Miracle-dz/UniFAR-FTUs huggingface dataset:
Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets

ABSTRACT Pancreatic islets play an essential role in regulating blood glucose levels. Age-dependent development of glucose intolerance and insulin resistance results in hyperglycemia, which in turn stimulates insulin synthesis and secretion from aged islets, to fulfill the increased demand for insulin. However, the mechanism underlying enhanced insulin secretion remains unknown. Glutamic acid decarboxylase 67 (GAD67) catalyzes the conversion of glutamate into γ-aminobutyric acid (GABA) and CO2. Both glutamate and GABA can affect islet function. Here, we investigated the role of GAD67 in insulin secretion in young (3 month old) and aged (24 month old) C57BL/6J male mice. Unlike young mice, aged mice displayed glucose-intolerance and insulin-resistance. However, aged mice secreted more insulin and showed lower fed blood glucose levels than young mice. GAD67 levels in primary islets increased with aging and in response to high glucose levels. Inhibition of GAD67 activity using a potent inhibitor of GAD, 3-mercaptopropionic acid, abrogated glucose-stimulated insulin secretion from a pancreatic β-cell line and from young and aged islets. Collectively, our results suggest that blood glucose levels regulate GAD67 expression, which contributes to β-cell responses to impaired glucose homeostasis caused by advanced aging.
EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer

Abstract Background Although EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some EGFR mutant tumors do respond to these therapies; however, there is a lack of understanding of the characteristics of EGFR mutant lung tumors responsive to immune checkpoint blockade. Patients and methods We retrospectively analyzed de-identified clinical and molecular data on 171 cases of EGFR mutant lung tumors treated with immune checkpoint inhibitors from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, University of California Los Angeles, and Dana Farber Cancer Institute. A separate cohort of 383 EGFR mutant lung cancer cases with sequencing data available from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, and The Cancer Genome Atlas was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations. Results Compared with 212 EGFR wild-type lung cancers, outcomes with programmed cell death 1 or programmed death-ligand 1 (PD-(L)1) blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR (EGFRΔ19) but similar for EGFRL858R lung tumors. EGFRT790M status and PD-L1 expression did not impact response or survival outcomes to immune checkpoint blockade. PD-L1 expression was similar across EGFR alleles. Lung tumors with EGFRΔ19 alterations harbored a lower tumor mutation burden compared with EGFRL858R lung tumors despite similar smoking history. Conclusions EGFR mutant tumors have generally low response to immune checkpoint inhibitors, but outcomes vary by allele. Understanding the heterogeneity of EGFR mutant tumors may be informative for establishing the benefits and uses of PD-(L)1 therapies for patients with this disease.
Comparative Analysis of Noisy Time Series Clusterin

A comparative analysis of the clustering of sample time series was performed. The clustering sample contained time series of various types, among which atypical objects were present. In the numerical experiment, white noise with different variance was added to the time series. Clustering was performed by k-means and DBSCAN methods using various similarity functions of time series. The values of the quality functionals were quantitative measures of the quality of clustering. The best results were shown by the DBSCAN method using the Euclidean metric with a Complexity Invariant Distance. The method allows to separate a cluster with atypical series at different levels of additive noise. The results of the clustering of real time series confirmed the applicabil-ity of the DBSCAN method for detecting anomaly.
Systematic review versus structured critical analysis

ABSTRACT Objective: This analysis discusses common problems with systematic reviews (SRs) and presents a novel solution, the structured critical analysis (SCA) that can be incorporated into a SR or used as an alternative literature review design. Methods: A cross-sectional survey of current SRs related to interdisciplinary restorative dentistry was obtained by evaluating 100 current SRs for their self-reported methodological quality and its effect on scientific validity. Results: The preferred reporting items for systematic reviews and meta-analyses protocol (PRISMA) was used in 99/100 SRs, but only 8/100 reported a low risk of bias. High statistical heterogeneity precluding meta-analysis was found in 44/100 SRs. Only 94 paragraphs/100 SRs provided critical analysis. Discussion: Significant problems were found with current SRs that can compromise their reliability as the premier level of evidence for clinical science research. The reader must be aware of these deficiencies to correctly interpret the SR and cannot rely on the format alone.
Detection of Human Papillomavirus in Papanicolaou Smears: Correlation With Pathologic Findings and Clinical Outcome

The purpose of this study was to correlate the in situ detection of human papillomavirus (HPV) DNA in archival Papanicolaou (Pap) smears with the pathologic findings and, for atypical squamous cells of undetermined significance (ASCUS), clinical follow-up. Eighty-two Pap smears were destained and analyzed for HPV DNA by in situ hybridization using a consensus probe cocktail that could detect the oncogenic HPV types. “High-risk” HPV DNA was detected in 18 of 23 (78%) low grade SILs, 16 of 40 (40%) ASCUSs, and 1 of 19 (5%) normal Pap smears. The in situ detection of HPV DNA in ASCUS Pap smears with a corresponding biopsy-proven squamous intraepitheal lesion (SIL) within 6 months was significantly greater (14 of 21, 67%) than in smears with corresponding biopsy specimens were negative for SIL (2 of 19, 10%) (p < 0.05). Analysis of the smears negative for HPV using the high-risk probe cocktail with probes for low-risk HPV 6, 11, 42, 43, and 44 increased the percentage of positive smears to 91% (21 of 23) of low grade SILs and 50% (20 of 40) for ASCUS, including 81% (17 of 21) of the women in whom dysplasia developed; there was no change in the percentage of positive cases in normal Pap smears. It is concluded that the in situ detection of HPV DNA in ASCUS cells can help the clinician to differentiate those women at very high risk for a biopsy-proven SIL from those at low risk.
Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity

ABSTRACT Approximately 4.4% of the human genome is comprised of endogenous retroviral sequences, a record of an evolutionary battle between man and retroviruses. Much of what we know about viral immunity comes from studies using mouse models. Experiments using the Friend virus (FV) model have been particularly informative in defining highly complex anti-retroviral mechanisms of the intrinsic, innate and adaptive arms of immunity. FV studies have unraveled fundamental principles about how the immune system controls both acute and chronic viral infections. They led to a more complete understanding of retroviral immunity that begins with cellular sensing, production of type I interferons, and the induction of intrinsic restriction factors. Novel mechanisms have been revealed, which demonstrate that these earliest responses affect not only virus replication, but also subsequent innate and adaptive immunity. This review on FV immunity not only surveys the complex host responses to a retroviral infection from acute infection to chronicity, but also highlights the many feedback mechanisms that regulate and counter-regulate the various arms of the immune system. In addition, the discovery of molecular mechanisms of immunity in this model have led to therapeutic interventions with implications for HIV cure and vaccine development.
Development of an Inexpensive Sensor Network for Recognition of Sitting Posture

The aim of this work is the development of a network of wireless devices to determine, along with a time-stamp, postural changes of users that are to be used in personalized learning environments. For this purpose, we have designed a basic low-cost pressure sensor that can be built from components easily available. Several of these basic sensors (of sizes and shapes chosen specifically for the task) are integrated into a posture sensor cushion, which is electronically controlled by an Arduino microcontroller board. This accounts for experiments involving either a single cushion to be used by an individual end-user setting approach or classroom approaches where several of these cushions make up a sensor network via ZigBee wireless connections. The system thus formed is an excellent alternative to other more expensive commercial systems and provides a low-cost, easy-to-use, portable, scalable, autonomous, flexible solution with free hardware and software, which can be integrated with other sensing devices into a larger affect detection system, customizable to cope with postural changes at required time intervals and support single and collective oriented experimentation approaches.
A randomized controlled trial on local anesthetics in the wound: what do the numbers mean?

The recent article by Fredman et al. (1) and the accompanying editorial by Rowlingson (2) raise concerns about the validity of the conclusions drawn from the results (1) and the indirect inference (2) about the lack of utility of randomized controlled trials. In their article, Fredman et al. (1) make no mention of a post hoc power analysis, necessary to determine whether the failure to detect a difference is simply a result of an insufficiently low sample size. Using the data on “rescue” morphine administration (total morphine, mg/6 h; mean 6 sd: 16 6 17 [n 5 25] vs 18 6 14 [n 5 22]), such an analysis yields a power of ,10% to detect the 5-mg difference for a 5 0.01 (two-tailed), and ,20% for a 5 0.05 (two-tailed). Moreover, the results imply that there were patients with negative morphine consumption (*), raising further questions about the data and/or the need for a log transformation. The only valid conclusion that can be drawn is that the results are inconclusive and repetition of the trial with a sufficiently large sample size would be necessary. For example, assuming a sd of 14 for “rescue” morphine (mg/6 h), n 5 100 patients per group would be required to detect a difference of 5.58 mg at 80% power and a 5 0.05 (two-tailed). Dr. Rowlingson writes: “So much for randomized, controlled trials, eh? ” (2). Randomized controlled trials remain the gold standard for experimental design in clinical research and provide the crucial basis for the increasing trend toward evidence-based practice in anesthesiology (3). In order to be able to utilize these powerful research tools appropriately, however, it is imperative to carefully consider what the numbers actually mean.
3D Position Estimation of Badminton Shuttle Using Unsynchronized Multiple-View Videos

In this paper, we introduce a method to estimate 3D position of a badminton shuttle using unsynchronized multiple-view videos. The research of object tracking for sports is conducted as an application of Computer Vision to improve the tactics involved with such sports. This paper proposes a technique to stably estimate object's position by using motion blur that used be considered as observational noise in the ordinary works. Badminton shuttle has a large variation of the moving speed, the motion trajectory is unpredictable and moreover the observation size is very small. Thus, it cannot be grasped correctly with human eyes. We apply our proposed technique to badminton shuttle tracking to confirm the ability of our method to enhance the human vision. We also consider that there is some contribution to augment sports in future.
How Does iReadMore Therapy Change the Reading Network of Patients with Central Alexia?

Central alexia (CA) is an acquired reading disorder co-occurring with a generalized language deficit (aphasia). The roles of perilesional and ipsilesional tissue in recovery from poststroke aphasia are unclear. We investigated the impact of reading training (using iReadMore, a therapy app) on the connections within and between the right and left hemisphere of the reading network of patients with CA. In patients with pure alexia, iReadMore increased feedback from left inferior frontal gyrus (IFG) region to the left occipital (OCC) region. We aimed to identify whether iReadMore therapy was effective through a similar mechanism in patients with CA. Participants with chronic poststroke CA (n = 23) completed 35 h of iReadMore training over 4 weeks. Reading accuracy for trained and untrained words was assessed before and after therapy. The neural response to reading trained and untrained words in the left and right OCC, ventral occipitotemporal, and IFG regions was examined using event-related magnetoencephalography. The training-related modulation in effective connectivity between regions was modeled at the group level with dynamic causal modeling. iReadMore training improved participants' reading accuracy by an average of 8.4% (range, −2.77 to 31.66) while accuracy for untrained words was stable. Training increased regional sensitivity in bilateral frontal and occipital regions, and strengthened feedforward connections within the left hemisphere. Our data suggest that iReadMore training in these patients modulates lower-order visual representations, as opposed to higher-order, more abstract representations, to improve word-reading accuracy. SIGNIFICANCE STATEMENT This is the first study to conduct a network-level analysis of therapy effects in participants with poststroke central alexia. When patients trained with iReadMore (a multimodal, behavioral, mass practice, computer-based therapy), reading accuracy improved by an average 8.4% on trained items. A network analysis of the magnetoencephalography data associated with this improvement revealed an increase in regional sensitivity in bilateral frontal and occipital regions and strengthening of feedforward connections within the left hemisphere. This indicates that in patients with CA iReadMore engages lower-order, intact resources within the left hemisphere (posterior to their lesion locations) to improve word reading. This provides a foundation for future research to investigate reading network modulation in different CA subtypes, or for sentence-level therapy.
Novel miRNA, miR-sc14, promotes Schwann cell proliferation and migration

MicroRNAs refer to a class of endogenous, short non-coding RNAs that mediate numerous biological functions. MicroRNAs regulate various physiological and pathological activities of peripheral nerves, including peripheral nerve repair and regeneration. Previously, using a rat sciatic nerve injury model, we identified many functionally annotated novel microRNAs, including miR-sc14. Here, we used real-time reverse transcription-polymerase chain reaction to examine miR-sc14 expression in rat sciatic nerve stumps. Our results show that miR-sc14 is noticeably altered following sciatic nerve injury, being up-regulated at 1 day and diminished at 7 days. EdU and transwell chamber assay results showed that miR-sc14 mimic promoted proliferation and migration of Schwann cells, while miR-sc14 inhibitor suppressed their proliferation and migration. Additionally, bioinformatic analysis examined potential target genes of miR-sc14, and found that fibroblast growth factor receptor 2 might be a potential target gene. Specifically, our results show changes of miR-sc14 expression in the sciatic nerve of rats at different time points after nerve injury. Appropriately, up-regulation of miR-sc14 promoted proliferation and migration of Schwann cells. Consequently, miR-sc14 may be an intervention target to promote repair of peripheral nerve injury. The study was approved by the Jiangsu Provincial Laboratory Animal Management Committee, China on March 4, 2015 (approval No. 20150304-004).
Human representation of multimodal distributions as clusters of samples

Behavioral and neuroimaging evidence shows that human decisions are sensitive to the statistical regularities (mean, variance, skewness, etc.) of reward distributions. However, it is unclear what representations human observers form to approximate reward distributions, or probability distributions in general. When the possible values of a probability distribution are numerous, it is cognitively costly and perhaps unrealistic to maintain in mind the probability of each possible value. Here we propose a Clusters of Samples (CoS) representation model: The samples of the to-be-represented distribution are classified into a small number of clusters and only the centroids and relative weights of the clusters are retained for future use. We tested the behavioral relevance of CoS in four experiments. On each trial, human subjects reported the mean and mode of a sequentially presented multimodal distribution of spatial positions or orientations. By varying the global and local features of the distributions, we observed systematic errors in the reported mean and mode. We found that our CoS representation of probability distributions outperformed alternative models in accounting for subjects’ response patterns. The ostensible influence of positive/negative skewness on the over/under estimation of the reported mean, analogous to the “skewness preference” phenomenon in decisions, could be well explained by models based on CoS.
Rare variant association testing for multicategory phenotype

Genetic association studies have provided new insights into the genetic variability of human complex traits with a focus mainly on continuous or binary traits. Methods have been proposed to take into account disease heterogeneity between subgroups of patients when studying common variants but none was specifically designed for rare variants. Because rare variants are expected to have stronger effects and to be more heterogeneously distributed among cases than common ones, subgroup analyses might be particularly attractive in this context. To address this issue, we propose an extension of burden tests by using a multinomial regression model, which enables association tests between rare variants and multicategory phenotypes. We evaluated the type I error and the power of two burden tests, CAST and WSS, by simulating data under different scenarios. In the case of genetic heterogeneity between case subgroups, we showed an advantage of multinomial regression over logistic regression, which considers all the cases against the controls. We replicated these results on real data from Moyamoya disease where the burden tests performed better when cases were stratified according to age‐of‐onset. We implemented the functions for association tests in the R package “Ravages” available on Github.
Antibacterial Properties of Graphene-Based Nanomaterials

Bacteria mediated infections may cause various acute or chronic illnesses and antibiotic resistance in pathogenic bacteria has become a serious health problem around the world due to their excessive use or misuse. Replacement of existing antibacterial agents with a novel and efficient alternative is the immediate demand to alleviate this problem. Graphene-based materials have been exquisitely studied because of their remarkable bactericidal activity on a wide range of bacteria. Graphene-based materials provide advantages of easy preparation, renewable, unique catalytic properties, and exceptional physical properties such as a large specific surface area and mechanical strength. However, several queries related to the mechanism of action, significance of size and composition toward bacterial activity, toxicity criteria, and other issues are needed to be addressed. This review summarizes the recent efforts that have been made so far toward the development of graphene-based antibacterial materials to face current challenges to combat against the bacterial targets. This review describes the inherent antibacterial activity of graphene-family and recent advances that have been made on graphene-based antibacterial materials covering the functionalization with silver nanoparticles, other metal ions/oxides nanoparticles, polymers, antibiotics, and enzymes along with their multicomponent functionalization. Furthermore, the review describes the biosafety of the graphene-based antibacterial materials. It is hoped that this review will provide valuable current insight and excite new ideas for the further development of safe and efficient graphene-based antibacterial materials.
Report of Human Lightness Perception

Natural viewing challenges the visual system with images that have a dynamic range of light intensity (luminance) that can approach 1,000,000:1 and that often exceeds 10,000:1 [1, 2]. The range of perceived surface reflectance (lightness), however, can be well approximated by the Munsell matte neutral scale (N 2.0/ to N 9.5/), consisting of surfaces whose reflectance varies by about 30:1. Thus, the visual system must map a large range of surface luminance onto a much smaller range of surface lightness. We measured this mapping in images with a dynamic range close to that of natural images. We studied simple images that lacked segmentation cues that would indicate multiple regions of illumination. We found a remarkable degree of compression: at a single image location, a stimulus luminance range of 5,905:1 can be mapped onto an extended lightness scale that has a reflectance range of 100:1. We characterized how the luminance-to-lightness mapping changes with stimulus context. Our data rule out theories that predict perceived lightness from luminance ratios or Weber contrast. A mechanistic model connects our data to theories of adaptation and provides insight about how the underlying visual response varies with context.
Chemical composition and antiproliferative, antioxidant and trypanocidal activities of the fruits from Campomanesia xanthocarpa (Mart.) O. Berg (Myrtaceae)

Abstract Chemical investigation of the extracts of the fruits from Campomanesia xanthocarpa resulted in the isolation of six known compounds identified by NMR and comparison with literature data (2′,4′-dihydroxy-5′-methyl-6′-methoxychalcone (1), 2′,4′-dihydroxy-3′,5′-dimethyl-6′-methoxychalcone (2), 2′-hydroxy-3′-methyl-4′,6′-dimethoxychalcone (3), 2′,6′-dihydroxy-3′-methyl-4′-methoxychalcone (4), 5-hydroxy-7-methoxy-8-methylflavanone (5) and 7-hydroxy-5-methoxy-6-methylflavanone (6)). The considerable antioxidant capacity of the extracts was demonstrated by ORAC-FL and DPPH tests. The antiproliferative assay of the extracts and 5 was done in vitro, against many different cancer cell lines besides a healthy one. The extracts presented low cytotoxicity and the substance demonstrated promising results against all the cancer cell lines tested, with IC50 values ranging from 4.75 to 45.81 µmol L−1. The in vitro trypanocidal activity was evaluated against the epimastigote form of the Y strain of Trypanosoma cruzi and an improvement in the activity of the substances 2 (221.81 µmol L−1) and 5 (61.87 µmol L−1) was observed regarding the values obtained for the extracts. Graphical Abstract