Tag: pubmed

Mult Scler Relat Disord. 2022 Feb 8;59:103682. doi: 10.1016/j.msard.2022.103682. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine anti-SARS-Cov2 antibodies and T-cell immunity in convalescent people with multiple sclerosis (pwMS) and/or pwMS vaccinated against Covid-19, depending on the disease modifying therapy, and in comparison to healthy controls (HC).

METHODS: 75 participants were enrolled: Group 1-29 (38.7%) COVID-19 convalescent participants; Group 2-34 (45.3%) COVID-19 vaccinated; Group 3-12 (16.0%) COVID-19 convalescent participants who were later vaccinated against COVID-19. Cellular immunity was evaluated by determination of number of CD4+ and CD8+ cells secreting TNFα, IFNγ, and IL2 after stimulation with SARS-CoV-2 peptides.

RESULTS: pwMS treated with ocrelizumab were less likely to develop humoral immunity after COVID-19 recovery or vaccination. No difference was observed in the cellular immunity in all studied parameters between pwMS treated with ocrelizumab compared to HC or pwMS who were treatment naïve or on first line therapies. These findings were consistent in convalescent, vaccinated, and convalescent+vaccinated participants. COVID-19 vaccinated convalescent pwMS on ocrelizumab compared to COVID-19 convalescent HC who were vaccinated did not show statistically difference in the rate of seroconversion nor titers of SARS-CoV-2 antibodies.

CONCLUSION: Presence of cellular immunity in pwMS on B-cell depleting therapies is reassuring, as at least partial protection from more severe COVID-19 outcomes can be expected.

PMID:35158189 | DOI:10.1016/j.msard.2022.103682

Epilepsy Behav. 2022 Feb 11;128:108586. doi: 10.1016/j.yebeh.2022.108586. Online ahead of print.

ABSTRACT

OBJECTIVE: Developmental and epileptic encephalopathies (DEE) entail moderate to profound communication and other impairments that are poorly measured by typical clinical outcomes assessments (COA). We examined the potential of alternative approaches, specifically, the use of raw scores and COAs outside of their intended age ranges.

METHODS: In a cross-sectional survey, 120 parents of children with Dravet Syndrome, Lennox-Gastaut syndrome, KCNQ2-DEE, KCNB1-DEE, and SCN2A-DEE (ages 1-35 years) completed the Adaptive Behavior Assessment System-3 for ages 0-5 years, modified checklist for autism (mCHAT), communication and social behavior scales (CSBS), communication matrix (CM), and several parent-reported classifiers of communication. Adaptive Behavior Assessment System communication and social raw scores were the primary and adjunctive outcomes. Floor and ceiling effects, dispersion and convergence with related measures were assessed with appropriate parametric and nonparametric statistical techniques.

RESULTS: Median chronological age (CA) was 8.7 years (Interquartile range (IQR): 5.3-13.5). Adaptive Behavior Assessment Systemcommunication and social age equivalents were 12.5 months (IQR 7.5-28) and 16.5 months (IQR 9-31). Most raw scores corresponded to standardized scores indicating performance <3 standard deviations below the general population mean. Adaptive Behavior Assessment System raw scores demonstrated minimal floor and ceiling effects (<1-2.5%). In linear regression models, scores correlated with age under 6 years (communication, p = 0.001; social, p = 0.003) but significantly flattened out thereafter. Scores varied substantially by DEE group (both p < 0.001) and decreased with higher convulsive seizure frequency (communication, p = 0.01, social, p = 0.02). There was good convergence with mCHAT, CSBS, and CM scores (all r > 0.8).

SIGNIFICANCE: Raw scores and out-of-range COAs may provide measures that are sensitive at the very limited levels of functioning typical of profoundly impaired, older patients with DEEs. To ensure that targeted trial outcomes are responsive to meaningful change, development of these approaches will be essential to clinical trial readiness for novel therapies for rare DEEs.

PMID:35158285 | DOI:10.1016/j.yebeh.2022.108586

J Pharm Biomed Anal. 2022 Feb 8;212:114630. doi: 10.1016/j.jpba.2022.114630. Online ahead of print.

ABSTRACT

A sensitive and selective Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for the identification and quantification of two potential genotoxic impurities (PGIs) – viz. methyl N-((2′-(1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-N-nitroso-L-valinate (PGI-1) and N-nitroso Valsartan (PGI-2) – in the angiotensin II receptor blocker valsartan. Among these impurities, PGI-1 is a distinctive compound which has never been reported. For this, chromatographic separation was performed using a Waters XBridge BEH C18 column (150 mm × 4.6 mm, 2.5 µm), with ammonium acetate aqueous solution (0.01 mol/L) as mobile phase A and acetonitrile as mobile phase B, in a gradient elution mode at a 0.5 mL/min flow rate. Mass spectrometric conditions were optimized using electrospray ionization (ESI) in positive mode. Following the International Conference of Harmonization (ICH) guidelines, this methodology is capable of quantifying 2 PGIs at 0.016 ppm in samples at 50 mg/mL concentration. This validated approach presented good linearity over the concentration range of 0.016-0.06 ppm for 2 PGIs. The correlation coefficient of each impurity was observed greater than 0.999. The accuracy of this method was in the range of 83-113% for the aforementioned PGIs. In addition, expert knowledge rules (Derek-based) and statistical (Q) SAR evaluation system (Sarah-based) were used to evaluate and classify the genotoxicity of both valsartan-related PGIs as well as to define their standard limits. The predicted results were positive and classified into the third category, and the total nitrosamine limit was set to 0.03 ppm. As such, this approach represents a good quality control system for the simultaneous and precise quantitation of PGIs in valsartan.

PMID:35158183 | DOI:10.1016/j.jpba.2022.114630

Neural Netw. 2022 Feb 4;148:232-253. doi: 10.1016/j.neunet.2022.01.017. Online ahead of print.

ABSTRACT

We consider restricted Boltzmann machine (RBMs) trained over an unstructured dataset made of blurred copies of definite but unavailable “archetypes” and we show that there exists a critical sample size beyond which the RBM can learn archetypes, namely the machine can successfully play as a generative model or as a classifier, according to the operational routine. In general, assessing a critical sample size (possibly in relation to the quality of the dataset) is still an open problem in machine learning. Here, restricting to the random theory, where shallow networks suffice and the “grandmother-cell” scenario is correct, we leverage the formal equivalence between RBMs and Hopfield networks, to obtain a phase diagram for both the neural architectures which highlights regions, in the space of the control parameters (i.e., number of archetypes, number of neurons, size and quality of the training set), where learning can be accomplished. Our investigations are led by analytical methods based on the statistical-mechanics of disordered systems and results are further corroborated by extensive Monte Carlo simulations.

PMID:35158159 | DOI:10.1016/j.neunet.2022.01.017

Breast. 2022 Feb 8;62:114-122. doi: 10.1016/j.breast.2022.02.002. Online ahead of print.

ABSTRACT

BACKGROUND: The quantitative relationship between HER2 copy number and prognosis in HER2 positive adjuvant setting remain controversial, and few studies have focused on adjuvant setting to illustrate the potential clinical relevance of HER2 in cfDNA. Our study aim to develop a novel method in HER2 quantification and explore the relationship between HER2 copy number in primary tumors or cfDNA and prognosis in HER2 positive early breast cancer.

METHODS: Two hundred and two patients with early breast cancer were prospectively included in a study where primary tumors, matching non-cancer breast tissue, corresponding plasma, and the plasma from 20 healthy volunteers were collected. Cox proportional hazard analysis was employed to determine the prognostic value of HER2 gene copy number in tissue and cfDNA. Tissue based nomograms and time-dependent decision curve analysis were used to evaluate the practicality of HER2 copy number stratification.

RESULTS: HER2 amplification by CNVplex demonstrated a robust concordance with FISH (concordance 89.2%). A three-tiered system of tissue and a two-tiered system of cfDNA classification were shown to be independent prognostic factors. A tissue copy number-based nomogram was fitted and further evaluation revealed a good performance in discrimination (c statistic 0.801) and calibration.

