Miracle-dz/UniFAR-FTUs huggingface dataset:
Interspecies Comparison and Radiation Effect on Pharmacokinetics of BIO 300, a Nanosuspension of Genistein, after Different Routes of Administration in Mice and Non-Human Primates

BIO 300, a suspension of synthetic genistein nanoparticles, is being developed for mitigating the delayed effects of acute radiation exposure (DEARE). The purpose of the current study was to characterize the pharmacokinetic (PK) profile of BIO 300 administered as an oral or parenteral formulation 24 h after sham-irradiation, total-body irradiation (TBI) with 2.5–5.0% bone marrow sparing (TBI/BMx), or in nonirradiated sex-matched C57BL/6J mice and non-human primates (NHP). C57BL/6J mice were randomized to the following arms in two consecutive studies: sham-TBI [400 mg/kg, oral gavage (OG)], TBI/BM2.5 (400 mg/kg, OG), sham-TBI [200 mg/kg, subcutaneous (SC) injection], TBI/BM2.5 (200 mg/kg, SC), sham-TBI (100 mg/kg, SC), or nonirradiated [200 mg/kg, intramuscular (IM) injection]. The PK profile was also established in NHP exposed to TBI/BM5.0 (100 mg/kg, BID, OG). Genistein-aglycone serum concentrations were measured in all groups using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The PK profile demonstrates 11% and 19% reductions in Cmax and AUC0-inf, respectively, among mice administered 400 mg/kg, OG, after TBI/BM2.5 compared to the sham-TBI control arm. Administration of 200 mg/kg SC in mice exposed to TBI/BM2.5 showed a 53% increase in AUC0-inf but a 28% reduction in Cmax compared to the sham-TBI mice. The relative bioavailability of the OG route compared to the SC and IM routes in mice was 9% and 7%, respectively. After the OG route, the dose-normalized AUC0-inf was 13.37 (ng.h/mL)/(mg/kg) in TBI/BM2.5 mice compared to 6.95 (ng.h/mL)/(mg/kg) in TBI/BM5.0 NHPs. Linear regression of apparent clearances and weights of mice and NHPs yielded an allometric coefficient of 1.06. Based on these data, the effect of TBI/BMx on BIO 300 PK is considered minimal. Future studies should use SC and IM routes to maximize drug exposure when administered postirradiation. The allometric coefficient is useful in predicting therapeutic drug dose regimens across species for drug approval under the FDA animal rule.
Availability of Essential Antidotes and the Role of Community Pharmacists in the Management of Acute Poisoning: A Cross-Sectional Study in Ethiopia

Background Morbidity and mortality related to acute poisoning is a major public health issue in both developing and developed countries. Community pharmacists have a crucial role in ensuring drug availability, increasing drug safety, counseling patients, overdose risk reduction and management, and provision of appropriate drug information. This study aimed to assess the availability of necessary antidotes in community pharmacies in Gondar and Bahir-Dar cities, Ethiopia, and the role of community pharmacists in the management of acute poisoning. Methods A cross-sectional survey was conducted in Gondar and Bahir-Dar cities. A self-administered, structured questionnaire was used for data collection and Statistical Package for Social Sciences (SPSS) version 24.0 was used for data analysis. Chi-square analysis was computed to identify the associated factors with a confidence interval of 95% and a P value less than . 05 was used as a cut-point for statistical significance. Results Out of 101 community pharmacies invited to participate in the study, 80 of them completed the survey with a response rate of 79.2%. The overall mean antidote availability score was . 59 (SD = .837), which falls within the definition of Poor availability. None of the pharmacies had kept all of the antidotes, and the maximum number of an antidote kept by a single pharmacy was 7 out of nineteen essential antidotes surveyed. The most commonly reported reason for the unavailability of essential antidotes was stock was not ordered (56.3%) followed by stock ordered but not delivered from suppliers (wholesalers) (20.0%). More than 3 fourth of the respondents (83.8%) had poor knowledge about the antidotes for the common poisonings. Conclusion There was a significantly very low availability of essential antidotes in the community pharmacies. Strategies should be implemented to improve pharmacist’s knowledge about antidotes, and management of poisoning emergencies through on-job training and provision of reference materials.
Metabolic syndrome in women - correlation between BMI and waist circumference.

INTRODUCTION Metabolic syndrome (MetS), which includes abdominal obesity, hypertension, hypertriglyceridaemia, low high-density lipoprotein cholesterol and elevated fasting plasma glucose, is now well understood. The prevalence of MetS is increasing all over the world. Central obesity is the main and the most common component of MetS. The most simple, practical, and frequently used tool for assessing body weight is body mass index. The aim of our study was to show the correlation between waist circumference (WC) and BMI in women with MetS depending on its components. MATERIAL AND METHODS It was a study of 36-month duration (2016-2019) conducted in University Hospital No. 1 in Bydgoszcz, Poland. The study included 696 women with diagnosed MetS according to the 2009 International Diabetes Federation criteria. RESULTS In the study group, WC was found to be significantly correlated with BMI according to the arterial hypertension, T2DM, IFG, lower HDL-C, and higher TG level. CONCLUSION We should consider changing the WC guidelines for Europeans, but for this we need more prospective studies.
Characteristics of amelanotic acantholytic‐like melanoma resembling squamous cell carcinoma

Melanoma notoriously assumes a panoply of histopathologic appearances, many of which imitate other entities and represent a pitfall for diagnosticians. For example, some amelanotic melanomas with acantholytic-like features (acantholytic-like melanoma or melanoma with pseudo-acantholytic features) may mimic acantholytic squamous cell carcinoma (SCC), although this phenomenon is rarely reported and the underlying genetics are undefined. As clinicopathologic features often correlate with genomic alterations in common forms of melanoma, we sought to define clinical and histopathological features of acantholytic-like amelanotic melanomas and delineate whether these tumors show characteristic driver mutations that overlap with those seen in SCC.
The impact of tobacco smoking on survival of patients with oral squamous cell carcinoma: a population-based retrospective study

Abstract Background This article aims to evaluate the impact of smoking status, accumulated tobacco exposure (ATE), and smoking cessation on overall- and disease-free survival (OS and DFS) of patients with oral squamous cell carcinoma (OSCC). Material and Methods Patients with primary OSCC treated with curative intent between 2000 and 2019 in Copenhagen were included (n = 1808). Kaplan–Meier curves and multivariable Cox regression analyses were performed to compare the survival of patients with different smoking history. Interactions between ATE and (A) tumor subsite and (B) excessive alcohol consumption (EAC) on the survival were evaluated using multivariable Cox regression analyses with interaction terms. Results We included 1717 patients with known smoking status (62.8% males, median age: 64 years (IQR: 57–71 years)), who had a 5-year OS of 53.7% (95%CI: 49.8%–57.9%). Based on fully adjusted multivariable Cox regression analyses, significantly elevated hazard ratios (HRs) for OS and DFS were identified for current, but not former smokers, compared to never-smokers. An approximately linear relationship between continuous ATE and survival estimates was identified. ATE analyzed as a categorical variable showed significantly elevated HRs for OS of patients with all categories (0 x 30, 30 x 60, and 60 PYs), however only for DFS of patients with >60 PYs, compared to 0 PYs. Furthermore, an unfavorable long-term prognosis was evident after >3.5 (OS) and >2.5 (DFS) years from diagnosis for patients who continued smoking compared to patients with smoking cessation at diagnosis. The survival estimates of patients with different tumor subsite and alcohol consumption differed with increasing ATE. Conclusion Tobacco smoking (assessed as smoking status and ATE) was associated with inferior survival (OS and DFS) among patients with OSCC. Unfavorable long-term prognosis was significant for patients who continued smoking compared to patients with smoking cessation at diagnosis. The impact of ATE on survival of patients with OSCC may depend on the tumor subsite and/or alcohol consumption.
Molecular Tension Probes to Quantify Cell-Generated Mechanical Forces

