Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined Bacteriophage and Antibiotic Treatment Prevents Pseudomonas aeruginosa Infection of Wild Type and cftr- Epithelial Cells

With the increase of infections due to multidrug resistant bacterial pathogens and the shortage of antimicrobial molecules with novel targets, interest in bacteriophages as a therapeutic option has regained much attraction. Before the launch of future clinical trials, in vitro studies are required to better evaluate the efficacies and potential pitfalls of such therapies. Here we studied in an ex vivo human airway epithelial cell line model the efficacy of phage and ciprofloxacin alone and in combination to treat infection by Pseudomonas aeruginosa. The Calu-3 cell line and the isogenic CFTR knock down cell line (cftr-) infected apically with P. aeruginosa strain PAO1 showed a progressive reduction in transepithelial resistance during 24 h. Administration at 6 h p.i. of single phage, phage cocktails or ciprofloxacin alone prevented epithelial layer destruction at 24 h p.i. Bacterial regrowth, due to phage resistant mutants harboring mutations in LPS synthesis genes, occurred thereafter both in vitro and ex vivo. However, co-administration of two phages combined with ciprofloxacin efficiently prevented PAO1 regrowth and maintained epithelial cell integrity at 72 p.i. The phage/ciprofloxacin treatment did not induce an inflammatory response in the tested cell lines as determined by nanoString® gene expression analysis. We conclude that combination of phage and ciprofloxacin efficiently protects wild type and cftr- epithelial cells from infection by P. aeruginosa and emergence of phage resistant mutants without inducing an inflammatory response. Hence, phage-antibiotic combination should be a safe and promising anti-Pseudomonas therapy for future clinical trials potentially including cystic fibrosis patients.
Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat

Blood-brain barrier opening (BBBO) with pulsed Focused Ultrasound (pFUS) and microbubbles (MB) has received increasing interest as a method for neurotherapeutics of the central nervous system. In general, conventional MRI [i.e., T2w, T2∗w, gadolinium (Gd) enhanced T1w] is used to monitor the effects of pFUS+MB on BBBO and/or assess whether sonication results in parenchymal damage. This study employed multimodal MRI techniques and 18F-Fludeoxyglucose (FDG) PET to evaluate the effects of single and multiple weekly pFUS+MB sessions on morphology and glucose utilization levels in the rat cortex and hippocampus. pFUS was performed with 0.548 MHz transducer with a slow infusion over 1 min of OptisonTM (5–8 × 107 MB) in nine focal points in cortex and four in hippocampus. During pFUS+MB treatment, Gd-T1w was performed at 3 T to confirm BBBO, along with subsequent T2w, T2∗w, DTI and glucose CEST (glucoCEST)-weighted imaging by high field 9.4 T and compared with FDG-PET and immunohistochemistry. Animals receiving a single pFUS+MB exhibited minimal hypointense voxels on T2∗w. Brains receiving multiple pFUS+MB treatments demonstrated persistent T2w and T2∗ abnormalities associated with changes in DTI and glucoCEST when compared to contralateral parenchyma. Decreased glucoCEST contrast was substantiated by FDG-PET in cortex following multiple sonications. Immunohistochemistry showed significantly dilated vessels and decreased neuronal glucose transporter (GLUT3) expression in sonicated cortex and hippocampus without changes in neuronal counts. These results suggest the importance to standardize MRI protocols in concert with advanced imaging techniques when evaluating long term effects of pFUS+MB BBBO in clinical trials for neurological diseases.
Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells

Apoptosis plays a crucial role in maintaining the structural and functional integrity of the intestinal epithelial barrier. Autophagy mediates injury to and repair of the intestinal epithelial barrier through multiple pathways in pathophysiological conditions. Our earlier study has found that cucurbitacin E (CuE) regulates the proliferation, migration, and permeability of human intestinal epithelial cells (IECs); however, its effects and mechanisms on apoptosis and autophagy are still unclear. This study reported CuE induced apoptosis and promoted autophagy of IECs in a concentration-dependent manner. The results showed that CuE could inhibit the expression of apoptosis-related protein Bcl-2 and drove activation of caspase-3 and cleavage of its substrate poly (ADP-ribose) polymerase. CuE also facilitated the expression of endoplasmic reticulum stress-related proteins, CHOP and Grp78, and autophagy-related proteins, Beclin1 and LC3, while inhibiting the phosphorylation of AKT and mammalian target of rapamycin (mTOR). An autophagy inhibitor, 3-methyladenine, reduced CuE-induced apoptosis. These results suggest that CuE may induce apoptosis and autophagy in IECs via the PI3K/AKT/mTOR signaling pathway and that autophagy following endoplasmic reticulum stress participates in the pro-apoptotic process induced by CuE.
MAP4 as a New Candidate in Cardiovascular Disease

Microtubule and mitochondrial dysfunction have been implicated in the pathogenesis of cardiovascular diseases (CVDs), including cardiac hypertrophy, fibrosis, heart failure, and hypoxic/ischemic related heart dysfunction. Microtubule dynamics instability leads to disrupted cell homeostasis and cell shape, decreased cell survival, and aberrant cell division and cell cycle, while mitochondrial dysfunction contributes to abnormal metabolism and calcium flux, increased cell death, oxidative stress, and inflammation, both of which causing cell and tissue dysfunction followed by CVDs. A cytosolic skeleton protein, microtubule-associated protein 4 (MAP4), belonging to the family of microtubule-associated proteins (MAPs), is widely expressed in non-neural cells and possesses an important role in microtubule dynamics. Increased MAP4 phosphorylation results in microtubule instability. In addition, MAP4 also expresses in mitochondria and reveals a crucial role in maintaining mitochondrial homeostasis. Phosphorylated MAP4 promotes mitochondrial apoptosis, followed by cardiac injury. The aim of the present review is to highlight the novel role of MAP4 as a potential candidate in multiple cardiovascular pathologies.
Complement C7 (C7), a Potential Tumor Suppressor, Is an Immune-Related Prognostic Biomarker in Prostate Cancer (PC)

Objectives: Prostate cancer (PC) is the second most frequent tumor in men, which has a high recurrence rate and poor prognosis. Therefore, this study aimed to identify novel prognostic biomarkers and therapeutic targets for immunotherapy and small molecule drugs for PC treatment. Materials and Methods: The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to calculate immune scores and stromal scores of TCGA-PRAD data. Differentially expressed genes (DEGs) were identified using R package “limma. ” GO, KEGG, and DO analyses were performed to analyze DEGs. Overall survival and disease-free survival analyses were conducted for hub gene identification. To validate the hub gene at the mRNA and protein expression levels, genetic alterations were measured, and CCLE and Cox regression analyses were performed. Connectivity map (CMap) analysis and GSEA were performed for drug exploration and function analysis, respectively. Results: Immune scores ranged from −1795.98 to 2339.39, and stomal scores ranged from −1877.60 to 1659.96. In total, 45 tumor microenvironment (TME)-related DEGs were identified, of which Complement C7 (C7) was selected and validated as a hub gene. CMap analysis identified six small molecule drugs as potential agents for PC treatment. Further analysis demonstrated that C7 expression was significantly correlated with clinical T, pathological N, and immune infiltration level. Conclusions: In conclusion, of the 45 TME-related DEGs, C7 was shown to correlate with PC prognosis in patients, indicating it as a novel prognostic biomarker and immunotherapy target in PC. Additionally, six small molecule drugs showed strong therapeutic potential for PC treatment.
Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury

Cervical spinal cord trauma represents more than half of the spinal cord injury (SCI) cases worldwide. Respiratory compromise, as well as severe limb motor deficits, are among the main consequences of cervical lesions. In the present work, a Gellan Gum (GG)-based hydrogel modified with GRGDS peptide, together with adipose tissue-derived stem/stromal cells (ASCs) and olfactory ensheathing cells (OECs), was used as a therapeutic strategy after a C2 hemisection SCI in rats. Hydrogel or cells alone, and a group without treatment, were also tested. Four weeks after injury, compound muscle action potentials (CMAPs) were performed to assess functional phrenic motor neuron (PhMN) innervation of the diaphragm; no differences were observed amongst groups, confirming that the PhMN pool located between C3 and C5 was not affected by the C2 injury or by the treatments. In the same line, the vast majority of diaphragmatic neuromuscular junctions remained intact. Five weeks post-injury, inspiratory bursting of the affected ipsilateral hemidiaphragm was evaluated through EMG recordings of dorsal, medial and ventral subregions of the muscle. All treatments significantly increased EMG amplitude at the ventral portion in comparison to untreated animals, but only the combinatorial group presented increased EMG amplitude at the medial portion of the hemidiaphragm. No differences were observed in forelimb motor function, neither in markers for axonal regrowth (neuronal tracers), astrogliosis (GFAP) and inflammatory cells (CD68). Moreover, using Von Frey testing of mechanical allodynia, it was possible to find a significant effect of the group combining hydrogel and cells on hypersensitivity; rats with a SCI displayed an increased response of the contralateral forelimb to a normally innocuous mechanical stimulus, but after treatment with the combinatorial therapy this behavior was reverted almost to the levels of uninjured controls. These results suggest that our therapeutic approach may have beneficial effects on both diaphragmatic recovery and sensory function.
Weyl Fermions in VI3 Monolayer

We report the presence of a Weyl fermion in VI3 monolayer. The material shows a sandwich-like hexagonal structure and stable phonon spectrum. It has a half-metal band structure, where only the bands in one spin channel cross the Fermi level. There are three pairs of Weyl points slightly below the Fermi level in spin-up channel. The Weyl points show a clean band structure and are characterized by clear Fermi arcs edge state. The effects of spin-orbit coupling, electron correlation, and lattice strain on the electronic band structure were investigated. We find that the half-metallicity and Weyl points are robust against these perturbations. Our work suggests VI3 monolayer is an excellent Weyl half-metal.
Conceptual Study of a Real-Time Hybrid Simulation Framework for Monopile Offshore Wind Turbines Under Wind and Wave Loads

As an attractive renewable energy source, offshore wind plants are becoming increasingly popular for energy production. However, the performance assessment of offshore wind turbine (OWT) structure is a challenging task due to the combined wind-wave loading and difficulties in reproducing such loading conditions in laboratory. Real-time hybrid simulation (RTHS), combining physical testing and numerical simulation in real-time, offers a new venue to study the structural behavior of OWTs. It overcomes the scaling incompatibilities in OWT scaled model testing by replacing the rotor components with an actuation system, driven by an aerodynamic simulation tool running in real-time. In this study, a RTHS framework for monopile OWTs is proposed. A set of sensitivity analyses is carried out to evaluate the feasibility of this RTHS framework and determine possible tolerances on its design. By simulating different scaling laws and possible error contributors (delays and noises) in the proposed framework, the sensitivity of the OWT responses to these parameters are quantified. An example using a National Renewable Energy Lab (NREL) 5-MW reference OWT system at 1:25 scale is simulated in this study to demonstrate the proposed RTHS framework and sensitivity analyses. Three different scaling laws are considered. The sensitivity results show that the delays in the RTHS framework significantly impact the performance on the response evaluation, higher than the impact of noises. The proposed framework and sensitivity analyses presented in this study provides important information for future implementation and further development of the RTHS technology for similar marine structures.
TEMPERATURE REGULATION IN PUERTO RICAN ANOLIS LIZARDS: A FIELD TEST USING NULL HYPOTHESES'

