The impact of COVID-19 on open access publishing in radiology and nuclear medicine: an in-depth analysis.

In response to the COVID-19 pandemic, numerous initiatives have been implemented to ensure open access availability of COVID-19-related articles to make published articles accessible for anyone. This study aimed to assess the impact of the COVID-19 pandemic on open-access publishing in radiology and nuclear medicine. We conducted a comprehensive analysis of articles and reviews published in these fields during the COVID-19 publishing era using the Web of Science database. We analyzed several indicators between COVID-19 and non-COVID-19 related articles, including the number and percentage of open-access articles, the top ten cited articles, and the number of reviews. In total, 67,100 articles were published in radiology and nuclear medicine between January 2020 and June 2022. Among those, more than half (51.1%) were open-access articles. Among these publications, 2,336 were COVID-19-related, and 64,764 were non-COVID-19-related. However, articles related to COVID-19 had an open access rate of 91.5%, compared to only 49.6% of the non-COVID-19-related articles. Moreover, COVID-19-related articles had a higher percentage of highly cited and hot papers compared to articles not related to COVID-19. Moreover, most highly cited studies were related to chest computerized tomography (CT) scan findings in COVID-19 patients. The findings emphasize the significant proportion of open access COVID-19-related publications in radiology and nuclear medicine, facilitating widespread and timely access to everyone.

Genomic characterization of SARS-CoV-2 in Egypt: insights into spike protein thermodynamic stability.

The overall pattern of the SARS-CoV-2 pandemic so far has been a series of waves; surges in new cases followed by declines. The appearance of novel mutations and variants underlie the rises in infections, making surveillance of SARS-CoV-2 mutations and prediction of variant evolution of utmost importance. In this study, we sequenced 320 SARS-CoV-2 viral genomes isolated from patients from the outpatient COVID-19 clinic in the Children's Cancer Hospital Egypt 57357 (CCHE 57357) and the Egypt Center for Research and Regenerative Medicine (ECRRM). The samples were collected between March and December 2021, covering the third and fourth waves of the pandemic. The third wave was found to be dominated by Nextclade 20D in our samples, with a small number of alpha variants. The delta variant was found to dominate the fourth wave samples, with the appearance of omicron variants late in 2021. Phylogenetic analysis reveals that the omicron variants are closest genetically to early pandemic variants. Mutation analysis shows SNPs, stop codon mutation gain, and deletion/insertion mutations, with distinct patterns of mutations governed by Nextclade or WHO variant. Finally, we observed a large number of highly correlated mutations, and some negatively correlated mutations, and identified a general inclination toward mutations that lead to enhanced thermodynamic stability of the spike protein. Overall, this study contributes genetic and phylogenetic data, as well as provides insights into SARS-CoV-2 viral evolution that may eventually help in the prediction of evolving mutations for better vaccine development and drug targets.

Whole genome characterization of methicillin resistant Staphylococcus aureus in an Egyptian Tertiary Care Hospital.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant healthcare-associated (HA-MRSA) pathogen due to its increased morbidity and mortality rates. There is a paucity of data regarding MRSA clones circulating in the Middle East in the literature, especially from Egypt. We aimed to identify the pattern of resistance and virulence in the propagating clones using NGS technologies for the whole genome sequence. METHODS: From an 18-month surveillance program for MRSA-positive patients, 18 MRSA isolates from surgical healthcare associated infections were selected. The Vitek2 system was used to assess antimicrobial susceptibility. The whole genome sequencing was performed using the NovaSeq6000. The reads were mapped to the reference genome (Staphylococcus_aureus_ATCC_BAA_1680), used for variant calling, screened for virulence/resistance genes, and typed using multi-locus sequence typing and spa typing. Correlation between demographic and clinical data and molecular findings were performed. RESULTS: All the MRSA isolates were highly resistant to tetracycline followed by gentamicin (61%) and highly susceptible to trimethoprim/sulfamethoxazole. Most of the isolates showed a high virulence profile. ST239 was the predominant sequence type (6/18), while t037 was the predominant spa type (7/18). Five isolates shared the same ST239 and spa t037. ST1535, an emerging MRSA strain, was the second most prevalent in our study. One isolate showed a unique pattern of a high abundance of resistance and virulence genes. CONCLUSION: WGS elucidated the resistance and virulence profiles of MRSA isolated from clinical samples of HAI patients with high-resolution tracking of clones predominant in our healthcare facility.

Prevalence and species distribution of Candida bloodstream infection in children and adults in two teaching university hospitals in Egypt: first report of Candida kefyr.

BACKGROUND: Candidemia is a pervasive problem associated with significant morbidity and mortality in health care settings. This study aimed to determine the changing distribution of Candida species and the emergence of uncommon species. METHODS: This was a cross-sectional study performed in two Cairo University hospitals between 2019 and 2020. All Candida species isolates recovered from blood cultures of adults and pediatrics patients admitted to the hospitals were included. Candida isolates were identified by chromogenic Candida agar and Vitek2 YST identification card. Candida kefyr was confirmed by chip array. RESULTS: Candida species were responsible for 1.6% of bloodstream infections in adults and 10.8% in pediatric patients. C. albicans was the most prevalent species representing 27.8% in adults and 48.3% in pediatrics. Non-albicans species (NAC) represented the most isolated Candida species among adults and pediatrics (72.2% and 51.6%, respectively) with the predominance of C. tropicalis (27.8% and 22.5%, respectively) followed by C. parapsilosis (16.7% and 10.8%, respectively). The uncommon Candida, which is Candida species other than C. albicans, C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei, represents 16.6% and 14% of all candidemia in adults and pediatrics, respectively. Only one of each of C. lusitaniae, C. utilis, and C. kefyr were detected in adults. C. lusitaniae was the most frequently recovered uncommon Candida among pediatrics resulting in 6.4% of candidemia followed by C. famata (4.3%), C. utilis (2.2%), and C. kefyr (1.1%). CONCLUSIONS: C. albicans is still the primary species isolated from pediatrics and adults with candidemia despite the considerable shift to the non-albicans species. C. tropicalis and C. parapsilosis are the most prevalent NAC. The increased prevalence of uncommon Candida species is alarming and necessitates a prompt stewardship program.

Panoramic view of key cross-talks underpinning the oral squamous cell carcinoma stemness - unearthing the future opportunities.

The clinical management of oral cancer is often frequented with challenges that arise from relapse, recurrence, invasion and resistance towards the cornerstone chemo and radiation therapies. The recent conceptual advancement in oncology has substantiated the role of cancer stem cells (CSC) as a predominant player of these intricacies. CSC are a sub-group of tumor population with inherent adroitness to self-renew with high plasticity. During tumor evolution, the structural and functional reprogramming persuades the cancer cells to acquire stem-cell like properties, thus presenting them with higher survival abilities and treatment resistance. An appraisal on key features that govern the stemness is of prime importance to confront the current challenges encountered in oral cancer. The nurturing niche of CSC for maintaining its stemness characteristics is thought to be modulated by complex multi-layered components encompassing neoplastic cells, extracellular matrix, acellular components, circulatory vessels, various cascading signaling molecules and stromal cells. This review focuses on recapitulating both intrinsic and extrinsic mechanisms that impart the stemness. There are contemplating evidences that demonstrate the role of transcription factors (TF) in sustaining the neoplastic stem cell's pluripotency and plasticity alongside the miRNA in regulation of crucial genes involved in the transformation of normal oral mucosa to malignancy. This review illustrates the interplay between miRNA and various known TF of oral cancer such as c-Myc, SOX, STAT, NANOG and OCT in orchestrating the stemness and resistance features. Further, the cross-talks involved in tumor micro-environment inclusive of cytokines, macrophages, extra cellular matrix, angiogenesis leading pathways and influential factors of hypoxia on tumorigenesis and CSC survival have been elucidated. Finally, external factorial influence of oral microbiome gained due to the dysbiosis is also emphasized. There are growing confirmations of the possible roles of microbiomes in the progression of oral cancer. Given this, an attempt has been made to explore the potential links including EMT and signaling pathways towards resistance and stemness. This review provides a spectrum of understanding on stemness and progression of oral cancers at various regulatory levels along with their current therapeutic knowledge. These mechanisms could be exploited for future research to expand potential treatment strategies.

COVID-19-Associated Pulmonary Fungal Infection among Pediatric Cancer Patients, a Single Center Experience.

Patients with COVID-19 are at risk of developing secondary complications such as invasive pulmonary aspergillosis and mucormycosis. This is a retrospective study including all cancer children diagnosed with COVID-19-associated pulmonary fungal infection (CAPFI) during the period 2020-2021. A total of 200 patients were diagnosed with COVID-19, out of which 21 (10%) patients were diagnosed with CAPFI, 19 patients (90%) with COVID-aspergillosis (CAPA), and 2 (10%) patients with COVID-mucormycosis (CAM). Patients with CAPFI were classified using the "2020 ECMM/ISHAM consensus criteria"; proven in 2 (10%) patients, probable in 12 (57%), and possible in 7 (33%) patients. Although the hematological malignancy patients were already on antifungal prophylaxis, breakthrough fungal infection was reported in 16/21 (75%), 14 (65%) patients had CAPA while on echinocandin prophylaxis, while 2 (10%) patients had CAM while on voriconazole prophylaxis. Overall mortality was reported in 8 patients (38%) while CAPFI-attributable mortality was reported in 4 patients (20%). In conclusion, clinicians caring for pediatric cancer patients with COVID-19 should consider invasive pulmonary fungal infection, even if they are on antifungal prophylaxis, especially with worsening of the clinical chest condition. A better understanding of risk factors for adverse outcomes may improve clinical management in these patients.

SARS-CoV-2 genome variations and evolution patterns in Egypt: a multi-center study.

A serious global public health emergency emerged late November 2019 in Wuhan City, China, by a new highly pathogenic virus, SARS-CoV-2. The virus evolution spread has been tracked by three developing databases: GISAID, Nextstrain and PANGO to understand its circulating variants. In this study, 110 diagnosed positive COVID-19 patient's samples, were collected from Kasr Al-Aini Hospital and the Children Cancer Hospital Egypt 57357 between May 2020 and January 2021, with clinical severity ranging from mild to severe. The viral genomes were sequenced by next generation sequencing, and phylogenetic analysis was performed to understand viral transmission dynamics. According to Nextstrain clades, most of our sequenced samples belonged to clades 20A and 20D, which in addition to clade 20B were present from the beginning of sample collection in May 2020. Clades 19A and 19B, on the other hand, appeared in the mid and late 2020 respectively, followed by the disappearance of clade 20B at the end of 2020. We identified a relatively high prevalence of the D614G spike protein variant and novel patterns of mutations associated together and with different clades. We also identified four mutations, spike H49Y, ORF3a H78Y, ORF8 E64stop and nucleocapsid E378V, associated with higher disease severity. Altogether, our study contributes genetic, phylogenetic, and clinical correlation data about the spread of the SARS-CoV-2 pandemic in Egypt.

Hypochlorous acid as a disinfectant for high-risk HPV: Insight into the mechanism of action.

Medical instruments that are not autoclavable but may become contaminated with high-risk human papillomaviruses (HPVs) during use must be thoroughly disinfected to avoid the possibility of iatrogenic transmission of infection. There is an expectation that prolonged soaking of instruments in the United States Food and Drug Administration-cleared chemical disinfectant solutions will result in high-level decontamination, but HPV16 and HPV18 are known to be resistant to commonly used formulations. However, they are susceptible to a variety of oxidative agents, including those based on chlorine. Here, we tested the efficacy of homogeneous hypochlorous acid (HOCl) solutions against mature infectious virions of HPV16 and HPV18 dried onto butadiene styrene coupons and ultrasonic probes. Both viruses were inactivated to >4 log reduction value (LRV) after 15 s on coupons and 5 min on ultrasonic probes. Morphologic changes became evident within those contact times by transmission electron microscopy when HPV16 virus-like particles were exposed to HOCl under identical conditions. Mass spectrometry analysis of trypsin-digested products of L1 capsid proteins exposed to HOCl showed that mostly conserved residues were modified by oxidation and that these changes rapidly lead to instability of the protein demonstrable on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Modifications to these residues may contribute to rapid virus inactivation. The use of homogeneous HOCl solutions for HPV decontamination provides a highly effective means of assuring the safety of nonautoclavable medical instruments.

Carriage of distinct blaKPC-2 and blaOXA-48 plasmids in a single ST11 hypervirulent Klebsiella pneumoniae isolate in Egypt.

BACKGROUND: Carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) causes serious infections with significant morbidity and mortality. However, the epidemiology and transmission mechanisms of CR-hvKP and the corresponding carbapenem-resistant plasmids require further investigation. Herein, we have characterized an ST11 K. pneumoniae strain EBSI041 from the blood sample encoding both hypervirulence and carbapenem resistance phenotypes from a patient in Egypt. RESULTS: K. pneumoniae strain EBSI041 showed multidrug-resistance phenotypes, where it was highly resistant to almost all tested antibiotics including carbapenems. And hypervirulence phenotypes of EBSI041 was confirmed by the model of Galleria mellonella infection. Whole-genome sequencing analysis showed that the hybrid plasmid pEBSI041-1 carried a set of virulence factors rmpA, rmpA2, iucABCD and iutA, and six resistance genes aph(3')-VI, armA, msr(E), mph(E), qnrS, and sul2. Besides, blaOXA-48 and blaSHV-12 were harboured in a novel conjugative IncL-type plasmid pEBSI041-2. The blaKPC-2-carrying plasmid pEBSI041-3, a non-conjugative plasmid lacking the conjugative transfer genes, could be transferred with the help of pEBSI041-2, and the two plasmids could fuse into a new plasmid during co-transfer. Moreover, the emergence of the p16HN-263_KPC-like plasmids is likely due to the integration of pEBSI041-3 and pEBSI041-4 via IS26-mediated rearrangement. CONCLUSION: To the best of our knowledge, this is the first report on the complete genome sequence of KPC-2- and OXA-48-coproducing hypervirulent K. pneumoniae from Egypt. These results give new insights into the adaptation and evolution of K. pneumoniae during nosocomial infections.

The significance of endocan immunohistochemical expression in chronic plaque psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease with immune-mediated mechanism. Endocan is a soluble dermatan sulfate proteoglycan expressed by endothelium of blood vessels. AIMS: The present study aims to evaluate immunohistochemical localization of endocan in psoriatic skin in comparison with normal skin and to correlate its expression with the clinical and pathological data of psoriasis. PATIENTS/METHODS: Skin biopsies from 36 psoriatic patients and 40 normal subjects were taken and processed for immunohistochemical staining of endocan. RESULTS: Endocan was expressed in 63.9% and in 36.1% of epidermal keratinocytes and dermal endothelial and inflammatory cells of psoriatic skin, respectively, compared with its expression in 30% of epidermis of normal skin. Diffuse epidermal expression of endocan was in favor of cases with more angiogenesis and its intense expression was in favor of marked acanthosis and with cases affecting trunk as main presentation. Positive dermal endocan expression was significantly associated with marked parakeratosis and with more angiogenesis. CONCLUSION: Endocan is over-expressed in psoriatic skin from epidermal keratinocytes and dermal endothelial and inflammatory cells. Endocan enhances angiogenesis and proliferation of psoriatic skin contributing to pathogenic mechanisms of psoriasis.

Deciphering Multidrug-Resistant Acinetobacter baumannii from a Pediatric Cancer Hospital in Egypt.

Infection by multidrug-resistant (MDR) Acinetobacter baumannii is one of the major causes of hospital-acquired infections worldwide. The ability of A. baumannii to survive in adverse conditions as well as its extensive antimicrobial resistance make it one of the most difficult to treat pathogens associated with high mortality rates. The aim of this study was to investigate MDR A. baumannii that has spread among pediatric cancer patients in the Children's Cancer Hospital Egypt 57357. Whole-genome sequencing was used to characterize 31 MDR A. baumannii clinical isolates. Phenotypically, the isolates were MDR, with four isolates showing resistance to the last-resort antibiotic colistin. Multilocus sequence typing showed the presence of eight clonal groups, two of which were previously reported to cause outbreaks in Egypt, and one novel sequence type (ST), Oxf-ST2246. Identification of the circulating plasmids showed the presence of two plasmid lineages in the isolates, strongly governed by sequence type. A large number of antimicrobial genes with a range of resistance mechanisms were detected in the isolates, including ß-lactamases and antibiotic efflux pumps. Analysis of insertion sequences (ISs) revealed the presence of ISAba1 and ISAba125 in all the samples, which amplify ß-lactamase expression, causing extensive carbapenem resistance. Mutation analysis was used to decipher underlying mutations responsible for colistin resistance and revealed novel mutations in several outer membrane proteins, in addition to previously reported mutations in pmrB. Altogether, understanding the transmissibility of A. baumannii as well as its resistance and virulence mechanisms will help develop novel treatment options for better management of hospital-acquired infections. IMPORTANCE Acinetobacter baumannii represents a major health threat, in particular among immunocompromised cancer patients. The rise in carbapenem-resistant A. baumannii, and the development of resistance to the last-resort antimicrobial agent colistin, complicates the management of A. baumannii outbreaks and increases mortality rates. Here, we investigate 31 multidrug resistant A. baumannii isolates from pediatric cancer patients in Children's Cancer Hospital Egypt (CCHE) 57357 via whole-genome sequencing. Multilocus sequence typing (MLST) showed the presence of eight clonal groups including a novel sequence type. In silico detection of antimicrobial-resistant genes and virulence factors revealed a strong correlation between certain virulence genes and mortality as well as several point mutations in outer membrane proteins contributing to colistin resistance. Detection of CRISPR/Cas sequences in the majority of the samples was strongly correlated with the presence of prophage sequences and associated with failure of bacteriophage therapy. Altogether, understanding the genetic makeup of circulating A. baumannii is essential for better management of outbreaks.

Management and Outcome of Coronavirus Disease 2019 (COVID-19) in Pediatric Cancer Patients: A Single Centre Experience from a Developing Country.

INTRODUCTION: Sufficient data pertaining to the impact of the Coronavirus disease 2019 (COVID-19) on pediatric cancer patients is still lacking. The aim of this prospective study was to describe clinical management and outcomes of COVID-19 in pediatric oncology patients. PATIENTS AND METHODS: Conducted between May 1, 2020 and November 30, 2020, this study included 76 pediatric oncology patients with confirmed COVID-19. Remdesivir (RDV) was the antiviral therapy used. RESULTS: The median age of patients was 9 years. Sixty patients were on first line treatment. Hematological malignancies constituted 86.8% of patients. Severe to critical infections were 35.4% of patients. The commonest symptom was fever (93.4%). Chemotherapy was delayed in 59.2% of patients and doses were modified in 30.2%. The 60-day overall survival (OS) stood at 86.8%, with mortalities occurring only among critical patients. Of sixteen acute leukemia patients in the first induction therapy, 13 survived and 10 achieved complete remission. A negative RT-PCR within 2 weeks and improvement of radiological findings were statistically related to disease severity (P = .008 and .002, respectively). Better OS was associated with regression of radiological findings after 30 days from infection (P = .002). Forty-five patients received RDV, 42.1% had severe and critical forms of infection compared to 25.7% in the No-RDV group and yet OS was comparable in both groups. CONCLUSION: Most pediatric cancer patients with COVID-19 should have good clinical outcomes except for patients with critical infections. Cancer patients can tolerate chemotherapy including induction phase, alongside COVID-19 treatment. In severe and critical COVID-19, RDV might have a potential benefit.

Molecular characterization of carbapenem-resistant Acinetobacter baumannii clinical isolates from Egyptian patients.

Acinetobacter baumannii (A. baumannii) represents a global threat owing to its ability to resist most of the currently available antimicrobial agents. Moreover, emergence of carbapenem resistant A. baumannii (CR-AB) isolates limits the available treatment options. Enzymatic degradation by variety of ß-lactamases, have been identified as the most common mechanism of carbapenem resistance in A. baumannii. The alarming increase in the prevalence of CR-AB necessitates continuous screening and molecular characterization to appreciate the problem. The present study was performed to assess the prevalence and characterize carbapenemases among 206 CR-AB isolated from various clinical specimens collected from different intensive care units at Kasr Al-Aini Hospital. All isolates were confirmed to be A. baumannii by detection of the blaOXA-51-like gene. Molecular screening of 13 common Ambler class bla carbapenemases genes in addition to insertion sequence (IS-1) upstream OXA-23 were performed by using four sets of multiplex PCR, followed by identification using gene sequencing technology. Among the investigated genes, the prevalence of blaOXA-23, and blaOXA-58 were 77.7%, and 1.9%, respectively. The ISAba1 was detected in 10% of the blaOXA-23 positive isolates. The prevalence of metallo-ß-lactamases (MBLs) studied; blaNDM-1, blaSPM, blaVIM, blaSIM-1 were 11.7%, 6.3%, 0.5%, and 0.5% respectively. One of class A; bla KPC was detected in 10.7% of the investigated isolates. blaOXA-24/40, blaIMP, blaGES, blaVEB and blaGIM were not detected in any of the studied isolates. Moreover, 18.4% of the isolates have shown to harbor two or more of the screened bla genes. We concluded that the most prevalent type of ß-lactamases genes among CR-AB isolates collected from Egyptian patients were blaOXA-23 followed by blaNDM-1 and blaKPC.

Emergence of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Coharboring a blaNDM-1-Carrying Virulent Plasmid and a blaKPC-2-Carrying Plasmid in an Egyptian Hospital.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Egyptian hospitals has been reported. However, the genetic basis and analysis of the plasmids associated with carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) in Egypt have not been presented. Therefore, we attempted to decipher the plasmid sequences that are responsible for transferring the determinants of carbapenem resistance, particularly blaNDM-1 and blaKPC-2 Out of 34 K. pneumoniae isolates collected from two tertiary hospitals in Egypt, 31 were CRKP. Whole-genome sequencing revealed that our isolates were related to 13 different sequence types (STs). The most prevalent ST was ST101, followed by ST383 and ST11. Among the CRKP isolates, one isolate named EBSI036 has been reassessed by Nanopore sequencing. Genetic environment analysis showed that EBSI036 carried 20 antibiotic resistance genes and was identified as a CR-HvKP strain: it harbored four plasmids, namely, pEBSI036-1-NDM-VIR, pEBSI036-2-KPC, pEBSI036-3, and pEBSI036-4. The two carbapenemase genes blaNDM-1 and blaKPC-2 were located on plasmids pEBSI036-1-NDM-VIR and pEBSI036-2-KPC, respectively. The IncFIB:IncHI1B hybrid plasmid pEBSI036-1-NDM-VIR also carried some virulence factors, including the regulator of the mucoid phenotype (rmpA), the regulator of mucoid phenotype 2 (rmpA2), and aerobactin (iucABCD and iutA). Thus, we set out in this study to analyze in depth the genetic basis of the pEBSI036-1-NDM-VIR and pEBSI036-2-KPC plasmids. We report a high-risk clone ST11 KL47 serotype of a CR-HvKP strain isolated from the blood of a 60-year-old hospitalized female patient from the intensive care unit (ICU) in a tertiary care hospital in Egypt, which showed the cohabitation of a novel hybrid plasmid coharboring the blaNDM-1 and virulence genes and a blaKPC-2-carrying plasmid.IMPORTANCE CRKP has been registered in the critical priority tier by the World Health Organization and has become a significant menace to public health. The emergence of CR-HvKP is of great concern in terms of both disease and treatment. In-depth analysis of the carbapenemase-encoding and virulence plasmids may provide insight into ongoing recombination and evolution of virulence and multidrug resistance in K. pneumoniae Thus, this study serves to alert contagious disease clinicians to the presence of hypervirulence in CRKP isolates in Egyptian hospitals.

Cationic zinc (II) phthalocyanine nanoemulsions for photodynamic inactivation of resistant bacterial strains.

BACKGROUND: The growing emergence of microbial resistance to antibiotics represents a worldwide challenge. Antimicrobial photodynamic inactivation (aPDI) has been introduced as an alternative technique, especially when combined with nanotechnology. Therefore, this study was designed to investigate the therapeutic merits of combined aPDI and nanoemulsion in infections caused by resistant bacterial strains. METHODS: Cationic zinc (II) phthalocyanine nanoemulsions (ZnPc-NE) were prepared using isopropyl myristate (IPM) as oil phase, egg phosphatidylcholine (egg PC) as emulsifier, and N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB). Nanoemulsions were characterized for particle size, polydispersity, zeta potential, viscosity, and skin deposition. The in-vitro aPDI was investigated on human resistant pathogens; gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative Multidrug-resistant strain of Escherichia coli (MDR E. coli), under different experimental conditions. In addition, in-vivo model of abrasion wound infected by MDR E. coli was induced in rats to investigate the therapeutic potential of the selected formulation. RESULTS: It was evident that the selected ZnPc formulation (20 % IPM, 2 % egg PC and 0.5 % CTAB) displayed a particle size of 209.9 nm, zeta potential +73.1 mV, and 23.66 % deposition of ZnPc in skin layers. Furthermore, the selected formulation combined with light achieved almost 100 % eradication of the two bacterial strains, with superior bacterial load reduction and wound healing propertiesin-vivo, compared to either the nanoemulsion formulation or laser alone. CONCLUSION: ZnPc nanoemulsion improved antimicrobial photodynamic therapy in inactivating resistant bacterial infections and provided a promising therapeutic means of treating serious infections, and hence could be applied in diseases caused by other bacterial strains.

Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree.

BACKGROUND: Isolated sulfite oxidase deficiency (ISOD) is a life-threatening rare autosomal recessive disorder caused by pathogenic variants in SUOX (OMIM 606887) gene. The aim of our study was to establish a comprehensive genetic diagnosis strategy for the pathogenicity analysis of the SUOX gene within a limited time and to lay the foundation for precise genetic counseling, prenatal diagnosis, and preimplantation genetic diagnosis. METHODS: Two offspring from one set of parents were studied. Next-generation sequencing (NGS) was used to screen for disease-causing gene variants in a family with ISOD. Then, Sanger sequencing was performed to verify the presence of candidate variants. Sulfite, homocysteine and uric acid levels were detected in the patients. According to the ACMG/AMP guidelines, the pathogenicity level of novel variants was annotated. RESULTS: The nonsense pathogenic variant (c.1200C > G (p.Y400*)) and a duplication (c.1549_1574dup (p.I525 Mfs*102)) were found in the SUOX gene in the proband. The nonsense mutation (c.1200C > G (p.Y400*), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) has been reported as pathogenic and the duplication (c.1549_1574dup (p.I525 Mfs*102), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) was novel, which was classified as pathogenic according to the ACMG/AMP Standards and Guidelines. CONCLUSION: We established the pathogenicity assessment in ISOD patients based on ACMG/AMP Standards and Guidelines and this is the first ISOD patient reported in mainland China. We also discovered that ISOD is caused by SUOX gene duplication mutation, which enriches the spectrum of SUOX pathogenic variants.

Identification of Aspergillus species in human blood plasma by infrared spectroscopy and machine learning.

Invasive Aspergillosis is a challenging infection that requires convenient, efficient, and cost-effective diagnostics. This study addresses the potential of infrared spectroscopy to satisfy this clinical need with the aid of machine learning. Two models, based on Partial Least Squares-Discriminant Analysis (PLS-DA), have been trained by a set of infrared spectral data of 9 Aspergillus-spiked and 7 Aspergillus-free plasma samples, and a set of 200 spectral data simulated by oversampling these 16 samples. Two further models have also been trained by the same sets but with auto-scaling performed prior to PLS-DA. These models were assessed using 45 mock samples, simulating the challenging samples of patients at risk of Invasive Aspergillosis, including the presence of drugs (9 tested) and other common pathogens (5 tested) as potential confounders. The simple model shows good prediction performance, yielding a total accuracy of 84.4%, while oversampling and autoscaling improved this accuracy to 93.3%. The results of this study have shown that infrared spectroscopy can identify Aspergillus species in blood plasma even in presence of potential confounders commonly present in blood of patients at risk of Invasive Aspergillosis.

Author Correction: Genotypic characterization of multiple drug resistant Escherichia coli isolates from a pediatric cancer hospital in Egypt.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.