Living cells generate, sense, and respond to mechanical forces through their interaction with neighboring cells or extracellular matrix, thereby regulating diverse cellular processes such as growth, motility, differentiation, and immune responses. Dysregulation of mechanosensitive signaling pathways is found associated with the development and progression of various diseases such as cancer. Yet, little is known about the mechanisms behind mechano-regulation, largely due to the limited availability of tools to study it at the molecular level. The recent development of molecular tension probes allows measurement of cellular forces exerted by single ligand-receptor interaction, which has helped in revealing the hitherto unknown mechanistic details of various mechanosensitive processes in living cells. Here, we provide an introductory overview of two methods based on molecular tension probes, tension gauge tether (TGT), and molecular tension fluorescence microscopy (MTFM). TGT utilizes the irreversible rupture of double-stranded DNA tether upon application of force in the piconewton (pN) range, whereas MTFM utilizes the reversible extension of molecular springs such as polymer or single-stranded DNA hairpin under applied pN forces. Specifically, the underlying principle of how molecular tension probes measure cell-generated mechanical forces and their applications to mechanosensitive biological processes are described.
Evaluating the potency of blood long noncoding RNA PVT1 as candidate biomarker reflecting inflammation, multiple organ dysfunction, and mortality risk in sepsis patients

Long noncoding RNA plasmacytoma variant translocation 1 (lnc‐PVT1) promotes septic inflammation and organ injuries via multiple ways, while its clinical engagement in sepsis management is indistinct. This study aimed to investigate its relationship with inflammation, multiple organ dysfunction, and mortality risk in sepsis patients.
The antibacterial property of zinc oxide/graphene oxide modified porous polyetheretherketone against S. sanguinis, F. nucleatum and P. gingivalis

About 30% failures of implant are caused by peri-implantitis. Subgingival plaque, consisting of S. sanguinis, F. nucleatum, P. gingivalis et al, is the initiating factor of peri-implantitis. Polyetheretherketone (PEEK) is widely used for the fabrication of implant abutment, healing cap and temporary abutment in dental applications. As a biologically inert material, PEEK has shown poor antibacterial properties. To promote the antibacterial activity of PEEK, we loaded ZnO/GO on sulfonated PEEK. We screened out that when mass ratio of ZnO/GO was 4:1, dip-coating time was 25 min, ZnO/GO modified SPEEK shown the best physical and chemical properties. At the meantime, the ZnO/GO-SPEEK samples possess a good biocompatibility. The ZnO/GO-SPEEK inhibits P. gingivalis obviously, and could exert an antibacterial activity to S. sanguinis in the early stage, prevents biofilm formation effectively. With the favorable in vitro performances, the modification of PEEK with ZnO/GO is promising for preventing peri-implantitis.
Pulmonary functional imaging (PFI): A historical review and perspective

PFI Pulmonary Functional Imaging (PFI) refers to visualization and measurement of ventilation, perfusion, gas flow and exchange as well as biomechanics. In this review, we will highlight the historical development of PFI, describing recent advances and listing the various techniques for PFI offered per modality. Challenges PFI is facing and requirements for PFI from a clinical point of view will be pointed out. Hereby the review is meant as an introduction to PFI.
Effect of Human Synovial Fluid From Osteoarthritis Patients and Healthy Individuals On Lymphatic Contractile Activity.

The lymphatic system has been proposed to play a crucial role in preventing the development and progression of osteoarthritis (OA). As OA develops and progresses, inflammatory cytokines and degradation by-products of joint tissues build up in the synovial fluid (SF) providing a feedback system to exacerbate disease. The lymphatic system plays a critical role in resolving inflammation and maintaining joint homeostasis, however, there is evidence that the lymphatics can become dysfunctional during OA. We hypothesized that the functional mechanics of lymphatic vessels (LVs) draining the joint could be directly compromised due to factors within SF derived from OA patients (OASF). Here, we utilized OASF and SF derived from healthy individuals (HSF) to investigate effects of SF entering the draining lymph on migration of lymphatic endothelial cells (LECs) in vitro, and lymphatic contractility of rat femoral LVs (RFLVs) ex vivo. Dilutions of OASF and HSF led to an increased migratory response in vitro compared to LECs treatment with media without serum. Ex vivo, OASF and HSF treatments were administered within the lumen of isolated LVs under controlled pressures. OASF treatment transiently enhanced the RFLVs tonic contractions while phasic contractions were significantly reduced after 1 hr of treatment and complete ceased after overnight treatment. HSF treatment on the other hand displayed a gradual decrease in lymphatic contractility (both tonic and phasic contractions). The observed variations after SF treatments suggest the pump function of LV draining the joint could be directly compromised in OA and thus might present a new therapeutic target.
Exploring the roles of microbes in facilitating plant adaptation to climate change