I used null hypotheses about basking behavior and body temperatures (Tb) to evaluate the extent and effectiveness of behavioral temperature regulation in Anolis cristatellus and A. gundlachi. I sampled these species in January and August near the extremes of their altitudinal distributions in Puerto Rico. Hollow electroformed copper lizard models, randomly positioned within habitats occupied by the lizards, served as operative temperature (Te) thermometers, providing baseline predictions about basking rates and Tb of nonthermoregulating lizards. Comparison of the basking behavior and Tb of lizards to the basking rates and tem- peratures of the models provided unambiguous evidence of nonrandom thermoregulatory activity in some of the lizard populations. Although basking opportunities were similar in the habitats occupied by both species, basking rates differed markedly: A. cristatellus basked more frequently than did randomly positioned models, and its basking rates were higher at high elevation and in January; A. gundlachi used basking sites at random at both elevations in both months. In addition, A. cristatellus limited its activity, particularly at high elevation, to times when operative temperatures were relatively high or basking sites were available (i.e., sunny weather). As a result of its opportunistic basking activity, mean Tb of A. cristatellus was often elevated above mean Te, and A. cristatellus populations experienced only limited variation of mean Tb with elevation and season. In contrast, A. gundlachi mean Tb approximated mean Te, and the Tb of A. gundlachi varied more with elevation and season. Mean Tb in A. cristatellus was always higher than the mean Tb of A. gundlachi at every elevation and month combination. The data also suggest that the low Tb experienced by A. gundlachi at high elevation might dramatically reduce sprinting ability, whereas the Tb experienced by A. cristatellus allows a majority of lizards at high elevation to sprint quickly.
Extraction of Thysanoptera from Samples of Foliage

None of the published methods of extracting Thysanoptera from foliage samples proved suitable for the estimation of Thrips nigropilosus Uzel on pyrethrum. A new method was therefore evolved which is described in detail and which was found to be effective not only for this problem but for several others involving small leaf or flower-dwelling insects. In addition a coarse technique for field estimations and for use by farmers is briefly described.
Editorial: The Importance of Diversity in Precision Medicine Research

Personalized or precision medicine is meant to distinguish tailored treatment from trial and error. The contemporary concept has evolved to specifically include the ‘omic profile of a patient in the prevention, diagnosis, and treatment of disease. Rapid genomic discoveries made possible through genome-wide association studies (GWAS) coupled with decreasing costs of sequencing and genotyping have shifted precision medicine from an academic exercise to clinical reality for some conditions (e.g., Wigle et al., 2017; Claassens et al., 2019; Hamdan et al., 2019; Lim, 2019; Roden, 2019), while others are not far behind. The emergence of electronic health records (EHRs) now makes it possible to both perform population-scale research and effectively deliver personalized medicine to the individual patient through clinical decision support. While the promise of precision medicine is great, several identifiable gaps exist in current research that limit its reach to all potential patients. One key deficiency is the lack of diversity among biomedical research participants, which limits both the generalizability and availability of genomic-based treatments or prevention strategies. The vast under-representation of diverse populations in genetic/genomic studies (e.g., Sirugo et al., 2019) is highly problematic as genetic information gleaned from one population is not automatically transferrable across populations (Popejoy and Fullerton, 2016). Without sample diversity, signals revealing powerful insights into genetic association and/or drug response can go undetected due to differences in linkage disequilibrium, allele frequencies, and genetic architecture. New initiatives and studies are now in place to ensure the inclusion of traditionally underrepresented groups, defined by race/ethnicity, socioeconomic status and/or position, geography, and age, in genomic research (Bentley et al., 2020). We therefore anticipate a swell of new data andmethodologies accelerating the already rapid pace of precision medicine research. Our goal for this Research Topic was to present original research, commentaries, perspectives, and reviews on the impact and importance of diversity in precision medicine research. Below, we briefly overview the nine accepted manuscripts and the context in which they address this goal.
Detection of Antimicrobial Resistance Genes in the Milk Production Environment: Impact of Host DNA and Sequencing Depth

Over the past decades, antimicrobial resistance (AMR) has been recognized as one of the most serious threats to public health. Although originally considered a problem to human health, the emerging crisis of AMR requires a “One Health” approach, considering human, animal, and environmental reservoirs. In this regard, the extensive use of antibiotics in the livestock production systems to treat mastitis and other bacterial diseases can lead to the presence of AMR genes in bacteria that contaminate or naturally occur in milk and dairy products, thereby introducing them into the food chain. The recent development of high-throughput next-generation sequencing (NGS) technologies is improving the fast characterization of microbial communities and their functional capabilities. In this context, whole metagenome sequencing (WMS), also called shotgun metagenomic sequencing, allows the generation of a vast amount of data which can be interrogated to generate the desired evidence, including the resistome. However, the amount of host DNA poses a major challenge to metagenome analysis. Given the current absence of literature concerning the application of WMS on milk to detect the presence of AMR genes, in the present study, we evaluated the effect of different sequencing depths, host DNA depletion methods and matrices to characterize the resistome of a milk production environment. WMS was conducted on three aliquots of bulk tank milk and three aliquots of the in-line milk filter collected from a single dairy farm; a fourth aliquot of milk and milk filter was bioinformatically subsampled. Two commercially available host DNA depletion methods were applied, and metagenomic DNA was sequenced to two different sequencing depth. Milk filters proved to be the most suitable matrices to evaluate the presence of AMR genes; besides, the pre-extraction host DNA depletion method was the most efficient approach to remove host reads. To our knowledge, this is the first study to evaluate the limitations posed by the host DNA in investigating the milk resistome with a WMS approach, confirming the circulation of AMR genes in the milk production environment.
A NEW SPECIES AND A NEW SUBSPECIES OF THE GENUS TYLOTOTRITON (CAUDATA, SALAMANDRIDAE)

