt analysis showed that the predominant pathway was metabolism function, and most bacterial gene sequences seem to be independent of the disease severity level. The Biolog Eco results showed that the utilization rates of carbon sources decrease with increasing disease severity level. The current study revealed the microbial community’s characteristic of tobacco wildfire disease with different disease severity levels, providing scientific references for the control of tobacco wildfire disease.

Abstract Background The immunoglobulin superfamily protein Trem2 (triggering receptor expressed on myeloid cells 2) is primarily expressed on myeloid cells where it functions to regulate macrophage‐related immune response induction. While macrophages are essential mediators of diabetic wound healing, the specific regulatory role that Trem2 plays in this setting remains to be established. Objective This study was developed to explore the potential importance of Trem2 signalling in diabetic wound healing and to clarify the underlying mechanisms through which it functions. Methods and results Following wound induction, diabetic model mice exhibited pronounced upregulation of Trem2 expression, which was primarily evident in macrophages. No cutaneous defects were evident in mice bearing a macrophage‐specific knockout of Trem2 (T2‐cKO), but they induced more pronounced inflammatory responses and failed to effectively repair cutaneous wounds, with lower levels of neovascularization, slower rates of wound closure, decreased collagen deposition following wounding. Mechanistically, we showed that interleukin (IL)‐4 binds directly to Trem2, inactivating MAPK/AP‐1 signalling to suppress the expression of inflammatory and chemoattractant factors. Co‐culture of fibroblasts and macrophages showed that macrophages from T2‐cKO mice suppressed the in vitro activation and proliferation of dermal fibroblasts through upregulation of leukaemia inhibitory factor (Lif). Injecting soluble Trem2 in vivo was also sufficient to significantly curtail inflammatory responses and to promote diabetic wound healing. Conclusions These analyses offer novel insight into the role of IL‐4/Trem2 signalling as a mediator of myeloid cell‐fibroblast crosstalk that may represent a viable therapeutic target for efforts to enhance diabetic wound healing.

Abstract Atmospheric precipitable water vapor (PWV) is a crucial factor affecting precipitation and the atmospheric environment. To quantitatively investigate the spatio‐temporal distribution and characteristics of the PWV in Fujian, China, its diurnal and seasonal variations are analyzed based on the global navigation satellite system (GNSS) data from 2010 to 2023, ground meteorological observations, meteorological sounding data and ERA5 data. Moreover, the spatio‐temporal characteristics of the monthly PWV are assessed by using the empirical orthogonal function (EOF), the Mann‐Kendall test and the sliding t‐test. The results indicate that the ground‐based GNSS PWV data is able to reveal the distribution and variation of PWV over Fujian. Specifically, the diurnal distribution of the PWV varies remarkably with time, and the PWV in the eastern coastal areas is generally higher than in the western mountainous areas. The seasonal variation characteristics of the PWV are consistent with the atmospheric circulation variations, with the largest amount of PWV in summer, followed by spring, autumn and winter. Moreover, the EOF spatial modes show that the PWV distributions are different in the eastern coastal areas and inland mountainous areas. The oscillation intensity of the PWV strengthens from the northwest to the southeast, and the corresponding time series of the PWV displays apparent seasonal variations. The observed precipitation is inconsistent with the PWV and is more affected by local terrain and thermodynamic conditions. The Mann‐Kendall test and the sliding t‐test indicate that the PWV over Fujian has not undergone abrupt changes during the past 13 years, but there is a possibility of sudden changes in the future.

Abstract Haplotype-resolved genome assembly plays a crucial role in understanding allele-specific functions. However, obtaining haplotype-resolved assembly for auto-polyploid genomes remains challenging. Existing methods can be classified into reference-based phasing, assembly-based phasing, and gamete binning. Nevertheless, there is a lack of cost-effective and efficient methods for haplotyping auto-polyploid genomes. In this study, we propose a novel phasing algorithm called PolyGH, which combines Hi-C and gametic data. We conducted experiments on tetraploid potato cultivars and divided the method into three steps. Firstly, gametic data was utilized to bin non-collapsed contigs, followed by merging adjacent fragments of the same type within the same contig. Secondly, accurate Hi-C signals related to differential genomic regions were acquired using unique k-mers. Finally, collapsed fragments were assigned to haplotigs based on combined Hi-C and gametic signals. Comparing PolyGH with Hi-C-based and gametic data-based methods, we found that PolyGH exhibited superior performance in haplotyping auto-polyploid genomes when integrating both data types. This approach has the potential to enhance haplotype-resolved assembly for auto-polyploid genomes.

Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid β-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection.

The burden of fungal infections on human health is increasing worldwide. Aspergillus, Candida, and Cryptococcus are the top three human pathogenic fungi that are responsible for over 90% of infection-related deaths. Moreover, effective antifungal therapeutics are lacking, primarily due to host toxicity, pathogen resistance, and immunodeficiency. In recent years, nanomaterials have proved not only to be more efficient antifungal therapeutic agents but also to overcome resistance against fungal medication. This review will examine the limitations of standard antifungal therapy as well as focus on the development of nanomaterials.

Although rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended.

Cryptococcosis is a life-threatening invasive fungal infection with significantly increasing mortality worldwide, which is mainly caused by Cryptococcus neoformans and Cryptococcus gattii. These two species complexes have different epidemiological and clinical characteristics, indicating the importance of accurate differential diagnosis. However, the clinically used culture method and cryptococcal capsular antigen detection couldn’t achieve the above goals. Herein, we established a novel duplex flap probe-based isothermal assay to identify the Cryptococcus neoformans and Cryptococcus gattii within 1 hour. This assay combined the highly sensitive nucleic acid isothermal amplification and highly specific fluorescence probe method, which could effectively distinguish the sequence differences of the two species complexes using two different fluorescence flap probes in a single reaction system. This novel method showed excellent detection performance with sensitivity (10 copies/μL each) and specificity (100%) compared to traditional culture and sequencing methods. Furthermore, we applied this method to spiked clinical samples, 30 cerebrospinal fluids and 30 bronchoalveolar lavage fluids, which kept good detection performance. This novel rapid duplex flap probe-based isothermal assay is a promising and robust tool for applications in differential diagnosis of the Cryptococcus neoformans and Cryptococcus gattii in clinical settings, especially when clinical suspicion for cryptococcal disease is high and epidemiological studies.

De novo assembly plays a pivotal role in metagenomic analysis, and the incorporation of third-generation sequencing technology can significantly improve the integrity and accuracy of assembly results. Recently, with advancements in sequencing technology (Hi-Fi, ultra-long), several long-read-based bioinformatic tools have been developed. However, the validation of the performance and reliability of these tools is a crucial concern. To address this gap, we present MCSS (microbial community simulator based on structure), which has the capability to generate simulated microbial community and sequencing datasets based on the structure attributes of real microbiome communities. The evaluation results indicate that it can generate simulated communities that exhibit both diversity and similarity to actual community structures. Additionally, MCSS generates synthetic PacBio Hi-Fi and Oxford Nanopore Technologies (ONT) long reads for the species within the simulated community. This innovative tool provides a valuable resource for benchmarking and refining metagenomic analysis methods.Code available at:https://github.com/panlab-bio/mcss

ObjectiveTo summarize the experience with intraluminal esophageal stretching elongation (ILESE) in the successful treatment of long-gap esophageal atresia (LGEA) at a single center.MethodsClinical data of 68 neonates who underwent LGEA between February 2015 and January 2022 were retrospectively analyzed. Four patients died of multiple associated severe malformations and did not undergo ILESE. Esophageal anastomosis was successfully performed in 60 cases (93.75%) and failed in 4 cases (6.25%) treated with ILESE. The ILESE techniques, esophageal reconstruction, results, postoperative complications, and follow-up treatment were analyzed.ResultsThe beginning time of performing ILESE preoperation was 53.4 ± 39.4 days after birth, and the age of esophageal reconstruction was 122.2 ± 70.3 days after birth in 60 cases. The gap length of proximal and distal esophageal segments which were evaluated the first time at admission was 4.8 ± 1.3 vertebral bodies, whereas the gap before anastomosis was −0.46 ± 0.90 vertebral bodies. Among the patients with esophageal primary-anastomosis, 55 received thoracoscopic surgery, and 5 underwent thoracotomy in the early stage. Of the 60 children with ILESE, 58 underwent end-to-end esophagostomy, of which 17 cases were combined with circular esophagotomy (livaditis), and 2 cases of esophageal lengthening were combined with the reversal of the ligulate loop of the proximal esophagus (flap). Overall, 59 cases were cured (98.3%), and 1 patient died of respiratory failure postoperatively. All patients were followed up for 7–96 months. Postoperative anastomotic leakage occurred in 16 patients (27.6%), all of whom were successfully treated conservatively. Anastomotic stenosis occurred in 49 cases (83.1%), all of which were successfully managed by non-surgical treatment, including 12.7 ± 9.3 times of esophageal balloon dilatation and 2 cases of stent dilatation. Gastroesophageal reflux occurred in 44 patients (74.6%), including associated or acquired esophageal hiatal hernia in 22 patients, and Nissen fundoplication was performed in 17 patients.ConclusionsILESE is an effective method for prolonging the proximal and distal esophagus of the LGEA to reconstruct esophageal continuity using its esophageal tissue, with an efficacy rate of 93.75%. Postoperative anastomotic stricture and gastroesophageal reflux are common and require long-term, standardized follow-up and treatment.

Abstract As current trend for physician tools, ChatGPT can sift through massive amounts of information and solve problems through easy-to-understand conversations, ultimately improving efficiency. Mycosis is currently facing great challenges, including high fungal burdens, high mortality, limited choice of antifungal drugs and increasing drug resistance. To address these challenges, We asked ChatGPT for fungal infection scenario-based questions and assessed its appropriateness, consistency, and potential pitfalls. We concluded ChatGPT can provide compelling responses to most prompts, including diagnosis, recommendations for examination, treatment and rational drug use. Moreover, we summarized exciting future applications in mycosis, such as clinical work, scientific research, education and healthcare. However, the largest barriers to implementation are deficits in indiviudal advice, timely literature updates, consistency, accuracy and data safety. To fully embrace the opportunity, we need to address these barriers and manage the risks. We expect that ChatGPT will become a new weapon in in the battlefield of mycosis.

Abstract Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.

Abstract Background The global burden of invasive fungal infections (IFIs) has shown an upsurge in recent years due to the higher load of immunocompromised patients suffering from various diseases. The role of early and accurate diagnosis in the aggressive containment of the fungal infection at the initial stages becomes crucial thus, preventing the development of a life-threatening situation. With the changing demands of clinical mycology, the field of fungal diagnostics has evolved and come a long way from traditional methods of microscopy and culturing to more advanced non-culture-based tools. With the advent of more powerful approaches such as novel PCR assays, T2 Candida, microfluidic chip technology, next generation sequencing, new generation biosensors, nanotechnology-based tools, artificial intelligence-based models, the face of fungal diagnostics is constantly changing for the better. All these advances have been reviewed here giving the latest update to our readers in the most orderly flow. Main text A detailed literature survey was conducted by the team followed by data collection, pertinent data extraction, in-depth analysis, and composing the various sub-sections and the final review. The review is unique in its kind as it discusses the advances in molecular methods; advances in serology-based methods; advances in biosensor technology; and advances in machine learning-based models, all under one roof. To the best of our knowledge, there has been no review covering all of these fields (especially biosensor technology and machine learning using artificial intelligence) with relevance to invasive fungal infections. Conclusion The review will undoubtedly assist in updating the scientific community’s understanding of the most recent advancements that are on the horizon and that may be implemented as adjuncts to the traditional diagnostic algorithms.

In the of local fan for mine fan switch, it’s easy to have a short stop wind that cause the safe production of gas concentration transfinite problem. In order to avoid the phenomenon of air volume suspension caused by fan switching, according to the principle of constant air volume switching, the intelligent switching control system of local fan with constant air volume is studied. By using the principle of constant air volume feedback fuzzy regulation control, a new intelligent remote control system of mine local fan and an intelligent monitoring device of ZFJ1140 local fan are developed. It realizes the remote and real-time monitoring of constant air volume and fan running parameters in the process of fan switching. The aerodynamic performance test was carried out in four places: the air inlet, the air inlet, the air inlet and the air outlet of the collector. The results show that the aerodynamic performance of the fan is good, and the total pressure efficiency of the fan fluctuates in the range of 82.5%-85%. The application of ZFJ1140 local fan in 1010 auxiliary roadway of No.1 Coal mine of Shaanxi Coal Huangling Mining Group shows that the variation of roadway air volume is controlled within 8.89% during the air volume switching period. Compared with the traditional local fan switching mode, the constant air volume switching function of the intelligent local fan effectively ensures that the gas concentration in the roadway is maintained in a safe range during the air volume switching process.

