Miracle-dz/UniFAR-FTUs huggingface dataset:
Performance of Conventional Urine Culture Compared to 16S rRNA Gene Amplicon Sequencing in Children with Suspected Urinary Tract Infection

Concordance between conventional culture and 16S rRNA gene amplicon sequencing appears to be high. In children with equivocal culture results, 16S rRNA gene results may provide information that may help clarify the diagnosis. ABSTRACT Because some organisms causing urinary tract infection (UTI) may be difficult to culture, examination of bacterial gene sequences in the urine may provide a more accurate view of bacteria present during a UTI. Our objective was to estimate how often access to 16S rRNA gene amplicon sequencing alters diagnosis and/or clinical management. The study was designed as a cross-sectional study of a convenience sample of children with suspected UTI. The setting was the emergency department or outpatient clinic at six pediatric centers. Participants included children 2 months to 10 years of age suspected of UTI. We categorized the results of urine culture as follows: “likely UTI” (≥100,000 CFU/ml of a single uropathogen), “possible UTI” (10,000 to 99,000 CFU/ml of a uropathogen or ≥100,000 CFU/ml of a single uropathogen plus other growth), and “unlikely UTI” (no growth or growth of nonuropathogens). Similarly, we categorized the results of 16S rRNA gene sequencing into the same three categories using the following criteria: likely UTI (≥90% relative abundance of a uropathogen), possible UTI (50 to 89% relative abundance of a uropathogen), and unlikely UTI (remainder of samples). The main study outcome was concordance between conventional culture results and 16S rRNA gene sequencing. Concordance between the two methods was high in children with likely and unlikely UTI by conventional culture (95% and 87%, respectively). In children with possible UTI according to conventional culture, 71% had a single uropathogen at a relative abundance of ≥90% according to 16S rRNA gene sequencing data. Concordance between conventional culture and 16S rRNA gene amplicon sequencing appears to be high. In children with equivocal culture results, 16S rRNA gene results may provide information that may help clarify the diagnosis. IMPORTANCE Concordance between conventional culture and 16S rRNA gene amplicon sequencing appears to be high. In children with equivocal culture results, 16S rRNA gene results may provide information that may help clarify the diagnosis.
The skeletal muscle circadian clock regulates titin splicing through RBM20

Circadian rhythms are maintained by a cell autonomous, transcriptional-translational feedback loop known as the molecular clock. While previous research suggests a role of the molecular clock in regulating skeletal muscle structure and function, no mechanisms have connected the molecular clock to sarcomere filaments. Utilizing inducible, skeletal muscle specific, Bmal1 knockout (iMSBmal1-/-) mice, we showed that knocking out skeletal muscle clock function alters titin isoform expression using RNAseq, LC-MS, and SDS-VAGE. This alteration in titin’s spring length resulted in sarcomere length heterogeneity. We demonstrate the direct link between altered titin splicing and sarcomere length in vitro using U7 snRNPs that truncate the region of titin altered in iMSBmal1-/- muscle. We identified a mechanism whereby the skeletal muscle clock regulates titin isoform expression through transcriptional regulation of Rbm20, a potent splicing regulator of titin. Lastly, we used an environmental model of circadian rhythm disruption and identified significant down-regulation of Rbm20 expression. Our findings demonstrate the importance of the skeletal muscle circadian clock in maintaining titin isoform through regulation of RBM20 expression. Because circadian rhythm disruption is a feature of many chronic diseases, our results highlight a novel pathway that could be targeted to maintain skeletal muscle structure and function in a range of pathologies.
Disrupted Peyer’s Patch Microanatomy in COVID-19 Including Germinal Centre Atrophy Independent of Local Virus

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer’s patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis.
Consensus guidelines for the diagnosis and management of invasive fungal disease due to moulds other than Aspergillus in the haematology/oncology setting, 2021

Invasive fungal disease (IFD) due to moulds other than Aspergillus is a significant cause of mortality in patients with malignancies or post haemopoietic stem cell transplantation. The current guidelines focus on the diagnosis and management of the common non‐Aspergillus moulds (NAM), such as Mucorales, Scedosporium species (spp.), Lomentospora prolificans and Fusarium spp. Rare but emerging NAM including Paecilomyces variotii, Purpureocillium lilacinum and Scopulariopsis spp. are also reviewed. Culture and histological examination of tissue biopsy specimens remain the mainstay of diagnosis, but molecular methods are increasingly being used. As NAM frequently disseminate, blood cultures and skin examination with biopsy of any suspicious lesions are critically important. Treatment requires a multidisciplinary approach with surgical debridement as a central component. Other management strategies include control of the underlying disease/predisposing factors, augmentation of the host response and the reduction of immunosuppression. Carefully selected antifungal therapy, guided by susceptibility testing, is critical to cure. We also outline novel antifungal agents still in clinical trial which offer substantial potential for improved outcomes in the future. Paediatric recommendations follow those of adults. Ongoing epidemiological research, improvement in diagnostics and the development of new antifungal agents will continue to improve the poor outcomes that have been traditionally associated with IFD due to NAM.
Alzheimer's Disease Classification Model Based on MED-3D Transfer Learning

Alzheimer's disease (AD) is one of the most common forms of dementia and a common condition of old age. Its pathogenic mechanism is unknown, and it is also an irreversible neurodegenerative disease. Therefore, early detection and treatment are particularly critical for patients. In this paper, we adopt the idea of transfer learning, use the ADNI dataset to retrain the Med-3D network, and change the segmentation network into the whole connection layer of classification. At the same time, we retrain the Resnet-3D network and compare the Med-3D network. Experimental results show that the convergence rate of this migration model is faster, and the accuracy is higher than that of the ResNet network with corresponding layers. The final accuracy rate reached 83%.
Development of nanoparticles and their application in cancer treatment

With the rapid development of nanotechnology, we have stepped into a new era of nanotechnology. Functional nanoparticles provide a new way of thinking for nanomedicine and a new solution for major problems such as drug targeted therapy. By using nanoparticles as carriers, drugs can be transported to targeted areas as planned, reducing the toxic side effects caused by drug entry into other healthy tissues, and increasing the accuracy of drug targeting and therapeutic efficiency. Because nanoparticles can travel through a network of blood vessels, they could be used to deliver drugs directly to the target area with minimal side effects to healthy tissue, replacing traditional intravenous delivery. In the future, nanoparticles could be a solution to many currently incurable diseases, such as cancer - delivering anticancer drugs that directly kill cancer cells without harming normal ones. In this paper, the fabrication method, driving method and the application of nanoparticles in cancer treatment are mainly used to objectively evaluate the previous work and research, and to find out the status and role of nanoparticles in the field of research, as well as the significance and effect of nanoparticles in cancer.
Building a Mutually-Desirable Relationship between a Higher Education Institution’s Academic Schools and Its Adult/Continuing Education Unit: A Case Study Analysis of Abu Dhabi University and Its Knowledge Group (Abu Dhabi, United Arab Emirates)

Historically, many higher education institutions have been structurally and culturally compartmentalised and subunits such as continuing education have been marginalised, merged or divested. In response to a variety of external phenomena, some higher education institutions are re-examining their internal and external relationships, including the relationship between their academic and continuing education units. This research examines the efforts of a higher education institution in the United Arab Emirates to improve its overall effectiveness by changing the nature of the relationship between its academic and continuing education units. A review of theory- and practice-based higher education, organisational culture and inter-/intra-organisational relationship literature revealed significant support for each partner’s goals for the new relationship and was used to provide the parties with a series of recommendations for successful formulation, actualisation and governance. These results add to the literature and practice of higher education and continuing higher education, particularly in the area of relationship-building among organisational subunits and subcultures.
Enhanced Pathogenesis Caused by Influenza D Virus and Mycoplasma bovis Coinfection in Calves: a Disease Severity Linked with Overexpression of IFN-γ as a Key Player of the Enhanced Innate Immune Response in Lungs

Bovine respiratory disease (BRD) is among the most prevalent diseases in young cattle. BRD is due to complex interactions between viruses and/or bacteria, most of which have a moderate individual pathogenicity. ABSTRACT Bovine respiratory disease (BRD) is a major disease of young cattle whose etiology lies in complex interactions between pathogens and environmental and host factors. Despite a high frequency of codetection of respiratory pathogens in BRD, data on the molecular mechanisms and pathogenesis associated with viral and bacterial interactions are still limited. In this study, we investigated the effects of a coinfection with influenza D virus (IDV) and Mycoplasma bovis in cattle. Naive calves were infected by aerosol with a French IDV strain and an M. bovis strain. The combined infection shortened the incubation period, worsened the disease, and led to more severe macroscopic and microscopic lesions compared to these parameters in calves infected with only one pathogen. In addition, IDV promoted colonization of the lower respiratory tract (LRT) by M. bovis and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The gamma interferon (IFN-γ) gene was shown to be the gene most statistically overexpressed after coinfection at 2 days postinfection (dpi) and at least until 7 dpi, which correlated with the high level of lymphocytes in the LRT. Downregulation of the PACE4 and TMPRSS2 endoprotease genes was also highlighted, being a possible reason for the faster clearance of IDV in the lungs of coinfected animals. Taken together, our coinfection model with two respiratory pathogens that when present alone induce moderate clinical signs of disease was shown to increase the severity of the disease in young cattle and a strong transcriptomic innate immune response in the LRT, especially for IFN-γ. IMPORTANCE Bovine respiratory disease (BRD) is among the most prevalent diseases in young cattle. BRD is due to complex interactions between viruses and/or bacteria, most of which have a moderate individual pathogenicity. In this study, we showed that coinfection with influenza D virus (IDV) and Mycoplasma bovis increased the severity of the respiratory disease in calves in comparison with IDV or M. bovis infection. IDV promoted M. bovis colonization of the lower respiratory tract and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The IFN-γ gene in particular was highly overexpressed after coinfection, correlated with the disease severity, immune response, and white cell recruitment in the lungs. In conclusion, we showed that IDV facilitates coinfections within the BRD complex by modulating the local innate immune response, providing new insights into the mechanisms involved in severe respiratory diseases.
Contamination of Human Bocavirus Genotypes 1, 2, 3, and 4 in Environmental Waters in Thailand

Recently, we reported the detection of HBoV genotypes 1, 2, and 3 in pediatric patients with acute gastroenteritis, and the detection of HBoV1 and 2 in oysters in Thailand. In this study, we report the detection of HBoV1, 2, 3, and 4 contamination in environmental waters within the same geographic area. ABSTRACT Human bocavirus (HBoV) has been recognized as one of the common pathogens which cause respiratory disease and acute gastroenteritis in children worldwide. Recently, our studies reported the detection of HBoV in children with acute gastroenteritis and in oysters in Thailand. However, studies on the presence of HBoV in environmental waters in Thailand have not yet been conducted. In this study, 126 environmental water samples collected from November 2016 to July 2018 were investigated. Detection of HBoV was based on amplification of the VP1/VP2 region of the HBoV genome by nested PCR followed by nucleotide sequencing and phylogenetic analysis. HBoV was detected in 34 out of 126 samples (27.0%). All four HBoV genotypes, HBoV1 to HBoV4, were detected. HBoV2 was the most frequently detected genotype (61.8%), followed by HBoV1 (23.5%), HBoV4 (8.8%), and HBoV3 (5.9%). The highest detection rate of HBoV was observed during the warmest months in Thailand: April 2017 and March 2018. Phylogenetic analysis of VP1/VP2 nucleotide sequences of HBoV genotypes revealed that all four of the genotypes detected in environmental waters were closely related to genotypes detected in patients with acute gastroenteritis, which had been reported previously in the same geographical area. This study reports the existence of multiple HBoV genotypes in environmental waters and provides evidence of a considerably high magnitude of HBoV contamination in these waters. These findings demonstrate the potential risk of waterborne transmission of HBoV to humans. IMPORTANCE Recently, we reported the detection of HBoV genotypes 1, 2, and 3 in pediatric patients with acute gastroenteritis, and the detection of HBoV1 and 2 in oysters in Thailand. In this study, we reported the detection of HBoV1, 2, 3, and 4 contamination in environmental waters within the same geographic area. Phylogenetic analysis demonstrated that the HBoV genotypes detected in environmental waters and in oysters were closely related to HBoV detected in patients. These findings imply that HBoV contamination in oysters and in environmental waters could be a potential sources of foodborne and waterborne transmission to humans.
Reverted HIV-1 Mutants in CD4+ T-Cells Reveal Critical Residues in the Polar Region of Viral Envelope Glycoprotein

