Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroprotection Following Concussion: The Potential Role for Cannabidiol

ABSTRACT: Cannabidiol (CBD) has been generating increasing interest in medicine due to its therapeutic properties and an apparent lack of negative side effects. Research has suggested that high dosages of CBD can be taken acutely and chronically with little to no risk. This review focuses on the neuroprotective effects of a CBD, with an emphasis on its implications for recovering from a mild traumatic brain injury (TBI) or concussion. CBD has been shown to influence the endocannabinoid system, both by affecting cannabinoid receptors and other receptors involved in the endocannabinoid system such as vanilloid receptor 1, adenosine receptors, and 5-hydroxytryptamine via cannabinoid receptor-independent mechanisms. Concussions can result in many physiological consequences, potentially resulting in post-concussion syndrome. While impairments in cerebrovascular and cardiovascular physiology following concussion have been shown, there is unfortunately still no single treatment available to enhance recovery. CBD has been shown to influence the blood brain barrier, brain-derived neurotrophic factors, cognitive capacity, the cerebrovasculature, cardiovascular physiology, and neurogenesis, all of which have been shown to be altered by concussion. CBD can therefore potentially provide treatment to enhance neuroprotection by reducing inflammation, regulating cerebral blood flow, enhancing neurogenesis, and protecting the brain against reactive oxygen species. Double-blind randomized controlled trials are still required to validate the use of CBD as medication following mild TBIs, such as concussion.
Smoking and suicidal ideation among college students: Smoking expectancies as potential moderators

Abstract Objective: In the present study, we sought to establish a link between suicidal ideation (SI) and smoking in college students, determine whether psychopathology accounted for the association, and determine whether smoking expectancies were moderators. Participants: Participants (N = 607) were identified as nonsmokers, exsmokers, infrequent smokers, or daily smokers. Methods: Participants were assessed for smoking patterns, smoking expectancies, psychopathology, SI, and past suicide attempts. Results: Daily smokers had the highest level of SI. There was a dose-response relationship between smoking and SI, such that the higher the daily smoking rate, the greater the SI, even when controlling for depression, alcohol use, and drug use. Trend-level results indicated that at lower smoking rates, elevated smoking-related negative affect reduction (NAR) expectancies were associated with lower SI, while elevated NAR expectancies in combination with higher smoking rates were associated with greater SI. Conclusion: Smoking cessation programs for college students should screen for SI.
Analysis of Short-Term Effects of Air Pollution on Cardiovascular Disease Using Bayesian Spatio-Temporal Models

There has been an increasing number of clinical and epidemiologic research projects providing supporting evidence that short-term exposure to ambient air pollution contributes to the exacerbation of cardiovascular disease. However, few studies consider measurement error and spatial effects in the estimate of underlying air pollution levels, and less is known about the influence of baseline air pollution levels on cardiovascular disease. We used hospital admissions data for cardiovascular diseases (CVD) collected from an inland, heavily polluted city and a coastal city in Shandong Province, China. Bayesian spatio-temporal models were applied to obtain the underlying pollution level in each city, then generalized additive models were adopted to assess the health effects. The total cardiovascular disease hospitalizations were significantly increased in the inland city by 0.401% (0.029, 0.775), 0.316% (0.086, 0.547), 0.903% (0.252, 1.559), and 2.647% (1.607, 3.697) per 10 μg/m3 increase in PM2.5, PM10, SO2, and NO2, respectively. The total cardiovascular diseases hospitalizations were increased by 6.568% (3.636, 9.584) per 10μg/m3 increase in the level of NO2. Although the air pollution overall had a more significant adverse impact on cardiovascular disease hospital admissions in the heavily polluted inland city, the short-term increases in air pollution levels in the less polluted coastal areas led to excessive exacerbations of cardiovascular disease.
Extension of a multiphase tumour growth model to study nanoparticle delivery to solid tumours

