Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel H3K4me3 marks are enriched at human- and chimpanzee-specific cytogenetic structures

Human and chimpanzee genomes are 98.8% identical within comparable sequences. However, they differ structurally in nine pericentric inversions, one fusion that originated human chromosome 2, and content and localization of heterochromatin and lineage-specific segmental duplications. The possible functional consequences of these cytogenetic and structural differences are not fully understood and their possible involvement in speciation remains unclear. We show that subtelomeric regions—regions that have a species-specific organization, are more divergent in sequence, and are enriched in genes and recombination hotspots—are significantly enriched for species-specific histone modifications that decorate transcription start sites in different tissues in both human and chimpanzee. The human lineage-specific chromosome 2 fusion point and ancestral centromere locus as well as chromosome 1 and 18 pericentric inversion breakpoints showed enrichment of human-specific H3K4me3 peaks in the prefrontal cortex. Our results reveal an association between plastic regions and potential novel regulatory elements.
Immunohistochemical Investigation of S100 and NSE in Cases of Traumatic Brain Injury and Its Application for Survival Time Determination

Abstract The availability of markers able to provide insight into protein changes in the central nervous system after fatal traumatic brain injury (TBI) is limited. The present study reports on the semi-quantitative assessments of the immunopositive neuroglial cells (both astrocytes and oligodendrocytes) and neurons for S100 protein (S100), as well as neuronal specific enolase (NSE), in the cerebral cortex, hippocampus, and cerebellum with regard to survival time and cause of death. Brain tissues of 47 autopsy cases with TBI (survival times ranged between several minutes and 34 d) and 10 age- and gender-matched controls (natural deaths) were examined. TBI cases were grouped according to their survival time in acute death after brain injury (ABI, n=25), subacute death after brain injury (SBI, n=18) and delayed death after brain injury (DBI, n=4). There were no significant changes in the percentages of S100-stained astrocytes between TBI and control cases. The percentages of S100-positive oligodendrocytes i.
Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines

The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions. Weaker selection on insertions than deletions is consistent with our observed distribution of genome size determined by flow cytometry, which is skewed toward larger genomes. Insertion/deletion and single nucleotide polymorphisms are positively correlated with each other and with local recombination, suggesting that their nonrandom distributions are due to hitchhiking and background selection. Our cytogenetic analysis identified 16 polymorphic inversions in the DGRP. Common inverted and standard karyotypes are genetically divergent and account for most of the variation in relatedness among the DGRP lines. Intriguingly, variation in genome size and many quantitative traits are significantly associated with inversions. Approximately 50% of the DGRP lines are infected with Wolbachia, and four lines have germline insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP, and genome-wide analyses of quantitative traits identify novel candidate genes. The DGRP lines, sequence data, genotypes, quality scores, phenotypes, and analysis and visualization tools are publicly available.
Increased risk of colorectal neoplasia among family members of patients with colorectal cancer: a population-based study in Utah.

BACKGROUND & AIMS Colorectal cancer (CRC) frequently develops in multiple members of the same families, but more data are needed to prepare effective screening guidelines. We quantified the risk of CRC and adenomas in first-degree relatives (FDRs) and second-degree relatives and first cousins of individuals with CRC, and stratified risk based on age at cancer diagnosis. METHODS We performed a case-control study of Utah residents, 50-80 years old, who underwent colonoscopy from 1995 through 2009. Index cases (exposed to colonoscopy) were colonoscopy patients with a CRC diagnosis. Age- and sex-matched individuals, unexposed to colonoscopy (controls) were selected to form the comparison groups for determining risk in relatives. Colonoscopy results were linked to cancer and pedigree information from the Utah Population Database to investigate familial aggregation of colorectal neoplasia using Cox regression analysis. RESULTS Of 126,936 patients who underwent a colonoscopy, 3804 were diagnosed with CRC and defined the index cases. FDRs had an increased risk of CRC (hazard rate ratio [HRR], 1.79; 95% confidence interval [CI],1.59-2.03), as did second-degree relatives (HRR, 1.32; 95% CI, 1.19-1.47) and first cousins (HRR, 1.15; 95% CI, 1.07-1.25), compared with relatives of controls. This risk was greater for FDRs when index patients developed CRC at younger than age 60 years (HRR, 2.11; 95% CI, 1.70-2.63), compared with older than age 60 years (HRR, 1.77; 95% CI, 1.58-1.99). The risk of adenomas (HRR, 1.82; 95% CI, 1.66-2.00) and adenomas with villous histology (HRR, 2.43; 95% CI, 1.96-3.01) also were increased in FDRs. Three percent of CRCs in FDRs would have been missed if the current guidelines, which stratify screening recommendations by the age of the proband, were strictly followed. CONCLUSIONS FDRs, second-degree relatives, and first cousins of patients who undergo colonoscopy and are found to have CRC have a significant increase in the risk of colorectal neoplasia. These data should be considered when establishing CRC screening guidelines for individuals and families.
Examining the Interaction between Level of Risk and Dosage of Treatment

The risk principle suggests that effective correctional interventions should vary the intensity of treatment by offender risk, with higher risk offenders receiving more intense services than lower risk offenders. Although much research indicates that programs that target higher risk cases are more likely to be effective, relatively little research has examined the impact of varying levels of treatment dosage by risk. Consequently, this study seeks to identify the number of hours of treatment that are necessary to reduce recidivism in a sample of offenders placed in a residential community corrections facility. The sample for this study includes 689 adult male offenders successfully discharged from a Community-Based Correctional Facility in Ohio. The results provide support for providing higher levels of dosage to high-risk offenders, with substantial reductions in recidivism for high-risk offenders receiving 200 or more hours of treatment.
TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data

The evolution of cancer genomes within a single tumor creates mixed cell populations with divergent somatic mutational landscapes. Inference of tumor subpopulations has been disproportionately focused on the assessment of somatic point mutations, whereas computational methods targeting evolutionary dynamics of copy number alterations (CNA) and loss of heterozygosity (LOH) in whole-genome sequencing data remain underdeveloped. We present a novel probabilistic model, TITAN, to infer CNA and LOH events while accounting for mixtures of cell populations, thereby estimating the proportion of cells harboring each event. We evaluate TITAN on idealized mixtures, simulating clonal populations from whole-genome sequences taken from genomically heterogeneous ovarian tumor sites collected from the same patient. In addition, we show in 23 whole genomes of breast tumors that the inference of CNA and LOH using TITAN critically informs population structure and the nature of the evolving cancer genome. Finally, we experimentally validated subclonal predictions using fluorescence in situ hybridization (FISH) and single-cell sequencing from an ovarian cancer patient sample, thereby recapitulating the key modeling assumptions of TITAN.
Accurate, multi-kb reads resolve complex populations and detect rare microorganisms

Accurate evaluation of microbial communities is essential for understanding global biogeochemical processes and can guide bioremediation and medical treatments. Metagenomics is most commonly used to analyze microbial diversity and metabolic potential, but assemblies of the short reads generated by current sequencing platforms may fail to recover heterogeneous strain populations and rare organisms. Here we used short (150-bp) and long (multi-kb) synthetic reads to evaluate strain heterogeneity and study microorganisms at low abundance in complex microbial communities from terrestrial sediments. The long-read data revealed multiple (probably dozens of) closely related species and strains from previously undescribed Deltaproteobacteria and Aminicenantes (candidate phylum OP8). Notably, these are the most abundant organisms in the communities, yet short-read assemblies achieved only partial genome coverage, mostly in the form of short scaffolds (N50 = ∼2200 bp). Genome architecture and metabolic potential for these lineages were reconstructed using a new synteny-based method. Analysis of long-read data also revealed thousands of species whose abundances were <0.1% in all samples. Most of the organisms in this “long tail” of rare organisms belong to phyla that are also represented by abundant organisms. Genes encoding glycosyl hydrolases are significantly more abundant than expected in rare genomes, suggesting that rare species may augment the capability for carbon turnover and confer resilience to changing environmental conditions. Overall, the study showed that a diversity of closely related strains and rare organisms account for a major portion of the communities. These are probably common features of many microbial communities and can be effectively studied using a combination of long and short reads.
miR‐1915 inhibits Bcl‐2 to modulate multidrug resistance by increasing drug‐sensitivity in human colorectal carcinoma cells

Colorectal carcinoma is a frequent cause of cancer‐related death in the world for men and women. microRNAs are endogenous small noncoding RNAs that regulate gene expression negatively at post‐transcriptional level. Here, we investigated the possible role of microRNAs in the development of multidrug resistance (MDR) in colorectal carcinoma cells. We analyzed microRNA (miRNA) expression levels between multidrug resistant colorectal carcinoma cell line HCT116/L‐OHP and its parent cell line HCT116 using a miRNA microarray. miR‐1915 had the lowest expression of miRNA in HCT116/L‐OHP cells compared to its parental cells. Overexpression of Bcl‐2 is generally associated with tumor drug resistance, meanwhile Bcl‐2 is a predicted target of miR‐1915. We found that elevated levels of miR‐1915 in the mimics‐transfected HCT116/L‐OHP cells reduced Bcl‐2 protein level and the luciferase activity of a Bcl‐2 3′‐untranslated region‐based reporter, and also sensitized these cells to some anticancer drugs. Taken together, our findings suggest that miR‐1915 could play a role in the development of MDR in colorectal carcinoma cells at least in part by modulation of apoptosis via targeting Bcl‐2. © 2011 Wiley Periodicals, Inc.
Caring for patients who use the Gerson method - an unorthodox nutritional program of cancer management

treatments. Finally, she chose to follow the Gerson method of cancer management. The Gerson therapy required that Amanda drink freshly prepared juices almost every hour, eat freshly prepared fruits, vegetables, and grains, take oral and injectable megadose supplements every hour while awake, eliminate toxins from the environment, and administer coffee enemas every four hours as well as whenever she felt sick. In addition, Amanda incorporated daily physical and spiritual exercises into her regimen (Table 1) (8). Sensing that her physical condition was deteriorating, Amanda, who lived alone, hired private duty nurses under the supervision of the public health nursing association to help her with cooking, detoxification enemas, administration of supplements, and toxin elimination. As one of those nurses, knowing little about the Gerson method, I was uneasy about caring for this patient. Information from the patient was scanty on the supplements’ mechanism of action and side effects, or on the proper preparation of the natural juices and meals, or on the means of administering coffee or castor oil enemas. She became uncommunicative and frustrated by our clumsiness and errors, and we wondered if we were making progress. The foregoing illustrates the problems occurring when caring for a cancer patient who chooses an unorthodox therapy; the lack of relevant information available to nurses may diminish the effectiveness of nursing care. Since the number of individuals using . unorthodox nutritional therapies is growing and since the Gerson method or a modification of it is
Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations.

BACKGROUND & AIMS Patients with Lynch syndrome carry germline mutations in single alleles of genes encoding the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2; when the second allele becomes mutated, cancer can develop. Increased screening for Lynch syndrome has identified patients with tumors that have deficiency in MMR, but no germline mutations in genes encoding MMR proteins. We investigated whether tumors with deficient MMR had acquired somatic mutations in patients without germline mutations in MMR genes using next-generation sequencing. METHODS We analyzed blood and tumor samples from 32 patients with colorectal or endometrial cancer who participated in Lynch syndrome screening studies in Ohio and were found to have tumors with MMR deficiency (based on microsatellite instability and/or absence of MMR proteins in immunohistochemical analysis, without hypermethylation of MLH1), but no germline mutations in MMR genes. Tumor DNA was sequenced for MLH1, MSH2, MSH6, PMS2, EPCAM, POLE, and POLD1 with ColoSeq and mutation frequencies were established. RESULTS Twenty-two of 32 patients (69%) were found to have 2 somatic (tumor) mutations in MMR genes encoding proteins that were lost from tumor samples, based on immunohistochemistry. Of the 10 remaining tumors 3 had one somatic mutation in a MMR gene, with possible loss of heterozygosity that could lead to MMR deficiency, 6 were found to be false-positive results (19%), and 1 had only one mutation in a MMR gene and remained unexplained. All of the tumors found to have somatic MMR mutations were of the hypermutated phenotype (>12 mutations/megabase); 6 had mutation frequencies >200/megabase, and 5 of these had somatic mutations in POLE, which encodes a DNA polymerase. CONCLUSIONS Some patients are found to have tumors with MMR defects during screening for Lynch syndrome, yet have no identifiable germline mutations in MMR genes. We found that almost 70% of these patients acquire somatic mutations in MMR genes, leading to a hypermutated phenotype of tumor cells. Patients with colon or endometrial cancers with MMR deficiency not explained by germline mutations might undergo analysis for tumor mutations in MMR genes to guide future surveillance guidelines.
The effect of blue‐light blocking spectacle lenses on visual performance, macular health and the sleep‐wake cycle: a systematic review of the literature

Blue‐blocking (BB) spectacle lenses, which attenuate short‐wavelength light, are being marketed to alleviate eyestrain and discomfort when using digital devices, improve sleep quality and potentially confer protection from retinal phototoxicity. The aim of this review was to investigate the relative benefits and potential harms of these lenses.
Cellular location and expression of Na+, K+‐ATPase α subunits affect the anti‐proliferative activity of oleandrin

The purpose of this study was to investigate whether intracellular distribution of Na+, K+‐ATPase α3 subunit, a receptor for cardiac glycosides including oleandrin, is differentially altered in cancer versus normal cells and whether this altered distribution can be therapeutically targeted to inhibit cancer cell survival. The cellular distribution of Na+, K+‐ATPase α3 isoform was investigated in paired normal and cancerous mucosa biopsy samples from patients with lung and colorectal cancers by immunohistochemical staining. The effects of oleandrin on α3 subunit intracellular distribution, cell death, proliferation, and EKR phosphorylation were examined in differentiated and undifferentiated human colon cancer CaCO‐2 cells. While Na+, K+‐ATPase α3 isoform was predominantly located near the cytoplasmic membrane in normal human colon and lung epithelia, the expression of this subunit in their paired cancer epithelia was shifted to a peri‐nuclear position in both a qualitative and quantitative manner. Similarly, distribution of α3 isoform was also shifted from a cytoplasmic membrane location in differentiated human colon cancer CaCO‐2 cells to a peri‐nuclear position in undifferentiated CaCO‐2 cells. Intriguingly, oleandrin exerted threefold stronger anti‐proliferative activity in undifferentiated CaCO‐2 cells (IC50, 8.25 nM) than in differentiated CaCO‐2 cells (IC50, >25 nM). Oleandrin (10 to 20 nM) caused an autophagic cell death and altered ERK phosphorylation in undifferentiated but not in differentiated CaCO‐2 cells. These data demonstrate that the intracellular location of Na+, K+‐ATPase α3 isoform is altered in human cancer versus normal cells. These changes in α3 cellular location and abundance may indicate a potential target of opportunity for cancer therapy. © 2012 Wiley Periodicals, Inc.
Cyclic Head Rotations Produce Modest Brain Injury in Infant Piglets.

