Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Approaches to Modulate Endothelial Cell Migration and Angiogenesis

Angiogenesis, the process of neovascularization from pre-existing vasculature, is fundamental to development and tissue repair. However, aberrant angiogenesis exacerbates progression of a number of diseases including but not limited to cancer and diabetic retinopathy. Endothelial cell (EC) migration, a key event for angiogenesis, is a highly regulated process that critically relies on the dynamic remodeling of the actin cytoskeleton via orchestrated actions of various actin-binding proteins. An important aspect of the dynamic remodeling of the actin cytoskeleton, cell migration, and angiogenesis is stimulus-induced regulation of de novo synthesis of many important molecular components of the actin cytoskeleton by MKL (Megakaryoblastic Leukemia)–SRF (Serum-Response Factor) transcriptional machineries. Given the previous genetic evidence for the importance of MKL/SRF signaling in EC migration and angiogenesis, we first set out to explore whether angiogenesis is susceptible to small molecule-mediated inhibition of the MKL/SRF pathway. Our studies showed that CCG-1423, a small molecule inhibitor of MKL, causes a prominent defect in EC migration and angiogenesis in vitro, ex vivo, and in vivo. Inhibition of MKL led to prominent depletion of actin-binding protein Profilin-1 (Pfn1), an important molecular player of membrane protrusion and EC migration/angiogenesis, but through an unconventional indirect mechanism that involves a cellular externalization control [Angiogenesis (2017) 20(4):663-672; J. Biol Chem. (2017) 292(28):11777-11791]. Next, guided by computational-based rational design, we identified the first-generation small molecule inhibitors of the Pfn1:actin interaction, and further demonstrated the ability of these small molecules to inhibit EC migration, proliferation, and angiogenesis in vitro and ex vivo [J Biol Chem (2017) Dec 27, epub]. Finally, to gain new insights on the regulation of Pfn1, we identified and explored the consequence of novel phosphorylation event which caused insoluble aggregation of Pfn1 and actin molecules [PLoS One (2016) 26;11(5):e0156313].
Broadening the reach and investigating the potential of prime editors through fully viral gene-deleted adenoviral vector delivery

Abstract Prime editing is a recent precision genome editing modality whose versatility offers the prospect for a wide range of applications, including the development of targeted genetic therapies. Yet, an outstanding bottleneck for its optimization and use concerns the difficulty in delivering large prime editing complexes into cells. Here, we demonstrate that packaging prime editing constructs in adenoviral capsids overcomes this constrain resulting in robust genome editing in both transformed and non-transformed human cells with up to 90% efficiencies. Using this cell cycle-independent delivery platform, we found a direct correlation between prime editing activity and cellular replication and disclose that the proportions between accurate prime editing events and unwanted byproducts can be influenced by the target-cell context. Hence, adenovector particles permit the efficacious delivery and testing of prime editing reagents in human cells independently of their transformation and replication statuses. The herein integrated gene delivery and gene editing technologies are expected to aid investigating the potential and limitations of prime editing in numerous experimental settings and, eventually, in ex vivo or in vivo therapeutic contexts.
Retrospective evaluation of intravenous fosfomycin in multi-drug resistant infections at a tertiary care hospital in Lebanon.

INTRODUCTION Fosfomycin has re-emerged as a possible therapeutic alternative for the treatment of resistant bacterial pathogens. Its main mechanism of action is the inhibition of the initial step of cell wall synthesis and is active against both Gram-positive and Gram-negative bacteria. However, its clinical effectiveness against multidrug resistant bacteria remains largely unknown. Therefore, we aim to evaluate the clinical and microbiological effectiveness of intravenous fosfomycin as well as its safety in a tertiary care teaching hospital in Lebanon. METHODOLOGY This is a retrospective chart review of adult patients who had presented to the hospital and were treated with intravenous fosfomycin for at least 24 hours for any type of infection between 2014 and 2019. RESULTS Among 31 episodes treated with intravenous fosfomycin, 68% had an overall favorable clinical response. In 84% of the episodes, fosfomycin was administered in combination with other antibiotics, commonly tigecycline. Of those with available cultures at end of therapy, 73% achieved microbiological success. No relapse was documented within 30 days of completion of therapy. In the episodes secondary to resistant pathogens, the rates of favorable clinical outcome and microbiological success at the end of therapy were 71% and 73%, respectively. Fosfomycin resistance developed in two cases and mild adverse events occurred in 65% of the episodes during the course of treatment. CONCLUSIONS Fosfomycin is a safe and effective option in the treatment of multi-drug resistant infections. Nevertheless, careful stewardship is important to maintain its efficacy and to reduce the risk of selection of antimicrobial resistance.
Gadolinium-labelled iron/iron oxide core/shell nanoparticles as T1–T2 contrast agent for magnetic resonance imaging

Magnetic resonance imaging (MRI) is indispensable and powerful in modern clinical diagnosis and has some advantages such as non-invasiveness and high penetration depth. Furthermore, dual T1–T2 MR imaging has attracted crucial interest as it can decrease the risk of pseudo-positive signals in diagnosing lesions. And it's worth nothing that the dual-mode MR imaging displays a vital platform to provide relatively comprehensive diagnosis information and receive accurate results. Herein, we report a dual T1–T2 MR imaging contrast agent (CA) grounded on the iron/iron oxide core/shell nanomaterials conjugated with gadolinium chelate. The Gd-labeled Fe@Fe3O4 NPs reveal the feasibility to utilize them to serve as a dual T1–T2 MR imaging CA, and the relaxivity results in a 0.5 T MR system showed a longitudinal relaxivity value (r1) and transverse relaxivity value (r2) of 7.2 mM−1 s−1 and 109.4 mM−1 s−1, respectively. The MTT results demonstrate the Gd-labeled Fe@Fe3O4 NPs have no obvious cytotoxicity and a good compatibility. The in vitro and in vivo MRI generated a brighter effect and darkening in T1-weighted MR imaging and T2-weighted images, respectively. The results clearly indicate that Gd-labeled Fe@Fe3O4 NPs have potential as a magnetic resonance imaging contrast reagent.
Increasing self–other similarity modulates ethnic bias in sensorimotor resonance to others’ pain

Abstract The tendency to simulate the pain of others within our own sensorimotor systems is a vital component of empathy. However, this sensorimotor resonance is modulated by a multitude of social factors including similarity in bodily appearance, e.g. skin colour. The current study investigated whether increasing self–other similarity via virtual transfer to another colour body reduced ingroup bias in sensorimotor resonance. A sample of 58 white participants was momentarily transferred to either a black or a white body using virtual reality technology. We then employed electroencephalography to examine event-related desynchronization (ERD) in the sensorimotor beta (13–23 Hz) oscillations while they viewed black, white and violet photorealistic virtual agents being touched with a noxious or soft object. While the noxious treatment of a violet agent did not increase beta ERD, amplified beta ERD in response to black agent’s noxious vs soft treatment was found in perceivers transferred to a black body. Transfer to the white body dismissed the effect. Further exploratory analysis implied that the pain-related beta ERD occurred only when the agent and the participant were of the same colour. The results suggest that even short-lasting changes in bodily resemblance can modulate sensorimotor resonance to others’ perceived pain.
Association between oral health and cardiovascular outcomes in patients with hypertension: a nationwide cohort study

Objective: Studies on the association of oral hygiene indicators with cardiovascular disease in hypertensive patients have been lacking. Oral hygiene is directly or indirectly associated with systemic inflammation, one of the essential mechanisms of cardiovascular disease. Therefore, we hypothesized that oral hygiene would be related to the risk of cardiovascular diseases in hypertensive patients. Methods: We included 52 677 hypertensive participants who completed oral health checkups from the Korean National Health Insurance Service-National Health Screening Cohort between 2003 and 2004. We collected data on periodontitis diagnosis and treatment history, number of teeth loss, number of dental caries, and frequency of tooth brushing from medical records of health claims and oral health examination. The primary outcome was defined as composite outcomes of stroke and myocardial infarction. Follow-up was done until the date of primary outcome, or 31 December 2015. Results: During the 11.26 ± 2.39 years (mean ± standard deviation) of the study follow-up, 3292 participants developed primary outcomes [stroke (n = 2430), myocardial infarction (n = 862)]. In multivariable Cox regression analyses, participants with dental caries (≥ 5) were independently associated with occurrence of a primary outcome [adjusted hazard ratio: 1.37; 95% confidence interval (CI):1.10–1.72; P = 0.006]. Frequent tooth brushing (≥ 2 times/day) was significantly related to lower risk of primary outcomes (adjusted hazard ratio: 0.88; 95% CI: 0.81–0.96; P = 0.002). Conclusion: Our study demonstrated that multiple dental caries were related to the risk of cardiovascular diseases in hypertensive patients. Better oral hygiene may attenuate the risk of cardiovascular events in hypertensive patients.
Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism

Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process.
Linking Physical Activity to Breast Cancer: Text Mining Results and a Protocol for Systematically Reviewing Three Potential Mechanistic Pathways