One of the main challenges in increasing the efficacy of conventional chemotherapeutics is the fact that they do not reach cancerous cells at a sufficiently high dosage. In order to remedy this deficiency, nanoparticle-based drugs have evolved as a promising novel approach to more specific tumour targeting. Nevertheless, several biophysical phenomena prevent the sufficient penetration of nanoparticles in order to target the entire tumour. We therefore extend our vascular multiphase tumour growth model, enabling it to investigate the influence of different biophysical factors on the distribution of nanoparticles in the tumour microenvironment. The novel model permits the examination of the interplay between the size of vessel-wall pores, the permeability of the blood-vessel endothelium and the lymphatic drainage on the delivery of particles of different sizes. Solid tumours develop a non-perfused core and increased interstitial pressure. Our model confirms that those two typical features of solid tumours limit nanoparticle delivery. Only in case of small nanoparticles is the transport dominated by diffusion, and particles can reach the entire tumour. The size of the vessel-wall pores and the permeability of the blood-vessel endothelium have a major impact on the amount of delivered nanoparticles. This extended in-silico tumour growth model permits the examination of the characteristics and of the limitations of nanoparticle delivery to solid tumours, which currently complicate the translation of nanoparticle therapy to a clinical stage.
Endoscopist’s Judgment Is as Useful as Risk Scores for Predicting Outcome in Peptic Ulcer Bleeding: A Multicenter Study

Background: Guidelines recommend using prognostic scales for risk stratification in patients with non-variceal upper gastrointestinal bleeding. It remains unclear whether risk scores offer greater accuracy than clinical evaluation. Objective: Compare the diagnostic accuracy of the endoscopist’s judgment against different risk-scoring systems (Rockall, Glasgow–Blatchford, Baylor and the Cedars–Sinai scores) for predicting outcomes in peptic ulcer bleeding (PUB). Methods: Between February 2006 and April 2010 we prospectively recruited 401 patients with peptic ulcer bleeding; 225 received endoscopic treatment. The endoscopist recorded his/her subjective assessment (“endoscopist judgment”) of the risk of rebleeding and death immediately after endoscopy for each patient. Independent evaluators calculated the different scores. Area under the receiver-operating-characteristics (ROC) curve, sensitivity, specificity, positive and negative predictive values were calculated for rebleeding and mortality. Results: The areas under ROC curve of the endoscopist’s clinical judgment for rebleeding (0.67–0.75) and mortality (0.84–0.9) were similar or even superior to the different risk scores in both the whole group and in patients receiving endoscopic therapy. Conclusions: The accuracy of the currently available risk scores for predicting rebleeding and mortality in PUB patients was moderate and not superior to the endoscopist’s judgment. More precise prognostic scales are needed.
TiO2 Nanomaterials Non-Controlled Contamination Could Be Hazardous for Normal Cells Located in the Field of Radiotherapy

Among nanomaterials (NMs), titanium dioxide (TiO2) is one of the most manufactured NMs and can be found in many consumers’ products such as skin care products, textiles and food (as E171 additive). Moreover, due to its most attractive property, a photoactivation upon non-ionizing UVA radiation, TiO2 NMs is widely used as a decontaminating agent. Uncontrolled contaminations by TiO2 NMs during their production (professional exposure) or by using products (consumer exposure) are rather frequent. So far, TiO2 NMs cytotoxicity is still a matter of controversy depending on biological models, types of TiO2 NMs, suspension preparation and biological endpoints. TiO2 NMs photoactivation has been widely described for UV light radiation exposure, it could lead to reactive oxygen species production, known to be both cyto- and genotoxic on human cells. After higher photon energy exposition, such as X-rays used for radiotherapy and for medical imaging, TiO2 NMs photoactivation still occurs. Importantly, the question of its hazard in the case of body contamination of persons receiving radiotherapy was never addressed, knowing that healthy tissues surrounding the tumor are indeed exposed. The present work focuses on the analysis of human normal bronchiolar cell response after co-exposition TiO2 NMs (with different coatings) and ionizing radiation. Our results show a clear synergistic effect, in terms of cell viability, cell death and oxidative stress, between TiO2 NMS and radiation.
PRMT5-TRIM21 interaction regulates the senescence of osteosarcoma cells by targeting the TXNIP/p21 axis

