Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0–12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen‐matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event‐free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety‐one of 167 patients (55%) failed front‐line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up‐front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post‐IST failure (P 0·73). Acute graft‐versus‐host disease (GVHD) grade II‐IV was 8% in MFD graft vs. 25% for HSCT post‐IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post‐IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first‐line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option.
Biped locomotion using CPG with sensory interaction

This article presents the design and analysis of a controller based on a biologically inspired central pattern generator (CPG) network of mutually coupled Matsuoka nonlinear oscillators to generate adaptive rhythmic human like movement for biped robots. The paper focuses on the way in which the sensory signals feedback contribute to generate dynamic, stable and sustained rhythmic movements with robust gaits for biped robots. In addition, the paper shows how the driving input and external perturbation affect the speed of locomotion and change the period of its own active phase. The new design was studied through interaction between simulated interconnection coupling dynamics with 6 links and a musculoskeletal model with 6 degrees of freedom (DOFs) of a biped robot. The robot used the weighted outputs of mutually inhibited oscillators as torques to actuate its joints. The implemented model helps to realize the interaction between the controller, the mechanism of the robot, and the environment. In addition, it helps to study the necessary conditions for efficient generation of stable rhythmic walking at different speed, on different type of terrains and robustness in response to disturbances. Evaluations of the developed CPG based adaptive bipedal locomotion are carried out through simulations with successful testing results.
Generation of switchable multiwavelength solitons with wide wavelength spacing at 2  μm.

We demonstrated an all-fiber multiwavelength mode-locking thulium-doped fiber laser employing a cascaded single-mode step-index multimode-graded-index multimode single-mode-fiber (SMF-SIMF-GIMF-SMF) saturable absorber (SA). Based on the linear and nonlinear multimode interference effect of the proposed device, this structure can act both as a filter and as a SA. A stable triwavelength (1857/1897/1934 nm) mode-locking operation with the adjacent wavelength interval of approximately 40 nm was obtained. The triwavelength mode locking can also be quickly switched either pair-by-pair or one-by-one by adjusting the polarization controller properly. Our results indicate that the SMF-SIMF-GIMF-SMF structure provides a simpler and more compact solution for switchable multiwavelength mode locking in fiber lasers.
Quality Assurance Methods Assessing Instructional Design in MOOCs that implement Active Learning Pedagogies: An evaluative case study

Since more and more Massive Open Online Courses (MOOCs) appear, constituting an innovative part of online education, they should also undergo quality assurance to assess their pedagogical design similarly to other online courses. Recently, new studies have appeared presenting quality assurance methods (QA) for assessing the instructional design in MOOCs with pedagogical innovations, like those implementing active learning pedagogies (e.g. collaboration, gamification), which provide designers and instructors with useful strategies in order to design more interactive MOOCs. However, it is not that clear how these efforts are being addressed and up to which point are appropriate to assess active learning pedagogies. Therefore, a Systematic Literature Review (SLR) was conducted to identify the most mature existing MOOC QA methods. Afterwards, an evaluative case study was carried out, based on the Evaluand-oriented Responsive Evaluation Model (EREM), to apply the selected methods to a MOOC implementing active learning pedagogies. As the results suggest, the instruments of the selected QA methods need enrichment to assess effectively the instructional design based on active learning pedagogies, by providing specific questions proper for this kind of MOOCs or, by stating the underlying pedagogical model clearly so that the designers could consider beforehand if it is appropriate or not for their case. The results of the study are a first step to define new, enriched quality assessment methods for MOOCs that apply active learning approaches.
Comprehensive Genomic Profiling Identifies Novel Genetic Predictors of Response to Anti–PD-(L)1 Therapies in Non–Small Cell Lung Cancer

Purpose: Immune checkpoint inhibitors (ICI) have revolutionized cancer management. However, molecular determinants of response to ICIs remain incompletely understood. Experimental Design: We performed genomic profiling of 78 patients with non–small cell lung cancer (NSCLC) who underwent anti–PD-(L)1 therapies by both whole-exome and targeted next-generation sequencing (a 422-cancer-gene panel) to explore the predictive biomarkers of ICI response. Tumor mutation burden (TMB), and specific somatic mutations and copy-number alterations (CNA) were evaluated for their associations with immunotherapy response. Results: We confirmed that high TMB was associated with improved clinical outcomes, and TMB quantified by gene panel strongly correlated with WES results (Spearman's ρ = 0.81). Compared with wild-type, patients with FAT1 mutations had higher durable clinical benefit (DCB, 71.4% vs. 22.7%, P = 0.01) and objective response rates (ORR, 57.1% vs. 15.2%, P = 0.02). On the other hand, patients with activating mutations in EGFR/ERBB2 had reduced median progression-free survival (mPFS) compared with others [51.0 vs. 70.5 days, P = 0.0037, HR, 2.47; 95% confidence interval (CI), 1.32–4.62]. In addition, copy-number loss in specific chromosome 3p segments containing the tumor-suppressor ITGA9 and several chemokine receptor pathway genes, were highly predictive of poor clinical outcome (survival rates at 6 months, 0% vs. 31%, P = 0.012, HR, 2.08; 95% CI, 1.09–4.00). Our findings were further validated in two independently published datasets comprising multiple cancer types. Conclusions: We identified novel genomic biomarkers that were predictive of response to anti–PD-(L)1 therapies. Our findings suggest that comprehensive profiling of TMB and the aforementioned molecular markers could result in greater predictive power of response to ICI therapies in NSCLC.
Relationship Between Perfectionism and Depression Among Chinese College Students With Self-Esteem as a Mediator

Objectives This study is designed to examine the mediating role of self-esteem (SE) in the relationship between perfectionism and depression among a nonclinical sample of 918 Chinese college students. Methods Participants completed a questionnaire battery that included measures of perfectionism (Almost Perfect Scale-Revised), depression (Center for Epidemiologic Studies Depression), and self-esteem (The Rosenberg Self-Esteem Scale). Results The results showed that maladaptive perfectionism significantly and positively predicted depression, while adaptive perfectionism and self-esteem negatively predicted depression. More importantly, self-esteem partially mediated the prediction of depression from both adaptive perfectionism and maladaptive perfectionism. Conclusion Self-esteem was a significant mediator on the relationship between perfectionism and depression. Elevating student self-esteem may be a way of reducing depression, particularly among maladaptive perfectionists.
Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3

Chitinase 1 (CHIT1) plays a role in the pathogenesis of pulmonary fibrosis by modulating canonical and noncanonical TGF-β signaling via interaction with TGFBRAP1 and FOXO3. These findings highlight the CHIT1/SMAD7 axis as a potential biomarker and therapeutic target of pulmonary fibrosis. TGF-β1 is a critical mediator of tissue fibrosis in health and disease whose effects are augmented by chitinase 1 (CHIT1). However, the mechanisms that CHIT1 uses to regulate TGF-β1–mediated fibrotic responses have not been defined. Here, we demonstrate that CHIT1 enhances TGF-β1–stimulated fibrotic cellular and tissue responses and TGF-β1 signaling. Importantly, we also demonstrate that these effects are mediated by the ability of CHIT1 to inhibit TGF-β1 induction of its feedback inhibitor, SMAD7. CHIT1 also interacted with TGF-β receptor associated protein 1 (TGFBRAP1) and forkhead box O3 (FOXO3) with TGFBRAP1 playing a critical role in CHIT1 enhancement of TGF-β1 signaling and effector responses and FOXO3 playing a critical role in TGF-β1 induction of SMAD7. These pathways were disease relevant because the levels of CHIT1 were increased and inversely correlated with SMAD7 in tissues from patients with idiopathic pulmonary fibrosis or scleroderma-associated interstitial lung disease. These studies demonstrate that CHIT1 regulates TGF-β1/SMAD7 axis via TGFBRAP1 and FOXO3 and highlight the importance of these pathways in the pathogenesis of pulmonary fibrosis.
Evaluation of testis hormonal and histopathological alterations in type I and type II diabetic rats

Diabetes is a devastating metabolic disease that causes long‐term damage to various organs. An important leading complication of diabetes is a degenerative effect on the reproductive system including infertility and gonadal dysfunction. This study aimed to evaluate the effects of experimental type I and II diabetes on the levels of luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and testosterone.
Scientist-teacher partnerships as professional development: An action research study

SUBMITTED AS A DOCTORAL DISSERTATION IN COMPLETION OF REQUIREMENTS FOR THE DEGREE OF ED.D THROUGH WASHINGTON STATE UNIVERSITY. The overall purpose of this action research study was to explore the experiences of ten middle school science teachers involved in a three-year partnership program between scientists and teachers at a Department of Energy national laboratory, including the impact of the program on their professional development, and to improve the partnership program by developing a set of recommendations based on the study’s findings. This action research study relied on qualitative data including field notes recorded at the summer academies and data from two focus groups with teachers and scientists. Additionally, the participating teachers submitted written reflections in science notebooks, participated in open-ended telephone interviews that were transcribed verbatim, and wrote journal summaries to the Department of Energy at the end of the summer academy. The analysis of the data, collaboratively examined by the teachers, the scientists, and the science education specialist acting as co-researchers on the project, revealed five elements critical to the success of the professional development of science teachers. First, scientist-teacher partnerships are a unique contribution to the professional development of teachers of science that is not replicated in other forms of teacher training. Second, the role of the science education specialist as a bridge between the scientists and teachers is a unique and vital one, impacting all aspects of the professional development. Third, there is a paradox for classroom teachers as they view the professional development experience from two different lenses – that of learner and that of teacher. Fourth, learning for science teachers must be designed to be constructivist in nature. Fifth, the principles of the nature of science must be explicitly showcased to be seen and understood by the classroom teacher.
Elucidating Tau function and dysfunction in the era of cryo-EM

Tau is a microtubule-associated protein involved in the regulation of axonal microtubules in neurons. In pathological conditions, it forms fibrils that are molecular hallmarks of neurological disorders known as tauopathies. In the last 2 years, cryo-EM has given unprecedented high-resolution views of Tau in both physiological and pathological conditions. We review here these new findings and put them into the context of the knowledge about Tau before this structural breakthrough. The first structures of Tau fibrils, a molecular hallmark of Alzheimer's disease (AD), were based on fibrils from the brain of an individual with AD and, along with similar patient-derived structures, have set the gold standard for the field. Cryo-EM structures of Tau fibers in three distinct diseases, AD, Pick's disease, and chronic traumatic encephalopathy, represent the end points of Tau's molecular trajectory. We propose that the recent Tau structures may call for a re-examination of databases that link different Tau variants to various forms of dementia. We also address the question of how this structural information may link Tau's functional and pathological aspects. Because this structural information on Tau was obtained in a very short period, the new structures should be viewed in light of earlier structural observations and past and present functional data to shed additional light on Tau function and dysfunction.
Internet Use and E-mail Communications Between Patients and Providers: A Survey of Rheumatology Outpatients

Background:As health care costs rise in the United States and elsewhere, adopting health information technology is being advocated to reduce costs and improve efficiency. Patient:Physician e-mail communication is a frequently proposed tool in this strategy. Objectives:We examined the interest of rheumatology outpatients in using E-mail for communication with their rheumatologist. We sought to identify their privacy and cost concerns on this issue, and examine the patients' demographics, internet usage, and preferences. Methods:An anonymous survey was given to 150 consecutive patients. Patients responded to questions on demographics, rheumatic diseases, comorbidities, computer/internet access, E-mail use, privacy concerns, payment issues, and preferences regarding communication with their rheumatologist. Statistical analyses on the relationships between demographics and patient preferences on communications with their rheumatologist were conducted. Results:There were 145 respondents; the mean age was 52.3 years, mean education level was 13.6 years. The sample tended to be women (74%), retired/disabled (46%) or employed full time (35%). Most had internet access (74.5%). Differences were found based on gender, age, education, and income levels. Younger adults were more likely to desire E-mail communication with their rheumatologists, especially if paid by insurance. More men than women had concerns about privacy; persons with higher income levels were more willing to self-pay for E-mail. Conclusion:As a significant number of patients with rheumatic diseases express interest in E-mail communication with their providers, rheumatologists need to be cognizant of patients' preferences. To deliver patient-centered care, rheumatology practices might consider incorporating E-mail communication into their practices.
Tart Cherry Concentrate Does Not Alter the Gut Microbiome, Glycaemic Control or Systemic Inflammation in a Middle-Aged Population

Limited evidence suggests that the consumption of polyphenols may improve glycaemic control and insulin sensitivity. The gut microbiome produces phenolic metabolites and increases their bioavailability. A handful of studies have suggested that polyphenol consumption alters gut microbiome composition. There are no data available investigating such effects in polyphenol-rich Montmorency cherry (MC) supplementation. A total of 28 participants (aged 40–60 years) were randomized to receive daily MC or glucose and energy-matched placebo supplementation for 4 wk. Faecal and blood samples were obtained at baseline and at 4 wk. There was no clear effect of supplementation on glucose handling (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Gutt indices), although the Matsuda index decreased significantly in the MC group post-supplementation, reflecting an increase in serum insulin concentration. Contrastingly, placebo, but not MC supplementation induced a 6% increase in the Oral Glucose Insulin Sensitivity (OGIS) estimate of glucose clearance. Serum IL-6 and C reactive protein were unaltered by either supplement. The faecal bacterial microbiome was sequenced; species richness and diversity were unchanged by MC or placebo and no significant correlation existed between changes in Bacteroides and Faecalibacterium abundance and any index of insulin sensitivity. Therefore, 4 weeks of MC supplementation did not alter the gut microbiome, glycaemic control or systemic concentrations of IL-6 and CRP in a middle-aged population.
Tuning of brain–autonomic coupling by prior threat exposure: Implications for internalizing problems in Mexican-origin adolescents

Abstract Exposure to threat increases the risk for internalizing problems in adolescence. Deficits in integrating bodily cues into representations of emotion are thought to contribute to internalizing problems. Given the role of the medial prefrontal cortex in regulating bodily responses and integrating them into representations of emotional states, coordination between activity in the medial prefrontal cortex and autonomic nervous system responses may be influenced by past threat exposure with consequences for the emergence of internalizing problems. A sample of 179 Mexican-origin adolescents (88 female) reported on neighborhood and school crime, peer victimization, and discrimination when they were 10–16 years old. At age 17, participants underwent a functional neuroimaging scan during which they viewed pictures of emotional faces while respiratory sinus arrhythmia (RSA) and skin conductance responses were measured. Adolescents also reported symptoms of internalizing problems. Greater exposure to threats across adolescence was associated with more internalizing problems. Threat exposure was also associated with stronger negative coupling between the ventromedial prefrontal cortex and RSA. Stronger negative ventromedial prefrontal cortex–RSA coupling was associated with fewer internalizing problems. These results suggest the degree of coordinated activity between the brain and parasympathetic nervous system is both enhanced by threat experiences and decreased in adolescents with more internalizing problems.
Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder. In 2007, a novel locus, SAX2, which is located on chromosome 17p13 and contains 3 genes, ankyrin repeat and FYVE domain-containing 1 (ANKFY1), β-arrestin 2 (ARRB2) and kinesin family member 1C (KIF1C), was linked to ARSACS. We generated Ankfy1 heterozygous (Ankfy1/+) mice to establish an animal model and examine the pathophysiological basis of ARSACS. The transgenic mice displayed an abnormal gait with progressive motor and cerebellar nerve dysfunction that was highly reminiscent of ARSACS. These clinical features were accompanied by an early-onset and progressive loss of Purkinje cells, followed by gliosis. Additionally, the loss of Ankfy1 function resulted in an abnormal expression of neurotrophic factors (NTFs) in the Ankfy1/+ mouse cerebellum. Moreover, Purkinje cells cultured from neonatal Ankfy1/+ mice exhibited a shorter dendritic length and decreased numbers of dendritic spines. Importantly, cerebellar Purkinje cells from Ankfy1/+ mice and cells transfected with a lentiviral Ankfy1 shRNA underwent apoptosis. We propose that transgenic Ankfy1/+ mice are a useful model for studying the pathogenesis of ARSACS and for exploring the molecular mechanisms involved in this neurodegenerative disease.
Effect of a background Ca2+ entry pathway mediated by TRPC1 on myocardial damage of broilers with induced ascites syndrome

ABSTRACT Ascites syndrome (AS) in chickens is associated with profound vascular remodelling and increased pulmonary artery pressure as well as right ventricular hypertrophy. Classical transient receptor potential cation channels (TRPCs) are key regulators of cardiac hypertrophy that act via regulation of calcium influx in mammals. We investigated whether classical transient receptor potential channels in chickens with right ventricular hypertrophy still possess this mechanism for regulating Ca2+ flux. Intravenous injection of cellulose particles was successfully used to induce AS in chickens, and tissues were examined 22 days after treatment. The chickens in the test group showed cardiac hypertrophy with oedema of the cardiac muscle and disruption of myofilaments. The right-to-total ventricle weight ratio (RV/TV), the levels of serum aspartate aminotransferase (AST) and creatine kinase (CK) of the test group were significantly higher than in the control group. Intracellular calcium levels were significantly increased in cardiomyocytes from chickens in the test group. Gene expression of TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7 in heart tissues from the test group showed no significant differences compared with controls. However, TRPC1 protein levels, as well as mRNA levels, were down-regulated in the heart muscle of AS chickens (P < 0.05). Although we observed an increase in calcium concentration, the expression of TRPC1 decreased in cardiac cells. We hypothesized that an increase in intracellular free calcium concentration could inversely regulate calcium channel expression. RESEARCH HIGHLIGHTS Intracellular Ca2+ levels were increased in the myocardium of AS broilers. Expression of TRPC1, which mediates calcium influx, was decreased in the myocardium of AS broilers. The relationship between intracellular Ca2+ levels and expression of TRPC1 requires further study.
Immunoglobulin mRNA stability varies during B lymphocyte differentiation.

During differentiation of B lymphocytes, the change in the amount of immunoglobulin heavy chain produced is reflected by a change in the steady state level of heavy chain mRNA. At the pre‐B cell stage, the earliest stage at which immunoglobulin chain is produced, and later at the small resting B cell stage, there is a low steady state level of heavy chain mRNA. After the small B cell has differentiated to become a plasma cell, the steady state level of heavy chain mRNA is much higher. We confirm that the transcription rate at the immunoglobulin mu heavy chain gene does not change during differentiation from the pre‐B cell to the plasma cell stage. In contrast, we show here that differences in the stability of mu mRNA are sufficient to account for the differences in the steady state level at the various differentiation stages.