Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-specific effects of BCG vaccination on morbidity among children in Greenland: a population-based cohort study.

Background The potential non-specific effects of BCG (Bacillus Calmette-Guérin) vaccination, with reported reduction of infectious disease morbidity among vaccinated children, in addition to the protective effect against tuberculosis (TB), are highly debated. In Greenland, BCG vaccination was introduced in 1955, but temporarily discontinued from 1991 to 1996 due to nationwide policy changes. Using the transient vaccination stop, we aimed to investigate possible non-specific effects of BCG vaccination by measuring nation-wide hospitalization rates due to infectious diseases other than TB among vaccinated and unvaccinated children. Methods A retrospective cohort study including all children born in Greenland aged 3 months to 3 years from 1989 to 2004. A personal identification number assigned at birth allowed for follow-up through national registers. Information on hospitalization due to infectious diseases was obtained from the Greenlandic inpatient register using ICD-8 and ICD-10 codes. Participants with notified TB were censored. Incidence rate ratios (IRR) were estimated using Poisson regression. Results Overall, 19 363 children, hereof 66% BCG-vaccinated, were followed for 44 065 person-years and had 2069 hospitalizations due to infectious diseases. IRRs of hospitalization in BCG-vaccinated as compared with BCG-unvaccinated children were 1.07 [95% confidence interval (CI) 0.96-1.20] for infectious diseases overall, and specifically 1.10 (95% CI 0.98-1.24) for respiratory tract infections. Among BCG-vaccinated children aged 3 to 11 months, the IRR of hospitalization due to infectious diseases was 1.00 (95% CI 0.84-1.19) as compared with BCG-unvaccinated children. Conclusion Our results do not support the hypothesis that neonatal BCG vaccination reduces morbidity in children caused by infectious diseases other than TB.
22 MOLECULAR GENETIC ANALYSIS SUBDIVIDED BY ADVERSITY EXPOSURE SUGGESTS ETIOLOGIC HETEROGENEITY IN MAJOR DEPRESSION

OBJECTIVE The extent to which major depression is the outcome of a single biological mechanism or represents a final common pathway of multiple disease processes remains uncertain. Genetic approaches can potentially identify etiologic heterogeneity in major depression by classifying patients on the basis of their experience of major adverse events. METHOD Data are from the China, Oxford, and VCU Experimental Research on Genetic Epidemiology (CONVERGE) project, a study of Han Chinese women with recurrent major depression aimed at identifying genetic risk factors for major depression in a rigorously ascertained cohort carefully assessed for key environmental risk factors (N=9,599). To detect etiologic heterogeneity, genome-wide association studies, heritability analyses, and gene-by-environment interaction analyses were performed. RESULTS Genome-wide association studies stratified by exposure to adversity revealed three novel loci associated with major depression only in study participants with no history of adversity. Significant gene-by-environment interactions were seen between adversity and genotype at all three loci, and 13.2% of major depression liability can be attributed to genome-wide interaction with adversity exposure. The genetic risk in major depression for participants who reported major adverse life events (27%) was partially shared with that in participants who did not (73%; genetic correlation=+0.64). Together with results from simulation studies, these findings suggest etiologic heterogeneity within major depression as a function of environmental exposures. CONCLUSIONS The genetic contributions to major depression may differ between women with and those without major adverse life events. These results have implications for the molecular dissection of major depression and other complex psychiatric and biomedical diseases.
qpure: A Tool to Estimate Tumor Cellularity from Genome-Wide Single-Nucleotide Polymorphism Profiles

Tumour cellularity, the relative proportion of tumour and normal cells in a sample, affects the sensitivity of mutation detection, copy number analysis, cancer gene expression and methylation profiling. Tumour cellularity is traditionally estimated by pathological review of sectioned specimens; however this method is both subjective and prone to error due to heterogeneity within lesions and cellularity differences between the sample viewed during pathological review and tissue used for research purposes. In this paper we describe a statistical model to estimate tumour cellularity from SNP array profiles of paired tumour and normal samples using shifts in SNP allele frequency at regions of loss of heterozygosity (LOH) in the tumour. We also provide qpure, a software implementation of the method. Our experiments showed that there is a medium correlation 0.42 (-value = 0.0001) between tumor cellularity estimated by qpure and pathology review. Interestingly there is a high correlation 0.87 (-value 2.2e-16) between cellularity estimates by qpure and deep Ion Torrent sequencing of known somatic KRAS mutations; and a weaker correlation 0.32 (-value = 0.004) between IonTorrent sequencing and pathology review. This suggests that qpure may be a more accurate predictor of tumour cellularity than pathology review. qpure can be downloaded from https://sourceforge.net/projects/qpure/.
Genetic and epigenetic divergence of duplicate genes in two legume species.