Osteosarcoma (OS) is the most common bone malignancy in adolescents and has poor clinical outcomes. Protein arginine methyltransferase 5 (PRMT5) has recently been shown to be aberrantly expressed in various cancers, yet its role in OS remains elusive. Here, we found that PRMT5 was overexpressed in OS and its overexpression predicted poor clinical outcomes. PRMT5 knockdown significantly triggered pronounced senescence in OS cells, as evidenced by the increase in senescence-associated β-galactosidase (SA-β-gal)-stained cells, induction of p21 expression, and upregulation of senescence-associated secretory phenotype (SASP) gene expression. In addition, we found that PRMT5 plays a key role in regulating DNA damaging agents-induced OS cell senescence, possibly, via affecting the repair of DNA damage. Furthermore, we found that TXNIP acts as a key factor mediating PRMT5 depletion-induced DNA damage and cellular senescence. Mechanistically, TRIM21, which interacts with PRMT5, was essential for the regulation of TXNIP/p21 expression. In summary, we propose a model in which PRMT5, by interaction with TRIM21, plays a key role in regulating the TXNIP/p21 axis during senescence in OS cells. The present findings suggest that PRMT5 overexpression in OS cells might confer resistance to chemotherapy and that targeting the PRMT5/TRIM21/TXNIP signaling may enhance the therapeutic efficacy in OS.
Differential Gene Profiling of the Heartwood Formation Process in Taiwania cryptomerioides Hayata Xylem Tissues

Taiwania (Taiwania cryptomerioides) is an important tree species in Taiwan because of the excellent properties of its wood and fascinating color qualities of its heartwood (HW), as well as the bioactive compounds therein. However, limited information is available as to the HW formation of this species. The objective of this research is to analyze the differentially expressed genes (DEGs) during the HW formation process from specific Taiwania xylem tissues, and to obtain genes that might be closely associated with this process. The results indicated that our analyses have captured DEGs representative to the HW formation process of Taiwania. DEGs related to the terpenoid biosynthesis pathway were all up-regulated in the transition zone (TZ) to support the biosynthesis and accumulation of terpenoids. Many DEGs related to lignin biosynthesis, and two DEGs related to pinoresinol reductase (PrR)/pinoresinol lariciresinol reductase (PLR), were up-regulated in TZ. These DEGs together are likely involved in providing the precursors for the subsequent lignan biosynthesis. Several transcription factor-, nuclease-, and protease-encoding DEGs were also highly expressed in TZ, and these DEGs might be involved in the regulation of secondary metabolite biosynthesis and the autolysis of the cellular components of ray parenchyma cells in TZ. These results provide further insights into the process of HW formation in Taiwania.
Correlates of hopelessness in clinically stable nigerian adults with sickle cell disease

Objective: Hopelessness is the most significant predictor of suicide among the clinical and nonclinical populations. The aim of this study is to examine the correlates and predictors of hopelessness among Nigerian adults with sickle cell disease (SCD). Subjects and Methods: Adopting a convenience sampling technique, 123 clinically stable SCD adult patients were selected from three hematological centers in Southwestern Nigeria. They completed a sociodemographic and illness-related questionnaire in addition to the Beck Hopelessness Scale (BHS), the Hospital Anxiety and Depression Scale (HADS), the 10-item Connor-Davidson Resilience Scale (CDRISC-10), and the Sickle Cell Self-Efficacy Scale (SCSES). The relationship between hopelessness and the other study variables was examined using correlational analysis (Spearman's rho). The extent of the variance these measures contributed to the score on the BHS was evaluated applying hierarchical regression analysis. The level of statistical significance was set at P value less than 0.05. Results: The mean age (years) of the participants was 25.38 ± 6.73 years. There were 68 (55.3%) females. The mean BHS score was 2.89 ± 3.30. Hopelessness had modest negative correlations with hemoglobin concentration (r = −0.366, P < 0.001), resilience (r = −0.483, P < 0.001), and self-efficacy (r = −0.318, P < 0.001), while modest positive correlations were observed with the HADS-Anxiety (r = 0.351, P < 0.001) and Depression (r = 0.530, P < 0.001) subscales. The hemoglobin concentration, resilience, and depression were the main predictors of hopelessness. Conclusion: Hopelessness among clinically stable Nigerian adults with SCD is significantly influenced by hemoglobin concentration and psychological variables (resilience and depression). These variables can serve as templates for the development of health promotion strategies (medical and psychological) aimed specifically at the amelioration of the severity of hopelessness within this population.
Electrophysiological Characterization of Transport Across Outer‐Membrane Channels from Gram‐Negative Bacteria in Presence of Lipopolysaccharides

