Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell-Free DNA Analysis by Whole-Exome Sequencing for Hepatocellular Carcinoma: A Pilot Study in Thailand

Simple Summary Liquid biopsy for cell-free DNA (cfDNA) is a non-invasive technique to characterize the genetic profile of a tumor. Despite being a valuable tool, there is no mutational profile of cfDNA from hepatocellular carcinoma (HCC) in patients from Thailand, where HCC is prevalent. The present study aimed to demonstrate the utility of using whole-exome sequencing of cfDNA to define the somatic mutation profiles of HCC in Thai patients who underwent nonoperative therapies. The level of cfDNA was higher in HCC patients than in chronic hepatitis patients. Single nucleotide variations were present in somatic genes in cfDNA, including in ZNF814, HRNR, ZNF492, ADAMTS12, FLG, OBSCN, TP53, and TTN. The co-occurrence of HRNR and TTN mutations in cfDNA was associated with shorter overall survival. These findings indicate that the mutational profiles of cfDNA reflected those of HCC tissue, and cfDNA could serve as a useful biomarker for diagnosis and prognosis in HCC patients. Abstract Cell-free DNA (cfDNA) has been used as a non-invasive biomarker for detecting cancer-specific mutations. However, the mutational profile of cfDNA in Thai patients with hepatocellular carcinoma (HCC) has not been investigated. Here, we demonstrated the utility of using whole-exome sequencing (WES) of cfDNA to define the somatic mutation profiles of HCC in Thai patients. The comprehensive profile of cfDNA was determined with WES to identify variants in matched cfDNA and germline DNA from 30 HCC patients in Thailand who underwent nonoperative therapies. The level of cfDNA was higher in HCC patients compared with chronic hepatitis patients (p-value < 0.001). Single nucleotide variants were present in somatic genes in cfDNA, including in ZNF814 (27%), HRNR (20%), ZNF492 (20%), ADAMTS12 (17%), FLG (17%), OBSCN (17%), TP53 (17%), and TTN (17%). These same mutations were matched to HCC mutation data from The Cancer Genome Atlas (TCGA) and a previous Thai HCC study. The co-occurrence of HRNR and TTN mutations in cfDNA was associated with shorter overall survival in HCC patients (hazard ratio = 1.60, p-value = 0.0196). These findings indicate that the mutational profile of cfDNA accurately reflected that of HCC tissue and suggest that cfDNA could serve as a useful biomarker for diagnosis and prognosis in Thai HCC patients. In addition, we demonstrated the use of the pocket-sized sequencer of Oxford Nanopore Technology to detect copy-number variants in HCC tissues that could be applied for onsite clinical detection/monitoring of HCC.
Glutathione in the Brain

Glutathione (GSH) is the most abundant non-protein thiol, and plays crucial roles in the antioxidant defense system and the maintenance of redox homeostasis in neurons. GSH depletion in the brain is a common finding in patients with neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, and can cause neurodegeneration prior to disease onset. Excitatory amino acid carrier 1 (EAAC1), a sodium-dependent glutamate/cysteine transporter that is selectively present in neurons, plays a central role in the regulation of neuronal GSH production. The expression of EAAC1 is posttranslationally controlled by the glutamate transporter-associated protein 3–18 (GTRAP3-18) or miR-96-5p in neurons. The regulatory mechanism of neuronal GSH production mediated by EAAC1 may be a new target in therapeutic strategies for these neurodegenerative diseases. This review describes the regulatory mechanism of neuronal GSH production and its potential therapeutic application in the treatment of neurodegenerative diseases.
Challenges to Mitigating the Urban Health Burden of Mosquito-Borne Diseases in the Face of Climate Change

