Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of genetic predisposition to molecular subtypes of breast cancer in Brazilian patients

Introduction BRCA1 and BRCA2 germline pathogenic variants (GPVs) account for most of the 5-10% of breast cancer (BC) that is attributable to inherited genetic variants. BRCA1 GPVs are associated with the triple negative subtype, whereas BRCA2 GPVs are likely to result in higher grade, estrogen-receptor positive BCs. The contribution of other genes of high and moderate risk for BC has not been well defined and risk estimates to specific BC subtypes is lacking, especially for an admixed population like Brazilian. Objective The aim of this study is to evaluate the value of a multigene panel in detecting germline mutations in cancer-predisposing genes for Brazilian BC patients and its relation with molecular subtypes and the predominant molecular ancestry. Patients and methods A total of 321 unrelated BC patients who fulfilled NCCN criteria for BRCA1/2 testing between 2016-2018 were investigated with a 94-genes panel. Molecular subtypes were retrieved from medical records and ancestry-specific variants were obtained from off-target reads obtained from the sequencing data. Results We detected 83 GPVs in 81 patients (positivity rate of 25.2%). Among GPVs, 47% (39/83) were identified in high-risk BC genes (BRCA1/2, PALB2 and TP53) and 18% (15/83) in moderate-penetrance genes (ATM, CHEK2 and RAD51C). The remainder of the GPVs (35% - 29/83), were identified in lower-risk genes. As for the molecular subtypes, triple negative BC had a mutation frequency of 31.6% (25/79), with predominance in BRCA1 (12.6%; 10/79). Among the luminal subtypes, except Luminal B HER2-positive, 18.7% (29/155) had GPV with BRCA1/2 genes contributing 7.1% (11/155) and non-BRCA1/2 genes, 12.9% (20/155). For Luminal B HER2-positive subtype, 40% (16/40) had GPVs, with a predominance of ATM gene (15% - 6/40) and BRCA2 with only 2.5% (1/40). Finally, HER2-enriched subtype presented a mutation rate of 30.8% (4/13) with contribution of BRCA2 of 7.5% (1/13) and non-BRCA1/2 of 23% (3/13). Variants of uncertain significance (VUS) were identified in 77.6% (249/321) of the patients and the number of VUS was increased in patients with Asian and Native American ancestry. Conclusion The multigene panel contributed to identify GPVs in genes other than BRCA1/2, increasing the positivity of the genetic test from 9.6% (BRCA1/2) to 25.2% and, considering only the most clinically relevant BC predisposing genes, to 16.2%. These results indicate that women with clinical criteria for hereditary BC may benefit from a multigene panel testing, as it allows identifying GPVs in genes that directly impact the clinical management of these patients and family members.
Aberrant pattern of regional cerebral blood flow in mild cognitive impairment: A meta-analysis of arterial spin labeling magnetic resonance imaging

In mild cognitive impairment (MCI), cognitive decline is associated with abnormal changes of cerebral blood flow (CBF). Arterial spin labeling magnetic resonance imaging (ASL-MRI) is an effective method for assessing regional cerebral blood flow (rCBF). However, the CBF estimated via ASL-MRI in MCI often differs between studies, and the consistency of CBF changes in MCI is unclear. In this study, 13 ASL-MRI studies with 495 MCI patients and 441 health controls were screened out from PubMed, Embase, Cochrane, Web of Science, Wanfang, and CNKI. An activation likelihood estimation (ALE) meta-analysis was performed to explore the brain regions with abnormal CBF in MCI. It showed that the decreased CBF in MCI was identified in the precuneus, inferior parietal lobule (IPL), superior occipital gyrus (SOG), middle temporal gyrus (MTG), and middle occipital gyrus (MOG), while the increased CBF in MCI was identified in the lentiform nucleus (LN) compared with healthy controls. The study characterized the abnormal pattern of regional CBF in MCI, which would promote our knowledge of MCI and might be used as a biomarker in clinic. Systematic review registration https://www.crd. york.ac. uk/prospero/display_record. php? RecordID=259633.
Educational attainment and offspring birth weight: A bidirectional Mendelian randomization study

