Miracle-dz/UniFAR-FTUs huggingface dataset:
Methotrexate-related central neurotoxicity: clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemia

Symptomatic methotrexate-related central neurotoxicity (MTX neurotoxicity) is a severe toxicity experienced during acute lymphoblastic leukemia (ALL) therapy with potential long-term neurologic complications. Risk factors and long-term outcomes require further study. We conducted a systematic, retrospective review of 1,251 consecutive Australian children enrolled on Berlin-Frankfurt-Münster or Children's Oncology Group-based protocols between 1998-2013. Clinical risk predictors for MTX neurotoxicity were analyzed using regression. A genome-wide association study (GWAS) was performed on 48 cases and 537 controls. The incidence of MTX neurotoxicity was 7.6% (n=95 of 1,251), at a median of 4 months from ALL diagnosis and 8 days after intravenous or intrathecal MTX. Grade 3 elevation of serum aspartate aminotransferase (P=0.005, odds ratio 2.31 [range, 1.28–4.16]) in induction/consolidation was associated with MTX neurotoxicity, after accounting for the only established risk factor, age ≥10 years. Cumulative incidence of CNS relapse was increased in children where intrathecal MTX was omitted following symptomatic MTX neurotoxicity (n=48) compared to where intrathecal MTX was continued throughout therapy (n=1,174) (P=0.047). Five-year central nervous system relapse-free survival was 89.2±4.6% when intrathecal MTX was ceased compared to 95.4±0.6% when intrathecal MTX was continued. Recurrence of MTX neurotoxicity was low (12.9%) for patients whose intrathecal MTX was continued after their first episode. The GWAS identified single-nucletide polymorphism associated with MTX neurotoxicity near genes regulating neuronal growth, neuronal differentiation and cytoskeletal organization (P<1x10-6). In conclusion, increased serum aspartate aminotransferase and age ≥10 years at diagnosis were independent risk factors for MTX neurotoxicity. Our data do not support cessation of intrathecal MTX after a first MTX neurotoxicity event.
Effect of liraglutide on neural and peripheral markers of metabolic function during antipsychotic treatment in rats

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that prevents metabolic side effects of the antipsychotic drugs (APDs) olanzapine and clozapine through unknown mechanisms. Aim: This study aimed to investigate the effect of chronic APD and liraglutide co-treatment on key neural and peripheral metabolic signals, and acute liraglutide co-treatment on clozapine-induced hyperglycaemia. Methods: In study 1, rats were administered olanzapine (2 mg/kg), clozapine (12 mg/kg), liraglutide (0.2 mg/kg), olanzapine + liraglutide co-treatment, clozapine + liraglutide co-treatment or vehicle for six weeks. Feeding efficiency was examined weekly. Examination of brain tissue (dorsal vagal complex (DVC) and mediobasal hypothalamus (MBH)), plasma metabolic hormones and peripheral (liver and kidney) cellular metabolism and oxidative stress was conducted. In study 2, rats were administered a single dose of clozapine (12 mg/kg), liraglutide (0.4 mg/kg), clozapine + liraglutide co-treatment or vehicle. Glucose tolerance and plasma hormone levels were assessed. Results: Liraglutide co-treatment prevented the time-dependent increase in feeding efficiency caused by olanzapine, which plateaued by six weeks. There was no effect of chronic treatment on melanocortinergic, GABAergic, glutamatergic or endocannabionoid markers in the MBH or DVC. Peripheral hormones and cellular metabolic markers were unaltered by chronic APD treatment. Acute liraglutide co-treatment was unable to prevent clozapine-induced hyperglycaemia, but it did alter catecholamine levels. Conclusion: The unexpected lack of change to central and peripheral markers following chronic treatment, despite the presence of weight gain, may reflect adaptive mechanisms. Further studies examining alterations across different time points are required to continue to elucidate the mechanisms underlying the benefits of liraglutide on APD-induced metabolic side effects.
Isolation, identification, and antimicrobial susceptibility pattern of Campylobacter jejuni and Campylobacter coli from cattle, goat, and chicken meats in Mekelle, Ethiopia

Campylobacter jejuni and Campylobacter coli are globally recognized as a major cause of bacterial foodborne gastroenteritis. A cross-sectional study was conducted from October 2015 to May 2016 in Mekelle city to isolate, identify, and estimate the prevalence of C. jejuni and C. coli in raw meat samples and to determine their antibiotic susceptibility pattern. A total of 384 raw meat samples were randomly collected from bovine (n = 210), goat (n = 108), and chicken (n = 66), and isolation and identification of Campylobacter spp. were performed using standard bacteriological techniques and PCR. Antibiotic susceptibility test was performed using disc diffusion method. Of the total 384 raw meat samples, 64 (16.67%) were found positive for Campylobacter spp. The highest prevalence of Campylobacter spp. was found in chicken meat (43.93%) followed by bovine meat (11.90%) and goat meat (9.25%). The most prevalent Campylobacter spp. isolated from meat samples was C. jejuni (81.25%). The overall prevalence of Campylobacter in restaurants, butcher shops, and abattoir was 43.93%, 18.30%, and 9.30%, respectively. 96.8%, 81.25%, 75%, and 71% of the Campylobacter spp. isolates were sensitive to norfloxacin, erythromycin, chloramphenicol, and sulphamethoxazole-trimethoprim, respectively. However, 96.9%, 85.9%, and 50% of the isolates were resistant to ampicillin, amoxicillin, and streptomycin, respectively. Strains that developed multi-drug resistant were 68.7%. The result of this study revealed the occurrence of Campylobacter in bovine, goat, and chicken meats. Hence, there is a chance of acquiring infection via consumption of raw or undercooked meat. Thus, implementation of hygienic practices from a slaughterhouse to the retailers, proper handling and cooking of foods of meat are very important in preventing Campylobacter infection.
Efficacy of copeptin in distinguishing COVID‐19 pneumonia from community‐acquired pneumonia

The clinical symptoms of community‐acquired pneumonia (CAP) and coronavirus disease 2019 (COVID‐19)‐associated pneumonia are similar. Effective predictive markers are needed to differentiate COVID‐19 pneumonia from CAP in the current pandemic conditions. Copeptin, a 39‐aminoacid glycopeptide, is a C‐terminal part of the precursor pre‐provasopressin (pre‐proAVP). The activation of the AVP system stimulates copeptin secretion in equimolar amounts with AVP. This study aims to determine serum copeptin levels in patients with CAP and COVID‐19 pneumonia and to analyze the power of copeptin in predicting COVID‐19 pneumonia. The study consists of 98 patients with COVID‐19 and 44 patients with CAP. The basic demographic and clinical data of all patients were recorded, and blood samples were collected. The receiver operating characteristic (ROC) curve was generated and the area under the ROC curve (AUC) was measured to evaluate the discriminative ability. Serum copeptin levels were significantly higher in COVID‐19 patients compared to CAP patients (10.2 ± 4.4 ng/ml and 7.1 ± 3.1 ng/ml; p < .001). Serum copeptin levels were positively correlated with leukocyte, neutrophil, and platelet count (r = −.21, p = .012; r = −.21, p = .013; r = −.20, p = .018; respectively). The multivariable logistic regression analysis revealed that increased copeptin (odds ratio [OR] = 1.183, 95% confidence interval [CI], 1.033–1.354; p = .015) and CK‐MB (OR = 1.052, 95% CI, 1.013–1.092; p = .008) levels and decreased leukocyte count (OR = 0.829, 95% CI, 0.730–0.940; p = .004) were independent predictors of COVID‐19 pneumonia. A cut‐off value of 6.83 ng/ml for copeptin predicted COVID‐19 with a sensitivity of 78% and a specificity of 73% (AUC: 0.764% 95 Cl: 0.671–0.856, p < .001). Copeptin could be a promising and useful biomarker to be used to distinguish COVID‐19 patients from CAP patients.
Association study between KCNQ1 and KCNQ1OT1 genetic polymorphisms and gastric cancer susceptibility and survival in a Chinese Han population: a case-control study

