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Classical swine fever virus (CSFV) identification has witnessed significant advancements with the development of rapid reverse‐transcription loop‐mediated isothermal amplification (RT‐LAMP) assays. However, conventional RT‐LAMP assays for CSFV diagnosis are hindered by a laborious RNA extraction step. Moreover, the need for thermal incubators and expensive micropipettes has limited their application in field settings. Addressing these challenges, our study presents a groundbreaking solution—an electro‐free and point‐of‐care (POC) tool known as the field‐LAMP assay—for the rapid clinical detection of CSFV. By eliminating the RNA extraction requirement, advancing the colorimetric read‐out and lyophilized reaction reagents, our field‐LAMP assay streamlines the diagnostic process, saving valuable time and effort. This novel approach also overcomes the dependency on electric‐dependent thermal incubators and expensive micropipettes, making it practical and accessible for use in the field. The successful development of the field‐LAMP assay marks a significant milestone in CSFV detection. This electro‐free and POC tool offers several advantages, including its ability to deliver rapid results without compromising accuracy, facilitating prompt response and containment measures. [ABSTRACT FROM AUTHOR]

Michelle Cheng,1,* Samantha Ho,1,* Jun Hwan Yoo,1,2,* Deanna Hoang-Yen Tran,1,* Kyriaki Bakirtzi,1 Bowei Su,1 Diana Hoang-Ngoc Tran,1 Yuzu Kubota,1 Ryan Ichikawa,1 Hon Wai Koon1 1Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Republic of Korea *These authors share co-first authorship Background: Cathelicidin (LL-37 in humans and mCRAMP in mice) represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT) of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the human colonic CCD-18Co fibroblasts promoted human colon cancer HT-29 cell proliferation. Cathelicidin pretreatment inhibited colon cancer cell proliferation mediated by media conditioned by human colonic CCD-18Co fibroblasts. Cathelicidin disrupted tubulin distribution in colonic fibroblasts. Disruption of tubulin in fibroblasts reduced fibroblast-supported colon cancer cell proliferation. Conclusion: Cathelicidin effectively inhibits colon cancer development by interfering with EMT and fibroblast-supported colon cancer cell proliferation. Keywords: colon cancer, epithelial–mesenchymal transition, fibroblasts

CONTEXT: Patients often combine prescription medications with herbal and dietary substances (herein referred to as herbal medicines). A variety of potential adverse herb-drug interactions exist based on the pharmacological properties of herbal and prescription medications. OBJECTIVE: To determine the incidence of potential and observed adverse herb-drug interactions in patients using herbal medicines with prescription medications. DESIGN: Consecutive patients were questioned about their use of herbal medicines in 6 outpatient clinics. Patients reporting use of these products provided a list of their prescription medications, which were reviewed for any potential adverse herb-drug interactions using a comprehensive natural medicine database. Any potential adverse herb-drug interactions prompted a review of the patient's chart for evidence of an observed adverse herb-drug interaction. MAIN OUTCOME MEASURE: The rate of potential and observed adverse herb-drug interactions. RESULTS: Eight hundred four patients were surveyed, and 122 (15%) used herbal medicines. Eighty-five potential adverse herb-drug interactions were found in 49 patients (40% of herbal medicine users). Twelve possible adverse herb-drug interactions in 8 patients (7% of herbal medicine users) were observed. In all 12 cases, the severity scores were rated as mild, including 8 cases of hypoglycemia in diabetics taking nopal (prickly pear cactus). CONCLUSIONS: A substantial number of potential adverse herb-drug interactions were detected and a small number of adverse herb-drug interactions observed, particularly in diabetics taking nopal. Screening for herbal medicine usage in 804 patients did not uncover any serious adverse interactions with prescription medications. [ABSTRACT FROM AUTHOR]

Purpose/background: Despite the growing use of bioabsorbable mesh in ventral hernia repairs (VHR), the evidence of its impact on patient outcomes remains limited. This study aims to investigate the efficacy and safety profile of poly-4-hydroxybutyrate (P4HB) mesh for ventral hernia repair through a systematic review and meta-analysis., Methods: A literature search of five databases (PubMed, Embase, Ovid, Medline, and Google Scholar) produced a list of publications that analyzed the use of P4HB mesh in ventral hernia repair in both clean and contaminated cases. The primary postoperative outcomes of hernia recurrence, surgical site infections (SSI), and any complications were analyzed through a pooled meta-analysis., Results: In our systematic review, 21 studies met the inclusion criteria with a total of 1858 patients (933 males and 925 females) and an average age of 56.8 years. The median follow-up ranged from 1.6 to 62.3 months. In our meta-analysis, the use of P4HB mesh in VHR in proportion of events demonstrated a recurrence rate of 9% [6%; 15%], SSI of 10% [6%; 16%] and 35% [9%; 42%] for rate of any complications. Sub-meta-analysis restricted to studies with follow up > 18 months continues to show low rates of recurrence of 9% (95%CI, 4-17%), SSI of 9% (95%CI, 4-16%), and 31% (95%CI, 23-41%) for any complications., Conclusion: Our study demonstrates that the use of P4HB mesh is both safe and effective in ventral hernia repairs. When further analyzed past 18 months, the time where P4HB mesh fully resorbs, the rates of hernia recurrence, SSI, and any complications remain low of upwards of 5 years and comparable to the rates seen in synthetic and biologics in similar patient populations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Purine nucleotides are vital for RNA and DNA synthesis, signaling, metabolism, and energy homeostasis. To synthesize purines, cells use two principal routes: the de novo and salvage pathways. Traditionally, it is believed that proliferating cells predominantly rely on de novo synthesis, whereas differentiated tissues favor the salvage pathway. Unexpectedly, we find that adenine and inosine are the most effective circulating precursors for supplying purine nucleotides to tissues and tumors, while hypoxanthine is rapidly catabolized and poorly salvaged in vivo. Quantitative metabolic analysis demonstrates comparative contribution from de novo synthesis and salvage pathways in maintaining purine nucleotide pools in tumors. Notably, feeding mice nucleotides accelerates tumor growth, while inhibiting purine salvage slows down tumor progression, revealing a crucial role of the salvage pathway in tumor metabolism. These findings provide fundamental insights into how normal tissues and tumors maintain purine nucleotides and highlight the significance of purine salvage in cancer., Competing Interests: Declaration of interests R.J.D. is an advisor for Agios Pharmaceuticals and Vida Ventures. S.J.M. is an advisor for Frequency Therapeutics and Protein Fluidics, as well as a stockholder in G1 Therapeutics and Mereo Biopharma. H.Z. has a sponsored research agreement with Alnylam Pharmaceuticals, consults for Flagship Pioneering and Chroma Medicines, and serves on the SAB of Ubiquitix. J.B. is an employee/paid consultant for Arrowhead, Calithera, Esai, Exelixis, and Johnson & Johnson and reports receiving commercial research grants from Arrowhead., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Metastatic uveal melanoma (mUM) is a difficult to treat disease. The liver is the primary site of metastasis in most patients, though uveal melanoma spreads widely in advanced disease. The only FDA approved immunotherapy medication for metastatic uveal melanoma is the HLA-A02:01 restricted bispecific T cell engager drug, Tebentafusp. Checkpoint inhibitor strategies and combination approaches have been tried with some limited success. We describe our experience treating patients at the University of Minnesota., Methods: Patients were included if they had biopsy-confirmed mUM. Twenty-five (25) patients meeting the criteria were identified. Medical records were reviewed and data extracted for patient baseline characteristics and response to treatments., Results: Median time to metastasis from the time of local therapy to the eye was 14.2 months (IQR; 9.3-22.0), and first site of metastasis was liver in 92% of patients. Two patients (8%) did not receive systemic therapy or radiation therapy for metastatic disease. Twenty-three (92%) patients received systemic therapy, 13 patients (52%) received ipilimumab-nivolumab as the first-line, while 4 patients (16%) received pembrolizumab. Landmark survival analysis by receipt of systemic therapy and radiation therapy treatments within 6 months of biopsy confirmed diagnosis is shown. Twenty patients (80%) received systemic therapy within 6 months of mUM diagnosis. Thirteen patients (52%) received liver directed radiation therapy within 6 months of mUM diagnosis., Discussion: Within our cohort, there was no overall survival benefit for patients receiving treatment of metastatic disease within 6 months of mUM diagnosis, versus those electing later or no treatment at all. There was remarkable clinical activity of ipilimumab and nivolumab in a subset of patients with mUM, in agreement with prior studies, and metastatic PD-L1 positive tumors were associated with a prolonged survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tran, Shanley, Giubellino, Tang, Koozekanani, Yuan, Dusenbery and Domingo-Musibay.)

