Miracle-dz/UniFAR-FTUs huggingface dataset:
Prioritizing Palliative Care: Assess Undergraduate Nursing Curriculum, knowledge and Attitude among Nurses Caring End-of-Life Patients

Palliative Care (PC) education and awareness is considered by Saudi Arabia health care system, as a matter of high priority and understanding the experiences of intensive care nurses in providing care at the end of life, is an important first step for improving terminal care in the intensive care unit Objectives: to identify nurses' attitude, knowledge and experiences on prioritizing palliative care and assess adequacy of the palliative care content in the undergraduate nursing curriculum from teaching members' perspectives. Methods: A cross sectional quantitative survey study was conducted on 100 nurses working in selected hospitals in Taif City and faculty members in Nursing Department, Taif University. Results: Above half of nurses had poor knowledge regarding palliative care, but most of them showed positive attitude regarding end-of-life care especially above diploma degree holders. While most of the content of End-Of-Life (EOL) care in nursing educational program was perceived by faculty members as inadequate and they agreed on the importance of EOL as a part of nursing curriculum. They also perceived that the greatest barriers for improving EOL care were "Inadequate content", "No special training for end of life", and "No special governmental hospital" Conclusions: most of nurse participants' highly prioritizing need for PC training. Where reviewing for the undergraduate nursing programs regarding PC and bridging the inadequacy are mandatory Recommendations: Attention should be given towards PC by the national health policy and incorporated in the national curriculum of nurse education and training. Key wards: Quality of Nursing Interventions, Palliative care, End-of-Life Care.
Evolutionary History of the Toll-Like Receptor Gene Family across Vertebrates

Abstract Adaptation to a wide range of pathogenic environments is a major aspect of the ecological adaptations of vertebrates during evolution. Toll-like receptors (TLRs) are ancient membrane-bound sensors in animals and are best known for their roles in detecting and defense against invading pathogenic microorganisms. To understand the evolutionary history of the vertebrate TLR gene family, we first traced the origin of single-cysteine cluster TLRs that share the same protein architecture with vertebrate TLRs in early-branching animals and then analyzed all members of the TLR family in over 200 species covering all major vertebrate clades. Our results indicate that although the emergence of single-cysteine cluster TLRs predates the separation of bilaterians and cnidarians, most vertebrate TLR members originated shortly after vertebrate emergence. Phylogenetic analyses divided 1,726 vertebrate TLRs into 8 subfamilies, and TLR3 may represent the most ancient subfamily that emerged before the branching of deuterostomes. Our analysis reveals that purifying selection predominated in the evolution of all vertebrate TLRs, with mean dN/dS (ω) values ranging from 0.082 for TLR21 in birds to 0.434 for TLR11 in mammals. However, we did observe patterns of positive selection acting on specific codons (527 of 60,294 codons across all vertebrate TLRs, 8.7‰), which are significantly concentrated in ligand-binding extracellular domains and suggest host–pathogen coevolutionary interactions. Additionally, we found stronger positive selection acting on nonviral compared with viral TLRs, indicating the more essential nonredundant function of viral TLRs in host immunity. Taken together, our findings provide comprehensive insight into the complex evolutionary processes of the vertebrate TLR gene family, involving gene duplication, pseudogenization, purification, and positive selection.
MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma

The modification of chimeric antigen receptor (CAR) endowing T cells with tumor‐specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR‐T therapy. The purpose of our study was to find and verify the potentials of CAR‐T therapies for patients with head and neck squamous cell carcinoma (HNSCC). First, we selected MUC1 as our research target and verified its differential expression in cancer tissues and adjacent non‐neoplastic tissues (ANNT). Next, we constructed a second‐generation CAR and validated the cytotoxic function in vitro. In our study, we found that exogenous addition human IL22 recombinant protein could increase the MUC1 expression and enhance the function of T cells. In addition, we constructed a fourth‐generation CAR that secretes IL22. Finally, we verified the antitumor function of two different CAR‐T cells in vitro and in vivo, respectively. CAR‐MUC1‐IL22 T cells were found to have a stronger and more effective cytotoxic function against MUC1 + HNSCC cells. Taken together, these results demonstrate the potential effectiveness of CAR‐T in the treatment of patients with HNSCC and provide evidence‐based of MUC1 + CAR‐T therapy.
Growth and Metabolic Response of Chinese Perch to Different Dietary Protein-to-Energy Ratios in Artificial Diets

The effect of dietary nutrients on novel farm species has always garnered wide research and economic interest. Chinese perch, an economically important carnivorous fish, accepts an artificial diet after taming, so it is essential to evaluate and optimize the nutritional and metabolic demands of this species. However, little is known about the effect of an artificial diet on the growth and metabolism of Chinese perch. Therefore, the present study evaluated the growth and metabolic responses of Chinese perch to experimental diets with different dietary protein/energy (P/E) ratios. Five isoenergetic diets (18 kJ/g) with graded levels of P/E ratios of 30.58, 33.22, 35.90, 38.6, and 41.35 mg/kJ (named A, B, C, D, and E) were formulated. A total of 225 Chinese perch (64.89 ± 0.28 g) were divided into five groups (triplicate tanks for each group), distributed into 15 (350 L) fiberglass tanks, and fed twice a day at 4% of fish wet body weight with the respective P/E ratio diets for 10 weeks. Compared with the other groups, Chinese perch in Group C showed significantly improved growth performance, weight gain (WG), specific growth rate (SGR), viscerosomatic index (VSI), hepatosomatic index (HSI), intraperitoneal fat (IPF), feed utilization, feed intake (FI), feed conversion ratio (FCR), protein efficiency ratio (PER), protein retention efficiency (PRE), energy retention efficiency (ERE), and feed efficiency (FE) as well as whole-body, muscle, and liver composition. Chinese perch in Group A, on the other hand, had the lowest growth performance, feed utilization, and body composition compared with the other groups. The activities of nitrogen metabolism-related enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST) glutamate dehydrogenase (GDH), and adenosine 5′-monophosphate deaminase (AMPD)) as well as the mRNA expression of the GDH and AMPD genes were significantly lower than those in the other groups. Similarly, the expression of NPY and AgRp were significantly higher in Group C compared with the other groups. However, the gene expression of CART and POMC was not affected by the dietary P/E ratios. In Group A, the expression of mTOR, S6K, and 4EBP1 was significantly lower and that of AMPK, LKB1, and eEF2 was significantly higher when compared with the other groups. Biochemical analysis of blood showed that ALT, AST, total protein (TP), alkaline phosphatase (ALP), glucose (GLU), blood urea nitrogen (BUN), and triglyceride (TG) levels were also affected by the dietary P/E ratio. From our results, we concluded that Chinese perch growth performance and nutrient metabolism were significantly affected by the P/E ratio of the artificial diet. Second-order polynomial regression analysis revealed that Chinese perch growth performance was optimal at a P/E ratio of 37.98 in the artificial diet.
Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer

Metabolic remodelling is a hallmark of cancer, however little has been unravelled in its role in chemoresistance, which is a major hurdle to cancer control. Lung cancer is a leading cause of death by cancer, mainly due to the diagnosis at an advanced stage and to the development of resistance to therapy. Targeted therapeutic agents combined with comprehensive drugs are commonly used to treat lung cancer. However, resistance mechanisms are difficult to avoid. In this review, we will address some of those therapeutic regimens, resistance mechanisms that are eventually developed by lung cancer cells, metabolic alterations that have already been described in lung cancer and putative new therapeutic strategies, and the integration of conventional drugs and genetic and metabolic-targeted therapies. The oxidative stress is pivotal in this whole network. A better understanding of cancer cell metabolism and molecular adaptations underlying resistance mechanisms will provide clues to design new therapeutic strategies, including the combination of chemotherapeutic and targeted agents, considering metabolic intervenients. As cancer cells undergo a constant metabolic adaptive drift, therapeutic regimens must constantly adapt.
Dizziness in patients with cognitive impairment