Epidemiologic research suggests that physical activity is associated with a reduced risk of breast cancer, but the causal nature of this link is not clear. Investigating mechanistic pathways can provide evidence of biological plausibility and improve causal inference. This project will examine three putative pathways (sex steroid hormones, insulin signaling, and inflammation) in a series of two-stage systematic reviews. Stage 1 used Text Mining for Mechanism Prioritisation (TeMMPo) to identify and prioritize relevant biological intermediates. Stage 2 will systematically review the findings from studies of (i) physical activity and intermediates and (ii) intermediates and breast cancer. Ovid MEDLINE, EMBASE, and SPORTDiscus will be searched using a combination of subject headings and free-text terms. Human intervention and prospective, observational studies will be eligible for inclusion. Meta-analysis will be performed where possible. Risk of bias will be assessed using the Cochrane Collaboration tool, or the ROBINS-I or ROBINS-E tool, depending on study type. Strength of evidence will be assessed using the GRADE system. In addition to synthesizing the mechanistic evidence that links physical activity with breast cancer risk, this project may also identify priority areas for future research and help inform the design and implementation of physical activity interventions. See related reviews by Swain et al., p. 16 and Drummond et al., p. 28
microRNAs trip down memory lane

A new study by Islam et al, in this issue of EMBO Molecular Medicine, reports three microRNAs in the blood that are linked to inter‐individual differences in cognition, prior to any sign of cognitive decline. The novel miRNA biomarkers may assist in predicting the risk of cognitive decline and later of developing dementia and can contribute to decision strategies about early therapeutic interventions.
Shape Coexistence in the Highly Neutron-Deficient Nuclei 175-Au and 179-Au.

Excited states in neutron-deficient isotopes Au and Au have been populated following Ru(Kr,p2n) and Mo(Sr,p2n) fusion evaporation reactions, respectively. Both experiments were performed at the University of Jyväskylä Accelerator Laboratory. γ-rays detected in the Jurogam and Great germanium detectors were correlated with the isotopes of interest via their characteristic α-decays following a recoil implantation in the Great DSSD detector. Four collective structures have been identified comprising approximately 40 γ rays. These have been unambiguously assigned to the decay of Au considerably extending the previously reported level scheme. Specifically these γ rays have been interpreted to decay into the known isomeric α-decaying state of Au. The structures have been interpreted in terms of proton-hole and proton-intruder configurations. Nine new γ rays associated with the groundstate α decay of Au have been identified via a correlation with Ir, the daughter of Au. Approximately 30 γ rays have been assigned to Au confirming previous studies on this nucleus. The γ rays have been ordered into four collective bands and their structure has been interpreted as πi13/2, πh9/2 and πf7/2⊗h9/2 prolate configurations. Additionally two new γ rays associated with Au have been identified and are observed to decay from an isomeric state.
APPENDIX I 1957 Report on “ Method for Preparing Artificial Hemoglobin Corpuscles ”

The red corpuscle, once it has passed the reticulocyte stage, is almost without metabolic activity and is little more than a hemoglobin containing shell1. This pointed towards the possibility that perhaps an artificially produced hemoglobin corpuscle may be used as a physiologically functioning red blood cell. With this possibility in mind, first, a survey of the literature concerning erythrocytes, hemoglobin and possible artificial membranes was made; then possible methods of getting hemoglobin into corpuscles of microscopic sizes were tried.
Prevalence and identification of tick species on large ruminants from district Rajanpur in Punjab Pakistan

ABSTRACT Ticks are most prevalent vectors for the transmission of tick-borne diseases to animals (both wild and domesticated) as well as humans. Due to the favourable subtropical conditions of Pakistan, ticks are abundant and parasitize ruminants resulting in their morbidity and mortality causing economic losses to owners. In the present study, a total of 991 ticks from bovines (n = 690 from cattle; n = 301 from buffaloes) were collected during July to October 2019 from six sampling sites in Rajanpur District to report identification and prevalence of collected tick species. During the current investigation, 16 species of ticks belonging to 3 genera were identified: Hyalomma (Hy.) anatolicum, Hy. excavatum, Hy. dromedarii, Hy. impeltatum, Hy. marginatum, Hy. impressum, Hy. scupense, Hy. rufipes, Hy. detritum, Hy. truncatum, Rhiphicephalus (Rh.) sanguineus, Rh. turanicus, Rh. annulatus, Rh. parvas, Ixodes (Ix.) pilosus and I. ricinus. Hyalomma ticks were most prevalent (85%) followed by Rhipicephalus (10%) and Ixodes (4%) on enrolled animals. Tick prevalence varied between sampling sites (P = 0.007). Tick infestation was significantly higher (P < 0.001) in cattle (70%) than buffaloes (30%). Udder was the most preferred site of tick infestation in enrolled animals (P < 0.05) as compared to other predilection sites.
Survival of diapausing females of two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae) submerged in water