Identification of somatic mutations (SMs) is essential for characterizing cancer genomes. While DNA-seq is the prevalent method for identifying SMs, RNA-seq provides an alternative strategy to discover tumor mutations in the transcribed genome. Here, we have developed a machine learning based pipeline to discover SMs based on RNA-seq data (designated as RNA-SMs). Subsequently, we have conducted a pan-cancer analysis to systematically identify RNA-SMs from over 8,000 tumors in The Cancer Genome Atlas (TCGA). In this way, we have identified over 105,000 novel SMs that had not been reported in previous TCGA studies. These novel SMs have significant clinical implications in designing targeted therapy for improved patient outcomes. Further, we have combined the SMs identified by both RNA-seq and DNA-seq analyses to depict an updated mutational landscape across 32 cancer types. This new online SM atlas, OncoDB ( https://oncodb.org ), offers a more complete view of gene mutations that underline the development and progression of various cancers., (© 2024. The Author(s).)

Drought is considered the most severe water-related disaster in the Cauto river basin, which is the longest river and the main agricultural producer in Cuba. Better understanding of drought characteristics is crucial to drought management. Given the sparsity of ground-based precipitation observations in the Cauto, this study aims at using gridded global precipitation to analyze the spatio-temporal variations of drought in this river basin. Firstly, the monthly Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS) was calibrated with the gauged precipitation using the Thiessen polygon-based method and linear least squares regression equations. Then, the gridded standardized precipitation index (SPI) with time scales of 3, 6, 9 months and drought characteristics, namely, drought frequency, duration and intensity were calculated using the calibrated CHIRPS. Finally, the spatio-temporal analysis was performed to investigate the variations of drought in the Cauto river basin in time and space. The obtained results show that the calibrated CHIRPS is highly consistent with the gauged observations and is capable of determining the magnitude, time, and spatial extent of drought events in the Cauto river basin. The trend analysis by the Mann-Kendall test reveals that although the trend is not statistically significant, the SPI tends to decrease with time in the dry season, which indicates the more severe drought. The spatial analysis indicates that the lower altitude area of the Cauto river basin is suffered from longer drought duration and higher drought intensity than the upper one. This study expresses the importance of open global precipitation data sources in monitoring and quantifying drought characteristics in data-scarce regions., (© 2024. The Author(s).)

