NON-PHARMACEUTICAL TREATMENT OF DEPRESSION USING A MULTIMODAL APPROACH

One hundred forty-one individuals suffering from chronic depression, unresponsive to previous drug therapy, were treated with a 44-hour program of education, Cranial Electrical Stimulation (CES), Brain Wave Synchronization (BWS), musical conditioning, and a mentally programmed quartz or glass "crystal" randomly assigned with therapists and patients blinded to the crystal's composition. Eighty· four percent of the depressed patients were improved at the end of two weeks of therapy, apparently as a result of the multimodal therapy and group interaction. The results at three months follow-up suggest a positive subtle energy effect of quartz: 70% of the depressed patients who received quartz remained improved, while only 31.5% of the depressed patients receiving glass remained improved. These differences are highly statistically significant. It appears that mentally "programmed" quartz may offer a significant reinforcement to allow patients better long-term recovery than would occur with placebo (glass). The cost effectiveness of such a therapeutic approach is significant. Other therapists are encouraged to replicate these studies

Density-dependent, central-place foraging in a grazing herbivore: competition and tradeoffs in time allocation near water

Optimal foraging theory addresses one of the core challenges of ecology: predicting the distribution and abundance of species. Tests of hypotheses of optimal foraging, however, often focus on a single conceptual model rather than drawing upon the collective body of theory, precluding generalization. Here we demonstrate links between two established theoretical frameworks predicting animal movements and resource use: central-place foraging and density-dependent habitat selection. Our goal is to better understand how the nature of critical, centrally placed resources like water (or minerals, breathing holes, breeding sites, etc.) might govern selection for food (energy) resources obtained elsewhere - a common situation for animals living in natural conditions. We empirically test our predictions using movement data from a large herbivore distributed along a gradient of water availability (feral horses, Sable Island, Canada, 2008–2013). Horses occupying western Sable Island obtain freshwater at ponds while in the east horses must drink at self-excavated wells (holes). We studied the implications of differential access to water (time needed for a horse to obtain water) on selection for vegetation associations. Consistent with predictions of density-dependent habitat selection, horses were reduced to using poorer-quality habitat (heathland) more than expected close to water (where densities were relatively high), but were free to select for higher-quality grasslands farther from water. Importantly, central-place foraging was clearly influenced by the type of water-source used (ponds vs. holes, the latter with greater time constraints on access). Horses with more freedom to travel (those using ponds) selected for grasslands at greater distances and continued to select grasslands at higher densities, whereas horses using water holes showed very strong density-dependence in how habitat could be selected. Knowledge of more than one theoretical framework may be required to explain observed variation in foraging behavior of animals where multiple constraints simultaneously influence resource selection

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

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

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

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

Epigenetic regulation during cancer transitions across 11 tumour types

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasi

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies