Miracle-dz/UniFAR-FTUs huggingface dataset:
Prenatal Transfer of Gut Bacteria in Rock Pigeon

Vertebrates evolved in concert with bacteria and have developed essential mutualistic relationships. Gut bacteria are vital for the postnatal development of most organs and the immune and metabolic systems and may likewise play a role during prenatal development. Prenatal transfer of gut bacteria is shown in four mammalian species, including humans. For the 92% of the vertebrates that are oviparous, prenatal transfer is debated, but it has been demonstrated in domestic chicken. We hypothesize that also non-domestic birds can prenatally transmit gut bacteria. We investigated this in medium-sized Rock pigeon (Columba livia), ensuring neonates producing fair-sized first faeces. The first faeces of 21 neonate rock pigeons hatched in an incubator, contained a microbiome (bacterial community) the composition of which resembled the cloacal microbiome of females sampled from the same population (N = 5) as indicated by multiple shared phyla, orders, families, and genera. Neonates and females shared 16.1% of the total number of OTUs present (2881), and neonates shared 45.5% of their core microbiome with females. In contrast, the five females shared only 0.3% of the 1030 female OTUs present. These findings suggest that prenatal gut bacterial transfer may occur in birds. Our results support the hypothesis that gut bacteria may be important for prenatal development and present a heritability pathway of gut bacteria in vertebrates.
Mdm2 is a target and mediator of IRP2 in cell growth control

Iron is an essential element to all living organisms and plays a vital role in many cellular processes, such as DNA synthesis and energy production. The Mdm2 oncogene is an E3 ligase and known to promote tumor growth. However, the role of Mdm2 in iron homeostasis is not certain. Here, we showed that Mdm2 expression was increased by iron depletion but decreased by iron repletion. We also showed that Iron Regulatory Protein 2 (IRP2) mediated iron‐regulated Mdm2 expression. Specifically, Mdm2 expression was increased by ectopic IRP2 but decreased by knockdown or knockout of IRP2 in human cancer cells as well as in mouse embryonic fibroblasts. In addition, we showed that IRP2‐regulated Mdm2 expression was independent of tumor suppressor p53. Mechanistically, we found that IRP2 stabilized Mdm2 transcript via binding to an iron response element (IRE) in the 3ʹUTR of Mdm2 mRNA. Finally, we showed that Mdm2 is required for IRP2‐mediated cell proliferation and Mdm2 expression is highly associated with IRP2 in both the normal and cancerous liver tissues. Together, we uncover a novel regulation of Mdm2 by IRP2 via mRNA stability and that the IRP2‐Mdm2 axis may play a critical role in cell growth.
Portable 3D-Head Computed Tomography (CT) Navigation-Guided Key-Hole Microsurgery for Spontaneous Hypertensive Hemorrhages

Background This case series study evaluated the outcome and effect of portable 3D-head computed tomography (CT, MCT-I, 16 rows mobile CT made in China) navigation-guided key-hole microsurgery for supratentorial hypertensive hematomas. Material/Methods Thirty-five consecutive unconscious patients with a significant volume of hypertensive intracranial hemorrhages (HICH) were treated with 3D image-guided key-hole microsurgery, and the clinical features were summarized. Preoperative and postoperative hematoma volumes and reduction in midline shifts were calculated and recorded. The preoperative and postoperative (initial, discharge, and 180th day after stroke onset) neurological status was assessed by Glasgow Outcome Scale (GOS), Glasgow Coma Scale (GCS), and modified Rankin Scale (mRS) score, respectively. Results The range of hematoma volumes of surgical patients was 24–99 ml (median, 50 ml). The median time of CT scan (from the time of the request to navigation finish) was 11 min. Total and near-total (>90%) hematoma evacuation was achieved in 96.9% cases. Compared with the initial state of neurological assessment, there was a significant improvement in MRS and GCS at discharge (P<0.001). After 6 months, 57.1% of patients had achieved functional recovery (GOS 4–5) and 2 patients had died. Conclusions As a minimally invasive technique, image-guided transcortical sulci or transsylvian approach is highly effective for immediate and complete hematoma evacuation.
Synaptotagmin‐11 regulates the functions of caveolae and responds to mechanical stimuli in astrocytes

Caveolae play crucial roles in intracellular membrane trafficking and mechanosensation. In this study, we report that synaptotagmin‐11 (Syt11), a synaptotagmin isoform associated with Parkinson’s disease and schizophrenia, regulates both caveolae‐mediated endocytosis and the caveolar response to mechanical stimuli in astrocytes. Syt11‐knockout (KO) accelerated caveolae‐mediated endocytosis. Interestingly, the caveolar structures on the cell surface were markedly fewer in the absence of Syt11. Caveolar disassembly in response to hypoosmotic stimuli and astrocyte swelling were both impaired in Syt11‐KO astrocytes. Live imaging revealed that Syt11 left caveolar structures before cavin1 during hypoosmotic stress and returned earlier than cavin1 after isoosmotic recovery. Chronic hypoosmotic stress led to proteasome‐mediated Syt11 degradation. In addition, Syt11‐KO increased the turnover of cavin1 and EH domain‐containing protein 2 (EHD2), accompanied by compromised membrane integrity, suggesting a mechanoprotective role of Syt11. Direct interactions between Syt11 and cavin1 and EHD2, but not caveolin‐1, are found. Altogether, we propose that Syt11 stabilizes caveolar structures on the cell surface of astrocytes and regulates caveolar functions under physiological and pathological conditions through cavin1 and EHD2.
The Essential Oil and Hydrolats from Myristica fragrans Seeds with Magnesium Aluminometasilicate as Excipient: Antioxidant, Antibacterial, and Anti-inflammatory Activity

Nutmeg (Myristica fragrans) essential oil has antimicrobial, antiseptic, antiparasitic, anti-inflammatory, and antioxidant properties. We have recently demonstrated that hydrodistillation of nutmeg essential oil by applying magnesium aluminometasilicate as an excipient significantly increases both the content and amount of bioactive substances in the oil and hydrolats. In this study, we aimed to compare the antioxidant, antimicrobial, and anti-inflammatory activity of hydrolats and essential oil obtained by hydrodistillation in the presence and absence of magnesium aluminometasilicate as an excipient. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method revealed that magnesium aluminometasilicate did not significantly improved antioxidant activity of both essential oil and hydrolat. Antibacterial efficiency was evaluated by monitoring growth of 15 bacterial strains treated by a range of dilutions of the essential oil and the hydrolats. Essential oil with an excipient completely inhibited the growth of E. faecalis, S. mutans (referent), and P. multocida, whereas the pure oil was only efficient against the latter strain. Finally, the anti-inflammatory properties of the substances were assessed in a fibroblast cell culture treated with viral dsRNR mimetic Poly I:C. The essential oil with an excipient protected cells against Poly I:C-induced necrosis more efficiently compared to pure essential oil. Also, both the oil and the hydrolats with aluminometasilicate were more efficient in preventing IL-6 release in the presence of Poly I:C. Our results show that the use of magnesium aluminometasilicate as an excipient might change and in some cases improve the biological activities of nutmeg essential oil and hydrolats.
Targeting Tumor Neoangiogenesis via Targeted Adenoviral Vector to Achieve Effective Cancer Gene Therapy for Disseminated Neoplastic Disease

The application of cancer gene therapy has heretofore been restricted to local, or locoregional, neoplastic disease contexts. This is owing to the lack of gene transfer vectors, which embody the requisite target cell selectivity in vivo required for metastatic disease applications. To this end, we have explored novel vector engineering paradigms to adapt adenovirus for this purpose. Our novel strategy exploits three distinct targeting modalities that operate in functional synergy. Transcriptional targeting is achieved via the hROBO4 promoter, which restricts transgene expression to proliferative vascular endothelium. Viral binding is modified by incorporation of an RGD4C peptide in the HI loop of the fiber knob for recognition of cellular integrins. Liver sequestration is mitigated by ablation of factor X binding to the major capsid protein hexon by a serotype swap approach. The combination of these technologies into the context of a single-vector agent represents a highly original approach. Studies in a murine model of disseminated cancer validated the in vivo target cell selectivity of our vector agent. Of note, clear gains in therapeutic index accrued these vector modifications. Whereas there is universal recognition of the value of vector targeting, very few reports have validated its direct utility in the context of cancer gene therapy. In this regard, our article validates the direct gains that may accrue these methods in the stringent delivery context of disseminated neoplastic disease. Efforts to improve vector targeting thus represent a critical direction to fully realize the promise of cancer gene therapy.
Costs and Complications: Delayed Gastric Emptying after Pancreaticoduodenectomy