CONCLUSIONS: We first report CNVplex as a viable alternative for HER2 detection. Quantitative evaluation of HER2 presents tremendous potential for use in risk stratification. We also uncover the potential for using HER2 copy number in cfDNA as a biomarker for prognosis in a HER2 positive adjuvant setting.

PMID:35158152 | DOI:10.1016/j.breast.2022.02.002

Int J Med Inform. 2022 Feb 7;160:104714. doi: 10.1016/j.ijmedinf.2022.104714. Online ahead of print.

ABSTRACT

Histopathology reports are a primary data source for the case definition phase of a Cancer Registry. By reading the histopathology report, the operator that evaluates an oncology case can define the morphology and topography of cancer, and validate the case with the highest diagnosis base. The key problem of the Catania-Messina-Enna Integrated Cancer Registry (RTI) is that these reports are written in natural language and relevant information for cancer evaluation is only a little part of the total annual histopathological reports. In this population-based retrospective cohort study, we try to optimize the working time spent by the RTI operators in seeking and selecting the right information among the histopathology reports in the east Sicily population, by developing a binary classifier on a training set of labeled historical data and validating its outcome by a test set of labeled data created by the operators during the years. Using a machine learning algorithm we built a classification model that evaluates each free text report and returns a score that indicates the probability that it contains oncologic relevant information. The best performing algorithm, among the eight analyzed in this study, was the LightGBM that reached an F1-Score of 98.9%. Using the chosen classifier we shortened the time for case evaluation, improving the timeliness of cancer statistics.

PMID:35158153 | DOI:10.1016/j.ijmedinf.2022.104714

J Stroke Cerebrovasc Dis. 2022 Feb 11;31(4):106347. doi: 10.1016/j.jstrokecerebrovasdis.2022.106347. Online ahead of print.

ABSTRACT

PURPOSE: Anticoagulation (AC) is the main preventive strategy for ischemic stroke in atrial fibrillation (AF) patients. We aim to investigate the association of prior AC with thrombus composition and clinical outcome in AF patients with acute ischemic stroke (AIS).

MATERIALS AND METHODS: From January 2019 to December 2020, consecutive AIS patients with AF treated with mechanical thrombectomy (MT) in our center were included in this analysis. Retrieved thrombi were stained with hematoxylin and eosin (H&E) and Martius Scarlet blue (MSB). The relative fractions of red blood cell (RBC), white blood cell (WBC), fibrin, and platelet were quantitatively analyzed. Procedural and clinical outcomes were compared between patients with and without prior AC.

RESULTS: A total of 133 patients were enrolled in this study, with 39 in AC group and 94 in non-AC (NAC) group. Thrombi in AC group contained more fibrins (36% vs 20%, p<0.001), more platelets (36% vs 24%, p<0.001) and fewer RBCs (25% vs 54%, p<0.001). No difference was detected in terms of successful recanalization evaluated with modified Thrombolysis in Cerebral Infarction scale (mTICI 2b-3, 97% vs 86%, p=0.065), functional independence at 90 days with modified Rankin Score (mRS 0-2, 44% vs 33%, p=0.246).

CONCLUSION: Thrombi retrieved from AF patients with prior AC contained more fibrins, more platelets and fewer RBCs compared with those of NAC patients. A trend of higher successful reperfusion rate was observed in AC patients but failed to reach statistical significance.

PMID:35158148 | DOI:10.1016/j.jstrokecerebrovasdis.2022.106347

Cancer Treat Rev. 2022 Feb 7;104:102355. doi: 10.1016/j.ctrv.2022.102355. Online ahead of print.

