Miracle-dz/UniFAR-FTUs huggingface dataset:
Chitinase-3-like-1 protein complexes modulate macrophage-mediated immune suppression in glioblastoma.

Glioblastoma is a highly malignant and incurable brain tumor characterized by intrinsic and adaptive resistance to immunotherapies. However, how glioma cells induce tumor immunosuppression and escape immunosurveillance remains poorly understood. Here, we find upregulation of cancer-intrinsic Chitinase-3-like-1 (CHI3L1) signaling modulating an immunosuppressive microenvironment by reprogramming tumor-associated macrophages (TAMs). Mechanistically, CHI3L1 binding with Galectin-3 (Gal3) selectively promotes TAM migration and infiltration with a protumor M2-like but not an antitumor M1-like phenotype in vitro and in vivo, governed by a transcriptional program of NFκB/CEBPβ in the CHI3L1/Gal3-PI3K/AKT/mTOR axis. Conversely, Galectin-3-binding protein (Gal3BP) negatively regulates this process by competing with Gal3 to bind CHI3L1. Administration of a Gal3BP mimetic peptide in syngeneic glioblastoma mouse models reverses immune suppression and attenuates tumor progression. These results shed light on the role of CHI3L1 protein complexes in immune evasion by glioblastoma and as a potential immunotherapeutic target for this devastating disease.
Myoelectric control of robotic lower limb prostheses: a review of electromyography interfaces, control paradigms, challenges and future directions

Objective. Advanced robotic lower limb prostheses are mainly controlled autonomously. Although the existing control can assist cyclic movements during locomotion of amputee users, the function of these modern devices is still limited due to the lack of neuromuscular control (i.e. control based on human efferent neural signals from the central nervous system to peripheral muscles for movement production). Neuromuscular control signals can be recorded from muscles, called electromyographic (EMG) or myoelectric signals. In fact, using EMG signals for robotic lower limb prostheses control has been an emerging research topic in the field for the past decade to address novel prosthesis functionality and adaptability to different environments and task contexts. The objective of this paper is to review robotic lower limb Prosthesis control via EMG signals recorded from residual muscles in individuals with lower limb amputations. Approach. We performed a literature review on surgical techniques for enhanced EMG interfaces, EMG sensors, decoding algorithms, and control paradigms for robotic lower limb prostheses. Main results. This review highlights the promise of EMG control for enabling new functionalities in robotic lower limb prostheses, as well as the existing challenges, knowledge gaps, and opportunities on this research topic from human motor control and clinical practice perspectives. Significance. This review may guide the future collaborations among researchers in neuromechanics, neural engineering, assistive technologies, and amputee clinics in order to build and translate true bionic lower limbs to individuals with lower limb amputations for improved motor function.
Ocimum tenuiflorum mitigates iron‐induced testicular toxicity via modulation of redox imbalance, cholinergic and purinergic dysfunctions, and glucose metabolizing enzymes activities

Oxidative stress is a primary culprit in the pathophysiology of infertility conditions in males. This study investigated the effects of Ocimum tenuiflorum on redox imbalance, cholinergic and purinergic dysfunctions and glucose dysmetabolism in oxidative‐mediated testicular toxicity using in vitro, ex vivo and in silico models. Induction of oxidative testicular injury was carried out by incubating normal testicular tissue with 0.1 mM FeSO4 and treated by co‐incubating with different concentrations of O. tenuiflorum infusion for 30 min at 37°C. O. tenuiflorum displayed significant ferric reducing power activity while scavenging DPPH and hydroxyl (OH˙) free radicals in vitro. Oxidative testicular injury significantly reduced the glutathione level and superoxide dismutase and catalase activities with concomitant elevation of malondialdehyde and nitric oxide levels and acetylcholinesterase, ATPase, fructose‐1,6‐bisphosphatase and glycogen phosphorylase (GlyP) activities. Incubation with the infusion significantly reversed these levels and activities. The phytochemical constituent of the infusion was detected by gas chromatography–mass spectroscopy analysis and revealed favourable binding energies when docked with some of the studied proteins. These results suggest O. tenuiflorum exerts a protective effect against Fe2+ induced testicular toxicity via mitigation of redox imbalance while modulating metabolic dysfunctions linked to male infertility.
Hormetic endoplasmic reticulum stress in hematopoietic stem cells

Purpose of review Hematopoietic stem cells (HSCs) possess the ability to regenerate over a lifetime in the face of extreme cellular proliferation and environmental stress. Yet, mechanisms that control the regenerative properties of HSCs remain elusive. ER stress has emerged as an important signaling event that supports HSC self-renewal and multipotency. The purpose of this review is to summarize the pathways implicating ER stress as cytoprotective in HSCs. Recent findings Recent studies have shown multiple signaling cascades of the unfolded protein response (UPR) are persistently activated in healthy HSCs, suggesting that low-dose ER stress is a feature HSCs. Stress adaptation is a feature ascribed to cytoprotection and longevity of cells as well as organisms, in what is known as hormesis. However, assembling this information into useful knowledge to improve the therapeutic application of HSCs remains challenging and the upstream activators and downstream transcriptional programs induced by ER stress that are required in HSCs remain to be discovered. Summary The maintenance of HSCs requires a dose-dependent simulation of ER stress responses that involves persistent, low-dose UPR. Unraveling the complexity of this signaling node may elucidate mechanisms related to regeneration of HSCs that can be harnessed to expand HSCs for cellular therapeutics ex vivo and transplantation in vivo.
Dominance, reward, and affiliation smiles modulate the meaning of uncooperative or untrustworthy behaviour

ABSTRACT We investigated the effects of different types of smiles on the perception of uncooperative or untrustworthy behaviour. In five studies, participants assigned to one group played an economic game with a representative of another group. In an initial round, the representative acted uncooperatively by favouring their group and then displayed a dominance, reward, or affiliation smile. Participants rated the motives of the representative and played a second round of the game with a different member of the same outgroup. Following uncooperative or untrustworthy behaviour, affiliation smiles communicated less positivity and superiority, and a greater desire to both repair the relationship between groups and change the uncooperative decision than reward or dominance smiles. Perceptions of a desire to repair the relationship and to change the decision were associated with trust and cooperation in a subsequent round of the game. Together, these findings show that smiles that are subtly different in their morphology can convey different messages and highlight the importance of these expressions in influencing the perceptions of others’ intentions.
Structural and functional insights on vitamin D receptor and CYP24A1 deleterious single nucleotide polymorphisms: A computational and pharmacogenomics perpetual approach

The development of chronic kidney disease (CKD) drugs remains a challenge due to the variations in the genes. The vitamin D receptor (VDR) and Cytochrome 24A1 (CYP24A1) genetic variants might affect the drug potency, efficacy and pathway. Here we have to analyse and determine the deleterious single‐nucleotide polymorphisms (nsSNPs) of VDR and CYP24A1 genes and their different population's drug responses in different populations to understand the key role in CKD. Among that the large scale of nsSNP, we used certain computational tools that predicted six missense variants are observed to be significantly damaging effect and SNP variability with large differences in various populations. Molecular docking studies were carried out by clinical and our screened compounds to VDR and CYP24A1. Docking results revealed all the compounds have a good binding affinity (Score). The screened compounds (TCM_2868 and UNPD_141613) show good binding affinity when compared to known compounds. The QM/MM study revealed that the compounds have electron transfer ability and act as a donor/acceptor to mutated proteins. The structural and conformational changes of protein complexes were analysed by molecular dynamics study. Hence, this study helps to identify suitable drugs through drug discovery in CKD treatment. The abovementioned compounds have more binding affinity, efficacy, and potency of both wild and mutant of VDR and CYP24A1.
Pharmacogenomics in Cardiovascular Diseases

Cardiovascular pharmacogenomics is the study and identification of genomic markers that are associated with variability in cardiovascular drug response, cardiovascular drug−related outcomes, or cardiovascular drug−related adverse events. This overview presents an introduction and historical background to cardiovascular pharmacogenomics, and a protocol for designing a cardiovascular pharmacogenomics study. Important considerations are also included for constructing a cardiovascular pharmacogenomics phenotype, designing the replication or validation strategy, common statistical approaches, and how to put the results in context with the cardiovascular drug or cardiovascular disease under investigation. © 2021 Wiley Periodicals LLC.
Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure

Supplemental Digital Content is available in the text. Background: Current paradigms suggest that nitric oxide (NO) produced by endothelial cells (ECs) through endothelial nitric oxide synthase (eNOS) in the vessel wall is the primary regulator of blood flow and blood pressure. However, red blood cells (RBCs) also carry a catalytically active eNOS, but its role is controversial and remains undefined. This study aimed to elucidate the functional significance of RBC eNOS compared with EC eNOS for vascular hemodynamics and nitric oxide metabolism. Methods: We generated tissue-specific loss- and gain-of-function models for eNOS by using cell-specific Cre-induced gene inactivation or reactivation. We created 2 founder lines carrying a floxed eNOS (eNOSflox/flox) for Cre-inducible knockout (KO), and gene construct with an inactivated floxed/inverted exon (eNOSinv/inv) for a Cre-inducible knock-in (KI), which respectively allow targeted deletion or reactivation of eNOS in erythroid cells (RBC eNOS KO or RBC eNOS KI mice) or in ECs (EC eNOS KO or EC eNOS KI mice). Vascular function, hemodynamics, and nitric oxide metabolism were compared ex vivo and in vivo. Results: The EC eNOS KOs exhibited significantly impaired aortic dilatory responses to acetylcholine, loss of flow-mediated dilation, and increased systolic and diastolic blood pressure. RBC eNOS KO mice showed no alterations in acetylcholine-mediated dilation or flow-mediated dilation but were hypertensive. Treatment with the nitric oxide synthase inhibitor Nγ-nitro-l-arginine methyl ester further increased blood pressure in RBC eNOS KOs, demonstrating that eNOS in both ECs and RBCs contributes to blood pressure regulation. Although both EC eNOS KOs and RBC eNOS KOs had lower plasma nitrite and nitrate concentrations, the levels of bound NO in RBCs were lower in RBC eNOS KOs than in EC eNOS KOs. Reactivation of eNOS in ECs or RBCs rescues the hypertensive phenotype of the eNOSinv/inv mice, whereas the levels of bound NO were restored only in RBC eNOS KI mice. Conclusions: These data reveal that eNOS in ECs and RBCs contribute independently to blood pressure homeostasis.
Outcomes of Person-centered Care for Persons with Dementia in the Acute Care Setting: A Pilot Study

ABSTRACT Objectives This pilot study assessed clinical outcomes and quality care for persons with dementia in an acute hospital with PCC, compared with usual care. Methods Forty-seven consented persons 60 years and over with dementia were assigned to PCC (n = 26) or usual care (control) (n = 21). Hospital nurses and allied health staff received 3 h of face-to-face education in PCC, and practice support by four PCC-trained nurse champions. Control group staff received 3 h of face-to-face education on dementia and delirium care clinical guidelines. Primary outcomes behavioral/neuropsychiatric symptoms and care quality were analyzed based on repeated measures at baseline (Time 1), 4–5 days after baseline (Time 2) and day 8–10 after baseline (Time 3) where available. Results Compared with controls, at Time 2 PCC produced statistically significant improvements in behavioral/neuropsychiatric symptoms (adjusted p = .036) and care quality (adjusted p = .044). Where length of stay exceeded 8 days after baseline (Time 3), there was a sustained improvement in quality care (p = .007), but not in behavioral/neuropsychiatric symptoms (p = .27). Conclusions PCC can improve care quality for persons with dementia; nursing; agitation; paid caregivers with dementia and reduce behavioral/neuropsychiatric symptoms during short hospital stays. Clinical Implications Hospital systems need to support PCC to reduce behavioral/neuropsychiatric symptoms in dementia during long hospital stays.
Identifying the Basis for VirS/VirR Two-Component Regulatory System Control of Clostridium perfringens Beta-Toxin Production

Clostridium perfringens beta toxin (CPB) is only produced by type B and C strains. Production of CPB is essential for the pathogenesis of type C-associated infections, which include hemorrhagic necrotizing enteritis and enterotoxemia in both humans and animals. ABSTRACT Clostridium perfringens toxin production is often regulated by the Agr-like quorum sensing (QS) system signaling the VirS/VirR two-component regulatory system (TCRS), which consists of the VirS membrane sensor histidine kinase and the VirR response regulator. VirS/VirR is known to directly control expression of some genes by binding to a DNA binding motif consisting of two VirR boxes located within 500 bp of the target gene start codon. Alternatively, the VirS/VirR system can indirectly regulate production levels of other proteins by increasing expression of a small regulatory RNA, VR-RNA. Previous studies demonstrated that C. perfringens beta-toxin (CPB) production by C. perfringens type B and C strains is positively regulated by both the Agr-like QS and the VirS/VirR TCRS, but the mechanism has been unclear. The current study first inactivated the vrr gene encoding VR-RNA to show that VirS/VirR regulation of cpb expression does not involve VR-RNA. Subsequently, bioinformatic analyses identified a potential VirR binding motif, along with a predicted strong promoter, ∼1.4 kb upstream of the cpb open reading frame (ORF). Two insertion sequences were present between this VirR binding motif/promoter region and the cpb ORF. PCR screening of a collection of strains carrying cpb showed that the presence and sequence of this VirR binding motif/promoter is highly conserved among CPB-producing strains. Reverse transcription-PCR (RT-PCR) and a GusA reporter assay showed this VirR binding motif is important for regulating CPB production. These findings indicate that VirS/VirR directly regulates cpb expression via VirS binding to a VirR binding motif located unusually distant from the cpb start codon. IMPORTANCE Clostridium perfringens beta-toxin (CPB) is only produced by type B and C strains. Production of CPB is essential for the pathogenesis of type C-associated infections, which include hemorrhagic necrotizing enteritis and enterotoxemia in both humans and animals. In addition, CPB can synergize with other toxins during C. perfringens gastrointestinal diseases. CPB toxin production is cooperatively regulated by the Agr-like quorum sensing (QS) system and the VirS/VirR two-component regulatory system. This study now reports that the VirS/VirR regulatory cascade directly controls expression of the cpb gene via a process involving a VirR box binding motif located unusually far (∼1.4 kb) upstream of the cpb ORF. This study provides a better understanding of the regulatory mechanisms for CPB production by the VirS/VirR regulatory cascade.
Endovascular administration of magnetized nanocarriers targeting brain delivery after stroke

The increasing use of mechanical thrombectomy in stroke management has opened the window to local intraarterial brain delivery of therapeutic agents. In this context, the use of nanomedicine could further improve the delivery of new treatments for specific brain targeting, tracking and guidance. In this study we take advantage of this new endovascular approach to deliver biocompatible poly(D-L-lactic-co-glycolic acid) (PLGA) nanocapsules functionalized with superparamagnetic iron oxide nanoparticles and Cy7.5 for magnetic targeting, magnetic resonance and fluorescent molecular imaging. A complete biodistribution study in naïve (n = 59) and ischemic (n = 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraordinary advantage of the intraarterial route for brain delivery with a specific improvement in cortical targeting when using a magnetic device in both control and ischemic conditions. Safety was evaluated in ischemic mice (n = 69) showing no signs of systemic toxicity nor increasing mortality, infarct lesions or hemorrhages. In conclusion, the challenging brain delivery of therapeutic nanomaterials could be efficiently and safely overcome with a controlled endovascular administration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke.
Solvent extraction of Zr and Hf from hydrochloric acid using tributylphosphate for the extraction of element 104, rutherfordium

Summary For the solvent extraction experiment on element 104 (Rf), solvent extraction of Zr and Hf as its homologues was performed in tributylphosphate (TBP)/hydrochloric acid (HCl) system using the carrier-free radiotracers 88Zr and 175Hf. Time dependences of the distribution ratios of Zr and Hf were investigated using 6.1 and 10.0M HCl and 0.5 and 2.0M TBP benzene solutions. The distribution ratios in equilibrium were determined for these elements as a function of HCl concentrations in the range of 4.1-10.2M. We found that the neutral chloride complexes of Zr and Hf were formed and extracted into the organic phase within 20 min in HCl with a concentration higher than 6 M. From the results, we propose that solvent extraction of Rf from 4-8M HCl into 2.0M TBP benzene is suitable for investigating the chloride complexation properties of Rf. In addition, for the development of the rapid liquid-liquid extraction apparatus, three types of microchannel devices, namely, a micro reactor, capillary tube and micro-chemical chip, were tested as a mixing-solution part in the apparatus. The chemical reactions of Zr and Hf in the extraction were found to be fast only when using the microchemical chip, which is important for investigations with the 68-s 261Rf.
Peroral cholecystoscopy using a multibending ultraslim endoscope through a lumen-apposing metal stent for endoscopic ultrasound-guided gallbladder drainage: a feasibility study

Abstract Background Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using a lumen-apposing metal stent (LAMS) has rendered endoscopic gallbladder assessment through a stent possible, but an appropriate endoscope is required. We assessed the feasibility of peroral cholecystoscopy (POCC) using a multibending ultraslim endoscope passed through a LAMS after EUS-GBD. Methods 14 patients with a LAMS for EUS-GBD who consecutively underwent POCC were included. POCC was performed using a multibending endoscope inserted through the LAMS. The primary outcome was the technical success rate, defined as complete endoscopic examination of the gallbladder from the orifice of the cystic duct to the fundus. The types of intervention and adverse events were recorded. Results 17 POCCs were performed in 14 patients. Of the 17 POCCs, 15 (88.2 %) were technically successful. Narrow-band imaging endoscopy was performed in 12 procedures (70.6 %), and cholecystoscopy-guided target biopsies were obtained in six. Gallstone extraction was performed in two patients. After POCC, all LAMSs remained stable and no adverse events were observed. Conclusions POCC using a multibending ultraslim endoscope can be effectively and safely performed through a LAMS after EUS-GBD.
Systematic reviews: Structure, form and content

This article aims to provide an overview of the structure, form and content of systematic reviews. It focuses in particular on the literature searching component, and covers systematic database searching techniques, searching for grey literature and the importance of librarian involvement in the search. It also covers systematic review reporting standards such as PRISMA-P and PRISMA, critical appraisal and tools and resources to support the review and ensure it is conducted efficiently and effectively. Finally, it summarizes the requirements when screening search results for inclusion in the review, and the statistical synthesis of included studies’ findings.
Digital Breast Tomosynthesis: Potential Benefits in Routine Clinical Practice

Digital breast tomosynthesis (DBT) is gradually being implemented in routine clinical breast imaging practice. The technique of image acquisition reduces the confounding effect of overlapping breast tissue, which substantially affects cancer detection, abnormal recall, and interval cancer rates in a screening/ surveillance setting. In a diagnostic setting, tomosynthesis also allows for improved lesion localization and characterization over conventional imaging, which potentially improves the accuracy and improved workflow efficiency. To optimize the utility of tomosynthesis, imagers should be aware of the pertinent aspects of image acquisition as it relates to interpretation, the appearance of benign and malignant pathologies, and sources of possible misinterpretation. This article aims to provide a practical knowledge base of DBT and demonstrate its potential benefits when incorporated into routine clinical practice.
Size-dependent anatase to rutile phase transformation and particle growth

Phase transformation and particle growth are fundamental processes that govern final particle size and morphology, as well as phase composition. At the nanoscale, these processes can be significantly affected by initial particle size. Rates of anatase growth and its transformation to rutile increase with decreasing initial size under hydrothermal conditions at pH 1 and pH 3. Overall, rates are slower at the higher pH. At pH 1, the data fit well to a kinetic model developed based on a dissolution–precipitation mechanism. However, at pH 3, it deviates substantially from the model, indicating that the transformation occurs via a different mechanism or a mixture of dissolution–precipitation and another mechanism, which likely involves aggregation. Finally, the compactness of the aggregates affects the processes significantly. That is, densely aggregated particles show higher transformation and growth rates, compared to loosely aggregated ones.