Miracle-dz/UniFAR-FTUs huggingface dataset:
Disease Exacerbation after the Cessation of Fingolimod Treatment in Japanese Patients with Multiple Sclerosis

Objective In Japan, following the launch of dimethyl fumarate (DMF) after fingolimod as a disease-modifying drug in multiple sclerosis (MS), some patients switched from fingolimod to DMF. The aim of this study was to determine the follow-up status of MS patients who switched to DMF after fingolimod cessation. Methods Clinical and magnetic resonance imaging (MRI) data in 19 patients with MS who switched to DMF were collected for at least for 6 months after fingolimod cessation. Results Ten patients (52.6%) experienced clinical or MRI exacerbation after fingolimod cessation. The peripheral blood lymphocyte counts at the time of fingolimod cessation in those with disease exacerbation were significantly lower than in those without exacerbation. The patients with disease exacerbation were further classified into three groups based on MRI findings: those with some new T2-weighted lesions with or without gadolinium (Gd) enhancement (group I), those with more new and/or enlarged T2-weighted lesions with Gd enhancement compared to pre-fingolimod induction (group II), and those with multifocal tumefactive demyelinating lesions. In group II, the clinical disease activity, which was similar to that at fingolimod initiation in group I, was higher than the clinical disease activity observed before fingolimod initiation. Conversely, group III exhibited unexpected new MRI findings that were not evident before fingolimod initiation. Conclusion Cessation of fingolimod might precipitate rebound or reactivation of clinical disease in patients with MS, and careful follow-up is necessary for patients who discontinue fingolimod.
A LINE-1 Insertion in DLX6 Is Responsible for Cleft Palate and Mandibular Abnormalities in a Canine Model of Pierre Robin Sequence

Cleft palate (CP) is one of the most commonly occurring craniofacial birth defects in humans. In order to study cleft palate in a naturally occurring model system, we utilized the Nova Scotia Duck Tolling Retriever (NSDTR) dog breed. Micro-computed tomography analysis of CP NSDTR craniofacial structures revealed that these dogs exhibit defects similar to those observed in a recognizable subgroup of humans with CP: Pierre Robin Sequence (PRS). We refer to this phenotype in NSDTRs as CP1. Individuals with PRS have a triad of birth defects: shortened mandible, posteriorly placed tongue, and cleft palate. A genome-wide association study in 14 CP NSDTRs and 72 unaffected NSDTRs identified a significantly associated region on canine chromosome 14 (24.2 Mb–29.3 Mb; praw = 4.64×10−15). Sequencing of two regional candidate homeobox genes in NSDTRs, distal-less homeobox 5 (DLX5) and distal-less homeobox 6 (DLX6), identified a 2.1 kb LINE-1 insertion within DLX6 in CP1 NSDTRs. The LINE-1 insertion is predicted to insert a premature stop codon within the homeodomain of DLX6. This prompted the sequencing of DLX5 and DLX6 in a human cohort with CP, where a missense mutation within the highly conserved DLX5 homeobox of a patient with PRS was identified. This suggests the involvement of DLX5 in the development of PRS. These results demonstrate the power of the canine animal model as a genetically tractable approach to understanding naturally occurring craniofacial birth defects in humans.
Learning from Linnaeus: towards developing the foundation for a general structure concept for morphology*

Morphology has fundamental problems regarding aperspectival objectivity of its data—morphological terminology is often based on homology assumptions, lacks standardization, and has problems with comparability, reproducibility, and transparency. This is astonishing given that with his sexual system Linnaeus had already established a high degree of aperspectival objectivity in morphology that unfortunately has been lost subsequently. In the first part of the article a brief introduction to the history of classification is given that provides an answer to the question why morphology only initially has been gripped by the general trend towards objectification that started in the seventeenth century. The conceptual shortcomings of Aristotle’s concept of essences and its link to the definition of species and taxa in natural philosophy play an important part in this development. The only solution to the problem of essences was to link it to the evolutionary concept of homology, which explains why morphological terminology today often rests on homology assumptions. By taking a closer look at Linnaeus’ sexual system, basic principles for developing a general structure concept for morphology are discussed, which would provide the conceptual basis for establishing a high degree of aperspectival objectivity for morphological data. The article concludes with discussing the role of data bases and ontologies for developing a data standard in morphology. A brief introduction to the basic principles of Resource Description Framework (RDF) ontologies is given. A morphological ontology has high potential for establishing a general morphological structure concept if it is developed on grounds of the following principles: morphological terms and concepts must be defined taxon-independently, homology-free, preferably purely anatomically, and if functionally only by clearly indicating the trait’s active participation in a specific biological process.
Recovery in Borderline Personality Disorder (BPD): A Qualitative Study of Service Users' Perspectives

Background Symptom improvement in Borderline Personality Disorder (BPD) is more common than previously hypothesised. However, it remains unclear whether it reflects service users' personal goals of recovery. The present study aimed to explore what service users with BPD view as recovery. Methods 48 service users were recruited from secondary mental health services and their views on their personal goals and the meaning of recovery were explored in in-depth semi-structured interviews. The study drew on grounded theory and thematic analysis. Results Service users believed that recovery involved developing self-acceptance and self-confidence, gaining control over emotions, improving relationships, employment, and making progress in symptoms like suicidality and self-harming. They felt that psychotherapies for BPD often had an extreme focus on specific areas, like self-harming or relationships, and that some of their goals were neglected. Although full recovery was seen as a distant goal, interviewees felt that they could learn how to deal with their problems in more effective ways and make meaningful progress in their lives. Conclusions Specialist therapies for BPD explicitly address some of the recovery goals that are important to service users, whereas other goals are only indirectly or poorly addressed. Professionals might need to work with service users towards devising comprehensive individualised case formulations, including all treatment targets that are important to service users, their priorities, and long-term plans on how their targets might be met and which services might be involved.
Effects of high intensity training and continuous endurance training on aerobic capacity and body composition in recreationally active runners.

The aim of the study was to examine the effects of two different training programs (high-intensity-training vs. continuous endurance training) on aerobic power and body composition in recreationally active men and women and to test whether or not participants were able to complete a half marathon after the intervention period. Thirty-four recreational endurance runners were randomly assigned either to a Weekend-Group (WE, n = 17) or an After-Work- Group (AW, n = 17) for a 12 week-intervention period. WE weekly completed 2 h 30 min of continuous endurance running composed of 2 sessions on the weekend. In contrast, AW performed 4 30 min sessions of high intensity training and an additional 30 min endurance run weekly, always after work. During an exhaustive treadmill test aerobic power was measured and heart rate was continuously recorded. Body composition was assessed using bio-impedance. Following the intervention period all subjects took part in a half-marathon. AW significantly improved peak oxygen uptake (VO2 peak) from 36.8 ± 4.5 to 43.6 ± 6.5 [mL.min(-1). kg(-1)], velocity at lactate threshold (VLT) from 9.7 ± 2.2 to 11.7 ± 1.8 [km.h(-1)] and visceral fat from 5.6 ± 2.2 to 4.7 ± 1.9 In WE VO2 peak signifi-cantly increased from 38.8 ± 5.0 to 41.5 ± 6.0 [mL.min(-1). kg(-1)], VLT from 9.9 ± 1.3 to 11.2 ± 1.7 [km.h(-1)] and visceral fat was reduced from 5.7 ± 2.1 to 5.4 ± 1.9 (p < 0.01). Only the improvements of VO2 peak were significantly greater in AW compared with WE (pre/post group interaction: F=15.4, p = 0.01, η(2) = 0.36). Both groups completed a half marathon with no significant differences in performance (p = 0.63). Short, intensive endurance training sessions of about 30 min are effective in improving aerobic fitness in recreationally active runners. Key pointsContinuous endurance training and high intensity training lead to significant improvements of aerobic capacity and body compositionBoth training methods enable recreationally active runners to finish a half-marathonHigh intensity training is favorable to improve VO2 peak.
Bank Behaviour with Access to Credit Risk Transfer Markets

One of the most important recent innovations in financial markets has been the development of credit derivative products that allow banks to more actively manage their credit portfolios than ever before.We analyze the effect that access to these markets has had on the lending behavior of a sample of banks, using a sample of banks that have not accessed these markets as a control group. We find that banks that adopt advanced credit risk management techniques (proxied by the issuance of at least one collateralized loan obligation) experience a permanent increase in their target loan levels of around 50%. Partial adjustment to this target, however, means that the impact on actual loan levels is spread over several years.Our findings confirm the general efficiency enhancing implications of new risk management techniques in a world with frictions suggested in the theoretical literature.
Entrepreneurship Education and Entrepreneurial Role Models: How Do They Affect Entrepreneurial Intentions? (Studies at Management and Business Students in Indonesia Universities)

This study aim is to describe the effect of entrepreneurship education and entrepreneurial role models toward entrepreneurial intention of university students, both directly and through mediation of perceived desirability and perceived feasibility. The population is business and management students at four public universities in Indonesia who have followed entrepreneurship education. Sampling was conducted through stratified proportional random sampling method; numbers of respondents are 209 students. Data is analyzed by structural equation modeling using a generalized structural component analysis (GSCA) software to measure the relationship and accuracy (fitness) of the models and Sobel test to detect the mediation variables. The study results proved that entrepreneurship education affect to increase the entrepreneurial intention through student’s self-perception to entrepreneurial capabilities (perceived feasibility). On other hand, a direct effect of entrepreneurship education on entrepreneurial intention is negative. The type of entrepreneurship education at public universities is awareness education. It potentially could become the cause of negative effect between them. Entrepreneurial role models improve student’s entrepreneurial intention through the mediation of perceived desirability and perceived feasibility. Entrepreneurial role models do not have direct effect on entrepreneurial intention. Entrepreneurial characteristics difference between role models and students could potentially become the cause the low effect between them. The study results show inconsistency with the previous studies that examine the relationship between entrepreneurship education and entrepreneurial intention. Furthermore, this study results also indicate the mediation function of perceived desirability and perceived feasibility on relationship between entrepreneurial role models and entrepreneurial intention which received less attention in previous research. The research results are beneficial for managers and stakeholders of entrepreneurship education in universities to make graduates choose an entrepreneurial career.
Visual assessment of atrophy on magnetic resonance imaging in the diagnosis of pathologically confirmed young-onset dementias.

OBJECTIVES To investigate the diagnostic accuracy of visual inspection of magnetic resonance imaging (MRI) in a range of pathologically confirmed diseases causing young-onset dementia and to assess the sensitivity and specificity of atrophy patterns for Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD). DESIGN Sixty-two patients with pathologically confirmed diseases that may present as young-onset dementia were selected from a biopsy and postmortem series. The first diagnostic T1-weighted volumetric MRI was obtained for each patient, together with images from 22 healthy control subjects. All MRIs were assessed for regional atrophy independently by 3 neuroradiologists, blinded to all clinical details except age. Observers were also asked to use their clinical judgment to form a diagnosis. RESULTS Eighty-seven percent of dementia cases were distinguished from controls after visual inspection of MRI, and a correct pathologically confirmed diagnosis was given in 58% of cases. Hippocampal atrophy was noted in 92% of AD cases but was commonly seen in other dementias and controls. A bilateral symmetrical pattern of hippocampal atrophy discriminated AD from FTLD with 47% specificity, while posterior greater than anterior gradient of atrophy was 92% specific for AD. Atrophy of the anterior, inferior, and lateral temporal lobes was suggestive of FTLD pathology (> or =90% sensitivity), while anterior greater than posterior gradient of atrophy and hemispheric asymmetry of atrophy were each at least 85% specific for FTLD. CONCLUSION Despite variation and overlap of atrophy patterns, visual inspection of regional atrophy on MRI may aid in discriminating AD and FTLD.
SPICE simulation of single-electron electronics compared to measurement results

