Miracle-dz/UniFAR-FTUs huggingface dataset:
Mother–child transmission of epigenetic information by tunable polymorphic imprinting

Significance First, our work provides critical biological interpretation of intermediate DNA methylation readouts at the nc886 differentially methylated region (DMR). nc886 was identified in multiple large-scale epigenome-wide association studies (EWAS) that did not recognize that this region acts as a contiguous DMR imposed by genomic imprinting, highlighting the need to reexamine several 450k data sets. Second, strict control of genomic imprinting was thought to be required for organismal viability. Reports of polymorphic imprinting are limited to specific tissue types such as placenta and brain. In blood and somatic tissues, we show nc886 imprinting is mosaic in the population and influenced by maternal environment. Genomic imprinting mediated by DNA methylation restricts gene expression to a single allele determined by parental origin and is not generally considered to be under genetic or environmental influence. Here, we focused on a differentially methylated region (DMR) of approximately 1.9 kb that includes a 101-bp noncoding RNA gene (nc886/VTRNA2-1), which is maternally imprinted in ∼75% of humans. This is unlike other imprinted genes, which demonstrate monoallelic methylation in 100% of individuals. The DMR includes a CTCF binding site on the centromeric side defining the DMR boundary and is flanked by a CTCF binding site on the telomeric side. The centromeric CTCF binding site contains an A/C polymorphism (rs2346018); the C allele is associated with less imprinting. The frequency of imprinting of the nc886 DMR in infants was linked to at least two nongenetic factors, maternal age at delivery and season of conception. In a separate cohort, nc886 imprinting was associated with lower body mass index in children at 5 y of age. Thus, we propose that the imprinting status of the nc886 DMR is “tunable” in that it is associated with maternal haplotype and prenatal environment. This provides a potential mechanism for transmitting information, with phenotypic consequences, from mother to child.
Guidelines for patient selection and performance of carotid artery stenting

Background: The endovascular treatment of carotid atherosclerosis with carotid artery stenting (CAS) remains controversial. Carotid endarterectomy remains the benchmark in terms of procedural mortality and morbidity. At present, there are no consensus Australasian guidelines for the safe performance of CAS.
Short- and long-term outcomes of laparoscopy-assisted versus open total gastrectomy for gastric cancer: a propensity score-matched analysis

Background Few studies have been designed to evaluate the short- and long-term outcomes of laparoscopy-assisted total gastrectomy (LATG), and a retrospective study of a large patient cohort is valuable before conducting randomized controlled clinical trials. Results Among all patients, age, tumor location, histologic type, pT stage, pN stage and pTNM stage significantly differed between the LATG group and OTG group. After the propensity score matching, the clinicopathological characteristics did not significantly differ between groups. The operation time, estimated blood loss, time to first flatus and the number of retrieved lymph nodes (P < 0.05) were better in the LATG group than the OTG group. Morbidity and mortality were lower in the LATG group than the OTG group (P < 0.05) for pre-matched patients. However, significant intergroup differences in morbidity were not identified after propensity matching. Although overall survival did not significantly differ between groups for the pre-matched patients, the 3-year cumulative survival rates were significantly lower in the LATG group (89.9%) than the OTG group (97.7%) for patients with stage I disease (P = 0.028). After propensity score matching, the analysis of the cumulative survival curve did not show a significant difference for any cancer stage. Materials and Methods We prospectively collected data from 1096 patients who underwent total gastrectomy for gastric cancer. Propensity score matching was applied to compare the covariates between the LATG group and the open total gastrectomy (OTG) group. Operative outcomes and long-term outcomes were compared between the two groups. Conclusions Implementation of LATG for gastric cancer is a safe, reliable and minimally invasive procedure with long-term outcomes similar to those of OTG. Further randomized controlled clinical trials can be conducted to provide valuable evidence of the safety and efficacy of LATG in treating gastric cancer.
Plasma Peptide YY and Ghrelin Levels in Infants and Children with Prader-Willi Syndrome

An insatiable appetite is a cardinal feature of Prader-Willi syndrome (PWS) with stomach rupturing as a reported consequence. Peptide YY, secreted by the intestine and released post-prandially, inhibits appetite, while ghrelin, secreted by the stomach during mealtime hunger, stimulates appetite. Both peptide YY and ghrelin act at the brain level, particularly the hypothalamus. Recently, plasma ghrelin levels were reported to be elevated in children and adults with PWS but peptide YY levels have not been studied in this syndrome or ghrelin in infants with PWS. To further address the abnormal eating behavior in PWS, we obtained fasting plasma peptide YY and ghrelin levels in 12 infants and children with PWS ranging in age from 2.5 months to 13.3 years and compared them with values from normal populations reported in the literature. Plasma ghrelin levels in our patients with PWS were similar to those of other children with PWS and were significantly higher than those reported in obese children without PWS. Our infants with PWS had similar plasma ghrelin levels compared with our children with PWS but peptide YY levels in our children and infants with PWS were lower than reported in similarly aged individuals without PWS. In addition, we performed preliminary gene expression analysis of ghrelin and peptide YY and their receptors in patients with PWS using established lymphoblastoid cell lines but gene expression did not correlate with plasma ghrelin or peptide YY levels.
Three-dimensional kinematic corridors of the head, spine, and pelvis for small female driver seat occupants in near- and far-side oblique frontal impacts

Abstract Objectives: Analyses of recent automotive accident data indicate an increased risk of injury for small female occupants compared to males in similar accidents. Females have been shown to be more susceptible to spinal injuries than males. To protect this more vulnerable population, advanced anthropomorphic test devices (ATDs) and computer human body models are being developed and require biofidelity curves for validation. The aim of this study is to generate female-specific 3D kinematic corridors in near- and far-side oblique frontal impacts for the head, spine, and pelvis. Methods: Eight specimens were procured and prescreened for mass, stature, and quantitative computed tomography bone mineral density and preexisting injuries to minimize biologic variability. Sets of 4 noncolinear retroreflective targets were placed on the back of the head; dorsal spine at T1, T8, and L2; and posterior sacrum. Instrumented computed tomography scans were obtained to measure the orientation and position of the markers relative to anatomic fiducials. The specimens were placed on a buck representative of a generic automotive driver’s seat environment designed to minimize lower-extremity and pelvic motion. The buck was oriented such that the buck centerline was seated 30° from the impact vector in either a near- or far-side oblique frontal configuration. Preposition of the occupant was specified to the 50th percentile male H-point location, thigh and tibial angles, and torso angle. Impact was delivered via a servo-acceleration sled to the base of the buck with a 30 km/h 9 g trapezoidal pulse. Occupants were restrained by a standard 3-point belt that had a custom load-limiter device set to 2 kN at the D-ring side of the shoulder belt. Target motion was recorded at 1 kHz using a 3D optical motion capture system. Anatomic motion of the head, spine, and pelvis was calculated relative to the seat, and the average response was determined from 4 near-side and 4 far-side tests. The borders of the corridor were determined by calculating a standard deviational ellipse in the x, y, and z planes at each time step. Results: Plots of the biofidelity corridors for near- and far-side tests are shown in planes parallel to the seat from the lateral, rear, and overhead directions. Averaged peak excursions in the fore/aft and lateral directions are compared for the near- and far-side corridors. Near-side female and male tests are similarly compared. Conclusions: In general, average peak excursions were greater in the far-side configuration than in the near-side configuration. Peak excursion results compared well with similar tests conducted on male postmortem human subjects (PMHS). The kinematic corridors developed in the current study serve as a set of biofidelity corridors for the development of current and future physical and computational surrogates.
Association between HPV infection and prostate cancer in a Mexican population

Abstract The aim of this study was to evaluate the association between prostate cancer (PCa) and Human papillomavirus (HPV) infection in the Mexican population. We studied 356 paraffin-embedded tissues from unrelated Mexican men with PCa or benign prostatic hyperplasia (BPH), with the latter serving as control. HPV detection was performed by polymerase chain reaction (PCR) using universal primers, and viral genotypes were detected using sequencing or multiplex PCR. Light microscopy analyses enabled the identification of koilocytes in samples subsequently analyzed for HPV detection by in situ PCR and for p16-INK4A expression by immunohistochemistry. The results showed that high risk- (HR) HPVs were detected in 37/189 (19.6%) PCa specimens compared to 16/167 (9.6%) of BHP specimens (odds ratio 2.3; 95% CI= 1.2 to 4.3; p=0.01). These data suggest HR-HPV may play a role in PCa. HPV 52 and 58 were the most frequent genotypes (33 and 17%, respectively) detected in the population studied. Koilocytes were detected in all in situ PCR-HPV-positive samples, representing a pathognomonic feature of infection, and we observed the overexpression of p16-INK4A in HPV-positive samples compared to HPV-negative samples, indirectly suggesting the presence of HR-HPV E7 oncoprotein. These results suggest that HPV infection plays an important role in prostate cancer development.
Missing a beat: assessment of circadian rhythm abnormalities in bipolar disorder in the genomic era

Circadian rhythm abnormalities have been recognized as a central feature of bipolar disorder (BD) but a coherent biological explanation for them remains lacking. Using genetic mutation of ‘clock genes’, robust animal models of mania and depression have been developed that elucidate key aspects of circadian rhythms and the circadian clock-mood connection. However, translation of this knowledge into humans remains incomplete. In recent years, very large genome-wide association studies (GWAS) have been conducted and the genetic underpinnings of BD are beginning to emerge. However, these genetic studies in BD do not match well with the evidence from animal studies that implicate the circadian clock in mood regulation. Even larger GWAS have been conducted for circadian phenotypes including chronotype, rhythm amplitude, sleep duration, and insomnia. These studies have identified a diverse set of associated genes, including a minority with previously well-characterized functions in the circadian clock. Taken together, the data from recent GWAS of BD and circadian phenotypes indicate that the genetic organization of the circadian clock, both in health and in BD is complex. The findings from GWAS elucidate potentially novel circadian mechanism that may be partly distinct from those identified in animal models. Pleiotropy, epistasis and nongenetic factors may play important roles in regulating circadian rhythms, some of which may underlie circadian rhythm disturbances in BD.
‘It is a dilemma’: perspectives of nurse practitioners on health screening of newly arrived migrants

Background Screening newly arrived migrants from countries with high burden of communicable diseases of public health significance is part of the Swedish national strategy against the spread of these diseases. However, little is known about its implementation. Objective This study aimed at exploring caregivers’ experiences in screening newly arrived migrants to generate knowledge that could inform policy and clinical practice. Design Using an interpretive description framework, we conducted semistructured interviews between November and December 2011 in four Swedish counties, with 15 purposively selected nurses with experience in screening migrants. Data were analyzed using thematic analysis. Results Participants described a range of challenges including discordant views between migrants and the nurses about medical screening, inconsistencies in rules and practices, and conflicting policies. Participants indicated that sociocultural differences resulted in divergent expectations with migrants viewing the participants as agents of migration authorities. They also expressed concern over being given a new assignment without training and being expected to share responsibilities with staff from other agencies without adequate coordination. Finally, they indicated that existing policies can be confusing and raise ethical issues. All these were compounded by language barriers, making their work environment extremely complex and stressful. Conclusions These findings illuminate complex challenges that could limit access to, uptake, and delivery of health screening and undermine public health goals, and highlight the need for a multilevel approach. This entails avoiding the conflation of migration with health issues, harmonizing existing policies to make health care services more accessible and acceptable to migrants, and facilitating health professionals’ work in promoting public health, improving interagency collaboration and the skills of all staff involved in understanding and effectively responding to migrants’ needs, and improving migrants’ health literacy through community outreach interventions.
A collection of annotated and harmonized human breast cancer transcriptome datasets, including immunologic classification.

The increased application of high-throughput approaches in translational research has expanded the number of publicly available data repositories. Gathering additional valuable information contained in the datasets represents a crucial opportunity in the biomedical field. To facilitate and stimulate utilization of these datasets, we have recently developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB). In this note, we describe a curated compendium of 13 public datasets on human breast cancer, representing a total of 2142 transcriptome profiles. We classified the samples according to different immune based classification systems and integrated this information into the datasets. Annotated and harmonized datasets were uploaded to GXB. Study samples were categorized in different groups based on their immunologic tumor response profiles, intrinsic molecular subtypes and multiple clinical parameters. Ranked gene lists were generated based on relevant group comparisons. In this data note, we demonstrate the utility of GXB to evaluate the expression of a gene of interest, find differential gene expression between groups and investigate potential associations between variables with a specific focus on immunologic classification in breast cancer. This interactive resource is publicly available online at: http://breastcancer.gxbsidra. org/dm3/geneBrowser/list.
Reliability of ultrasound in combination with surface electromyogram for evaluating the activity of abdominal muscles in individuals with and without low back pain

This study investigated the reliability of ultrasound in combination with surface electromyogram (EMG) for evaluating the activity of the abdominal muscles in individuals with and without low back pain during the abdominal drawing-in maneuver (ADIM). The study recruited ten individuals with or without low back pain, respectively. While the participants were performing the ADIM, the activities of the transversus abdominis (TrA) and the internal oblique (IO) were measured using ultra-sound, while the activities of the external oblique (EO) and the rectus abdominis (RA) were measured using surface EMG. Intra-class correlation coefficients (ICC) were used to verify the inter-rater reliability of ultrasound in combination with surface EMG at rest and during the ADIM, and Bland-Altman plots were used to verify intra-rater reliability. The inter-rater reliability for the two groups at rest and during the ADIM was excellent (ICC2,1 = 0.77–0.95). In the Bland-Altman plots, the mean differences and 95% limits of agreement in the abdominal muscles of the two groups at rest were −0.03∼0.03 mm (−0.66 to 0.60 mm) and −0.12∼ −0.05 (−0.58 to 0.48% MVIC), respectively. The mean differences and 95% limits of agreement in the abdominal muscles of the two groups during the ADIM were −0.04∼0.02 mm (−0.73 to 0.65 mm) and −0.19∼0.05% MVIC (−1.24 to 1.34% MVIC), respectively. The ultrasound in combination with surface EMG showed excellent inter-rater and intra-rater reliability at rest and during the ADIM.
Perceived Organizational Support for Enhancing Welfare at Work: A Regression Tree Model

When trying to examine outcomes such as welfare and well-being, research tends to focus on main effects and take into account limited numbers of variables at a time. There are a number of techniques that may help address this problem. For example, many statistical packages available in R provide easy-to-use methods of modeling complicated analysis such as classification and tree regression (i.e., recursive partitioning). The present research illustrates the value of recursive partitioning in the prediction of perceived organizational support in a sample of more than 6000 Italian bankers. Utilizing the tree function party package in R, we estimated a regression tree model predicting perceived organizational support from a multitude of job characteristics including job demand, lack of job control, lack of supervisor support, training, etc. The resulting model appears particularly helpful in pointing out several interactions in the prediction of perceived organizational support. In particular, training is the dominant factor. Another dimension that seems to influence organizational support is reporting (perceived communication about safety and stress concerns). Results are discussed from a theoretical and methodological point of view.
Belowground fungal community diversity and composition associated with Norway spruce along an altitudinal gradient

Altitudinal gradients provide valuable information about the effects of environmental variables on changes in species richness and composition as well as the distribution of below ground fungal communities. Since most knowledge in this respect has been gathered on aboveground communities, we focused our study towards the characterization of belowground fungal communities associated with two different ages of Norway spruce (Picea abies) trees along an altitudinal gradient. By sequencing the internal transcribed spacer (ITS) region on the Illumina platform, we investigated the fungal communities in a floristically and geologically relatively well explored forest on the slope of Mt. Iseler of the Bavarian Alps. From fine roots and rhizosphere of a total of 90 of Norway spruce trees from 18 plots we detected 1285 taxa, with a range of 167 to 506 (average 377) taxa per plot. Fungal taxa are distributed over 96 different orders belonging to the phyla Ascomycota, Basidiomycota, Chrytridiomycota, Glomeromycota, and Mucoromycota. Overall the Agaricales (438 taxa) and Tremellales (81 taxa) belonging to the Basidiomycota and the Hypocreales (65 spp.) and Helotiales (61 taxa) belonging to the Ascomycota represented the taxon richest orders. The evaluation of our multivariate generalized mixed models indicate that the altitude has a significant influence on the composition of the fungal communities (p < 0.003) and that tree age determines community diversity (p < 0.05). A total of 47 ecological guilds were detected, of which the ectomycorrhizal and saprophytic guilds were the most taxon-rich. Our ITS amplicon Illumina sequencing approach allowed us to characterize a high fungal community diversity that would not be possible to capture with fruiting body surveys alone. We conclude that it is an invaluable tool for diverse monitoring tasks and inventorying biodiversity, especially in the detection of microorganisms developing very ephemeral and/or inconspicuous fruiting bodies or lacking them all together. Results suggest that the altitude mainly influences the community composition, whereas fungal diversity becomes higher in mature/older trees. Finally, we demonstrate that novel techniques from bacterial microbiome analyses are also useful for studying fungal diversity and community structure in a DNA metabarcoding approach, but that incomplete reference sequence databases so far limit effective identification.
Sleep Drives Metabolite Clearance from the Adult Brain

Taking Out the Trash The purpose of sleep remains mysterious. Using state-of-the-art in vivo two-photon imaging to directly compare two arousal states in the same mouse, Xie et al. (p. 373; see the Perspective by Herculano-Houzel) found that metabolic waste products of neural activity were cleared out of the sleeping brain at a faster rate than during the awake state. This finding suggests a mechanistic explanation for how sleep serves a restorative function, in addition to its well-described effects on memory consolidation. During sleep, metabolic waste products are removed from the extracellular spaces in the brain. [Also see Perspective by Herculano-Houzel] The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.