Surveillance of the SARS-CoV-2 genome has become a crucial technique in the management of COVID-19, aiding the pandemic response and supporting effective public health interventions. Typically, whole-genomic sequencing is used along with PCR-based target enrichment techniques to identify SARS-CoV-2 variants, which is a complicated and time-consuming process that requires central laboratory facilities. Thus, there is an urgent need to develop rapid and cost-effective tools for precise on-site detection and identification of SARS-CoV-2 strains. In this study, we demonstrate the rapid diagnosis of COVID-19 and identification of SARS-CoV-2 variants by amplification and sequencing of the entire SARS-CoV-2 S gene using isothermal enzymatic recombinase amplification combined with the advanced Oxford nanopore sequencing technique. The entire procedure, from sampling to sequencing, takes less than 8 hours and can be performed with limited resources. The newly developed method has noteworthy implications for examining the transmission dynamics of the virus, detecting novel genetic variants, and assessing the effect of mutations on diagnostic approaches, antiviral treatments, and vaccines., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Bone marrow vascular endothelial cells (BM EC) regulate multiple myeloma pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating multiple myeloma. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote multiple myeloma growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in multiple myeloma-supportive ECs. Expression of ephrin B2 (EFNB2), the binding partner for EPHB1 and EPHB4, was significantly increased in multiple myeloma cells. Silencing EPHB1 or EPHB4 in ECs suppressed multiple myeloma growth in coculture. Similarly, loss of EFNB2 in multiple myeloma cells blocked multiple myeloma proliferation and survival in vitro, abrogated multiple myeloma engraftment in immune-deficient mice, and increased multiple myeloma sensitivity to chemotherapy. Administration of an EFNB2-targeted single-chain variable fragment also suppressed multiple myeloma growth in vivo. In contrast, overexpression of EFNB2 in multiple myeloma cells increased STAT5 activation, increased multiple myeloma cell survival and proliferation, and decreased multiple myeloma sensitivity to chemotherapy. Conversely, expression of mutant EFNB2 lacking reverse signaling capacity in multiple myeloma cells increased multiple myeloma cell death and sensitivity to chemotherapy and abolished multiple myeloma growth in vivo. Complementary analysis of multiple myeloma patient data revealed that increased EFNB2 expression is associated with adverse-risk disease and decreased survival. This study suggests that EFNB2 reverse signaling controls multiple myeloma pathogenesis and can be therapeutically targeted to improve multiple myeloma outcomes., Significance: Ephrin B2 reverse signaling mediated by endothelial cells directly regulates multiple myeloma progression and treatment resistance, which can be overcome through targeted inhibition of ephrin B2 to abolish myeloma., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: To explore optimal feedback methodologies to enhance trainee skill acquisition in simulated surgical bimanual skills learning during brain tumor resections., Hypotheses: (1) Providing feedback results in better learning outcomes in teaching surgical technical skill when compared to practice alone with no tailored performance feedback. (2) Providing more visual and visuospatial feedback results in better learning outcomes when compared to providing numerical feedback., Design: A prospective 4-parallel-arm randomized controlled trial., Setting: Neurosurgical Simulation and Artificial Intelligence Learning Centre, McGill University, Canada., Participants: Medical students (n = 120) from 4 Quebec medical schools., Results: Participants completed a virtually simulated tumor resection task 5 times while receiving 1 of 4 feedback based on their group allocation: (1) practice-alone without feedback, (2) numerical feedback, (3) visual feedback, and (4) visuospatial feedback. Outcome measures were participants' scores on 14-performance metrics and the number of expert benchmarks achieved during each task. There were no significant differences in the first task which determined baseline performance. A statistically significant interaction between feedback allocation and task repetition was found on the number of benchmarks achieved, F (10.558, 408.257)=3.220, p < 0.001. Participants in all feedback groups significantly improved their performance compared to baseline. The visual feedback group achieved significantly higher number of benchmarks than the practice-alone group by the third repetition of the task, p = 0.005, 95%CI [0.42 3.25]. Visual feedback and visuospatial feedback improved performance significantly by the second repetition of the task, p = 0.016, 95%CI [0.19 2.71] and p = 0.003, 95%CI [0.4 2.57], respectively., Conclusion: Simulations with autonomous visual computer assistance may be effective pedagogical tools in teaching bimanual operative skills via visual and visuospatial feedback information delivery., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Neurosurgeons treat nonfunctioning pituitary adenomas by surgical resection. Based on the adherence of the tumor to the normal pituitary gland, operative risks may include hormone replacement therapy for postoperative hypopituitarism with gross total resection that injures the gland or recurrent tumor with subtotal resection and purposeful avoidance of gland manipulation. None of the patients presented in this article had a preoperative preference regarding extent of resection. This study aimed to evaluate postoperative patient preferences regarding extent of resection., Methods: Adult patients who underwent resection of adenomas between 2015 and 2023 were retrospectively reviewed and surveyed. After surgery, participating patients were asked for their preference regarding 100% tumor resection with lifelong daily hormone replacement therapy versus 90% tumor resection with a chance of recurrence in the hypothetical situation where the neurosurgeon encounters tumor adherent to the normal gland., Results: Of the 73 patients included, 54 (74.0%) responded to the survey, with the majority (36 [66.7%]) preferring 90% resection with the chance of tumor recurrence. Tumor recurrence (odds ratio 2.3, 95% confidence interval 2.1-2.5, P = 0.03) and steroid avoidance (odds ratio 2.2, 95% confidence interval 2.0-2.4, P = 0.04) were the 2 variables that were significant predictors of patient preference in multivariate regression analysis., Conclusions: Although patients may not have the preoperative insight or experience to have a strong conviction regarding the extent of adenoma resection, the consequences following surgery clearly influence their preference. Most patients in our study, including patients with gross total resection and especially patients who experienced side effects of steroid therapy, preferred subtotal resection with the chance of tumor recurrence over hormone replacement therapy., (Published by Elsevier Inc.)

Objectives: This study aims to determine the malnutrition status among Vietnamese patients newly diagnosed with gastric cancer (GC)., Background: GC remains the top rank of common and deadly diseases. With limited clinical manifestation, most GC patients were diagnosed at late stages when tumor is not radically resected. Malnutrition was associated with poor prognosis of GC, such as prolonged hospitalization, limited treatment efficacy and low survival rate., Methods: The cross-sectional descriptive study recruited 77 patients newly diagnosed with GC and 90 healthy individuals (HC). The data used for this study were approved by the local Ethical Committee. The data were analysed on STATA 14.0 and GraphPad Prism 8.0., Results: We observed the male dominant distribution in GC cohort and over 65% of GC were firstly diagnosed at advanced stages (III and IV). Anemia was detected in about 50% of GC patients. Hyponutrition was prevalent in newly diagnosed GC. We found the decreased tendency of anemia related indexes from HC to early stages (I and II) and advanced stages (III and IV) of GC patients., Conclusion: Anemia and hypoproteinemia occurred frequently among Vietnamese newly diagnosed GC. The nutrition therapy would benefit GC patients (Tab. 4, Fig. 4, Ref. 20).

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening., Competing Interests: VN VTCN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN HTN is affiliated with Gene Solutions. The author has no other competing interests to declare, ND NNTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TMQP is affiliated with Gene Solutions. The author has no other competing interests to declare, GN GTHN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN TDN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTTT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV, TP, TJ, VN, HN, TN, QD, TD, AT, VN, VN, LH, QT, TP, TH, BN, TN, TN, DP, BP, TV, TN, TT, MT, NT, TL, TT, MD, HB, VK, TP, DT, TL, TP, ML, VC, TD No competing interests declared, TN THHN is affiliated with Gene Solutions. The author has no other competing interests to declare, LH LAKH is affiliated with Gene Solutions. The author has no other competing interests to declare, TT THT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV DHV is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TMTT is affiliated with Gene Solutions. The author has no other competing interests to declare, MN MNN is affiliated with Gene Solutions. The author has no other competing interests to declare, TV TTVV is affiliated with Gene Solutions. The author has no other competing interests to declare, AN ANN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTT is affiliated with Gene Solutions. The author has no other competing interests to declare, VT VUT is affiliated with Gene Solutions. The author has no other competing interests to declare, ML MPL is affiliated with Gene Solutions. The author has no other competing interests to declare, TD TTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TVP is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HDN is affiliated with Gene Solutions. The author has no other competing interests to declare, DN DSN holds equity in Gene Solutions.DSN is affiliated with Gene Solutions. The author has no other competing interests to declare, DT DKT is affiliated with Gene Solutions. The author has no other competing interests to declare, HT HST is affiliated with Gene Solutions. The author has no other competing interests to declare, HG HG holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HG who is inventor on the patent application (USPTO 17930705).HG is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HNN holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HNN who is inventor on the patent application (USPTO 17930705).HNN is affiliated with Gene Solutions. The author has no other competing interests to declare, MP MDP holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for MDP who is inventor on the patent application (USPTO 17930705).MDP is affiliated with Gene Solutions. The author has no other competing interests to declare, LT LST holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for LST who is inventor on the patent application (USPTO 17930705).LST is affiliated with Gene Solutions. The author has no other competing interests to declare, (© 2023, Nguyen, Nguyen et al.)

Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family of receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib suppressed SARS-CoV-2 entry and later stages of the viral life cycle and showed synergistic effect with the direct-acting antiviral nirmatrelvir. We discovered that ErbB1, ErbB2, and ErbB4 bind SARS-CoV-2 S1 protein and regulate viral and ACE2 internalization, and they are required for VEEV infection. In human lung organoids, lapatinib protected from SARS-CoV-2-induced activation of ErbB-regulated pathways implicated in non-infectious lung injury, proinflammatory cytokine production, and epithelial barrier injury. Lapatinib suppressed VEEV replication, cytokine production, and disruption of blood-brain barrier integrity in microfluidics-based human neurovascular units, and reduced mortality in a lethal infection murine model. We validated lapatinib-mediated inhibition of ErbB activity as an important mechanism of antiviral action. These findings reveal regulation of viral replication, inflammation, and tissue injury via ErbBs and establish a proof of principle for a repurposed, ErbB-targeted approach to combat emerging viruses.

In Vietnam, colorectal cancer is one of the top diagnosed cancers, with 5-10% originating from inherited mutations. This study aims to define the mutation spectrum associated with hereditary colorectal cancer syndromes (HCCS) in Vietnam, evaluate the influence of genetic testing on carriers' awareness, and also investigate the barriers in familial testing. Genetic test reports were collected to identify HCCS cases, then cases underwent a survey investigating self-risk and familial-risk awareness, proactive cancer screening, and familial testing barriers. Participant characteristics, mutation prevalence, and results from the survey were descriptively analyzed and reported. Of all genetic test results, 3% (49/1632) were identified with mutations related to HCCS. Over 77% of them belonged to Lynch syndrome. PMS2 appeared to be the gene with the highest mutation frequency, while MLH1 was the lowest. 44% of cases further undertook cancer screening tests, and 48% of cases' families had uptake genetic testing. The biggest barrier of familial members for not taking genetic test was psychological reasons (fear, not being interested, or not feeling necessary). This study provided new evidence for HCCS mutation spectrum in Vietnamese population and the success in promoting cascade test in high-risk family members through financial and technical support. Also, study has suggested the needs of an innovative genetic testing process focusing on the quality of pre-and post-test consultancy, an increase in follow-ups, and the change in policy for permission of contacting relatives directly to improve the rate of cascade testing and proactive cancer screening., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Neoantigen-based immunotherapy has emerged as a promising strategy for improving the life expectancy of cancer patients. This therapeutic approach heavily relies on accurate identification of cancer mutations using DNA sequencing (DNAseq) data. However, current workflows tend to provide a large number of neoantigen candidates, of which only a limited number elicit efficient and immunogenic T-cell responses suitable for downstream clinical evaluation. To overcome this limitation and increase the number of high-quality immunogenic neoantigens, we propose integrating RNA sequencing (RNAseq) data into the mutation identification step in the neoantigen prediction workflow., Methods: In this study, we characterize the mutation profiles identified from DNAseq and/or RNAseq data in tumor tissues of 25 patients with colorectal cancer (CRC). Immunogenicity was then validated by ELISpot assay using long synthesis peptides (sLP)., Results: We detected only 22.4% of variants shared between the two methods. In contrast, RNAseq-derived variants displayed unique features of affinity and immunogenicity. We further established that neoantigen candidates identified by RNAseq data significantly increased the number of highly immunogenic neoantigens (confirmed by ELISpot) that would otherwise be overlooked if relying solely on DNAseq data., Discussion: This integrative approach holds great potential for improving the selection of neoantigens for personalized cancer immunotherapy, ultimately leading to enhanced treatment outcomes and improved survival rates for cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nguyen, Tran, Nguyen, Nguyen, Pham, Nguyen, Tran, Nguyen, Tran, Pham, Le, Phan, Giang, Nguyen and Tran.)

This paper investigates the security-reliability of simultaneous wireless information and power transfer (SWIPT)-assisted amplify-and-forward (AF) full-duplex (FD) relay networks. In practice, an AF-FD relay harvests energy from the source (S) using the power-splitting (PS) protocol. We propose an analysis of the related reliability and security by deriving closed-form formulas for outage probability (OP) and intercept probability (IP). The next contribution of this research is an asymptotic analysis of OP and IP, which was generated to obtain more insight into important system parameters. We validate the analytical formulas and analyze the impact on the key system parameters using Monte Carlo simulations. Finally, we propose a deep learning network (DNN) with minimal computation complexity and great accuracy for OP and IP predictions. The effects of the system's primary parameters on OP and IP are examined and described, along with the numerical data.

Background: After an intensive care unit (ICU) admission, nearly 20% of survivors of chronic critical illness require admission to a long-term acute care hospital (LTACH) for continued subspecialty care. The effect of the burden of medical comorbidities on discharge disposition after LTACH admission remains unclear., Methods: A retrospective cohort study was performed involving patients with chronic critical illness who were discharged from the medical ICU and admitted to an LTACH between 2016 and 2018. The patients' Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Nutrition Risk in the Critically Ill (NUTRIC), and Charlson Comorbidity Index (CCI) scores at the time of LTACH admission were calculated from electronic medical records. The mean scores on each instrument were compared by discharge disposition., Results: A total of 156 patients were admitted to the LTACH from the medical ICU between 2016 and 2018. They had a mean (SD) age of 61.5 (13.3) years, a mean (SD) body mass index of 28.1 (8.3), a median (IQR) ICU stay of 16.3 (1-108) days, and a median (IQR) LTACH stay of 38.2 (1-227) days. Patients who were discharged home had lower mean (SD) APACHE II (14.6 [5.0] vs 18.2 [5.4], P = .01), SOFA (3.3 [2.1] vs 4.6 [2.1], P = .03), NUTRIC (3.3 [1.4] vs 4.6 [1.4], P = .001), and CCI (4.3 [2.5] vs 6.1 [2.8], P = .02) scores on admission to the LTACH than those who were not discharged home., Conclusion: Severity-of-illness scores on admission to an LTACH can be used to predict patients' likelihood of being discharged home., (©2023 American Association of Critical-Care Nurses.)

Crosstalk between hormones and secondary metabolites regulates the interactions between plants and stress. However, little is known about the effects of hormone crosstalk on the concentration of flavonoids in seeds. In this study, we identified abscisic acid (ABA) as a negative regulator of flavonoid accumulation in soybean seeds under drought-stress conditions. Alterations in flavonoid accumulation at several intensities of water stress, followed by a recovery period, were measured during the soybean seed-filling stage. Low soil moisture (SM 10%) significantly decreased the total flavonoid content in seeds. The decline in flavonoid content was proportional to the severity of drought stress and was dependent on the activities of phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), two key phenylpropanoid pathway enzymes. The expression of phenylalanine ammonia-lyase 1 (GmPAL1), chalcone isomerase 1A (GmCHI1A), and chalcone synthase 8 (GmCHS8) was associated with phenolic and flavonoid accumulation in soybean seeds of plants subjected to drought stress. Interestingly, the expression levels of GmCHS8 were highly correlated with flavonoid levels under drought stress and water recovery conditions. Cinnamic acid, which is a biosynthesis precursor shared by both phenylpropanoid metabolism and salicylic acid (SA) biosynthesis, decreased under drought stress conditions. Notably, exogenous ABA suppressed the expression of GmPAL1, which encodes the first rate-limiting enzyme in the phenylpropanoid biosynthesis pathway and affects downstream products such as SA and flavonoids. In conclusion, drought stress altered the phenylpropanoid-derived compounds, at least with regard to flavonoid and SA accumulation in seeds, which was regulated by antagonistic interactions with ABA., (© 2023 Scandinavian Plant Physiology Society.)