Postoperative delayed gastric emptying (DGE) is a very common complication after a pancreaticoduodenectomy (PD). This along with other complications can lead to increased health-care costs. This study investigates the costs and length of stay (LOS) associated with these. A retrospective study of 131 patients undergoing PD between 2000 and 2016 at Loma Linda University Health was performed. Chi-squared test was used to determine statistically significant differences between patients with and without DGE (according to the definition of the International Study Group of Pancreatic Surgery). Multiple logistic and linear regression analyses were performed to obtain adjusted odds ratios for variables of interest in association with DGE and relationship to LOS. Of 150 patients undergoing PD, 131 patients with tumors were analyzed. The overall incidence of DGE was 56 per cent. No pre- or postoperative factors were associated with increased risk of DGE. The median LOS for patients with DGE was 15 days versus 9 days for patients without DGE. Patients with DGE added $21,198 to the overall cost of hospitalization. Fourteen patients (10.7%) were readmitted, of whom 11 were because of DGE. Further studies assessing the utility of intraoperative G-tube placement in decreasing hospital costs and readmissions are needed.
Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of the Pathogenic Yeast Candida albicans

The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.
The 27th annual Nucleic Acids Research database issue and molecular biology database collection

Abstract The 2020 Nucleic Acids Research Database Issue contains 148 papers spanning molecular biology. They include 59 papers reporting on new databases and 79 covering recent changes to resources previously published in the issue. A further ten papers are updates on databases most recently published elsewhere. This issue contains three breakthrough articles: AntiBodies Chemically Defined (ABCD) curates antibody sequences and their cognate antigens; SCOP returns with a new schema and breaks away from a purely hierarchical structure; while the new Alliance of Genome Resources brings together a number of Model Organism databases to pool knowledge and tools. Major returning nucleic acid databases include miRDB and miRTarBase. Databases for protein sequence analysis include CDD, DisProt and ELM, alongside no fewer than four newcomers covering proteins involved in liquid–liquid phase separation. In metabolism and signaling, Pathway Commons, Reactome and Metabolights all contribute papers. PATRIC and MicroScope update in microbial genomes while human and model organism genomics resources include Ensembl, Ensembl genomes and UCSC Genome Browser. Immune-related proteins are covered by updates from IPD-IMGT/HLA and AFND, as well as newcomers VDJbase and OGRDB. Drug design is catered for by updates from the IUPHAR/BPS Guide to Pharmacology and the Therapeutic Target Database. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been revised, updating 305 entries, adding 65 new resources and eliminating 125 discontinued URLs; so bringing the current total to 1637 databases. It is available at http://www.oxfordjournals. org/nar/database/c/.
Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment

Previous studies have reported that the regulatory function of the different c-Jun N-terminal kinases isoforms (JNK1, JNK2, and JNK3) play an essential role in neurological disorders, such as epilepsy and metabolic-cognitive alterations. Accordingly, JNKs have emerged as suitable therapeutic strategies. In fact, it has been demonstrated that some unspecific JNK inhibitors exert antidiabetic and neuroprotective effects, albeit they usually show high toxicity or lack therapeutic value. In this sense, natural specific JNK inhibitors, such as Licochalcone A, are promising candidates. Nonetheless, research on the understanding of the role of each of the JNKs remains mandatory in order to progress on the identification of new selective JNK isoform inhibitors. In the present review, a summary on the current gathered data on the role of JNKs in pathology is presented, as well as a discussion on their potential role in pathologies like epilepsy and metabolic-cognitive injury. Moreover, data on the effects of synthetic small molecule inhibitors that modulate JNK-dependent pathways in the brain and peripheral tissues is reviewed.
Advanced Simulation Tools Applied to Materials Development and Design Predictions

This thematic issue on advanced simulation tools applied to materials development and design predictions gathers selected extended papers related to power generation systems, presented at the XIX International Colloquium on Mechanical Fatigue of Metals (ICMFM XIX) organized at University of Porto, Portugal, in 2018. Guest editors express special thanks to all contributors for the success of this special issue—authors, reviewers, and journal staff.
Effects of Influenza Vaccination in the United States during the 2018-2019 Influenza Season.

BACKGROUND Current multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018-2019 influenza season in the US included prolonged circulation of both A(H1N1)pdm09 viruses well-matched to the vaccine strain, and A(H3N2) viruses the majority of which were mismatched to the vaccine. We estimate the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season. METHODS We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UI) of influenza-associated outcomes prevented by vaccination in the US. The model incorporated age-specific estimates of national 2018-2019 influenza vaccine coverage, influenza virus-specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network. RESULTS Influenza vaccination prevented an estimated 4.4 million (95% UI: 3.4 million-7.1 million) illnesses, 2.3 million (95% UI: 1.8 million-3.8 million) medical visits, 58,000 (95% UI: 30,000-156,000) hospitalizations, and 3,500 (95% UI: 1,000-13,000) deaths due to influenza viruses during the US 2018-2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among young children aged 6 months-4 years. CONCLUSIONS Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the US, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated health care utilization even in a season in which a vaccine component does not match to a circulating virus.
Projected impact and cost-effectiveness of community-based versus targeted azithromycin administration strategies for reducing child mortality in sub-Saharan Africa.

BACKGROUND Trials of mass drug administration (MDA) of azithromycin (AZM) report reductions in child mortality in sub-Saharan Africa (SSA). AZM targeted to high-risk children may preserve benefit while minimizing antibiotic exposure. We modeled the cost-effectiveness of MDA to children 1-59 months of age, MDA to children 1-5 months of age, AZM administered at hospital discharge, and the combination of MDA and post-discharge AZM. METHODS AND FINDINGS Models employed a payer perspective with a 1-year time horizon. Cost-effectiveness was presented as cost per DALY averted and death averted, with probabilistic sensitivity analyses. The model included parameters for macrolide resistance, adverse events, hospitalization, and mortality sourced from published data. Assuming a base-case 1.64% mortality risk among children 1-59 months old, 3.1% among children 1-5 months old, 4.4% mortality risk post-discharge, and 13.5% mortality reduction per trial data, post-discharge AZM would avert ~45,000 deaths, at a cost of $2.84/DALY (95% uncertainty interval [UI]: 1.71-5.57) averted. MDA to only children 1-5 months old would avert ~186,000 deaths at a cost of $4.89/DALY averted (95% UI: 2.88-11.42), MDA to all under-5 children would avert ~267,000 deaths a cost of $14.26/DALY averted (95% UI: 8.72-27.08). Cost-effectiveness decreased with presumed diminished efficacy due to macrolide resistance. CONCLUSIONS Targeting AZM to children at highest risk of death may be an antibiotic-sparing and cost-effective, or even cost-saving, strategy to reduce child mortality. However, targeted AZM averts fewer absolute deaths and may not reach all children who would benefit. Any AZM administration decision must consider implications for antibiotic resistance.
Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus Renders Neuroprotection through the Suppression of Hippocampal Apoptosis: An Experimental Animal Study