In this article three well known singleelectron tunnelling (SET) circuits are discussed. Both measurement results and simulation results on the three SET circuits are shown. The simulation results were obtained using a SPICE model for a single SET junction. The experimental data from SET circuits is used for validation purposes of the SPICE model. The SPICE model performed good on all experimental data. This is the only SPICE model available, that is able to predict the measurement results correctly for the so called single-electron pump circuit.
ARTIFICIAL IMMUNE SYSTEMS - MODELS, ALGORITHMS AND APPLICATIONS

Artificial Immune Systems (AIS) are computational paradigms that belong to the computational intelligence family and are inspired by the biological immune system. During the past decade, they have attracted a lot of interest from researchers aiming to develop immune-based models and techniques to solve complex computational or engineering problems. This work presents a survey of existing AIS models and algorithms with a focus on the last five years.
Delay minimization for reliable data collection on overhead transmission lines in smart grid

Due to the rapid growth of power demand, the aging problem of transmission lines becomes serious and has caused many problems to electric utilities and customers in terms of system reliability, power quality and customer satisfaction. In order to efficiently monitoring the power transmission system, a large number of sensors are deployed on the transmission line to form a Power Line Sensornet (PLSN). For efficient data collection in the PLSN, direct cellular links can be used to improve the delay performance. However, all previous research has an unrealistic assumption that the transmission links in the PLNS are reliable. In this paper, we investigate the reliable data collection problem in PLSNs with lossy wireless links. With the objective of minimizing the delay, we propose a time-efficient algorithm to setup direct cellular links on a subset of nodes in the PLSN. Extensive simulations are conducted to show that our algorithm can significantly improve the delay performance.
A Predicted Mannoprotein Participates in Cryptococcus gattii Capsular Structure

Cryptococcus gattii has the ability to escape from the host’s immune system through poorly understood mechanisms and can lead to the death of healthy individuals. The role of mannoproteins in C. gattii pathogenicity is not completely understood. The present work characterized a protein, Kpr1, that is essential for the maintenance of C. gattii main virulence factor, the polysaccharide capsule. Our data contribute to the understanding of the role of Kpr1 in capsule structuring, mainly by modulating the distribution of glucans in C. gattii cell wall. ABSTRACT The yeast-like pathogen Cryptococcus gattii is an etiological agent of cryptococcosis. The major cryptococcal virulence factor is the polysaccharide capsule, which is composed of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins (MPs). The GXM and GalXM polysaccharides have been extensively characterized; however, there is little information about the role of mannoproteins in capsule assembly and their participation in yeast pathogenicity. The present study characterized the function of a predicted mannoprotein from C. gattii, designated Krp1. Loss-of-function and gain-of-function mutants were generated, and phenotypes associated with the capsular architecture were evaluated. The null mutant cells were more sensitive to a cell wall stressor that disrupts beta-glucan synthesis. Also, these cells displayed increased GXM release to the culture supernatant than the wild-type strain did. The loss of Krp1 influenced cell-associated cryptococcal polysaccharide thickness and phagocytosis by J774.A1 macrophages in the early hours of interaction, but no difference in virulence in a murine model of cryptococcosis was observed. In addition, recombinant Krp1 was antigenic and differentially recognized by serum from an individual with cryptococcosis, but not with serum from an individual with candidiasis. Taken together, these results indicate that C. gattii Krp1 is important for the cell wall structure, thereby influencing capsule assembly, but is not essential for virulence in vivo. IMPORTANCE Cryptococcus gattii has the ability to escape from the host’s immune system through poorly understood mechanisms and can lead to the death of healthy individuals. The role of mannoproteins in C. gattii pathogenicity is not completely understood. The present work characterized a protein, Kpr1, that is essential for the maintenance of C. gattii main virulence factor, the polysaccharide capsule. Our data contribute to the understanding of the role of Kpr1 in capsule structuring, mainly by modulating the distribution of glucans in C. gattii cell wall.
15 Control of Synaptic Function by Local Protein Synthesis and Degradation

Synaptic plasticity—the dynamic modification of functional synaptic strength between neurons of the central nervous system—is generally believed to be a physical mechanism underlying learning and memory. An individual neuron in the mammalian CNS may contain up to 10,000 synaptic connections. Furthermore, small groups of synapses can be independently regulated: Synaptic enhancement induced at one location on the dendritic arbor does not spread throughout the entire arbor (Andersen et al. 1977; Bonhoeffer et al. 1989; Schuman and Madison 1994; Engert and Bonhoeffer 1999). The precision with which a neuron is able to fine-tune its synaptic inputs is likely related to the information-processing capacity of that individual cell. Without the ability to independently regulate its inputs, the neuron probably could not distinguish among the myriad inputs it receives. Although dendritic spines are highly dynamic postsynaptic structures, sometimes growing and shrinking in response to neuronal activity, the overall size and structure of a neuron are relatively fixed in the adult animal (Fiala et al. 2002; Harris et al. 2003). Rather than constantly growing new synapses, changes in synaptic strength are achieved through changing the complement and concentration of synaptic proteins, as well as modifying protein function by covalent modifications. The local concentration of synaptic proteins is influenced by many processes, including protein trafficking, buffering, and sequestration, as well as protein synthesis and degradation. For example, in the presynaptic compartment, rapid axonal transport can provide many of the proteins and vesicles required to maintain and modulate synaptic function. In addition, the calcium-binding.
Suicide ideation and its relationship with depression and hope trait in college freshmen

Objectives:To explore the relationship of suicide ideation with depression and hope trait in college freshmen.Methods:In the selected 4372 freshmen in one university,4211 finished the questionnaire.They were assessed with the item 15 of Symptom Checklist 90(SCL-90) to evaluate suicide ideation,and assessed with the Self-Rating Depression Scale(SDS) and Dispositional Hope Scale(DHS) to evaluate depression symptom and hope trait respectively.Results: The suicide ideation rate in the previous week was 4.5%(189/4211) in this sample.The suicide rate was higher in females than in males(6.7% vs.3.7%,P0.05). The score of SDS in the students with suicide ideation was higher than ones without [(42.0±7.3) vs.(34.2±6.3),P0.05],and the score of DHS in the students with suicide ideation was lower than in ones without [(43.6±8.8) vs.(49.8±8.1),P0.05]. The higher of the score of SDS,the more likely to have the suicide ideation(OR=1.15,P0.01),while the higher of the score of DHS,the more unlikely to have the suicide ideation(OR=0.95,P0.05). Conclusion: It suggests that the suicide ideation in college freshmen may be associated to depression,while hope trait may be the protective factor,so it is important to assess their depression in college students with suicide ideation.
Contributions of individual layer 6 pyramidal neurons to local circuitry in macaque primary visual cortex

We have studied the contributions of individual layer 6 pyramidal neurons in macaque primary visual cortex to local cortical circuitry by intracellular labeling and analysis of the morphologies of 58 neurons. These neurons are separated based on the laminar specificity of axonal and dendritic arbors into two classes, class I and class II, and into several types within these classes. Class I neurons project axons heavily and predominantly to layer 4C, whereas class II neurons have axonal projections primarily to layers other than 4C. Only 16 of the 58 neurons in our sample (28 percent) project to the white matter. Class I projection neurons are found at the top and bottom of layer 6, suggesting that they project to the lateral geniculate nucleus, whereas class II projection neurons are located in the middle of layer 6, suggesting that they project to the claustrum. The different types of class I neurons are distinguished from one another based on the sublaminar specificity of their axonal and dendritic arbors within layer 4, where they are biased toward compartments dominated by input from different functional streams. They are also distinct in their distributions within the depth of layer 6. The distinctive characteristics of the neuronal types we have identified suggest that each receives input from different sources and projects to a set of targets that is functionally appropriate. Thus, each type is likely to contribute uniquely to computations within V1 and extrinsically.