Soybean (Glycine max) and common bean (Phaseolus vulgaris) share a polyploidy event ~59 MYA, followed by a Glycine-specific whole genome duplication (WGD) ~8-13 MYA. Duplicated genes were classified into five categories: singletons, dispersed, proximal, tandem, or WGD/segmental and found strong correlations between gene category and functional annotation. Photosynthesis and transcriptional regulation-related Gene Ontology terms were significantly over-represented in singletons and WGD genes, respectively, aligning with the gene balance hypothesis. We found that the divergence of gene expression and DNA methylation between WGD-derived paralogs increased with age and that WGD genes, initially retained via dosage constraints, subsequently underwent expression divergence, associated with other factors such as DNA methylation. Genes derived from different modes of duplication differed in breadth, level, and specificity of expression in both species. Orthologous genes and ungrouped genes (genes not in an ortholog group) differed in expression patterns. The protein divergence rates of WGD paralog pairs containing an ungrouped gene were higher than those for which both copies had orthologs. We propose that many ungrouped genes are derived from divergent and redundant gene copies, concordant with the neofunctionalization hypothesis. Tandemly duplicated genes were distinct from WGD-derived genes, indicating that mode of duplication contributes to the evolutionary fate of duplicated genes.
The Persistent Homotopy Type Distance

We introduce the persistent homotopy type distance dHT to compare real valued functions defined on possibly different homotopy equivalent topological spaces. The underlying idea in the definition of dHT is to measure the minimal shift that is necessary to apply to one of the two functions in order that the sublevel sets of the two functions become homotopically equivalent. This distance is interesting in connection with persistent homology. Indeed, our main result states that dHT still provides an upper bound for the bottleneck distance between the persistence diagrams of the intervening functions. Moreover, because homotopy equivalences are weaker than homeomorphisms, this implies a lifting of the standard stability results provided by the L-infty distance and the natural pseudo-distance dNP. From a different standpoint, we prove that dHT extends the L-infty distance and dNP in two ways. First, we show that, appropriately restricting the category of objects to which dHT applies, it can be made to coincide with the other two distances. Finally, we show that dHT has an interpretation in terms of interleavings that naturally places it in the family of distances used in persistence theory.
Robust presurgical functional MRI at 7 T using response consistency

Functional MRI is valuable in presurgical planning due to its non‐invasive nature, repeatability, and broad availability. Using ultra‐high field MRI increases the specificity and sensitivity, increasing the localization reliability and reducing scan time. Ideally, fMRI analysis for this application should identify unreliable runs and work even if the patient deviates from the prescribed task timing or if there are changes to the hemodynamic response due to pathology. In this study, a model‐free analysis method—UNBIASED—based on the consistency of fMRI responses over runs was applied, to ultra‐high field fMRI localizations of the hand area. Ten patients with brain tumors and epilepsy underwent 7 Tesla fMRI with multiple runs of a hand motor task in a block design. FMRI data were analyzed with the proposed approach (UNBIASED) and the conventional General Linear Model (GLM) approach. UNBIASED correctly identified and excluded fMRI runs that contained little or no activation. Generally, less motion artifact contamination was present in UNBIASED than in GLM results. Some cortical regions were identified as activated in UNBIASED but not GLM results. These were confirmed to show reproducible delayed or transient activation, which was time‐locked to the task. UNBIASED is a robust approach to generating activation maps without the need for assumptions about response timing or shape. In presurgical planning, UNBIASED can complement model‐based methods to aid surgeons in making prudent choices about optimal surgical access and resection margins for each patient, even if the hemodynamic response is modified by pathology. Hum Brain Mapp 38:3163–3174, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Red blood cell transfusions during sickle cell anemia vaso‐occlusive crises: a report from the magnesium in crisis (MAGiC) study

Little is known about red blood cell (RBC) transfusion practices for children hospitalized for a sickle cell vaso‐occlusive pain crisis (VOC). We hypothesized that transfusion would be associated with the development of acute chest syndrome (ACS), lower hemoglobin (Hb) concentration, and lack of hydroxyurea therapy.
Cross-coupled open-loop resonator bandpass filter with independently tunable center frequency and bandwidth

This paper presents a twofold tunable cross-coupled open-loop resonator bandpass filter to simultaneously and independently control the center frequency and the bandwidth. Frequency selectivity is increased by introducing two transmission zeros via cross coupled resonators. Tunability is achieved by using thin film barium strontium titanate (BST) varactors. The structure is applicable in future seamless and band less cognitive radio systems. The center frequency is adjusted by varactors which are loading the open-loop resonators, while coupling varactors between the resonators enable the control of bandwidth. The proposed filter structure is designed for a center frequency range from 1.5 GHz to 1.75 GHz with a constant bandwidth of 100 MHz and a tunable bandwidth between 70 MHz and 180 MHz at a fixed center frequency of 1.625 GHz. The functionality of the design is experimentally validated.
Top–down signal transmission and global hyperconnectivity in auditory‐visual synesthesia: Evidence from a functional EEG resting‐state study

Auditory‐visual (AV) synesthesia is a rare phenomenon in which an auditory stimulus induces a “concurrent” color sensation. Current neurophysiological models of synesthesia mainly hypothesize “hyperconnected” and “hyperactivated” brains, but differ in the directionality of signal transmission. The two‐stage model proposes bottom–up signal transmission from inducer‐ to concurrent‐ to higher‐order brain areas, whereas the disinhibited feedback model postulates top–down signal transmission from inducer‐ to higher‐order‐ to concurrent brain areas. To test the different models of synesthesia, we estimated local current density, directed and undirected connectivity patterns in the intracranial space during 2 min of resting‐state (RS) EEG in 11 AV synesthetes and 11 nonsynesthetes. AV synesthetes demonstrated increased parietal theta, alpha, and lower beta current density compared to nonsynesthetes. Furthermore, AV synesthetes were characterized by increased top–down signal transmission from the superior parietal lobe to the left color processing area V4 in the upper beta frequency band. Analyses of undirected connectivity revealed a global, synesthesia‐specific hyperconnectivity in the alpha frequency band. The involvement of the superior parietal lobe even during rest is a strong indicator for its key role in AV synesthesia. By demonstrating top–down signal transmission in AV synesthetes, we provide direct support for the disinhibited feedback model of synesthesia. Finally, we suggest that synesthesia is a consequence of global hyperconnectivity. Hum Brain Mapp 39:522–531, 2018. © 2017 Wiley Periodicals, Inc.
Rabies virus‐mediated oligodendrocyte labeling reveals a single oligodendrocyte myelinates axons from distinct brain regions

Oligodendrocytes myelinate neuronal axons during development and increase conduction velocity of neuronal impulses in the central nervous system. Neuronal axons extend from multiple brain regions and pass through the white matter; however, whether oligodendrocytes ensheath a particular set of axons or do so randomly within the mammalian brain remains unclear. We developed a novel method to visualize individual oligodendrocytes and axon derived from a particular brain region in mouse white matter using a combinational injection of attenuated rabies virus and adeno‐associated virus. Using this method, we found that some populations of oligodendrocytes in the corpus callosum predominantly ensheathed axons derived from motor cortex or sensory cortex, while others ensheathed axons from both brain regions, suggesting heterogeneity in preference of myelination toward a particular subtype of neurons. Moreover, our newly established method is a versatile tool for analyzing precise morphology of each oligodendrocyte in animal models for demyelinating disorders and addressing the role of oligodendrocyte in higher brain functions. GLIA 2016. GLIA 2017;65:93–105
Is less more? Comparing chemotherapy alone with chemotherapy and radiation for high‐risk grade 2 glioma: An analysis of the National Cancer Data Base

The addition of chemotherapy to adjuvant radiotherapy (chemotherapy and radiation therapy [CRT]) improves overall survival (OS) for patients with high‐risk grade 2 gliomas; however, the impact of chemotherapy alone (CA) is unknown. This study compares the OS of patients with high‐risk grade 2 gliomas treated with CA versus CRT.
Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.
Serotonergic system antagonists target breast tumor initiating cells and synergize with chemotherapy to shrink human breast tumor xenografts

Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype. Notably, inhibitors of tryptophan hydroxylase 1 (TPH1), required for 5-HT biosynthesis in select non-neuronal cells, the serotonin reuptake transporter (SERT) and several 5-HT receptors compromised BTIC activity as assessed by functional sphere-forming assays. Consistent with these findings, human breast tumor cells express TPH1, 5-HT and SERT independent of their molecular or clinical subtype. Exposure of breast tumor cells ex vivo to sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), reduced BTIC frequency as determined by transplanting drug-treated tumor cells into immune-compromised mice. Moreover, another SSRI (vilazodone; Viibryd) synergized with chemotherapy to shrink breast tumor xenografts in immune-compromised mice by inhibiting tumor cell proliferation and inducing their apoptosis. Collectively our data suggest that antidepressants in combination with cytotoxic anticancer therapies may be an appropriate treatment regimen for testing in clinical trials.
The History Began from AlexNet: A Comprehensive Survey on Deep Learning Approaches

Deep learning has demonstrated tremendous success in variety of application domains in the past few years. This new field of machine learning has been growing rapidly and applied in most of the application domains with some new modalities of applications, which helps to open new opportunity. There are different methods have been proposed on different category of learning approaches, which includes supervised, semi-supervised and un-supervised learning. The experimental results show state-of-the-art performance of deep learning over traditional machine learning approaches in the field of Image Processing, Computer Vision, Speech Recognition, Machine Translation, Art, Medical imaging, Medical information processing, Robotics and control, Bio-informatics, Natural Language Processing (NLP), Cyber security, and many more. This report presents a brief survey on development of DL approaches, including Deep Neural Network (DNN), Convolutional Neural Network (CNN), Recurrent Neural Network (RNN) including Long Short Term Memory (LSTM) and Gated Recurrent Units (GRU), Auto-Encoder (AE), Deep Belief Network (DBN), Generative Adversarial Network (GAN), and Deep Reinforcement Learning (DRL). In addition, we have included recent development of proposed advanced variant DL techniques based on the mentioned DL approaches. Furthermore, DL approaches have explored and evaluated in different application domains are also included in this survey. We have also comprised recently developed frameworks, SDKs, and benchmark datasets that are used for implementing and evaluating deep learning approaches. There are some surveys have published on Deep Learning in Neural Networks [1, 38] and a survey on RL [234]. However, those papers have not discussed the individual advanced techniques for training large scale deep learning models and the recently developed method of generative models [1].
Effect of French maritime pine bark extract on endometriosis as compared with leuprorelin acetate.

OBJECTIVE To clarify the effect of Pycnogenol (Horphag Research, Geneva, Switzerland), French maritime pine bark extract, on endometriosis. STUDY DESIGN Fifty-eight women were included in this study. They were operated on conservatively for endometriosis and surgically diagnosed with the condition. All patients were followed at 4, 12, 24 and 48 weeks after starting treatment to check for endometriosis signs and symptoms, including changes in CA-125 and estrogen levels (E2). Thirty-two patients in the Pycnogenol treatment group took 60 mg Pycnogenol orally a day for 48 weeks. The 26 patients who received gonadotropin-releasing hormone agonist (Gn-RHa) were treated in the standard way. RESULTS Treatment with Pycnogenol slowly but steadily reduced the symptom scores. Treatment with Gn-RHa reduced the scores more efficiently; however, 24 weeks after the end of treatment, the scores suggested a recurrence of signs. No influence of treatment on menstrual cycles or E2 was observed in the Pycnogenol group. CA-125 decreased in both treatment groups. Patients with smaller endometriomas responded better to treatment as compared to patients with larger endometriomas. In the Gn-RHa group, the lowering of CA-125 concentrations was far more pronounced; however, a clear rebound effect was observed. CONCLUSION Pycnogenol is a therapeutic alternative to Gn-RHa in the treatment of endometriosis.
Reducing obesity indicators through brief physical activity counseling (pace) in italian primary care settings

Background: There is an alarming prevalence of obesity and sedentariness in Western countries. An ideal context for health promotion and preventive medicine seems to be the setting of primary care provided by the general practitioner (GP). Purpose: Therefore, this study evaluated the impact of GPs’brief physical activity counseling for overweight and obese patients.Methods: Individuals recruited during routine physician visits were randomly split into an experimental (n = 48) group that received the Patient-centered Assessment and Counseling for Exercise (PACE) protocol, and a usual-care control (n = 48) group. Body mass index (BMI) and abdominal girth were assessed as objective biometrical parameters. Patients in the experimental group self-reported their readiness for physical activity and self-efficacy.Results: The experimental group had significantly better BMI and abdominal girth compared with the control group after a 5- to 6-month follow-up. Furthermore, the experimental group progressed in their stage of physical activity readiness and increased their self-efficacy.Conclusions: The GPs’counseling for physical activity using the PACE protocol influenced mediators and biometrical outcomes in an Italian primary care context.