Background: Ultrasound serves as a valuable tool for the early detection of fetal bowel dilatation, yet the correlation between fetal bowel dilatation and gastrointestinal malformations remains to be further investigated. This study aims to explore the relationship by conducting a follow-up and analysis of fetuses with bowel dilation. Methods: A retrospective analysis was conducted on 113 fetuses with bowel dilatation at our center from July 2014 to December 2019. The location and degree of bowel dilatation were analyzed. ROC curves were constructed based on the diameter of the bowel and its ratio to fetal gestational age. Results: In total, 40 of 41 cases (97.6%) with upper gastrointestinal dilatation (double-bubble sign) and 46 of 72 cases (63.9%) with lower gastrointestinal dilatation were diagnosed with gastrointestinal malformations postnatally. The AUC of the dilatation diameter was 0.854 with a cutoff value of 18.05 mm in patients with lower gastrointestinal dilatation. The ratio of the diameter to gestational age (D/GA) showed a higher AUC of 0.906 with a cutoff value of 0.4931. Conclusions: The presence of the double-bubble sign in fetuses indicates a close association with duodenal obstruction. The risk of gastrointestinal malformations increases when the bowel diameter exceeds 18.05 mm, particularly when the D/GA surpasses 0.4931.

Background: Reactive cutaneous capillary endothelial proliferation (RCCEP) is a common, burdensome adverse event that occurs in up to 88% of patients treated with camrelizumab. Without treatment, RCCEP is associated with social stigma and low quality of life. However, the optimal management of RCCEP remains inconclusive. Aims and Objectives: to elucidate the pathogenesis and clinical manifestations of RCCEP and systematically review the existing different therapeutic options for this dermatologic toxicity to encourage the selection of the most appropriate approaches for individual comprehensive management. Materials and Methods: As far as we know, we have systematically reviewed all cases complicated with RCCEP worldwide, and summarized the advantages and disadvantages of existing treatment methods. In addition, we report a successful case of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in a 61-year-old male Chinese patient who developed RCCEP after camrelizumab immunotherapy. Owing to the patient's advanced age, complicated medication history, and hyperalgesia, ALA-PDT was performed. The multiple lesions on his chest and buttocks showed rapid relief within 1 week of a single treatment session. Clinical recurrence was not observed within 6 months following treatment. Results: The current treatment of RCCEP is challenging and there is a lack of globally recommendations based on strict therapeutic regimens or clinical trials. Based on this case, we found that ALA-PDT is a safe and effective treatment option for RCCEP. This case also highlights the coexistence of several camrelizumab-induced dermatologic immune-related adverse events, which has never been reported before. Conclusion: New therapies for RCCEP have emerged in recent years. Dermatologists should raise better awareness of the complexity of drug eruption and the need for early diagnosis and medical intervention.

Taste determination in small molecules is critical in food chemistry but traditional experimental methods can be time-consuming. Consequently, computational techniques have emerged as valuable tools for this task. In this study, we explore taste prediction using various molecular feature representations and assess the performance of different machine learning algorithms on a dataset comprising 2601 molecules. The results reveal that GNN-based models outperform other approaches in taste prediction. Moreover, consensus models that combine diverse molecular representations demonstrate improved performance. Among these, the molecular fingerprints + GNN consensus model emerges as the top performer, highlighting the complementary strengths of GNNs and molecular fingerprints. These findings have significant implications for food chemistry research and related fields. By leveraging these computational approaches, taste prediction can be expedited, leading to advancements in understanding the relationship between molecular structure and taste perception in various food components and related compounds.

The gut microbiota is a dynamic and highly diverse microbial ecosystem that affects many aspects of the host’s physiology. An improved understanding of the gut microbiota could lead to better strategies for the diagnosis and therapy of cryptococcal meningitis (CM), but the impact of Cryptococcus infection and anti-fungal treatment on the gut microbiota has rarely been studied. We characterized the diversity and composition of the gut microbiota in CM patients at diagnosis and healthy controls (HCs) using metagenomic sequencing and determined the effects of anti-fungal drugs. We found that CM patients had distinct bacterial and fungal compositions compared with HCs, with eight differentially abundant fungal and 72 differentially abundant bacterial species identified between the two groups. CM patients showed an increased abundance of Enterococcus avium, Leuconostoc mesenteroides, and Weissella cibaria, and a decreased abundance of Prevotella spp. compared with HCs. However, anti-fungal treatment only led to minor changes in the intestinal microbiota. Moreover, both positive and negative correlations existed in fungal, bacterial, and clinical indicators. Our study suggests that the Cryptococcus neoformans infection caused a distinct dysbiosis of the gut microbiota and contributes valuable information implying potential links between the CM and gut microbiota.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membranes (e.g., mouth, esophagus, and vagina). Compared with that of other infectious diseases, the immune pathogenic mechanism of CMC is still poorly understood. We identified a signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutation in a CMC patient. Single-cell transcriptional profiling on peripheral blood mononuclear cells from this patient revealed decreases in immature B cells and monocytes. Further analysis revealed several differentially expressed genes related to immune regulation, including RGS1, TNFAIP3, S100A8/A9, and CTSS. In our review of the literature on signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutations, we identified seven cases in total. The median age of onset for CMC (n=4, data lacking for three cases) was 10.5 years (range: birth to 11 years), with an average onset age of 8 years. There were no reports linking tumors to the c.Y289C mutation, and the incidence of pre-existing clinical disease in patients with the c.Y289C mutation was similar to previous data.

During metastasis cancer cells must adapt to survive loss of anchorage and evade anoikis. An important pro-survival adaptation is the ability of metastatic tumor cells to increase their antioxidant capacity and restore cellular redox balance. Although much is known about the transcriptional regulation of antioxidant enzymes in response to stress, how cells acutely adapt to alter antioxidant enzyme levels is less well understood. Using ovarian cancer cells as a model, we demonstrate that an increase in mitochondrial superoxide dismutase SOD2 protein expression is a very early event initiated in response to detachment, an important step during metastasis that has been associated with increased oxidative stress. SOD2 protein synthesis is rapidly induced within 0.5–2 h of matrix detachment, and polyribosome profiling demonstrates an increase in the number of ribosomes bound to SOD2 mRNA, indicating an increase in SOD2 mRNA translation in response to anchorage-independence. Mechanistically, we find that anchorage-independence induces cytosolic accumulation of the RNA binding protein HuR/ELAVL1 and promotes HuR binding to SOD2 mRNA. Using HuR siRNA-mediated knockdown, we show that the presence of HuR is necessary for the increase in SOD2 mRNA association with the heavy polyribosome fraction and consequent nascent SOD2 protein synthesis in anchorage-independence. Cellular detachment also activates the stress-response mitogen-activated kinase p38, which is necessary for HuR-SOD2 mRNA interactions and induction of SOD2 protein output. These findings illustrate a novel translational regulatory mechanism of SOD2 by which ovarian cancer cells rapidly increase their mitochondrial antioxidant capacity as an acute stress response to anchorage-independence.

Objective:Fetal MRI has played an essential role in the evaluation and management of congenital diaphragmatic hernia (CDH). We aimed to investigate whether the mediastinal shift angle (MSA) value was associated with the prognosis and the severity of left CDH and explore the relationship between the MSA value and fetal and neonatal cardiac structures and functions.MethodsFrom January 2012 to December 2020, the fetal MSA values of left CDH in our institution were retrospectively measured. Other prenatal parameters and clinical outcomes of them are collected. We also measured the fetal and postnatal echocardiography parameters to analyze linear correlation with MSA values.ResultsA total of 94 patients with left CDH were included. MSA was significantly higher in the deceased group than in the survived group [((38.3 ± 4.7)° vs. 32.3 ± 5.3)°, p < 0.001]. The MSA value of the high-risk defect group [CDH Study Group (CDHSG) C/D type] was significantly higher than that of the low-risk defect group [CDHSG A/B type; (36.0 ± 4.9)° vs. (30.1 ± 4.8)°, p < 0.001]. The AUC for severity was 0.766 (95% CI, 0.661–0.851, p < 0.0001) and the best cut-off value for MSA was 30.7°. Higher MSA correlates with decreased fetal Z-score of left ventricle (LV) width, the diameter of the mitral valve (MV), peak velocity of MV and tricuspid valve (TV), and neonatal LV end-diastolic diameter (LVEDD) and velocity of tricuspid regurgitation (TR; p < 0.05).ConclusionA high MSA value can effectively predict high-risk defects and high mortality of left CDH. The higher the MSA value, the worse the neonatal conditions, the respiratory and cardiovascular prognosis. The MSA values could reflect the level of left heart underdevelopment, including decreased dimensions and diastolic dysfunction of the left ventricle.

Abstract Due to the high complexity of cancer genome, it is too difficult to generate complete cancer genome map which contains the sequence of every DNA molecule until now. Nevertheless, phasing each chromosome in cancer genome into two haplotypes according to germline mutations provides a suboptimal solution to understand cancer genome. However, phasing cancer genome is also a challenging problem, due to the limit in experimental and computational technologies. Hi-C data is widely used in phasing in recent years due to its long-range linkage information and provides an opportunity for solving the problem of phasing cancer genome. The existing Hi-C based phasing methods can not be applied to cancer genome directly, because the somatic mutations in cancer genome such as somatic SNPs, copy number variations and structural variations greatly reduce the correctness and completeness. Here, we propose a new Hi-C based pipeline for phasing cancer genome called HiCancer. HiCancer solves different kinds of somatic mutations and variations, and take advantage of allelic copy number imbalance and linkage disequilibrium to improve the correctness and completeness of phasing. According to our experiments in K562 and KBM-7 cell lines, HiCancer is able to generate very high-quality chromosome-level haplotypes for cancer genome with only Hi-C data.

We investigated the relative humidity (RH) vertical distribution characteristics before precipitation using microwave radiometer measurements over southeast China in 2021. The superposed epoch method is used to analyze the profile and vertical statistical characteristics and evolution of RH during precipitation events. There is a shallow, high-humidity area on the ground, with a thickness of about 0.1–0.2 Km, from 12 to 8 h before precipitation. An obvious dry layer appears in the lower layer near the ground 8–0 h before precipitation, with a thickness of about 1 km and humidity of less than 80%, which continues until the appearance of precipitation. The water vapor content in the air begins to accumulate and the humidity increases before the occurrence of LRs, MRs, and HRs, classified by total rainfall. The SDPs, MDPs, and LDPs, which are classified by precipitation duration, showed more obvious and significant characteristics of humidity increase. The statistical analysis of the 44 precipitation cases shows that the relative humidity on the ground and in the air increases significantly before precipitation, and the vertical distribution of the relative humidity and the increase in the water vapor content in the air have a more direct and obvious impact on the precipitation duration. The deep and high-humidity area of 2–4 km is conducive to maintaining the precipitation process for a long time.

Abstract Neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) is a rare but extremely malignant subtype of gallbladder cancer (GBC). The genetic and molecular signatures of GB-NEC are poorly understood; thus, molecular targeting is currently unavailable. In the present study, we applied whole-exome sequencing (WES) technology to detect gene mutations and predicted somatic single-nucleotide variants (SNVs) in 15 cases of GB-NEC and 22 cases of general GBC. In 15 GB-NECs, the C > T mutation was predominant among the 6 types of SNVs. TP53 showed the highest mutation frequency (73%, 11/15). Compared with neuroendocrine carcinomas of other organs, significantly mutated genes (SMGs) in GB-NECs were more similar to those in pulmonary large-cell neuroendocrine carcinomas (LCNECs), with driver roles for TP53 and RB1. In the COSMIC database of cancer-related genes, 211 genes were mutated. Strikingly, RB1 (4/15, 27%) and NAB2 (3/15, 20%) mutations were found specifically in GB-NECs; in contrast, mutations in 29 genes, including ERBB2 and ERBB3, were identified exclusively in GBC. Mutations in RB1 and NAB2 were significantly related to downregulation of the RB1 and NAB2 proteins, respectively, according to immunohistochemical (IHC) data (p values = 0.0453 and 0.0303). Clinically actionable genes indicated 23 mutated genes, including ALK, BRCA1, and BRCA2. In addition, potential somatic SNVs predicted by ISOWN and SomVarIUS constituted 6 primary COSMIC mutation signatures (1, 3, 30, 6, 7, and 13) in GB-NEC. Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch, WNT, Hippo, and RTK-RAS pathways. In summary, we have systematically identified the mutation landscape of GB-NEC, and these findings may provide mechanistic insights into the specific pathogenesis of this deadly disease.

Abstract Background The clinical profiles and outcomes of cryptococcal meningitis have been shown to vary depending on the underlying condition. The aim of this study was to investigate clinical characteristics and outcomes in patients with and without type II diabetes mellitus. Methods A retrospective study was performed. Clinical data of HIV-negative cryptococcal meningitis patients with type II diabetes mellitus (n = 26) and without type II diabetes mellitus (n = 52) referring to the Jiangxi Chest Hospital between January 2012 to December 2018 were analyzed. The data were analyzed using chi square, none-parametric tests, and logistic regression. P-values

Skin cancer has drawn attention for the increasing incident rates and high morbidity worldwide. Timely diagnosis and efficient treatment are of paramount importance for prompt and effective therapy. Thus, the development of novel skin cancer diagnosis and treatment strategies is of great significance for both fundamental research and clinical practice. Recently, the emerging field of nanotechnology has profoundly impact on early diagnosis and better treatment planning of skin cancer. In this review, we will discuss the current encouraging advances in functional nanomaterials for skin cancer theranostics. Challenges in the field and safety concerns of nanomaterials will also be discussed.

Abstract By 2040, ~100 million people will have glaucoma. To date, there are a lack of high-efficiency glaucoma diagnostic tools based on visual fields (VFs). Herein, we develop and evaluate the performance of ‘iGlaucoma’, a smartphone application-based deep learning system (DLS) in detecting glaucomatous VF changes. A total of 1,614,808 data points of 10,784 VFs (5542 patients) from seven centers in China were included in this study, divided over two phases. In Phase I, 1,581,060 data points from 10,135 VFs of 5105 patients were included to train (8424 VFs), validate (598 VFs) and test (3 independent test sets—200, 406, 507 samples) the diagnostic performance of the DLS. In Phase II, using the same DLS, iGlaucoma cloud-based application further tested on 33,748 data points from 649 VFs of 437 patients from three glaucoma clinics. With reference to three experienced expert glaucomatologists, the diagnostic performance (area under curve [AUC], sensitivity and specificity) of the DLS and six ophthalmologists were evaluated in detecting glaucoma. In Phase I, the DLS outperformed all six ophthalmologists in the three test sets (AUC of 0.834–0.877, with a sensitivity of 0.831–0.922 and a specificity of 0.676–0.709). In Phase II, iGlaucoma had 0.99 accuracy in recognizing different patterns in pattern deviation probability plots region, with corresponding AUC, sensitivity and specificity of 0.966 (0.953–0.979), 0.954 (0.930–0.977), and 0.873 (0.838–0.908), respectively. The ‘iGlaucoma’ is a clinically effective glaucoma diagnostic tool to detect glaucoma from humphrey VFs, although the target population will need to be carefully identified with glaucoma expertise input.

Abstract Background Despite being associated with a high mortality and economic burden, data regarding candidemia are scant in Algeria. The aim of this study was to unveil the epidemiology of candidemia in Algeria, evaluate the antifungal susceptibility pattern of causative agents and understand the molecular mechanisms of antifungal resistance where applicable. Furthermore, by performing environmental screening and microsatellite typing we sought to identify the source of infection. Methods We performed a retrospective epidemiological-based surveillance study and collected available blood yeast isolates recovered from the seven hospitals in Algiers. To identify the source of infection, we performed environmental screening from the hands of healthcare workers (HCWs) and high touch areas. Species identification was performed by API Auxa-Color and MALDI-TOF MS and ITS sequencing was performed for species not reliably identified by MALDI-TOF MS. Antifungal susceptibility testing followed CLSI M27-A3/S4 and included all blood and environmental yeast isolates. ERG11 sequencing was performed for azole-resistant Candida isolates. Microsatellite typing was performed for blood and environmental Candida species, where applicable. Results Candida tropicalis (19/66) was the main cause of candidemia in these seven hospitals, followed by Candida parapsilosis (18/66), Candida albicans (18/66), and Candida glabrata (7/66). The overall mortality rate was 68.6% (35/51) and was 81.2% for C. tropicalis-infected patients (13/16). Fluconazole was the main antifungal drug used (12/51); 41% of the patients (21/51) did not receive any systemic treatment. Candida parapsilosis was isolated mainly from the hands of HCWs (7/28), and various yeasts were collected from high-touch areas (11/47), including Naganishia albida, C. parapsilosis and C. glabrata. Typing data revealed interhospital transmission on two occasions for C. parapsilosis and C. glabrata, and the same clone of C. parapsilosis infected two patients within the same hospital. Resistance was only noted for C. tropicalis against azoles (6/19) and fluconazole-resistant C. tropicalis isolates (≥8 μg/ml) (6/19) contained a novel P56S (5/6) amino acid substitution and a previously reported one (V234F; 1/6) in Erg11p. Conclusions Collectively, our data suggest an urgent need for antifungal stewardship and infection control strategies to improve the clinical outcome of Algerian patients with candidemia. The high prevalence of C. tropicalis joined by fluconazole-resistance may hamper the therapeutic efficacy of fluconazole, the frontline antifungal drug used in Algeria.

Abstract Background To investigate the long term surgical outcomes of cataract surgery in severe and end stage glaucoma patients with preoperative intraocular pressure less than 21 mmHg, and to detect the associated factors. Methods A retrospective study of primary angle closure glaucoma patients was conducted on who underwent cataract surgery or combined with goniosynechialysis from March 2015 to April 2018. Main outcome measures were visual acuity, intraocular pressure, number of glaucoma medications and complications. Results Sixteen patients (19 eyes) were included. The mean age was 64.89 ± 11.68 years and the mean followed up duration was 21.89 ± 7.85 months. The final visual acuity was significantly improved from 0.69 ± 0.55 to 0.46 ± 0.52 logMAR, within 12 (63.2%) eyes improved, 4 (21.1%) eyes kept unchanged, and 3 (15.8%) eyes reduced. Linear regression analysis indicated that higher mean deviation, higher visual field index and lower glaucoma stage associated with better final visual acuity (r = − 0.511, r = − 0.493, r = 0.537 respectively). Moreover, the final number of medications were reduced from 1.26 ± 0.99 to 0.26 ± 0.56 (p

The rapid growth of China's economy has greatly accelerated the process of urbanization during China's reform periods. Urbanization has significantly caused land use and land cover (LULC) changes and thus has impacts on the local climate and ecosystem. This study chooses Quanzhou, a fast-developing city of southeast China, as an example to detect and quantify the LULC and ecological changes from 1989 to 2018 by using the remotely sensed technique. The LULC of Quanzhou was derived from the four Landsat images taken in 1989, 1999, 2007 and 2018, and the land-use-degree ratio index and land-use-change method were used to estimate the change of land use. The remote sensing based ecological index (RSEI) was used to detect the ecological changes of the city. The built-up land expansion intensity and annual built-up land expansion rate were carried out for seven districts of Quanzhou. The results show that the urban area of Quanzhou has drastically grown by 192.99 km2 at the expense of forest, water, and cropland land during the 1989~2018 period. Moreover, the built-up land of seven districts had expanded at the average rate of 0.027~0.154 per year and the built-up expansion intensity was higher than 0.59. The average RSEI value of Quanzhou city dropped from 0.78 in 1989 to 0.34 in 2018, which suggested an overall decline in ecological quality. The proportion of areas with an RSEI rating good decreased from 30.84% to 11.52% while the proportion of areas with rating bad increased from 4.73% to 19.11% during the past 29 years. This study has shown the built-up land expansion intensity is negatively correlated with the ecological quality change, and the increase in built-up land can greatly accelerate the decline of the ecological quality. Government policies play a profound impact on land use changes, urbanization and eco-environment changes. Therefore, the policy decision-makers should take enough action and consider integrating the concept of ecology to enable the healthy and sustainable development of the city.

