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Author(s): P. Ramachandran [sup.1] , R. Dobie [sup.1] , J. R. Wilson-Kanamori [sup.1] , E. F. Dora [sup.1] , B. E. P. Henderson [sup.1] , N. T. Luu [sup.2] [sup.3] [...], Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2.sup.+CD9.sup.+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1.sup.+ and PLVAP.sup.+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFR[alpha].sup.+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis. Single-cell RNA sequencing is used to characterize and compare the functional diversity of cells from liver biopsies of human scarred and normal liver, and identifies markers for scar-associated macrophages and endothelial cells.

The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune‐mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGβ1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ1 is a novel strategy to improve the anti‐inflammatory efficacy of MSCs. [ABSTRACT FROM AUTHOR]

Objective: YouTube has become the preferred resource for trainees to learn and prepare for surgical cases. This study evaluated the educational quality of YouTube videos detailing thyroidectomy and parathyroidectomy. Method: YouTube was systematically searched using 11 terms related to thyroidectomy and parathyroidectomy. Four independent clinical reviewers assessed the videos using Laparoscopic Surgery Video Educational Guidelines as well as modified Laparoscopic Surgery Video Educational Guidelines subgroup tools. Results: Sixty-five videos were identified and evaluated. Overall Laparoscopic Surgery Video Educational Guidelines score was 8.58 ± 3.85 (mean subgroup score, 5.67 ± 2.40). Twenty-eight of 65, 25 of 65 and 12 of 65 videos were deemed medium, low and high quality, respectively. Inter-rater reliability was good for both attending surgeons and residents. Presence of audio or visual commentary had a positive correlation with total Laparoscopic Surgery Video Educational Guidelines scores (R2=0.38). Videos produced by otolaryngologists and US-based physicians scored higher on total scores compared to non-otolaryngology and non-US based physicians. Conclusion: Some YouTube videos on thyroidectomy and parathyroidectomy exhibit high educational value. Future efforts should increase the number of high-quality YouTube videos containing both audio and visual commentary or create an online repository of videos for medical students and residents to augment their surgical training. [ABSTRACT FROM AUTHOR]

In order to address optimization problems, artificial intelligence (AI) is employed in the construction industry, which aids in the growth and popularization of AI. This study utilizes a Hybrid algorithm called Adaptive Selection Slime Mold Algorithm (ASSMA), which combines the Tournament Selection (TS) and Slime Mould Algorithm (SMA) to address the four-factor optimization problem in projects. This combination will improve the original algorithm's performance, speed up result finding and achieve good convergence via Pareto Front. Hence, efficient resource management must be comprehended in order to optimize the time, cost, quality and environmental impact trade-off (TCQE). Case studies are used to illustrate the capabilities of the new model, and ASSMA results are compared to those of the data envelopment analysis (DEA) method used by the previous researcher. To improve the suggested model's superiority and effectiveness, it is compared to the multiple-target swarm algorithm (MOPSO), multi-objective artificial bee colony (MOABC) and non-dominant sort genetic algorithm (NSGA-II). Based on the overall results, it is clear that the ASSMA model illustrates diversification and offers a robust and convincing optimal solution for readers to understand the potential of the proposed model.

Ngày nay, các nguồn năng lượng tái tạo đang được sử dụng rộng rãi trên thế giới và ở Việt Nam, không chỉ trong khai thác để phục vụ sản xuất điện năng nhằm giảm sử dụng năng lượng hóa thạch và ô nhiễm môi trường mà còn là một giải pháp để quảng bá nhằm thúc đẩy và nâng cao ý thức của con người trong việc sử dụng năng lượng xanh, sạch và hiệu quả tiết kiệm. Do vậy, trong bài báo này, nhóm tác giả đã đưa ra mô hình thiết kế, kết nối các nguồn tái tạo cũng như ứng dụng phần mềm để kiểm tra kết cấu, ổn định đồng thời tính toán, lựa chọn, chế tạo và lắp đặt một cây năng lượng bao gồm nguồn điện gió và mặt trời trong thực tế, nhằm phục vụ cho mục đích công cộng và quảng bá du lịch cho thành phố Đà Nẵng.

Bicyclo[1.1.1]pentanes (BCP's) have been applied in medicinal chemistry as bioisosteres for phenyl groups. In pursuit of novel BCP analogs, we reported the first synthesis of 2,2‐difluorobicyclo[1.1.1]pentanes (BCP–F2) in 2019. Herein, we detail the extension of our effort in the synthesis of BCP‐F2 analogs. [ABSTRACT FROM AUTHOR]

Abstract This study presents the Slime Mold Algorithm (SMA) to solve the time—cost—quality trade-off problem in a construction project. The proposed SMA is a flexible and efficient algorithm in exploration and exploitation to reach the best optimal solution to process the input model’s data. This paper aims to discuss and solve the optimization problem and compare the evaluation with other algorithms such as Opposition-based Multiple Objective Differential Evolution, Non-dominated sorting genetic algorithm, Multiple objective particle swarm optimization, Multiple objective differential evolution and Chaotic initialized multiple objective differential evolution (CAMODE) to verify the efficiency and potential of the proposed algorithm. According to the analysis results, the SMA model generated a diversification measure for case studies, producing superior outcomes to those of previous algorithms.

The purpose of this research study is to solve a four-objective optimization problem in the construction industry using a hybrid model that combines the slime mould algorithm (SMA) with opposition-based learning. This hybrid model is known as the adaptive opposition slime mould algorithm (AOSMA). Two typical construction projects have introduced time, cost, quality, and safety trade-off (TCQS), which are the factors that have the greatest influence on the completion of a construction project and are represented by optimal results and obtained at Pareto, in order to better illustrate the potential of the proposed model. In order to compare AOSMA with a nondominated sorting genetic algorithm III (NSGA III), multiobjective particle swarm optimization (MOPSO), LHS-based NSGA III, and a hybrid model of MAWA (MAWA-TLBO, MAWA-GA, MAWA-AS, and MAWA-ACS-SGPU) and to assess the model’s potential and viability, performance evaluation indexes are applied. To assist project managers in planning time, cost, quality, and safety for construction investment projects, this study creates a hybrid model.

Intensive maize cultivation in the uplands of North-west Vietnam has resulted in soil erosion leading to reduced maize yields along with negative impacts downstream. Despite the introduction of sustainable agricultural technologies over many years, adoption rates are low mostly due to their incompatibility with existing farming systems and lack of secure markets for alternative crops. In addition, the temporary nature of development programmes and limited capacity of government extension systems have resulted in limited spread of technology, and where they have been introduced, unable to secure long-lasting commitments from farmers. In this study, we explore an alternative model involving maize value chain actors for attaining more durable transition towards sustainable maize farming systems. We find maize traders operating at lower levels of the value chain with active engagement with the farming community to be best suited for engaging in technology dissemination. While their involvement may require additional incentives and oversight from the government it is imperative that support for commercialization through promising market links are established to achieve a more meaningful shift towards sustainable farming methods.

Allogeneic natural killer (aNK) cell adoptive therapy has the potential to dramatically impact clinical outcomes of glioblastoma multiforme (GBM). However, in order to exert therapeutic activity, NK cells require tumor expression of ligands for activating receptors, such as MHC Class I peptide A/B (MICA/B) and ULBPs. Here, we describe the use of a blood–brain barrier (BBB) permissive supramolecular cationic drug vehicle comprising an inhibitor of the chaperone heat shock protein 90 (Hsp90), which sustains a cytotoxic effect on GBM cells, boosts the expression of MICA/B and ULBPs on the residual population, and augments the activity of clinical-grade aNK cells (GTA002). First, we identify Hsp90 mRNA transcription and gain of function as significantly upregulated in GBM compared to other central nervous system tumors. Through a rational chemical design, we optimize a radicicol supramolecular prodrug containing cationic excipients, SCI-101, which displays >2-fold increase in relative BBB penetration compared to less cationic formulations in organoids, in vitro. Using 2D and 3D biological models, we confirm SCI-101 sustains GBM cytotoxicity 72 h after drug removal and induces cell surface MICA/B protein and ULBP mRNA up to 200% in residual tumor cells compared to the naked drug alone without augmenting the shedding of MICA/B, in vitro. Finally, we generate and test the sequential administration of SCI-101 with a clinical aNK cell therapy, GTA002, differentiated and expanded from healthy umbilical cord blood CD34+ hematopoietic stem cells. Using a longitudinal in vitro model, we demonstrate >350% relative cell killing is achieved in SCI-101–treated cell lines compared to vehicle controls. In summary, these data provide a first-of-its-kind BBB-penetrating, long-acting inhibitor of Hsp90 with monotherapy efficacy, which improves response to aNK cells and thus may rapidly alter the treatment paradigm for patients with GBM.

Aims: Understanding of the perceived stress and coping strategies adopted by people is important for contemplating the consequences of a pandemic on mental health of people globally. In this study, we intended to assess the perceived stress status under quarantine/isolation globally during the COVID-19 pandemic.Methods: This is a multicentre, multinational cross-sectional study that recruited isolated/quarantined individuals suspected or confirmed to have COVID-19 to assess the psychological impact of the quarantine/isolation experience by answering a survey distributed online.Results: The study was conducted across 63 participating countries, gaining 1,871 valid responses. There was a higher proportion of female participants in the Moderate to High Perceived Stress Scores (MH-PSS) group compared to the Low Perceived Stress Score group (66.0 vs. 52.0%) and a higher proportion of individuals whose marital status was single had MH-PSS (57.1%). Also, individual's religion (Christian, Hindu, and Muslim), no formal education level, being exposed to a confirmed or suspected COVID-19 patient, being forced to be quarantined/isolated, uncomfortable feeling during quarantine period may significantly increase the risk of MH-PSS (p < 0.05).Conclusions: Many factors can predict stress in COVID-19 pandemic including female sex, being single, religion, no formal education, involuntary quarantine, location and reason of quarantine/isolation, and place of exposure.

Mục đích chính của bài báo nhằm cung cấp thông tin về hiện trạng chất lượng nước biển, trầm tích thông qua hai đợt khảo sát năm 2017 - 2018 ở 24 điểm thu mẫu trong quần đảo Nam Du. Kết quả nghiên cứu cho thấy hàm lượng tương đối thấp các các thông số dinh dưỡng (NO2-, NO3-, NH4+, PO43-) ghi nhận được tại các trạm quan trắc và chỉ số RQtt được tính bởi các thông số này đang ở ngưỡng an toàn về môi trường. Hàm lượng cyanide (CN-) trong nước biển dao động từ 0,96 đến 2,01µg/L trong khi hàm lượng kim loại nặng (Cd, As, Pb) dao động từ hàm lượng vết đến 0,09 µg/L; từ 2,5 đến 3,8 µg/L; từ 0,28 đến 1,78 µg/L; tương ứng. Nhìn chung, Các giá trị đo được ở mức dưới ngưỡng cho phép theo QCVN 10-MT:2015/BTNMT. Hàm lượng nitơ tổng (Nts) trong trầm tích dao động từ 39,2 đến 367,6 mg/kg trong khi hàm lượng photpho tổng (Pts) dao động từ 5,7 đến 39,4 mg/kg. Thành phần carbon hữu cơ dao động từ 0,29 đến 1,05%. Kết quả của nghiên cứu phục vụ cho việc bảo tồn và phát triển nguồn lợi rong biển tại đảo Nam Du.