Abstract Multi‐drug resistance in Gram‐negative bacteria is often associated with low permeability of the outer membrane. To investigate the role of membrane channels in the uptake of antibiotics, we present an approach using fusion of native outer membrane vesicles (OMVs) into a planar lipid bilayer, allowing characterization of membrane protein channels in their native environment. Two major membrane channels from E. coli, OmpF and OmpC, were overexpressed from the host and the corresponding OMVs were collected. Each OMV fusion surprisingly revealed only single or few channel activities. The asymmetry of the OMVs translates after fusion into the lipid membrane with the lipopolysaccharides (LPS) dominantly present at the side of OMV addition. Compared to the conventional reconstitution method, the channels fused from OMVs containing LPS have similar conductance but a much broader distribution and significantly lower permeation. We suggest using outer membrane vesicles for functional and structural studies of membrane channels in the native membrane.
The Integral Role of Tight Junction Proteins in the Repair of Injured Intestinal Epithelium

The intestinal epithelial monolayer forms a transcellular and paracellular barrier that separates luminal contents from the interstitium. The paracellular barrier consists of a highly organized complex of intercellular junctions that is primarily regulated by apical tight junction proteins and tight junction-associated proteins. This homeostatic barrier can be lost through a multitude of injurious events that cause the disruption of the tight junction complex. Acute repair after injury leading to the reestablishment of the tight junction barrier is crucial for the return of both barrier function as well as other cellular functions, including water regulation and nutrient absorption. This review provides an overview of the tight junction complex components and how they link to other plasmalemmal proteins, such as ion channels and transporters, to induce tight junction closure during repair of acute injury. Understanding the components of interepithelial tight junctions and the mechanisms of tight junction regulation after injury is crucial for developing future therapeutic targets for patients experiencing dysregulated intestinal permeability.
The INTERNET STUDY: A phase II study of everolimus in patients with fluorodeoxyglucose (18F) positron‐emission tomography positive intermediate grade pancreatic neuroendocrine tumors

This multicenter phase II trial evaluates the efficacy of everolimus in poor prognosis grade 2 (G2) pancreatic neuroendocrine tumors (PNETs), defined by 2‐[fluorine‐18]fluoro‐2‐deoxy‐d‐glucose (FDG) positron‐emission tomography (PET) avidity. FDG–PET avidity in NETs is associated with a significantly higher risk of death, outperforming Ki‐67 index or liver metastases as a poor prognostic factor. We hypothesized that everolimus has efficacy in patients with FDG–PET‐avid G2 PNETs and prospectively evaluated progression‐free survival (PFS) and response in the first‐line setting.
Chest CT in patients after lung transplantation: A retrospective analysis to evaluate impact on image quality and radiation dose using spectral filtration tin-filtered imaging

Objectives The purpose of this study was to investigate the impact of a 150kV spectral filtration chest imaging protocol (Sn150kVp) combined with advanced modeled iterative reconstruction (ADMIRE) on radiation dose and image quality in patients after lung-transplantation. Methods This study included 102 patients who had unenhanced chest-CT examinations available on both, a second-generation dual-source CT (DSCT) using standard protocol (100kVp, filtered-back-projection) and, on a third-generation DSCT using Sn150kVp protocol with ADMIRE. Signal-to-noise-ratio (SNR) was measured in 6 standardized regions. A 5-point Likert scale was used to evaluate subjective image quality. Radiation metrics were compared. Results The mean time interval between the two acquisitions was 1.1±0.7 years. Mean-volume-CT-dose-index, dose-length-product and effective dose were significantly lower for Sn150kVp protocol (2.1±0.5mGy;72.6±16.9mGy*cm;1.3±0.3mSv) compared to 100kVp protocol (6.2±1.8mGy;203.6±55.6mGy*cm;3.7±1.0mSv) (p<0.001), equaling a 65% dose reduction. All studies were considered of diagnostic quality. SNR measured in lung tissue, air inside trachea, vertebral body and air outside the body was significantly higher in 100kVp protocol compared to Sn150kVp protocol (12.5±2.7vs.9.6±1.5;17.4±3.6vs.11.8±1.8;0.7±0.3vs.0.4±0.2;25.2±6.9vs.14.9±3.3;p<0.001). SNR measured in muscle tissue was significantly higher in Sn150kVp protocol (3.2±0.9vs.2.6±1.0;p<0.001). For SNR measured in descending aorta there was a trend towards higher values for Sn150kVp protocol (2.8±0.6 vs. 2.7±0.9;p = 0.3). Overall SNR was significantly higher in 100kVp protocol (5.0±4.0vs.4.0±4.0;p<0.001). On subjective analysis both protocols achieved a median Likert rating of 1 (25th-75th-percentile:1–1;p = 0.122). Interobserver agreement was good (intraclass correlation coefficient = 0.73). Conclusions Combined use of 150kVp tin-filtered chest CT protocol with ADMIRE allows for significant dose reduction while maintaining highly diagnostic image quality in the follow up after lung transplantation when compared to a standard chest CT protocol using filtered back projection.
Sarco/endoplasmic reticulum calcium ATPase inhibitors: Beyond anticancer perspective.