Abstract Background In the last century, meconium peritonitis(MP)was once a highly fatal gastrointestinal. disease With the development of fetal radiological technology, abnormal signs, such as pseudocysts, can. be detected during the fetal period so that more patients can be diagnosed prenatally and receive surgery. in the early stage of life. The survival rate of MP has increased up to 80% in recent years. According to. a review of the treatment and outcomes of patients diagnosed with MP, we evaluated the influence of. early operation on survival rate and discussed the risk factors of prognosis. Methods We collected 79 cases of patients diagnosed with MP who were treated in our department. from October 2001 to December 2017. They were divided into 2 groups. Patients in group A were born. in our hospital. Patients in group B were born in a local hospital with suspicion of MP and then transferred. to our department. Results The birth weight (BW) and gestational age (GA) of patients were higher in group A than in. group B. There was no significant difference in the proportion of premature and low birth weight (LBW). patients between the two groups (p = 0.422, p = 0.970). Their age at the time of surgery was younger in. group A than in group B (1.4 ± 2.0 vs. 6.9 ± 14.9, p

Wickerhamomyces anomalus is an emerging pathogen, which has been associated with clonal outbreaks and poor clinical outcomes. Despite being an important emerging yeasts species, our understanding concerning the microbiological and clinical characteristics of infections due to this species is limited. Herein, we are reporting a retrospective analysis of fungemia patients with W. anomalus from a 2,100-bed hospital in Shanghai during 2014–2016. Moreover, we conducted an extensive literature review to gain a deeper clinical and microbiological insights. Detailed clinical data were recorded. Antifungal susceptibility testing (AFST) followed CLSI M27-A3, and isolates were identified using MALDI-TOF MS. In total, 13 patients were identified with a mortality rate of 38.5% (5/13). Central venous catheter (CVC), broad-spectrum antibiotic therapy, total parenteral nutrition (TPN), surgery, and mechanical ventilation were the most frequently observed risk factors. Eight patients (61.5%) experienced mixed bacterial/Candida bloodstream infections, and four patients developed mixed candidemia (MC). W. anomalus isolates showed high minimum inhibitory concentrations (MICs) against all azoles tested and flucytosine, while AMB showed the highest in vitro activity. Azoles were used for 84.6% (11/13) of the cases, while 36.4% (4/11) of them died. When combining with the AFST data and the literature review, our study highlights the poor efficacy of azoles and optimal efficacy of AMB and LAMB against infections caused by W. anomalus. In conclusion, our study highlights the emerging threat of W. anomalus affecting both neonates and adults. Furthermore, our results advocate the use of AMB formulations rather than azoles among patients infected with W. anomalus. Future studies are warranted to reach a definitive consensus regarding the utility of echinocandins among such patients.

Background: Recent studies from multiple countries have shown a high prevalence of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) among severely ill patients. Despite providing valuable insight into the clinical management of CAPA, large-scale prospective studies are limited. Here, we report on one of the largest multicenter epidemiological studies to explore the clinical features and prevalence of COVID-19-associated pulmonary mold infections (CAPMIs) among mechanically ventilated patients.Methods: Bronchoalveolar lavage (BAL) and serum samples were collected for culture, galactomannan (GM), and β-D-glucan (BDG) testing. Patients were classified as probable CAPMI based on the presence of host factors, radiological findings, and mycological criteria.Results: During the study period, 302 COVID-19 patients were admitted to intensive care units (ICUs), among whom 105 were mechanically ventilated for ≥4 days. Probable CAPMI was observed among 38% of patients (40/105), among whom BAL culture of 29 patients turned positive for molds, while galactomannan testing on BAL (GM index ≥1) and serum (GM index >0.5) samples were positive for 60% (24/40) and 37.5% (15/39) of patients, respectively. Aspergillus (22/29; 75.8%) and Fusarium (6/29; 20.6%) constituted 96.5% of the molds isolated. Diaporthe foeniculina was isolated from a COVID-19 patient. None of the patients who presented with CAPMI were treated with antifungal drugs.Conclusion: Despite being prevalent, the absence of appropriate antifungal treatment highlights that CAPMI is a neglected complication among mechanically ventilated COVID-19 patients admitted to ICUs. CAPMI can be caused by species other than Aspergillus.

Abstract Background To investigate the occurrence of ciliochoroidal detachment (CCD), its risk factors and its impact on the success rate after Ahmed glaucoma valve (AGV) implantation. Methods This is a retrospective observational study carried out at Eye Hospital of Wenzhou Medical University, Zhejiang, China. Patients with uncontrolled glaucoma who underwent AGV implantation alone or combined with phacoemulsification (AGV-Phaco) in the hospital from April 1, 2013 to July 31, 2016 were included. The preoperative and postoperative CCD was defined when the detachment between ciliary body and choroid was detected by the ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) respectively. The main outcomes included the incidence of CCD and the success rate at 6 months after surgery. Results In total, 97 male and 56 female patients were included. CCD was observed in 92 (57.8%) eyes. The glaucoma diagnosis in the Non-CCD and CCD group included primary open angle glaucoma (21(31.3%) vs 33(35.9%)), primary angle closure glaucoma (10(14.9%) vs 13(14.1%)), secondary glaucoma (25(37.3%) vs (28(30.4%)) and so on. The preoperative median IOP (interquartile range) were 21.7(16.0,32.0) mmHg and 23.0(16.0,33.0) mmHg in the Non-CCD group and CCD group. Previous surgical history (95% confidence interval (CI), 1.24 to 13.34; odds ratio (OR) 4.06; p = 0.02) and shorter axial length (95% CI, 0.62 to 0.97 OR 0.78; p = 0.02) were the two risk factors of CCD. The success rate between the CCD and Non-CCD group was not significantly different (64.3% vs 62.5%, p = 0.86) at 6 months. Conclusions The incidence of CCD is 57.8% after AGV surgery. Eyes with previous surgical procedure was prone to CCD occurrence and longer axial length was protective against CCD. But at 6 months postoperatively, CCD did not reduce the success rate of AGV surgery and may not be a worrisome complication.

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019–2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019–2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.