Cities worldwide are facing ever-increasing pressure to develop mitigation strategies for all sectors to deal with the impacts of climate change. Cities are expected to house 70% of the world’s population by 2050, and developing related resilient health systems is a significant challenge. Because of their physical nature, cities’ surface temperatures are often substantially higher than that of the surrounding rural areas, generating the so-called Urban Heat Island (UHI) effect. Whilst considerable emphasis has been placed on strategies to mitigate against the UHI-associated negative health effects of heat and pollution in cities, mosquito-borne diseases have largely been ignored. However, the World Health Organization estimates that one of the main consequences of global warming will be an increased burden of mosquito-borne diseases, many of which have an urban facet to their epidemiology and thus the global population exposed to these pathogens will steadily increase. Current health mitigation strategies for heat and pollution, for example, may, however, be detrimental for mosquito-borne diseases. Implementation of multi-sectoral strategies that can benefit many sectors (such as water, labor, and health) do exist or can be envisaged and would enable optimal use of the meagre resources available. Discussion among multi-sectoral stakeholders should be actively encouraged.
Platelet-Derived Growth Factor-Modulated Guided Tissue Regeneration with a Bioresorbable Membrane in Class III Furcation Defects: A Histometric Study in the Monkey

It was the aim of this study to histometrically evaluate guided tissue regeneration (bioresorbable membrane plus bone mineral) (GTR) with or without platelet-derived growth factor (PDGF) in two different types of class III furcation defects (small keyhole defects and horizonal defects) in monkeys. In six cynomolgus monkeys, two types of class III furcation defects were created and allowed to chronify for 5 months in mandibular first and second molars. After a hygiene program the molars were assigned to GTR group (collagen membrane plus bovine bone mineral), PDGF group (collagen membrane plus bovine bone mineral plus PDGF), or negative control group (flap reposition only). Histologic sections were made after 7 months of healing and descriptive statistics were provided from the histometric parameters. Postoperative healing was uneventful despite marginal membrane exposures in the GTR and PDGF group. Bone regeneration of 23–35% of the original defect area was found in the two treatment groups. In none of the evaluated key parameters (formation of bone, root cementum, connective tissue, or epithelium) differences were detected between GTR and PDGF groups. However, the negative control teeth exhibited better bone regeneration than the treatment groups. The type of class III defect did not influence the regenerative outcome. Within the limits of this study PDGF was not able to enhance the histologic regeneration of class III furcation areas in monkeys compared to bone mineral enhanced GTR treatment regardless of the defect configuration. Membrane exposure during early healing might have influenced these outcomes.
Energy Conservation for Internet of Things Tracking Applications Using Deep Reinforcement Learning

The Internet of Things (IoT)-based target tracking system is required for applications such as smart farm, smart factory, and smart city where many sensor devices are jointly connected to collect the moving target positions. Each sensor device continuously runs on battery-operated power, consuming energy while perceiving target information in a particular environment. To reduce sensor device energy consumption in real-time IoT tracking applications, many traditional methods such as clustering, information-driven, and other approaches have previously been utilized to select the best sensor. However, applying machine learning methods, particularly deep reinforcement learning (Deep RL), to address the problem of sensor selection in tracking applications is quite demanding because of the limited sensor node battery lifetime. In this study, we proposed a long short-term memory deep Q-network (DQN)-based Deep RL target tracking model to overcome the problem of energy consumption in IoT target applications. The proposed method is utilized to select the energy-efficient best sensor while tracking the target. The best sensor is defined by the minimum distance function (i.e., derived as the state), which leads to lower energy consumption. The simulation results show favorable features in terms of the best sensor selection and energy consumption.
Development and Validation of the Pain and State of Health Inventory (PHI): Application for the Perioperative Setting

Currently, general measurements and evaluations of the quality of recovery are difficult because no adequate measuring tools are available. Therefore, there is an urgent need for a universal tool that assesses patient-relevant criteria—postoperative pain, state of health, and somatic parameters. For this purpose, a pain and state of health inventory (PHI, Schmerz- und Befindlichkeitsinventar (SBI) in German) has been developed. In this study, we describe its development and validation. The development phase was led by an expert panel and was divided into three subphases: determining the conceptual structure, testing the first editions, and adjusting the inventory for a finalized edition. For the purpose of validation, the PHI was filled in by 132 patients who have undergone total knee replacement and was analyzed using principal component analysis. Construct validity was tested by correlating the items with validated questionnaires. The results showed that the inventory can test pain, state of health, and somatic parameters with great construct validity. Furthermore, the inventory is accepted by patients, map changes, and supports to initiate adequate treatment. In conclusion, the PHI is a universal tool that can be used to assess the quality of recovery in the perioperative setting and allow immediate intervention.
Silver Nanoparticle-Anchored Human Hair Kerateine/PEO/PVA Nanofibers for Antibacterial Application and Cell Proliferation