The sarco/endoplasmic reticulum calcium ATPase (SERCA), which plays a key role in the maintenance of Ca2+ ion homeostasis, is an extensively studied enzyme, the inhibition of which has a considerable impact on cell life and death decision. To date, several SERCA inhibitors have been thoroughly studied and the most notable one, a derivative of the sesquiterpene lactone thapsigargin, is gradually approaching a clinical application. Meanwhile, new compounds with SERCA-inhibiting properties of natural, synthetic or semisynthetic origin are being discovered and/or developed; some of these might be also suitable for the development of new drugs with improved performance. This review brings an up-to-date comprehensive overview of recently discovered compounds with the potential of SERCA inhibition, discusses their mechanism of action, and it highlights their potential clinical applications, such as cancer treatment.
Kirigami-Based Highly Stretchable Thin Film Solar Cells that are Mechanically Stable for More than 1000 Cycles.

Exploiting stretchable solar cells that can accommodate large strain and feature high cyclic mechanical endurance is challenging for wearable and skin-interfaced electronics application. In this work, we demostrated such solar cells using the kirigami design. Experiments and mechanical simulations showed that the kirigami structure effectively imparted stretchability to perovskite solar cells (PSCs) through out-of-plane deformation which significantly reduced the stress in devices. The kirigami-based PSCs with optimal geometric parameters exhibited high mechanical deformability, including stretchability (strain up to 200%), twistability (angle up to 450o) and bendability (radius down to 0.5mm). More importantly, the kirigami PSCs revealed high mechanical endurance with almost unchanged performance even after repetitive 1000 stretching, twisting and bending cycles. This kirigami design for stretchable PSCs presented here provides a promising strategy to achieve high deformability for solar cells as well as other optoelectronic devices.
Regulation of MT1-MMP Activity through Its Association with ERMs

Membrane-bound proteases play a key role in biology by degrading matrix proteins or shedding adhesion receptors. MT1-MMP metalloproteinase is critical during cancer invasion, angiogenesis, and development. MT1-MMP activity is strictly regulated by internalization, recycling, autoprocessing but also through its incorporation into tetraspanin-enriched microdomains (TEMs), into invadopodia, or by its secretion on extracellular vesicles (EVs). We identified a juxtamembrane positively charged cluster responsible for the interaction of MT1-MMP with ERM (ezrin/radixin/moesin) cytoskeletal connectors in breast carcinoma cells. Linkage to ERMs regulates MT1-MMP subcellular distribution and internalization, but not its incorporation into extracellular vesicles. MT1-MMP association to ERMs and insertion into TEMs are independent phenomena, so that mutation of the ERM-binding motif in the cytoplasmic region of MT1-MMP does not preclude its association with the tetraspanin CD151, but impairs the accumulation and coalescence of CD151/MT1-MMP complexes at actin-rich structures. Conversely, gene deletion of CD151 does not impact on MT1-MMP colocalization with ERM molecules. At the plasma membrane MT1-MMP autoprocessing is severely dependent on ERM association and seems to be the dominant regulator of the enzyme collagenolytic activity. This newly characterized MT1-MMP/ERM association can thus be of relevance for tumor cell invasion.