Cryptococcus neoformans

CircRNAs are a recently well-known regulator that mediates a variety of biological processes. Cryptococcus neoformans is an environmental fungal pathogen that can cause fatal cryptococcal meningitis in immunocompromised individuals. However, the involvement of circRNA in cryptococcal infection remains unclear. In this study, high-throughput microarray was performed to identify the circRNA expression profile in cryptococcal meningitis patients. Circ_0001806 was significantly decreased in cryptococcal meningitis individuals. Then the effects of circ_0001806 and its interaction with miRNAs were explored in vivo and in vitro. The knock-down of circ_0001806 led to higher fungal infection and shorter survival in an experimental murine cryptococcosis model. Transcriptome analysis showed that decreased circ_0001806 regulated pathways related to the host antimicrobe response in T cells. Furthermore, in vitro experiments showed that circ_0001806 positively modulates ADM level, decreasing cell apoptosis and G1S arrest in T cells. Finally, we found circ_0001806 exerted its effects by sponging miRNA-126 in T cells. Taken together, our results reveal the role of circRNA-1806/miRNA-126 in the regulation of cell cycle and apoptosis in cryptococcal infection and can provide a new insights of the pathogenesis of cryptococcal infection.

Ubiquitin is a highly conserved protein required for various fundamental cellular processes in eukaryotes. Herein, we first report the contribution of the ubiquitin fusion protein Ubi1 (a ubiquitin monomer fused with the ribosome protein L40e, Rpl40e) in the growth and pathogenicity of Cryptococcus neoformans. UBI1 deletion resulted in severe growth restriction of C. neoformans, whose growth rate was positively correlated with UBI1 expression level. The growth defect of the ubi1Δ strain could be closely associated with its morphological abnormalities, such as its reduced ribosome particles. In addition, the ubi1Δ mutant also displayed increased cell ploidy, cell cycle arrest, and decreased intracellular survival inside macrophages. All these phenotypes were reversed by the reconstitution of the full-length UBI1 gene or RPL40a domain. Mouse survival and fungal burden assays further revealed a severely attenuated pathogenicity for the ubi1Δ mutant, which is probably associated with its reduced stress tolerance and the induction of T-helper 1-type immune response. Taken together, Ubi1 is required for maintaining the vegetative growth, morphological homeostasis, cell cycle progression, and pathogenicity in vivo of C. neoformans. The pleiotropic roles of Ubi1 are dependent on the presence of Rpl40e and associated with its regulation of cryptococcal ribosome biogenesis.

Candida tropicalis is the fourth leading cause of candidemia in Turkey. Although C. tropicalis isolates from 1997 to 2017 were characterized as fully susceptible to antifungals, the increasing global prevalence of azole-non-susceptible (ANS) C. tropicalis and the association between high fluconazole tolerance (HFT) and fluconazole therapeutic failure (FTF) prompted us to re-evaluate azole susceptibility of C. tropicalis in Turkey. In this study, 161 C. tropicalis blood isolates from seven clinical centers were identified by ITS rDNA sequencing, genotyped by multilocus microsatellite typing, and tested for susceptibility to five azoles, two echinocandins, and amphotericin B (AMB); antifungal resistance mechanisms were assessed by sequencing of ERG11 and FKS1 genes. The results indicated that C. tropicalis isolates, which belonged to 125 genotypes grouped into 11 clusters, were fully susceptible to echinocandins and AMB; however, 18.6% of them had the ANS phenotype but only two carried the ANS-conferring mutation (Y132F). HFT was recorded in 52 isolates, 10 of which were also ANS. Large proportions of patients infected with ANS and HFT isolates (89 and 40.7%, respectively) showed FTF. Patients infected with azole-susceptible or ANS isolates did not differ in mortality, which, however, was significantly lower for those infected with HFT isolates (P = 0.007). There were significant differences in mortality (P = 0.02), ANS (P = 0.012), and HFT (P = 0.007) among genotype clusters. The alarming increase in the prevalence of C. tropicalis blood isolates with ANS and HFT in Turkey and the notable FTF rate should be a matter of public health concern.

Objectives: Development and validation of a single-step and accurate reverse transcriptase loop-mediated isothermal amplification technique (RT-LAMP) for rapid identification of SARS-CoV-2 relative to commercial quantitative reverse transcriptase real-time PCR (qRT-PCR) assays to allow prompt initiation of proper medical care and containment of virus spread.Methods: Primers showing optimal in-silico features were subjected to analytical sensitivity and specificity to assess the limit of detection (LOD) and cross-reaction with closely- and distantly-related viral species, and clinically prominent bacterial and fungal species. In order to evaluate the clinical utility, our RT-LAMP was subjected to a large number of clinical samples, including 213 negative and 47 positive patients, relative to two commercial quantitative RT-PCR assays.Results: The analytical specificity and sensitivity of our assay was 100% and 500 copies/ml when serial dilution was performed in both water and sputum. Subjecting our RT-LAMP assay to clinical samples showed a high degree of specificity (99.5%), sensitivity (91.4%), positive predictive value (97.7%), and negative predictive value (98.1%) when used relative to qRT-PCR. Our RT-LAMP assay was two times faster than qRT-PCR and is storable at room temperature. A suspected case that later became positive tested positive using both our RT-LAMP and the two qRT-PCR assays, which shows the capability of our assay for screening purposes.Conclusions: We present a rapid RT-LAMP assay that could extend the capacity of laboratories to process two times more clinical samples relative to qRT-PCR and potentially could be used for high-throughput screening purposes when demand is increasing at critical situations.

Clonal expansion of fluconazole resistant (FLZ-R) Candida parapsilosis isolates is increasingly being identified in many countries, while there is no study exploring the antifungal susceptibility pattern, genetic diversity, and clinical information for Iranian C. parapsilosis blood isolates. Candida parapsilosis species complex blood isolates (n = 98) were recovered from nine hospitals located in three major cities, identified by MALDI-TOF MS, and their genetic relatedness was examined by AFLP fingerprinting. Antifungal susceptibility testing followed CLSI-M27-A3 and ERG11, MRR1 and hotspots 1/2 (HS1/2) of FKS1 were sequenced to assess the azole and echinocandin resistance mechanisms, respectively. Ninety-four C. parapsilosis and four Candida orthopsilosis isolates were identified from 90 patients. Only 43 patients received systemic antifungal drugs with fluconazole as the main antifungal used. The overall mortality rate was 46.6% (42/90) and death mostly occurred for those receiving systemic antifungals (25/43) relative to those not treated (17/47). Although, antifungal-resistance was rare, one isolate was multidrug-resistant (FLZ = 16 μg/ml and micafungin = 8 μg/ml) and the infected patient showed therapeutic failure to FLZ prophylaxis. Mutations causing azole and echinocandin resistance were not found in the genes studied. AFLP revealed five genotypes (G) and G1 was the main one (59/94; 62.7%). Clinical outcome was significantly associated with city (P = 0.02, α