Plants benefit from their close association with soil microbes which assist in their response to abiotic and biotic stressors. Yet much of what we know about plant stress responses is based on studies where the microbial partners were uncontrolled and unknown. Under climate change, the soil microbial community will also be sensitive to and respond to abiotic and biotic stressors. Thus, facilitating plant adaptation to climate change will require a systems-based approach that accounts for the multi-dimensional nature of plant–microbe–environment interactions. In this perspective, we highlight some of the key factors influencing plant–microbe interactions under stress as well as new tools to facilitate the controlled study of their molecular complexity, such as fabricated ecosystems and synthetic communities. When paired with genomic and biochemical methods, these tools provide researchers with more precision, reproducibility, and manipulability for exploring plant–microbe–environment interactions under a changing climate.
Primary Nonfunction and Early Allograft Dysfunction after Liver Transplantation

Background: Despite continuous progress in the field of liver transplantation, considerable proportion of patients still suffer from the postoperative graft dysfunction. Clinically, it presents as early allograft dysfunction (EAD), and its more severe form defined as primary nonfunction (PNF). Posttransplant liver dysfunction translates into significantly worse treatment outcomes. Summary: Both entities are multifactorial, with donor (graft), recipient, and procedure-related factors playing the key roles. Ischemia-reperfusion injury is a major driver of their development. So far, various noninvasive (pharmacological) and invasive strategies have been tested to mitigate its negative effects. This article presents the current approach to diagnosis, prediction, and management of EAD and PNF. Key Messages: Different pharmacological interventions may be considered to improve graft function after liver transplantation. Machine perfusion seems to be the most effective method at the moment.
Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis

Although anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes. This is the first study to prospectively investigate viable anaerobic bacteria present in the sputum microbiota and their relationship with long-term outcomes in adults with CF. We performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. We examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV1 change. The presence of Porphyromonas pasteri and Prevotella nanceiensis were associated with a greater annual rate of FEV1 change; −52.3 ml yr−1 (95 % CI-87.7;−16.9), –67.9 ml yr−1 (95 % CI-115.6;−20.1), respectively. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV1 decline of −3.7 ml yr−1 (95 % CI: −6.1 to −1.3, P=0.003) and −5.3 ml yr−1 (95 % CI: −8.7 to −1.9, P=0.002) for each log2 increment of abundance, respectively. The presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline. The pathogenicity of anaerobic bacteria in the CF airways should be confirmed with further longitudinal prospective studies with a larger cohort of participants.
Remediation of petroleum hydrocarbon contaminated soil using hydrocarbonoclastic rhizobacteria, applied through Azadirachta indica rhizosphere

