Bio-imaging and serum analysis of zinc and other trace elements in a study of age-related diseases using inductively-coupled plasma mass spectrometry

Trace elements participate in numerous biological processes and understanding their activity is essential in monitoring various diseases. Zinc has long been recognized as a fundamental component of various tissues, being highly concentrated in the retina and an essential structural component of many proteins. It plays a crucial role in many biological activities including homeostasis, immune function, oxidative stress, and aging disorders. During aging, the systemic metabolism of iron, zinc and copper changes, and this disruption in metal homeostasis appears to be associated with age-related disorders such as Alzheimer s disease (AD) and Age related macular degeneration (AMD). As understanding the role of these metals is critical in finding the underlying causes for such diseases, and providing proper diagnosis and treatments, the distribution of these crucial elements in AD and AMD has been investigated. A rapid, accurate technique using sector field inductively coupled plasma mass spectrometry (SF-ICP-MS) was developed for the preparation and analysis of small volume (30 µl) biological samples. Analytical performance was evaluated using Serum UTAK certified reference material and the method was applied to Zn, Cu and Fe determination in 81 human serum samples from AD and AMD patients. No significant difference was found in Zn and Cu levels between AD and AMD patients, whereas Fe in AMD patients was slightly higher than AD patients. The results showed a decrease in serum Zn and Fe, and a notable increase in serum Cu in both AD and AMD patients compared to healthy controls. Elemental bio-imaging using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was successfully employed for Zn imaging in 12 rat retina sections given either a conventional or a Zn-containing diet. A new data processing method, involving fitting Gaussian peaks to individual LA-ICP-MS line scans, was established. The RPE/retina peak area ratio was used to evaluate the differences in Zn content between supplemented and non-supplemented rats. In general, the difference between the three differentially fed rat groups was not statistically significant for the relatively small group of twelve rats investigated here. Thickness of Zn bands was also found to vary between controls and supplemented rats. This technique has the potential to support biologists in recognising possible new biomarkers for disease, related to specific trace elements

ТЕМПЕРАТУРНОЕ ПОЛЕ ВЫХЛОПНЫХ ГАЗОВ АВТОМОБИЛЕЙ И РАСЧЁТЫ СТАТИСТИЧЕСКИХ СВЕДЕНИЙ

There are too many problems from the gases which constantly fly out from the exhaust pipes of cars and lorries, especially if this process takes place in the closed apartment (garage, laboratory, class, station of diagnostic or repair for transport systems with diesel or petrol engine). Practically all gases poison air, bring essentially injury to the health of people and for the all nature. Hitherto, many scientists affirm that gases create the negative hotbed effect in the atmosphere and influence to the appearance of the ozone holes. Some important experiments and investigations at the present day didn’t make.In this article there are several technical decisions not only how to decrease the negative influence of gases but the special calculations using personal computer and statistical information to describe the process by a chart.  Существует много проблем с газами, которые вылетают постоянно из выхлопных труб легковых автомобилей и грузовиков, особенно если имеет место этот процесс в закрытых помещениях (гараж, лаборатория, класс, станция диагностики или ремонта транспортных систем с дизельным или бензиновым двигателем). Практически все газы отравляют воздух, приносят существенный вред здоровью людей и всей природе. Поэтому многие учёные утверждают, что газы создают негативный парниковый эффект в атмосфере и влияют на появление озоновых дыр. Некоторые важные эксперименты и исследования в настоящее время сделаны.В этой статье есть несколько технических решений не только как уменьшить негативное влияние газов, но и специальные расчёты, используя персональный компьютер и статистическую информацию, чтобы описать процесс графически.

Mechanical and Spectroscopic Analysis of Retrieved/Failed Dental Implants

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A 70-W Asymmetrical Doherty Power Amplifier for 5G Base Stations

YesMuch attention has been paid to making 5G developments more en-ergy efficient, especially in view of the need for using high data rates with more complex modulation schemes within a limited bandwidth. The concept of the Doherty power amplifier for improving amplifier efficiency is explained in addi-tion to a case study of a 70W asymmetrical Doherty power Amplifier using two GaN HEMTs transistors with peak power ratings of 45W and 25W. The rationale for this choice of power ratio is discussed. The designed circuit works in the 3.4GHz frequency band with 200 MHz bandwidth. Rogers RO4350B substrate with dielectric constant εr=4.66 and thickness 0.035 mm is used. The perfor-mance analysis of the Doherty power amplifier is simulated using AWR MWO software. The simulated results showed that 54-64% drain efficiency has been achieved at 8 dB back-off within the specified bandwidth with an average gain of 10.7 dB

The T cell differentiation landscape is shaped by tumour mutations in lung cancer

Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours and whether this affects patient outcomes is unknown. Here, we paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated NSCLC to examine these relationships. TMB was associated with compartment-wide T cell differentiation skewing, characterized by loss of TCF7-expressing progenitor-like CD4 T cells, and an increased abundance of dysfunctional CD8 and CD4 T cell subsets with strong phenotypic and transcriptional similarity to neoantigen-reactive CD8 T cells. A gene signature of redistribution from progenitor-like to dysfunctional states was associated with poor survival in lung and other cancer cohorts. Single-cell characterization of these populations informs potential strategies for therapeutic manipulation in NSCLC

Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: a report of the international immuno-oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting