Miracle-dz/UniFAR-FTUs huggingface dataset:
Progress in finding pathogenic DNA copy number variations in dyslipidemia

Purpose of review DNA copy number variations (CNVs) are large-scale mutations that include deletions and duplications larger than 50 bp in size. In the era when single-nucleotide variations were the major focus of genetic technology and research, CNVs were largely overlooked. However, CNVs clearly underlie a substantial proportion of clinical disorders. Here, we update recent progress in identifying CNVs in dyslipidemias. Recent findings Until last year, only the LDLR and LPA genes were appreciated as loci within which clinically relevant CNVs contributed to familial hypercholesterolemia and variation in Lp(a) levels, respectively. Since 2017, next-generation sequencing panels have identified pathogenic CNVs in at least five more genes underlying dyslipidemias, including a PCSK9 whole-gene duplication in familial hypercholesterolemia; LPL, GPIHBP1, and APOC2 deletions in hypertriglyceridemia; and ABCA1 deletions in hypoalphalipoproteinemia. Summary CNVs are an important class of mutation that contribute to the molecular genetic heterogeneity underlying dyslipidemias. Clinical applications of next-generation sequencing technologies need to consider CNVs concurrently with familiar small-scale genetic variation, given the likely implications for improved diagnosis and treatment.
Numerical production of vowels and diphthongs using finite element methods

Recentment, les simulacions tridimensionals per ordinador han esdevingut bastant populars per modelar l’acustica del tracte vocal. Aquestes son capaces de superar algunes de les limitacions classiques de les tecniques unidimensionals i permeten incloure tots els detalls de la geometria del tracte vocal, millorant d’aquesta manera la qualitat dels sons generats. El metode dels elements finits (FEM) es probablement l’aproximacio mes indicada per resoldre les equacions subjacents de la veu. En la primera part de la tesi s’aborda el problema de generacio de vocals. S’utilitza FEM per resoldre l’equacio d’ones per a la pressio acustica, la qual es combina amb una capa perfectament adaptada (PML) per tal de considerar condicions de radiacio en camp lliure. Aixo permet la simulacio d’ones acustiques propagant-se a traves del tracte vocal i emanant de l’obertura de la boca. L’aproximacio FEM proposada es valida despres mitjancant experiments realitzats en repliques simplificades del tracte vocal. A continuacio s’adapta el metode de la funcio de transferencia entre dos microfons per tal de calcular impedancies del tracte vocal. Aquest s’utilitza a posteriori per a analitzar els efectes de radiacio en vocals que comporten simplificacions del cap huma. Finalment, es proposa realitzar simulacions en dues dimensions (2D) basades en un proces d’ajust que permet a tractes vocals 2D imitar en gran mesura l’acustica de tractes vocals 3D, aconseguint un molt bon balanc entre cost computacional i qualitat de la veu. En la segona part de la tesi es generen diftongs. Per a aquesta finalitat es desenvolupa un esquema estabilitzat d’elements finits que resol l’equacio d’ones en forma mixta expressada en un marc Lagrangia-Euleria Arbitrari (ALE). Es produeixen diftongs tant usant tractes vocals mobils 3D com ara tractes vocals 2D. L’enfocament proposat per a vocals i diftongs permet no nomes visualitzar ones propagant-se a traves del tracte vocal sino tambe escoltar-ne els corresponents sons generats.
Cortical and thalamic connectivity of occipital visual cortical areas 17, 18, 19 and 21 of the domestic ferret (Mustela putorius furo)

The present study describes the ipsilateral and contralateral cortico-cortical and cortico-thalamic connectivity of the occipital visual areas 17,18, 19 and 21 in the ferret using standard anatomical tract-tracing methods. In line with previous studies of mammalian visual cortex connectivity, substantially more anterograde and retrograde label was present in the hemisphere ipsilateral to the injection site compared to the contralateral hemisphere. Ipsilateral reciprocal connectivity was the strongest within the occipital visual areas, while weaker connectivity strength was observed in the temporal, suprasylvian and parietal visual areas. Callosal connectivity tended to be strongest in the homotopic cortical areas, and revealed a similar areal distribution to that observed in the ipsilateral hemisphere, although often less widespread across cortical areas. Ipsilateral reciprocal connectivity was observed throughout the visual nuclei of the dorsal thalamus, with no contralateral connections to the visual thalamus being observed. The current study, along with previous studies of connectivity in the cat, identified the posteromedial lateral suprasylvian visual area (PMLS) as a distinct network hub external to the occipital visual areas in carnivores, implicating PMLS as a potential gateway to the parietal cortex for dorsal stream processing. These data will also contribute to the Ferretome (www.ferretome.org), a macro connectome database of the ferret brain, providing essential data for connectomics analyses and cross-species analyses of connectomes and brain connectivity matrices, as well as providing data relevant to additional studies of cortical connectivity across mammals and the evolution of cortical connectivity variation.
Synergistic interaction of Deltex and Hrp48 leads to JNK activation

The communication among the cells plays a seminal role in metazoan development by coordinating multiple cellular processes that, in turn, helps in the maintenance of biological homeostasis. Our previous study demonstrated that Dx and Hrp48 together downregulate Notch signaling and induce cell death in Drosophila. To understand the signaling events behind the Dx and Hrp48‐induced cell death in a greater detail, we performed a set of genetic experiments followed by immunocytochemical analyses. Our data revealed that Dx along with Hrp48 induced JNK activation and consequently cell death in the eye tissue. Additionally, using genetic and molecular approaches, we identified the domain of Dx protein responsible for its synergistic activity with Hrp48. Altogether, our analyses suggest that coexpression of Dx and Hrp48 activates JNK pathway to induce cell death in eye disc of Drosophila melanogaster.
Analysis of a Huge Accumulated Database of a General Population of People Who Underwent Medical Checkups: The Saitama Cardio metabolic Disease and Organ Impairment Study

between abnormal weight (obesity and underweight) and the etiology of cardio metabolic diseases because we believe that abnormal body weight has significant effects on the development, progression, and prognosis of key diseases, especially those related to diabetes and endocrine disorders [2,3] and because the associations involve multiple factors. Therefore, this multidisciplinary observational retrospective epidemiological study focuses on cardio metabolic diseases and related fields of internal medicine, as well as apparently unrelated fields such as orthopedics, otolaryngology, and ophthalmology. The study is also examining the possible effects of daily lifestyle factors, such as eating behavior and sleep duration. One of the plausible strengths of our study is that the database includes a huge number of subjects without abnormal clinical data, a so-called healthy population, while a small proportion of subjects have borderline clinical findings consistent with preclinical/subclinical disease. The database also includes a very small proportion of subjects (typically 5–10%, depending on the disease) with overt disease and abnormal clinical data. These groups of subjects are either diagnosed for the first time with a disease based on the results of the medical checkup or they were diagnosed with a disease a long time before the checkups but avoided treatment until now. When we deal with a vast amount of data in a cross-sectional study, we can find gradual changes in or effects of factors described above ranging from normal to subclinical and overt disease. Additionally, a broad spectrum of males and females aged 20–85 years have been enrolled, allowing us to consider or account for the possible effects of age on the etiology of a disease.
Application of deep convolutional neural networks in classification of protein subcellular localization with microscopy images

Single‐cell microscopy image analysis has proved invaluable in protein subcellular localization for inferring gene/protein function. Fluorescent‐tagged proteins across cellular compartments are tracked and imaged in response to genetic or environmental perturbations. With a large number of images generated by high‐content microscopy while manual labeling is both labor‐intensive and error‐prone, machine learning offers a viable alternative for automatic labeling of subcellular localizations. Contrarily, in recent years applications of deep learning methods to large datasets in natural images and other domains have become quite successful. An appeal of deep learning methods is that they can learn salient features from complicated data with little data preprocessing. For such purposes, we applied several representative types of deep convolutional neural networks (CNNs) and two popular ensemble methods, random forests and gradient boosting, to predict protein subcellular localization with a moderately large cell image data set. We show a consistently better predictive performance of CNNs over the two ensemble methods. We also demonstrate the use of CNNs for feature extraction. In the end, we share our computer code and pretrained models to facilitate CNN's applications in genetics and computational biology.
Thermal Stability and Thermoelectric Properties of NaZnSb

A layered Zintl antimonide NaZnSb (PbClF or Cu₂Sb structure type; P4/nmm) was synthesized using the reactive sodium hydride NaH precursor. This method provides comprehensive compositional control and facilitates the fast preparation of high-purity samples in large quantities. NaZnSb is highly reactive to humidity/air and hydrolyzes to NaOH, ZnO, and Sb in aerobic conditions. On the other hand, NaZnSb is thermally stable up to 873 K in vacuum, as no structural changes were observed from high-temperature synchrotron powder X-ray diffraction data in the 300⁻873 K temperature range. The unit cell expansion upon heating is isotropic; however, interatomic distance elongation is not isotropic, consistent with the layered structure. Low- and high-temperature thermoelectric properties were measured on pellets densified by spark plasma sintering. The resistivity of NaZnSb ranges from 11 mΩ∙cm to 31 mΩ∙cm within the 2⁻676 K range, consistent with heavily doped semiconductor behavior, with a narrow band gap of 0.23 eV. NaZnSb has a large positive Seebeck coefficient (244 μV∙K-1 at 476 K), leading to the maximum of zT of 0.23 at 675 K. The measured thermoelectric properties are in good agreement with those predicted by theoretical calculations.
Using Machine Learning to Predict Lower-Extremity Injury in US Special Forces

CONNABOY, C. , S. R. EAGLE, C. D. JOHNSON, S. D. FLANAGAN, Q. MI, and B. C. NINDL. Using Machine Learning to Predict Lower-Extremity Injury in US Special Forces. Med. Sci. Sports Exerc. , Vol. 51, No. 5, pp. 1073–1079, 2019. Introduction : Muscu-loskeletal injury rates in military personnel remain unacceptably high. Application of machine learning algorithms could be useful in multivariate models to predict injury in this population. The purpose of this study was to investigate if interaction between individual predictors, using a decision tree model, could be used to develop a population-specific algorithm of lower-extremity injury (LEI) risk. Methods : One hundred forty Air Force Special Forces Operators (27.4 T 5.0 yr, 177.6 T 5.8 cm, 83.8 T 8.4 kg) volunteered for this prospective cohort study. Baseline testing included body composition, isokinetic strength, flexibility, aerobic/anaerobic capacity, anaerobic power, and landing biomechanics. To evaluate unilateral landing patterns, subjects jumped off two-feet from a distance (40% of their height) over a hurdle and landing single-legged on a force plate. Medical chart reviews were conducted 365 d postbaseline. W 2 automatic interaction detection (CHAID) was used, which compares predictor variables to LEI and assigns a population-specific ‘‘cut-point’’ for the most relevant predictors. Results : Twenty-seven percent of operators ( n = 38) suffered LEI. A maximum knee flexion angle difference of 25.1% had the highest association with injury in this population ( P = 0.006). Operators with 9 25.1% differences in max knee flexion angle ( n = 13) suffered LEI at a 69.2% rate. Seven of the 13 Operators with 9 25.1% difference in max knee flexion angle weighed 9 81.8 kg, and 100% of those operators suffered LEI ( P = 0.047; n = 7). Only 33% of operators with 9 25.1% difference in max knee flexion angle that weighed G 81.8 kg suffered LEI. Conclusions : This study demonstrated increased risk of LEI over a 365-d period in Operators with greater differences in single-leg landing strategies and higher body mass. The CHAID approach can be a powerful tool to analyze population-specific risk factors for injury, along with how those factors may interact to enhance risk.
Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of facioscapulohumeral muscular dystrophy