Abstract Crude oil/petroleum hydrocarbons (PHs) are major pollutants worldwide. In the present study, three bacterial isolates -Pseudomonas aeruginosa BB-BE3, P. aeruginosa BBBJ, and Gordonia amicalis BB-DAC were selected for their efficient hydrocarbon degradation and plant growth promotion (PGP) abilities. All three isolates were positive for siderophore production, phosphate solubilization, and IAA production, even in the presence of crude oil. The rhizoremediation ability was validated through pot trials where all three isolates promoted the growth of the Azadirachta indica plant in crude oil-contaminated soils. Treatment with the combination of the plant (A. indica) and bacteria, i.e., Pseudomonas aeruginosa BB-BE3; P. aeruginosa BBBJ; Gordonia amicalis BB-DAC showed 95.71, 93.28, and 89.88% removal of TPHs respectively, while the treatment with the plant (only) resulted in 13.44% removal of TPHs whereas, in the control (Sterile bulk soil + Crude oil), the hydrocarbon removal percentage was only 5.87%. The plant tissues were analyzed for catalase (CAT) and peroxidase (POX) activities, and the plants augmented with bacterial strains had significantly low CAT and POX activities as compared to uninoculated control. Therefore, the results suggest that the A. indica plant, in symbiotic association with these hydrocarbonoclastic rhizobacteria, could be used for bioremediation of crude oil-polluted soil. Novelty Statement The main objective of the present study is to evaluate the potential of plant–microbe associations, also including Gordonia amicalis with the Azadirachta indica, for the rhizoremediation of petroleum hydrocarbon (PHs) polluted soil. For rhizoremediation strategy, a stable plant-bacteria partnership is important, along with effective remediation, and the Gordonia amicalis–Azadirachta indica pair is being described here for the first time, for this purpose. This plant-microbe pair was highly effective as also validated through pot trials. The hydrocarbonoclastic rhizobacteria (G. amicalis BB-DAC), in symbiotic association with the A. indica plant, has significantly degraded TPHs.
Growing Up: Digital: How the Web Changes Work, Education, and the Ways People Learn

n 183 1 Michael Faraday built a small generator that produced electricity, but a generation passed before an industrial version was built, then another 25 years before all the necessary I accoutrements for electrification came into place-power companies, neighborhood wiring, appliances (like light bulbs) that required electricity, and so on. But when that infrastructure finally took hold, everything changed-homes, work places, transportation, entertainment, architecture, what we ate, even when we went to bed. Worldwide, electricity became a transformative medium for social practices.
Reconstruction of Cranial Bone Defects Using Polyamide 12 Patient-Specific Implant: Long Term Follow Up

Abstract: The main objective of this study was to evaluate the use of patient-specific polyamide 12 implants in cranial bone defect reconstruction. Ten patients who underwent prior decompression craniectomy were selected for the current study. Skull scanning by computerized tomography was performed and used to make virtual planning of the implants to be transformed into physical implant using selective laser sintering. Cranioplasty was performed through coronal surgical approach where cranial implants were fixated using 2.0-mm mini-screws, and plates. Patients follow-up was from 12 to 36 months. Glasgow Outcome Score recorded 1 (good recovery) for all patients. Patient and surgeon satisfaction for the esthetic outcome were measured using visual analog scale as mean of 10 ± 0 and 9 ± 1, respectively. Cranial symmetry index was calculated as mean score of 98% ± 1%, indicating highly accurate symmetry, and preoperative virtual planning and postoperative outcome were compared for accuracy analysis with a mean difference of 0.3197 ± 0.1649, which indicates high accuracy. Polyamide12 cranial implants seem to offer a promising option to cranial bone reconstruction with patient-specific implants. This study ensures proper cosmetic and clinical outcome.
Multivariate selection mediated by aridity predicts divergence of drought‐resistant traits along natural aridity gradients of an invasive weed

Summary Geographical variation in the environment underpins selection for local adaptation and evolutionary divergence among populations. Because many environmental conditions vary across species' ranges, identifying the specific environmental variables underlying local adaptation is profoundly challenging. We tested whether natural selection mediated by aridity predicts clinal divergence among invasive populations of capeweed (Arctotheca calendula) that established and spread across southern Australia during the last two centuries. Using common garden experiments with two environmental treatments (wet and dry) that mimic aridity conditions across capeweed’s invasive range, we estimated clinal divergence and effects of aridity on fitness and multivariate phenotypic selection in populations sampled along aridity gradients in Australia. We show that: (1) capeweed populations have relatively high fitness in aridity environments similar to their sampling locations; (2) the magnitude and direction of selection strongly differs between wet and dry treatments, with drought stress increasing the strength of selection; and (3) differences in directional selection between wet and dry treatments predict patterns of clinal divergence across the aridity gradient, particularly for traits affecting biomass, flowering phenology and putative antioxidant expression. Our results suggest that aridity‐mediated selection contributes to trait diversification among invasive capeweed populations, possibly facilitating the expansion of capeweed across southern Australia.