Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of tumour microenvironment: a new vision for cholangiocarcinoma

Cholangiocarcinoma (CCA) is a relatively rare malignant and lethal tumour derived from bile duct epithelium and the morbidity is now increasing worldwide. This disease is difficult to diagnose at its inchoate stage and has poor prognosis. Therefore, a clear understanding of pathogenesis and major influencing factors is the key to develop effective therapeutic methods for CCA. In previous studies, canonical correlation analysis has demonstrated that tumour microenvironment plays an intricate role in the progression of various types of cancers including CCA. CCA tumour microenvironment is a dynamic environment consisting of authoritative tumour stromal cells and extracellular matrix where tumour stromal cells and cancer cells can thrive. CCA stromal cells include immune and non‐immune cells, such as inflammatory cells, endothelial cells, fibroblasts, and macrophages. Likewise, CCA tumour microenvironment contains abundant proliferative factors and can significantly impact the behaviour of cancer cells. Through abominably intricate interactions with CCA cells, CCA tumour microenvironment plays an important role in promoting tumour proliferation, accelerating neovascularization, facilitating tumour invasion, and preventing tumour cells from organismal immune reactions and apoptosis. This review summarizes the recent research progress regarding the connection between tumour behaviours and tumour stromal cells in CCA, as well as the mechanism underlying the effect of tumour stromal cells on the growth of CCA. A thorough understanding of the relationship between CCA and tumour stromal cells can shed some light on the development of new therapeutic methods for treating CCA.
Astrocytic Regulation of Glutamate Transmission in Schizophrenia

According to the glutamate hypothesis of schizophrenia, the abnormality of glutamate transmission induced by hypofunction of NMDA receptors (NMDARs) is causally associated with the positive and negative symptoms of schizophrenia. However, the underlying mechanisms responsible for the changes in glutamate transmission in schizophrenia are not fully understood. Astrocytes, the major regulatory glia in the brain, modulate not only glutamate metabolism but also glutamate transmission. Here we review the recent progress in understanding the role of astrocytes in schizophrenia. We focus on the astrocytic mechanisms of (i) glutamate synthesis via the glutamate-glutamine cycle, (ii) glutamate clearance by excitatory amino acid transporters (EAATs), (iii) D-serine release to activate NMDARs, and (iv) glutamatergic target engagement biomarkers. Abnormality in these processes is highly correlated with schizophrenia phenotypes. These findings will shed light upon further investigation of pathogenesis as well as improvement of biomarkers and therapies for schizophrenia.
Effects of an animal‐assisted intervention on social behaviour, emotions, and behavioural and psychological symptoms in nursing home residents with dementia

The positive effects of animal‐assisted interventions (AAIs) in people with dementia have been frequently reported in the literature. However, it remains unclear if the positive effects are directly due to the presence of the animal. The aim of this study was to investigate if the inclusion of an animal adds value to psychosocial interventions for people with dementia.
Identifying and Controlling Important Neurons in Neural Machine Translation

Neural machine translation (NMT) models learn representations containing substantial linguistic information. However, it is not clear if such information is fully distributed or if some of it can be attributed to individual neurons. We develop unsupervised methods for discovering important neurons in NMT models. Our methods rely on the intuition that different models learn similar properties, and do not require any costly external supervision. We show experimentally that translation quality depends on the discovered neurons, and find that many of them capture common linguistic phenomena. Finally, we show how to control NMT translations in predictable ways, by modifying activations of individual neurons.
Mesenchymal Stem Cell Therapy for Ischemic Tissues

Ischemic diseases such as myocardial infarction, ischemic stroke, and critical limb ischemia are immense public health challenges. Current pharmacotherapy and surgical approaches are insufficient to completely heal ischemic diseases and are associated with a considerable risk of adverse effects. Alternatively, human mesenchymal stem cells (hMSCs) have been shown to exhibit immunomodulation, angiogenesis, and paracrine secretion of bioactive factors that can attenuate inflammation and promote tissue regeneration, making them a promising cell source for ischemic disease therapy. This review summarizes the pathogenesis of ischemic diseases, discusses the potential therapeutic effects and mechanisms of hMSCs for these diseases, and provides an overview of challenges of using hMSCs clinically for treating ischemic diseases.
Epidemiology of venous leg ulcers in primary health care: Incidence and prevalence in a health centre—A time series study (2010‐2014)

The aims of the study were to describe and analyse the temporal trend of the prevalence and incidence of venous leg ulcers (VLU) over the years 2010 to 2014, to determine healing times and temporal trends in the study period, and to evaluate related aspects such as the use of the Ankle‐Brachial Pressure Index (ABPI) in a primary care health centre. This was a retrospective study based on a time series (years 2010‐2014) of the prevalence and incidence of VLUs in people aged over 40 years in a primary care centre in Barcelona City. We reviewed 3920 electronic health records selecting patients, per year (2010‐2014), with VLUs based on the ICD‐10 diagnoses. For prevalence, we took into account any patient with an active VLU in the year of study. For incidence, we took into account patients with a new VLU in the year of study. A descriptive analysis was carried out based on each of the collected variables. The variables were examined according to the years of study (time series) by one‐factor analysis of variance (anova) or Kruskal–Wallis non‐parametric test, as appropriate. A survival analysis by Kaplan–Meier curves and log‐rank test was also performed. A total of 139 patients met the VLU criteria. Among them, only 79.2% were classified as having a VLU and had a correct ICD diagnosis. The prevalence and incidence increased over the years, doubling in patients aged over 65 years. Incidence increased from 0.5 new cases per 1000 people/year in 2010 to 1 new case for every 1000 people/year in 2014. Moreover, the prevalence ranged between 0.8 and 2.2 patients with VLU for every 1000 people/year. During the study period, a total of 84.2% of the VLUs healed (117/139 VLU). Regarding average annual time to healing, the trend indicates that lesions took less time to heal (Kruskal–Wallis test, P = 0.004), ranging between 453,9 weeks in 2005 to 19 weeks in 2014. The use of ABPI also evolved and was found to be increasingly performed prior to the appearance of the lesion. The epidemiological profile of people affected by VLUs continues to be, mainly, that of women of an advanced age, over 70 years. The frequency of VLU occurrence rose continually over the years, but healing took less time, and use of ABPI improved. Assigning a reference nurse in the wounds unit and the organisational structure around this problem may have an influence on improving care and the approach to these types of lesions.
Perioperative application of dexmedetomidine for postoperative systemic inflammatory response syndrome in patients undergoing percutaneous nephrolithotomy lithotripsy: results of a randomised controlled trial

Objective Our previous retrospective study demonstrated that perioperative dexmedetomidine (Dex) administration was associated with low systemic inflammatory response syndrome (SIRS) incidence. The present study was designed to investigate whether perioperative administration of Dex decreases the incidence of postpercutaneous nephrolithotomy lithotripsy (PCNL) SIRS in patients who undergo PCNL. Design A randomised controlled trial was designed. Participants A total of 190 patients were randomly assigned to receive Dex (DEX group, n=95) or saline control (CON group, n=95) and completed the study. In the DEX group, Dex was loaded (1 µg/kg) before anaesthesia induction and was infused (0.5 µg/kg/h) during surgery. Outcomes The incidences of postoperative SIRS were recorded. Serum interleukin-6 (IL-6) and tumour necrosis factor α(TNF-α) were measured. Results The incidence rates of SIRS were significantly lower in the DEX group than in the CON group (35.8% vs 50.5%, p=0.04). No patients developed sepsis in either group. These results might be attributed to inhibition of inflammatory responses and the resulting lower serum levels of IL-6 and TNF-α, caused by Dex administration. However, compared with the CON group, the lower incidence rate of SIRS in the DEX group did not result in better outcomes, such as shorter postoperative hospitalisation stays and lower costs. Conclusion The present study showed that Dex administration during PCNL might be beneficial for decreasing the incidence of SIRS through inhibiting the release of inflammatory mediators, but not clinical consequences such as postoperative hospitalisation duration and costs. Further effects of Dex administration on SIRS in patients who are scheduled for PCNL should be explored in future studies. Trial registration number ChiCTR-ICR-15006167.
Composites with carbon nanotubes and graphene: An outlook

Composite materials with carbon nanotube and graphene additives have long been considered as exciting prospects among nanotechnology applications. However, after nearly two decades of work in the area, questions remain about the practical impact of nanotube and graphene composites. This uncertainty stems from factors that include poor load transfer, interfacial engineering, dispersion, and viscosity-related issues that lead to processing challenges in such nanocomposites. Moreover, there has been little effort to identify selection rules for the use of nanotubes or graphene in composite matrices for specific applications. This review is a critical look at the status of composites for developing high-strength, low-density, high-conductivity materials with nanotubes or graphene. An outlook of the different approaches that can lead to practically useful nanotube and graphene composites is presented, pointing out the challenges and opportunities that exist in the field.
Biking to School: The Role of Bicycle-Sharing Programs in Adolescents.

BACKGROUND The purpose of this study was to: (1) describe modes of transport to school, with a specific focus on the use of public bicycle share programs (PBSP); and (2) assess sociodemographic, psychosocial, and environmental correlates of bike and PBSP use to go to school. METHODS A group of 465 adolescents from the International Physical Activity and the Environment Network (IPEN) Adolescent Study (Valencia, Spain) participated in the research. Mixed regression analyses were conducted on the data obtained. RESULTS Not having bicycle access, a PBSP card, or a public bike lane close to the school is negatively associated with bicycle use. PBSP is positively associated with physical self-efficacy and bicycle availability and negatively associated with the number of vehicles per drivers at home and not having PBSP stations close to the school. CONCLUSIONS The strongest predictive factor, as regards cycling as an active mode of transport to school among adolescents is having a PBSP card. Schools have a crucial role in promoting bicycle use through collaboration when designing public policies that consider access to bike lane networks and PBSP stations and therefore should encourage local government implementation policies and/or increase PBSP stations within 250 m of the school.
Familial Mediterranean Gene (MEFV) Mutation in Parents of Children with Familial Mediterranean Fever: What Are the Exceptions?

Objectives Familial Mediterranean Fever (FMF) is one of the most prevalent periodic fever syndromes; MEFV, the responsible gene for the disease, is in the short arm of chromosome16. In the considerable count of the FMF patients, only one mutation is found in the MEFV and parents, who were the obligatory carriers for that mutation, were asymptomatic. The aim of this study was to evaluate these asymptomatic parents in regard to mutation in MEFV gene and similarity between parents and offspring patients. Methods In this cross-sectional study, asymptomatic parents of FMF patients enrolled the study were referred to periodic fever clinic or pediatric rheumatology clinic of Tehran University of Medical Sciences. The patients should have at least one mutation in MEFV gene and none of them had any family history of autoinflammatory disease. Twelve mutations in MEFV gene were assessed in the parents by Vienna Lab FMF Strip Assay kit by MAS PCR/Reverse hybridization. Results Forty-three patients and their parents participated in the study. Sixty-three percent (27) of patients were male. Onset of disease symptoms in 31 patients (72%) was before 4 years of old. Nine (21%) of the patients had homozygote, 16 (37%) compound heterozygote, and 17(40%) heterozygote for MEFV mutation; there was a case of complex alleles mutations (2%). M694V/M694V in 4 patients (9%) was the most homozygote genotype, and M694V/R761H in 4 (9%) and E148Q in 7 (16%) were the most compound heterozygote and heterozygote genotype, respectively. M694V, M680I, and E148Q were the most mutation in the parents. Overall, 41 patients had mutations similar to their parents' mutation, except 2 whose parents had no mutation, but a patient did. Conclusion It seems that occurrence of new mutations in offspring is not prevalent among FMF patients and there are other reasons for different clinical presentation in similar mutation carriers. On the other hand, in ethnicities with high prevalence of FMF, new mutation in descendant may occur, infrequently.
How deep is deep enough? - Optimizing deep neural network architecture

Deep neural networks use stacked layers of feature detectors to repeatedly transform the input data, so that structurally different classes of input become well separated in the final layer. While the method has turned out extremely powerful in many applications, its success depends critically on the correct choice of hyperparameters, in particular the number of network layers. Here, we introduce a new measure, called the generalized discrimination value (GDV), which quantifies how well different object classes separate in each layer. Due to its definition, the GDV is invariant to translation and scaling of the input data, independent of the number of features, as well as independent of the number and permutation of the neurons within a layer. We compute the GDV in each layer of a Deep Belief Network that was trained unsupervised on the MNIST data set. Strikingly, we find that the GDV first improves with each successive network layer, but then gets worse again beyond layer 30, thus indicating the optimal network depth for this data classification task. Our further investigations suggest that the GDV can serve as a universal tool to determine the optimal number of layers in deep neural networks for any type of input data.
Adaptation and Resilience in Families of Children With Spina Bifida in South Korea

Purpose The purpose of this study, which was guided by the Family Resilience Model, was twofold: (1) to assess the risk and protective factors related to adaptation and resilience in families of children with spina bifida (SB) in South Korea and (2) to examine predictors of family adaptation and resilience. Design This is a descriptive study using survey methodology. Methods Data were collected from 203 parents of children with SB between June 2013 and February 2014 at the SB clinic in South Korea and analyzed using stepwise linear regression. Findings The best predictors of family adaptation and resilience in children with SB included one risk factor (parental depression) and four protective factors (parental health, family cohesion, family communication skills, and supportive friends/relatives). These five factors explained 39.7% of the total variance in family functioning (an indicator of family adaptation and resilience; F = 26.43, p < .001). Conclusion and Clinical Relevance Findings suggest that nursing interventions designed to strengthen protective factors and reduce risk factors are likely to promote adaptation and resilience in families of children with SB.
Familial NEDD4L variant in periventricular nodular heterotopia and in a fetus with hypokinesia and flexion contractures

Mutations in the HECT domain of NEDD4L have recently been identified in a cohort of eight patients with a syndromic form of bilateral periventricular nodular heterotopia (PVNH) in association with neurodevelopmental delay, cleft palate, and toe syndactyly (PVNH7).
End-to-end Sound Source Separation Conditioned on Instrument Labels

Can we perform an end-to-end music source separation with a variable number of sources using a deep learning model? This paper presents an extension of the Wave-U-Net [1] model which allows end-to-end monaural source separation with a non-fixed number of sources. Furthermore, we propose multiplicative conditioning with instrument labels at the bottleneck of the Wave-U-Net and show its effect on the separation results. This approach can be further extended to other types of conditioning such as audio-visual source separation and score-informed source separation.
Pectin Methylesterases: Cell Wall Remodeling Proteins Are Required for Plant Response to Heat Stress

Heat stress (HS) is expected to be of increasing worldwide concern in the near future, especially with regard to crop yield and quality as a consequence of rising or varying temperatures as a result of global climate change. HS response (HSR) is a highly conserved mechanism among different organisms but shows remarkable complexity and unique features in plants. The transcriptional regulation of HSR is controlled by HS transcription factors (HSFs) which allow the activation of HS-responsive genes, among which HS proteins (HSPs) are best characterized. Cell wall remodeling constitutes an important component of plant responses to HS to maintain overall function and growth; however, little is known about the connection between cell wall remodeling and HSR. Pectin controls cell wall porosity and has been shown to exhibit structural variation during plant growth and in response to HS. Pectin methylesterases (PMEs) are present in multigene families and encode isoforms with different action patterns by removal of methyl esters to influencing the properties of cell wall. We aimed to elucidate how plant cell walls respond to certain environmental cues through cell wall-modifying proteins in connection with modifications in cell wall machinery. An overview of recent findings shed light on PMEs contribute to a change in cell-wall composition/structure. The fine-scale modulation of apoplastic calcium ions (Ca2+) content could be mediated by PMEs in response to abiotic stress for both the assembly and disassembly of the pectic network. In particular, this modulation is prevalent in guard cell walls for regulating cell wall plasticity as well as stromal aperture size, which comprise critical determinants of plant adaptation to HS. These insights provide a foundation for further research to reveal details of the cell wall machinery and stress-responsive factors to provide targets and strategies to facilitate plant adaptation.
The Effect of Whole-Body Cryotherapy at Different Temperatures on Proinflammatory Cytokines, Oxidative Stress Parameters, and Disease Activity in Patients with Ankylosing Spondylitis

Purpose Patients with ankylosing spondylitis (AS) have increased production of proinflammatory cytokines, increased oxidants, and decreased antioxidant capacity. The aim of this study was to determine the effect of whole-body cryotherapy (WBC) at −110°C and −60°C, on disease activity, selected proinflammatory cytokines, and oxidative stress in patients with AS. Methods Sixty-five patients with AS were recruited to one of three study procedures: WBC at −110°C, −60°C, or exercise therapy (non-WBC). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP), concentration of C-reactive protein (CRP), and the concentrations of interleukin 8 and 17 (IL-8, IL-17) were measured at the beginning of the study and at the end of the intervention. The concentration of thiobarbituric acid reactive substances (TBARS), as a lipid peroxidation result, and total antioxidant status, an antioxidant organism potential, were measured. Results All the studied groups showed significantly decreased posttherapy disease activity expressed as a function of the BASDAI, ASDAS-CRP, and the IL-8 concentration. We found that the TBARS concentration after therapy was significantly increased in the WBC at −110°C group. A comparison of the therapeutic effects between the treatment groups showed a significantly lower BASDAI after therapy in the WBC at −110°C group compared to the non-WBC group. Conclusion WBC at −110°C had a positive effect on lowering AS clinical activity as measured by the BASDAI.
Occult uterine leiomyosarcoma in women undergoing abdominal and minimally invasive surgeries for myomas.

OBJECTIVES To estimate (i) the incidence of occult uterine leiomyosarcoma (LMS) in patients operated on for presumedmyomas, and (ii) the proportion of occult LMS to preoperatively diagnosed LMS in a tertiary center. MATERIAL AND METHODS An Institutional Review Board-approved retrospective cohort study was performed. The electronicdatabase of 30,476 patients was searched for women who had undergone surgery due to presumed myomas (N = 2675) as well as those with uterine LMS recognized via histology (N = 10) between January 2010 and December 2016. RESULTS Six of the 2675 treated women had occult LMS (incidence 1:446; 0.002; CI 0.0-0.013), and one underwent power morcellation (incidence 1:951; 0.001; CI 0.0-0.006). Parallel searching revealed that 6 of the 10 cases (60%) with uterine LMS recognized via histology were diagnosed postoperatively, whereas 4 of the 10 (40%) were diagnosed preoperatively. The incidence of LMS morcellation during laparoscopy was 1:951 and, when all MIS cases were included, 1:1178. The patient who underwent LMS morcellation was operated in the general surgery ward 5 years after laparoscopy (omental recurrence). CONCLUSIONS These results are similar to the first and recent conservative FDA estimations, but two-times lower for procedures with laparoscopic morcellation and all MIS procedures than for abdominal. Because above half of LMS may be recognized after surgery, the risk of occult LMS and the delay of targeted surgical treatment should be included in all informed consent forms for conservative management of presumed myomas without histology.