Background The present study analyzed gene polymorphisms in the potassium voltage-gated channel KQT-like subfamily member 1 (KCNQ1) and the long noncoding RNA, KCNQ1OT1, and their impacts on genetic susceptibility and survival in a Chinese Han population with gastric cancer (GC). Methods We designed a case-control study that included 681 patients with GC and 756 healthy controls. Three single-nucleotide polymorphisms (SNPs) in the KCNQ1 gene region and eight SNPs in the KCNQ1OT1 gene region were selected for further research. Results Among the 11 SNPs, we found no significant differences in the genotype and allele frequencies between GC patients and the healthy population. Hierarchical analysis by the log-additive model indicated that the KCNQ1 rs231348 CT genotype was significantly associated with an increased GC risk in individuals aged ≥55 years, regardless of gender. The KCNQ1OT1 rs231352 CC and rs7128926 AA genotypes increased the risk of GC in individuals with stage III/IV tumors larger than 5 cm in diameter. On evaluating the genotype polymorphism and survival analysis, we detected that the AA genotypes of the KCNQ1OT1 rs7128926 and rs7939976 polymorphisms presented a significant survival advantage over the GA/GG genotypes, especially in patients with the following characteristics: age >55, Helicobacter pylori infection, BMI >24, tumor in the non-cardia region with a diameter greater than 5 cm, clinical stage II, and postoperative adjuvant chemotherapy. Conclusions Our results suggest that the KCNQ1 rs231348 and KCNQ1OT1 rs231352 polymorphisms might be independent predictors of the risk of GC susceptibility depending on certain factors, such as the age of the individual and the tumor stage and diameter. Simultaneously, genotype polymorphism of the rs7128926 and rs7939976 loci of the KCNQ1OT1 gene independently predicted the recurrence-free survival (RFS) and overall survival (OS) of GC patients.
Rituximab in Myasthenia Gravis - Where do we stand?

ABSTRACT Introduction: Myasthenia gravis (MG) is an antibody-mediated disease with diverse serology and clinical presentation. Currently, MG is managed by untargeted immunomodulatory agents. About 15% patients are refractory to these therapies. Several novel and targeted treatments are on the horizon. Rituximab, a monoclonal antibody, is reported to be highly effective with widespread oof-label usage in MG, particularly in patients with antibody against muscle-specific kinase or refractory disease. However, a recent trial showed negative results. Compared to conventional oral immunosuppressive therapies used in MG, Rituximab has several benefits. Regular hematological monitoring is not required though serious side effects can occur. Current status of Rituximab in MG and newer immunosuppressants is discussed. Areas explored: Biologic features, clinical effectiveness, safety profile, and newer preparations of Rituximab. Expert opinion: Rituximab provides a promising option for management of MG, particularly in patients with muscle-specific kinase antibodies or those with refractory disease. Several knowledge gaps remain due to scarcity of data from randomized controlled studies. Despite lack of regulatory approval Rituximab has found widespread usage in MG. Large, well-designed studies are needed to assess the comparative efficacy of Rituximab and its optimal regimen in MG.
The New Hyperspectral Satellite PRISMA: Imagery for Forest Types Discrimination

Different forest types based on different tree species composition may have similar spectral signatures if observed with traditional multispectral satellite sensors. Hyperspectral imagery, with a more continuous representation of their spectral behavior may instead be used for their classification. The new hyperspectral Precursore IperSpettrale della Missione Applicativa (PRISMA) sensor, developed by the Italian Space Agency, is able to capture images in a continuum of 240 spectral bands ranging between 400 and 2500 nm, with a spectral resolution smaller than 12 nm. The new sensor can be employed for a large number of remote sensing applications, including forest types discrimination. In this study, we compared the capabilities of the new PRISMA sensor against the well-known Sentinel-2 Multi-Spectral Instrument (MSI) in recognition of different forest types through a pairwise separability analysis carried out in two study areas in Italy, using two different nomenclature systems and four separability metrics. The PRISMA hyperspectral sensor, compared to Sentinel-2 MSI, allowed for a better discrimination in all forest types, increasing the performance when the complexity of the nomenclature system also increased. PRISMA achieved an average improvement of 40% for the discrimination between two forest categories (coniferous vs. broadleaves) and of 102% in the discrimination between five forest types based on main tree species groups.
Long non-coding RNA LINC00997 silencing inhibits the progression and metastasis of colorectal cancer by sponging miR-512-3p