The main core of wound treatment is cell growth and anti-infection. To accelerate the proliferation of fibroblasts in the wound and prevent wound infections, various strategies have been tried. It remains a challenge to obtain good cell proliferation and antibacterial effects. Here, human hair kerateine (HHK)/poly(ethylene oxide) (PEO)/poly(vinyl alcohol) (PVA) nanofibers were prepared using cysteine-rich HHK, and then, silver nanoparticles (AgNPs) were in situ anchored in the sulfur-containing amino acid residues of HHK. After the ultrasonic degradation test, HHK/PEO/PVA nanofibrous mats treated with 0.005-M silver nitrate were selected due to their relatively complete structures. It was observed by TEM-EDS that the sulfur-containing amino acids in HHK were the main anchor points of AgNPs. The results of FTIR, XRD and the thermal analysis suggested that the hydrogen bonds between PEO and PVA were broken by HHK and, further, by AgNPs. AgNPs could act as a catalyst to promote the thermal degradation reaction of PVA, PEO and HHK, which was beneficial for silver recycling and medical waste treatment. The antibacterial properties of AgNP-HHK/PEO/PVA nanofibers were examined by the disk diffusion method, and it was observed that they had potential antibacterial capability against Gram-positive bacteria, Gram-negative bacteria and fungi. In addition, HHK in the nanofibrous mats significantly improved the cell proliferation of NIH3T3 cells. These results illustrated that the AgNP-HHK/PEO/PVA nanofibrous mats exhibited excellent antibacterial activity and the ability to promote the proliferation of fibroblasts, reaching our target applications.
Liquid Biopsy for Small Cell Lung Cancer either De Novo or Transformed: Systematic Review of Different Applications and Meta-Analysis

Simple Summary Small cell lung cancer (SCLC) is an aggressive tumor, which can occur either de novo or from the histologic transformation of non-small cell lung cancer. Liquid biopsy has demonstrated its capability to detect, characterize and monitor different cancers. The aim of this systematic review was to assess the potential added value of liquid biopsy, in terms of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), in the management of SCLC, either de novo or transformed. We found ctDNA analysis as the most valuable and feasible technology to be integrated into clinical for disease monitoring (response, relapse, transformation) or for genomic profiling of SCLC, with a potential use also for prognostic stratification. CTCs hold a strong prognostic significance, as confirmed by our meta-analysis (even if potentially biased), but the heterogeneity of available data, the lack of agreed cut-offs, and the less affordable technology make CTCs more difficult to be integrated into present clinical practice. Abstract Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.
Melanoma Progression under Obesity: Focus on Adipokines

Simple Summary Obesity is a rapidly growing public health problem and the reason for numerous diseases in the human body, including cancer. This article reviews the current knowledge of the effect of molecules secreted by adipose tissue-adipokines on melanoma progression. We also discuss the role of these factors as markers of incidence, metastasis, and melanoma patient survival. Understanding the functions of adipokines will lead to knowledge of whether and how obesity promotes melanoma growth. Abstract Obesity is a growing problem in the world and is one of the risk factors of various cancers. Among these cancers is melanoma, which accounts for the majority of skin tumor deaths. Current studies are looking for a correlation between obesity and melanoma. They suspect that a potential cause of its development is connected to the biology of adipokines, active molecules secreted by adipose tissue. Under physiological conditions, adipokines control many processes, including lipid and glucose homeostasis, insulin sensitivity, angiogenesis, and inflammations. However, when there is an increased amount of fat in the body, their secretion is dysregulated. This article reviews the current knowledge of the effect of adipokines on melanoma growth. This work focuses on the molecular pathways by which adipose tissue secreted molecules modify the angiogenesis, migration, invasion, proliferation, and death of melanoma cells. We also discuss the role of these factors as markers of incidence, metastasis, and melanoma patient survival. Understanding the functions of adipokines will lead to knowledge of whether and how obesity promotes melanoma growth. Further studies may contribute to the innovations of therapies and the use of adipokines as predictive and/or prognostic biomarkers.
Enabling Reliable UAV Control by Utilizing Multiple Protocols and Paths for Transmitting Duplicated Control Packets

