Miracle-dz/UniFAR-FTUs huggingface dataset:
An Efficient and Flexible Method for Deconvoluting Bulk RNA-Seq Data with Single-Cell RNA-Seq Data

Estimating cell type compositions for complex diseases is an important step to investigate the cellular heterogeneity for understanding disease etiology and potentially facilitate early disease diagnosis and prevention. Here, we developed a computationally statistical method, referring to Multi-Omics Matrix Factorization (MOMF), to estimate the cell-type compositions of bulk RNA sequencing (RNA-seq) data by leveraging cell type-specific gene expression levels from single-cell RNA sequencing (scRNA-seq) data. MOMF not only directly models the count nature of gene expression data, but also effectively accounts for the uncertainty of cell type-specific mean gene expression levels. We demonstrate the benefits of MOMF through three real data applications, i.e., Glioblastomas (GBM), colorectal cancer (CRC) and type II diabetes (T2D) studies. MOMF is able to accurately estimate disease-related cell type proportions, i.e., oligodendrocyte progenitor cells and macrophage cells, which are strongly associated with the survival of GBM and CRC, respectively.
SnRK2 Protein Kinases and mRNA Decapping Machinery Control Root Development and Response to Salt1[OPEN]

Salinity stress shapes root development through control of mRNA stability and requires the partially redundant function of SnRK2 protein kinases to modulate transcript levels. SNF1-RELATED PROTEIN KINASES 2 (SnRK2) are important components of early osmotic and salt stress signaling pathways in plants. The Arabidopsis (Arabidopsis thaliana) SnRK2 family comprises the abscisic acid (ABA)–activated protein kinases SnRK2.2, SnRK2.3, SnRK2.6, SnRK2.7, and SnRK2.8, and the ABA-independent subclass 1 protein kinases SnRK2.1, SnRK2.4, SnRK2.5, SnRK2.9, and SnRK2.10. ABA-independent SnRK2s act at the posttranscriptional level via phosphorylation of VARICOSE (VCS), a member of the mRNA decapping complex, that catalyzes the first step of 5′mRNA decay. Here, we identified VCS and VARICOSE RELATED (VCR) as interactors and phosphorylation targets of SnRK2.5, SnRK2.6, and SnRK2.10. All three protein kinases phosphorylated Ser-645 and Ser-1156 of VCS, whereas SnRK2.6 and SnRK2.10 also phosphorylated VCS Ser-692 and Ser-680 of VCR. We showed that subclass 1 SnRK2s, VCS, and 5′ EXORIBONUCLEASE 4 (XRN4) are involved in regulating root growth under control conditions as well as modulating root system architecture in response to salt stress. Our results suggest interesting patterns of redundancy within subclass 1 SnRK2 protein kinases, with SnRK2.1, SnRK2.5, and SnRK2.9 controlling root growth under nonstress conditions and SnRK2.4 and SnRK2.10 acting mostly in response to salinity. We propose that subclass 1 SnRK2s function in root development under salt stress by affecting the transcript levels of aquaporins, as well as CYP79B2, an enzyme involved in auxin biosynthesis.
The association of early life stressors with pain sensitivity and pain experience at 22 years.

Early life stress (ELS) can significantly influence biological pathways associated with nociception, increasing vulnerability to future heightened pain sensitivity and subsequent risk of pain events. However, very little human research has investigated the association of ELS, measured across multiple domains, with future pain sensitivity. Data from Gen1 and Gen2 of the Raine Study were used to assess the association between a wide range of early life stressors, including in antenatally, and pressure and cold pain sensitivity at young adulthood. Participants were classified into two groups according to their cold pain sensitivity. Additionally, the interaction between ELS, pain sensitivity and pain experience (based on Örebro Musculoskeletal Pain Questionnaire) at age 22 years was examined. Analysis was done using both a complete case and multiple imputation approach, adjusting for contemporaneous 22 year correlates, with comparable results in each model. More problematic behaviour at age two was associated with less pressure pain sensitivity at 22 years (13.7kPa, 95%CI:1.0 to 27.0, p=0.037), with no interaction between problematic behaviour and pain experience at 22 years. For those reporting a moderate/high pain experience at 22 years, poor family functioning increased the odds ratio for high cold pain sensitivity (3.0, 95%CI: 1.6 to 5.6), but for those reporting no/low pain experience it did not (OR:1.2, 95%CI: 0.8 to 1.8). This study provides the most comprehensive investigation of the relationship between ELS and pressure and cold pain sensitivity in young adults supporting early life as a critical period of development influencing future nociceptive processing.
Development of an Aryloxazole Derivative as a Brain-Permeable Anti-Glioblastoma Agent

Glioblastoma drug development has been difficult due to the extremely low blood brain barrier (BBB) penetration of conventional anti-cancer agents. P-glycoprotein, an efflux membrane transporter, is responsible for the poor brain uptake of small and hydrophobic drug substances. To develop brain-penetrable anti-tumor agents, we designed colchicine derivatives containing an aryloxazole moiety, which is known to inhibit P-glycoprotein. Among those tested, an aryloxazole derivative named KIST-G1 showed the strongest anti-glioblastoma cell proliferation activity (IC50 = 3.2 ± 0.8 nM). Compared to colchicine, KIST-G1 showed dramatically increased BBB-permeable properties presenting 51.7 ± 0.5 (10−6 cm/s) parallel artificial membrane permeability assay (PAMPA) permeability and 45.0 ± 6.0% of P-gp inhibition. Aid by the BBB-permeable properties, KIST-G1 (5 mg/kg) suppressed glioblastoma cell growth and migration almost completely in the brain of glioblastoma xenograft models by showing 98.2 ± 0.1% reduced tumor area compared with phosphate buffered saline (PBS)-injected control. In comparison, temozolomide, which is the most widely used drug for glioblastoma, showed only moderate effects. Our results demonstrate the effectiveness of an aryloxazole moiety in targeting brain tumors and suggest KIST-G1 as a potent anti-glioblastoma agent.
Biological effects of melatonin on human adipose-derived mesenchymal stem cells

Mesenchymal stem cells (MSCs) are capable of differentiating into other cell types and exhibit immunomodulatory effects. MSCs are affected by several intrinsic and extrinsic signaling modulators, including growth factors, cytokines, extracellular matrix and hormones. Melatonin, produced by the pineal gland, is a hormone that regulates sleep cycles. Recent studies have shown that melatonin improves the therapeutic effects of stem cells. The present study aimed to investigate whether melatonin enhances the biological activities of human adipose-derived MSCs. The results demonstrated that treatment with melatonin promoted cell proliferation by inducing SRY-box transcription factor 2 gene expression and preventing replicative senescence. In addition, melatonin exerted anti-adipogenic effects on MSCs. PCR analysis revealed that the expression of the CCAAT enhancer binding protein a gene, a key transcription factor in adipogenesis, was decreased following melatonin treatment, resulting in reduced adipogenic differentiation in an in vitro assay. The present study also examined the effect of melatonin on the immunomodulatory response using a co-culture system of human peripheral blood mononuclear cells and MSCs. Activated T cells were strongly inhibited following melatonin exposure compared with those in the control group. Finally, the favorable effects of melatonin on MSCs were confirmed using luzindole, a selective melatonin receptor antagonist. The proliferation-promoting, anti-inflammatory effects of melatonin suggested that melatonin-treated MSCs may be used for effective cell therapy.
A Shared-Electrode and Nested-Tube Structure Triboelectric Nanogenerator for Motion Energy Harvesting

Triboelectric nanogenerators with the function of harvesting human motion energy have attracted wide attention. Here, we demonstrate a shared-electrode and nested-tube structure triboelectric nanogenerator (SNTN) for harvesting human motion energy. The design of the SNTN employs flexible silicone rubber as the negative friction material and Ni-coated polyester conductive textile as the positive friction material and the electrode material. The entire structure consists of an inner triboelectric unit and an outer triboelectric unit. The inner triboelectric unit is formed by a hollow inner tube and a hollow middle tube, while the hollow middle tube and a hollow outer tube constitute the outer triboelectric unit. The hollow middle tube is used as the shared tube, and the electrode in the middle tube is used as the shared electrode of the two triboelectric units. Our research demonstrates that the output performance of the SNTN was improved significantly compared with a single triboelectric unit due to the cooperation of the two triboelectric units. When the SNTN is pressed by 300 N external force, output open-circuit voltage of 180 V and output short-circuit current of 8.5 μA can be obtained. The output electrical energy can light up 31 light-emitting diodes (LEDs) connected serially (displaying “XZTC”) and can drive a digital clock after rectifying storage, which shows application prospects in the field of illuminating devices and portable electronics.
Intraoperative cone-beam CT spatial priors for diffuse optical fluorescence tomography

A hybrid system for intraoperative cone-beam CT (CBCT) imaging and continuous-wave fluorescence tomography (FT) has been developed using an image-guidance framework. Intraoperative CBCT images with sub-millimeter spatial resolution are acquired with a flat-panel C-Arm. Tetrahedral meshes are generated from CBCT for finite element method implementation of diffuse optical tomography (NIRFAST). Structural data from CBCT is incorporated directly into the optical reconstruction process using Laplacian-type regularization (‘soft spatial priors’). Experiments were performed using an in-house optical system designed for indocyanine green (ICG) fluorescence. A dynamic non-contact geometry was achieved using a stereoscopic optical tracker for real-time localization of a laser diode and CCD camera. Source and detector positions were projected onto the boundary elements of the tissue mesh using algorithms for ray-triangle intersection and camera lens calibration. Simulation studies showed the capabilities of a soft-prior approach, even in the presence of segmentation uncertainties. Experiments with ICG targets embedded in liquid phantoms determined the improvements in the quantification of the fluorophore yield, with errors of 85% and <20% for no priors and spatial priors, respectively. Similar results were observed with the ICG target embedded in ex vivo porcine loin, with errors of 52% and 12%, respectively. A proof-of-principal animal study was performed in a VX2-tumor in vivo rabbit model using liposomal nanoparticles co-encapsulating contrast for CT (iohexol) and fluorescence (ICG) imaging. Fusion of CBCT and FT reconstructions demonstrated concurrent anatomical and functional delineations of contrast enhancement around the periphery of the buccal tumor. These developments motivate future clinical translation of the FT system into an ongoing CBCT-guided head and neck surgery trial.
Spatially-variant image-based modeling of PSF deformations with application to a limited angle geometry from a dual-panel breast-PET imager

Dual-panel PET system configuration can lead to spatially variable point-spread functions (PSF) of considerable deformations due to depth-of-interaction effects and limited angular coverage. If not modelled properly, these effects result in decreased and inconsistent recovery of lesion activity across the field-of-view (FOV), as well as mispositioning of lesions in the reconstructed image caused by strong PSF asymmetries. We implemented and evaluated models of such PSF deformations with spatially-variant image-based resolution modeling (IRM) within reconstruction (varRM) using the Direct Image REConstruction for Time-of-flight (DIRECT) method and within post-reconstruction deconvolution methods. In addition, DIRECT reconstruction was performed with a spatially-invariant IRM (invRM) and without resolution modeling (noRM) for comparison. The methods were evaluated using simulated data for a realistic breast model with a set of 5 mm lesions located throughout the FOV of a dual-panel Breast-PET scanner. We simulated high-count data to focus on the ability of each method to correctly recover the PSF deformations, and a clinically realistic count level to assess the impact of low count data on the quantitative performance of the evaluated techniques. Performance of the methods evaluated herein was assessed by comparing lesion activity recovery (%BIAS), consistency (%SD) across the FOV, overall error (%RMSE), and recovery of each lesion location. As expected, all techniques using IRM provide considerable improvement over the noRM reconstruction. For the high-count cases, the overall quantitative performance of all IRM techniques, whether within reconstruction or within post-reconstruction, is similar if the lesion location misplacements are ignored. However, invRM provides less consistent performance on activity across lesions and is not able to recover accurate lesion locations. For a clinically realistic count level, varRM reconstruction consistently outperforms all compared approaches, while the post-reconstruction IRM approaches exhibit higher %SD and %RMSE values due to being more affected by the data noise than the within-reconstruction IRM approaches.
6-Shogaol Suppresses 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b] Pyridine (PhIP)-Induced Human 786-O Renal Cell Carcinoma Osteoclastogenic Activity and Metastatic Potential

2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) which can be detected in processed meats and red meats, is a potential carcinogen for renal cell carcinoma (RCC). Approximately 30% of patients with metastatic RCC have bone metastases, and the prognosis of RCC with bone metastases is poor. Thus, the aim of the present study was to investigate whether PhIP induced bone metastases and to develop novel therapeutic agents. Our data revealed that PhIP pre-treatment increased the production of parathyroid hormone-related protein (PTHrP) in human 786-O renal cell carcinoma cells. Subsequently, the cultures of human osteoblasts with PhIP-stimulated condition medium of 786-O increased the expression of the macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL), and decreased the expression of osteoprotegerin (OPG). In addition, PhIP-mediated PTHrP up-regulated as well as increased IL-8 secretion in 786-O cells, and then contributed to 786-O-mediated bone resorption. Furthermore, 6-shogaol, which is an active ingredient in ginger, showed suppressive effects on PhIP-mediated bone resorption. In summary, this is the first study to demonstrate that PhIP pre-treatment increases the stimulatory effect of human renal cell carcinoma 786-O on osteoclastogenesis activity directly by PTHrP. In addition, 6-shogaol treatment reverses PhIP-mediated bone resorption. It suggests that 6-shogaol treatment results in bone resorption activity in the RCC model in vitro.
Neonatal Antifungal Consumption Is Dominated by Prophylactic Use; Outcomes From The Pediatric Antifungal Stewardship: Optimizing Antifungal Prescription Study.

BACKGROUND Diagnostic challenges combined with the vulnerability of neonates to develop invasive candidiasis (IC) may lead to antifungal administration in the absence of IC. A modified point-prevalence study was performed to obtain an improved insight and understanding of antifungal prescribing in this specific patient population. METHODS Neonates and infants ≤90 days of age receiving systemic antifungals from 12 centers in England were included. Data were collected prospectively during 26 consecutive weeks and entered into an online REDCap database. RESULTS Two hundred eighty neonates and infants were included, the majority ≤1 month of age (68.2%). Prematurity was the commonest underlying condition (68.9%). Antifungals were prescribed for prophylactic reason in 79.6%; of those, 64.6% and 76.3% were extreme low birth weight infants and prematurely born neonates, respectively. Additional risk factors were present in almost all patients, but only 44.7% had ≥3 risk factors rendering them more susceptible to develop IC. Nonpremature and non extremely low birth weight premature infants only scored ≥3 risk factors in 32.6% and 15%, respectively. Fluconazole was the most common antifungal used (76.7% of all prescriptions), and commonly underdosed as treatment. The number of microbiological proven IC was low, 5.4%. CONCLUSIONS Neonatal antifungal prophylaxis is commonly prescribed outside the recommendations based on known risk profiles. Fluconazole is the main antifungal prescribed in neonates and infants, with underdosing frequently observed when prescribed for treatment. Number of proven IC was very low. These observations should be taken into consideration to develop a national pediatric Antifungal Stewardship program aiming to guide rational prescribing.
Neuroanatomy and function of human sexual behavior: A neglected or unknown issue?

Sexual desire, arousal, and orgasm are mediated by complex, yet still not fully understood, interactions of the somatic and autonomic nervous systems operating at the central and peripheral levels. Disruption of endocrine, neural, or vascular response, caused by aging, medical illness, neurological diseases, surgery, or drugs, can lead to sexual dysfunctions, thus significantly affecting patients' quality of life.
The use of aquatic therapy among rehabilitation professionals for individuals with spinal cord injury or disorder

Context/Objective: Aquatic therapy (AT) has been used to enhance balance and mobility in people with disabilities; however, AT is reported to be underused among people with spinal cord injury or disorder (SCI/D). We aimed to understand the perceptions of AT use by physical therapists (PT), PT assistants (PTA) and kinesiologists (KIN) across Canada for clients with SCI/D. Design/Methods: Individual semi-structured interviews were completed with PT, PTA and KIN (phone or in-person). PT, PTA and KIN who had used AT with at least one client with SCI/D in the past year were eligible. Interview questions queried each participant’s AT setting, AT approaches, and perceived facilitators and barriers to AT implementation for clients with SCI/D. Interviews were audio recorded and transcribed verbatim. Thematic analysis was used to identify themes and subthemes. Results: Six PT (2 male, 4 female), three PTA (female) and 1 KIN (female) participated. The following four themes were identified: (1) multi-system benefits from AT (e.g. from impairment to function, confidence and enjoyment); (2) application of AT (e.g. based on principles of the water); (3) perceived barriers to implementing AT (e.g. pool accessibility, client comorbidities); and (4) water as an enabler to function on land. Conclusions: The participants reported AT was a unique and versatile approach that benefits the multi-dimensional aspects of the health of individuals with SCI/D. They successfully integrated AT into their clinical practice despite the barriers faced by professionals and clients.
ARGAS (PERSICARGAS) GIGANTEUS SOFT TICK INFECTION WITH RICKETTSIA HOOGSTRAALI AND RELAPSING FEVER BORRELIA ON WILD AVIAN SPECIES OF THE DESERT SOUTHWEST, USA

Abstract: Changing climatic conditions and the northward expansion of ticks and pathogens are of immense importance to human, animal, and environmental health assessment and risk management. From 2014 through 2015, a wildlife rehabilitation center in south-central Arizona, US noted soft ticks (Argasidae) infesting 23 birds, including Cooper's Hawks (Accipiter cooperii), Gray Hawks (Buteo plagiatus), Harris's Hawks (Parabuteo unicinctus), Red-tailed Hawks (Buteo jamaicensis), Great Horned Owls (Bubo virginianus), Common Ravens (Corvus corax), and a Greater Roadrunner (Geococcyx californianus), during the late summer seasonal rainy seasons. The parasites numbered in the hundreds on individual birds. Infested birds were moribund, obtunded, or paralyzed on presentation, with no prior histories of illness or evidence of trauma. Tick and avian blood samples were collected for vector-borne pathogen analysis focusing on the molecular detection of Rickettsia and Borrelia species. Ticks were identified as the neotropical species of soft tick, Argas (Persicargas) giganteus; their occurrence in the southern US on raptors represented an expansion of host range. Pathogen testing of ticks showed that 41% of 54 ticks were infected with Rickettsia hoogstraalii and 23% of 26 ticks were infected with a relapsing fever Borrelia; both agents are associated with uncertain health consequences. Among the blood samples, one was infected with the same Borrelia spp. ; this Red-tailed Hawk also had Borrelia-positive ticks. With supportive therapy, the majority of birds, 74% (17/23), recovered and were released or permanent residents. The management of soft tick–infested birds and mitigation of future disease risk will require additional characterizations of these poorly studied soft ticks and their associated pathogens.
Development and Validity of a Workplace Health Promotion Best Practices Assessment.

OBJECTIVE To explore the factor structure of the HERO Scorecard to develop a reduced version and examine the reliability and validity of that version. METHODS A reduced version of the HERO Scorecard was developed through formal statistical analyses on data collected from 845 organizations that completed the original HERO Scorecard. RESULTS The final factors in the reduced Scorecard represented content pertaining to Organizational & Leadership Support, Program Comprehensiveness, Program Integration, and Incentives. All four implemented practices were found to have a strong, statistically significant effect on Perceived Effectiveness. Organizational & Leadership Support had the strongest effect (β = 0.56), followed by Incentives (β = 0.23). CONCLUSION The condensed version of the HERO Scorecard has the potential to be a promising tool for future research on the extent to which employers are adopting best practices in their HWB initiatives.
Plasmon-enhanced linear and second-order surface nonlinear optical response of silver nanoparticles fabricated using a femtosecond pulse

We present the plasmon-enhanced linear and second-order surface nonlinear optical response of silver nanoparticles (Ag NPs) fabricated using a femtosecond pulse. Theoretical analysis indicates Ag NPs with a diameter of ∼100 nm have excellent linear response within the visible band, and the electric field intensity enhancement factor reaches ∼105 under excitation of continuous light of 632.8 nm. Meanwhile, the simulation result of second-order surface nonlinear optical response shows that the second harmonic conversion efficiency of the Ag NPs dimer is two orders of magnitude higher than that of a single Ag NP, under excitation of a femtosecond pulse. In experiment, the linear response of Ag NPs is examined using surface-enhanced Raman spectroscopy (SERS) with a Raman enhancement factor of ∼1.7 × 1010, revealing the excellent linear optical response of Ag NPs. Moreover, the spectra of the second harmonic can be measured clearly under conditions of an average pump power of 40 μW, revealing the excellent second-order surface nonlinear optical response of Ag NPs.