Miracle-dz/UniFAR-FTUs huggingface dataset:
MiR-34a inhibits spinal cord injury and blocks spinal cord neuron apoptosis by activating phatidylinositol 3-kinase (PI3K)/AKT pathway through targeting CD47.

OBJECTIVE Dysregulation of miR-34a has been reported for its implication in neuronal development. This study aims to explore the effect and possible mechanism of miR-34a on neuron apoptosis induced by spinal cord injury (SCI). METHODS SCI rats were established using Allen's weight-drop method and rats in the sham group were performed with laminectomy without weight-drop injury. Basso Bcattie Bresnahan (BBB) rating scale was applied to evaluate locomotor function of rats. Pathological changes of spinal cord tissues in SCI rats were observed after hematoxylin and eosin (HE) staining. Rats were separately injected with miR-34a agomir, miR-34a agomir NC, si-CD47 and si-CD47 NC before their spinal cord tissues were collected for TUNEL staining. Expressions of miR-34a, si-CD47, apoptosis related proteins and AKT pathway related proteins were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. RESULTS SCI rat models were successfully established evidenced by decreased BBB scores and HE staining. Injection of miR-34a agomir and/or si-CD47 could suppress neuron cell apoptosis, with deceased apoptotic index (AI) and pro-apoptotic protein (cleaved caspase-3 and Bax) levels, and increased expressions of anti-apoptotic proteins (Bcl-2 and Mcl-1). Phosphorylated levels of PI3K and AKT were further increased in rats injected with miR-34a agomir and si-CD47, compared with miR-34a agomir or si-CD47 injection alone. CONCLUSION MiR-34a can downregulate CD47 expression to activate PI3K/AKT signal pathway, and thus inhibit SCI induced spinal neuron apoptosis.
Vaccination Capability Inventory of Community, Migrant, and Homeless Health Centers: A Survey Report

Supplemental Digital Content is Available in the Text. Context: Federally funded Community, Migrant, and Homeless Health Centers provide health services to the most vulnerable communities in the United States. However, little is known about their capabilities and processes for providing vaccinations to adults. Program: We conducted the first national survey of health centers assessing their inventory, workflow, capacity for, and barriers to provision of routinely recommended adult vaccines. In addition, we asked health center leaders' perceptions regarding best practices and policy recommendations for adult vaccinations. Implementation: A survey was developed on the basis of domains elicited from advisory panels and focus groups and was sent electronically to leaders of 762 health centers throughout the United States and its territories; data were collected and analyzed in 2018. Evaluation: A total of 319 survey responses (42%) were obtained. Health centers reported stocking most routinely recommended vaccines for adults; zoster vaccines were not stocked regularly due to supply and storage issues. Respondents most commonly reported adequate reimbursement for vaccination services from private insurance and Medicaid. Most vaccinations were provided during primary care encounters; less than half of health centers reported providing vaccines during specialist visits. Vaccines administered at the health center were most commonly documented in an open field of the electronic health record (96%) or in an immunization information system (72%). Recommendations for best practices related to better documentation of vaccinations and communication with immunization information systems were provided. Discussion: Health centers provide most adult vaccines to their patients despite financial and technological barriers to optimal provisioning. Further studies at point of care could help identify mechanisms for system improvements.
Impact of Marijuana Legalization on Prevalence of Maternal Marijuana Use and Perinatal Outcomes

Abstract Objective We aimed to assess whether marijuana legalization was associated with a difference in prevalence of prenatal use or an increase in incidence of adverse perinatal outcomes. Study Design The present study is a retrospective cohort of September and October deliveries in the years 2012 through 2015 at a tertiary center in Colorado. Primary outcome of the study was use of marijuana, defined by self-report or biodetection. Secondary outcomes of the study included growth restriction, spontaneous preterm birth, stillbirth, preeclampsia, and neonatal or maternal death. Marijuana use prevalence was compared by year, and secondary outcomes between two periods, before and after the opening of the first recreational dispensary. Results A total of 2,392 pregnant women were included (1,165 before legalization and 1,227 after). More women used marijuana over the period of legalization (trend p = 0.01). Odds of marijuana use were higher after legalization versus before (adjusted odds ratio [aOR] = 1.8, 95% confidence interval [CI]: 1.2–2.6). Incidence of growth restriction was higher after legalization (2.9 vs. 5.1%, p = 0.0084). This difference persisted after adjustment for ethnicity and other drugs in multivariable modeling (aOR = 1.9, 95%CI: 1.2–3.0). Conclusion The prevalence of prenatal marijuana use increased over the time of legalization. Further investigation into the population impact of legalization on obstetrical outcomes is warranted given the observed increase in growth restriction.
In vivo therapeutic effect of wollastonite and hydroxyapatite on bone defect

The treatment of large-area bone defects is a huge challenge and the current research hot spot is to prepare composite materials to promote the new bone formation. In this study, the rat skull defect was repaired by implanting pure wollastonite and hydroxyapatite composites, which proved that it has a good effect on the treatment of bone defects. 60 SD rats were used as research objects. The animals were randomly divided into wollastonite group, wollastonite-hydroxyapatite composite group and hydroxyapatite group. The three groups of bone scaffolds were filled into the rats’ skull defects. At 6 and 12 weeks after surgery, we conducted Micro-CT analysis, HE staining, Masson trichrome staining, Alizarin red staining and Microfil analysis, to assess the therapeutic and regeneration effects of three groups. At 6 weeks after implantation, the morphology results showed that little newly formed bone was observed in wollastonite group, on the contrary, more new bone in the surgical defects formed in the wollastonite-hydroxyapatite composite group and hydroxyapatite group. At 12 weeks after surgery, histology analyses revealed that the regenerated bone became more mature in each groups. The morphology showed that the maturity of new bone was improved and the scaffold material was partially absorbed in wollastonite-hydroxyapatite composite group. CT scan observation showed that on the coronal plane, the defect repair area of wollastonite-hydroxyapatite composite group was integrated with the surrounding normal bone tissue, and the sacffold material was tightly integrated with the defect edge. The results of Microfil showed that compared with wollastonite group and hydroxyapatite group, wollastonite-hydroxyapatite composite group formed more blood vessels after 12 weeks of surgery. The wollastonite-hydroxyapatite composite biomaterial can promote the formation and growth of new bone in the defect area, and it is considered safe.
Comparison of Differential Flavor Metabolites in Meat of Lubei White Goat, Jining Gray Goat and Boer Goat

Flavor is one of the most important sensory characteristics of meat. The development of taste and aroma can be attributed to thousands of flavor molecules and precursors that are present in meat tissues. As a result, the identification of these flavor compounds and an improved understanding of their roles are necessary for improving the sensory quality and customer appeal of meat products. In the current study, we compared the metabolic profiles of meat specimens from the Lubei white goats (LBB), Boer goats (BE) and Jining grey goats (JNQ) by untargeted liquid chromatography-mass spectrometry. Our metabolomic data revealed that the three types of goat meat showed significantly different profiles of fatty acids, aldehydes, ketones, lactones, alkaloids, flavonoids, phenolics and drug residues, which could underpin the nuances of their flavors. Taken together, our results provided insights into the molecular basis for sensory variations between different goat meat products.
SNP and Haplotype-Based Genomic Selection of Quantitative Traits in Eucalyptus globulus

Eucalyptus globulus (Labill.) is one of the most important cultivated eucalypts in temperate and subtropical regions and has been successfully subjected to intensive breeding. In this study, Bayesian genomic models that include the effects of haplotype and single nucleotide polymorphisms (SNP) were assessed to predict quantitative traits related to wood quality and tree growth in a 6-year-old breeding population. To this end, the following markers were considered: (a) ~14 K SNP markers (SNP), (b) ~3 K haplotypes (HAP), and (c) haplotypes and SNPs that were not assigned to a haplotype (HAP-SNP). Predictive ability values (PA) were dependent on the genomic prediction models and markers. On average, Bayesian ridge regression (BRR) and Bayes C had the highest PA for the majority of traits. Notably, genomic models that included the haplotype effect (either HAP or HAP-SNP) significantly increased the PA of low-heritability traits. For instance, BRR based on HAP had the highest PA (0.58) for stem straightness. Consistently, the heritability estimates from genomic models were higher than the pedigree-based estimates for these traits. The results provide additional perspectives for the implementation of genomic selection in Eucalyptus breeding programs, which could be especially beneficial for improving traits with low heritability.
Elimination of Osteosarcoma by Necroptosis with Graphene Oxide-Associated Anti-HER2 Antibodies

The prognosis for non-resectable or recurrent osteosarcoma (OS) remains poor. The finding that the majority of OS overexpress the protooncogene HER2 raises the possibility of using HER2 as a therapeutic target. However, clinical trials on the anti-HER2 antibody trastuzumab (TRA) in treating OS find no therapeutic benefit. HER2 overexpression in OS is not generally associated with gene amplification, with low-level expression regarded as HER2 “negative”, as per criteria used to classify breast cancer HER2 status. Nevertheless, active HER2-targeting approaches, such as virus-based HER2 vaccines or CAR-T cells have generated promising results. More recently, it has been found that the noncovalent association of TRA with nanomaterial graphene oxide (GO) generates stable TRA/GO complexes capable of rapidly killing OS cells. TRA/GO induces oxidative stress and strong HER2 signaling to elicit immediate degradation of both cIAP (cellular inhibitor of apoptosis protein) and caspase 8, leading to activation of necroptosis. This is an attractive mechanism of cancer cell death as chemo/apoptosis-resistant tumors may remain susceptible to necroptosis. In addition, necroptosis is potentially immunogenic to promote tumor immunity, as opposed to apoptosis that tends to silence tumor immunity. Currently, no established anticancer therapeutics are known to eliminate cancers by necroptosis. The aim of this article is to review the rationale and mechanisms of TRA/GO-mediated cytotoxicity.
Meta-analysis of fish consumption and risk of pancreatic cancer in 13 prospective studies with 1.8 million participants

A previous meta-analysis suggested no association between fish consumption and risk of pancreatic cancer. As several prospective studies with a large number of pancreatic cancer cases have emerged after that meta-analysis, we updated the evidence and examined the relationship in greater depth. We performed a literature search on PubMed and EMBASE databases through March 30, 2019 to identify potentially eligible studies. We used a random-effects model to compute summary relative risk (RR) with corresponding 95% confidence interval (CI). A total of 13 prospective studies comprising 4994 pancreatic cancer cases and 1,794,601 participants were included in the final analyses. Results of the meta-analysis showed that fish consumption was not significantly associated with risk of pancreatic cancer (RR 50-g/day = 1.03, 95% CI: 0.95–1.12), which was confirmed when stratifying the analysis by various methodological and population characteristics. There was a suggestion of difference by adjustment for family history of pancreatic cancer (Pdifference = 0.05), with fish consumption being associated with higher risk of pancreatic cancer in studies without adjustment for participants’ family history (RR50-g/day = 1.09, 95% CI: 1.02–1.18), and a non-significant inverse association among studies with the adjustment (RR50-g/day = 0.93, 95% CI: 0.82–1.05). Results of this updated meta-analysis suggest that fish consumption is unlikely to be substantially associated with risk of pancreatic cancer.
Risk Factors for the Development of Psoriasis

Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. In the past decade, biologics targeting tumor necrosis factor-α, interleukin (IL)-23, and IL-17 have been developed and approved for the treatment of psoriasis. These biologics have dramatically changed the treatment and management of psoriasis. In contrast, various triggering factors can elicit the disease in genetically predisposed individuals. Recent studies suggest that the exacerbation of psoriasis can lead to systemic inflammation and cardiovascular comorbidity. In addition, psoriasis may be associated with other auto-inflammatory and auto-immune diseases. In this review, we summarize the risk factors, which can be divided into two groups (namely, extrinsic and intrinsic risk factors), responsible for the onset and exacerbation of psoriasis in order to facilitate its prevention.
Understanding diagnostic disagreement in angle closure assessment between anterior segment optical coherence tomography and gonioscopy

Background/aims Although being a more objective tool for assessment and follow-up of angle closure, reliability studies have reported a moderate diagnostic performance for anterior segment optical coherence tomography (OCT) technologies when comparing with gonioscopy as the reference standard. We aim to determine factors associated with diagnostic disagreement in angle closure when assessed by anterior segment swept source OCT (SS-OCT, CASIA SS-1000; Tomey, Nagoya, Japan) and gonioscopy. Methods Cross-sectional study. A total of 2027 phakic subjects aged ≥50 years, with no relevant previous ophthalmic history, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy and SS-OCT (128 radial scans) for the entire circumference of the angle were performed for each subject. A two-quadrant closed gonioscopic definition was used. On SS-OCT images, angle closure was defined as iridotrabecular contact (ITC) to the extent of ≥35%, ≥50% and ≥75% of the circumferential angle. Diagnostic disagreements between both methods, that is, false positives or overcalls and false negatives or undercalls were defined, respectively, as gonioscopic open/closed angles inversely assessed as closed/open by SS-OCT. Results Two hundred and seventy-two (14.7%) resulted in overcall results (false positives) when ≥50% of the angle circumference was closed using SS-OCT. These eyes had significantly wider (anterior chamber width, 11.7 vs 11.6 mm, p<0.001) and deeper (anterior chamber depth (ACD), 2.4 vs 2.2 mm, p<0.001) anterior chambers than eyes assessed by both methods as closed (true positives). Deeper ACD (OR 9.31) and lower lens vault (LV) (OR 0.04) were significantly associated with a false positive diagnosis in the multivariate analysis. Most of these cases had short (52.6%) or irregular (39%) ITC in SS-OCT images. Conclusions We found that anterior chamber dimensions, determined by ACD and LV, were factors significantly associated with diagnostic disagreement between anterior segment SS-OCT and gonioscopy in angle closure assessment.
Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper

Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice.
Inflammatory Response to Different Toxins in Experimental Sepsis Models

Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection. Despite serious mortality and morbidity, no sepsis-specific drugs exist. Endotoxemia is often used to model the hyperinflammation associated with early sepsis. This model classically uses lipopolysaccharide (LPS) from Gram-negative pathogens to activate the immune system, leading to hyperinflammation, microcirculatory disturbances and death. Other toxins may also be used to activate the immune system including Gram-positive peptidoglycan (PG) and lipoteichoic acid (LTA). In addition to these standard toxins, other bacterial components can induce inflammation. These molecules activate different signaling pathways and produce different physiological responses which can be taken advantage of for sepsis modeling. Endotoxemia modeling can provide information on pathways to inflammation in sepsis and contribute to preclinical drug development.
Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus)

Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is the primary cause of acute, highly fatal, hemorrhagic diseases in young Asian elephants. Although monocytopenia is frequently observed in EEHV-HD cases, the role monocytes play in EEHV-disease pathogenesis is unknown. This study seeks to explain the responses of monocytes/macrophages in the pathogenesis of EEHV-HD. Samples of blood, frozen tissues, and formalin-fixed, paraffin-embedded (FFPE) tissues from EEHV1A-HD, EEHV4-HD, co-infected EEHV1A and 4-HD, and EEHV-negative calves were analyzed. Peripheral blood mononuclear cells (PBMCs) from the persistent EEHV4-infected and EEHV-negative calves were also studied. The results showed increased infiltration of Iba-1-positive macrophages in the inflamed tissues of the internal organs of elephant calves with EEHV-HD. In addition, cellular apoptosis also increased in the tissues of elephants with EEHV-HD, especially in the PBMCs, compared to the EEHV-negative control. In the PBMCs of persistent EEHV4-infected elephants, cytokine mRNA expression was high, particularly up-regulation of TNF-α and IFN-γ. Moreover, viral particles were observed in the cytoplasm of the persistent EEHV4-infected elephant monocytes. Our study demonstrated for the first time that apoptosis of the PBMCs increased in cases of EEHV-HD. Furthermore, this study showed that monocytes may serve as a vehicle for viral dissemination during EEHV infection in Asian elephants.
European hedgehogs (Erinaceus europaeus) as a natural reservoir of methicillin-resistant Staphylococcus aureus carrying mecC in Denmark

Objectives A recent study from Sweden showed that European hedgehogs may constitute a reservoir for methicillin-resistant Staphylococcus aureus (MRSA), but this host-parasite relationship remains to be investigated in other countries. In this study, we therefore sought to: 1) determine the dissemination of MRSA in European hedgehogs throughout Denmark; 2) investigate determinants of MRSA carriage in hedgehogs; 3) determine the potential for zoonotic transmission of MRSA from hedgehogs to humans; and 4) characterise the detected MRSA on both a phenotypic and molecular level. Methods Nasal swabs were taken from 188 dead hedgehogs collected by volunteers throughout Denmark to determine the occurrence of MRSA. Additionally, 16 hedgehog rehabilitators were tested for potential zoonotic transmission of MRSA from hedgehogs to humans. The swabs were incubated in tryptic soy broth supplemented with 6.5% NaCl, followed by spread of 10 μl on Brilliance MRSA 2 agar. One presumptive MRSA colony from each plate was subcultured on 5% blood agar. All S. aureus subcultures were verified by a PCR assay detecting mecA, mecC, lukF-PV, scn, and spa, followed by spa typing. Results A total of 114 (61%) hedgehogs carried mecC-MRSA, whereas none carried mecA-MRSA. The detected mecC-MRSA belonged to two genetic lineages CC130 (spa-types: t528, t843, t1048, t3256, t3570, t6220, t17133) and CC1943 (spa-types: t978, t2345, t3391, t8835, t16868), 52% of which were spa-type t843 (CC130). The detection rate of mecC-MRSA in the hedgehogs was similar regardless of cause of death, sex, region and habitat type. None of the hedgehog rehabilitators carried MRSA. Conclusions This nationwide study confirms a high occurrence of mecC-MRSA in hedgehogs, which could serve as a natural reservoir for this specific type of MRSA. Furthermore, our study did not find signs of zoonotic transmission of mecC-MRSA to hedgehog rehabilitators.