Repetitive back-and-forth head rotation from vigorous shaking is purported to be a central mechanism responsible for diffuse white matter injury, subdural hemorrhage, and retinal hemorrhage in some cases of abusive head trauma (AHT) in young children. Although animal studies have identified mechanisms of traumatic brain injury (TBI) associated with single rapid head acceleration-decelerations at levels experienced in a motor vehicle crash, few experimental studies have investigated TBI from repetitive head rotations. The objective of this study was to systematically investigate the post-injury pathological time-course after cyclic, low-velocity head rotations in the piglet and compare them with single head rotations. Injury metrics were the occurrence and extent of axonal injury (AI), extra-axial hemorrhage (EAH), red cell neuronal/axonal change (RCNAC), and ocular injury (OI). Hyperflexion/extension of the neck were purposefully avoided in the study, resulting in unscaled angular accelerations at the lower end of reported infant surrogate shaking kinematics. All findings were at the mild end of the injury spectrum, with no significant findings at 6 h post-injury. Cyclic head rotations, however, produced modest AI that significantly increased with time post-injury (p < 0.035) and had significantly greater amounts of RCNAC and EAH than noncyclic head rotations after 24 h post-injury (p < 0.05). No OI was observed. Future studies should investigate the contributions of additional physiological and mechanical features associated with AHT (e.g., hyperflexion/extension, increased intracranial pressure from crying or thoracic compression, and more than two cyclic episodes) to enhance our understanding of the causality between proposed mechanistic factors and AHT in infants.
Chemosurgery: Microscopically Controlled Surgery for Skin Cancer

In this new and updated volume on chemosurgery, Mohs includes considerable material bearing on the freshtissue techniques and melanoma treated by chemosurgery. In a clear manner, he presents his special method of treating primary and recurrent cancer not only on the skin surface but also from areas subjacent to the surface of the skin or approachable through orifices adjacent to the lesions. Sections concerning benign tumors, infections, and gangrene treated by the technique or modifications of the technique are also included. Many years of painstakingly gathered statistics bearing on cure and recurrence rates as well as good blackand-white photographs document the essential conservatism and effectiveness of microscopically controlled surgical excision of cancer and other tumors. This volume is sufficiently complete and detailed, down to the specifics of equipment, personnel, and layout, for a chemosurgery office or clinic. Of special interest are Mohs's observations on how and where skin cancers spread
Dosage of Epsilon-Aminocaproic Acid to Reduce Postoperative Blood Loss

Postoperative blood loss, blood and blood-product requirements, and complications were compared for 3 commonly used doses of epsilon-aminocaproic acid in 150 patients undergoing first-time coronary artery bypass surgery. The patients were randomly assigned to one of 4 groups. Group 1 (n = 30) served as a control, group 2 (n = 30) received a single dose of 150 mg·kg−1 of epsilon-aminocaproic acid after anesthetic induction, group 3 (n = 30) received a loading dose of 150 mg·kg−1 followed by infusion of 1 g·h−1 for 6 hours, and group 4 (n = 60) received doses of 150 mg·kg−1 at induction, on bypass, and after protamine. No patients, including those who had endarterectomies, experienced any complications attributable to epsilon-aminocaproic acid administration. All patients who received epsilon-aminocaproic acid had significantly less bleeding compared to controls. Groups 3 and 4 had the least blood loss and packed-cell requirements.
Clinical Guide to Laboratory Tests

The Clinical Guide to Laboratory Tests potentially provides valuable information in a condensed format, especially for the house officer or nurse needing a quick reference. Despite these advantages, it is a difficult book to review, particularly because its very strengths in presenting large amounts of information result in weaknesses. For example, explanations on serum glucose measurements and the glucose tolerance test are as complete as expected, including references from the National Diabetes Data Group. Conversely, descriptions of the sweat chloride test include only a mention of reference values established at the University of Kentucky Medical Center, Lexington, and a questionable comment on possible false-negative results caused by "excessive sweating during hot weather. " In addition, there is no reference to the Cystic Fibrosis Report ( J Pediatr 1976; 88(II):711-750) or a similar report that might provide an authoritative source of information. Unfortunately many other test discussions also cite only textbooks or locally