Gastric cancer (GC) is the remaining concern of cancer-associated health burden. Valuable predictive and prognostic indicators support the early diagnosis and improve outcome. Immune escape and inflammation are important cancer hallmarks. The prognostic and diagnostic value of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) was reported in some cancers. But these cheap and convenient indexes are far from clinical use. Thus, investigation the alteration of those index on GC is needed to impose the use of those indexes in clinic. The study recruited seventy-seven hospitalized patients newly diagnosed with GC and 90 healthy individuals. The clinical and preclinical data of participants were collected from Hospital Information Management system. This study were approved by the Ethical Committee, Vietnam Military Medical University. The data were analyzed on STATA version 14.0 and GraphPad Prism 8.0. The alteration of immunological system was reported by significantly higher white blood cell count, neutrophils, platelets, PLR, and NLR as well as decreased lymphocytes on GC, compared to healthy individuals. Those indexes were elevated on advanced stage GC, compared to early stage GC. Our receiver operating characteristic curve analysis showed the significant specificity and sensitivity of PLR (cutoff 135.0) and NLR (cutoff 2.0) on GC diagnosis with respective area under receiver operating characteristic curve of 84.74% and 85.17%, P < .0001. Besides, our results reported the tendency of increased PLR and NLR and short time from clinical signs to being diagnosed. PLR and NLR have significant specificity and sensitivity in diagnosis and prognosis of GC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Pancreaticoduodenectomy in patients with CA stenosis due to median arcuate ligament often required carefully collateral pathways management to avoid hepatic ischemic complications., Cases Presentation: Case 1: A 63-year-old man was referred to our department because of jaundice with distal common bile duct tumor. Pancreaticoduodenectomy with left posterior SMA first approach and circumferential lymphadenectomy was performed. Case 2: A 48-year-old man was referred to our department because of right-upper-quadrant abdominal pain with Vater tumor. Laparoscopic pancreaticoduodenectomy with left posterior SMA first approach and circumferential lymphadenectomy was performed. Postoperatively, in all two cases, three-dimensional reconstruction images showed developed collateral pathways around the pancreatic head, and the CA was stenosis in 75% and 70% due to MAL, respectively. Intraoperatively, in all two cases, we confirmed poor blood flow in the common hepatic artery (CHA) by palpation and observation. So that in the first case, we have decided to proceed a no-touch technique of GDA segmental resection en bloc with the tumor and reconstructed with an end-to-end GDA anastomosis; in the second cases, we have decided to proceed gastroduodenal collateral preservation. When preserving these collateral pathways, we confirmed that the PHA flow remained pulsatile as an indicator that the blood flow was adequate., Conclusion: Celiac axis stenosis was a rare but difficult-to-managed condition associated with pancreaticoduodenectomy. Collateral pathways management depends on variety of collateral pathways., (© 2023. The Author(s).)

Cassava is a valuable export commodity crop that is often attacked by pests, causing economic losses for this crop. The papaya mealybug Paracoccus marginatus has become a major pest of cassava in Vietnam. The parasitoid wasp Acerophagus papayae has been demonstrated to be the most efficient parasitoid wasp for controlling P. marginatus in many regions. We observed the occurrence of A. papayae in Vietnam, studied the biological characteristics of A. papayae , and investigated its parasitic activity on P. marginatus . The results showed that A. papayae occurred more frequently than Anagyrus loecki , another known parasitoid of P. marginatus . The lifespan of A. papayae was approximately 16 days. In the absence of hosts, a 50% honey solution was an essential diet to increase the longevity of both female and male of A. papayae . The second instar of P. marginatus was a suitable host stage for parasitism by A. papayae . Female A. papayae laid approximately 60.8 eggs within 17 days, mostly during the first 6 to 7 days. These findings suggest that A. papayae has the potential to control P. marginatus , and could inform the development of more effective pest management strategies for cassava crops in Vietnam and other regions affected by this pest.

Background: Chicken infectious anemia (CIA) caused by the CIA virus (CIAV) is considered one of the most important immunosuppressive diseases affecting chickens and recently poses a great economic burden to the poultry industry worldwide., Aim: This study aims to identify the presence of CIAV in the Mekong Delta (MD), Vietnam, and to determine genotypes of CIAVs that are currently circulating in this area., Methods: Organ samples (spleen, liver, and thymus) of 144 chickens suspected with CIA from 47 poultry farms were collected. A total of 47 pooled samples, each containing 2-4 chickens from each farm, were tested for the presence of CIAV., Results: Twenty out of 47 pooled organ samples (pool of 2-4 chickens per farm) were positive for CIAV using polymerase chain reaction targeting the viral VP1 gene. The VP1 amplicons of eight representative CIAVs were subjected to sequencing and genetic characterization. Phylogenetic analysis based on partial VP1 gene sequence revealed that the CIAVs detected in the MD grouped into different genotypes of II, IIIa, and IIIc together with CIAVs previously detected in the northern Vietnam and other Asian countries. The phylogenetic analysis also confirmed that detected CIAVs genetically differed from vaccine strains. In addition, deduced amino acids of the VP1 identified several critical amino acid substitutions in the VP1 protein that are likely associated with the virulence of CIAV., Conclusion: This is the first report to detect and determine the genetic characterization of the circulating CIAVs in the MD. Therefore, this study provides an important understanding of the evolution of CIAVs and highlights the importance of implementing prompt control measures against CIAVs in the MD and Vietnam., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article.