The core objective of this study was to determine the neuroprotective properties of deep brain stimulation of the pedunculopontine tegmental nucleus on the apoptosis of the hippocampus. The pedunculopontine tegmental nucleus is a prime target for Parkinson′s disease and is a crucial component in a feedback loop connected with the hippocampus. Deep brain stimulation was employed as a potential tool to evaluate the neuroprotective properties of hippocampal apoptosis. Deep brain stimulation was applied to the experimental animals for an hour. Henceforth, the activity of Caspase-3, myelin basic protein, Bcl-2, BAX level, lipid peroxidation, interleukin-6 levels, and brain-derived neurotrophic factor levels were evaluated at hours 1, 3 and 6 and compared with the sham group of animals. Herein, decreased levels of caspases activity and elevated levels of Bcl-2 expressions and inhibited BAX expressions were observed in experimental animals at the aforementioned time intervals. Furthermore, the ratio of Bcl-2/BAX was increased, and interleukin -6, lipid peroxidation levels were not affected by deep brain stimulation in the experimental animals. These affirmative results have explained the neuroprotection rendered by hippocampus apoptosis as a result of deep brain stimulation. Deep brain stimulation is widely used to manage neuro-motor disorders. Nevertheless, this novel study will be a revelation for a better understanding of neuromodulatory management and encourage further research with new dimensions in the field of neuroscience.
SdsA1, a secreted sulfatase, contributes to the in vivo virulence of Pseudomonas aeruginosa in mice

Mucin is a glycoprotein that is the primary component of the mucus overlaying the epithelial tissues. Because mucin functions as a first line of the innate immune system, Pseudomonas aeruginosa appears to require interaction with mucin to establish infection in the host. However, the interactions between P. aeruginosa and mucin have been poorly understood. In this study, using in vivo expression technology (IVET), we attempted to identify mucin‐inducible promoters that are likely to be involved in the establishment of P. aeruginosa infection. The IVET analysis revealed that the genes encoding glycosidases, sulfatases, and peptidases that are thought to be required for the utilization of mucin as a nutrient are present in 13 genes downstream of the identified promoters. Our results indicated that, among them, sdsA1 encoding a secreted sulfatase plays a central role in the degradation of mucin. It was then demonstrated that disruption of sdsA1 leads to a decreased release of sulfate from mucin and sulfated sugars. Furthermore, the sdsA1 mutant showed a reduction in the ability of mucin gel penetration and an attenuation of virulence in leukopenic mice compared with the wild‐type strain. Collectively, these results suggest that SdsA1 plays an important role as a virulence factor of P. aeruginosa.
Treatment and outcomes of a Danish ovarian cancer population.

INTRODUCTION Ovarian cancer has the highest mortality rate among gynaecological cancers and is the tenth most frequent cancer among women. 80% of patients with advanced stage disease will experience a progression either during or after treatment. METHODS This was a retrospective, observational study of all women referred to adjuvant or neoadjuvant treatment for ovarian cancer between 1 June 2013 and 31 May 2014 at two university hospitals in Denmark. RESULTS We included 142 women diagnosed with ovarian cancer. The median overall survival from diagnosis was 48.5 months (95% confidence interval (CI): 36.6-57.9 months). Median survival after the first, second, third, fourth and fifth progression was 19.3 (95% CI: 13.9-27-3), 11.4 (95% CI: 7.7-18.8), 9.5 (95% CI: 6.3-12.7), 8.3 (95% CI: 7.6-11.5) and 5.6 (95% CI: 2.9-not assessed) months, respectively. Median progression-free survival from diagnosis was 15.6 months (95% CI: 14.3-18.4 months). Median progression-free survival after first, second, third, fourth and fifth progression was 9.2 (95% CI: 7.7-10.6), 6.0 (95% CI: 3.5-7.7), 3.3 (95% CI: 2.6-4.6), 4.9 (95% CI: 3.6-8.3) and 3.0 (95% CI: 2.4-5.7) months, respectively. The most frequently used treatment at first progression was carboplatin and pegylated liposomal doxorubicin (n = 37). The most used non-platinum containing treatment at progression was pegylated liposomal doxorubicin (n = 26) followed by paclitaxel (n = 23). CONCLUSIONS Ovarian cancer remains a highly aggressive disease with most patients diagnosed in advanced stages. Treatment has not changed much in the past 15 years and the same is evident for the overall survival. FUNDING Tobias Berg received an unrestricted research grant from the Danish Cancer Society. TRIAL REGISTRATION not relevant.