Background: Several non-invasive markers have been reported as being effective for the assessment of fibrosis in adults with chronic viral hepatitis. The infantile liver is more susceptible to cholestasis, and it is important to promptly evaluate liver fibrosis to guide the clinical treatment. However, the clinical value of these markers in infants with cholestasis remains unknown.Aim: To investigate the correlation between serum laminin (LN), hyaluronic acid (HA), procollagen III N-terminal peptide (PIIINP) level, and liver fibrosis stage in infants with cholestasis.Methods: One hundred and thirty-seven term infants with cholestasis were included. Laparoscopic exploration and cholangiography were performed to diagnose or rule out biliary atresia. Serum LN, HA, and PIIINP were measured prior to laparoscopic exploration. Liver biopsy was performed for all patients. Liver fibrosis was staged on a five-point scale (F0–F4) according to the METAVIR scoring system. The correlation between serum markers and liver fibrosis stage was assessed. A receiver operator characteristic analysis was performed to determine the accuracy of serum markers for predicting the liver fibrosis stage.Results: Serum PIIINP and HA were positively correlated with liver fibrosis stage (r = 0.622, P < 0.001, and r = 0.41, P < 0.001, respectively). There was no significant correlation between serum LN and liver fibrosis stage (P > 0.05). Serum aspartate aminotransferase, total bilirubin, direct bilirubin, and PIIINP were independently correlated with the fibrosis stage on multivariate ordinal regression analysis. Receiver operating curve (ROC) analysis showed that serum PIIINP was the most effective for the diagnosis of fibrosis grade. The area under the ROC curves (AUROCs) for serum PIIINP for diagnosing fibrosis stages ≥F1, ≥F2, ≥F3, and F4 (cirrhosis) were 0.843, 0.789, 0.82, and 0.891, respectively. The cut-off serum PIIINP value for predicting fibrosis stage ≥F1 was 242.3 ng/mL, with 73.8% sensitivity and 90% specificity. The cut-off value for predicting cirrhosis was 698.7 ng/mL, with 75% sensitivity and 96% specificity.Conclusion: Serum PIIINP is a promising biomarker for predicting liver fibrosis stage, especially cirrhosis. Its assessment is a simple and non-invasive diagnostic method for liver fibrosis in infants with cholestasis.

Purpose. To evaluate two different approaches of anterior vitrectomy combined with hyaloidotomy, zonulectomy, and iridectomy (VHZI) for fluid misdirection syndrome (FMS) secondary to phacoemulsification with intraocular lens implantation combined with goniosynechialysis (phaco-IOL-GSL). Methods. Nine patients with FMS who developed after a phaco-IOL-GSL procedure, were retrospectively studied from May 2015 to February 2018. They were treated with VHZI, in which 5 cases underwent local anterior vitrectomy via anterior chamber approach, and the others underwent comprehensive vitrectomy via pars plana approach. Main outcome measures were pre- and postoperative intraocular pressure (IOP), number of antiglaucoma medications, and relapse rate. Results. Incidence of FMS secondary to phaco-IOL-GSL was 1.4% (9 in 652 eyes), which was promptly resolved in all affected cases. VHZI via anterior chamber approach resulted in a significant decrease in the mean IOP from 40.2 ± 9.7 mm Hg at presentation to 15.2 ± 4.8 mm Hg postoperatively (P=0.01). The median number of antiglaucoma medications reduced from 3 to 2 (P=0.066). Meanwhile, VHZI via pars plana approach also resulted in the reduction of the mean IOP values from 26.0 ± 5.7 mm Hg at presentation to 15.2 ± 3.3 mm Hg postoperatively (P=0.092). The median number of antiglaucoma medications also reduced from 3.5 to 1.5 (P=0.059). Relapse rate of the treatment through pars plana approach (0%, 0/4) was much lower than that through anterior chamber approach (40%, 2/5), although the difference was not statistically significant (P=0.444). Conclusions. FMS is a rare but severe complication secondary to phaco-IOL-GSL. Compared to VHZI with local anterior vitrectomy via anterior chamber approach, VHZI with comprehensive anterior vitrectomy via pars plana approach might be a more effective procedure to treat FMS. The study has been registered in Contact ClinicalTrials.gov PRS Identifier: NCT04172857.

Abstract Background Candida albicans, Candida glabrata, and Candida parapsilosis are three prevalent causes of candidiasis, worldwide. These species are considered as nine medically important complex species. Limited knowledge about these newly recognized species prompted us to develop a one-step, multiplex PCR to detect and identify them in clinical settings. Methods Primers targeting Hyphal Wall Protein I gene for the C. albicans, C. dubliniensis, C. africana, Intergenic Spacer for the C. glabrata, C. nivariensis, C. bracarensis, and Intein and ITS rDNA for the C. parapsilosis, C. orthopsilosis, and C. metapsilosis were designed. Using 168 CBS reference strains and 280 clinical isolates, the specificity and reproducibility of the developed assay were evaluated. Results Our developed assay successfully identified and distinguished all the nine species. No cross-reaction with closely- and distantly-related yeast species, Aspergillus species and human DNA was observed, resulting in 100% specificity. The ambiguous results obtained by MALDI-TOF for C. albicans and C. africana were corrected by our 9-plex PCR assay. This assay identified all the cryptic complex species from two test sets from Iran and China, correctly. Conclusions Our developed multiplex assay is accurate, specific, cost/time-saving, and works without the tedious DNA extraction steps. It could be integrated into routine clinical laboratories and as a reliable identification tool and has the potential to be implemented into epidemiological studies to broaden the limited knowledge of cryptic species complexes.

Cases of tuberculosis/cryptococcosis co-infection are rapidly increasing in China. However, most studies addressing this co-infection have been published in Chinese journals, and this publication strategy has obscured this disease trend for scientists in other parts of the world. Our investigation found that 62.9% of all co-infection cases worldwide were reported in the Chinese population (n=197) between 1965 and 2016, and 56.3% of these Chinese cases were reported after 2010. Nearly all cases originated from the warm and wet monsoon regions of China. HIV-positive subjects tended to correlate with more severe manifestations of a tuberculosis/cryptococcosis co-infection than those without HIV. Notablely, dual tubercular/cryptococcal meningitis was the most frequent (54.0%) and most easily misdiagnosed (95.2%, n=40/42) co-infection. We also found that the combined use of cerebrospinal fluid pressure and concentrations of glucose, protein and chlorine might be an inexpensive and effective indicator to differentiate tubercular/cryptococcal co-infection meningitis from tubercular meningitis and cryptococcal meningitis.Emerging Microbes & Infections (2017) 6, e73; doi:10.1038/emi.2017.61; published online 23 August 2017