Our previous mutagenesis study revealed that serine at position 534 of HIV-1 Env is critical for viral infectivity. We found that HIV-1 Env containing serine to proline mutation at position 534 (S534P) are incapable of supporting virus-cell and cell-cell fusion. ABSTRACT HIV-1 envelope glycoprotein (Env) interacts with cell surface receptors and induces membrane fusion to enter cells and initiate infection. HIV-1 Env on virions comprises trimers of the gp120 and gp41 subunits. The polar region (PR) in the N-terminus of gp41 is composed of 17 conserved residues, including seven polar amino acids. We have reported that the PR is crucial for Env trimer stability and fusogenicity. Mutations of three highly conserved residues (S534P, T536A, or T538A) in the PR of HIV-1NL4-3 significantly decrease or eliminate viral infectivity due to defective fusion and increased gp120 shedding. To identify compensatory Env mutations that restore viral infectivity, we infected a CD4+ T-cell line with PR mutants pseudotyped with wild-type (WT) HIV-1 Env or vesicular stomatitis virus envelope glycoprotein (VSV-G). We found that PR mutant-infected CD4+ T-cells produced infectious viruses at 7 days postinfection (dpi). Sequencing of the env cDNA from cells infected with the recovered HIV-1 revealed that the S534P mutant reverted to serine or threonine at residue 534. Interestingly, the combined PR-mutant HIV-1 (S534P/T536A or S534P/T536A/T538A) recovered its infectivity and reverted to S534, but maintained the T536A or T538A mutation, suggesting that HIV-1 replication in CD4+ T-cells can tolerate T536A and T538A Env mutations, but not S534P. Moreover, VSV-G-pseudotyped HIV-1 mutants with a fusion-defective Env also recovered infectivity in CD4+ T-cells through reverted Env mutations. These new observations help define the Env residues critical for HIV-1 infection and demonstrate that Env-defective HIV-1 mutants can rapidly regain replication competency in CD4+ T-cells. IMPORTANCE Our previous mutagenesis study revealed that serine at position 534 of HIV-1 Env is critical for viral infectivity. We found that HIV-1 Env containing serine to proline mutation at position 534 (S534P) are incapable of supporting virus-cell and cell-cell fusion. To investigate whether these mutant viruses can recover infectivity and what amino acid changes account for recovered infectivity, we infected CD4+ T-cells with Env-mutant HIV-1 pseudotyped with WT HIV-1 Env or VSV-G and monitored cultures for the production of infectious viruses. Our results showed that most of the pseudotyped viruses recovered their infectivity within 1-week postinfection, and all the recovered viruses mutated proline at position 534. These observations help define the Env residues critical for HIV-1 replication. Because Env-defective HIV-1 mutants can rapidly regain replication competency in CD4+ T-cells, it is important to carefully monitor viral mutations for biosafety consideration when using HIV-1-derived lentivirus vectors pseudotyped with Env.
Molecular Mechanisms Driving the In Vivo Development of KPC-71-Mediated Resistance to Ceftazidime-Avibactam during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections

In this study, we report an ST11-type clinical CRKP isolate that produces KPC-71, a novel plasmid backbone KPC variant that confers the development of CZA resistance during treatment. Furthermore, we reveal that resistance to CZA is mediated by the 182S insertion mutation in the KPC enzyme, which increases ceftazidime affinity and decreases avibactam inhibition. ABSTRACT Here, we characterized the mechanisms resulting in the development of KPC-71-mediated resistance to ceftazidime-avibactam (CZA) during treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. CZA-susceptible and CZA-resistant K. pneumoniae strains, namely, KP357 and KP697, were isolated from the same patient. Whole-genome sequencing revealed that KP357 and KP697 belonged to the ST11 type and KP697 strain possessed a mutation in the plasmid-borne blaKPC-2 gene. Compared to KPC-2, this blaKPC gene (blaKPC-71) showed a mutated nucleotide and an insertion of 3 nucleotides at positions 542 to 545, which resulted in a variant with the subsequent insertion of a serine between the Ambler positions 182 and 183. This plasmid, carrying blaKPC-71, successfully transformed its CZA-resistant phenotype to Escherichia coli DH5α. Cloning and expression of blaKPC-71 in E. coli DH5α demonstrated that KPC-71 resulted in a 16-fold increase in the MIC value for CZA. Kinetic parameters showed that KPC-71, compared to wild-type KPC-2, exhibited a lower (∼13-fold) Km with ceftazidime and a higher (∼14-fold) 50% inhibitory concentration with avibactam. In addition, both blaKPC-2 and blaKPC-71 gene expression have a negative impact on fitness. In conclusion, we detected a novel KPC variant, KPC-71, in a clinical ST11 CRKP strain resulting in CZA resistance development during treatment. The KPC-71 enzyme was associated with a higher affinity toward ceftazidime and a reduced sensitivity to avibactam, conferring resistance to CZA. Considering the wide application of CZA, clinicians should pay attention to the risk of the development of CZA resistance in CRKP strains under treatment pressure. IMPORTANCE In this study, we report an ST11-type clinical CRKP isolate that produces KPC-71, a novel plasmid backbone KPC variant that confers the development of CZA resistance during treatment. Furthermore, we reveal that resistance to CZA is mediated by the 182S insertion mutation in the KPC enzyme, which increases ceftazidime affinity and decreases avibactam inhibition. In addition, KPC-71 has reduced hydrolysis activity, which leads to susceptibility to carbapenems. To the best of our knowledge, this is a novel KPC-2 variant conferring resistance to CZA and the first report of its emergence. Considering the widespread presence of the ST11 CRKP strain in China, clinicians should pay attention to the risk of the development of CZA resistance in CRKP strains under treatment pressure.
Walk on the Wild Side Designers of the PolyBot Robot System Solve the Challenges of Locomotion by Mimicking Locomotion in the Animal World

P olyBot is a robot system made of many repeated simple modules. These modules can be connected together to form a variety of shapes to form a new system enabling a variety of functionalities. As the number of modules increases, these systems become more and more complex and start to resemble organic systems. The analog in architecture is the building of a cathedral from many simple bricks. In nature, the analog is higher order organisms like mammals that have billions of cells but only hundreds of cell types. Modular self-reconfigurable robot systems, sometimes called metamorphic [1], can also reconfigure (re-arrange) their own modules. This increases the versatility of the system. For example, in an earthquake search and rescue application, the robot may use a powerefficient, fast gait like a rolling track (Fig. 1) over flat terrain to approach a rubble pile. It could use a snake-like gait (Fig. 2) to slither through tight spots or crawl through pipes and finally reconfigure into a support structure (Fig. 3) around a victim if the rubble is still unstable. Other applications for these robots include those that require this high versatility (planetary exploration, undersea mining, etc.) where the optimal shape is unknown. There are a growing number of modular reconfigurable robotic systems, as exemplified in [2]-[4] and [7]. However, the practical application outside of research has yet to be seen. While the number of modules has been large in simulation, the physical implementation of these systems has rarely had more than ten modules.