Chronic copper exposure could cause potential nephrotoxicity and effective therapy strategies are limited. This study investigated the protective effects of curcumin on copper sulfate (CuSO 4 )-induced renal damage in a mouse model and the underlying molecular mechanisms. Mice were administrated orally with CuSO 4 (100 mg/kg per day) in combination with or without curcumin (50, 100 or 200 mg/kg per day, orally) for 28 days. Results showed that curcumin supplementation significantly reduce the Cu accumulation in the kidney tissues of mice and improved CuSO 4 -induced renal dysfunction. Furthermore, curcumin supplantation also significantly ameliorated Cu exposure-induced oxidative stress and tubular necrosis in the kidneys of mice. Moreover, compared to the CuSO 4 alone group, curcumin supplementation at 200 mg/kg per day significantly decreased CuSO 4 -induced the expression of p53, Bax, IL-1β, IL-6, and TNF-α proteins, levels of NF-κB mRNA, levels of caspases-9 and - 3 activities, and cell apoptosis, and significantly increased the levels of Nrf2 and HO-1 mRNAs in the kidney tissues. In conclusion, for the first time, our results reveal that curcumin could trigger the inhibition of oxidative stress, mitochondrial apoptotic, p53, and NF-κB pathways and the activation of Nrf2/HO-1 pathway to ameliorate Cu overload-induced nephrotoxicity in a mouse model. Our study highlights that curcumin supplementation may be a promising treatment strategy for treating copper overload-caused nephrotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is one of the most complicated and dangerous diseases in pigs with high mortality since it modulates the immune system of the lungs and has been closely associated with secondary infection of other lethal bacteria and viruses. The gold standard of molecular diagnosis for PRRSV, reverse transcription (RT)-PCR, is time-consuming, expensive and requires transportation of samples to a specialized laboratory. In this study, a direct colorimetric RT-loop-mediated isothermal amplification (RT-LAMP) method was developed to specifically and rapidly detect PRRSV. The RT-LAMP outcomes can be visualized by the naked eye after 45 min of incubation at 65˚C without any cross-reactivity recorded with the bacteria and other viruses tested. In particular, the mobile, non-instrumented, commercial pocket hand warmers were demonstrated to su-ccessfully provide constant temperature for consistent nucleic acid amplification throughout the RT-LAMP reactions. The limit of detection of the assay was defined as the genomic RNA concentration extracted from a known viral titer of 10-2.5 TCID50/ml. The direct use of clinical serum samples required a simple dilution to maintain the performance of the colorimetric RT-LAMP assay. Therefore, the direct colorimetric RT-LAMP assay developed is well-qualified for producing a ready-to-use kit for PRRSV diagnosis in the field. Keywords: porcine reproductive and respiratory syndrome; rapid testing; RT-LAMP; colorimetric; direct detection; instrument-free.

Background: Colorectal cancer (CRC) is the fifth most common cancer with rising prevalence in Vietnam. However, there is no data about the mutational landscape and actionable alterations in the Vietnamese patients. During post-operative surveillance, clinical tools are limited to stratify risk of recurrence and detect residual disease., Method: In this prospective multi-center study, 103 CRC patients eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissue and paired white blood cells were sequenced to profile all tumor-derived somatic mutations in 95 cancer-associated genes. Our bioinformatic algorithm identified top mutations unique for individual patient, which were then used to monitor the presence of circulating tumor DNA (ctDNA) in serial plasma samples., Results: The top mutated genes in our cohort were APC , TP53 and KRAS . 41.7% of the patients harbored KRAS and NRAS mutations predictive of resistance to Cetuximab and Panitumumab respectively; 41.7% had mutations targeted by either approved or experimental drugs. Using a personalized subset of top ranked mutations, we detected ctDNA in 90.5% of the pre-operative plasma samples, whereas carcinoembryonic antigen (CEA) was elevated in only 41.3% of them. Interim analysis after 16-month follow-up revealed post-operative detection of ctDNA in two patients that had recurrence, with the lead time of 4-10.5 months ahead of clinical diagnosis. CEA failed to predict recurrence in both cases., Conclusion: Our assay showed promising dual clinical utilities in residual cancer surveillance and actionable mutation profiling for targeted therapies in CRC patients. This could lay foundation to empower precision cancer medicine in Vietnam and other developing countries., Competing Interests: V-AH, T-AT, TH, DQN, Y-TL, H-NN, HG and LT are current employees of Gene Solutions, Vietnam. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nguyen, Nguyen, Nguyen Hoang, Tran, Le Trinh, Le, Nguyen Tran, Pham, Dinh, Nguyen, Nguyen The, Mai, Chu, Pham, Nguyen, Ngo Ha, Nguyen, Nguyen, Lu, Do Thi, Truong, Nguyen, Nguyen, Giang and Tu.)

BACKGROUND Spontaneous oropharyngeal hemorrhage is rare and is often associated with other predisposing factors. This can result in hemodynamic instability in the presence of other bleeding sources. It is oftentimes difficult to diagnose due to its limitations to visual inspection of the oropharyngeal structures. It is commonly mistaken for hemoptysis or hematemesis upon initial evaluation. Trauma, infection, pulmonary pathologies (ie, lung cancer or tuberculosis), gastrointestinal pathologies (ie, esophageal/gastric varices, Mallory-Weiss tears, esophagitis), coagulopathies, medications, and prolonged intubation have been shown to increase the risk of oropharyngeal hemorrhage. CASE REPORT A 54-year-old man with a medical history of alcohol use disorder, liver cirrhosis, portal hypertension, and gastric varices presented with altered mental status. He was subsequently intubated for airway protection. Bleeding from the oropharynx was later found. Esophagogastroduodenoscopy (EGD) and bronchoscopy were unrevealing. Computed tomography angiography (CTA) of the head and neck revealed active bleeding of the right posterior pharyngeal artery, which was emergently embolized. Over the next few days, he continued to bleed from the oropharynx and became hemodynamically unstable. CTA abdomen showed bleeding from gastric varices and large-volume hemoperitoneum with multiple sources of active bleeding from the liver, duodenum, and jejunum. CONCLUSIONS We present a rare case of spontaneous oropharyngeal hemorrhage and gastric variceal bleeding resulting in hemorrhagic shock in a cirrhotic patient with multiple predisposing factors. If a patient presents with spontaneous oropharyngeal hemorrhage, clinicians should consider bleeding from the oropharynx if EGD and bronchoscopy are unrevealing. Thus, an emergent CTA of the head and neck should be strongly considered to further evaluate a potential source of active bleeding, as delayed diagnosis can be life-threatening.