Background: The association between educational attainment (EA) and offspring birth weight (BW) has been reported by several traditional epidemiological studies. However, evidence for this association tends to be mixed and confounded. This study aimed to investigate the causal association between EA of parents and offspring BW. Methods: Here, we carried out a two-sample bidirectional Mendelian randomization (MR) analysis to examine the causal association between EA of males (n = 131,695) and females (n = 162,028) and offspring BW using genetic instruments. Summary statistics of EA associated single nucleotide polymorphisms (SNPs) were extracted from a GWAS incorporating 293,723 individuals of European descent performed by the Social Science Genetic Association Consortium (SSGAC), and the effects of these SNPs on offspring BW were estimated using a GWAS meta-analysis of 86,577 participants of European descent from 25 studies. Univariable MR analyses were conducted using the inverse-variance weighted (IVW) method and four other methods. Further sensitivity analyses were carried out to test the viability of the results. Multivariable MR was used to examine the confounders between the exposure and outcome. Results: The result shows evidence that the offspring BW is positively causally affected by female EA. Each one standard deviation (SD) increase in female EA was associated with 0.24 SD higher of offspring BW (95% confidence interval [CI], 0.10 to 0.37, p < 0.001 for the IVW method). Similarly, change in offspring BW was 0.21 SD (95% CI: 0.07 to 0.34, p = 2.82 × 10–3) per one SD higher in male EA. No causal effect of BW on EA was found by any of the five methods. The causal association between female EA and offspring BW maintained after adjusting for alcoholic drinks per week and BMI. The effect of male EA on offspring BW was attenuated when we adjusted for BMI and alcoholic drinks per week using multivariable MR analysis. Conclusion: Our study indicated that female EA is positively causally associated with offspring BW. The association between male EA and offspring BW may be confounded by alcoholic drinks per week and BMI.
Gasdermin D: A potential mediator and prognostic marker of bladder cancer

Background: Bladder cancer is considered one of the commonest widespread cancers, its presentation ranges from non-muscle invasive form to being muscle-invasive. The gasdermin family of proteins consists of six proteins. Members of gasdermin family are involved in pyroptosis; which is considered as type of inflammatory apoptosis via participation of gasdermin D and inflammatory caspases. Purpose: The goal of this research was to look into the potential involvement of gasdermin D in pathogenesis of bladder cancer, In addition, to investigate its potential role as a prognostic marker of bladder cancer. Methods: Gasdermin D gene and protein expression was examined in fresh frozen 80 bladder cancer specimens (30 NMIBC, and 50 MIBC) and the matching 80 control tissue samples utilizing real-time polymerase chain reaction and western blotting. Furthermore, the immunoreactivity of gasdermin D protein was also detected by immunohistochemistry. Results: Gasdermin D gene and protein expression showed a highly significant difference between the control and the two bladder cancer groups (p < 0.001), as demonstrated by real-time PCR, western blotting and immunohistochemistry. Cox proportional hazards regression models showed that lower gasdermin D gene expression in cancer patients (≤1.58-fold), and younger age (≤53 years) were linked with a higher risk of local tumor recurrence. Moreover, higher gasdermin D gene expression (>2.18-fold), and lymph nodes’ involvement were associated with an increased mortality. Conclusion: Gasdermin D is involved in the pathogenesis of bladder cancer and muscle invasion, in addition, tissue gasdermin D expression may be used as useful tool to predict local tumor recurrence.
Clinical vitamin D levels are associated with insular volume and inferior temporal gyrus white matter surface area in community-dwelling individuals with knee pain

Context Vitamin D is an essential, fat soluble micronutrient long-known for its effects on calcium homeostasis and bone health. With advances in technology, it is being discovered that Vitamin D exerts its effects beyond the musculoskeletal system. Vitamin D has since been noted in nervous system health and functioning, and is becoming a target of interest in brain health, aging, and chronic pain outcomes. Objectives We and others have previously shown that deficient Vitamin D status is associated with greater pain severity across a variety of conditions, however the reason as to why this relationship exists is still being understood. Here, we sought to examine associations between Vitamin D status and brain structure in those with chronic knee pain. Methods Structural MRI imaging techniques and whole brain analyses were employed and serum Vitamin D were collected on 140 participants with chronic pain. Covariates included age, sex, race and site, as these data were collected at two separate institutions. ANOVAs using the clinical cut points for Vitamin D status (deficient, insufficient, and optimal) as well as continuous regression-based Vitamin D effects were employed to observe differences in brain volume. P-value was set to 0.017 after correction for multiple comparisons. Results We discovered that individuals in our sample (age = 50+; 63.6% female; 52.1% Non-Hispanic Black) who were either clinically deficient (<20 ng/mL) or insufficient (20–30 ng/mL) in serum Vitamin D had significant differences in the gray matter of the left circular insular cortex, left inferior temporal gyrus, right middle temporal gyrus, as well as decreased white matter surface area in the right inferior temporal gyrus compared to those considered to have optimal levels (>30 ng/mL) of serum Vitamin D. Conclusion Evidence from these data suggests that Vitamin D, or lack thereof, may be associated with pain outcomes by mediating changes in regions of the brain known to process and interpret pain. More research understanding this phenomenon as well as the effects of Vitamin D supplementation is warranted.
CEPLJENJE RAZLIČNIH SORT NAVADNE BUKVE (Fagus sylvatica L.)

Raziskava je bila narejena v letu 2008 na navadni bukvi (Fagus sylvatica L.) na Fakulteti za kmetijstvo in biosistemske vede Univerze v Mariboru. Cepili smo stiri razlicne sorte navadne bukve in sicer 'Pendula', 'Atropunica', 'Zlatia' in 'Tricolor'. Cepili smo v spomladanskem obdobju na budno oko, z nacinom cepljenja dolaga s strani. Preucevali smo vpliv posamezne sorte na uspeh cepljenja. Pri vsaki posamezni sorti pa smo preucevali vpliv debeline podlage, dolžine cepica in teže cepica na uspeh cepljenja. Posamezne sorte imajo statisticno znacilen vpliv na uspeh cepljenja. Uspeh cepljenja je bil statisticno znacilno boljsi pri sortah 'Pendula' (80 %) in 'Zlatia' (78 %), v primerjavi s sortama 'Atropunica' (50 %) in 'Tricolor' (2 %). Na uspeh cepljenja ne vpliva debelina podlage, dolžina cepica in teža cepica.
Genetic restoration on complex pedigrees

Analyses of genetic data observed on groups of related individuals frequently require the computation of probabilities on pedigrees. Existing methods are computationally intensive and can be infeasible on large and complex pedigrees. The estimation of genotypic configurations on pedigrees from phenotypic data, whether for prior studies of the likely power of potential data to decide between alternative genetic hypotheses, as an implicit stage in fitting a genetic model, or as an end result in a genetic counselling context, is one component of such analyses. An alternative approach to this reconstruction problem can be based on procedures used in Imaging Analysis, all closely related to the method of Metropolis. These procedures exploit the local nature of the information in a pedigree thus permitting the definition of a neighbourhood system whereby, conditional on the neighbours, the genotypes of individuals are independent. The ICM procedure iteratively updates the genotype estimate of each individual in turn, replacing the current estimate by the mode of the local conditional posterior distribution. Increase and convergence of the overall posterior probability of genotypes given phenotypes is assured, but the restoration does not necessarily converge to a global maximum of the posterior distribution. Alternatively, one can update a vector of single-individual genotype probabilities rather than the discrete genotype, again conditionally on current neighbouring values. Another possibility is to update each individual's genotype estimate by sampling from the local conditional posterior distribution. This method is known as the Gibbs sampler. Multiple realisations of the Gibbs sampler can provide estimates of the true posterior distribution of genotypes given phenotypes on the pedigree, and, when used in conjunction with simulated annealing can find the global maximum of this distribution. These approaches to genotypic restoration are modified and tested by application to a very complicated pedigree of Greenland Eskimos. The areas of Pedigree Analysis to which such approaches are most directly relevant include genetic counselling and selective animal breeding together with questions about ancestral genotypes and the ancestral paths of rare alleles.
Planning and Control

"Planning and Control" explores planning and control by reformulating the two areas in a common control framework, developing the corresponding techniques side-by-side, and identifying opportunities for integrating their ideas and methods. This book is organized around the central roles of prediction, observation, and computation control. The first three chapters deal with predictive models of physical systems based on temporal logic and the differential calculus. Chapter 4 and 5 present some basic concepts in planning and control, including controllability, observability, stability, feedback control, task reduction, conditional plans, and the relationship between goals and preferences. Chapters 6 and 7 consider issues of uncertainty, covering state estimation and the Kalman filter, stochastic dynamic programming, probabilistic modeling, and graph-based decision models. The remaining chapters investigate selected topics in time-critical decision making, adaptive control, and hybrid control architectures. Throughout, the reader is led to consider critical tradeoffs involving the accuracy of prediction, the availability of information from observation, and the costs and benefits of computation in dynamic environments. This book is useful to researchers in artificial intelligence and control theory, and others concerned with the design of complex applications in robotics, automated manufacturing, and time-critical decision support.
Application and Network Measurements For Multiple Description Coded Video Sequences

Multiple description coding has received a lot of interest lately, because it allows to split one source of information in multiple entities, where each of the entities is decodable. The more of these entities are received the more information of the original source can be restored. This opens the door for new applications in many fields of mobile communications. Unfortunately the multiple description coding comes with the price of higher bandwidth requirements. This overhead is caused by the coding process itself and the related network transport. In this work we present a solid investigation of the overhead arising from the splitting process for video coding. Several well known and new video sequences in the QCIF and CIF video format were encoded for multiple descriptors using H.263 and H.26L encoder. The overhead caused by the encoding and underlying network protocols is given separately. Furthermore we investigate the quality of the decoded video in dependency of the received percentage of descriptors. Our results show that the overhead depends dramatically on the video codec chosen and that for eight descriptors the overhead differs from 5% to 200%. A main conclusion we draw here is that we have to consider the scenario carefully whether or not multiple description coding should be chosen over single description coding.
Extending information retrieval system model to improve interactive web searching

The research set out with the broad objective of developing new tools to support Web information searching. A survey showed that a substantial number of interactive search tools were being developed but little work on how these new developments fitted into the general aim of helping people find information. Due to this it proved difficult to compare and analyse how tools help and affect users and where they belong in a general scheme of information search tools. A key reason for a lack of better information searching tools was identified in the ill-suited nature of existing information retrieval system models. The traditional information retrieval model is extended by synthesising work in information retrieval and information seeking research. The purpose of this new holistic search model is to assist information system practitioners in identifying, hypothesising, designing and evaluating Web information searching tools. Using the model, a term relevance feedback tool called ‘Tag and Keyword’ (TKy) was developed in a Web browser and it was hypothesised that it could improve query reformulation and reduce unnecessary browsing. The tool was laboratory experimented and quantitative analysis showed statistical significances in increased query reformulations and in reduced Web browsing (per query). Subjects were interviewed after the experiment and qualitative analysis revealed that they found the tool useful and saved time. Interestingly, exploratory analysis on collected data identified three different methods in which subjects had utilised the TKy tool. The research developed a holistic search model for Web searching and demonstrated that it can be used to hypothesise, design and evaluate information searching tools. Information system practitioners using it can better understand the context in which their search tools are developed and how these relate to users’ search processes and other search tools.
Semantic scaffolding in first language acquisition : the acquisition of raising-to-object and object control

Susannah Kirby Semantic scaffolding in first language acquisition: The acquisition of raising-to-object and object control (Under the direction of Misha Becker) This dissertation joins the debates on whether language is innate and/or modular, by examining English-speaking children’s acquisition of raising-to-object (RO; (1)) and object control (OC; (2)) utterances. 1. RO: Suki wanted/needed Neili [ti to kiss Louise] 2. OC: Suki asked/told Neili [PROi to kiss Louise] While these verbs may appear in the same surface string, they map onto two distinct underlying structures. As a result, they differ in their syntactic and semantic behaviors, including the interpretation of embedded passives, and whether the subject of the embedded clause may be expletive or inanimate. Several truth-value and sentence judgment tasks yielded the following results: • Children have adultlike comprehension of active RO/OC utterances by age 4. • Children who fail on tests of matrix passives can interpret passives embedded under RO verbs (despite their greater length and syntactic complexity), but not under OC verbs (which have syntax more like matrix passives).
Listening from within

This article is devoted to the description of the experience associated with listening to a sound. In the first part, we describe the method we used to gather descriptions of auditory experience and to analyse these descriptions. This work of explicitation and analysis has enabled us to identify a threefold generic structure of this experi- ence, depending on whether the attention of the subject is directed towards (1) the event which is at the source of the sound, (2) the sound in itself, considered independently from its source, (3) the felt sound. In the second part of the article, we describe this structure. The third part is devoted to a discussion of these results and the paths they open up in various fields of theoretical and applied research.
Network Models in Railroad Planning and Scheduling

The past few decades have witnessed numerous applications of operations research in logistics, and these applications have resulted in substantial cost savings. However, the U.S. railroad industry has not benefited from the advances, and most of the planning and scheduling processes do not use modeling and optimization. Indeed, most of the planning and scheduling problems arising in railroads, which involve billions of dollars of resources annually, are currently being solved manually. The main reason for not using OR models and methodologies is the mathematical difficulty of these problems, which prevented the development of decision tools that railroads can use to obtain implementable solutions. However, now this situation is gradually changing. We are developing cutting-edge operations research algorithms, by using state-of-the-art ideas from linear and integer programming, network flows, discrete optimization, heuristics, and very large-scale neighborhood (VLSN) search, that railroads have already started using and from which they have started deriving immense benefits. This chapter gives an overview of the railroad planning and scheduling problems, including the railroad blocking problem, train scheduling problem, yard location problem, train dispatching problem, locomotive scheduling problem, and crew scheduling problem. Some of these problems are very large-scale integer programming problems containing billions or even trillions of integer variables. We will describe algorithms that can solve these problems to near-optimality within one to two hours of computational time. We present computational results of these algorithms on the data provided by several U.S. railroads, demonstrating potential benefits from tens to hundreds of millions annually.
"Jenseits von Jedem?" Grundverhältnisse, Beziehungsformen und Interaktionsmuster im musiktherapeutischen Erstkontakt mit schizophrenen Patienten

Die Arbeit widmet sich der Erforschung von musiktherapeutischen Erstkontakten mit schizophrenen Patienten. Vor dem Hintergrund des ausfuhrlich dargestellten Selbst- und Welterlebens schizophrener Menschen sowie der einschlagigen psychoanalytisch orientierten Fachliteratur zum Themenkreis werden die innerhalb der Erstkontakte intonierten musikalischen Improvisationen sowie die Transkriptionen der Gesprache mit (modifizierten) Methoden der morphologischen Wirkungsforschung vergleichend psychologisch untersucht. Die Arbeit geht vor allem der Frage nach, ob sich in der musiktherapeutischen Improvisation typische Gestaltungsmerkmale zeigen und in wie weit diese auf Grundverhaltnisse schizophrenen In-der-Welt-Seins einerseits und auf individuelle Ressourcen der jeweiligen Patienten und Potentiale des Mediums Musik wie des Improvisierens im Rahmen des musiktherapeutischen Erstkontaktes andererseits verweisen.