ABSTRACT We aimed to study the role of LINC00997 in the metastasis of colorectal cancer (CRC). LINC00997 and miR-512-3p expression in the primary colorectal cancer (NCRC) tissues and metastatic colorectal cancer (MCRC) tissues were detected using RT-qPCR. The Cancer Genome Atlas database was used to evaluate LINC00997 levels in the NCRC and MCRC tissues, and the correlations of LINC00997 expression with distant metastasis (M), regional lymph node metastasis (N), age and tumor stage were analyzed. Subsequently, RT-qPCR was performed to determine the expression of metastasis-related genes in MCRC tissues and analyze the correlation of LINC00997 or miR-512-3p level with the protein expression of metastasis-related genes. In vitro, LINC00997 expression in several CRC cell lines was examined. After LINC00997 silencing, cell invasion and migration were evaluated with Transwell and wound healing assays, respectively. The expression of metastasis- and EMT-related proteins was measured. Additionally, the potential interaction between LINC00997 and miR-512-3p was verified using a luciferase reporter assay. Rescue assays were conducted to clarify the regulatory effects of LINC00997 and miR-512-3p on CRC development. Results revealed that LINC00997 was frequently overexpressed in MCRC tissues, which was positively related to the tumor metastasis and stage. Additionally, LINC00997 was significantly elevated in CRC cells and LINC00997 silencing inhibited the invasion, migration and EMT of CRC cells, which was restored by miR-512-3p inhibitor. Luciferase reporter assay confirmed that LINC00997 could target miR-512-3p. In conclusion, LINC00997 regulated the metastasis of CRC by targeting miR-512-3p, providing some insights into the regulatory mechanism of CRC. Graphical Abstract
National Trends in US Otolaryngology Surgical Volume During the Early COVID-19 Pandemic.

National Trends in US Otolaryngology Surgical Volume During the Early COVID-19 Pandemic The coronavirus disease 2019 (COVID-19) pandemic resulted in tectonic shifts in the delivery of American health care, including surgical care. In the early days of the pandemic, the US Centers for Medicare & Medicaid Services (CMS) recommended that surgeons “postpone nonessential surgeries and other procedures,”1 a recommendation endorsed by the American Academy of Otolaryngology–Head and Neck Surgery. Emergency declarations by many states to suspend elective procedures resulted in an abrupt cessation of surgery in the US in March 2020.2 We sought to describe the resulting changes in US otolaryngology surgical volumes surrounding the COVID-19 pandemic.
Nonlinear electro-optical spectroscopy of liquid crystals possessing polar order

Electro-optical measurements of the second, third and fourth harmonic frequencies have been performed in prototype antiferroelectric liquid crystal materials: 4-(1-methyl-heptyloxycarbonyl) phenyl 4′-octyloxybiphenyl-4-carboxylate (MHPOBC) and 4-(1-methyl-heptyloxycarbonyl) phenyl 4-(4′-octyloxyphenylcarbonyloxy) benzoate (MHPOPB). These two substances possess a very rich sequence of phase transitions between various helical smectic subphases. The analysis of the observed anomalous behavior of the real and imaginary parts of the second, third and fourth harmonics of the electro-optical response spectra can serve for identification of various liquid crystalline phases. The anomalies of the nonlinear electro-optical response of the investigated liquid crystals have been compared with the linear electro-optical measurements.
The impact of outdoor air pollution on COVID-19: a review of evidence from in vitro, animal, and human studies

