Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequency of S492R mutations in the epidermal growth factor receptor: analysis of plasma DNA from patients with metastatic colorectal cancer treated with panitumumab or cetuximab monotherapy

ABSTRACT Background Antibodies against epidermal growth factor receptor (EGFR), panitumumab, a fully human monoclonal antibody, and cetuximab, a human/mouse chimeric monoclonal antibody, have shown clinical efficacy in metastatic colorectal cancer (mCRC). In the phase 3 noninferiority ASPECCT (ClinicalTrials.gov, NCT01001377) study, panitumumab was demonstrated to be noninferior to cetuximab and provided a similar overall survival benefit for patients with chemotherapy-refractory wild-type KRAS exon 2 mCRC. However, some patients eventually develop resistance to anti-EGFR therapy. EGFR p.S492R mutation was previously identified as conferring resistance to cetuximab, but not to panitumumab. Methods This biomarker study analyzed plasma samples from ASPECCT collected at both baseline and posttreatment. Results No EGFR p.S492R mutations were identified at baseline; however, after treatment the EGFR p.S492R mutation was detected in 1% of patients treated with panitumumab versus 16% of those treated with cetuximab, supporting that, in a large population, this mutation is more likely to be induced by cetuximab than by panitumumab. There were, however, no significant differences in progression-free survival or overall survival between patients who were wild-type compared with those with the S492R mutation within the cetuximab arm or the overall population. Conclusions These results may support targeting treatment to small patient subgroups based on the presence of emerging EGFR mutations and provide a molecular rationale for rechallenging with a different anti-EGFR agent in patients who develop resistance. Prospective studies are needed to evaluate the efficacy of panitumumab in the EGFR p.S492R mutant population.
Optical Processes in PMMA, SiO2, and Hybrid Organic-Inorganic Sol-Gel Films Colored with Rhodamine 6GDN

The sol-gel technique was used to incorporate rhodamine 6GDN (Rh 6GDN) into thin layers of SiO2 and into an organic-inorganic hybrid matrix (OIHM). The OIHM is composed of a mixture of SiO2 and an acrylic copolymer. The Rh 6GDN was also incorporated into poly(methyl methacrylate) (PMMA) matrices. To investigate the influence of the different matrices on the optical behavior of the Rh 6GDN-colored layers on glass substrates, the optical absorption and photoluminescence were measured and analyzed. The absorption spectra show the presence of two main bands related to the monomer and dimer absorption, the relative intensity of these band depends on the type of matrix and on the hydrolyzation/condensation time. The strongest luminescence intensity was observed when the dye was embedded in the PMMA matrix; it was 20% larger than that observed in the OIHM layers. The weakest luminescence corresponds to the dye in the SiO2 matrix, which was up to 90% below the values observed when PMMA matrices were used. The absorption spectra of the dye show an unusual intense band at a wavelength of 310 nm when it is embedded in the PMMA matrix. A band in this position, which emits at 308 nm, is desirable for excimer laser applications. A simple quantum mechanical model is used, which treats the dye molecules as two-dimensional potential wells for delocalized electrons. The model fits reasonably well the experimental optical transitions determined from absorption and fluorescence spectra.
Multimodal Vigilance Estimation Using Deep Learning

The phenomenon of increasing accidents caused by reduced vigilance does exist. In the future, the high accuracy of vigilance estimation will play a significant role in public transportation safety. We propose a multimodal regression network that consists of multichannel deep autoencoders with subnetwork neurons (MCDAE $_{sn}$ ). After we define two thresholds of “0.35” and “0.70” from the percentage of eye closure, the output values are in the continuous range of 0–0.35, 0.36–0.70, and 0.71–1 representing the awake state, the tired state, and the drowsy state, respectively. To verify the efficiency of our strategy, we first applied the proposed approach to a single modality. Then, for the multimodality, since the complementary information between forehead electrooculography and electroencephalography features, we found the performance of the proposed approach using features fusion significantly improved, demonstrating the effectiveness and efficiency of our method.
Serious shortcomings in assessment and treatment of asylum seekers’ mental health needs

Background The prevalence of psychological complaints is known to be very high in populations of asylum seekers. Despite this, data on the health care system’s ability to adequately meet these high-risk populations’ mental health needs are scarce. This article investigates how well the German outpatient health care system is able to detect and adequately treat them. Methods To this end, we combined data from a cross-sectional survey with billing data from the local social welfare office from the year 2015. Using descriptive statistics, the data of the cross-sectional study are used to quantify the psychological health care needs of asylum seekers while the secondary data analysis indicates the actual access to and extent of psychological treatment. Results In the cross-sectional study, 54% of patients were screened positive for symptoms of depression, 41% for symptoms of anxiety disorder and 18% for symptoms of Posttraumatic Stress Disorder. In total, 59% were screened positive for at least one of these three disorders. However, when contrasting these screening-based prevalences with the prevalences based on data from the health care system, a mismatch becomes apparent: According to the social welfare office’s billing data, only 2.6% of asylum seekers received the diagnosis of depression, 1.4% were diagnosed with anxiety disorder and 2.9% with Posttraumatic Stress Disorder (PTSD). In combination, 4.9% were diagnosed with at least one of these three disorders. Overall, less than one tenth of asylum seekers with symptoms of depression, anxiety or PTSD received the corresponding diagnosis by the health care system. Among those who were diagnosed, about 45% received no treatment at all, while 38% were treated with drugs alone. Only 1% of all patients received psychotherapy. Conclusions Psychological complaints are very common among asylum seekers, yet only a small proportion of this population receives the corresponding diagnoses and treatment. While various factors can contribute to these shortcomings, there is an urgent need to systematically address this deficit and introduce measures to improve mental health care for this high-risk population.
4-Oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione Derivatives as NMDA Receptor- and VGCC Blockers with Neuroprotective Potential

The impact of excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptor overactivation and voltage gated calcium channel (VGCC) depolarization is prominent among the postulated processes involved in the development of neurodegenerative disorders. NGP1-01, a polycyclic amine, has been shown to be neuroprotective through modulation of the NMDA receptor and VGCC, and attenuation of MPP+-induced neurotoxicity. Recently, we reported on the calcium modulating effects of tricycloundecene derivatives, structurally similar to NGP1-01, on the NMDA receptor and VGCC of synaptoneurosomes. In the present study, we investigated novel 4-oxatricyclo[5.2. 1.02,6]dec-8-ene-3,5-dione derivatives for their cytotoxicity, neuroprotective effects via attenuation of MPP+-induced neurotoxicity and calcium influx inhibition abilities through the NMDA receptor and VGCC using neuroblastoma SH-SY5Y cells. All compounds, in general, showed low or no toxicity against neuroblastoma cells at 10–50 µM concentrations. At 10 µM, all compounds significantly attenuated MPP+-induced neurotoxicity as evident by the enhancement in cell viability between 23.05 ± 3.45% to 53.56 ± 9.29%. In comparison to known active compounds, the derivatives demonstrated mono or dual calcium modulating effect on the NMDA receptor and/or VGCC. Molecular docking studies using the NMDA receptor protein structure indicated that the compounds are able to bind in a comparable manner to the crystallographic pose of MK-801 inside the NMDA ion channel. The biological characteristics, together with results from in silico studies, suggest that these compounds could act as neuroprotective agents for the purpose of halting or slowing down the degenerative processes in neuronal cells.
Sketch-a-Segmenter: Sketch-Based Photo Segmenter Generation

Given pixel-level annotated data, traditional photo segmentation techniques have achieved promising results. However, these photo segmentation models can only identify objects in categories for which data annotation and training have been carried out. This limitation has inspired recent work on few-shot and zero-shot learning for image segmentation. In this article, we show the value of sketch for photo segmentation, in particular as a transferable representation to describe a concept to be segmented. We show, for the first time, that it is possible to generate a photo-segmentation model of a novel category using just a single sketch and furthermore exploit the unique fine-grained characteristics of sketch to produce more detailed segmentation. More specifically, we propose a sketch-based photo segmentation method that takes sketch as input and synthesizes the weights required for a neural network to segment the corresponding region of a given photo. Our framework can be applied at both the category-level and the instance-level, and fine-grained input sketches provide more accurate segmentation in the latter. This framework generalizes across categories via sketch and thus provides an alternative to zero-shot learning when segmenting a photo from a category without annotated training data. To investigate the instance-level relationship across sketch and photo, we create the SketchySeg dataset which contains segmentation annotations for photos corresponding to paired sketches in the Sketchy Dataset.
Phylogenetic relationships of Greek Apis mellifera subspecies based on sequencing of mtDNA segments (COI and ND5)

Summary Honey bee Apis mellifera L. populations from various areas of Albania, Bulgaria, Cyprus, Greece, Italy, Slovenia and Turkey, together with a genetically improved commercial strain exported all over the world were studied using sequencing analysis of two mitochondrial regions, the ND5 and the COI gene segments. The aim of this study was to examine the phylogenetic relationships among these honey bee populations, to investigate the existence of gene flow as a result of migratory beekeeping and commercial breeding, and to find out if these subspecies can be discriminated. Seven and eight different haplotypes were revealed for the COI and ND5 gene segments respectively, while the combined data set consisted of twelve different haplotypes. Among the two DNA segments studied, the highest genetic divergence values were observed in COI. In both genes the highest divergence value was among A. m. ligustica colonies and all others. All the phylogenetic trees constructed by Maximum Parsimony, Neighbour-Joining and Bayesian Inference analyses exhibited exactly the same topology for COI and ND5 separately, as well as for the concatenated data set; A. m. ligustica forms the most distinct clade. Our study presents the first comprehensive sequencing analysis of A. mellifera subspecies occurring in Greece and it is the first time that sequencing data from ND5 mtDNA gene segment have been obtained at the population level.
DICER1-associated metastatic abdominopelvic primitive neuroectodermal tumor with an EWSR1 rearrangement in a 16-yr-old female

We report a case of a DICER1-associated EWSR1-rearranged malignant primitive neuroectodermal tumor (PNET) arising in a patient with DICER1 tumor predisposition syndrome. A 16-yr-old female with a history of multinodular goiter presented with a widely metastatic abdominal small round blue cell tumor with neuroectodermal differentiation. EWSR1 gene rearrangement was identified in the tumor by fluorescence in situ hybridization (FISH). Genetic analysis revealed biallelic pathogenic DICER1 variation. The patient was treated with an aggressive course of chemotherapy, surgery, and radiation with complete pathologic response. We believe this case to represent a new expression of the DICER1 tumor predisposition syndrome, an entity caused by deleterious germline mutations in the DICER1 gene, encoding a ribonuclease active in the processing of miRNA. Patients with germline mutations in DICER1 develop a diverse group of benign and malignant tumors. Some of these tumors have been noted to have immature neuroepithelium as a component, including the ciliary body medulloepithelioma and the recently described DICER1-associated presacral malignant teratoid neoplasm. To our knowledge, abdominal sarcomas that resemble PNET histology with an EWSR1 rearrangement have not previously been described as a classical expression of the DICER1 syndrome phenotype.
Left ventricular long-axis function in hypertrophic cardiomyopathy - Relationships between e`, early diastolic excursion and duration, and systolic excursion

Background The peak velocity of early diastolic mitral annular motion (e`) is believed to provide sensitive detection of left ventricular (LV) diastolic dysfunction in hypertrophic cardiomyopathy (HCM), but other aspects of LV long-axis function in HCM have received less attention. Systolic mitral annular excursion (SExc) is also reduced in HCM and must be an intrinsic limitation to the extent of the subsequent motion during diastole. However, the effects of HCM on excursion during early diastole (EDExc) and atrial contraction (AExc), the duration of early diastolic motion (EDDur), and the relationships of EDExc with SExc, and of e`with EDExc and EDDur, are all unknown. Methods The study group was 22 subjects with HCM and there were 22 age and sex matched control subjects. SExc, EDExc, e`, AExc and EDDur were measured from pulsed wave tissue Doppler signals acquired from the septal and lateral walls. In the combined group of HCM and control subjects, multivariate analyses were performed to identify independent predictors of EDExc and e`for both LV walls. Results SExc, EDExc and e`were all lower, and EDDur was longer in the HCM group compared to the control group for both LV walls (p<0.05 for all). In contrast, AExc was lower for the septal wall in the HCM group (p<0.05), but not different between the groups for the lateral wall. In regression analyses of the combined group, EDExc was positively correlated with SExc, and SExc explained 57–86% of the variances in septal and lateral EDExc, e`was positively correlated with EDExc, and EDExc explained 58–68% of the variances of e`, whereas the combination of EDExc with EDDur explained 87–92% of the variances in e`. A diagnosis of HCM was not an independent predictor of EDExc when in combination with SExc, but was a minor contributor to the prediction of e`in combination with EDExc and EDDur. Conclusion In HCM, the decrease in LV longitudinal contraction is the major mechanism accounting for a lower EDExc, the lower e`is accounted for by contributions from the lower EDExc and prolongation of early diastolic motion, and there is no atrial compensation for the reduction of long-axis contraction.
Symmetric All Convolutional Neural-Network-Based Unsupervised Feature Extraction for Hyperspectral Images Classification

Recently, deep-learning-based feature extraction (FE) methods have shown great potential in hyperspectral image (HSI) processing. Unfortunately, it also brings a challenge that the training of the deep learning networks always requires large amounts of labeled samples, which is hardly available for HSI data. To address this issue, in this article, a novel unsupervised deep-learning-based FE method is proposed, which is trained in an end-to-end style. The proposed framework consists of an encoder subnetwork and a decoder subnetwork. The structure of the two subnetworks is symmetric for obtaining better downsampling and upsampling representation. Considering both spectral and spatial information, 3-D all convolution nets and deconvolution nets are used to structure the encoder subnetwork and decoder subnetwork, respectively. However, 3-D convolution and deconvolution kernels bring more parameters, which can deteriorate the quality of the obtained features. To alleviate this problem, a novel cost function with a sparse regular term is designed to obtain more robust feature representation. Experimental results on publicly available datasets indicate that the proposed method can obtain robust and effective features for subsequent classification tasks.
THE EFFECTS OF REALSIL (SILYBIN-PHOSPHOLIPID-VITAMIN E COMPLEX) ON LIVER ENZYMES IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) OR NON-ALCOHOLIC STEATO-HEPATITIS (NASH): A SYSTEMATIC REVIEW AND META-ANALYSIS OF RCTS.

Background The aim of the present study was to systematically review the effects of Realsil (silybin-phospholipid-vitamin E complex) on liver enzymes in patients with NAFLD or NASH. Methods We searched Web of Science, MEDLINE, Google Scholar, Cochrane Library, Science Direct, ProQuest, Scopus, and 1868 articles were found up to December 2018. Four studies that examined the effect of Realsil intake on liver enzymes among NAFLD or NASH patients were included. Exclusion criteria include: animal studies, studies with the design other than clinical trials, studies on non-adult individuals, studies that assess the effect of vitamin E, silybin, or phospholipid solely, studies that examined the effect of Realsil on other outcomes, or studies with insufficient data. Results The analysis demonstrated that Realsil intake led to a significant decrease in Gamma-Glutamyl Transpeptidase (GGT) levels (standardized mean difference (SMD) =-0.37; 95% confidence interval (CI]): -0.68 to -0.06). Realsil intake non-significantly decrease alanine transaminase (ALT) levels (SMD=-1.02 U/L; 95% CI: -2.23 to 0.20) and non-significantly increase aspartate aminotransferase (AST) levels (SMD = 0.17 U/L; 95% CI: -0.26-0.61). Conclusion Realsil intake was associated with a significantly decreased circulating GGT level without any significant effect on AST and ALT levels.
Long-term relapse prevention strategies among poly-substance users in Ghana: New insights for clinical practice

Abstract In spite of several decades of research and treatment efforts, the rate of relapse to substance abuse remains high, averaging about 75% within a 3- to 6-month duration after treatment. Recent research has focused on exploring contextually relevant relapse prevention approaches. This study explores relapse prevention strategies utilized by individuals to support their abstinence efforts four years after treatment for poly-substance use disorders in a Psychiatric Rehabilitation Unit in Ghana. Using a qualitative exploratory approach (descriptive phenomenology), semi-structured interviews were conducted with 14 individuals previously treated for poly-substance use disorders. Interviews were digitally recorded, transcribed verbatim, and analyzed thematically with an inductive approach. Participants employed a multitude of factors and strategies, including finding a sense of purpose and meaning in life, religious and spiritual engagements, family and social support, and self-initiated schemes to maintain long-term sobriety. Clinicians should collaborate with and thoroughly explore personal, familial, and contextual factors and strategies that support the abstinence efforts of individuals recovering from poly-substance use disorder.
Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial

Purpose: Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced tumor gene expression, and overall survival (OS). Patients and Methods: Patients with AST received SBRT (30–50 Gy in 3–5 fractions) to two to four metastases followed by pembrolizumab (200 mg i.v. every 3 weeks). SBRT was prescribed to a maximum tumor volume of 65 mL. Small metastases received the complete prescribed coverage (complete-Rx), while larger metastases received partial coverage (partial-Rx). Treated metastasis control (TMC) was defined as a lack of progression for an irradiated metastasis. Landmark analysis was used to assess the relationship between TMC and OS. Thirty-five biopsies were obtained from 24 patients: 19 pre-SBRT and 16 post-SBRT (11 matched) prior to pembrolizumab and were analyzed via RNA microarray. Results: Sixty-eight patients (139 metastases) were enrolled with a median follow-up of 10.4 months. One-year TMC was 89.5% with no difference between complete-Rx or partial-Rx. On multivariable analysis, TMC was independently associated with a reduced risk for death (HR, 0.36; 95% confidence interval, 0.17–0.75; P = 0.006). SBRT increased expression of innate and adaptive immune genes and concomitantly decreased expression of cell cycle and DNA repair genes in the irradiated tumors. Elevated post-SBRT expression of DNASE1 correlated with increased expression of cytolytic T-cell genes and irradiated tumor response. Conclusions: In the context of SBRT+P, TMC independently correlates with OS. SBRT impacts intratumoral immune gene expression associated with TMC. Randomized trials are needed to validate these findings.
Multi-target approach for Alzheimer’s disease treatment: computational biomolecular modeling of cholinesterase enzymes with a novel 4-N-phenylaminoquinoline derivative reveal promising potentials

Abstract The identification of dual inhibitors targeting the active sites of the cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), have lately surfaced as a multi-approach towards Alzheimer treatment. More recently, a novel series of 4-N-phenylaminoquinolines was synthesized and evaluated against AChE and BuChE in which one of the compounds displayed appreciable inhibition compared to the standard compound, galantamine. To provide a clearer picture of the inhibition mechanism of this potent compound at the molecular level, computational biomolecular modeling was carried out. The investigation was initiated with the exploration of the chemical properties of the identified compound 11 b and reference drug, galantamine. Density functional theory (DFT) calculations reveal some conceptual parameters that provide information on the stability and reactivity of the compounds as potential inhibitors. To unveil the binding mechanism, energetics and enzyme-ligand interactions, molecular dynamics (MD) simulations of six different systems were executed over a period. Calculated binding free energy values are in the same order with experimental IC50 data. Identification of the main residues driving optimum binding of the active compound 11 b to the binding region of both AChE and BuChE showed Trp81 and Trp110 as the most important, respectively. It was proposed that the studied compound could serve as a dual inhibitor for AChE and BuChE, therefore, would potentially be a promising moiety in a multi-target approach for the treatment of Alzheimer’s disorder. Communicated by Ramaswamy H. Sarma