Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-omics Analysis of Ferroptosis Regulation Patterns and Characterization of Tumor Microenvironment in Patients with Oral Squamous Cell Carcinoma

Ferroptosis is a newly recognized mechanism of regulated cell death. It was reported to be highly associated with immune therapy and chemotherapy. However, its mechanism of regulation in the tumor microenvironment (TME) and influence on oral squamous cell carcinoma (OSCC) therapy are unknown. We identified a ferroptosis-specific gene-expression signature, an FPscore, developed by a principal component analysis (PCA) algorithm to evaluate the ferroptosis regulation patterns of individual tumor. Multi-omics analysis of ferroptosis regulation patterns was conducted. Three distinct ferroptosis regulation subtypes, which linked to outcomes and the clinical relevance of each patient, were established. A high FPscore of patients with OSCC was associated with a favorable prognosis, a ferroptosis-related immune-activation phenotype, potential sensitivities to the chemotherapy and immunotherapy. Importantly, a high FPscore correlated with a low gene copy number burden and high immune checkpoint expressions. We validated the prognostic value of the FPscore using independent immunotherapy and pan-cancer cohorts. Comprehensive evaluation of individual tumors with distinct ferroptosis regulation patterns provides new mechanistic insights, which may be clinically relevant for the application of combination therapies in OSCC.
Cutaneous Manifestations of COVID-19: An Experience From Oman

Objectives: To identify the cutaneous manifestations in COVID-19 disease in Oman. Methods: The study was conducted in two phases with initial cross-sectional data collection with subsequent telemedical investigations of late skin manifestations including confirmed COVID-19 patients evaluated at Al-Nahdha Hospital and local health centers in Muscat from March 22 to June 2, 2020. Results: The total number of patients included in the study was 374. Cutaneous manifestations were observed in 1.87% (n=7) of patients at presentation with an additional 1.6% (n=5) on follow-up. The types of skin reactions included maculopapular rash (n=6), urticaria (n=2), transient pruritic erythema (n=1), pruritic palmoplantar erythema (n=1), pustular eruption (n=1) and flare-up of atopic dermatitis (n=1). Conclusions: The low percentage of skin lesions is not contradicting previous data and it might just reflect under-reporting of skin rash in the context of the presence of more severe symptoms in our sample population. Skin lesions can still be utilized to treat patients as suspected cases until proven otherwise as it can be a silent clue in asymptomatic patients.
Endoscopic third ventriculostomy in the treatment of hydrocephalus: A 20-year retrospective analysis of 209 consecutive cases

Background: Endoscopic third ventriculostomy (ETV) has been shown to be a sufficient alternative to shunts in surgical treatment of obstructive hydrocephalus. Long-term failure, age limitations, and outcome by cause are some of the issues debated in literature. The objective of this article is to analyze the clinical success and failure of ETV and its main complications. Methods: A total of 209 patients with hydrocephalus were submitted to ETV, including a mixed population of children and adults (from 0 to 59 years). Patients were divided into five groups: A – tumors, B – aqueductal stenosis, C – myelomeningocele, D – infection and hemorrhage, and E – arachnoid cyst. Variables were analyzed: age, ETV success rate, cerebrospinal fluid (CSF) fistula, mortality, and complications. Results: The two main causes of hydrocephalus were tumors (44.9%) and aqueductal stenosis (25.3%). The overall success rate was of 82.8%, and patients in Group E had the highest rate 90.9%. Group A had a success rate of 89.3%, and Group B had a rate of 88.6%. The ETV success rate was significantly higher in patients older than 1 year (P < 0.001); the former also had a lower risk of CSF fistula (P < 0.0001). The overall mortality rate was 2.8%. Conclusion: Better results were observed in the groups of patients with tumors, aqueductal stenosis, and arachnoid cysts, while those whose primary causes of hydrocephalus were myelomeningocele, infections, or bleeding had higher rates of failure after the procedure. This study demonstrated that age under 1 year and hydrocephalus caused by myelomeningocele, bleeding, and infection were considered independent risk factors of poor prognosis in ETV.
The Role of Imaging Modalities in Diagnosing Dysphagia: A Clinical Review

