Notes

Simple Approach to Reading through any Radiograph inside the Neonate.
The development of high-throughput drug screening (HTS) using primary cultures provides a promising, clinically translatable approach to tailoring treatment strategies for patients with cancer. However, this has been challenging for solid tumors because of often limited amounts of tissue available. In most cases, in vitro expansion is required before HTS, which may lead to overgrowth and contamination by non-neoplastic cells.

In this study, hematoxylin and eosin staining and immunohistochemical staining were performed on 129 cytopathology cases from 95 patients. These cytopathology cases comprised cell block preparations derived from primary tumor specimens or patient-derived xenografts as part of a pediatric precision oncology trial. Cytopathology cases were compared with the morphology and immunohistochemical staining profile of the original tumor. Cases were reported as tumor cells present, equivocal, or tumor cells absent. The HTS results from cytopathologically validated cultures were incorporated into a multidisciplinary tumor board report issued to the treating clinician to guide clinical decision making.

On cytopathologic examination, tumor cells were present in 77 of 129 cases (60%) and were absent in 38 of 129 cases (29%), whereas 14 of 129 cases (11%) were equivocal. Cultures that contained tumor cells resembled the tumors from which they were derived.

Cytopathologic examination of tumor cell block preparations is feasible and provides detailed morphologic characterization. Cytopathologic examination is essential for ensuring that samples submitted for HTS contain representative tumor cells and that in vitro drug sensitivity data are clinically translatable.
Cytopathologic examination of tumor cell block preparations is feasible and provides detailed morphologic characterization. Cytopathologic examination is essential for ensuring that samples submitted for HTS contain representative tumor cells and that in vitro drug sensitivity data are clinically translatable.
The estimate of people with clinical Alzheimer's disease (AD) and mild cognitive impairment provides an understanding of the disease burden.

We estimated people with cognitive impairment using a quasibinomial regression model in 10,342 participants with cognitive test scores.

The 2020 US Census-adjusted prevalence of clinical AD was 11.3% (95% confidence interval [CI]=10.7-11.9) 10.0% among non-Hispanic Whites, 14.0% among Hispanics, and 18.6% among non-Hispanic Blacks. We estimate that in 2020, 6.07 (95% CI=5.75-6.38) million people were living with clinical AD, which increases to 13.85 (95% CI=12.98-14.74) million in 2060, 423% higher among Hispanics, 192% higher among Blacks, and 63% higher among Whites. However, there are predicted to be more significant increases in later years among those over 85 and women compared to men.

The number of people with clinical AD will increase as the "baby boom" generation reaches older ages, exerting a strong upward influence on disease burden.
The number of people with clinical AD will increase as the "baby boom" generation reaches older ages, exerting a strong upward influence on disease burden.
Sarcopenia is a prevalent condition in elderly patients and has been associated with adverse outcomes following transcatheter aortic valve replacement (TAVR). The present study aimed to determine the predictive value of serum creatinine-cystatin C ratio, that is, "Sarcopenia Index" (SI) as a surrogate marker of sarcopenia, and investigate its association with clinical outcomes after TAVR.

We conducted a retrospective observational study of patients undergoing TAVR between January, 2016 and December, 2018 at Hospital Italiano de Buenos Aires, Argentina. Patients were excluded if <65-years old, presented previous surgical aortic valve replacement, severe chronic kidney disease, or hemodialysis requirement. The SI was obtained at baseline before TAVR. All-cause mortality and/or readmissions for congestive heart failure (CHF) were defined as the primary endpoint.

In total 100 patients met inclusion criteria for the purpose of the study. Sarcopenia Index was significantly correlated with Timed Up and Go (r=-0.272, p=.010) and Gait Speed (r=-0.278, p=.005). During follow-up, 5/100 patients died within 30 days and a total of 10/100 patients died at 1-year follow-up. Moreover, survival curves were significantly worse (Log-rank test=p=.02) and CHF readmissions were more prevalent in the lowest SI tertile (Log-rank test=p=.01). In multivariate Cox regression analysis, we identified low SI (cutoff ≤66) as an independent predictor of long-term adverse outcomes (HR=4.01, 95% CI=1.31-12.27, p=.015) at 1-year follow-up.

Sarcopenia Index, surrogate for the degree of skeletal muscle mass (SMM), could be used as a predictor of adverse outcomes in patients undergoing TAVR.
Sarcopenia Index, surrogate for the degree of skeletal muscle mass (SMM), could be used as a predictor of adverse outcomes in patients undergoing TAVR.
Generalized myasthenia gravis (gMG) is an autoimmune disease that causes disabling weakness via damage to the neuromuscular junction. In most patients, the disease is mediated by autoantibodies to the acetylcholine receptor, which activate the complement cascade. Our objective was to analyze response profiles in adult patients with anti-acetylcholine receptor antibody-positive refractory gMG treated with eculizumab-a terminal complement inhibitor-in the REGAIN study or its open-label extension (OLE).

We retrospectively analyzed Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores recorded during REGAIN and its OLE. Early/late responses were defined as improvement in MG-ADL score (≥3 points) or QMG score (≥5 points) at ≤12 or >12weeks, respectively, after eculizumab initiation.

The analysis included 98 patients. By Week 12 and conclusion of the OLE, MG-ADL response had been achieved at some point by 67.3% and 84.7% of patients, respectively, and QMG response by 56.1% and 71.4%, respectively. Response was observed over multiple consecutive assessments for most patients. At Week 130, the least-squares mean percentage changes (95% CI) from baseline in MG-ADL score were -61.9% (-69.9%, -53.9%) and -47.5% (-59.0%, -36.0%) in early and late MG-ADL responders, respectively; the least-squares mean percentage changes from baseline in QMG score were -40.8% (-48.3%, -33.4%) and -55.5% (-68.4%, -42.7%) in early and late QMG responders, respectively.

The findings suggest that, although most patients with refractory gMG will achieve clinical response by Week 12 of eculizumab treatment, first responses can be observed with longer-term treatment.
The findings suggest that, although most patients with refractory gMG will achieve clinical response by Week 12 of eculizumab treatment, first responses can be observed with longer-term treatment.Meta-analytic structural equation modeling (MASEM) refers to fitting structural equation models (SEMs) (such as path models or factor models) to meta-analytic data. Currently, fitting MASEMs may be challenging for researchers that are not accustomed to working with R software and packages. Therefore, we developed webMASEM; a web application for MASEM. This app implements the one-stage MASEM approach, and allows users to apply MASEM in a user-friendly way. The aim of this article is to provide a tutorial on one-stage MASEM and a practical guide to webMASEM. We will pay specific attention to how the data should be structured and prepared for webMASEM, because mistakes in this step may lead to faulty results without receiving an error message. The use of webMASEM is illustrated with an analysis of a meta-analytic path model in which the path coefficients are moderated by a study-level variable, a meta-analytic factor model in which the factor loadings are moderated by a study-level variable, and a meta-analytic panel model in which the effects are moderated by a study-level variable. All used datafiles and R scripts are available online.Both single-cell RNA sequencing (scRNAseq) and single-nucleus RNA sequencing (snRNAseq) can be used to characterize the transcriptional profile of individual cells, and based on these transcriptional profiles, help define cell type distribution in mixed cell populations. However, scRNAseq analyses are confounded if some of the cells are large (>50 µm) or if some of cells adhere more tightly to some adjacent cells than to others. Further, single cell isolation for scRNAseq requires fresh tissue, which may not be available for human or animal model tissues. Additionally, the current enzymatic and mechanical methods for single-cell dissociation can lead to stress-induced transcriptional artifacts. Nuclei for snRNAseq, on the other hand, can be isolated from any cell, regardless of size, and from either fresh or frozen tissues, and compared to whole cells, they are more resistant to mechanical pressures and appear not to exhibit as many cell isolation-based transcriptional artifacts. Here, we describe a time- and cost-effective procedure to isolate nuclei from mammalian cells and tissues. The protocol incorporates steps to mechanically disrupt samples to release nuclei. Compared to conventional nuclei isolation protocols, the approach described here increases overall efficiency, eliminates risk of contaminant exposure, and reduces volumes of expensive reagents. A series of RNA quality control checks are also incorporated to ensure success and reduce costs of subsequent snRNAseq experiments. Nuclei isolated by this procedure can be separated on the 10× Genomics Chromium system for either snRNAseq and/or Single-Nucleus ATAC-Seq (snATAC-Seq), and is also compatible with other single cell platforms. © 2021 Wiley Periodicals LLC. Basic Protocol 1 Sample preparation and quality control check via RNA Isolation and Analysis Basic Protocol 2 Nuclei Isolation.Several life-threatening diseases, also known as 'Channelopathies' are linked to irregularities in ion transport proteins. Significant research efforts have fostered the development of artificial transport systems that facilitates to restore the functions of impaired natural transport proteins. Indeed, a few of these artificial ionophores demonstrate the rare combination of transmembrane ion transport and important biological activity, offering early promises of suitability in 'channel replacement therapy'. In this review, structural facets and functions of both cationophores and anionophores are discussed. Ionophores that are toxic to various bacteria and yeast, could be exploited as antimicrobial agent. Nevertheless, few non-toxic ionophores offer the likelihood of treating a wide range of genetic diseases caused by the gene mutations. In addition, their ability to disrupt cellular homeostasis and to alter lysosomal pH endow ionophores as promising candidates for cancer treatment. Overall, critically outlining the advances in artificial ionophores in terms of in vitro ion transport, possible modes of action and biological activities enables us to propose possible future roadmaps in this research area.Orofacial granulomatosis (OFG) is a rare disorder with varied etiological, immunological and infectious mechanisms implicated and is believed to be a umbrella term which includes Melkersson Rosethal syndrome (MRS). We describe a 17 year old female who was diagnosed with OFG and was successfully treated with a combination of minocycline and clofazimine without oral steroids with significant improvement within 1 month of therapy.
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