Miracle-dz/UniFAR-FTUs huggingface dataset:
Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures

The stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells.
Non‐destructive detection of matrix stabilization correlates with enhanced mechanical properties of self‐assembled articular cartilage

Tissue engineers rely on expensive, time‐consuming, and destructive techniques to monitor the composition, microstructure, and function of engineered tissue equivalents. A non‐destructive solution to monitor tissue quality and maturation would greatly reduce costs and accelerate the development of tissue‐engineered products. The objectives of this study were to (a) determine whether matrix stabilization with exogenous lysyl oxidase‐like protein‐2 (LOXL2) with recombinant hyaluronan and proteoglycan link protein‐1 (LINK) would result in increased compressive and tensile properties in self‐assembled articular cartilage constructs, (b) evaluate whether label‐free, non‐destructive fluorescence lifetime imaging (FLIm) could be used to infer changes in both biochemical composition and biomechanical properties, (c) form quantitative relationships between destructive and non‐destructive measurements to determine whether the strength of these correlations is sufficient to replace destructive testing methods, and (d) determine whether support vector machine (SVM) learning can predict LOXL2‐induced collagen crosslinking. The combination of exogenous LOXL2 and LINK proteins created a synergistic 4.9‐fold increase in collagen crosslinking density and an 8.3‐fold increase in tensile strength as compared with control (CTL). Compressive relaxation modulus was increased 5.9‐fold with addition of LOXL2 and 3.4‐fold with combined treatments over CTL. FLIm parameters had strong and significant correlations with tensile properties (R2 = 0.82; p < 0.001) and compressive properties (R2 = 0.59; p < 0.001). SVM learning based on FLIm‐derived parameters was capable of automating tissue maturation assessment with a discriminant ability of 98.4%. These results showed marked improvements in mechanical properties with matrix stabilization and suggest that FLIm‐based tools have great potential for the non‐destructive assessment of tissue‐engineered cartilage.
Analysis of Receptor Tyrosine Kinase ROS1-Positive Tumors in Non–Small Cell Lung Cancer: Identification of a FIG-ROS1 Fusion

Purpose: To deepen our understanding of mutant ROS1 expression, localization, and frequency in non–small cell lung cancer (NSCLC), we developed a highly specific and sensitive immunohistochemistry (IHC)-based assay that is useful for the detection of wild-type and mutant ROS1. Experimental Design: We analyzed 556 tumors with the ROS1 D4D6 rabbit monoclonal antibody IHC assay to assess ROS1 expression levels and localization. A subset of tumors was analyzed by FISH to determine the percentage of these tumors harboring ROS1 translocations. Using specific and sensitive IHC assays, we analyzed the expression of anaplastic lymphoma kinase (ALK), EGFR L858R, and EGFR E746-A750del mutations in a subset of lung tumors, including those expressing ROS1. Results: In our NSCLC cohort of Chinese patients, we identified 9 (1.6%) tumors expressing ROS1 and 22 (4.0%) tumors expressing ALK. FISH identified tumors with ALK or ROS1 rearrangements, and IHC alone was capable of detecting all cases with ALK and ROS1 rearrangements. ROS1 fusion partners were determined by reverse transcriptase PCR identifying CD74-ROS1, SLC34A2-ROS1, and FIG-ROS1 fusions. Some of the ALK and ROS1 rearranged tumors may also harbor coexisting EGFR mutations. Conclusions: NSCLC tumors with ROS1 rearrangements are uncommon in the Chinese population and represent a distinct entity of carcinomas. The ROS1 IHC assay described here is a valuable tool for identifying patients expressing mutant ROS1 and could be routinely applied in clinical practice to detect lung cancers that may be responsive to targeted therapies. Clin Cancer Res; 18(16); 4449–57. ©2012 AACR.
Segmentation of the ECG Signal by Means of a Linear Regression Algorithm

The monitoring and processing of electrocardiogram (ECG) beats have been actively studied in recent years: new lines of research have even been developed to analyze ECG signals using mobile devices. Considering these trends, we proposed a simple and low computing cost algorithm to process and analyze an ECG signal. Our approach is based on the use of linear regression to segment the signal, with the goal of detecting the R point of the ECG wave and later, to separate the signal in periods for detecting P, Q, S, and T peaks. After pre-processing of ECG signal to reduce the noise, the algorithm was able to efficiently detect fiducial points, information that is transcendental for diagnosis of heart conditions using machine learning classifiers. When tested on 260 ECG records, the detection approach performed with a Sensitivity of 97.5% for Q-point and 100% for the rest of ECG peaks. Finally, we validated the robustness of our algorithm by developing an ECG sensor to register and transmit the acquired signals to a mobile device in real time.
High expression of MUC20 drives tumorigenesis and predicts poor survival in endometrial cancer

Mucins (MUCs) have been reported to play a critical role in the tumorigenesis of different cancers. This study was performed to explore the effect of MUC20 in endometrial cancer (EC). A total of 541 patients with EC were examined from The Cancer Genome Atlas. The relationship between MUC20 expression and clinical characteristics was analyzed with the Wilcoxon signed‐rank test and logistic regression. The Kaplan‐Meier method and the Cox regression model was performed to evaluate the prognosis. Gene set enrichment analysis (GSEA) was conducted. MUC20 high expression was associated with age, histology, positive peritoneal cytology, advanced stage, and lymph node metastasis (P < 0.05). Kaplan‐Meier survival showed that patients with MUC20 high expression had a poorer prognosis than those with MUC20 low expression. Furthermore, multivariate analysis showed that MUC20 high expression was an independent prognostic factor for worse overall survival (hazard ratio = 1.93, 95% confidence interval = 1.00‐3.74). Moreover, interferon α/γ response, cell‐cell adhesion, O‐glycan processing, and reactive oxygen species (ROS) pathway were associated with MUC20 high expression. MUC20 high expression may be a potential prognostic molecular factor of poor survival. The interferon α/γ response, cell‐cell adhesion, O‐glycan processing, and ROS pathway may be the key processes regulated by MUC20 in EC.
Low- and High-Frequency Repetitive Transcranial Magnetic Stimulation Effects on Resting-State Functional Connectivity Between the Postcentral Gyrus and the Insula

The insular cortex supports the conscious awareness of physical and emotional sensations, and the ability to modulate the insula could have important clinical applications in psychiatry. Repetitive transcranial magnetic stimulation (rTMS) uses transient magnetic fields to induce electrical currents in the superficial cortex. Given its deep location in the brain, the insula may not be directly stimulated by rTMS; however, rTMS may modulate the insula via its functional connections with superficial cortical regions. Furthermore, low- versus high-frequency rTMS is thought to have opposing effects on cortical excitability, and the present study investigated these effects on brain activity and functional connectivity with the insula. Separate groups of healthy participants (n = 14 per group) received low (1 Hz)- or high (10 Hz)-frequency rTMS in five daily sessions to the right postcentral gyrus, a superficial region known to be functionally connected to the insula. Resting-state functional connectivity (RSFC) was measured pre- and post-rTMS. Both 1 and 10 Hz rTMS increased RSFC between the right postcentral gyrus and the left insula. These results suggest that low- and high-frequency rTMS has similar long-term effects on brain activity and RSFC. However, given the lack of difference, we cannot exclude the possibility that these effects are simply due to a nonspecific effect. Given this limitation, these unexpected results underscore the need for acoustic- and stimulation-matched sham control conditions in rTMS research.
Surface-Electromyography-Based Gesture Recognition by Multi-View Deep Learning

Gesture recognition using sparse multichannel surface electromyography (sEMG) is a challenging problem, and the solutions are far from optimal from the point of view of muscle–computer interface. In this paper, we address this problem from the context of multi-view deep learning. A novel multi-view convolutional neural network (CNN) framework is proposed by combining classical sEMG feature sets with a CNN-based deep learning model. The framework consists of two parts. In the first part, multi-view representations of sEMG are modeled in parallel by a multistream CNN, and a performance-based view construction strategy is proposed to choose the most discriminative views from classical feature sets for sEMG-based gesture recognition. In the second part, the learned multi-view deep features are fused through a view aggregation network composed of early and late fusion subnetworks, taking advantage of both early and late fusion of learned multi-view deep features. Evaluations on 11 sparse multichannel sEMG databases as well as five databases with both sEMG and inertial measurement unit data demonstrate that our multi-view framework outperforms single-view methods on both unimodal and multimodal sEMG data streams.
Dissimilar responses of fungal and bacterial communities to soil transplantation simulating abrupt climate changes

Both fungi and bacteria play essential roles in regulating soil carbon cycling. To predict future carbon stability, it is imperative to understand their responses to environmental changes, which is subject to large uncertainty. As current global warming is causing range shifts toward higher latitudes, we conducted three reciprocal soil transplantation experiments over large transects in 2005 to simulate abrupt climate changes. Six years after soil transplantation, fungal biomass of transplanted soils showed a general pattern of changes from donor sites to destination, which were more obvious in bare fallow soils than in maize cropped soils. Strikingly, fungal community compositions were clustered by sites, demonstrating that fungi of transplanted soils acclimatized to the destination environment. Several fungal taxa displayed sharp changes in relative abundance, including Podospora, Chaetomium, Mortierella and Phialemonium. In contrast, bacterial communities remained largely unchanged. Consistent with the important role of fungi in affecting soil carbon cycling, 8.1%–10.0% of fungal genes encoding carbon‐decomposing enzymes were significantly (p < 0.01) increased as compared with those from bacteria (5.7%–8.4%). To explain these observations, we found that fungal occupancy across samples was mainly determined by annual average air temperature and rainfall, whereas bacterial occupancy was more closely related to soil conditions, which remained stable 6 years after soil transplantation. Together, these results demonstrate dissimilar response patterns and resource partitioning between fungi and bacteria, which may have considerable consequences for ecosystem‐scale carbon cycling.
Enhancing the Radiologist-Patient Relationship through Improved Communication: A Quantitative Readability Analysis in Spine Radiology

BACKGROUND AND PURPOSE: More than 75 million Americans have less than adequate health literacy skills according to the National Center for Education Statistics. Readability scores are used as a measure of how well populations read and understand patient education materials. The purpose of this study was to assess the readability of Web sites dedicated to patient education for radiologic spine imaging and interventions. MATERIALS AND METHODS: Eleven search terms relevant to radiologic spine imaging were searched on the public Internet, and the top 10 links for each term were collected and analyzed to determine readability scores by using 10 well-validated quantitative readability assessments from patient-centered education Web sites. The search terms included the following: x-ray spine, CT spine, MR imaging spine, lumbar puncture, kyphoplasty, vertebroplasty, discogram, myelogram, cervical spine, thoracic spine, and lumbar spine. RESULTS: Collectively, the 110 articles were written at an 11.3 grade level (grade range, 7.1–16.9). None of the articles were written at the American Medical Association and National Institutes of Health recommended 3rd-to-7th grade reading levels. The vertebroplasty articles were written at a statistically significant (P < .05) more advanced level than the articles for x-ray spine, CT spine, and MR imaging spine. CONCLUSIONS: Increasing use of the Internet to obtain health information has made it imperative that on-line patient education be written for easy comprehension by the average American. However, given the discordance between readability scores of the articles and the American Medical Association and National Institutes of Health recommended guidelines, it is likely that many patients do not fully benefit from these resources.
Investigation of activation energies for dissociation of host-guest complexes in the gas phase using low-energy collision induced dissociation.

A low-energy collision induced dissociation (CID) (low-energy CID) approach that can determine both activation energy and activation entropy has been used to evaluate gas-phase binding energies of host-guest (H-G) complexes of a heteroditopic hemicryptophane cage host (Zn (II)@1) with a series of biologically relevant guests. In order to use this approach, preliminary calibration of the effective temperature of ions undergoing resonance excitation is required. This was accomplished by employing blackbody infrared radiative dissociation (BIRD) which allows direct measurement of activation parameters. Activation energies and pre-exponential factors were evaluated for more than 10 H-G complexes via the use of low-energy CID. The relatively long residence time of the ions inside the linear ion trap (maximum of 60 s) allowed the study of dissociations with rates below 1 s-1 . This possibility, along with the large size of the investigated ions, ensures the fulfilment of rapid energy exchange (REX) conditions and, as a consequence, accurate application of the Arrhenius equation. Compared with the BIRD technique, low-energy CID allows access to higher effective temperatures, thereby permitting one to probe more endothermic decomposition pathways. Based on the measured activation parameters, guests bearing a phosphate (-OPO3 2- ) functional group were found to bind more strongly with the encapsulating cage than those having a sulfonate (-SO3 - ) group; however, the latter ones make stronger bonds than those with a carboxylate (-CO2 - ) group. In addition, it was observed that the presence of trimethylammonium (-N(CH3 )3 + ) or phenyl groups in the guest's structure improves the strength of H-G interactions. The use of this technique is very straightforward, and it does not require any instrumental modifications. Thus, it can be applied to other H-G chemistry studies where comparison of bond dissociation energies is of paramount importance.
Grain Legumes and Fear of Salt Stress: Focus on Mechanisms and Management Strategies

Salinity is an ever-present major constraint and a major threat to legume crops, particularly in areas with irrigated agriculture. Legumes demonstrate high sensitivity, especially during vegetative and reproductive phases. This review gives an overview of legumes sensitivity to salt stress (SS) and mechanisms to cope with salinity stress under unfavorable conditions. It also focuses on the promising management approaches, i.e., agronomic practices, breeding approaches, and genome editing techniques to improve performance of legumes under SS. Now, the onus is on researchers to comprehend the plants physiological and molecular mechanisms, in addition to various responses as part of their stress tolerance strategy. Due to their ability to fix biological nitrogen, high protein contents, dietary fiber, and essential mineral contents, legumes have become a fascinating group of plants. There is an immense need to develop SS tolerant legume varieties to meet growing demand of protein worldwide. This review covering crucial areas ranging from effects, mechanisms, and management strategies, may elucidate further the ways to develop SS-tolerant varieties and to produce legume crops in unfavorable environments.
The Significance of Yolk Sac Number in Monoamniotic Twins

Background: Detection of a single yolk sac on early first trimester ultrasound was previously thought to be a reliable diagnostic feature of monochorionic monoamniotic (MCMA) twin pregnancies. Objectives: To determine the frequency of two yolk sacs in MCMA twin pregnancies and the association of yolk sac number with pregnancy outcomes. Methods: A retrospective cohort analysis of MCMA twins managed at a tertiary obstetric centre from January 2003 until February 2017. All MCMA twin pregnancies were diagnosed on tertiary centre ultrasound and, where possible, placental histopathology postnatally. All MCMA twin pregnancies, including conjoined twins, with available first trimester ultrasounds from 5 to 11 weeks’ gestation were included in the analysis. MCMA pregnancies without available first trimester ultrasounds and triplet pregnancies which included a MCMA pair were excluded from the study. Results: Sixty-seven MCMA cases were identified over 14 years. Thirty-eight cases were included in the analysis. There was one yolk sac identified in 26 cases (68%) and two yolk sacs in 12 cases (32%). Two yolk sacs were associated with a higher proportion of male fetuses (33%, 4 out of 12, vs. 8%, 2 out of 26; p = 0.01). There were no other significant differences between one and two yolk sacs for maternal or neonatal outcomes. Conclusions: Two yolk sacs are present in up to a third of all MCMA twin pregnancies, dispelling the original concept that a single yolk sac is diagnostic of MCMA pregnancies. Yolk sac number should not be used to determine amnionicity. The presence of two yolk sacs on first trimester ultrasound is associated with an increased rate of male fetuses. The number of yolk sacs has no other significant impact on perinatal outcomes.
Complete mitochondrial genome of Pseudolaubuca engraulis (Pisces: Cyprinidae, Cultrinae)

Abstract The complete mitogenome of Pseudolaubuca engraulis was determined using long-distance polymerase chain reaction and sequenced by primer walking method. It is 16,612 bp in length and contains 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA (tRNA) genes and 1 A + T-rich control region. The gene arrangement and characterization of P. engraulis are similar to most vertebrates. The overall base composition of the heavy strand is 27.1% A, 27.5% C, 25.9% T and 19.5% G, with a slight A + T bias. The shortest tRNA-Ser2 lacks the dihydrouridine arm and is replaced with a simple loop. The termination-associated sequence and the conserved sequence blocks (1–3) are found in the control region.
Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects

Significance Amyotrophic lateral sclerosis (ALS) is a devastating, motor neuron degenerative disease without any cure to date. About 95% of ALS patients feature abnormalities in the RNA/DNA binding protein TDP-43, involving its nucleus-cytoplasmic mislocalization in spinal motor neurons. How TDP-43 pathology triggers neuronal apoptosis remains unclear. Here, we report that TDP-43 participates in the DNA damage response and its nuclear clearance in motor neurons causes DNA double-strand break repair defects in ALS. Our findings uncover a link between TDP-43 pathology and impaired DNA repair, and suggest potential avenues for DNA repair-targeted therapies for TDP-43–ALS. Genome damage and their defective repair have been etiologically linked to degenerating neurons in many subtypes of amyotrophic lateral sclerosis (ALS) patients; however, the specific mechanisms remain enigmatic. The majority of sporadic ALS patients feature abnormalities in the transactivation response DNA-binding protein of 43 kDa (TDP-43), whose nucleo-cytoplasmic mislocalization is characteristically observed in spinal motor neurons. While emerging evidence suggests involvement of other RNA/DNA binding proteins, like FUS in DNA damage response (DDR), the role of TDP-43 in DDR has not been investigated. Here, we report that TDP-43 is a critical component of the nonhomologous end joining (NHEJ)-mediated DNA double-strand break (DSB) repair pathway. TDP-43 is rapidly recruited at DSB sites to stably interact with DDR and NHEJ factors, specifically acting as a scaffold for the recruitment of break-sealing XRCC4-DNA ligase 4 complex at DSB sites in induced pluripotent stem cell-derived motor neurons. shRNA or CRISPR/Cas9-mediated conditional depletion of TDP-43 markedly increases accumulation of genomic DSBs by impairing NHEJ repair, and thereby, sensitizing neurons to DSB stress. Finally, TDP-43 pathology strongly correlates with DSB repair defects, and damage accumulation in the neuronal genomes of sporadic ALS patients and in Caenorhabditis elegans mutant with TDP-1 loss-of-function. Our findings thus link TDP-43 pathology to impaired DSB repair and persistent DDR signaling in motor neuron disease, and suggest that DSB repair-targeted therapies may ameliorate TDP-43 toxicity-induced genome instability in motor neuron disease.