Dysphagia, which is characterized by difficulty in oro-gastric bolus transit, is a common condition. It is broadly classified into oropharyngeal or esophageal pathology. A wide array of differentials for dysphagia and initial clinical suspicion of oropharyngeal or esophagus etiology can assist in further evaluation. Fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallow study (VFSS) are the preferred modalities for assessing oropharyngeal bolus transit, residual, as well as determining the risk of laryngeal aspiration. High-resolution pharyngeal manometry (HRPM) is an emerging modality for optimal topographical and pressure assessment of pharyngeal anatomy. HRPM provides improved assistance in evaluating the strength of the pharyngeal muscular contraction. Esophagogastroduodenoscopy (EGD) is the preferred exam for patients with suspected esophageal etiology of dysphagia. Barium swallow provides luminal assessment and assists in evaluating esophageal motility; it is non-invasive, but therapeutic interventions like biopsy cannot be performed. High-resolution esophageal manometry (HREM) has added another dimension in the diagnosis of esophageal motility disorders. The purpose of this review article is to help internists and primary care providers get a better understanding of the role of various imaging modalities in diagnosing dysphagia in the elderly population. This article also provides a comprehensive review and detailed comparison of these imaging modalities based on the latest evidence.
Effectiveness of the Heads-Up Surgery System for Retinal Surgery in a Patient with Severe Photophobia

Background The reported features and effectiveness of heads-up surgery (HUS) for ophthalmic surgery include greater resolution, teaching, and significantly reduced endoillumination power. Objective To report how to care for severe intraoperative photophobia using the HUS system during bilateral rhegmatogenous retinal detachment (RD) surgery in a patient with severe photophobia. Case Report A man in his 50s, who had been followed up for photophobia and visual impairment underwent five ophthalmic surgeries for bilateral RD. In his early 40s, he had been referred to our hospital because of a complaint of bilateral visual impairment, including severe photophobia, approximately 2 years prior. His decimal best-corrected visual acuities were 0.7 and 0.6 in his right and left eyes, respectively. Optical coherence tomography showed diffuse thinning of the entire retinal layer in the macula of both eyes, which was considered to be a cause of the decrement of visual acuity and photophobia. Twelve years after his first visit, he noticed multiple floaters in his left eye. For RD excluding the macular area, we planned cataract and retinal surgery under retrobulbar anesthesia. However, as we could not continue retinal surgery after cataract surgery due to severe photophobia, we performed general anesthesia (GA) during the second surgery. Seventeen months after the surgery, he underwent the third surgery for RD in his right eye under GA. For RD recurring twice, we performed surgery with the HUS system under retrobulbar anesthesia for the fourth and fifth surgeries, which avoided photophobia due to the significantly reduced light stimulation of the HUS system. Conclusion Lower light intensity achieved by the HUS system enabled us to eliminate the patient’s intraoperative discomfort. Consequently, we could perform the surgery under local anesthesia in this patient with RD who complained of severe photophobia that required GA using a conventional surgical system.
Remarkable adsorptive removal of nitrogen-containing compounds from hydrotreated fuel by molecularly imprinted poly-2-(1H-imidazol-2-yl)-4-phenol nanofibers

Molecularly imprinted polymer (MIP) nanofibers were prepared by the electrospinning of poly 2-(1H-imidazol-2-yl)-4-phenol (PIMH) in the presence of various nitrogen containing compounds (N-compounds). Molecularly imprinted polymer nanofibers show selectivity for various target model nitrogen-containing compounds with adsorption capacities of 11.7 ± 0.9 mg g−1, 11.9 ± 0.8 mg g−1 and 11.3 ± 1.1 mg g−1 for quinoline, pyrimidine and carbazole, respectively. Molecular modelling based upon density functional theory (DFT) indicated that hydrogen bond interactions may take place between the lone-pair nitrogen atom of model compounds (quinoline and pyrimidine) and the –OH and –NH groups of the PIMH nanofibers. The adsorption mode followed the Freundlich (multi-layered) adsorption isotherm, which indicated possible nitrogen–nitrogen compound interactions. Molecularly imprinted polymer nanofibers show potential for the removal of nitrogen-containing compounds in fuel.
Enteroaggregative Escherichia coli is associated with antibiotic resistance and urinary tract infection symptomatology

Background Uropathogenic Escherichia coli (UPEC) is the causative agent of uncomplicated urinary tract infections (UTIs) in ambulatory patients. However, enteroaggregative E. coli (EAEC), an emergent bacterial pathogen that causes persistent diarrhoea, has recently been associated with UTIs. The aim of this study was to determine the frequency of EAEC virulence genes, antibiotic resistance, as well as biofilm production of UPEC isolates obtained from ambulatory patients with non-complicated UTIs that attended to the ISSSTE clinic in Chilpancingo, Guerrero, Mexico, and correlate these with the patients’ urinary tract infection symptomatology. Methods One hundred clinical isolates were obtained. The identification of clinical isolates, antimicrobial susceptibility testing, and extended spectrum beta-lactamases (ESBLs) production were performed using the Vitek automated system. Assignment of E. coli phylogenetic groups was performed using the quadruplex phylo-group assignment PCR assay. UPEC virulence genes (hlyA, fimH, papC, iutA, and cnf1) and EAEC virulence genes (aap, aggR, and aatA) were detected by multiple PCR. Results We found that 22% of the isolates carried the aggR gene and were classified as UPEC/EAEC. The main phylogenetic group was B2 (44.1% were UPEC and 77.27% UPEC/EAEC isolates, respectively). Over half of the UPEC/EAEC isolates (63.64%) were obtained from symptomatic patients, however the aatA gene was the only one found to be associated with the risk of developing pyelonephritis (OR = 5.15, p = 0.038). A total of 77.71% of the UPEC/EAEC isolates were ESBL producers and 90.91% multidrug-resistant (MDR). In conclusion, UPEC/EAEC isolates are more frequent in symptomatic patients and the aatA gene was associated with a higher risk of developing pyelonephritis, along with UPEC genes hlyA and cfn1. UPEC/EAEC isolates obtained from UTI showed ESBL production and MDR.
Appropriateness of Empirical Fluoroquinolones Therapy in Patients Infected with Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa: The Importance of the CLSI Breakpoints Revision

Purpose Empirical antibiotic therapy should follow the local bacterial susceptibility, and the breakpoints revisions of the antimicrobial susceptibility testing can reflect the changes in the antimicrobial susceptibility of bacteria. This study aimed to analyze whether the changes in the antimicrobial susceptibility to antibiotics caused by the breakpoint revision will affect the empirical antibiotic therapy and its appropriateness. Patients and Methods A retrospective study was conducted among 831 hospitalized patients infected by Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa from April 10, 2018, to April 11, 2020. We evaluated the appropriateness of empirical therapy based on the antimicrobial susceptibility testing results. The rate of empirical use and appropriateness of fluoroquinolones was calculated, and logistic regression was used to analyze influencing factors of empirical use of fluoroquinolones. Results The susceptibility rate of the three bacteria to levofloxacin (50.78% vs 32.06%) and ciprofloxacin (48.45% vs 21.90%) was decreased (P<0.001), while the resistance rate to levofloxacin (45.74% vs 58.73%) and ciprofloxacin (46.90% vs 66.67%) was increased (P<0.001) after the breakpoints revision. The empirical usage rate of fluoroquinolones in patients infected with Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa was 20.94%, which was influenced by the breakpoint revision (P=0.022), age (P=0.007), and the department (P=0.006); the appropriateness rate was 28.74%, affected by the pathogenic bacteria (P=0.001) and multidrug-resistant microorganism (P=0.001), department (P=0.024), and the length of stay before the empirical therapy (P=0.016). Conclusion The susceptibility of bacteria to antibiotics has changed significantly after the breakpoint revision while the clinicians’ empirical therapy failure to change accordingly, which results in the decrease of the appropriateness of empirical use. It is enlightened that we should conduct more research to evaluate the rational use of antibiotics from the laboratory perspective and carry out interventions such as education and supervision to strengthen the collaboration between the microbiology laboratories and clinicians to improve the empirical antibiotic therapy and slow down the antimicrobial resistance.
CT and MRI Findings of Focal Splenic Lesions and Ascites in Generalized Lymphatic Anomaly, Kaposiform Lymphangiomatosis, and Gorham-Stout Disease

Objectives: This study aimed to evaluate the CT and MRI findings of focal splenic lesions and ascites in generalized lymphatic anomaly (GLA), kaposiform lymphangiomatosis (KLA), and Gorham-Stout disease (GSD). Material and Methods: Twenty-three patients (10 with GLA, 5 with KLA, and 8 with GSD) who underwent abdominal CT and/or MRI before treatment were included in this study, and their imaging findings were retrospectively evaluated. Results: Focal splenic lesions were observed in nine patients; these lesions were observed frequently in GLA (n = 5; 50%) or KLA (n = 3; 60%) compared with GSD (n = 1; 13%); however, no significant differences were found between the three groups (P = 0.190). On CT images among eight patients (4 with GLA, 3 with KLA, and 1 with GSD) with focal splenic lesions who underwent CT, the number of focal splenic lesions per patient ranged from 2 to 189 (mean, 42) and the maximum diameter of focal splenic lesions ranged from 2 to 39 mm (mean, 8 mm), while more than 30 focal splenic lesions per patient were observed in 2 (50%) GLA and focal splenic lesions with maximum diameters of ≥10 mm were observed in 4 (100%) GLA but not in KLA or GSD. Ascites was observed in five patients; significant differences were observed among KLA (n = 4; 80%), GLA (n = 1; 10%), and GSD (n = 0; 0%) (P < 0.01). Ascites was significantly more frequent in KLA than in GSD (P < 0.05). Conclusion: More than 30 focal splenic lesions per patient and/or focal splenic lesions with maximum diameters of ≥10 mm were observed only in GLA. Focal splenic lesions tended to be less frequent in GSD, whereas ascites tended to be frequent in KLA.
Prolonged Honeymoon Period in a Thai Patient with Adult-Onset Type 1 Diabetes Mellitus

Objective To describe a usual case of adult-onset T1DM with prolonged honeymoon period for more than 5 years. Methods Repeated mixed meal stimulation tests for a period of 6–12 months together with monitoring pancreatic autoantibodies and laboratory data were followed following the onset of diagnosis. Results We report a 24-year-old Thai patient with T1DM with sustained remission without antidiabetic medication for more than 5 years while maintaining low-carbohydrate intake and regular exercise. Repeated mixed meal stimulation tests for a period of 6–12 months revealed preserved beta-cell functions. Interestingly, repeated pancreatic autoantibodies at 5 years after diagnosis still showed positive anti-GAD, anti-IA2, and anti-ZnT8. Conclusion Restored beta-cell function with complete insulin withdrawal in new-onset T1DM has been reported in very few cases with some common factors as in our patient (low-carbohydrate intake with regular exercise). Delaying autoimmune activity by reducing metabolic load in newly diagnosed T1DM might play a role in maintaining the honeymoon period and could lead to an innovative therapeutic option in new-onset T1DM.
A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

Simple Summary Glioma patients that present a somatic mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a significantly better prognosis and overall survival than patients with the wild-type genotype. An IDH1 mutation is hypothesized to occur early during cellular transformation and leads to further genetic instability. A genome-wide profiling of glioma patients in the Catalogue of Somatic Mutations in Cancer (COSMIC) database was performed to classify the genetic differences in IDH1-mutant versus IDH1-wildtype patients. This classification will aid in a better understanding of how this specific mutation influences the genetic make-up of glioma and the resulting prognosis. Key differences in co-mutation and gene expression levels were identified that correlate with an improved prognosis. Abstract Gliomas are differentiated into two major disease subtypes, astrocytoma or oligodendroglioma, which are then characterized as either IDH (isocitrate dehydrogenase)-wild type or IDH-mutant due to the dramatic differences in prognosis and overall survival. Here, we investigated the genetic background of IDH1-mutant gliomas using the Catalogue of Somatic Mutations in Cancer (COSMIC) database. In astrocytoma patients, we found that IDH1 is often co-mutated with TP53, ATRX, AMBRA1, PREX1, and NOTCH1, but not CHEK2, EGFR, PTEN, or the zinc finger transcription factor ZNF429. The majority of the mutations observed in these genes were further confirmed to be either drivers or pathogenic by the Cancer-Related Analysis of Variants Toolkit (CRAVAT). Gene expression analysis showed down-regulation of DRG2 and MSN expression, both of which promote cell proliferation and invasion. There was also significant over-expression of genes such as NDRG3 and KCNB1 in IDH1-mutant astrocytoma patients. We conclude that IDH1-mutant glioma is characterized by significant genetic changes that could contribute to a better prognosis in glioma patients.
Effect of including extra phenylazo moiety on the mesophase behaviour of three-ring azo/ester molecules

ABSTRACT Five homologous series of the four-ring 4-substituted phenylazo phenyl 4ʹ-(4ʹ-alkoxy phenylazo) benzoates (Ina–e) were prepared and their mesophase behaviour investigated by differential scanning calorimetry (DSC) and phases identified by polarised light microscopy (PLM). Compounds prepared were structurally characterised via infrared, 1H-NMR, mass spectroscopy, thermogravimetric and elemental analysis. Transition temperatures were first correlated with the alkoxy-chain length (n, that varies between 6, 8, 10, 14, and 16 carbons) within each homologous series, and again with the polarisability anisotropy (ΔαX) of the Ar-X bond, where X changes between CH3O, CH3, H, Br, and CN groups . Comparative studies were made to investigate the effect of introducing the extra phenyl azo moiety into the previously investigated three-ring compounds, 4-substituted phenyl 4′-(4″-alkoxyphenylazo) benzoates (IIna–e), 4-substituted phenylazo 4′-(4″- alkoxy phenyl) benzoates (IIIna–e), and 4-(4′-alkoxy phenylazo) phenyl 4″-substituted benzoates (IVna–e), each bear the same polar group, X, and the alkoxy group, n . Graphical Abstract
Overview of the Main Anti-SARS-CoV-2 Vaccines: Mechanism of Action, Efficacy and Safety

Abstract This review takes into consideration the principal vaccines developed against the SARS-CoV-2 in this unprecedented period of Covid-19 pandemic. We evaluated the mechanism of action of each vaccine as well as the efficacy, the safety and the storage temperature. In addition, the problem of the dose units, the vaccinal strategy, the activity of alternative compounds such as the monoclonal antibodies and especially the issue of the virus variants were also described in detail. Four vaccines are currently used in Italy: Pfizer-BioNTech mRNA BNT162b2 (Comirnaty) (USA), Moderna mRNA 1273 (USA), Astra-Zeneca ChAdOx1-S (recombinant) viral vector adenovirus belonging to Oxford (UK) and Pomezia (Italy), Janssen (two recombinant viral vector adenoviruses) belonging to Johnson & Johnson (USA). The efficacy of Pfizer and Moderna for preventing disease or severe disease results 95–87.5% and 94.5–100%, respectively. The efficacy of Astra-Zeneca and Janssen is about 70% and 65%, respectively; in the case of Janssen, it depends on the geographical area ranging from 72% to 57%. The problem of the administrated doses (one dose, two doses from the same vaccine or from different vaccines, half dose) is also discussed. The vaccination strategy based on the age group remains the simplest, most transparent and fair criterion. This strategy is also based on accelerating the administration of the vaccines, so that as many subjects as possible can be vaccinated quickly for achieving the “herd immunity”. The monoclonal antibodies appeared to be a valid solution for the treatment of Covid-19 disease. Two antibodies (bamlanivimab and etesevimab) have just been approved by the FDA. They could also be used for the infection by virus variants which represent a big problem due to their higher transmissibility and virulence and to their lower response to the vaccines.
Integrating Monitoring of Volume Status and Blood Volume-Controlled Ultrafiltration into Extracorporeal Kidney Replacement Therapy

Purpose Volume management in hemodialysis (HD) requires the ability to assess volume status objectively and determine treatment strategies that achieve euvolemia without compromising hemodynamic stability. The aim of this study was to compare dialysis with and without blood volume-controlled ultrafiltration (UF) in combination with body composition monitoring, and to evaluate indicators for adequate dialysis (Kt/V), ultrafiltration volume, fluid status, and the occurrence of intradialytic morbid events (IME). Patients and Methods Patients undergoing hemodialysis or on-line hemodiafiltration with support of a blood volume monitor (BVM) – a feedback control device integrated into the 5008 and 6008 HD systems – were enrolled. Patients received treatment for four weeks using the 6008 CAREsystem and the BVM (6008+). Data on dialysis dose (Kt/V), UF volume and predialysis fluid status were documented. This data was also documented retrospectively for four weeks with (5008+) and without (5008−) the use of the BVM with the 5008 system. Comparisons were analyzed using linear mixed models. Results Twenty-four patients were enrolled. Kt/V was unaffected by blood volume-controlled UF (5008− vs 5008+: p=0.230) and was equally achieved with both HD systems (5008+ vs 6008+: p=0.922). The UF volume and fluid status achieved were comparable, independent of the use of UF control with BVM (5008− vs 5008+; UF volume: p=0.166; fluid overload: p=0.390) or the HD system (5008+ vs 6008+: UF volume: p=0.003; fluid overload: p=0.838), except for UF volume being higher in the 6008+ phase. IMEs occurred in less than 3% of treatments, with no difference between study phases. Conclusion This study demonstrates that a clinical approach to kidney replacement therapy that tracks volume status and manages intradialytic fluid removal by blood volume-controlled UF delivers adequate dialysis without compromising fluid removal. It maintains volume status and ensures low incidence of IMEs.