Zirconium- 89 Labeled Antibody K1-70 for PET Imaging of Thyroid-stimulating Hormone Receptor Expression in Thyroid Cancer.

PURPOSE: Thyroid-stimulating hormone receptor (TSHR) is a G-protein coupled receptor that is highly expressed on benign and malignant thyroid tissues. TSHR binding and activation has long been a component of thyroid cancer molecular imaging and radiotherapy, by promoting expression of the sodium-iodide symporter (NIS) and incorporation of I-131 into thyroid hormones. Here, we report the radiosynthesis and preclinical evaluation of a Zirconium-89 (89Zr) labeled TSHR antibody to serve as a positron emission tomography (PET) diagnostic correlate for therapeutic agents targeting TSHR without reliance on NIS. PROCEDURES: TSHR human monoclonal antibody K1-70 was conjugated to chelator desferrioxamine-p-benzyl-isothiocyanate, followed by labeling with Zr-89, yielding the radiotracer 89Zr-DFO-TSHR-Ab. The in vitro cellar uptake and binding affinity of 89Zr-DFO-TSHR-Ab were analyzed in three new TSHR stable overexpressing tumor cell lines and their corresponding wild types (WT) with low or no TSHR expression. 89Zr-DFO-TSHR-Ab PET/CT imaging of TSHR expression was evaluated in tumor mouse models bearing one TSHR-positive tumor and other negative control with or without the coinjection of antibody K1-70, and then verified by radiotracer biodistribution study and tumor immunohistochemistry (IHC). RESULTS: The conjugate DFO-TSHR-Ab was labeled with Zr-89 at 37 °C for 60 min and purified by PD-10 column in radiochemical yields of 68.8 ± 9.9%, radiochemical purities of 98.7 ± 0.8%, and specific activities of 19.1 ± 2.7 mCi/mg (n = 5). In vitro cell studies showed 89Zr-DFO-TSHR-Ab had significantly high uptake on TSHR expressing tumor cells with nanomolar affinity and high potency. Preclinical PET/CT imaging revealed that 89Zr-DFO-TSHR-Ab selectively detected TSHR expressing thyroid tumors and displayed improved in vivo performance with the coinjection of unlabeled TSHR antibody K1-70 leading to higher uptake in TSHR expressing tumors than parental WT tumors and physiologic tissues; this observation was confirmed by the biodistribution and immunostaining analyses. CONCLUSIONS: We synthesized 89Zr-labeled antibody K1-70 as a new radiopharmaceutical for PET imaging of TSHR. 89Zr-DFO-TSHR-Ab has high radioactive uptake and retention in TSHR expressing tumors and cleared quickly from most background tissues in mouse models. Our study demonstrated that 89Zr-DFO-TSHR-Ab has the potential for PET imaging of TSHR-positive thyroid cancer and monitoring TSHR-targeted therapy.

Drug repurposing: identification of SARS-CoV-2 potential inhibitors by virtual screening and pharmacokinetics strategies.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused global health, economic, and population loss. Variants of the coronavirus contributed to the severity of the disease and persistent rise in infections. This study aimed to identify potential drug candidates from fifteen approved antiviral drugs against SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike protein (6M0J) using virtual screening and pharmacokinetics to gain insights into COVID-19 therapeutics. METHODOLOGY: We employed drug repurposing approach to analyze binding performance of fifteen clinically approved antiviral drugs against the main protease of SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike proteins bound to ACE-2 receptor (6M0J), to provide an insight into the therapeutics of COVID-19. AutoDock Vina was used for docking studies. The binding affinities were calculated, and 2-3D structures of protein-ligand interactions were drawn. RESULTS: Rutin, hesperidin, and nelfinavir are clinically approved antiviral drugs with high binding affinity to proteins 6LU7, 5B6O, and 6M0J. These ligands have excellent pharmacokinetics, ensuring efficient absorption, metabolism, excretion, and digestibility. Hesperidin showed the most potent interaction with spike protein 6M0J, forming four H-bonds. Nelfinavir had a high human intestinal absorption (HIA) score of 0.93, indicating maximum absorption in the body and promising interactions with 6LU7. CONCLUSIONS: Our results indicated that rutin, hesperidin, and nelfinavir had the highest binding results against the proposed drug targets. The computational approach effectively identified SARS-CoV-2 inhibitors. COVID-19 is still a recurrent threat globally and predictive analysis using natural compounds might serve as a starting point for new drug development against SARS-CoV-2 and related viruses.

Public misconceptions and attitudes towards persons diagnosed with epilepsy in the Kingdom of Bahrain: A cross-sectional study.

BACKGROUND: Despite significant advancements in the understanding and treatment of epilepsy, the quality of life for persons diagnosed with Epilepsy (PdwE) can still be negatively impacted due to prevalent misconceptions and societal attitudes. This study aimed to investigate the knowledge, misconceptions, and attitudes towards epilepsy in Bahrain. METHODS: This cross-sectional study involved 1079 participants aged ≥ 18 years living in Bahrain. Data collection occurred between June and December 2023 through an online questionnaire. The questionnaire consisted of four sections: sociodemographic characteristics, sources of information, knowledge about epilepsy, and attitudes toward PdwE. RESULTS: Most participants (1063 out of 1179) were familiar with epilepsy, with social media being the main source of information (56.7%). While 75.6% correctly recognized epilepsy as a nervous system disorder. About 30% of participants believed that body shaking and falling to the ground were the only types of seizures. In terms of attitudes, 47.9% believed that PdwE could achieve high levels of education, but 40% thought they might face job loss due to their condition. Additionally, 27.5% disagreed with the idea of marrying someone with epilepsy or allowing a family member to do so. Being female, young, highly educated, and having a family member with epilepsy were associated with significantly more positive attitudes compared to other groups. CONCLUSION: The studied sample of the Bahraini public demonstrated a satisfactory level of knowledge about epilepsy. However, they still held certain misconceptions that could impact their attitudes towards PdwE. Community awareness campaigns can address this knowledge gap and reduce epilepsy stigma.

Knowledge of Sickle Cell Disease Among Medical Students at Al-Baha University, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Sickle cell disease (SCD) presents a major health challenge in Saudi Arabia due to its high prevalence. The important role of medical students as future healthcare leaders necessitates high awareness and knowledge about the disease. AIM: To assess SCD awareness among Al-Baha University medical students, and to evaluate its relation to gender and academic level. METHODS: A cross-sectional study was conducted, including 105 medical students from the first to sixth year at Al-Baha University. Data collection utilized an online self-administered questionnaire, covering demographic characteristics and assessing SCD knowledge. Fisher's exact and Pearson Chi-squared tests were employed to analyze associations between gender, academic level, and SCD awareness. RESULTS: The majority of male participants 52 (89.6%) and all females 47 (100%) demonstrated awareness of SCD. Clinical year enrollment (68.6%) correlated with heightened awareness across various aspects of SCD compared to the preclinical year. Most participants were in clinical years (68.6%), and 94.3% of them had knowledge about SCD. Approximately, 75 (71%) of participants correctly identified features of sickle cell crisis, 83 (79%) reported the accurate cause of SCD, and 75 (71%) cited the appropriate preventive measures. Only 15 (14%) demonstrated knowledge of correct management of SCD. Contrarily, 84 (80%) were aware of SCD complications, 66 (63%) recognized different SCD types, 67 (64%) felt adequately informed about SCD, and 34 (32%) were involved in SCD counseling. Male participants exhibited greater awareness of SCD features than females. Notably, involvement in SCD counseling was more prevalent among students of clinical years. CONCLUSION: This study underscores the need for targeted educational initiatives, particularly among preclinical year students to enhance SCD awareness among students. We also emphasize the role of clinical education in fostering a comprehensive understanding of SCD, with increased participation in counseling programs.

Course and predictors of excellent response to therapy in patients with differentiated thyroid cancer at long-term follow-up.

OBJECTIVES: To investigate the long-term outcomes of differentiated thyroid cancer (DTC) and the predictive factors for excellent and incomplete responses to therapy on long-term follow-up of patients. METHODS: A retrospective chart review and analysis was carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Demographic, histological, and therapeutic data were collected from patients older than 13 years at the time of diagnosis, with a minimum follow-up of 18 months. Outcomes were divided into excellent, indeterminate, biochemically incomplete, and structurally incomplete responses. Odds ratios (ORs) for predictors of incomplete response at the last visit were determined. We first tested associations univariately with incomplete responses, and then variables with significant associations were included in a multivariable logistic model. RESULTS: Among 230 patients with DTC, 61.7% had excellent responses to therapy on long-term follow-up, and 24.3% had incomplete biochemical and structural responses. The median follow-up was 4.6 years. Factors significantly associated with incomplete response to therapy in the multivariate analysis (p<0.05) were age >55 years (OR=5) and lymph node (OR=3.4) and distant metastases (OR=29). Older age did not affect the outcome in low-risk patients with DTC but was significantly associated with incomplete responses in those with intermediate risk (p=0.04) and high risk (p=0.003). CONCLUSION: We strongly advocate incorporating age into recurrence risk assessment for patients with DTC.

Knowledge, Attitude, and Practice of Qualitative Research Among Health Sciences Faculty.

Background The importance of qualitative research in health sciences is rising. Qualitative research needs more attention from healthcare practitioners. Hence, some questions in the healthcare field may only be answered through qualitative research methodologies. In this study, we aimed to assess the knowledge, practice, and attitude among health sciences faculty about qualitative research. Methodology This cross-sectional study was conducted at King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS). A convenient sampling technique was used to collect data from health sciences faculty participants. Participants were included from five different colleges, i.e., College of Medicine, Applied Health Sciences, Nursing, Pharmacy, and College of Dentistry. A 20-question, self-made questionnaire was given to each participant. The questionnaire had five attitude questions, 10 knowledge questions, and five practice questions. Results A total of 236 participants completed the study questionnaire. The majority of the study participants (198, 84%) had an overall poor knowledge of qualitative research methodologies. Most participants (214, 91%) agreed that qualitative research is important in health sciences. More than half of the participants had never attended a qualitative methods workshop (140, 59%). About three-quarters of the participants (175, 74%) had never participated in a qualitative research project. Conclusions The overall knowledge and practice of qualitative research methodologies were poor among KSAU-HS health sciences faculty while they had a good attitude toward its importance in health sciences.

PPE Barcoding Identifies Biclonal Mycobacterium ulcerans Buruli Ulcer, Côte d'Ivoire.

Mycobacterium ulcerans, an environmental opportunistic pathogen, causes necrotic cutaneous and subcutaneous lesions, named Buruli ulcers, in tropical countries. PCR-derived tests used to detect M. ulcerans in environmental and clinical samples do not allow one-shot detection, identification, and typing of M. ulcerans among closely related Mycobacterium marinum complex mycobacteria. We established a 385-member M. marinum/M. ulcerans complex whole-genome sequence database by assembling and annotating 341 M. marinum/M. ulcerans complex genomes and added 44 M. marinum/M. ulcerans complex whole-genome sequences already deposited in the NCBI database. Pangenome, core genome, and single-nucleotide polymorphism (SNP) distance-based comparisons sorted the 385 strains into 10 M. ulcerans taxa and 13 M. marinum taxa, correlating with the geographic origin of strains. Aligning conserved genes identified one PPE (proline-proline-glutamate) gene sequence to be species and intraspecies specific, thereby genotyping the 23 M. marinum/M. ulcerans complex taxa. PCR sequencing of the PPE gene correctly genotyped nine M. marinum/M. ulcerans complex isolates among one M. marinum taxon and three M. ulcerans taxa in the African taxon (T2.4). Further, successful PPE gene PCR sequencing in 15/21 (71.4%) swabs collected from suspected Buruli ulcer lesions in Côte d'Ivoire exhibited positive M. ulcerans IS2404 real-time PCR and identified the M. ulcerans T2.4.1 genotype in eight swabs and M. ulcerans T2.4.1/T2.4.2 mixed genotypes in seven swabs. PPE gene sequencing could be used as a proxy for whole-genome sequencing for the one-shot detection, identification, and typing of clinical M. ulcerans strains, offering an unprecedented tool for identifying M. ulcerans mixed infections. IMPORTANCE We describe a new targeted sequencing approach that characterizes the PPE gene to disclose the simultaneous presence of different variants of a single pathogenic microorganism. This approach has direct implications on the understanding of pathogen diversity and natural history and potential therapeutic implications when dealing with obligate and opportunistic pathogens, such as Mycobacterium ulcerans presented here as a prototype.

CRISPR-Based Detection, Identification and Typing of Mycobacterium tuberculosis Complex Lineages.

The polymerase chain reaction (PCR)-based detection of Mycobacterium tuberculosis (M. tuberculosis) complex (MTC) in clinical samples is a first-line approach by which to diagnose tuberculosis in clinical microbiology laboratories. In this study, the genome-wide profiling of 3,156 mycobacterial genomes using Roary determined the CRISPR-csm4 gene as specific for MTB. Real time (RT)-PCR and the PCR-sequencing of CRISPR-csm4, tested on a collection of 20 MTC and 5 nontuberculous mycobacteria, confirmed the 20 MTC isolates, whereas the 5 nontuberculous isolates were not detected. Further, 65 of the leftover clinical samples, including 25 GeneXpert-positive and 40 GeneXpert-negative samples, that were used to evaluate the CRISPR-csm4-MTB assay in the clinical microbiology laboratory setting yielded expected results in every case, further allowing for the identification of the M. tuberculosis Beijing lineage. RT-PCR and the PCR-sequencing of CRISPR-csm4 could be implanted in the clinical microbiology laboratory to complement the currently used assays, with the potential of increasing the specification of the MTC pathogens responsible for tuberculosis. IMPORTANCE The whole-genome sequence comparison of the Mycobacterium tuberculosis complex (MTC) genomic sequences that are available in the NCBI database identified a unique, specific gene to be used directly on clinical diagnostic samples to detect MTC against all species of mycobacteria and to differentiate between MTC species, lineages, and sublineages.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Introducing clinical nanorachaeaology: Isolation by co-culture of Nanopusillus massiliensis sp. nov.

BACKGROUND: Nanoarchaeota, obligate symbiont of some environmental archaea with reduced genomes, have been described in marine thermal vent environments, yet never detected in hosts, including humans. METHODS: Here, using laboratory tools geared towards the detection of nanoarchaea including PCR-sequencing, WGS, microscopy and culture. RESULTS: We discovered a novel nanoarchaea, Nanopusillus massiliensis, detected in dental plate samples by specific PCR-based assays. Combining fluorescent in situ hybridization (FISH) with scanning electron microscopy disclosed close contacts between N. massiliensis and the archaea Methanobrevibacter oralis in these samples. Culturing one sample yielded co-isolation of M. oralis and N. massiliensis with a 606,935-bp genome, with 23.6% GC encoded 16 tRNA, 3 rRNA and 942 coding DNA sequences, of which 400 were assigned to clusters of orthologous groups. CONCLUSION: The discovery of N. massiliensis, made publicly available in collection, extended our knowledge of human microbiota diversity, opening a new field of research in clinical microbiology here referred to as clinical nanoarchaeology.

A New Filter Based Cultivation Approach for Improving Aspergillus Identification using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS).

Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is widely used in clinical laboratories for routine identification of bacteria and yeasts. However, methodological difficulties are still apparent when applied to filamentous fungi. The liquid cultivation method recommended by Bruker Daltonics GmbH for identification of filamentous fungi by MALDI-TOF MS is labour intensive and time-consuming. In this study, growth of Aspergillus species on different (porous) surfaces was investigated with the aim to develop a more reliable, quicker and less laborious identification method using MALDI-TOF MS. Mycelial growth without sporulation mimicking liquid cultivation and reliable MALDI-TOF MS spectra were obtained when A. fumigatus strains were grown on and in between a polycarbonate membrane filter on Sabouraud dextrose agar. A database of in-house reference spectra was created by growing Aspergillus reference strains (mainly focusing on sections Fumigati and Flavi) under these selected conditions. A test set of 50 molecularly identified strains grown under different conditions was used to select the best growth condition for identification and to perform an initial validation of the in-house database. Based on these results, the cultivation method on top of a polycarbonate filter proved to be most successful for species identification. This method was therefore selected for the identification of two sets of clinical isolates that mainly consisted of Aspergilli (100 strains originating from Indonesia, 70 isolates from Qatar). The results showed that this cultivation method is reliable for identification of clinically relevant Aspergillus species, with 67% and 76% correct identification of strains from Indonesia and Qatar, respectively. In conclusion, cultivation of Aspergilli on top of a polycarbonate filter showed improved results compared to the liquid cultivation protocol recommended by Bruker in terms of percentage of correct identification, ease of MSP creation, time consumption, cost and labour intensity. This method can be reliably applied for identification of clinically important Aspergilli and has potential for identification of other filamentous fungi.

Molecular epidemiology of clinical filamentous fungi in Qatar beyond Aspergillus and Fusarium with notes on the rare species.

Due to an increasing number of patients at risk (i.e., those with a highly compromised immune system and/or receiving aggressive chemotherapy treatment), invasive fungal infections (IFI) are increasingly being reported and associated with high mortality rates. Aspergillus spp., particularly A. fumigatus, is the major cause of IFI caused by filamentous fungi around the world followed by Fusarium spp., however, other fungi are emerging as human pathogens. The aim of this study was to explore the epidemiology and prevalence of the non-Aspergillus and non-Fusarium filamentous fungi in human clinical samples over an 11-year period in Qatar using molecular techniques. We recovered 53 filamentous fungal isolates from patients with various clinical conditions. Most patients were males (75.5%), 9.4% were immunocompromised, 20.7% had IFI, and 11.3% died within 30 days of diagnosis. The fungal isolates were recovered from a variety of clinical samples, including the nasal cavity, wounds, respiratory samples, body fluids, eye, ear, tissue, abscess, and blood specimens. Among the fungi isolated, 49% were dematiaceous fungi, followed by Mucorales (30%), with the latter group Mucorales being the major cause of IFI (5/11, 45.5%). The current study highlights the epidemiology and spectrum of filamentous fungal genera, other than Aspergillus and Fusarium, recovered from human clinical samples in Qatar, excluding superficial infections, which can aid in the surveillance of uncommon and emerging mycoses.

We recovered 53 non-Aspergillus and non-Fusarium filamentous fungal isolates from 53 patients in Qatar. Dematiaceous (black) fungi were the most isolated fungi followed by Mucorales, with the latter group Mucorales being the major cause of invasive infections in this study.

Molecular detection of Mycobacterium tuberculosis sensu stricto in the soil of Niger.

Mycobacterium tuberculosis (MTB) complex is comprising of pathogenic mycobacteria responsible for human and animal tuberculosis, a major public health problem in Niger. Although infected individuals are paramount sources of contamination, nevertheless alternative, neglected sources may play some role in minority forms of the infection. Accordingly, we investigated the presence of Mycobacterium tuberculosis complex in soil samples in Niger. A total of 103 soil samples were collected in six different areas in Niger in October and November 2018 and April and May 2020 from residential areas of tuberculosis patients. Screening PCR targeting M. tuberculosis complex CRISPR-Csm4 and Xpert MTB/RIF Ultra assay were applied to detect the M. tuberculosis complex. M. tuberculosis DNA was positively detected in five of 103 (5/103; 4.8%) soil samples (Dosso: one sample, Zinder: one sample and Niamey: three samples) using the CRISPR-Csm4 system. CRISPR-Csm4 gene sequence identified four M. tuberculosis sensu stricto (may be lineages 1, 3 or 4) and one M. tuberculosis L2 lineage (Beijing). Moreover, the five positive samples were confirmed by Xpert MTB/RIF Ultra assay as rifampicin-susceptible M. tuberculosis complex strains. However, culture remained negative after 42 days. In this study, we announced for the first time the presence of M. tuberculosis sensu stricto in the soil of Niger. Moreover, these detected lineages were identical to the dominant M. tuberculosis lineages in patients. The presence of common lineages of M. tuberculosis between the soil and human highlight the risk of transmission from the soil to human.

Serum Cytokine Profile in Patients with Candidemia versus Bacteremia.

Bloodstream Candida infections constitute a major threat for hospitalized patients in intensive care units and immunocompromised hosts. Certain serum cytokines play a decisive role in anti-microbial host defense. Cytokines may act as discriminatory biomarkers that can significantly increase in candidemia compared to bacteremia patients. The concentration of secreted cytokine/chemokines was determined using a multiplexed cytometric bead array run on a cell analyzer. The cytokines tested during the study were interleukin (IL)-1ß, IL-6, IL-17A, IL-10, IFN-γ, IL-4, IL-2, IL-8, IL-12p70 and the tumor necrosis factor (TNF)-α. The cytokines of 51 candidemia patients were characterized and compared to the cytokine levels of 20 bacteremia patients. Levels were significantly elevated in patients with bloodstream infections compared to healthy controls. Cytokines comprising IL-2, IL-17A, IL-6 and IL-10 were significantly elevated in the patients with bloodstream Candida infection as compared to the patients having bloodstream bacterial infections. The levels were found to be promising as a potential diagnostic marker for bloodstream Candida infections.

Bayesian and Classical Inference for the Generalized Log-Logistic Distribution with Applications to Survival Data.

The generalized log-logistic distribution is especially useful for modelling survival data with variable hazard rate shapes because it extends the log-logistic distribution by adding an extra parameter to the classical distribution, resulting in greater flexibility in analyzing and modelling various data types. We derive the fundamental mathematical and statistical properties of the proposed distribution in this paper. Many well-known lifetime special submodels are included in the proposed distribution, including the Weibull, log-logistic, exponential, and Burr XII distributions. The maximum likelihood method was used to estimate the unknown parameters of the proposed distribution, and a Monte Carlo simulation study was run to assess the estimators' performance. This distribution is significant because it can model both monotone and nonmonotone hazard rate functions, which are quite common in survival and reliability data analysis. Furthermore, the proposed distribution's flexibility and usefulness are demonstrated in a real-world data set and compared to its submodels, the Weibull, log-logistic, and Burr XII distributions, as well as other three-parameter parametric survival distributions, such as the exponentiated Weibull distribution, the three-parameter log-normal distribution, the three-parameter (or the shifted) log-logistic distribution, the three-parameter gamma distribution, and an exponentiated Weibull distribution. The proposed distribution is plausible, according to the goodness-of-fit, log-likelihood, and information criterion values. Finally, for the data set, Bayesian inference and Gibb's sampling performance are used to compute the approximate Bayes estimates as well as the highest posterior density credible intervals, and the convergence diagnostic techniques based on Markov chain Monte Carlo techniques were used.

Where the infection is isolated rather than the specific species correlates with adherence strength, whereas biofilm density remains static in clinically isolated Candida and arthroconidial yeasts.

To colonize and infect the host, arthroconidial yeasts must avoid being killed by the host's defenses. The formation of biofilms on implanted devices allows fungi to avoid host responses and to disseminate into the host. To better study the mechanisms of infection by arthroconidial yeasts, adherence and biofilm formation were assayed using patient samples collected over 10 years. In clinical samples, adherence varies within species, but the relative adherence is constant for those samples isolated from the same infection site. Herein we document, for the first time, in-vitro biofilm formation by Trichosporon dohaense, T. ovoides, T. japonicum, T. coremiiforme, Cutaneotrichosporon mucoides, Cutaneotrichosporon cutaneum, Galactomyces candidus, and Magnusiomyces capitatus on clinically relevant catheter material. Analysis of biofilm biomass assays indicated that biofilm mass changes less than 2-fold, regardless of the species. Our results support the hypothesis that most pathogenic fungi can form biofilms, and that biofilm formation is a source of systemic infections.

Mathematical search technique for detecting moving novel coronavirus disease (COVID-19) based on minimizing the weight function.

The study of search plans has found considerable interest between searchers due to its interesting applications in our real life like searching for located and moving targets. This paper develops a method for detecting moving targets. We propose a novel strategy based on weight function W ( Z ) , W ( Z ) = λ H ( Z ) + ( 1 - λ ) L ( Z ) , where H ( Z ) , L ( Z ) are the total probabilities of un-detecting, and total effort respectively, is searching for moving novel coronavirus disease (COVID-19) cells among finite set of different states. The total search effort will be presented in a more flexible way, so it will be presented as a random variable with a given distribution. The objective is searching for COVID-19 which hidden in one of n cells in each fixed number of time intervals m and the detection functions are supposed to be known to the searcher or robot. We look in depth for the optimal distribution of the total effort which minimizes the probability of undetected the target over the set of possible different states. The effectiveness of this model is illustrated by presenting a numerical example.

Role of Bacteria in the Incidence of Common GIT Cancers: The Dialectical Role of Integrated Bacterial DNA in Human Carcinogenesis.

Despite the wide medical knowledge about the direct role of many viruses in the pathogenesis of certain cancers, there is still ambiguity and hazy vision about the direct role of bacteria in cancer incidence. Understanding the role of bacteria in carcinogenesis is no longer a scientific luxury, but it has become an urgent and extremely important necessity to realize the pathogenesis of cancer caused by oncogenic bacteria as an attempt to overcome the oncogenic mechanisms exhibited by these oncogenic bacteria. This review shed the light on the indirect role of the host's inflammatory and immunological responses in the pathogenesis of bacteria-induced cancer. Also, this review discussed the indirect role of the bacterial toxins and virulence factors in the induction of common gastrointestinal cancers, such as gallbladder cancer (GBC), colorectal cancer (CRC), and gastric cancer (GC). Finally, this review dealt with the debate about the possibility of bacterial DNA integration into the human genome and cancer incidence.