Miracle-dz/UniFAR-FTUs huggingface dataset:
Lung Expression of Human Angiotensin-Converting Enzyme 2 Sensitizes the Mouse to SARS-CoV-2 Infection

Preclinical mouse models that recapitulate some characteristics of coronavirus disease (COVID-19) will facilitate focused study of pathogenesis and virus–host responses. Human agniotensin-converting enzyme 2 (hACE2) serves as an entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to infect people via binding to envelope spike proteins. Herein we report development and characterization of a rapidly deployable COVID-19 mouse model. C57BL/6J (B6) mice expressing hACE2 in the lung were transduced by oropharyngeal delivery of the recombinant human adenovirus type 5 that expresses hACE2 (Ad5-hACE2). Mice were infected with SARS-CoV-2 at Day 4 after transduction and developed interstitial pneumonia associated with perivascular inflammation, accompanied by significantly higher viral load in lungs at Days 3, 6, and 12 after infection compared with Ad5-empty control group. SARS-CoV-2 was detected in pneumocytes in alveolar septa. Transcriptomic analysis of lungs demonstrated that the infected Ad5-hACE mice had a significant increase in IFN-dependent chemokines Cxcl9 and Cxcl10, and genes associated with effector T-cell populations including Cd3 g, Cd8a, and Gzmb. Pathway analysis showed that several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the data set, including cytokine–cytokine receptor interaction, the chemokine signaling pathway, the NOD-like receptor signaling pathway, the measles pathway, and the IL-17 signaling pathway. This response is correlative to clinical response in lungs of patients with COVID-19. These results demonstrate that expression of hACE2 via adenovirus delivery system sensitized the mouse to SARS-CoV-2 infection and resulted in the development of a mild COVID-19 phenotype, highlighting the immune and inflammatory host responses to SARS-CoV-2 infection. This rapidly deployable COVID-19 mouse model is useful for preclinical and pathogenesis studies of COVID-19.
Identification and characterization of molecular mechanisms driving the functional specification of motor neurons The Delta like homolog 1 protein

Spinal Motor neurons are playing a decisive role in body posture and locomotion by controlling skeletal muscle contraction via their motor axon termini. During embryonic development motor neurons arise from neural progenitor cells, move to their appropriate position and differentiate in order to innervate their proper muscle fibres. During this process, all motor neurons controlling a certain muscle organize in one distinct cluster termed motor pool . Some of the mechanisms responsible for the initial stages of motor neuron development, like motor column and motor pool formation have already been understood during the recent years. However, the molecular mechanisms underlying the final steps of motor neuron specification remained unknown so far. During these steps, motor neurons are specified into different functional motor neuron types (FMNT) in order to match their physiological properties with that of the different muscle fibre types they innervate. The aim of this work was to identify molecular markers for the different fast or slow motor neuron types and to elucidate their role in the formation and function of different FMNT populations.
Patterns of distribution and conservation status of freshwater fishes in South Africa

The combined fish collection databases of the Albany Museum and the J.L. B. Smith Institute of Ichthyology are used to identify hotspots of endemism and threatened fish distributions in South Africa. Hotspots of fish species richness occur in the north-eastern lowveld sectors of South Africa and along the ecotone between the tropical/ subtropical and temperate faunal zones. Hotspots of endemic fish richness occur within both the tropical and temperate faunal regions, notably in the Olifants River system, Western Cape and in areas of high relief such as the Cape Fold Mountains, the Amatola-Wrnterberg (Eastern Cape), and the Drakensberg Escarpment {Kwazulu/ Natal-Eastern Transvaal). Threatened taxa are concentrated in the hotspots of endemic species richness which coincide largely with areas of major river conservation concern. There is limited scope for fish conservation within the ambit of formal (or informal) declared reserves, and the survival of the fauna depends on the success of river catchment conser.
Integrative Multi-Omics Analysis in Calcific Aortic Valve Disease Reveals a Link to the Formation of Amyloid-Like Deposits

Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease in the developed world, yet no pharmacological therapy exists. Here, we hypothesize that the integration of multiple omic data represents an approach towards unveiling novel molecular networks in CAVD. Databases were searched for CAVD omic studies. Differentially expressed molecules from calcified and control samples were retrieved, identifying 32 micro RNAs (miRNA), 596 mRNAs and 80 proteins. Over-representation pathway analysis revealed platelet degranulation and complement/coagulation cascade as dysregulated pathways. Multi-omics integration of overlapping proteome/transcriptome molecules, with the miRNAs, identified a CAVD protein–protein interaction network containing seven seed genes (apolipoprotein A1 (APOA1), hemoglobin subunit β (HBB), transferrin (TF), α-2-macroglobulin (A2M), transforming growth factor β-induced protein (TGFBI), serpin family A member 1 (SERPINA1), lipopolysaccharide binding protein (LBP), inter-α-trypsin inhibitor heavy chain 3 (ITIH3) and immunoglobulin κ constant (IGKC)), four input miRNAs (miR-335-5p, miR-3663-3p, miR-21-5p, miR-93-5p) and two connector genes (amyloid beta precursor protein (APP) and transthyretin (TTR)). In a metabolite–gene–disease network, Alzheimer’s disease exhibited the highest degree of betweenness. To further strengthen the associations based on the multi-omics approach, we validated the presence of APP and TTR in calcified valves from CAVD patients by immunohistochemistry. Our study suggests a novel molecular CAVD network potentially linked to the formation of amyloid-like structures. Further investigations on the associated mechanisms and therapeutic potential of targeting amyloid-like deposits in CAVD may offer significant health benefits.
El uso de granos secos de destilería con solubles (DDGS) en dietas sorgo-soya para pollos de engorda y gallinas de postura Use of distillers dried grains with soluble (DDGS) on sorghum-soybean meal diets for broilers and laying hens

In order to study the productive performance in broilers and hens fed DDGS, two experiments were conducted: In Exp 1, 704 Ross chicks were used from 1 to 49 d of age, divided in four treatments with eight replicates of 22 birds each one, in a completely randomized design. The treatments were: T1) sorghum-soybean meal basal diet, T2) as 1 +7% DDGS, T3) as 1 +14% DDGS, 4) as 1 +21% DDGS. In Exp 2, 288 hens Bovans White 35 wk of age were used, kept in cages for 56 d of experimentation. A completely randomized design with four treatments and three replicates of 12 hens each one was used. The treatments were: 1) sorghumsoybean meal basal diet, 2) as 1 +3% DDGS, 3) as 1 +6% DDGS, 4) as 1 +9% DDGS. The results in Exp 1, indicated (P>0.05) than the addition of 7 % of GSDS, did not affect performance and carcass yield. The results in Exp 2 showed that the use of 3, 6 and 9 % of DDGS (P>0.05) did not affect performance. There was a beneficial effect (P>0.05) in the pigmentation of egg yolk, being higher in DDGS treatments. With the results obtained in this study, we conclude that the addition of DDGS in sorghum-soybean meal diets until 7 % in broilers and 9 % in laying hens is an alternative source of protein and energy.
Improving drought tolerance in rice: Ensuring food security through multi-dimensional approaches.

Drought has been highly prevalent around the world especially in Sub-Saharan Africa and South-East Asian countries. Consistent climatic instabilities and unpredictable rainfall patterns are further worsening the situation. Rice is a C3 staple cereal and an important food crop for the majority of the world's population and drought stress is one of the major growth retarding threats for rice that slashes down grain quality and yield. Drought deteriorates rice productivity and induces various acclimation responses that aids in stress mitigation. However, the complexity of traits associated with drought tolerance has made the understanding of drought stress-induced responses in rice a challenging process. An integrative understanding based on physiological adaptations, omics, transgenic and molecular breeding approaches successively backed up to developing drought stress-tolerant rice. The review represents a step forward to develop drought-resilient rice plants by exploiting the knowledge that collaborates with omics-based developments with integrative efforts to ensure the compilation of all the possible strategies undertaken to develop drought stress-tolerant rice. This article is protected by copyright. All rights reserved.
Homeopathic Treatment as an Add‐On Therapy May Improve Quality of Life and Prolong Survival in Patients with Non‐Small Cell Lung Cancer: A Prospective, Randomized, Placebo‐Controlled, Double‐Blind, Three‐Arm, Multicenter Study

Abstract Lessons Learned Conventional medicine and homeopathy work well together. Quality of life improves with additive homeopathy in patients with non‐small cell lung cancer (NSCLC). Survival improves with additive homeopathy in patients with NSCLC. Background Patients with advanced non‐small cell lung cancer (NSCLC) have limited treatment options. Alongside conventional anticancer treatment, additive homeopathy might help to alleviate side effects of conventional therapy. The aim of the present study was to investigate whether additive homeopathy might influence quality of life (QoL) and survival in patients with NSCLC. Methods In this prospective, randomized, placebo‐controlled, double‐blind, three‐arm, multicenter, phase III study, we evaluated the possible effects of additive homeopathic treatment compared with placebo in patients with stage IV NSCLC, with respect to QoL in the two randomized groups and survival time in all three groups. Treated patients visited the outpatients' centers every 9 weeks: 150 patients with stage IV NSCLC were included in the study; 98 received either individualized homeopathic remedies (n = 51) or placebo (n = 47) in a double‐blinded fashion; and 52 control patients without any homeopathic treatment were observed for survival only. The constituents of the different homeopathic remedies were mainly of plant, mineral, or animal origin. The remedies were manufactured by stepwise dilution and succussion, thereby preparing stable Good Manufacturing Practice grade formulations. Results QoL as well as functional and symptom scales showed significant improvement in the homeopathy group when compared with placebo after 9 and 18 weeks of homeopathic treatment (p < .001). Median survival time was significantly longer in the homeopathy group (435 days) versus placebo (257 days; p = .010) as well as versus control (228 days; p < .001). Survival rate in the homeopathy group differed significantly from placebo (p = .020) and from control (p < .001). Conclusion QoL improved significantly in the homeopathy group compared with placebo. In addition, survival was significantly longer in the homeopathy group versus placebo and control. A higher QoL might have contributed to the prolonged survival. The study suggests that homeopathy positively influences not only QoL but also survival. Further studies including other tumor entities are warranted.
A New Approach to 3D Modeling of Inhomogeneous Populations of Viral Regulatory RNA

Tertiary structure (3D) is the physical context of RNA regulatory activity. Retroviruses are RNA viruses that replicate through the proviral DNA intermediate transcribed by hosts. Proviral transcripts form inhomogeneous populations due to variable structural ensembles of overlapping regulatory RNA motifs in the 5′-untranslated region (UTR), which drive RNAs to be spliced or translated, and/or dimerized and packaged into virions. Genetic studies and structural techniques have provided fundamental input constraints to begin predicting HIV 3D conformations in silico. Using SimRNA and sets of experimentally-determined input constraints of HIVNL4-3 trans-activation responsive sequence (TAR) and pairings of unique-5′ (U5) with dimerization (DIS) or AUG motifs, we calculated a series of 3D models that differ in proximity of 5′-Cap and the junction of TAR and PolyA helices; configuration of primer binding site (PBS)-segment; and two host cofactors binding sites. Input constraints on U5-AUG pairings were most compatible with intramolecular folding of 5′-UTR motifs in energetic minima. Introducing theoretical constraints predicted metastable PolyA region drives orientation of 5′-Cap with TAR, U5 and PBS-segment helices. SimRNA and the workflow developed herein provides viable options to predict 3D conformations of inhomogeneous populations of large RNAs that have been intractable to conventional ensemble methods.
The Performance of Colorectal Cancer Screening in Brazil: The First Two Years of the Implementation Program in Barretos Cancer Hospital

Colorectal cancer is the second most common cancer in Brazil. Yet, a nationally organized colorectal screening program is not implemented. Barretos Cancer Hospital (BCH) is one of the largest Brazilian institution that cares for underserved patients. BCH developed a fecal immunochemical test (FIT)-based organized colorectal cancer screening program to improve colorectal cancer outcomes. This study aims to present the quality/performance measures of the first 2 years of the FIT-based colorectal cancer screening program and its impact on the colorectal cancer disease stage. Between 2015 and 2017, a total of 6,737 individuals attending the Outpatient Department of Prevention or the Mobile Unit of BCH, which visits 18 cities of Barretos county, ages 50 to 65 years, were personally invited by a health agent/nurse practitioner. Exclusion criteria were personal history of colorectal cancer, adenomatous polyps, inflammatory bowel disease, and colonoscopy, or flexible sigmoidoscopy performed in the past 5 years. European Union (EU) guidelines for colorectal cancer screening programs were evaluated. Overall, 92.8% returned the FIT, with an inadequate examination rate of 1.5%. Among the 6,253 adequately tested, 12.5% had a positive result. The colonoscopy compliance and completion rates were 84.6 and 98.2%, respectively. The PPVs were 60.0%, 16.5%, and 5.6% for adenoma, advanced adenoma, and cancer, respectively. Stage distribution of screen-detected cancers shows earlier stages than clinically diagnosed colorectal cancer cancers reported at BCH and Brazilian cancer registries. Our colorectal cancer screening program achieved desirable quality metrics, aligned with the EU guidelines. The observed shift toward earlier colorectal cancer stages suggests an exciting opportunity to improve colorectal cancer–related cancers in Brazil.
Optimization, characterization and evaluation of ZnO/polyvinylidene fluoride nanocomposites for orthopedic applications: improved antibacterial ability and promoted osteoblast growth

Abstract Herein, electrospun zinc oxide nanoparticle/poly (vinylidene fluoride) (ZnONP/PVDF) composite fiber membranes were designed, fabricated, and tested for improved orthopedic applications. A single factor screening study was conducted to determine the optimal ZnONP/PVDF formulation based on osteoblast (bone forming cells) proliferation and antibacterial properties. Further, ZnONP/PVDF materials were characterized for their morphology, crystallinity, roughness, piezoelectric properties, and chemistry to understand such cell results. The optimal concentration of high molecular weight PVDF (18%, w/v) and a low concentration of ZnONPs (1 mg/ml) were identified for electrospinning at room temperature in order to inhibit bacterial colonization (without resorting to antibiotic use) and promote osteoblast proliferation. Compared to no ZnO/PVDF scaffold without Piezo-excited group,the study showed that on the 1 mg/ml ZnO/PVDF scaffolds with piezo-excitation, the density of SA and E.coli decreased by 68% and 56%. The density of osteoblasts doubled within three days(compared to the control). In summary, ZnONP/PVDF composite fiber membranes were formulated by electrospinning showing an exceptional ability to eliminate bacteria colonization while at the same time promote osteoblast functions and, thus, they should be further studied for a wide range of orthopedic applications.
Acid-sensing Ion Channel 3 Overexpression in Incisions Regulated by Nerve Growth Factor Participates in Postoperative Nociception in Rats

Background: Acid-sensing ion channel 3 (ASIC3) upregulation has been reported in dorsal root ganglion neurons after incision and contributes to postoperative nociception. This study hypothesized that upregulation of ASIC3 in incised tissues is induced by nerve growth factor through the phosphoinositide 3–kinase/protein kinase B signaling pathway. Methods: A plantar incision model was established in adult male and female Sprague–Dawley rats. ASIC3 was inhibited by APETx2 treatment, small interfering RNA treatment, or ASIC3 knockout. Sciatic nerve ligation was performed to analyze ASIC3 transport. A nerve growth factor antibody and a phosphoinositide 3–kinase inhibitor were used to investigate the mechanism by which nerve growth factor regulates ASIC3 expression. Results: Acid-sensing ion channel 3 inhibition decreased incisional guarding and mechanical nociception. ASIC3 protein levels were increased in skin and muscle 4 h after incision (mean ± SD: 5.4 ± 3.2-fold in skin, n = 6, P = 0.001; 4.3 ± 2.2-fold in muscle, n = 6, P = 0.001). Sciatic nerve ligation revealed bidirectional ASIC3 transport. Nerve growth factor antibody treatment inhibited the expression of ASIC3 (mean ± SD: antibody 2.3 ± 0.8-fold vs. vehicle 4.9 ± 2.4-fold, n = 6, P = 0.036) and phosphorylated protein kinase B (mean ± SD: antibody 0.8 ± 0.3-fold vs. vehicle 1.8 ± 0.8-fold, n = 6, P = 0.010) in incised tissues. Intraplantar injection of nerve growth factor increased the expression of ASIC3 and phosphorylated protein kinase B. ASIC3 expression and incisional pain–related behaviors were inhibited by pretreatment with the phosphoinositide 3–kinase inhibitor LY294002. Conclusions: Acid-sensing ion channel 3 overexpression in incisions contributes to postoperative guarding and mechanical nociception. Bidirectional transport of ASIC3 between incised tissues and dorsal root ganglion neurons occurs through the sciatic nerve. Nerve growth factor regulates ASIC3 expression after plantar incision through the phosphoinositide 3–kinase/protein kinase B signaling pathway. Using a rat model of surgical incision, it was shown that both male and female animals demonstrated less wound area sensitization when acid-sensing ion channel 3 channels were pharmacologically blocked or knocked down using small interfering RNA. Anti–nerve growth factor treatment blocked the upregulation of acid-sensing ion channel 3 expression after incision and reduced the pain-related behaviors.
Nutrient and Dietary Patterns in Relation to the Pathogenesis of Postmenopausal Osteoporosis—A Literature Review

Postmenopausal women tend to be susceptible to primary osteoporosis due to its association with oestrogen deficiency. There is emerging evidence that an unhealthy dietary pattern drives an increase in the risk of postmenopausal osteoporosis (PO), whereas a healthy dietary pattern may decrease its occurrence. In this narrative literature review, we sought to review the role of nutrient and dietary patterns in the pathogenesis of PO. Therefore, we searched and reported all research articles from 2001 to May 2020 in Web of Science, Cinahl and Scopus that have researched a relationship between nutrient and/or dietary patterns and postmenopausal osteoporosis. Nutrients such as calcium, phosphorus, magnesium and vitamin D have been proven to be beneficial for bone health. Meanwhile, for the dietary patterns, foods such as dairy products especially milk, fibre and protein-rich foods, e.g., meat were directly linked to a positive association with bone mineral density (BMD). Likewise, fruits, vegetables and probiotic and prebiotic foods were reported for its positive relationship with BMD. Therefore, aside from physical activity, nutrition and diet in adequate proportions are suggested to be an important tool for ameliorating osteoporosis and bone health issues in older age.
P2X7 Receptors

Chronic low-grade inflammation contributes to the development of several diseases, including cardiovascular disease. Adequate strategies to target inflammation in cardiovascular disease are in their infancy and remain an avenue of great interest. The purinergic receptor P2X7 is a ubiquitously expressed receptor that predominately mediates inflammation and cellular death. P2X7 is a ligand-gated cation channel that is activated in response to high concentrations of extracellular ATP, triggering the assembly and activation of the NLRP3 (nuclear oligomerization domain like receptor family pyrin domain containing 3) inflammasome and subsequent release of proinflammatory cytokines IL (interleukin)-1β and IL-18. Increased P2X7 activation and IL-1β and IL-18 concentrations have been implicated in the development of many cardiovascular conditions including hypertension, atherosclerosis, ischemia/reperfusion injury, and heart failure. P2X7 receptor KO (knockout) mice exhibit a significant attenuation of the inflammatory response, which corresponds with reduced disease severity. P2X7 antagonism blunts blood pressure elevation in hypertension and progression of atherosclerosis in animal models. IL-1β and IL-18 inhibition has shown efficacy in clinical trials reducing major adverse cardiac events, including myocardial infarction, and heart failure. With several P2X7 antagonists available with proven safety margins, P2X7 antagonism could represent an untapped potential for therapeutic intervention in cardiovascular disorders.
Role of Structural, Metabolic, and Functional MRI in Monitoring Visual System Impairment and Recovery

The visual system, consisting of the eyes and the visual pathways of the brain, receives and interprets light from the environment so that we can perceive the world around us. A wide variety of disorders can affect human vision, ranging from ocular to neurologic to systemic in nature. While other noninvasive imaging techniques such as optical coherence tomography and ultrasound can image particular sections of the visual system, magnetic resonance imaging (MRI) offers high resolution without depth limitations. MRI also gives superior soft‐tissue contrast throughout the entire pathway compared to computed tomography. By leveraging different imaging sequences, MRI is uniquely capable of unveiling the intricate processes of ocular anatomy, tissue physiology, and neurological function in the human visual system from the microscopic to macroscopic levels. In this review we discuss how structural, metabolic, and functional MRI can be used in the clinical assessment of normal and pathologic states in the anatomic structures of the visual system, including the eyes, optic nerves, optic chiasm, optic tracts, visual brain nuclei, optic radiations, and visual cortical areas. We detail a selection of recent clinical applications of MRI at each position along the visual pathways, including the evaluation of pathology, plasticity, and the potential for restoration, as well as its limitations and key areas of ongoing exploration. Our discussion of the current and future developments in MR ocular and neuroimaging highlights its potential impact on our ability to understand visual function in new detail and to improve our protection and treatment of anatomic structures that are integral to this fundamental sensory system.