Studies have pointed out that air pollution may be a contributing factor to the coronavirus disease 2019 (COVID-19) pandemic. However, the specific links between air pollution and severe acute respiratory syndrome-coronavirus-2 infection remain unclear. Here we provide evidence from in vitro, animal and human studies from the existing literature. Epidemiological investigations have related various air pollutants to COVID-19 morbidity and mortality at the population level, however, those studies suffer from several limitations. Air pollution may be linked to an increase in COVID-19 severity and lethality through its impact on chronic diseases, such as cardiopulmonary diseases and diabetes. Experimental studies have shown that exposure to air pollution leads to a decreased immune response, thus facilitating viral penetration and replication. Viruses may persist in air through complex interactions with particles and gases depending on: 1) chemical composition; 2) electric charges of particles; and 3) meteorological conditions such as relative humidity, ultraviolet (UV) radiation and temperature. In addition, by reducing UV radiation, air pollutants may promote viral persistence in air and reduce vitamin D synthesis. Further epidemiological studies are needed to better estimate the impact of air pollution on COVID-19. In vitro and in vivo studies are also strongly needed, in particular to more precisely explore the particle–virus interaction in air. Our review highlights that both short- and long-term exposures to air pollution may be important aggravating factors for SARS-CoV-2 transmission and COVID-19 severity and lethality through multiple mechanisms https://bit.ly/395aS9w
HDL Particle Subspecies and Their Association With Incident Type 2 Diabetes: The PREVEND Study

Abstract Context High-density lipoproteins (HDL) may be protective against type 2 diabetes (T2D) development, but HDL particles vary in size and function, which could lead to differential associations with incident T2D. A newly developed nuclear magnetic resonance (NMR)-derived algorithm provides concentrations for 7 HDL subspecies. Objective We aimed to investigate the association of HDL particle subspecies with incident T2D in the general population. Methods Among 4828 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline, HDL subspecies with increasing size from H1P to H7P were measured by NMR (LP4 algorithm of the Vantera NMR platform). Results A total of 265 individuals developed T2D (median follow-up of 7.3 years). In Cox regression models, HDL size and H4P (hazard ratio [HR] per 1 SD increase 0.83 [95% CI, 0.69-0.99] and 0.85 [95% CI, 0.75-0.95], respectively) were inversely associated with incident T2D, after adjustment for relevant covariates. In contrast, levels of H2P were positively associated with incident T2D (HR 1.15 [95% CI, 1.01-1.32]). In secondary analyses, associations with large HDL particles and H6P were modified by body mass index (BMI) in such a way that they were particularly associated with a lower risk of incident T2D, in subjects with BMI < 30 kg/m2. Conclusion Greater HDL size and lower levels of H4P were associated with a lower risk, whereas higher levels of H2P were associated with a higher risk of developing T2D. In addition, large HDL particles and H6P were inversely associated with T2D in nonobese subjects.
Reduced frequencies and functional impairment of dendritic cell subsets and non-classical monocytes in myelodysplastic syndromes

In myelodysplastic syndromes (MDS) the immune system is involved in pathogenesis as well as in disease progression. Dendritic cells (DC) are key players of the immune system by serving as regulators of immune responses. Their function has been scarcely studied in MDS and most of the reported studies didn’t investigate naturally occurring DC subsets. Therefore, we here examined the frequency and function of DC subsets and slan+ non-classical monocytes in various MDS risk groups. Frequencies of DC as well as of slan+ monocytes were decreased in MDS bone marrow compared to normal bone marrow samples. Transcriptional profiling revealed down-regulation of transcripts related to pro-inflammatory pathways in MDS-derived cells as compared to normal bone marrow. Additionally, their capacity to induce T-cell proliferation was impaired. Multidimensional mass cytometry showed that whereas healthy donor-derived slan+ monocytes supported Th1/Th17/Treg differentiation/expansion their MDS-derived counterparts also mediated substantial Th2 expansion. Our findings point to a role for an impaired ability of DC subsets to adequately respond to cellular stress and DNA damage in the immune escape and progression of MDS. As such, it paves the way toward potential novel immunotherapeutic interventions.