Accumulating evidences show that the vestibular system contributes to cognitive function, including visuospatial ability, memory, and attention. Conversely, cognitive processes appear to affect the vestibular system. Based on the assumption that cognitive impairment correlates to increased perception of dizziness, we recruited 308 adults with cognitive decline from neurodegenerative disorders and administered neuropsychological tests and the Dizziness Handicap Inventory. Global cognitive measures did not correlate with increased dizziness, whereas attentional and visuospatial cognitive ability was correlated with scores of the Dizziness Handicap Inventory. Furthermore, patients with both cognitive impairment and postural instability experienced notably worse dizziness than those without postural instability, suggesting that postural instability is an important determinant of dizziness.
The Anatomy of Asilisaurus kongwe, a Dinosauriform from the Lifua Member of the Manda Beds (~Middle Triassic) of Africa

The diagnosis of Dinosauria and interrelationships of the earliest dinosaurs relies on careful documentation of the anatomy of their closest relatives. These close relatives, or dinosaur “precursors,” are typically only documented by a handful of fossils from across Pangea and nearly all specimens are typically missing important regions (e.g., forelimbs, pelves, skulls) that appear to be important to help resolving the relationships of dinosaurs. Here, we fully describe the known skeletal elements of Asilisaurus kongwe, a dinosauriform from the Middle Triassic Manda Beds of the Ruhuhu Basin of Tanzania. The taxon is known from many disarticulated and partially articulated remains and, most importantly, from a spectacularly preserved associated skeleton of an individual containing much of the skull, pectoral and pelvic girdles, forelimb and hindlimb, and parts of the vertebral column including much of the tail. The unprecedented detail of the anatomy indicates that Asilisaurus kongwe had a unique skull that was short and had both a premaxillary and dentary edentulous margin, but retained a number of character states plesiomorphic for Archosauria, including a crocodylian‐like ankle configuration and a rather short foot with well‐developed metatarsals I and V. Additionally, character states present across the skeleton of Asilisaurus kongwe suggest it is more closely related to Silesaurus opolensis than to dinosaurs; thus suggesting high homoplasy and parallel trends within Silesauridae and within lineages of early dinosaurs. The anatomy of Asilisaurus kongwe and detailed description of early members of clades found outside Dinosauria are clearly needed to untangle the seemingly complex character evolution of the skeleton within avemetatarsalians. Anat Rec, 303:813–873, 2020. © 2019 American Association for Anatomy
Rosiglitazone enhances the apoptotic effect of 5-fluorouracil in colorectal cancer cells with high-glucose-induced glutathione

Colorectal cancer is one of the most prevalent noncommunicable diseases worldwide. 5-Fluorouracil is the mainstay of chemotherapy for colorectal cancer. Previously, we have demonstrated that high glucose diminishes the cytotoxicity of 5-fluorouracil by promoting cell cycle progression. The synergistic impact of rosiglitazone on 5-fluorouracil-induced apoptosis was further investigated in this study. Besides control cell lines (CCD-18Co), two human colonic carcinoma cell lines (HCT 116 and HT 29) were exposed to different treatments containing 5-fluorouracil, rosiglitazone or 5-fluorouracil/rosiglitazone combination under normal glucose (5.5 mM) and high-glucose (25 mM) conditions. The cellular oxidative stress level was evaluated with biomarkers of nitric oxide, advanced oxidation protein products, and reduced glutathione. The cell apoptosis was assessed using flow cytometry technique. High glucose caused the production of reduced glutathione in HCT 116 and HT 29 cells. Correspondingly, high glucose suppressed the apoptotic effect of 5-fluorouracil and rosiglitazone. As compared to 5-fluorouracil alone (2 µg/mL), addition of rosiglitazone significantly enhanced the apoptosis (increment rate of 5–20%) in a dose-dependent manner at normal glucose and high glucose levels. This study indicates that high-glucose-induced reduced glutathione confers resistance to apoptosis, but it can be overcome upon treatment of 5-fluorouracil and 5-fluorouracil/rosiglitazone combination. Rosiglitazone may be a promising antidiabetic drug to reduce the chemotherapeutic dose of 5-fluorouracil for colorectal cancer complicated with hyperglycemia.
Comparative genomics to develop a specific multiplex PCR assay for detection of Clavibacter michiganensis.

Clavibacter michiganensis (Cm) is a Gram-positive bacterial pathogen that proliferates in the xylem vessels of tomato, causing bacterial wilt and canker symptoms. Accurate detection is a crucial step in confirming outbreaks of bacterial canker and developing management strategies. A major problem with existing detection methods are false positive and negative results. Here, we report the use of comparative genomics of 37 diverse Clavibacter strains, including 21 strains sequenced in this study, to identify specific sequences that are Cm detection targets. Genome-wide phylogenic analyses revealed additional diversity within the genus Clavibacter. Pathogenic Cm strains varied in plasmid composition, highlighting the need for detection methods based on chromosomal targets. We utilized sequences of Cm specific loci two develop a multiplex PCR based diagnostic platform using two Cm chromosomal genes (rhuM and tomA) and an internal control amplifying both bacterial and plant DNA (16s rRNA). The multiplex PCR assay specifically detected Cm strains from a panel of 110 additional bacteria, including other Clavibacter species and bacterial pathogens of tomato. The assay was adapted to detect the presence of Cm in seeds and tomato plant materials with high sensitivity and specificity. In conclusion, the described method represents a robust, specific tool for detection of Cm in tomato seeds and infected plants.
Design of a programmable biosensor-CRISPRi genetic circuits for dynamic and autonomous dual-control of metabolic flux in Bacillus subtilis

Abstract Dynamic regulation is an effective strategy for fine-tuning metabolic pathways in order to maximize target product synthesis. However, achieving dynamic and autonomous up- and down-regulation of the metabolic modules of interest simultaneously, still remains a great challenge. In this work, we created an autonomous dual-control (ADC) system, by combining CRISPRi-based NOT gates with novel biosensors of a key metabolite in the pathway of interest. By sensing the levels of the intermediate glucosamine-6-phosphate (GlcN6P) and self-adjusting the expression levels of the target genes accordingly with the GlcN6P biosensor and ADC system enabled feedback circuits, the metabolic flux towards the production of the high value nutraceutical N-acetylglucosamine (GlcNAc) could be balanced and optimized in Bacillus subtilis. As a result, the GlcNAc titer in a 15-l fed-batch bioreactor increased from 59.9 g/l to 97.1 g/l with acetoin production and 81.7 g/l to 131.6 g/l without acetoin production, indicating the robustness and stability of the synthetic circuits in a large bioreactor system. Remarkably, this self-regulatory methodology does not require any external level of control such as the use of inducer molecules or switching fermentation/environmental conditions. Moreover, the proposed programmable genetic circuits may be expanded to engineer other microbial cells and metabolic pathways.
Interrater reliability assessment of pre-reduction MRI features identifying hazardous disc disruption in distractive-flexion cervical spine injuries.

AIM: This study assessed the interrater reliability of MRI when radiologists and orthopaedic surgeons assess intervertebral disc injury characteristics in distraction flexion (DF) injuries in the cervical spine. The most reliable MRI features of intervertebral disc injury are identified for future use METHODS:Pre-reduction MRI scans of 110 consecutive DF injuries were reviewed independently by a radiology and an orthopaedic surgical team. All cases were managed at a single tertiary referral unit over a ten-year period. Variables included for assessment were: disc herniation (posterior to the inferior vertebrae or above the level of the superior vertebrae's endplate), disc disruption, posterior longitudinal ligament disruption and disc containment. A double data entry method was used. Cohen's kappa value was used to determine interrater reliability RESULTS: Perfect agreement was never achieved between the two teams. The variables that had the highest interrater agreement were posterior disc prolapse and impression of containment. When disagreement occurred, the radiology team would tend to define the lesions as more severe than the orthopaedic team CONCLUSION: MRI assessment of disc injury characteristics carries moderate to fair interrater reliability at best. We conclude that the treating surgeon should review scan images personally prior to choosing a treatment algorithm, not relying solely on a written report. Posterior herniation and disc containment carry the highest interrater reliability.
Integrative In Silico and In Vitro Transcriptomics Analysis Revealed Gene Expression Changes and Oncogenic Features of Normal Cholangiocytes after Chronic Alcohol Exposure

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocyte. Prolonged alcohol consumption has been suggested as a possible risk factor for CCA, but there is no information about alcohol’s mechanisms in cholangiocyte. This study was designed to investigate global transcriptional alterations through RNA-sequencing by using chronic alcohol exposure (20 mM for 2 months) in normal human cholangiocyte MMNK-1 cells. To observe the association of alcohol induced CCA pathogenesis, we combined differentially expressed genes (DEGs) with computational bioinformatics of CCA by using publicly gene expression omnibus (GEO) datasets. For biological function analysis, Gene ontology (GO) analysis showed biological process and molecular function related to regulation of transcription from RNA polymerase II promoter, while cellular component linked to the nucleoplasm. KEGG pathway presented pathways in cancer that were significantly enriched. From KEGG result, we further examined the oncogenic features resulting in chronic alcohol exposure, enhanced proliferation, and migration through CCND-1 and MMP-2 up-regulation, respectively. Finally, combined DEGs were validated in clinical data including TCGA and immunohistochemistry from HPA database, demonstrating that FOS up-regulation was related to CCA pathogenesis. This study is the first providing more information and molecular mechanisms about global transcriptome alterations and oncogenic enhancement of chronic alcohol exposure in normal cholangiocytes.
A low‐cost laboratory‐based method for predicting newly diagnosed biopsy‐proven diabetic nephropathy in people with type 2 diabetes

To identify significant prognostic factors for newly diagnosed biopsy‐proven diabetic nephropathy using routine laboratory measures, from which to derive a low‐cost explanatory model, and to use this model to examine associations between the potential low‐cost test panels and the risk of diabetic nephropathy in people with type 2 diabetes with normal kidney function.
Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes

Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, including hepatic lipid accumulation and lipotoxicity. Plant-derived polyphenols have attracted considerable attention in the prevention of NAFLD. Lotus seedpod, rich in polyphenols, is a traditional Chinese herbal medicine. Previous studies have showed that lotus seedpod possess radioprotective, antioxidant, anti-cancer, and anti-inflammatory activities. In this study, the in vitro hepatoprotective effect of lotus seedpod extract (LSE) and its main component epigallocatechin (EGC) was examined. Firstly, oleic acid (OA), an unsaturated fatty acid, was used to induce the phenotype of NAFLD in human hepatocytes, HepG2 cells. LSE dose-dependently improved the OA-induced viability loss of HepG2 cells. Non-cytotoxic concentrations of LSE or EGC abolished intracellular lipid accumulation and oxidative stress in the OA-treated cells. In addition, LSE and EGC showed a minor effect on autophagy, and potential in reducing OA-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the formation of apoptotic bodies, the exposure of phosphatidylserine, and activation of caspases. Molecular data showed the anti-apoptotic effect of LSE might be mediated via downregulation of the mitochondrial pathway. Our data imply that EGC-enriched LSE potentially could be developed as an anti-NAFLD agent.
Free energy landscape of salt-actuated reconfigurable DNA nanodevices

Abstract Achieving rapid, noninvasive actuation of DNA structures is critical to expanding the functionality of DNA nanotechnology. A promising actuation approach involves introducing multiple, short pairs of single-stranded DNA overhangs to components of the structure and triggering hybridization or dissociation of the overhangs via changes in solution ionic conditions to drive structural transitions. Here, we reveal the underlying basis of this new approach by computing via molecular simulations the free energy landscape of DNA origami hinges actuated between open and closed states. Our results reveal how the overhangs collectively introduce a sharp free-energy minimum at the closed state and a broad energy barrier between open and closed states and how changes in ionic conditions modulate these features of the landscape to drive actuation towards the open or closed state. We demonstrate the critical role played by hinge confinement in stabilizing the hybridized state of the overhangs and magnifying the energy barrier to dissociation. By analyzing how the distribution of overhangs and their length and sequence modulate the energy landscape, we obtain design rules for tuning the actuation behavior. The molecular insights obtained here should be applicable to a broad range of systems involving DNA hybridization within confined systems.