ABSTRACT

Neuroblastoma survivors have an increased risk of unfavorable long-term health outcomes, of which developing subsequent neoplasms is one of the most serious. We aimed to provide an overview of the current knowledge on the risk of subsequent neoplasms in neuroblastoma survivors. We conducted a systematic literature search in Medline/Pubmed (01-01-1945-13-01-2022) to identify studies that reported on ≥ 100 neuroblastoma survivors and assessed subsequent neoplasms as an outcome. We identified 410 potentially eligible articles, of which we eventually included 13 reports. All articles described retrospective cohorts with sizes varying from 145 to 5,987 neuroblastoma survivors. Within these cohorts 0.7% – 17.2% of the survivors developed a subsequent neoplasm. A wide variety of types of subsequent malignant and non-malignant neoplasms were observed, of which thyroid carcinoma and acute myeloid leukemia were most frequently reported. The risk of developing a subsequent neoplasm was 2.8 to 10.4 times higher in neuroblastoma survivors than in the general population. Although no statistically significant risk factors for subsequent neoplasms were observed in multivariable analyses, high-risk group survivors, women and those treated with radiotherapy seemed to have a higher risk. In conclusion, the studies in this systematic review consistently show that neuroblastoma survivors are at elevated risk of developing subsequent neoplasms. Future research should further explore risk factors for subsequent neoplasms in neuroblastoma survivors, so future treatment protocols and follow-up care can be improved.

PMID:35158111 | DOI:10.1016/j.ctrv.2022.102355

Nurse Educ Today. 2022 Feb 8;111:105298. doi: 10.1016/j.nedt.2022.105298. Online ahead of print.

ABSTRACT

BACKGROUND: Although students are well prepared theoretically, they lack real-life practical skills because they have not faced an adequate number of emergencies such as neonatal resuscitation.

OBJECTIVES: This study was conducted with the objective of determining the impact of integrating serious game simulation (SGS) into neonatal resuscitation training on the neonatal resuscitation related knowledge, skills, satisfaction with training, and self confidence in learning of nursing students.

DESIGN: The study is a randomized controlled, pre-test post-test design and single-blind study.

SETTINGS AND PARTICIPANTS: This study was conducted on 90 undergraduate nursing students (SGS based training group = 45, control group = 45) enrolled in the fifth semester at the Faculty of Nursing.

METHODS: The students were allocated with simple randomization method to intervention and control groups. The training program prepared on the basis of neonatal resuscitation algorithm used a neonatal resuscitation serious game simulation method. At the same time, the serious game simulation method was used as a pre-test and post-test skill assessment tool. Support was obtained from a statistician in evaluation of the data and the data were analyzed using the SPSS (Statistical Package for Social Sciences) for Windows 25.0 program.

RESULTS: Post-test measurements indicated a statistically significant positive difference in the ventilation and chest compression performing skills of the intervention group compared to the control group (p = .011, p = .020, respectively). A considerable increase was found in the knowledge and skills level of both groups, after the neonatal resuscitation training (p < .05). The score averages of the Student Satisfaction and Self-Confidence in Learning Scale and its sub-dimensions were high for both groups.

CONCLUSIONS: It was concluded that the serious game simulation application used in neonatal resuscitation training was effective in raising the students’ ventilation and compression performing skills.

PMID:35158135 | DOI:10.1016/j.nedt.2022.105298

Chem Asian J. 2022 Feb 14. doi: 10.1002/asia.202200076. Online ahead of print.

ABSTRACT

A halogenated bowl-shaped guest, corannulene, was encapsulated in a cylindrical host, [4]cyclochrysenylene, to form a bowl-in-tube complex, which mimicked supramolecular complexes between bowl guests and carbon nanotubes. As was the case with carbon nanotubes, the cylindrical space of [4]cyclochrysenylene trapped multiple corannulene molecules in an array, and 1:2 complexes were commonly obtained with the corannulene guests with various halogen substituents (F, Cl, Br and I). Careful statistical analyses of isothermal titration calorimetry titration data succeeded in revealing the stoichiometry, and the molecular structures of the 1:2 complexes were further clarified by X-ray crystallographic analyses. Two fluorinated corannulene guests were stacked perpendicular to the cylinder axis, while two chlorinated guests were stacked with inclined orientations. The structural difference resulted in a large difference in the cooperativity of the two-stage association in solution: fluorinated corannulene guests showed negative cooperativity for the 1:2 complexation, and the other, larger halogenated corannulene guests showed positive cooperativity.

PMID:35156775 | DOI:10.1002/asia.202200076