Miracle-dz/UniFAR-FTUs huggingface dataset:
Next-generation sequencing reveals three novel variants in Polish patients with Usher syndrome

Aim: Usher syndrome is an autosomal recessive disorder which manifests as sensorineural hearing impairment with retinitis pigmentosa and, in some cases, also vestibular dysfunction. Material and methods: We studied the molecular basis of the disease in seven unrelated Polish patients with Usher syndrome. Patients underwent audiologic and ophthalmic examination. Next-generation sequencing on the diagnostic panel for Usher syndrome was performed in all patients. Results: Next-generation sequencing enabled identification of mutations on both alleles in five patients (71.4%). We describe three novel potentially pathogenic variants: c.14219G>T (p.(Gly4740Val)) in the GPR98 gene, c. 5206_5207insC (p.(Lys1737Glnfs*28)) in the MYO7A gene and c.11780A>G (p.(Asp3927Gly)) in the USH2A gene. In one patient, we identified two variants in two different genes: GPR98 and USH2A. Conclusions: Our results expand the mutational spectrum associated with Usher syndrome by a description of three novel likely pathogenic alterations and support the use of targeted next-generation sequencing in genetic diagnosis of patients with this syndrome.
Biomineralization induced by chitosan and collagen‐based materials with fluoride for dentin coverage: Chemical and morphological analysis

The prevention and treatment of erosive tooth wear are becoming increasingly important due to its increasing prevalence. The use of natural solutions to modify dental surfaces has become an area of research. Organic materials such as chitosan and hydrolyzed collagen may be a promising option to treat dentin. This in vitro study aimed to evaluate the influence of chitosan or hydrolyzed collagen, alone or combined with acidulated phosphate fluoride (APF) gel, on the composition and morphology of dentin after erosion. Bovine dentin samples were prepared (n = 84) and treated with artificial saliva (AS, negative control); APF gel (F, positive control); chitosan solution (Chi); hydrolyzed collagen solution (Col); fluoride/chitosan composition (F_Chi); and fluoride/hydrolyzed collagen composition (F_Col). Erosive cycles (six cycles of immersion in orange juice for 1 min, followed by immersion in AS for 1 hr) were performed. The materials were characterized by their morphology, composition, and particle size distribution. Micro‐energy dispersive X‐ray fluorescence spectroscopy and scanning electron were used to evaluate the dentin's inorganic chemical composition and morphology. The F_Col and F groups had a reduction in calcium loss by 17 and 26%, respectively (p < .001). Both of these groups still had a covering layer of agglomerates at the dentin surface after the erosive cycles. The fluoridated chitosan or collagen solutions improved the dentin resistance to erosion as a novel hybrid‐fluoride‐based material approach to provide surface protection from erosion.
Comparative Life Cycle Assessments of Lignocellulosic and Algae Biomass Conversion to Various Energy Products through Different Pathways

viii CHAPTER 1: INTRODUCTION 1 CHAPTER 2: BACKGROUND 8 2.1. Life Cycle Assessment 8 2.2. Current Status of Biofuels 11 2.3. Literature Review: LCAs on Algae Bioenergy Systems 15 2.4. Literature Review: LCAs on Lignocellulosic Bioenergy Systems 19 CHAPTER 3: ALGAE BIOMASS CONVERSION LCA 23 3.1. Analyzed Processes 23 3.1.1. Pre-Processing Stages of Algae Prior to the Energy Generation Stages 24 3.1.2. Evaluation Scenarios 25 3.1. 3. Process 1: Thermochemical Gasification and Conversion of Algae Biomass to Hydrocarbons 26 3.1. 4. Process 2: Anaerobic Digestion of Algae Biomass and Combined Heat and Power Process to Electricity 27 3.2. Goal and Scope 29 3.3. Life Cycle Inventory 30 3.3.1. Foreground Data 30 3.3.1.1. Process 1: Thermochemical Gasification and Conversion of Algae Biomass to Hydrocarbons 30 3.3.1.2. Process 2: Anaerobic Digestion of Algae Biomass and Combined Heat and Power Process to Electricity 32 3.3.2. Background Data 33 3.4. Impact Assessment 35 3.4. 1. Ecotoxicity 37 3.4. 2. Human Health Cancer 40
On the performance of microstrip antenna embedded in composite laminated substrates

Fiber‐reinforced composite structures can be tailored to desire mechanical properties and to embed microstrip antenna in aerospace applications. The electromagnetic characteristics of a microstrip antenna on isotropic and uniaxial substrates have been known, but that embedded in composite laminated substrates remain unavailable to date. This work aims at analyzing the performance of microstrip antenna embedded in composite laminated substrates by spectral domain analysis. Parameter studies are conducted to investigate the effects of the substrate's dielectric constants, the fiber directions (the orientation between the antenna and the laminate layers), and the stacking sequence on antenna's resonant frequency and radiation pattern. The antenna size when embedded in composite laminated substrates is larger than that when attached on isotropic substrates, or conversely, the resonant frequency will deviate lower if assuming the substrate as isotropic. The far‐field pattern in composite laminated substrates is more ‘directional’ than that in isotropic substrates. The antenna gain in the substrates of symmetric stacking with ±45° fiber direction is 20 dB better than that in isotropic substrates in some elevations. Copyright © 2014 John Wiley & Sons, Ltd.
A Study of 15 Sky Luminance Patterns against Hong Kong Data

A good knowledge of the sky luminance distribution is essential for efficient day lighting designs and developments. This paper studies a set of 15 standard skies established by Kittler, Perez and Darula using the measured sky luminance data from subtropical Hong Kong. A statistical analysis of the results has shown that the standard sky set is adequate to cover the various sky conditions. A reduction of the standard set to five skies is sufficient to model the luminance distributions. The ratio of zenith luminance to horizontal diffuse illuminance (L/zD) which can be used to define homogeneous sky standards was analysed based on these five selected skies. It has been shown that the trend of L/zDv ratios under different sky types followed the ranges described by Kittler et al.
Reflecting on an academic career: associations between past mentoring investments and career benefits

ABSTRACT Receiving mentoring is associated with lasting career benefits ; however, less is known about long-term career gains for mentors. A national sample of retired academics were surveyed to examine associations between past mentoring behaviors and current evaluations of their careers. Participants (N = 277) were on average 73.6 (SD = 6.2) years old with 34.9 (SD = 8.0) years of occupational tenure and 7.7 (SD = 5.8) years post-retirement. Structural equation modeling results demonstrated that having more protégés (β = .19, p = .024) and engaging in more mentoring behaviors (β = .18, p = .027) were associated with objective career achievements. However, mentoring behaviors, and not the number of protégés, were linked to subjective career achievements (β = .33, p < .001). While prior research demonstrates that mentors experience short-term benefits from mentoring, the present study’s findings suggest that mentors may also experience long-term objective and subjective career benefits.
Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease

Background Although autonomic imbalance is associated with an increased risk for metabolic disease, its effects on nonalcoholic fatty liver disease (NAFLD) remains unclear. We aimed to evaluate whether autonomic dysfunction predicts the risk for nonalcoholic fatty liver disease (NAFLD). Methods A total of 33,899 participants without NAFLD who underwent health screening programs between 2011 and 2018 were enrolled. NAFLD was identified by ultrasonography. Autonomic activity was estimated using heart rate variability (HRV). Time domain [standard deviation of the normal-to-normal interval (SDNN) and root mean square difference (RMSSD)]; frequency domain [total power (TP), low frequency (LF), and high frequency (HF), and LF/HF ratio were analyzed. Findings A total 6,466 participants developed NAFLD within a median of 5.7 years. Subjects with incident NAFLD showed decreased overall autonomic modulation and vagal activity with lowered SDNN, RMSSD, HF, normalized HF, compared to those without NAFLD. As the SDNN, RMSSD, TP, LF, and HF tertiles increased, the risk of NAFLD decreased with tertile 1 being the reference group [the hazard ratios (95% confidence intervals) of tertile 3 were 0.90 (0.85–0.96), 0.83 (0.78–0.88), 0.91 (0.86-0.97), 0.93 (0.87-0.99) and 0.89 (0.83-0.94), respectively] after adjusting for potential confounders. The risk for NAFLD was significantly higher in subjects in whom sustained elevated heart rate, normalized LF, and LF/HF ratio values than in those with sustained decrease in these parameters during follow-up. Conclusions Overall autonomic imbalance, decreased parasympathetic activity, and recently increased sympathetic activity might increase the risk of NAFLD.
Disinhibition of Primitive Reflexes in Attention Deficit and Hyperactivity Disorder: Insight Into Specific Mechanisms in Girls and Boys

Objective: Cognitive and motor disintegration and other functional disturbances in various neuropsychiatric disorders may be related to inhibitory deficits that may manifest as a persistence or re-expression of primitive reflexes and few recent data suggest that these deficits may occur in Attention Deficit and Hyperactivity Disorder (ADHD). Methods: We have tested a hypothesis to which extent ADHD symptoms and balance deficits are related to persisting primitive reflexes, such as Asymmetric Tonic Neck Reflex (ATNR) and Symmetric Tonic Neck Reflex (STNR) in 80 medication-naïve children with ADHD (40 boys and 40 girls) in the school age (8–11 years) and compared these data with a control group of 60 children (30 boys and 30 girls). Results: These data show new finding that ADHD symptoms and balance deficits are strongly and specifically associated with persistent ATNR in girls and STNR in boys. Conclusions: These results provide first evidence in medical literature that ADHD in girls and boys is specifically related to distinguished neurological developmental mechanisms related to disinhibition of primitive reflexes.
GSDMD Mediates LPS-Induced Septic Myocardial Dysfunction by Regulating ROS-dependent NLRP3 Inflammasome Activation

Myocardial dysfunction is a serious consequence of sepsis and contributes to high mortality. Currently, the molecular mechanism of myocardial dysfunction induced by sepsis remains unclear. In the present study, we investigated the role of gasdermin D (GSDMD) in cardiac dysfunction in septic mice and the underlying mechanism. C57BL/6 wild-type (WT) mice and age-matched Gsdmd-knockout (Gsdmd -/-) mice were intraperitoneally injected with lipopolysaccharide (LPS) (10 mg/kg) to mimic sepsis. The results showed that GSDMD-NT, the functional fragment of GSDMD, was upregulated in the heart tissue of septic WT mice induced by LPS, which was accompanied by decreased cardiac function and myocardial injury, as shown by decreased ejection fraction (EF) and fractional shortening (FS) and increased cardiac troponin I (cTnI), creatine kinase isoenzymes MB (CK-MB), and lactate dehydrogenase (LDH). Gsdmd -/- mice exhibited protection against LPS-induced myocardial dysfunction and had a higher survival rate. Gsdmd deficiency attenuated LPS-induced myocardial injury and cell death. Gsdmd deficiency prevented LPS-induced the increase of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum, as well as IL-1β and TNF-α mRNA levels in myocardium. In addition, LPS-mediated inflammatory cell infiltration into the myocardium was ameliorated and activation of NF-κB signaling pathway and the NOD-like receptor protein 3 (NLPR3) inflammasome were suppressed in Gsdmd -/- mice. Further research showed that in the myocardium of LPS-induced septic mice, GSDMD-NT enrichment in mitochondria led to mitochondrial dysfunction and reactive oxygen species (ROS) overproduction, which further regulated the activation of the NLRP3 inflammasome. In summary, our data suggest that GSDMD plays a vital role in the pathophysiology of LPS-induced myocardial dysfunction and may be a crucial target for the prevention and treatment of sepsis-induced myocardial dysfunction.
Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons

Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, and differentiation. In this study, we identified Cadherin-12 (CDH12), which encodes a type II classical cadherin, as a gene that promotes neurite outgrowth in an in vitro model of neurons with differentiated intrinsic growth ability. First, the effects of CDH12 on neurons were evaluated via RNA interference, and the results indicated that the knockdown of CDH12 expression restrained the axon extension of E18 neurons. The transcriptome profile of neurons with or without siCDH12 treatment revealed a set of pathways positively correlated with the effect of CDH12 on neurite outgrowth. We further revealed that CDH12 affected Rac1/Cdc42 phosphorylation in a PKA-dependent manner after testing using H-89 and 8-Bromo-cAMP sodium salt. Moreover, we investigated the expression of CDH12 in the brain, spinal cord, and dorsal root ganglia (DRG) during development using immunofluorescence staining. After that, we explored the effects of CDH12 on neurite outgrowth in vivo. A zebrafish model of CDH12 knockdown was established using the NgAgo-gDNA system, and the vital role of CDH12 in peripheral neurogenesis was determined. In summary, our study is the first to report the effect of CDH12 on axonal extension in vitro and in vivo, and we provide a preliminary explanation for this mechanism.
Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma

Background: Low-grade glioma (LGG) is considered a fatal disease for young adults, with overall survival widely ranging from 1 to 15 years depending on histopathologic and molecular subtypes. As a novel type of programmed cell death, ferroptosis was reported to be involved in tumorigenesis and development, which has been intensively studied in recent years. Methods: For the discovery cohort, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to identify the differentially expressed and prognostic ferroptosis-related genes (FRGs). The least absolute shrinkage and selection operator (LASSO) and multivariate Cox were used to establish a prognostic signature with the above-selected FRGs. Then, the signature was developed and validated in TCGA and Chinese Glioma Genome Atlas (CGGA) databases. By combining clinicopathological features and the FRG signature, a nomogram was established to predict individuals’ one-, three-, and five-year survival probability, and its predictive performance was evaluated by Harrell’s concordance index (C-index) and calibration curves. Enrichment analysis was performed to explore the signaling pathways regulated by the signature. Results: A novel risk signature contains seven FRGs that were constructed and were used to divide patients into two groups. Kaplan–Meier (K−M) survival curve and receiver-operating characteristic (ROC) curve analyses confirmed the prognostic performance of the risk model, followed by external validation based on data from the CGGA. The nomogram based on the risk signature and clinical traits was validated to perform well for predicting the survival rate of LGG. Finally, functional analysis revealed that the immune statuses were different between the two risk groups, which might help explain the underlying mechanisms of ferroptosis in LGG. Conclusion: In conclusion, this study constructed a novel and robust seven-FRG signature and established a prognostic nomogram for LGG survival prediction.
Intrinsic Mechanical Cues and Their Impact on Stem Cells and Embryogenesis

Although understanding how soluble cues direct cellular processes revolutionised the study of cell biology in the second half of the 20th century, over the last two decades, new insights into how mechanical cues similarly impact cell fate decisions has gained momentum. During development, extrinsic cues such as fluid flow, shear stress and compressive forces are essential for normal embryogenesis to proceed. Indeed, both adult and embryonic stem cells can respond to applied forces, but they can also detect intrinsic mechanical cues from their surrounding environment, such as the stiffness of the extracellular matrix, which impacts differentiation and morphogenesis. Cells can detect changes in their mechanical environment using cell surface receptors such as integrins and focal adhesions. Moreover, dynamic rearrangements of the cytoskeleton have been identified as a key means by which forces are transmitted from the extracellular matrix to the cell and vice versa. Although we have some understanding of the downstream mechanisms whereby mechanical cues are translated into changes in cell behaviour, many of the signalling pathways remain to be defined. This review discusses the importance of intrinsic mechanical cues on adult cell fate decisions, the emerging roles of cell surface mechano-sensors and the cytoskeleton in enabling cells to sense its microenvironment, and the role of intracellular signalling in translating mechanical cues into transcriptional outputs. In addition, the contribution of mechanical cues to fundamental processes during embryogenesis such as apical constriction and convergent extension is discussed. The continued development of tools to measure the biomechanical properties of soft tissues in vivo is likely to uncover currently underestimated contributions of these cues to adult stem cell fate decisions and embryogenesis, and may inform on regenerative strategies for tissue repair.
Inflammation-Related Long Non-Coding RNA Signature Predicts the Prognosis of Gastric Carcinoma

Background: Gastric carcinoma (GC) is a molecularly and phenotypically highly heterogeneous disease, making the prognostic prediction challenging. On the other hand, Inflammation as part of the active cross-talk between the tumor and the host in the tumor or its microenvironment could affect prognosis. Method: We established a prognostic multi lncRNAs signature that could better predict the prognosis of GC patients based on inflammation-related differentially expressed lncRNAs in GC. Results: We identified 10 differently expressed lncRNAs related to inflammation associated with GC prognosis. Kaplan-Meier survival analysis demonstrated that high-risk inflammation-related lncRNAs signature was related to poor prognosis of GC. Moreover, the inflammation-related lncRNAs signature had an AUC of 0.788, proving their utility in predicting GC prognosis. Indeed, our risk signature is more precise in predicting the prognosis of GC patients than traditional clinicopathological manifestations. Immune and tumor-related pathways for individuals in the low and high-risk groups were further revealed by GSEA. Moreover, TCGA based analysis revealed significant differences in HLA, MHC class-I, cytolytic activity, parainflammation, co-stimulation of APC, type II INF response, and type I INF response between the two risk groups. Immune checkpoints revealed CD86, TNFSF18, CD200, and LAIR1 were differently expressed between lowand high-risk groups. Conclusion: A novel inflammation-related lncRNAs (AC015660.1, LINC01094, AL512506.1, AC124067.2, AC016737.1, AL136115.1, AP000695.1, AC104695.3, LINC00449, AC090772.1) signature may provide insight into the new therapies and prognosis prediction for GC patients.
Cerebral Venous Thrombosis: Clinical, Radiological, Biological, and Etiological Characteristics of a French Prospective Cohort (FPCCVT)—Comparison With ISCVT Cohort

Introduction: Cerebral venous thrombosis (CVT) is a rare disease with highly variable clinical presentation and outcome. Etiological assessment may be negative. The clinical and radiological presentation and evolution can be highly variable. The mechanisms involved in this variability remain unknown. Objective: The aim of this multicenter French study registered on ClinicalTrials.gov (NCT02013635) was therefore to prospectively recruit a cohort of patients with cerebral venous thrombosis (FPCCVT) in order to study thrombin generation and clot degradation, and to evaluate their influence on clinical radiological characteristics. The first part of the study was to compare our cohort with a reference cohort. Methods: This prospective, multicenter, French study was conducted from July 2011 to September 2016. Consecutive patients (aged >15 years) referred to the stroke units of 21 French centers and who had a diagnosis of symptomatic CVT were included. All patients gave their written informed consent. The diagnosis of CVT had to be confirmed by imaging. Clinical, radiological, biological, and etiological characteristics were recorded at baseline, at acute phase, at 3 months and at last follow-up visit. Thrombophilia screening and the choice of treatment were performed by the attending physician. All data were compared with data from the International Study on CVT published by Ferro et al. Results: Two hundred thirty-one patients were included: 117 (50.6%) had isolated intracranial hypertension, 96 (41.5%) had focal syndrome. During hospitalization, 229 (99.1%) patients received anticoagulant treatment. Median length of hospital stay was 10 days. Five patients died during hospitalization (2.2%). At 3 months, 216 patients (97.0%) had follow-up with neurological data based on an outpatient visit. The mean duration of antithrombotic treatment was 9 months, and the mean time to last follow-up was 10.5 months. At the end of follow-up, eight patients had died, and 26 patients were lost to follow-up. At least one risk factor was identified in 200 patients. Conclusions: We demonstrated that the FPCCVT cohort had radiological, biological, and etiological characteristics similar to the historical ISCVT cohort. Nevertheless, the initial clinical presentation was less severe in our study probably due to an improvement in diagnostic methods between the two studies.
Aortic Stiffness: Epidemiology, Risk Factors, and Relevant Biomarkers

Aortic stiffness (AoS) is a maladaptive response to hemodynamic stress and both modifiable and non-modifiable risk factors, and elevated AoS increases afterload for the heart. AoS is a non-invasive marker of cardiovascular health and metabolic dysfunction. Implementing AoS as a diagnostic tool is challenging as it increases with age and varies amongst races. AoS is associated with lifestyle factors such as alcohol and smoking, as well as hypertension and comorbid conditions including metabolic syndrome and its components. Multiple studies have investigated various biomarkers associated with increased AoS, and this area is of particular interest given that these markers can highlight pathophysiologic pathways and specific therapeutic targets in the future. These biomarkers include those involved in the inflammatory cascade, anti-aging genes, and the renin-angiotensin aldosterone system. In the future, targeting AoS rather than blood pressure itself may be the key to improving vascular health and outcomes. In this review, we will discuss the current understanding of AoS, measurement of AoS and the challenges in interpretation, associated biomarkers, and possible therapeutic avenues for modulation of AoS.