Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of Distance on Radiant Exposure and Degree of Conversion Using Different Light-Emitting-Diode Curing Units.

OBJECTIVES To investigate the influence of curing distance on the degree of conversion (DC) of a resin-based composite (RBC) when similar radiant exposure was achieved using six different light-curing units (LCUs) and to explore the correlation among irradiance, radiant exposure, and DC. METHODS AND MATERIALS A managing accurate resin curing-resin calibrator system was used to collect irradiance data for both top and bottom specimen surfaces with a curing distance of 2 mm and 8 mm while targeting a consistent top surface radiant exposure. Square nanohybrid-dual-photoinitiator RBC specimens (5 × 5 × 2 mm) were cured at each distance (n=6/LCU/distance). Irradiance and DC (micro-Raman spectroscopy) were determined for the top and bottom surfaces. The effect of distance and LCU on irradiance, radiant exposure, and DC as well as their linear associations were analyzed using analysis of variance and Pearson correlation coefficients, respectively (α=0.05). RESULTS While maintaining a similar radiant exposure, each LCU exhibited distinctive patterns in decreased irradiance and increased curing time. No significant differences in DC values (63.21%-70.28%) were observed between the 2- and 8-mm distances, except for a multiple-emission peak LCU. Significant differences in DC were detected among the LCUs. As expected, irradiance and radiant exposure were significantly lower on the bottom surfaces. However, a strong correlation between irradiance and radiant exposure did not necessarily result in a strong correlation with DC. CONCLUSIONS The RBC exhibited DC values >63% when the top surface radiant exposure was maintained, although the same values were not reached for all lights. A moderate-strong correlation existed among irradiance, radiant exposure, and DC.
Genomic data in prognostic models—what is lost in translation? The case of deletion 17p and mutant TP53 in chronic lymphocytic leukaemia

Genomic technologies are revolutionizing the practice of haematology‐oncology, leading to improved disease detection, more accurate prognostication and targeted treatment decisions. These advances, however, have also introduced new clinical challenges, which include problems of prognostic underdetermination and its attendant risks of over‐ and undertreatment. Genomic data is generated from different technologies, from cytogenetics to next‐generation sequencing, which are often interpreted interchangeably and in a binary fashion—as the presence or absence of a given chromosomal deletion or mutation—an oversimplification which may lead to mistaken prognosis. We discuss the clinical use of one such prognostic marker, represented by sequence and copy number alterations in TP53, located on chromosome 17p. Mutations in TP53 are strongly linked to poor prognosis in a variety of haematological malignancies, including chronic lymphocytic leukaemia (CLL). We review studies in CLL which utilize the 17p deletion or TP53 mutations for prognostic stratification with specific focus on the technologies used for detection, the thresholds established for clinical significance, and the clinical contexts in which these alterations are identified. The case of CLL illustrates issues arising from simplistic, binary interpretation of genetic testing and highlights the need to apply a critical lens when incorporating genomics into prognostic models.
Higher-Order Mode Suppression in Antiresonant Nodeless Hollow-Core Fibers

Negative curvature hollow-core fibers (NC-HCFs) are useful as gas sensors. We numerically analyze the single-mode performance of NC-HCFs. Both single-ring NC-HCFs and nested antiresonant fibers (NANFs) are investigated. When the size of the cladding tubes is properly designed, higher-order modes (HOMs) in the fiber core can be coupled with the cladding modes effectively and form high-loss supermodes. For the single-ring structure, we propose a novel NC-HCF with hybrid cladding tubes to enable suppression of the first two HOMs in the core simultaneously. For the nested structure, we find that cascaded coupling is necessary to maximize the loss of the HOMs in NANFs, and, as a result, NANFs with five nested tubes have an advantage in single-mode guidance performance. Moreover, a novel NANF with hybrid extended cladding tubes is proposed. In this kind of NANF, higher-order mode extinction ratios (HOMERs) of 105 and even 106 are obtained for the LP11 and LP21 modes, respectively, and a similar level of 105 for the LP02 modes. Good single-mode performance is maintained within a broad wavelength range. In addition, the loss of the LP01 modes in this kind of NANF is as low as 3.90 × 10−4 dB/m.
Lexical Plasticity in Early Bilinguals Does Not Alter Phoneme Categories: II. Experimental Evidence

When listening to modified speech, either naturally or artificially altered, the human perceptual system rapidly adapts to it. There is some debate about the nature of the mechanisms underlying this adaptation. Although some authors propose that listeners modify their prelexical representations, others assume changes at the lexical level. Recently, Larsson, Vera, Sebastian-Galles, and Deco [Lexical plasticity in early bilinguals does not alter phoneme categories: I. Neurodynamical modelling. Journal of Cognitive Neuroscience, 20, 76–94, 2008] proposed a biologically plausible computational model to account for some existing data, one which successfully modeled how long-term exposure to a dialect triggers the creation of new lexical entries. One specific prediction of the model was that prelexical (phoneme) representations should not be affected by dialectal exposure (as long as the listener is exposed to both standard and dialectal pronunciations). Here we present a series of experiments testing the predictions of the model. Native listeners of Catalan, with extended exposure to Spanish-accented Catalan, were tested on different auditory lexical decision tasks and phoneme discrimination tasks. Behavioral and electrophysiological recordings were obtained. The results supported the predictions of our model. On the one hand, both error rates and N400 measurements indicated the existence of alternative lexical entries for dialectal varieties. On the other hand, no evidence of alterations at the phoneme level, either in the behavioral discrimination task or in the electrophysiological measurement (MMN), could be detected. The results of the present study are compared with those obtained in short-term laboratory exposures in an attempt to provide an integrative account.
Respiratory resistance and reactance in adults with sickle cell anemia: Part 2—Fractional-order modeling and a clinical decision support system for the diagnosis of respiratory disorders

Background A better understanding of sickle cell anemia (SCA) and improvements in drug therapy and health policy have contributed to the emergence of a large population of adults living with this disease. The mechanisms by which SCA produces adverse effects on the respiratory system of these patients are largely unknown. Fractional-order (FrOr) models have a high potential to improve pulmonary clinical science and could be useful for diagnostic purposes, offering accurate models with an improved ability to mimic nature. Part 2 of this two-part study examines the changes in respiratory mechanics in patients with SCA using the new perspective of the FrOr models. These results are compared with those obtained in traditional forced oscillation (FOT) parameters, investigated in Part 1 of the present study, complementing this first analysis. Methodology/Principal findings The data consisted of three categories of subjects: controls (n = 23), patients with a normal spirometric exam (n = 21) and those presenting restriction (n = 24). The diagnostic accuracy was evaluated by investigating the area under the receiver operating characteristic curve (AUC). Initially, it was observed that biomechanical changes in SCA included increased values of fractional inertance, as well as damping and hysteresivity (p<0.001). The correlation analysis showed that FrOr parameters are associated with functional exercise capacity (R = -0.57), pulmonary diffusion (R = -0.71), respiratory muscle performance (R = 0.50), pulmonary flows (R = -0.62) and airway obstruction (R = 0.60). Fractional-order modeling showed high diagnostic accuracy in the detection of early respiratory abnormalities (AUC = 0.93), outperforming spirometry (p<0.03) and standard FOT analysis (p<0.01) used in Part 1 of this study. A combination of machine learning methods with fractional-order modeling further improved diagnostic accuracy (AUC = 0.97). Conclusions FrOr modeling improved our knowledge about the biomechanical abnormalities in adults with SCA. Changes in FrOr parameters are associated with functional exercise capacity decline, abnormal pulmonary mechanics and diffusion. FrOr modeling outperformed spirometric and traditional forced oscillation analyses, showing a high diagnostic accuracy in the diagnosis of early respiratory abnormalities that was further improved by an automatic clinical decision support system. This finding suggested the potential utility of this combination to help identify early respiratory changes in patients with SCA.
Meta-analysis of spineless cactus feeding to meat lambs: performance and development of mathematical models to predict dry matter intake and average daily gain.

Spineless cactus is a useful feed for various animal species in arid and semiarid regions due to its adaptability to dry and harsh soil, high efficiency of water use and carbohydrates storage. This meta-analysis was carried out to assess the effect of spineless cactus on animal performance, and develop and evaluate equations to predict dry matter intake (DMI) and average daily gain (ADG) in meat lambs. Equations for predicting DMI and ADG as a function of animal and diet characteristics were developed using data from eight experiments. The dataset was comprised of 40 treatment means from 289 meat lambs, in which cactus was included from 0 to 75% of the diet dry matter (DM). Accuracy and precision were evaluated by cross-validation using the mean square error of prediction (MSEP), which was decomposed into mean bias, systematic bias and random error; concordance correlation coefficient, which was decomposed into accuracy (C b) and precision (ρ); and coefficient of determination (R 2). In addition, the data set was used to evaluate the predicting accuracy and precision of the main lamb feeding systems (Agricultural and Food Research Council, Small Ruminant Nutritional System, National Research Council and Institut National de la Recherche Agronomique) and also two Brazilian studies. The DMI, CP intake (CPI), metabolizable energy (ME) intake and ADG increased when cactus was included up to 499 g/kg DM (P500 g/kg DM) had a decreased DMI, CPI and NDF intake, but increased feed efficiency (P<0.001) and similar ADG compared with those without cactus addition. The DMI was positively correlated with initial BW, final BW, concentrate and ADG, while it was negatively correlated with cactus inclusion and ME of the diet. On other hand, ADG was positively correlated with DMI, initial and mean BW and concentrate, and it was negatively correlated with cactus inclusion. The two developed equations had high accuracy (Cb of 0.95 for DMI and 0.94 for ADG) and the random error of MSEP was 99% for both equations. The precision of both equations was moderate, with R2 values of 0.53 and 0.50 and ρ values of 0.73 and 0.71 for DMI and ADG, respectively. In conclusion, the developed equation to predict DMI had moderate precision and high accuracy, nonetheless, it was more efficient than those reported in the literature. The proposed equations can be a useful alternative to estimate intake and performance of lambs fed cactus.
Afatinib + Cetuximab First-line in EGFR-Mutant Lung Cancer—Letter

We read with great interest the article by Pirazzoli and colleagues on the ability of afatinib and cetuximab (AC) combination to delay resistance compared with afatinib alone (A) in a mouse model of EGFR-mutant lung adenocarcinoma ([1][1]). The main mechanism of resistance to AC in animals was the
A Deep Learning Model for Automated Sleep Stages Classification Using PSG Signals

Sleep disorder is a symptom of many neurological diseases that may significantly affect the quality of daily life. Traditional methods are time-consuming and involve the manual scoring of polysomnogram (PSG) signals obtained in a laboratory environment. However, the automated monitoring of sleep stages can help detect neurological disorders accurately as well. In this study, a flexible deep learning model is proposed using raw PSG signals. A one-dimensional convolutional neural network (1D-CNN) is developed using electroencephalogram (EEG) and electrooculogram (EOG) signals for the classification of sleep stages. The performance of the system is evaluated using two public databases (sleep-edf and sleep-edfx). The developed model yielded the highest accuracies of 98.06%, 94.64%, 92.36%, 91.22%, and 91.00% for two to six sleep classes, respectively, using the sleep-edf database. Further, the proposed model obtained the highest accuracies of 97.62%, 94.34%, 92.33%, 90.98%, and 89.54%, respectively for the same two to six sleep classes using the sleep-edfx dataset. The developed deep learning model is ready for clinical usage, and can be tested with big PSG data.
Exploring the behavioral and cognitive phenotype of KBG syndrome

KBG syndrome is a neurodevelopmental disorder, caused by dominant mutations in ANKRD11, that is characterized by developmental delay/intellectual disability, mild craniofacial dysmorphisms, and short stature. Behavior and cognition have hardly been studied, but anecdotal evidence suggests higher frequencies of ADHD‐symptoms and social‐emotional impairments. In this study, the behavioral and cognitive profile of KBG syndrome will be investigated in order to examine if and how cognitive deficits contribute to behavioral difficulties. A total of 18 patients with KBG syndrome and a control group consisting of 17 patients with other genetic disorders with comparable intelligence levels, completed neuropsychological assessment. Age‐appropriate tasks were selected, covering overall intelligence, attention, memory, executive functioning, social cognition and visuoconstruction. Results were compared using Cohen's d effect sizes. As to behavior, fewer difficulties in social functioning and slightly more attentional problems, hyperactivity, oppositional defiant behavior and conduct problems were found in the KBG syndrome group. Regarding cognitive functioning, inspection of the observed differences shows that patients with KBG syndrome showed lower scores on sustained attention, cognitive flexibility, and visuoconstruction. In contrast, the KBG syndrome group demonstrated higher scores on visual memory, social cognition and emotion recognition. The cognitive profile of KBG syndrome in this sample indicates problems in attention and executive functioning that may underlie the behavior profile which primarily comprises impulsive behavior. Contrary to expectations based on previous (case) reports, no deficits were found in social cognitive functioning. These findings are important for counseling purposes, for tailored education planning, and for the development of personalized intervention.
Combination therapy with dacarbazine and statins improved the survival rate in mice with metastatic melanoma

Malignant melanoma is a highly aggressive skin cancer, and the overall median survival in patients with metastatic melanoma is only 6–9 months. Although molecular targeted therapies have recently been developed and have improved the overall survival, melanoma patients may show no response and acquisition of resistance to these drugs. Thus, other molecular approaches are essential for the treatment of metastatic melanoma. In the present study, we investigated the effect of cotreatment with dacarbazine and statins on tumor growth, metastasis, and survival rate in mice with metastatic melanomas. We found that cotreatment with dacarbazine and statins significantly inhibited tumor growth and metastasis via suppression of the RhoA/RhoC/LIM domain kinase/serum response factor/c‐Fos pathway and enhanced p53, p21, p27, cleaved caspase‐3, and cleaved poly(ADP‐ribose) polymerase 1 expression in vivo. Moreover, the cotreatment significantly improved the survival rate in metastasis‐bearing mice. Importantly, treatment with dacarbazine plus 100 mg/kg simvastatin or fluvastatin prevented metastasis‐associated death in 4/20 mice that received dacarbazine + simvastatin and in 8/20 mice that received dacarbazine + fluvastatin (survival rates, 20% and 40%, respectively). These results suggested that cotreatment with dacarbazine and statins may thus serve as a new therapeutic approach to control tumor growth and metastasis in melanoma patients.
NMDA Receptor Signaling Mediates cFos Expression via Top2β-Induced DSBs in Glioblastoma Cells

The activation of Ca2+-permeable N-methyl-D-aspartic acid (NMDA) receptor channels (NMDARs) is crucial for the development and survival of neurons, but many cancers use NMDAR-mediated signaling as well, enhancing the growth and invasiveness of tumors. Thus, NMDAR-dependent pathways emerge as a promising target in cancer therapy. Here, we use the LN229 and U-87MG glioblastoma multiforme (GBM) cells and immunofluorescence staining of 53BP1 to analyze NMDAR-induced DNA double-strand breaks (DSBs), which represent an important step in the NMDAR signaling pathway in neurons by facilitating the expression of early response genes. Our results show that NMDAR activation leads to the induction of DSBs in a subpopulation of glioma cells. In a further analogy to neurons, our results demonstrate that the induction of DSBs in LN229 cells is dependent on the activity of topoisomerase IIβ (Top2β). Western blot analysis revealed that the inhibition of NMDARs, cAMP-responsive element binding transcription factor (CREB) and Top2β decreased the expression of the proto-oncogene cFos. Knockdown of Top2β with siRNAs resulted in a downregulation of cFos and increased the radiosensitivity of LN229 cells in clonogenic survival. We also observed impaired cFos expression upon NMDAR and Top2β inhibition in a primary GBM cell line, suggesting that NMDAR signaling may be widely used by GBMs, demonstrating the potential of targeting NMDAR signaling proteins for GBM therapy.
Dealing with insufficient liver remnant: Associating liver partition and portal vein ligation for staged hepatectomy

Liver resection for colorectal liver metastases has emerged to highly successful treatment in the last decades. Key to this success is complete hepatic tumor removal and systemic disease control by chemotherapy. Associating liver partition and portal vein ligation for staged hepatectomy is the most recent two‐stage resection strategy for patients with very small future liver remnant making complete tumor removal possible within 1 to 2 weeks. Oncological outcome data are being collected at the moment and first results from small series reveal promising results.
Ovine uterine artery hydrogen sulfide biosynthesis in vivo: effects of ovarian cycle and pregnancy†

Abstract Uterine vasodilation dramatically increases during the follicular phase of the estrous cycle and pregnancy, which are estrogen-dominant physiological states. Uterine vasodilation is believed to be mainly controlled by local uterine artery (UA) production of vasodilators and angiogenic factors. The extremely potent vasodilator and proangiogenic hydrogen sulfide (H2S) is synthesized via metabolizing L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH). This study was designed to determine if UA H2S production increases with augmented expression and/or activity of CBS and/or CTH during the ovarian cycle and pregnancy in sheep. Uterine arteries from intact nonpregnant (NP) luteal and follicular phase and late (130–135 days, term ≈ 145 days) pregnant (P) ewes were collected; endothelium-enriched proteins (UAendo) and endothelium-denuded smooth muscle (UAvsm) were mechanically prepared for accessing CBS and CTH proteins by immunoblotting; their cellular localization was determined by semi-quantitative immunofluorescence microscopy. H2S production was measured by the methylene blue assay. Immunoblotting revealed that CBS but not CTH protein was greater in P > > > NP follicular > luteal UAendo and UAvsm (P < 0.001). H2S production was greater in P > > > NP UAendo and UAvsm (P < 0.01). Pregnancy-augmented UAendo and UAvsm H2S production was inhibited by the specific CBS but not CTH inhibitor. CBS and CTH proteins were localized to both endothelium and smooth muscle; however, only CBS protein was significantly greater in P vs NP UA endothelium and smooth muscle. Thus, ovine UA H2S production is significantly augmented via selectively upregulating endothelium and smooth muscle CBS during the follicular phase and pregnancy in vivo. Summary Sentence Summary Sentence Ovine UA hydrogen sulfide production is significantly upregulated via selective upregulation of endothelium and smooth muscle cystathionine β-synthase expression in the follicular phase and pregnancy.
Polygenic risk for schizophrenia, disordered eating behaviours and body mass index in adolescents

Background Recent studies suggest psychotic and eating disorders can be comorbid and could have shared genetic liability. However, this comorbidity has been overlooked in the epidemiological literature. Aims To test whether polygenic risk scores (PRS) for schizophrenia are associated with disordered eating behaviours and body mass index (BMI) in the general population. Method Using data from the Avon Longitudinal Study of Parents and Children and random-effects logistic and linear regression models, we investigated the association between PRS for schizophrenia and self-reported disordered eating behaviours (binge eating, purging, fasting and excessive exercise) and BMI at 14, 16 and 18 years. Results Of the 6920 children with available genetic data, 4473 (64.6%) and 5069 (73.3%) had at least one disordered eating and one BMI outcome measurement, respectively. An s.d. increase in PRS was associated with greater odds of having binge eating behaviours (odds ratio, 1.36; 95% CI 1.16–1.60) and lower BMI (coefficient, −0.03; 95% CI, −0.06 to −0.01). Conclusions Our findings suggest the presence of shared genetic risk between schizophrenia and binge eating behaviours. Intermediate phenotypes such as impaired social cognition and irritability, previously shown to be positively correlated in this sample with schizophrenia PRS, could represent risk factors for both phenotypes. Shared genetic liability between binge eating and schizophrenia could also explain higher rates of metabolic syndrome in individuals with schizophrenia, as binge eating could be a mediator of this association in drug-naïve individuals. The finding of an association between greater PRS and lower BMI, although consistent with existing epidemiological and genetic literature, requires further investigation. Declaration of interest None.