ABSTRACT Two-spotted spider mite, Tetranychus urticae Koch, is a ubiquitous and highly polyphagous plant pest with a worldwide distribution. Diapause is essential for its survival in the areas with unfavourable seasonal conditions. We investigated whether female mites overwintering close to the soil surface may be adapted to seasonal flooding. Among the tested mites diapausing on leaf surfaces, 76.3 ± 13.1% (mean ± SE) survived submergence in water for 10 days, 4.8 ± 3.0% – for 20–24 days, 3.0 ± 2.1% – for 30 days, and 8.7 ± 5.9% – for 42–46 days. Among the tested mites diapausing inside wheat straws, 33.3 ± 9.0% remained alive after being flooded for ten days, but none survived being submerged for 30 days. Seasonal floodwaters may be an important factor in spider mite dispersal, geographic isolation, and gene flow. Flooding may also be partially responsible for the formation of species assemblages along rivers.
Peopling the Americas: Not “Out of Japan”

ABSTRACT A widely accepted model for the peopling of the Americas postulates a source population in the Northeast Asian maritime region, which includes northern Japan. The model is based on similarities in stone artifacts (stemmed points) found in North American sites dating as early as 15,000 years ago and those of comparable age in Japan and neighboring regions of Northeast Asia. Here we show, on the basis of data and analyses in biological anthropology, that the people who made stemmed points in northern Japan (labeled “Incipient Jomon” in the archaeological literature) represent an unlikely source population for the indigenous peoples of the Western Hemisphere.
Draft Genome Sequence of the White-Rot Fungus Phanerochaete sordida YK-624

Here, we report the draft genome sequence of the white-rot basidiomycete fungus Phanerochaete sordida YK-624 (ATCC 90872), which was isolated in Yakushima, Kagoshima, Japan. The genome of this strain was found to be 41.2 Mbp, with a G+C content of 58.7%, and to comprise 17,108 predicted protein-coding sequences. ABSTRACT Here, we report the draft genome sequence of the white-rot basidiomycete fungus Phanerochaete sordida YK-624 (ATCC 90872), which was isolated in Yakushima, Kagoshima, Japan. The genome of this strain was found to be 41.2 Mbp, with a G+C content of 58.7%, and to comprise 17,108 predicted protein-coding sequences.
Evolution of song and color in island birds

ABSTRACT Island birds are often less colorful and sing different songs than their mainland counterparts. Given that trade-offs can occur in the expression of costly sexually selected traits, it is not clear whether island species with less colorful plumage than their mainland counterparts have compensated with increased complexity of song structure. To examine potential trade-offs in sexually selected traits in island birds, we examined concurrent patterns of coloration and song structure in island and mainland (sub)species across 3 widespread and speciose songbird families: Fringillidae, Meliphagidae, and Monarchidae. Phylogenetically controlled analyses revealed a shift away from white plumage and toward melanin-based plumage in island (sub)species but only in the Meliphagidae. Contrary to our predictions, we found no evidence that song structure in island birds differed from their mainland counterparts. Although a number of inverse correlations were identified between song structure and plumage coloration when all birds were considered, this pattern became weaker when only island populations were examined. Instead, we found island size affected song structure leading to a lower number of syllables and lower minimum frequency on smaller islands. Birds on smaller islands also had reduced carotenoid plumage but this pattern was only significant in the Fringillidae. These results indicate that island environments can influence the evolution of both song and color in some taxa, but that selection is tempered by island size, rather than through correlated evolution across signaling modalities.
Fast Na‐Ion Intercalation in Zinc Vanadate for High‐Performance Na‐Ion Hybrid Capacitor

Na‐ion hybrid capacitors are an emerging class of inexpensive and sustainable devices that combine the high energy of batteries with the high power of capacitors. However, their development is strongly impeded by a limited choice of electrode materials that display good electrochemical kinetics and long‐term cyclability. Here, a reduced graphene oxide–Zn0.25V2O5·nH2O nanobelt composite is introduced as a high power anode for Na‐ion batteries and Na‐ion hybrid capacitors. The composite material possesses fast Na‐ion intercalation kinetics, high electronic conductivity, and small volume change during Na‐ion storage, which lead to outstanding rate capability and cycling stability in half‐cell tests. Pairing it with a hard salt–templated, highly ordered mesoporous carbon as a high‐performance capacitive cathode results in a Na‐ion hybrid capacitor, which delivers a high energy density (88.7 Wh kg−1 at 223 W kg−1), a high power density (12552 W kg−1 with 13.2 Wh kg−1 retained), and an impressive cycling performance (31.7 Wh kg−1 (i.e., 87%) retained after 2000 cycles at 1 A g−1). This work explores zinc vanadate, a typical example of a layered metal vanadate, as an intercalation anode material with high pseudocapacitance for Na‐ion hybrid capacitors, which may open a promising direction for high‐rate Na‐ion storage.