Miracle-dz/UniFAR-FTUs huggingface dataset:
Age-dependent neurodegeneration and organelle transport deficiencies in mutant TDP43 patient-derived neurons are independent of TDP43 aggregation

TAR DNA-binding protein 43 (TDP43) is a cause of familiar and sporadic amyotrophic lateral sclerosis (ALS). The diverse postulated mechanisms by which TDP43 mutations cause the disease are not fully understood. Human wildtype and TDP43 S393L and G294V mutant spinal motor neuron cultures were differentiated from patient-derived iPSCs. Mutant hTDP43 and wildtype motor neuron cultures did not differ in neuron differentiation capacity during early maturation stage. During aging we detected a dramatic neurodegeneration including neuron loss and pathological neurofilament abnormalities in TDP43 mutant cultures only. Additionally mitochondria and lysosomes of aging spinal motor neurons revealed robust TDP43 mutation dependent abnormal phenotypes in size, shape, speed and motility which all appeared without TDP43 mislocalization or aggregation formation. Furthermore, D-sorbitol – known to induce stress granules and cytoplasmic mislocalization of TDP43 – rescued axonal trafficking phenotypes without any signs of TDP43 mislocalization or aggregation formation. Our data indicate TDP43 mutation-dependent but cytosolic aggregation-independent mechanisms of motor neuron degeneration in TDP43 ALS.
Knowledge Distance, Cognitive-Search Processes, and Creativity

Prior research has provided conflicting arguments and evidence about whether people who are outsiders or insiders relative to a knowledge domain are more likely to demonstrate scientific creativity in that particular domain. We propose that the nature of the relationship between creativity and the distance of an individual’s expertise from a knowledge domain depends on his or her cognitive processes of problem solving (i.e., cognitive-search effort and cognitive-search variation). In an analysis of 230 solutions generated in a science contest platform, we found that distance was positively associated with creativity when problem solvers engaged in a focused search (i.e., low cognitive-search variation) and exerted a high level of cognitive effort. People whose expertise was close to a knowledge domain, however, were more likely to demonstrate creativity in that domain when they drew on a wide variety of different knowledge elements for recombination (i.e., high cognitive-search variation) and exerted substantial cognitive effort.
Inter-Simple Sequence Repeat Data Reveals High Genetic Diversity in Wild Populations of the Narrowly Distributed Endemic Lilium regale in the Minjiang River Valley of China

Lilium regale E.H. Wilson is endemic to a narrow geographic area in the Minjiang River valley in southwestern China, and is considered an important germplasm for breeding commercially valuable lily varieties, due to its vigorous growth, resistance to diseases and tolerance for low moisture. We analyzed the genetic diversity of eight populations of L. regale sampled across the entire natural distribution range of the species using Inter-Simple Sequence Repeat markers. The genetic diversity (expected heterozygosity= 0.3356) was higher than those reported for other narrowly distributed endemic plants. The levels of inbreeding (F st = 0.1897) were low, and most of the genetic variability was found to be within (80.91%) than amongpopulations (19.09%). An indirect estimate of historical levels of gene flow (N m =1.0678) indicated high levels of gene flow among populations. The eight analyzed populations clustered into three genetically distinct groups. Based on these results, we recommend conservation of large populations representing these three genetically distinct groups.
Joint modeling of multivariate longitudinal measurements and survival data with applications to Parkinson’s disease

In many clinical trials, studying neurodegenerative diseases including Parkinson’s disease (PD), multiple longitudinal outcomes are collected in order to fully explore the multidimensional impairment caused by these diseases. The follow-up of some patients can be stopped by some outcome-dependent terminal event, e.g. death and dropout. In this article, we develop a joint model that consists of a multilevel item response theory (MLIRT) model for the multiple longitudinal outcomes, and a Cox’s proportional hazard model with piecewise constant baseline hazards for the event time data. Shared random effects are used to link together two models. The model inference is conducted using a Bayesian framework via Markov Chain Monte Carlo simulation implemented in BUGS language. Our proposed model is evaluated by simulation studies and is applied to the DATATOP study, a motivating clinical trial assessing the effect of tocopherol on PD among patients with early PD.
High susceptibility of magpie (Pica pica) to experimental infection with lineage 1 and 2 West Nile virus

West Nile virus (WNV), a zoonotic pathogen naturally transmitted by mosquitoes whose natural hosts are birds, has spread worldwide during the last few decades. Resident birds play an important role in flavivirus epidemiology, since they can serve as reservoirs and facilitate overwintering of the virus. Herein, we report the first experimental infection of magpie (Pica pica) with two strains of West Nile virus, lineages 1 (NY-99) and 2 (SRB Novi-Sad/12), which are currently circulating in Europe. Magpies were highly susceptible to WNV infection, with similar low survival rates (30% and 42.8%) for both lineages. All infected magpies developed viremia detectable at 3 days post-infection with titers above those necessary for successful transmission of WNV to a mosquito. Neutralizing antibodies were detected at all time points analyzed (from 7 to 17 days post-infection). WNV genome was detected in the brains and hearts of all magpies that succumbed to the infection, and, in some of the surviving birds. WNV-RNA was amplified from swabs (oral and cloacal) at 3, 6 and 7 days post-infection and feather pulps, from 3 to 17 days post-infection, of infected animals. Even more, infectious virus was recovered from swabs up to 7 days post-infection and from feather pulps up to 10 days post infection. Sham-infected control animals were negative for viremia, viral RNA, and antibodies. These results suggest that the magpie, which is one of the most abundant corvid species in Europe, could represent a source of WNV transmission for birds and humans. Our observations shed light on the pathogenesis, transmission, and ecology of WNV and can benefit the implementation of surveillance and control programs.
A case study on pavement performance due to extreme moisture intrusion at untreated layers

ABSTRACT Previous studies reveal that a loss in Modulus of Resilience (Mr) has an adverse effect on pavement performances. However, no study investigated this during extreme moisture intrusion at granular and subgrade layers, which may be compared with a flooding situation. This study has aimed to assess the impact of change in Mr due to moisture increase on pavement performance using the HDM-4 and AASHTO 2008’s roughness prediction models. As a case study, the paper utilises seven selected flexible pavement road groups of Queensland, Australia that cover 50% of the major road network. Both the results match closely when pavement strength data are accurate. The deterioration predictions are verified with actual after flood data and t-tests for two major roads in Logan City, and found consistent. The study has observed some interesting findings on change in degree of saturation, pavements flood resilience and life-cycle performances with flooding scenarios. It is believed that these results would be useful in obtaining accurate ΔIRI change at varying Mr values due to a flood to select appropriate post-flood rehabilitation. A road authority can use pavements flood-resistance and life-cycle performance results for deriving a maintenance strategy. Moreover, pavement flood resilience, relationships between Mr loss and strength and Mr loss and deflection would help in pavement design, estimating existing structural strength and rehabilitation design. Finally, the paper highlights major assumptions and suggests some useful future works.
Evolution of Bow-Tie Architectures in Biology

Bow-tie or hourglass structure is a common architectural feature found in many biological systems. A bow-tie in a multi-layered structure occurs when intermediate layers have much fewer components than the input and output layers. Examples include metabolism where a handful of building blocks mediate between multiple input nutrients and multiple output biomass components, and signaling networks where information from numerous receptor types passes through a small set of signaling pathways to regulate multiple output genes. Little is known, however, about how bow-tie architectures evolve. Here, we address the evolution of bow-tie architectures using simulations of multi-layered systems evolving to fulfill a given input-output goal. We find that bow-ties spontaneously evolve when the information in the evolutionary goal can be compressed. Mathematically speaking, bow-ties evolve when the rank of the input-output matrix describing the evolutionary goal is deficient. The maximal compression possible (the rank of the goal) determines the size of the narrowest part of the network—that is the bow-tie. A further requirement is that a process is active to reduce the number of links in the network, such as product-rule mutations, otherwise a non-bow-tie solution is found in the evolutionary simulations. This offers a mechanism to understand a common architectural principle of biological systems, and a way to quantitate the effective rank of the goals under which they evolved.
Parent and Youth Engagement in Court-Mandated Substance Use Disorder Treatment

ABSTRACT While juvenile drug courts (JDCs) require treatment participation, youth and parent engagement in treatment cannot be mandated. We compared youths' and parents' self-reports of engagement in Risk Reduction Therapy for Adolescents (RRTA) and Treatment as Usual (TAU) in JDCs. Parents and youths receiving RRTA were more likely than those receiving TAU to report high engagement in treatment. High parent engagement in RRTA early in treatment predicted fewer missed appointments and lower youth substance use at three months. Emphasizing therapeutic techniques that increase parent engagement, as utilized in RRTA, could lead to improved participation and clinical outcomes in court-mandated treatment settings.
Specific genomic cues regulate Cajal body assembly

ABSTRACT The assembly of specialized sub-nuclear microenvironments known as nuclear bodies (NBs) is important for promoting efficient nuclear function. In particular, the Cajal body (CB), a prominent NB that facilitates spliceosomal snRNP biogenesis, assembles in response to genomic cues. Here, we detail the factors that regulate CB assembly and structural maintenance. These include the importance of transcription at nucleating gene loci, the grouping of these genes on human chromosomes 1, 6 and 17, as well as cell cycle and biochemical regulation of CB protein function. We also speculate on the correlation between CB formation and RNA splicing levels in neurons and cancer. The timing and location of these specific molecular events is critical to CB assembly and its contribution to genome function. However, further work is required to explore the emerging biophysical characteristics of CB assembly and the impact upon subsequent genome reorganization.
Childhood hospitalisation and related deaths in Hanoi, Vietnam: a tertiary hospital database analysis from 2007 to 2014

Objective To describe hospital admission and emergency visit rates and potential risk factors of prolonged hospitalisation and death among children in Hanoi. Study design A retrospective study reviewed 212 216 hospitalisation records of children (aged 0–17) who attended the Vietnam National Children's Hospital in Hanoi between 2007 and 2014. Four indicators were analysed and reported: (1) rate of emergency hospital visits, (2) rate of hospitalisation, (3) length of hospital stay and (4) number of deaths. The risk of prolonged hospitalisation was investigated using Cox proportion hazard, and the risk of death was investigated through logistic regressions. Results During 2007–2014, the average annual rate of emergency visits was 2.2 per 1000 children and the rate of hospital admissions was 13.8 per 1000 children. The annual rates for infants increased significantly by 3.9 per 1000 children during 2012–2014 for emergency visits and 25.1 per 1000 children during 2009–2014 for hospital admissions. Digestive diseases (32.0%) and injuries (30.2%) were common causes of emergency visits, whereas respiratory diseases (37.7%) and bacterial and parasitic infections (19.8%) accounted for most hospital admissions. Patients with mental and behavioural disorders remained in the hospital the longest (median=12 days). Morbidities related to the perinatal period dominated mortality causes (32.5% of deaths among those admitted to the hospital. Among the respiratory diseases, pneumonia was the leading cause of both prolonged hospitalisation and death. Conclusions Preventable health problems, such as common bacterial infections and respiratory diseases, were the primary causes of hospital admissions in Vietnam.
Do Changes in Trauma-Related Beliefs Predict PTSD Symptom Improvement in Prolonged Exposure and Sertraline?

Objective: Negative trauma-related belief change has been found to predict subsequent improvement in symptoms of posttraumatic stress disorder (PTSD) in prolonged exposure (PE) and other therapies, consistent with several psychological theories of treatment change (e.g., Foa & Kozak, 1986). However, belief change has not been examined in selective serotonin reuptake inhibitors such as sertraline. We examined processes associated with symptom improvement in 2 treatments for PTSD, hypothesizing that belief change would robustly predict PTSD improvement in patients treated with PE but not those treated with sertraline, reflecting moderation by treatment. Method: Patients with chronic PTSD (N = 134; 78% women, 71.6% Caucasian, M = 38.1 years, SD = 11.8) received 10 weeks of PE or sertraline in a randomized, controlled trial. Patients reported PTSD and depression symptoms, and trauma-related beliefs (Post-Traumatic Cognitions Inventory; Foa, Ehlers, Clark, D Tolin, & Orsillo, 1999) at pretreatment, every treatment session, and posttreatment. Results: Using time-lagged mixed regression models, change in trauma-related beliefs predicted subsequent PTSD symptom improvement, an effect moderated by treatment and particularly strong in PE (d = 0.93) compared with sertraline (d = 0.35). Belief change also predicted depressive symptom improvement but more modestly and bidirectionally, with no difference by treatment modality. Conclusions: Trauma-related belief change precedes PTSD improvement more robustly in PE than in sertraline and with greater specificity compared with depressive symptoms. These findings highlight potentially divergent processes contributing to symptom change in these PTSD treatments, with belief change as a key mechanism of PE.
Zero-Shot Learning via Latent Space Encoding

Zero-shot learning (ZSL) is typically achieved by resorting to a class semantic embedding space to transfer the knowledge from the seen classes to unseen ones. Capturing the common semantic characteristics between the visual modality and the class semantic modality (e.g., attributes or word vector) is a key to the success of ZSL. In this paper, we propose a novel encoder–decoder approach, namely latent space encoding (LSE), to connect the semantic relations of different modalities. Instead of requiring a projection function to transfer information across different modalities like most previous work, LSE performs the interactions of different modalities via a feature aware latent space, which is learned in an implicit way. Specifically, different modalities are modeled separately but optimized jointly. For each modality, an encoder–decoder framework is performed to learn a feature aware latent space via jointly maximizing the recoverability of the original space from the latent space and the predictability of the latent space from the original space. To relate different modalities together, their features referring to the same concept are enforced to share the same latent codings. In this way, the common semantic characteristics of different modalities are generalized with the latent representations. Another property of the proposed approach is that it is easily extended to more modalities. Extensive experimental results on four benchmark datasets [animal with attribute, Caltech UCSD birds, aPY, and ImageNet] clearly demonstrate the superiority of the proposed approach on several ZSL tasks, including traditional ZSL, generalized ZSL, and zero-shot retrieval.
Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison.

BACKGROUND Daratumumab (a human CD38-directed monoclonal antibody) and pomalidomide (an immunomodulatory drug) plus dexamethasone are both relatively new treatment options for patients with heavily pretreated multiple myeloma. A matching adjusted indirect comparison (MAIC) was used to compare absolute treatment effects of daratumumab versus pomalidomide + low-dose dexamethasone (LoDex; 40 mg) on overall survival (OS), while adjusting for differences between the trial populations. MATERIALS AND METHODS The MAIC method reduces the risk of bias associated with naïve indirect comparisons. Data from 148 patients receiving daratumumab (16 mg/kg), pooled from the GEN501 and SIRIUS studies, were compared separately with data from patients receiving pomalidomide + LoDex in the MM-003 and STRATUS studies. RESULTS The MAIC-adjusted hazard ratio (HR) for OS of daratumumab versus pomalidomide + LoDex was 0.56 (95% confidence interval [CI], 0.38-0.83; p = .0041) for MM-003 and 0.51 (95% CI, 0.37-0.69; p < .0001) for STRATUS. The treatment benefit was even more pronounced when the daratumumab population was restricted to pomalidomide-naïve patients (MM-003: HR, 0.33; 95% CI, 0.17-0.66; p = .0017; STRATUS: HR, 0.41; 95% CI, 0.21-0.79; p = .0082). An additional analysis indicated a consistent trend of the OS benefit across subgroups based on M-protein level reduction (≥50%, ≥25%, and <25%). CONCLUSION The MAIC results suggest that daratumumab improves OS compared with pomalidomide + LoDex in patients with heavily pretreated multiple myeloma. IMPLICATIONS FOR PRACTICE This matching adjusted indirect comparison of clinical trial data from four studies analyzes the survival outcomes of patients with heavily pretreated, relapsed/refractory multiple myeloma who received either daratumumab monotherapy or pomalidomide plus low-dose dexamethasone. Using this method, daratumumab conferred a significant overall survival benefit compared with pomalidomide plus low-dose dexamethasone. In the absence of head-to-head trials, these indirect comparisons provide useful insights to clinicians and reimbursement authorities around the relative efficacy of treatments.
Inhibition Effect of 3D Nanostructures on the Corrosion Resistance of 1-Dodecanethiol Self-Assembled Monolayers on Copper in Nacl Solution

A novel and simple method to improve the corrosion resistance of copper by constructing a 3D 1-dodecanethiol self-assembled monolayers (SAMs) in 3.5% NaCl solution is reported in this study. Several drops of 1% H3PO4 solution are thinly and uniformly distributed on copper surface to form a 3D nanostructure constituted by Cu3(PO4)2 nanoflowers. The anticorrosion properties of 1-dodecanethiol SAMs on copper surface and on copper surface treated with H3PO4 solution were evaluated. Results demonstrated that 1-dodecanethiol SAMs on bare copper surface exhibit good protection capacity, whereas a copper surface pretreated with H3PO4 solution can substantially enhance the corrosion resistance of 1-dodecanethiol SAMs.
On the Complexity of the Weighted Fused Lasso

The solution path of the one-dimensional fused lasso for an <inline-formula><tex-math notation="LaTeX">$n$</tex-math> </inline-formula>-dimensional input is piecewise linear with at most <inline-formula><tex-math notation="LaTeX"> $\mathcal {O}(n)$</tex-math></inline-formula> segments. However, existing proofs of this bound do not hold for the <italic>weighted</italic> fused lasso. At the same time, results for the generalized lasso, of which the weighted fused lasso is a special case, allow more than <inline-formula><tex-math notation="LaTeX">$\Omega (3^n)$</tex-math> </inline-formula> segments. In this letter, we prove that the number of segments in the solution path of the weighted fused lasso is <inline-formula><tex-math notation="LaTeX">$\mathcal {O}(n^2)$</tex-math></inline-formula>, and that, for some instances, it is <inline-formula><tex-math notation="LaTeX">$\Omega (n^2)$</tex-math></inline-formula>. We also give a new, very simple, proof of the <inline-formula><tex-math notation="LaTeX">$\mathcal {O}(n)$</tex-math> </inline-formula> bound for the fused lasso.
Resistance to Water Diffusion in the Stratum Corneum Is Depth-Dependent

The stratum corneum (SC) provides a permeability barrier that limits the inflow and outflow of water. The permeability barrier is continuously and dynamically formed, maintained, and degraded along the depth, from the bottom to the top, of the SC. Naturally, its functioning and structure also change dynamically in a depth-dependent manner. While transepidermal water loss is typically used to assess the function of the SC barrier, it fails to provide any information about the dynamic mechanisms that are responsible for the depth-dependent characteristics of the permeability barrier. This paper aims to quantitatively characterize the depth-dependency of the permeability barrier using in vivo non-invasive measurement data for understanding the underlying mechanisms for barrier formation, maintenance, and degradation. As a framework to combine existing experimental data, we propose a mathematical model of the SC, consisting of multiple compartments, to explicitly address and investigate the depth-dependency of the SC permeability barrier. Using this mathematical model, we derive a measure of the water permeability barrier, i.e. resistance to water diffusion in the SC, from the measurement data on transepidermal water loss and water concentration profiles measured non-invasively by Raman spectroscopy. The derived resistance profiles effectively characterize the depth-dependency of the permeability barrier, with three distinct regions corresponding to formation, maintenance, and degradation of the barrier. Quantitative characterization of the obtained resistance profiles allows us to compare and evaluate the permeability barrier of skin with different morphology and physiology (infants vs adults, different skin sites, before and after application of oils) and elucidates differences in underlying mechanisms of processing barriers. The resistance profiles were further used to predict the spatial-temporal effects of skin treatments by in silico experiments, in terms of spatial-temporal dynamics of percutaneous water penetration.