Lumpy skin disease (LSD) is a serious emerging infectious disease in cattle caused by a virus of the family Poxviridae. According to the Department of Animal Health, LSD first occurred in Vietnam at the end of October 2020 in Cao Bang and Lang Son provinces. So far, the disease has infected over 63,000 animals, resulting in 9170 deaths occurring in 32 different provinces in northern and central Vietnam. In this study, skin samples from lumpy skin disease virus (LSDV)-infected cattle from the northern provinces of Vietnam displaying clinical symptoms including fever (> 40 °C), runny nose, drooling, and skin lesions were used for genetic characterization and histopathology. Genetic analysis of the partial P32 (LSDV074), partial F (LSDV117), complete RPO30 (LSDV035), and complete G-protein-coupled-chemokine-like receptor (GPCR) (LSDV011) genes showed that all Vietnamese LSDV strains belonged to the genus Capripoxvirus and were closely related to LSDV strains isolated in China. Microscopic examination of the skin lesions showed thickening of the epidermal layer of the skin and hair follicles, hyperplasia of sebaceous glands, intracytoplasmic inclusion bodies, and hemorrhages in the mesoderm., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Aims: Early detection of colorectal cancer (CRC) provides substantially better survival rates. This study aimed to develop a blood-based screening assay named SPOT-MAS ('screen for the presence of tumor by DNA methylation and size') for early CRC detection with high accuracy. Methods: Plasma cell-free DNA samples from 159 patients with nonmetastatic CRC and 158 healthy controls were simultaneously analyzed for fragment length and methylation profiles. We then employed a deep neural network with fragment length and methylation signatures to build a classification model. Results: The model achieved an area under the curve of 0.989 and a sensitivity of 96.8% at 97% specificity in detecting CRC. External validation of our model showed comparable performance, with an area under the curve of 0.96. Conclusion: SPOT-MAS based on integration of cancer-specific methylation and fragmentomic signatures could provide high accuracy for early-stage CRC detection.

RNA viral infections, including those caused by respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Venezuelan Equine encephalitis virus (VEEV), pose a major global health challenge. Here, we report the synthesis and screening of a series of pyrrolo[2,3- b ]pyridines targeting RSV, SARS-CoV-2 and/or VEEV. From this campaign, a series of lead compounds was generated that demonstrated antiviral activity in the low single-digit micromolar range against the various viruses and did not show cytotoxicity. These findings highlight the potential of 3-alkynyl-5-aryl-7-aza-indoles as a promising chemotype for the development of broad-spectrum antiviral agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martinez-Gualda, Graus, Camps, Vanhulle, Saul, Azari, Nhu Tran, Vangeel, Chiu, Neyts, Schols, Einav, Vermeire and De Jonghe.)

Osteoarthritis (OA) is a common disease of joints that is more common in females than in males. It is characterized by severe knee degeneration, damaged cartilage and appearance of osteophytes. Hip geometry and morphometric parameters in the knee joint vary between the sexes and depend on the severity of OA and the presence of osteophytes. Very few studies have assessed this phenomenon; therefore in this study, we assessed the difference in hip geometry and morphometric parameters in the lower limbs of males and females and evaluated the association of the differences with the presence or absence of osteophytes. Three hundred and six knees volunteers (104 male knees and 202 female knees) from the Toei region were included in the study between 2012 and 2018. The parameters measured were from the anteroposterior and lateral views of the hip and anteroposterior view of the knee. The participants were divided into 4 groups based on the assessment for osteophytes: Group 1 had no osteophytes, Group 2 had lateral compartment osteophytes, Group 3 had medial compartment osteophytes, and Group 4 had osteophytes in both compartments. Males had an increased femoral neck-shaft angle, femoral-tibial angle, and plateau angle, and a decreased femoral offset, femoral neck length, fibular-tibial angle, and knee rotation index than females. Group 2 had a greater height of the hip center, the angle between the femoral mechanical axis and the femoral shaft axis, condylar-hip angle, and plateau angle than Group 1. Group 3 showed an increased abductor angle, the angle between the femoral mechanical axis and the femoral shaft axis. Group 4 showed an increased angle between the femoral mechanical axis and the femoral shaft axis, femoral-tibial angle, and a decreased patellar shift index and knee rotation index. The angle between the femoral mechanical axis and the femoral shaft axis, condylar-hip angle, femoral-tibial angle, plateau angle, patellar shift index, and knee rotation index were different in both sexes and may be dependent on the presence or absence of osteophytes., (© 2022. The Author(s).)

Background: The methodology of assessment and training of surgical skills is evolving to deal with the emergence of competency-based training. Artificial neural networks (ANNs), a branch of artificial intelligence, can use newly generated metrics not only for assessment performance but also to quantitate individual metric importance and provide new insights into surgical expertise., Objective: To outline the educational utility of using an ANN in the assessment and quantitation of surgical expertise. A virtual reality vertebral osteophyte removal during a simulated surgical spine procedure is used as a model to outline this methodology., Methods: Twenty-one participants performed a simulated anterior cervical diskectomy and fusion on the Sim-Ortho virtual reality simulator. Participants were divided into 3 groups, including 9 postresidents, 5 senior residents, and 7 junior residents. Data were retrieved from the osteophyte removal component of the scenario, which involved using a simulated burr. The data were manipulated to initially generate 83 performance metrics spanning 3 categories (safety, efficiency, and motion) of which only the most relevant metrics were used to train and test the ANN., Results: The ANN model was trained on 6 safety metrics to a testing accuracy of 83.3%. The contributions of these performance metrics to expertise were revealed through connection weight products and outlined 2 identifiable learning patterns of technical skills., Conclusion: This study outlines the potential utility of ANNs which allows a deeper understanding of the composites of surgical expertise and may contribute to the paradigm shift toward competency-based surgical training., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Purine nucleotides are necessary for various biological processes related to cell proliferation. Despite their importance in DNA and RNA synthesis, cellular signaling, and energy-dependent reactions, the impact of changes in cellular purine levels on cell physiology remains poorly understood. Here, we find that purine depletion stimulates cell migration, despite effective reduction in cell proliferation. Blocking purine synthesis triggers a shunt of glycolytic carbon into the serine synthesis pathway, which is required for the induction of cell migration upon purine depletion. The stimulation of cell migration upon a reduction in intracellular purines required one-carbon metabolism downstream of de novo serine synthesis. Decreased purine abundance and the subsequent increase in serine synthesis triggers an epithelial-mesenchymal transition (EMT) and, in cancer models, promotes metastatic colonization. Thus, reducing the available pool of intracellular purines re-routes metabolic flux from glycolysis into de novo serine synthesis, a metabolic change that stimulates a program of cell migration., (© 2022. The Author(s).)

Unstable, displaced, and persistently symptomatic osteochondritis dissecans of the knee typically requires surgical treatment. An arthroscopic, knotless fixation method using interlinked all-suture anchors is presented, with potential advantages over other current techniques in fixation over a broad zone, treatment versatility for a wide range of fragment types, retensioning ability after stressing, decreased risk of implant-breakage complications, and avoidance of additional surgery for implant removal., (© 2022 The Authors.)

Geopolymer foams are excellent materials in terms of mechanical loads and fire resistance applications. This study investigated the foaming process of geopolymers and foam stability, with a focus on the fire resistance performance when using polystyrene as the base layer. The main purpose is to define the influence of porosity on the physical properties and consequently to find applications and effectiveness of geopolymers. In this study, lightweight materials are obtained through a process called geopolymerization. Foaming was done by adding aluminum powder at the end of the geopolymer mortar preparation. The interaction between the aluminum powder and the alkaline solution (used for the binder during the mixing process) at room temperature is reactive enough to develop hydrogen-rich bubbles that increase the viscosity and promote the consolidation of geopolymers. The basic principle of thermodynamic reactions responsible for the formation of foams is characterized by hydrogen-rich gas generation, which is then trapped in the molecular structure of geopolymers. The geopolymer foams in this study are highly porous and robust materials. Moreover, the porosity distribution is very homogeneous. Experimental assessments were performed on four specimens to determine the density, porosity, mechanical strength, and thermal conductivity. The results showed that our geopolymer foams layered on polystyrene boards (with optimal thickness) have the highest fire resistance performance among others. This combination could withstand temperatures of up to 800 °C for more than 15 min without the temperature rising on the insulated side. Results of the best-performing geopolymer foam underline the technical characteristics of the material, with an average apparent density of 1 g/cm 3 , a volume porosity of 55%, a thermal conductivity of 0.25 W/mK, and excellent fire resistance.

In procedural-based medicine, the technical ability can be a critical determinant of patient outcomes. Psychomotor performance occurs in real-time, hence a continuous assessment is necessary to provide action-oriented feedback and error avoidance guidance. We outline a deep learning application, the Intelligent Continuous Expertise Monitoring System (ICEMS), to assess surgical bimanual performance at 0.2-s intervals. A long-short term memory network was built using neurosurgeon and student performance in 156 virtually simulated tumor resection tasks. Algorithm predictive ability was tested separately on 144 procedures by scoring the performance of neurosurgical trainees who are at different training stages. The ICEMS successfully differentiated between neurosurgeons, senior trainees, junior trainees, and students. Trainee average performance score correlated with the year of training in neurosurgery. Furthermore, coaching and risk assessment for critical metrics were demonstrated. This work presents a comprehensive technical skill monitoring system with predictive validation throughout surgical residency training, with the ability to detect errors., (© 2022. The Author(s).)

Identification of tumor-derived mutation (TDM) in liquid biopsies (LB), especially in early-stage patients, faces several challenges, including low variant-allele frequencies, interference by white blood cell (WBC)-derived mutations (WDM), benign somatic mutations and tumor heterogeneity. Here, we addressed the above-mentioned challenges in a cohort of 50 nonmetastatic colorectal cancer patients, via a workflow involving parallel sequencing of paired WBC- and tumor-gDNA. After excluding potential false positive mutations, we detected at least one TDM in LB of 56% (28/50) of patients, with the majority showing low-patient coverage, except for one TDM mapped to KMT2D that recurred in 30% (15/30) of patients.

Food and beverage poisoning is detrimental to people's health since it can lead to fever, stomachaches, and even death. To rapidly detect the presence of foodborne pathogens, conventional PCR assays are currently widely employed. Meanwhile, isothermal PCR methods, in which the amplification reactions take place at a low and constant temperature, have lately emerged as effective and alternative means for quickly identifying pathogens in low-resource settings. Staphylococcus aureus and Pseudomonas aeruginosa are two of the most concerning foodborne bacterial infections. In this work, an isothermal PCR assay based on the Recombinase Polymerase Amplification (RPA) method was developed to simultaneously detect S. aureus and P. aeruginosa with high sensitivity and specificity. The limit of detection for multiplex RPA was 10 and 30 fg/reaction of S. aureus and P. aeruginosa genomic DNA, respectively. Furthermore, the reaction time was reduced to only 25 minutes, with a low incubation temperature of 39°C. Multiplex RPA reactions, in particular, were successful in directly identifying as low as 1 and 5 CFU/reaction of S. aureus and P. aeruginosa cells, respectively, without the need for DNA genome extraction. Moreover, the multiplex RPA reliably detected the two foodborne bacteria in milk, fruit juice, and bottled water samples. In conclusion, the direct multiplex RPA reported in this work offers a quick, easy, sensitive, and effective alternative approach for detecting the presence of S. aureus and P. aeruginosa without the requirement of a pricey instrument or highly-trained personnel., Competing Interests: The authors declare no conflict of interest.

Introduction: With the increased use of computed tomography (CT) imaging, lung nodules are found yearly requiring tracking and guideline directed follow up imaging. We describe the structure of a clinic dedicated to lung nodule tracking, patient education and the outcomes of lung nodule follow up., Methods: Patient electronic medical record charts were reviewed for lung nodules requiring tracking to determine if a follow up study was ordered, completed by the patient, and completed in an appropriate time frame. Patients were grouped based on referral to pulmonary clinic, lung mass clinic, or no subspecialty clinic. 700 CT reports were extracted from the electronic medical record of which 350 (50%) had lung nodules reported on CT, and 111 (15.9%) were lung nodules that additionally recommended discrete follow up in the radiologist report at the Veterans Health Administration hospital in Baltimore. Of these 111 patients, 95% were male and 5% were female. The mean age of the population was 66.3 ± 7.7 years., Results and Discussion: Patients seen in the lung mass clinic had a statistically significant higher rate of the follow up study being ordered by the provider. The lung mass clinic also had a higher percentage of patients who completed the study and completed the study within the recommended time frame, however, this was not statistically significant., Conclusion: A dedicated lung mass clinic should be considered as a method of improving lung nodule tracking with the added benefit of patient education and multidisciplinary care., Competing Interests: Conflict of Interest No conflict of interest.

Background: Developing efficient and successful computational methods to infer potential miRNA-disease associations is urgently needed and is attracting many computer scientists in recent years. The reason is that miRNAs are involved in many important biological processes and it is tremendously expensive and time-consuming to do biological experiments to verify miRNA-disease associations., Methods: In this paper, we proposed a new method to infer miRNA-disease associations using collaborative filtering and resource allocation algorithms on a miRNA-disease-lncRNA tripartite graph. It combined the collaborative filtering algorithm in CFNBC model to solve the problem of imbalanced data and the method for association prediction established multiple types of known associations among multiple objects presented in TPGLDA model., Results: The experimental results showed that our proposed method achieved a reliable performance with Area Under Roc Curve (AUC) and Area Under Precision-Recall Curve (AUPR) values of 0.9788 and 0.9373, respectively, under fivefold-cross-validation experiments. It outperformed than some other previous methods such as DCSMDA and TPGLDA. Furthermore, it demonstrated the ability to derive new associations between miRNAs and diseases among 8, 19 and 14 new associations out of top 40 predicted associations in case studies of Prostatic Neoplasms, Heart Failure, and Glioma diseases, respectively. All of these new predicted associations have been confirmed by recent literatures. Besides, it could discover new associations for new diseases (or miRNAs) without any known associations as demonstrated in the case study of Open-angle glaucoma disease., Conclusion: With the reliable performance to infer new associations between miRNAs and diseases as well as to discover new associations for new diseases (or miRNAs) without any known associations, our proposed method can be considered as a powerful tool to infer miRNA-disease associations., (© 2021. The Author(s).)