In the last ten years, supported by the advances in technologies for unmanned aerial vehicles (UAVs), UAVs have developed rapidly and are utilized for a wide range of applications. To operate UAVs safely, by exchanging control packets continuously, operators should be able to monitor UAVs in real-time and deal with any problems immediately. However, due to any networking problems or unstable wireless communications, control packets can be lost or transmissions can be delayed, which causes the unstable drone control. To overcome this limitation, in this paper, we propose MuTran for enabling reliable UAV control. MuTran considers the packet type and duplicates only control packets, not data packets. After that, MuTran transmits the original and duplicate packets through multiple protocols and paths to improve the reliability of control packet transmissions. We designed MuTran and conducted a lot of theoretical analyses to demonstrate the validity of MuTran and analyze it from various aspects. We implemented MuTran on real devices and evaluated MuTran using the devices. We conducted experiments to verify the limitations of the existing systems and demonstrate that control packets can be transmitted more stably by using MuTran. Through the analysis and experimental results, we confirmed that MuTran reduces the control packet transfer delay, which improves the reliability and stability of controlling UAVs.
The Ubiquitin Proteasome System in Genome Stability and Cancer

Simple Summary Genomic instability is a major driving force of tumour development and evolution. Cells have developed sophisticated regulatory systems to preserve the stability of the genome and defects in these mechanisms can lead to the acquisition of mutations. In this review we look at the role of ubiquitination, a common post-translational modification, in the regulation of genomic integrity. Abstract Faithful DNA replication during cellular division is essential to maintain genome stability and cells have developed a sophisticated network of regulatory systems to ensure its integrity. Disruption of these control mechanisms can lead to loss of genomic stability, a key hallmark of cancer. Ubiquitination is one of the most abundant regulatory post-translational modifications and plays a pivotal role in controlling replication progression, repair of DNA and genome stability. Dysregulation of the ubiquitin proteasome system (UPS) can contribute to the initiation and progression of neoplastic transformation. In this review we provide an overview of the UPS and summarize its involvement in replication and replicative stress, along with DNA damage repair. Finally, we discuss how the UPS presents as an emerging source for novel therapeutic interventions aimed at targeting genomic instability, which could be utilized in the treatment and management of cancer.
Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.
The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease, Parkinson’s Disease and Multiple Sclerosis

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.
EGCG-Mediated Potential Inhibition of Biofilm Development and Quorum Sensing in Pseudomonas aeruginosa

Pseudomonas aeruginosa (P. aeruginosa), one of the dangerous multidrug resistance pathogens, orchestrates virulence factors production through quorum sensing (QS). Since the exploration of QS inhibitors, targeting virulence to circumvent bacterial pathogenesis without causing significant growth inhibition is a promising approach to treat P. aeruginosa infections. The present study has evaluated the anti-QS and anti-infective activity of epigallocatechin-3-gallate (EGCG), a bioactive ingredient of the traditional green tea, against P. aeruginosa. EGCG showed significant inhibitory effects on the development of biofilm, protease, elastase activity, swimming, and swarming motility, which was positively related to the production of C4-AHL. The expression of QS-related and QS-regulated virulence factors genes was also evaluated. Quantitative PCR analysis showed that EGCG significantly reduced the expression of las, rhl, and PQS genes and was highly correlated with the alterations of C4-AHL production. In-vivo experiments demonstrated that EGCG treatment reduced P. aeruginosa pathogenicity in Caenorhabditis elegans (C. elegans). EGCG increased the survival of C. elegans by 23.25%, 30.04%, and 36.35% in a dose-dependent manner. The findings of this study strongly suggest that EGCG could be a potential candidate for QS inhibition as an anti-virulence compound against bacterial infection.