DUX4 is a transcription factor whose misexpression in skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD). DUX4’s transcriptional activity has been extensively characterized, but the DUX4-induced proteome remains undescribed. Here, we report concurrent measurement of RNA and protein levels in DUX4-expressing cells via RNA-seq and quantitative mass spectrometry. DUX4 transcriptional targets were robustly translated, confirming the likely clinical relevance of proposed FSHD biomarkers. However, a multitude of mRNAs and proteins exhibited discordant expression changes upon DUX4 expression. Our dataset revealed unexpected proteomic, but not transcriptomic, dysregulation of diverse molecular pathways, including Golgi apparatus fragmentation, as well as extensive post-transcriptional buffering of stress-response genes. Key components of RNA degradation machineries, including UPF1, UPF3B, and XRN1, exhibited suppressed protein, but not mRNA, levels, explaining the build-up of aberrant RNAs that characterizes DUX4-expressing cells. Our results provide a resource for the FSHD community and illustrate the importance of post-transcriptional processes in DUX4-induced pathology.
Caregivers’ emotional distress due to neuropsychiatric symptoms of persons with amnestic mild cognitive impairment or Alzheimer’s disease

abstract Compared to the literature on Alzheimer’s disease (AD), less is known about the emotional distress of caregivers of persons with amnestic Mild Cognitive Impairment (aMCI). This study describes and compares emotional distress due to neuropsychiatric symptoms (NPS) among children and spousal caregivers of aMCI or mild AD care recipients. It also examined the association between the frequency and severity of NPS and caregivers’ emotional distress. In total, 108 spouses or children of persons with aMCI or mild AD were administered the Neuropsychiatric Inventory, measuring the frequency/severity of NPS in the patient as well as the associated caregiver’s emotional distress. Emotional distress due to each NPS was compared between children and spouses and the relationship between NPS and emotional distress was assessed. There was no significant difference in emotional distress between aMCI and mild AD spousal caregivers for all symptoms, but for children caregivers, emotional distress was significantly higher in the mild AD group than in the aMCI group. Regardless of the caregiver’s relationship to the patient or the condition (aMCI vs mild AD) of the latter, there was a positive relationship between the frequency/severity of NPS and caregiver emotional distress. Caregivers of persons with aMCI experienced emotional distress due to the presence of NPS in their significant others at a level that is generally similar to that experienced by caregivers of persons with mild AD. This study highlights the need for interventions to reduce emotional burden by helping caregivers manage NPS in care recipients.
Representing Knowledge of a Concept Map Assessment and Learning Environment: An Ontological Approach

In this paper, a brief description of the concept mapping assessment and learning environment referred to as COMPASS is given, focusing on its main features. Exploiting the benefits of using web ontologies to represent the knowledge of the system (domain knowledge and student model), this paper describes how Semantic Web technologies can be applied to the COMPASS environment.
Major depressive disorder in patients with diabetes mellitus in Pietermaritzburg, South Africa.

BACKGROUND Diabetes mellitus (DM) and major depressive disorder (MDD) constitute a major burden of disease. A study found that type 2 DM (DM2) is associated with a two-fold increase in risk of developing MDD worldwide - except in Africa. The present study challenges this statement. OBJECTIVES To determine the prevalence of MDD in a cohort of patients with DM and its effect on glycaemic control. METHODS A cross-sectional study was performed at a diabetes clinic at Edendale Hospital, Pietermaritzburg, South Africa (1 March - 31 May 2017). A total of 176 participants were enrolled. Participants completed the Patient Health Questionnaire-9 (PHQ-9), with a score of ≥10 representing a diagnosis of MDD. Higher PHQ-9 scores translate into more severe MDD. A surrogate for glycaemic control, glycated haemoglobin (HbA1c) blood testing, was also performed. RESULTS The majority of participants were female and suffered from DM2. The mean age was 54.4 years. The prevalence of MDD in the study population was 46.6%. A significantly positive linear relationship was shown between PHQ-9 score and HbA1c (p=0.018253). CONCLUSIONS MDD appears to constitute a large burden of disease in our population of individuals with DM. A relationship between the severity of the MDD and HbA1c suggests that prompt intervention in both conditions is likely to improve health outcomes.
Practical considerations for the static balancing of mechanisms of parallel architecture

Abstract This paper discusses the development of statically balanced spatial parallel platform mechanisms. A mechanism is statically balanced if its potential energy is constant for all possible configurations. This property is very convenient for robotic manipulators with large constant payloads, since it means that the mechanism is statically stable for any configuration, i.e., zero actuator torques are required whenever the manipulator is at rest. Furthermore, only inertial forces and moments have to be sustained while the manipulator is moving. This makes it possible to create passive devices that can assist humans to manipulate a heavy load, and to create robotic manipulators that require smaller actuators and/or consume less energy. Furthermore, by retrofitting existing machine tools, static deflection problems due to gravitational loads may be reduced. This paper (1) summarizes how static balancing can be implemented in a parallel manipulator with six degrees of freedom, (2) presents the design of a small-scale prototype, and (3) discusses general implementation issues.
A Review on Bioactivities of Tobacco Cembranoid Diterpenes

Cembranoids are carbocyclic diterpenes comprising four isoprene units and are natural products with a parent skeleton consisting of a 14-membered ring. They have gained wide interest in recent years and are a major hotspot in the research of natural product chemistry. Since 1962, various tobacco cembranoid diterpenes have been identified. This review systematically discusses and summarises the excellent antimicrobial, insecticidal, cytotoxic and neuroprotective activities of tobacco cembranoid diterpenes. These compounds show potential to be developed as botanical fungicides, cytotoxic drugs and drugs for the treatment of human immunodeficiency virus, Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases. However, there are relatively few studies on the structure–activity relationship (SAR) of tobacco cembranoid diterpenes. Therefore, future studies should focus on their structural modification, SAR and biogenic relationships.
Extensions of three-dimensional higher-derivative gravity

Driedimensionale zwaartekrachtmodellen met hogere afgeleiden, met in het bijzonder New Massive Gravity (NMG) en Topologically Massive Gravity (TMG), zijn speelmodellen die gebruikt worden door theoretische natuurkundigen om te onderzoeken hoe Einsteins algemene relativiteitstheorie verbeterd kan worden. Het doel van deze dissertatie is een beter begrip te krijgen van het theoretische raamwerk van NMG en TMG, door te onderzoeken of zij kunnen worden uitgebreid naar een bredere klasse van modellen. NMG en TMG zijn modellen in een driedimensionale ruimtetijd die spin-2-deeltjes bevatten. Deze dissertatie toont aan dat, wanneer de ruimtetijd bijna vlak is en de zwaartekracht zwak is, benaderende modellen van NMG en TMG kunnen worden uitgebreid om veel meer typen deeltjes te beschrijven, waaronder spin-1, spin-3/2, spin-2, spin-5/2, enzovoort. Ook toont deze dissertatie aan dat in sommige situaties de modellen van deze deeltjes uitgebreid kunnen worden naar ruimtetijddimensies groter dan drie. Bovendien kunnen de driedimensionale modellen van spin-2 en spin-3/2 worden gecombineerd in een type model, supergravitatie genaamd, dat ook behandeld wordt in deze dissertatie. De conclusie van deze dissertatie is dat de benaderende modellen voor NMG en TMG inderdaad kunnen worden uitgebreid naar een veel breder raamwerk van modellen.
Cognitive and behavioral differences in toddlers with autism spectrum disorder from multiplex and simplex families

Prospective, longitudinal designs utilizing “high‐risk” infant siblings of children diagnosed with Autism Spectrum Disorder (ASD‐sibs) have provided unique and valuable insights regarding the early ASD phenotype. However, it remains unclear whether these cases are representative of all children with ASD. The objective in the present study was to investigate whether the early development of toddlers with ASD from multiplex (MPX) families, who have an affected older sibling, is similar or different to toddlers with ASD from simplex (SPX) families, where there is no affected sibling. A further aim was to examine patterns of association between autism symptom severity and cognitive functioning within each group to inform possible mechanisms for group similarities/differences. Behavioral and cognitive assessment data from a sample of toddlers with ASD was utilized, comprising 45 MPX, 127 first‐born SPX, and 72 later‐born SPX toddlers. Participants in the MPX group had significantly higher developmental quotients on the Mullen Scales of Early Learning compared to those in the SPX groups, who did not differ from each other. However, all three groups were similar on their autism severity scores (measured using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview), and the pattern of relationships between cognitive ability and autism symptom severity. The results suggest that caution be exercised in generalizing findings from ASD‐sib samples to other samples of children with ASD. The higher cognitive abilities in the MPX group, in addition to biological differences, may also be an outcome of family environmental factors, which deserves further investigation. Autism Research 2019, 12: 682–693. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.