The burden of head trauma in rural and remote North Queensland, Australia

Background: Head trauma is a leading cause of death and disability worldwide. Young males, Indigenous people, and rural/remote residents have been identified as high-risk populations for head trauma, however, Australian research is limited. Our aim was to define and describe the incidence, demographics, causes, prehospital interventions, and outcomes of head trauma patients transported by aeromedical services within North Queensland, Australia. We hypothesized that young, Indigenous males living remotely would be disproportionately affected by head trauma. Methods: We conducted a retrospective study of all head trauma patients transferred by air to or between Townsville, Cairns, Mount Isa and Mackay Hospitals between January 1, 2016 and December 31, 2018. Patients were identified from the Trauma Care in the Tropics data registry and followed for a median 30-months postinjury. Primary endpoints were patient and injury characteristics. Secondary outcome measures were hospital stay and mortality. Results: A total of 981 patients were included and 31.1 % were Indigenous. Sixty-seven percent of injuries occurred remotely and the median time from injury to hospital was 5.8-hours (range 67–3780 min). Eighty percent of severe head injuries occurred in males (p = 0.007). Indigenous and remote patients were more likely to sustain mild injuries. The most common mechanism of injury overall was vehicle accident (37.5 %), compared to assault in the Indigenous subgroup (46.6 %, p<0.001). The overall mortality rate was 4.9 %, with older age and lower initial Glasgow Coma Score significant predictors of in-hospital mortality. Prehospital intubation was associated with a 7-fold increased risk of mortality (p = 0.056), while patients that received tranexamic acid (TXA) were almost 5-times more likely to die. Conclusions: In North Queensland, young Indigenous males are at highest risk of traumatic head injuries. Vehicle accidents are an important preventable cause of head injury in the region. TXA administration is an important consideration for remote head trauma retrievals, in which time to emergency care is prolonged. Appropriate treatment and risk stratification strategies considering time to definitive care, severity of injury, and other prehospital patient factors require further investigation

Conversion of Sox2-dependent Merkel cell carcinoma to a differentiated neuron-like phenotype by T antigen inhibition

Viral cancers show oncogene addiction to viral oncoproteins, which are required for survival and proliferation of the dedifferentiated cancer cell. Human Merkel cell carcinomas (MCCs) that harbor a clonally integrated Merkel cell polyomavirus (MCV) genome have low mutation burden and require viral T antigen expression for tumor growth. Here, we showed that MCV+ MCC cells cocultured with keratinocytes undergo neuron-like differentiation with neurite outgrowth, secretory vesicle accumulation, and the generation of sodium-dependent action potentials, hallmarks of a neuronal cell lineage. Cocultured keratinocytes are essential for induction of the neuronal phenotype. Keratinocyte-conditioned medium was insufficient to induce this phenotype. Single-cell RNA sequencing revealed that T antigen knockdown inhibited cell cycle gene expression and reduced expression of key Merkel cell lineage/MCC marker genes, including HES6, SOX2, ATOH1, and KRT20. Of these, T antigen knockdown directly inhibited Sox2 and Atoh1 expression. MCV large T up-regulated Sox2 through its retinoblastoma protein-inhibition domain, which in turn activated Atoh1 expression. The knockdown of Sox2 in MCV+ MCCs mimicked T antigen knockdown by inducing MCC cell growth arrest and neuron-like differentiation. These results show Sox2-dependent conversion of an undifferentiated, aggressive cancer cell to a differentiated neuron-like phenotype and suggest that the ontology of MCC arises from a neuronal cell precursor

CropPol: A dynamic, open and global database on crop pollination

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open, and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e., berry mass, number of fruits, and fruit density [kg/ha], among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), North America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001–2005 (21 studies), 2006–2010 (40), 2011–2015 (88), and 2016–2020 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA).Fil: Allen Perkins, Alfonso. Universidad Politécnica de Madrid; España. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Magrach, Ainhoa. Universidad Politécnica de Madrid; EspañaFil: Dainese, Matteo. Eurac Research. Institute for Alpine Environment; ItaliaFil: Garibaldi, Lucas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Kleijn, David. Wageningen University & Research; Países BajosFil: Rader, Romina. University of New England; AustraliaFil: Reilly, James R.. Rutgers University; Estados UnidosFil: Winfree, Rachael. Rutgers University; Estados UnidosFil: Lundin, Ola. Swedish University of Agricultural Sciences; SueciaFil: McGrady, Carley M.. North Carolina State University; Estados UnidosFil: Brittain, Claire. University of California at Davis; Estados UnidosFil: Biddinger, David J.. University of California Davis; Estados UnidosFil: Artz, Derek R.. United States Department of Agriculture. Agriculture Research Service; Estados UnidosFil: Elle, Elizabeth. University Fraser Simon; CanadáFil: Hoffman, George. State University of Oregon; Estados UnidosFil: Ellis, James D.. University of Florida; Estados UnidosFil: Daniels, Jaret. University of Florida; Estados Unidos. University Of Florida. Florida Museum Of History; Estados UnidosFil: Gibbs, Jason. University of Manitoba; CanadáFil: Campbell, Joshua W.. University of Florida; Estados Unidos. Usda Ars Northern Plains Agricultural Research Laboratory; Estados UnidosFil: Brokaw, Julia. University of Minnesota; Estados UnidosFil: Wilson, Julianna K.. Michigan State University; Estados UnidosFil: Mason, Keith. Michigan State University; Estados UnidosFil: Ward, Kimiora L.. University of California at Davis; Estados UnidosFil: Gundersen, Knute B.. Michigan State University; Estados UnidosFil: Bobiwash, Kyle. University of Manitoba; Canadá. University Fraser Simon; CanadáFil: Gut, Larry. Michigan State University; Estados UnidosFil: Rowe, Logan M.. Michigan State University; Estados UnidosFil: Boyle, Natalie K.. United States Department of Agriculture. Agriculture Research Service; Estados UnidosFil: Williams, Neal M.. University of California at Davis; Estados UnidosFil: Chacoff, Natacha Paola. Universidad Nacional de Tucumán. Instituto de Ecología Regional. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Ecología Regional; Argentin

Effect of pH of amine fluoride containing toothpastes on enamel remineralization in vitro

<p>Abstract</p> <p>Background</p> <p>One of the important factors of the demineralization and remineralization equilibrium of enamel is the pH of the surrounding solutions. Effort has been laid in the formulation of different fluoride compounds and the fluoride content in toothpastes but much less is known about the influence of the pH of the toothpastes on their effectiveness. It was therefore the aim of this study to investigate the influence of different pH levels on enamel remineralization in an in vitro experiment using polarization light microscopy and EDX quantitative element analysis.</p> <p>Methods</p> <p>A 5 × 5 mm window on the enamel surface of 40 caries free extracted human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 8 groups and the lower half of the window was covered with varnish serving as control. Each group was then immersed in toothpaste slurry containing amine fluoride (1400 ppm) at pH 4.1, 4.5, 5.1 and 6.9 or control toothpaste slurry without fluoride at pH 4.3, 4.7, 5.3 and 7.0. Serial sections were cut through the lesions and investigated with polarization light microscopy and quantitative EDX element analysis.</p> <p>Results</p> <p>The PLM results showed a decreased porous volume of the body of the lesion after incubation with fluoridated toothpaste at pH 4.53 and 5.16. No differences between the experimental window and the control window were found in the other groups. The quantitative element analysis showed no differences in the element content of any of the groups.</p> <p>Conclusion</p> <p>From the results it can be concluded that slightly acidified fluoridated dentifrices may have a certain positive effect on enamel remineralization.</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN