Miracle-dz/UniFAR-FTUs huggingface dataset:
The efficacy of gray matter atrophy and cognitive assessment in differentiation of aMCI and naMCI

Abstract Background Mild cognitive impairment (MCI) is a heterogeneous entity that can be categorized into related but different subtypes. In this study, we analyzed the gray matter structural changes of amnestic MCI (aMCI) and non-amnestic MCI (naMCI), and how it resulted in diverse cognitive impairment. Methods Altogether 77 individuals were recruited, including 28 cognitively normal controls (NC), 25 naMCI subjects, and 24 aMCI subjects. All participants underwent a 3.0 T magnetic resonance (MR) scan and a detailed neuropsychological examination. Cortical thickness and subcortical nuclei volume were extracted by Freesurfer software and compared among groups. The areas with significant differences were further analyzed by general linear regression to identify the risk factors of each cognitive impairment subtypes. Results Significant differences were observed in bilateral hippocampi, amygdala, thalamus, accumbens, left transverse temporal gyrus and left precuneus among groups. AMCI and naMCI were significantly different in the right hippocampus, bilateral amygdala, left precuneus, and left transverse temporal gyrus. Linear regression analysis revealed that the atrophy of left precuneus was a risk factor of memory, executive function (EF) and visuospatial impairment (p < 0.001). The atrophy of left amygdala, right accumbens and left thalamus were risk factors of memory, EF and language impairment respectively (p < 0.05). Conclusions These findings confirmed that different gray matter structural changes could lead to specific neuropsychological features in MCI subtypes. Thorough understanding of MCI subtypes and the underlying pathology would be beneficial for precise diagnosis and intervention.
Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review

It is over 50 years since the discovery of microtubules, and they have become one of the most important drug targets for anti-cancer therapies. Microtubules are predominantly composed of the protein tubulin, which contains a number of different binding sites for small-molecule drugs. There is continued interest in drug development for compounds targeting the colchicine-binding site of tubulin, termed colchicine-binding site inhibitors (CBSIs). This review highlights CBSIs discovered through diverse sources: from natural compounds, rational design, serendipitously and via high-throughput screening. We provide an update on CBSIs reported in the past three years and discuss the clinical status of CBSIs. It is likely that efforts will continue to develop CBSIs for a diverse set of cancers, and this review provides a timely update on recent developments.
Effect of conversion to implant-assisted removable partial denture in patients with mandibular Kennedy classification Ⅰ: A systematic review and meta-analysis.

OBJECTIVE This review evaluated the change in treatment outcomes after conversion from conventional removable partial denture (RPD) to implant-assisted removable partial denture (IARPD). The patient-reported outcome measures (PROMs), objective parameters for evaluation of functional performance, and biological and mechanical complication were evaluated. MATERIALS AND METHODS This systematic review was based on the Cochrane review methodology and followed the criteria of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus up to April 3, 2019. After the initial search, additional electronic and hand searches were performed to identify further studies, ongoing studies and gray literature, without restrictions on language, year of publication or publication type. RESULTS In total, 6,544 non-duplicate articles were identified, and 31 were eligible for full-text search. Finally, 19 publications based on 13 independent studies were selected. In the meta-analysis, general patient satisfaction was significantly increased (p < .05), and the improved mastication was remarkable oral function. In oral health-related quality of life, the oral health impact profile score was significantly improved, and improvements of physical pain and psychological disability were prominent (p < .05). Masticatory performance was improved in terms of maximum bite force, active occlusal contact area, and mandibular jaw movement (p < .05). The weighted mean survival rate of implants was 96.60%. CONCLUSIONS After conversion from conventional RPD to IARPD, the PROMs and masticatory performance significantly improved in partially edentulous patients under mandibular Kennedy classification Ⅰ.
CREB transcription in the medial prefrontal cortex regulates the formation of long-term associative recognition memory

The medial prefrontal cortex (mPFC) is known to be critical for specific forms of long-term recognition memory, however the cellular mechanisms in the mPFC that underpin memory maintenance have not been well characterized. This study examined the importance of phosphorylation of cAMP responsive element binding protein (CREB) in the mPFC for different forms of long-term recognition memory in the rat. Adenoviral transduction of the mPFC with a dominant-negative inhibitor of CREB impaired object-in-place memory following a 6 or 24 h retention delay, but no impairment was observed following delays of 5 min or 3 h. Long-term object temporal order memory and spatial temporal order memory was also impaired. In contrast, there were no impairments in novel object recognition or object location memory. These results establish, for the first time, the importance of CREB phosphorylation within the mPFC for memory of associative and temporal information crucial to recognition.
Crosstalk between PTEN/PI3K/Akt Signalling and DNA Damage in the Oocyte: Implications for Primordial Follicle Activation, Oocyte Quality and Ageing

The preservation of genome integrity in the mammalian female germline from primordial follicle arrest to activation of growth to oocyte maturation is fundamental to ensure reproductive success. As oocytes are formed before birth and may remain dormant for many years, it is essential that defence mechanisms are monitored and well maintained. The phosphatase and tensin homolog of chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, Akt) is a major signalling pathway governing primordial follicle recruitment and growth. This pathway also contributes to cell growth, survival and metabolism, and to the maintenance of genomic integrity. Accelerated primordial follicle activation through this pathway may result in a compromised DNA damage response (DDR). Additionally, the distinct DDR mechanisms in oocytes may become less efficient with ageing. This review considers DNA damage surveillance mechanisms and their links to the PTEN/PI3K/Akt signalling pathway, impacting on the DDR during growth activation of primordial follicles, and in ovarian ageing. Targeting DDR mechanisms within oocytes may be of value in developing techniques to protect ovaries against chemotherapy and in advancing clinical approaches to regulate primordial follicle activation.
Infection with Foamy Virus in Wild Ruminants—Evidence for a New Virus Reservoir?

Foamy viruses (FVs) are widely distributed and infect many animal species including non-human primates, horses, cattle, and cats. Several reports also suggest that other species can be FV hosts. Since most of such studies involved livestock or companion animals, we aimed to test blood samples from wild ruminants for the presence of FV-specific antibodies and, subsequently, genetic material. Out of 269 serum samples tested by ELISA with the bovine foamy virus (BFV) Gag and Bet antigens, 23 sera showed increased reactivity to at least one of them. High reactive sera represented 30% of bison samples and 7.5% of deer specimens. Eleven of the ELISA-positives were also strongly positive in immunoblot analyses. The peripheral blood DNA of seroreactive animals was tested by semi-nested PCR. The specific 275 bp fragment of the pol gene was amplified only in one sample collected from a red deer and the analysis of its sequence showed the highest homology for European BFV isolates. Such results may suggest the existence of a new FV reservoir in bison as well as in deer populations. Whether the origin of such infections stems from a new FV or is the result of BFV inter-species transmission remains to be clarified.
The Temporal Dynamics of Slums Employing a CNN-Based Change Detection Approach

Along with rapid urbanization, the growth and persistence of slums is a global challenge. While remote sensing imagery is increasingly used for producing slum maps, only a few studies have analyzed their temporal dynamics. This study explores the potential of fully convolutional networks (FCNs) to analyze the temporal dynamics of small clusters of temporary slums using very high resolution (VHR) imagery in Bangalore, India. The study develops two approaches based on FCNs. The first approach uses a post-classification change detection, and the second trains FCNs to directly classify the dynamics of slums. For both approaches, the performances of 3 × 3 kernels and 5 × 5 kernels of the networks were compared. While classification results of individual years exhibit a relatively high F1-score (3 × 3 kernel) of 88.4% on average, the change accuracies are lower. The post-classification results obtained an F1-score of 53.8% and the change-detection networks obtained an F1-score of 53.7%. According to the trajectory error matrix (TEM), the post-classification results scored higher for the overall accuracy but lower for the accuracy difference of change trajectories than the change-detection networks. Although the two methods did not have significant differences in terms of accuracy, the change-detection network was less noisy. Within our study area, the areas of slums show a small overall decrease; the annual growth of slums (between 2012 and 2016) was 7173 m2, in contrast to an annual decline of 8390 m2. However, these numbers hid the spatial dynamics, which were much larger. Interestingly, areas where slums disappeared commonly changed into green areas, not into built-up areas. The proposed change-detection network provides a robust map of the locations of changes with lower confidence about the exact boundaries. This shows the potential of FCNs for detecting the dynamics of slums in VHR imagery.
Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomized controlled phase 3 TAKT study

Abstract Objective To investigate the long-term efficacy and safety of the IL-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK). Methods Patients completing the randomized, double-blind, placebo-controlled period of the TAKT (Takayasu arteritis Treated with Tocilizumab) trial were followed up during open-label extended treatment with weekly s.c. tocilizumab 162 mg for up to 96 weeks or longer, with oral glucocorticoid tapering performed at the investigators’ discretion. Endpoints of the extension analysis included steroid-sparing effects of tocilizumab, imaging data, patient-reported outcomes (36-Item Short Form Health Survey) and safety. Results All 36 patients enrolled in the double-blind period entered the open-label extension; 28 patients received tocilizumab for 96 weeks. The median glucocorticoid dose was 0.223 mg/kg/day at the time of relapse before study entry, 0.131 mg/kg/day (interquartile range 0.099, 0.207) after 48 weeks and 0.105 mg/kg/day (interquartile range 0.039, 0.153) after 96 weeks. Overall, 46.4% of patients reduced their dose to <0.1 mg/kg/day, which was less than half the dose administered at relapse before study entry (mean difference –0.120 mg/kg/day; 95% CI −0.154, −0.087). Imaging evaluations indicated that most patients’ disease was improved (17.9%) or stable (67.9%) after 96 weeks compared with baseline. Mean 36-Item Short Form Health Survey physical and mental component summary scores and 7 of 8 domain scores were clinically improved from baseline and maintained over 96 weeks of tocilizumab treatment. No unexpected safety issues were reported. Conclusion These results in patients with Takayasu arteritis provide evidence of a steroid-sparing effect and improvements in well-being during long-term treatment with once-weekly tocilizumab 162 mg, with no new safety concerns. Trial registration JAPIC Clinical Trials Information, http://www.clinicaltrials. jp/user/cteSearch_e. jsp, JapicCTI-142616.
Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer.

Macrophages have been linked to tumor initiation, progression, metastasis and treatment resistance. However, the transcriptional regulation of macrophages driving the pro-tumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conservative non-coding sequence of csf-1r gene and promotes M2-like macrophage-mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating TCA cycle and UDP-GlcNAc biosynthesis thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAM) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti-PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non-small cell lung carcinoma (NSCLC) patients and critically regulates its immunosuppressive activity. Natural compound β-glucan downregulates c-Maf expression on macrophages leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy.
Machine learning approaches and databases for prediction of drug–target interaction: a survey paper

Abstract The task of predicting the interactions between drugs and targets plays a key role in the process of drug discovery. There is a need to develop novel and efficient prediction approaches in order to avoid costly and laborious yet not-always-deterministic experiments to determine drug–target interactions (DTIs) by experiments alone. These approaches should be capable of identifying the potential DTIs in a timely manner. In this article, we describe the data required for the task of DTI prediction followed by a comprehensive catalog consisting of machine learning methods and databases, which have been proposed and utilized to predict DTIs. The advantages and disadvantages of each set of methods are also briefly discussed. Lastly, the challenges one may face in prediction of DTI using machine learning approaches are highlighted and we conclude by shedding some lights on important future research directions.
Low Serum Interleukin-6 Is a Differential Marker of Obesity-Related Metabolic Dysfunction in Women and Men.

There is scant information regarding the role of interleukin (IL)-6 in obesity-related metabolic dysfunction in humans. Thus, we studied the serum levels of IL-6 in normal weight, overweight, and obese subjects, and examined associations of IL-6 with hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation. One hundred three women and men were included in the study. Anthropometric parameters, blood glucose, insulin, total cholesterol, and triglycerides were measured. Serum levels of tumor necrosis factor-alpha (TNF-alpha), IL-10, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance (ANOVA) showed a 2.5-fold significant decrease in serum IL-6 in overweight and obese individuals when compared with normal weight controls. Serum IL-6 exhibited significant inverse correlations with body mass index (r = -0.39/P < 0.0001), waist circumference (r = -0.42/P < 0.001), blood glucose (r = -0.40/P < 0.0001), triglycerides (r = -0.34/P < 0.0001), and TNF-alpha (r = -0.48/P < 0.0001), whereas a strongly positive correlation was found with IL-10 (r = 0.77/P < 0.0001). Multiple linear regression analysis revealed that behavior of IL-6 was mainly influenced by IL-10 (beta = 0.28/P = 1.95 × 10-6), TNF-alpha (beta = -0.67/P = 0.0017), and body fat percentage (beta = -5.95/P = 7.67 × 10-5) in women. In contrast, IL-10 (beta = 0.37/P = 1.34 × 10-9), TNF-alpha (beta = -0.85/P = 0.0005), and triglycerides (beta = 1.07/P = 0.0007) were major influencing factors of IL-6 in men. This study demonstrates that IL-6 is a marker of metabolic dysfunction that is differentially regulated in obese women and men.
Sensitizing fragrances in absorbent hygiene products

Allergenic fragrances are present in a wide range of products but they are not regulated in all industries to the same extent. In Europe, absorbent hygiene products (AHPs) are only covered by the general product safety directive and therefore fragrances can be used freely, whereas in cosmetics and toys the use of these ingredients is regulated.
HIV Partner Service Delivery Among Transgender Women — United States, 2013–2017

Transgender women* in the United States are disproportionately affected by human immunodeficiency virus (HIV) infection because of multiple factors, including stigma related to gender identity, unstable housing, limited employment options, and high-risk behaviors, such as sex work, unprotected receptive anal intercourse, and injection drug use, that tend to increase their vulnerability to becoming infected with HIV (1,2). In a recent meta-analysis of 88 U.S. studies conducted during 2006-2017, the mean estimated laboratory-confirmed prevalence of HIV infection among transgender women was 14.2%, and the mean self-reported prevalence estimate was 21.0% (3). The Ending the HIV Epidemic initiative calls for accelerating the implementation of evidence-based strategies in the right geographic areas targeted to the right persons to end the HIV epidemic in the United States (4). HIV partner services are effective strategies offered by public health workers to persons with a diagnosis of HIV infection (index persons) and their sex or needle-sharing partners (partners), who are notified of potential HIV exposure and offered HIV testing and related services. CDC analyzed HIV partner services data submitted by 61 health departments† during 2013-2017. Among 208,304 index persons, 1,727 (0.8%) were transgender women. Overall, 71.5% of index transgender women were interviewed for partner services, which was lower than that for all index persons combined (81.1%). Among 1,089 transgender women named as partners by index persons, 71.2% were notified of potential HIV exposure, which was lower than that for all partners combined (77.1%). Fewer than half (46.5%) of notified transgender women partners were tested for HIV, and approximately one in five (18.6%) of those who were tested received a new diagnosis of HIV infection, slightly higher than for all partners combined (17.6%). Additional efforts are needed to effectively implement partner services among transgender women and identify those whose infection with HIV is undiagnosed, provide timely prevention and care services, reduce HIV transmission, and contribute to ending the HIV epidemic.
Ocean Surface Cross Section for Bistatic HF Radar Incorporating a Six DOF Oscillation Motion Model

To investigate the characteristics of sea clutter, based on ocean surface electromagnetic scattering theory, the first- and second-order ocean surface scattering cross sections for bistatic high-frequency (HF) radar incorporating a multi-frequency six degree-of-freedom (DOF) oscillation motion model are mathematically derived. The derived radar cross sections (RCSs) can be reduced to the floating platform based monostatic case or onshore bistatic case for corresponding geometry setting. Simulation results show that the six DOF oscillation motion will result in more additional peaks in the radar Doppler spectra and the amplitudes and frequencies of these motion-induced peaks are decided by the amplitudes and frequencies of the oscillation motion. The effect of the platform motion on the first-order radar spectrum is greater than that of the second-order, and the motion-induced peaks in the first-order spectrum may overlap with the second-order spectrum. Furthermore, yaw is the dominant factor affecting the radar spectra, especially the second-order. Moreover, the effect of platform motion on radar spectra and the amplitudes of the second-order spectrum decreases as the bistatic angle increases. In addition, it should be noted that the amplitudes of the Bragg peaks may be lower than those of the motion-induced peaks due to the low frequency (LF) oscillation motion of the floating platform, which is an important finding for the applications of the floating platform based bistatic HF radar in moving target detection and ocean surface dynamics parameter estimation.
The right to silence and the permission to talk: Motivational interviewing and high-value detainees.

Motivational interviewing (MI) is an evidence-based intervention that has proved effective across diverse clinical contexts with clients ambivalent about and resistant to behavioral change. This article argues that the principles of MI can be successfully applied to law enforcement (LE) interviews with high-value detainees (HVDs; i.e., terrorist suspects). Although the forms of ambivalence and resistance may differ from those in clinical contexts, HVDs must make the decision whether to talk or not when they are interviewed. We argue there is likely ambivalence regarding this. We theorized that 4 MI-consistent (MI) skills may be useful for LE interviewers: reflective listening, summaries, rolling with resistance, and developing discrepancies. Using the Observing Rapport Based Interpersonal Techniques coding manual (Alison, Alison, Elntib, & Noone, 2012), we analyzed 804 tapes of LE interviews with 75 terrorism suspects in the United Kingdom. Multilevel structural equation modeling revealed that MI skills encouraged detainee engagement and subsequent information gain. It also revealed that any approach antithetical to MI had a profoundly negative impact on detainee engagement and subsequent information gain-potentially through creating reactance (a form of resistance based on motivations to regain a freedom when it is threatened). Overall, this research provides unique evidence for the use of specific skills and approaches that can increase or decrease HVD engagement and information provided. (PsycINFO Database Record (c) 2020 APA, all rights reserved).