The diagnosis of a new species and a new subspecies repotted in this papet ate given as follows:Tylototriton hainanensis sp. nov. (fig. 3. 4. 9)Holotype: No. 641111379, adult male; Nalong, Wuzhi Shan, Hainan, alt. 770 m; May 14, 1964.Allotype: No. 820619, adult female; Diaoluo Shan, Lingshui County, Hainan, alt. 950 m; May 1982.Paratypes;3♂♂ collected from the same locality as that of the holotype, May 14, 1964;6 ♀♀ and 5 subadultes collected from the same locality as that of the allotype, from April, May and November 1982,Diagnosis: This new species is closely related to Tylototriton asperrimus Unterstein, but differs from the latter in the following respects: 1) skull width much greater than its length, fronto-squamate arch rather narrow, the otic ramus of squamosum not extending back to the level of the occipital condyles; 2) body size larger, tips of fingers reaching the eye when foreleg laid forward; 3) dorsal tail fin-fold higher, straight and nearly parallel with the ventral fin, but from last 1/3 to 1/4 gradully converging toward tip of tail and ending in a blunt and rounded shape. In case of T. asperrimus, 1) skull width only slightly larger than length, fronto-squamate arch rather stout, the otic ramus of squamosum extending back to level of the occipital condyles; 2) body size smaller, tips of fingers reaching the nostril when laid forward; 3) dorsal tail fin-fold lower, tapering from the base and ending in a blunt point.Tylototriton asperrimus wenxianensis subsp. nov. (fig. 1. 5. 7)Holotype: No. 638164, adult male; type locality: Wenxian, Gansu, alt. 946 m; May 10, 1963; collected by Huang Nai-zhong.Paratypes: 6 ♂♂ collected from the same locality and date of the holotype.Diagnosis: The new subspecies differs from the nominate subspecies in the following respects: 1) lateral glands indistinctly separated from each other; 2) tubercles on both dorsal and ventral side rather uniform in size and no transverse wrinkles on the latter; 3) margin of anual slit dull black. In case of T. a. asperrimus, lateral glands roundish, prominent and well separated from each other; the ventral side of the body smoother than the dorsal side, with transverse wrinkles; margin of anual slit with whitish color.All type specimens are kept in Chengdu Institute of Biology and Beijing Natural His-tory Museum.
A Meta-Analysis of the “Erasing Race” Effect in the United States and Some Theoretical Considerations

The “erasing race” effect is the reduction of the salience of “race” as an alliance cue when recalling coalition membership, once more accurate information about coalition structure is presented. We conducted a random-effects model meta-analysis of this effect using five United States studies (containing nine independent effect sizes). The effect was found (ρ = 0.137, K = 9, 95% CI = 0.085 to 0.188). However, no decline effect or moderation effects were found (a “decline effect” in this context would be a decrease in the effect size over time). Furthermore, we found little evidence of publication bias. Synthetically correcting the effect size for bias stemming from the use of an older method for calculating error base rates reduced the magnitude of the effect, but the it remained significant. Taken together, these findings indicate that the “erasing race” effect generalizes quite well across experimental contexts and would, therefore, appear to be quite robust. We reinterpret the theoretical basis for these effects in line with Brunswikian evolutionary-developmental theory and present a series of predictions to guide future research in this area.