Miracle-dz/UniFAR-FTUs huggingface dataset:
Dissecting the Process of Activation of Cancer-promoting Zinc-requiring Ectoenzymes by Zinc Metalation Mediated by ZNT Transporters*

Zinc-requiring ectoenzymes, including both secreted and membrane-bound enzymes, are considered to capture zinc in their active site for their activation in the early secretory pathway. This idea has been confirmed by our studies conducted using tissue-nonspecific alkaline phosphatase (TNAP), which is elaborately activated by means of a two-step mechanism by zinc transporter 5 (ZNT5)-ZNT6 heterodimers and ZNT7 homodimers, through protein stabilization followed by enzyme activation with zinc in the early secretory pathway. However, the molecular basis of the activation process in other zinc-requiring ectoenzymes remains largely unknown. In this study, we investigated this activation process by using three cancer-promoting zinc-requiring ectoenzymes, autotaxin (ATX), matrix metalloproteinase 9 (MMP9), and carbonic anhydrase IX (CAIX), and the chicken DT40 cell mutants that we generated; we specifically focused on clarifying whether the same or a similar activation mechanism operates in these ectoenzymes. ATX activation required ZNT5-ZNT6 heterodimers and ZNT7 homodimers in a manner similar to TNAP activation, although the protein stability of ATX was differently regulated from that of TNAP. MMP9 required ZNT5-ZNT6 heterodimers and ZNT7 homodimers for its activation as well as secretion; MMP9 was not secreted into the spent medium unless both zinc-transport complexes were present. Finally, CAIX activation by zinc was mediated not only by ZNT5-ZNT6 heterodimers and ZNT7 homodimers but also by ZNT4 homodimers; thus, these three zinc-transport complexes redundantly contribute to CAIX activation. Our results provide pivotal insights into the activation processes of zinc-requiring ectoenzymes, and furthermore, they offer novel insights for potential cancer therapy applications given the cancer-promoting potencies of ATX, MMP9, and CAIX.
The effects of a client-centered leisure activity program on satisfaction, self-esteem, and depression in elderly residents of a long-term care facility

[Purpose] This study aimed to examine the effects of a client-centered leisure activity program on satisfaction, upper limb function, self-esteem, and depression in elderly residents of a long-term care facility. [Subjects and Methods] This study included 12 elderly subjects, aged 65 or older, residing in a nursing home. The subjects were divided into an experimental and a control group. Subjects in the control group received leisure activities already provided by the facility. The experimental group participated in a client-centered leisure activity program. The subjects conducted individual activities three times per week, 30 minutes per session. The group activity was conducted three times per week for eight weeks. Each subject’s performance of and satisfaction with the leisure activity programs, upper limb function, self-esteem, and depression were measured before and after the intervention. [Results] After participating in a program, significant improvements were seen in both the Canadian Occupational Performance Measure and upper limb function in the experimental group. Also after the intervention, the subjects’ self-esteem significantly increased and their depression significantly decreased. [Conclusion] A client-centered leisure activity program motivates elderly people residing in a long-term care facility and induces their voluntary participation. Such customized programs are therefore effective for enhancing physical and psychological functioning in this population.
Vehicle Detection Based on Deep Dual-Vehicle Deformable Part Models

Vehicle detection plays an important role in safe driving assistance technology. Due to the high accuracy and good efficiency, the deformable part model is widely used in the field of vehicle detection. At present, the problem related to reduction of false positivity rate of partially obscured vehicles is very challenging in vehicle detection technology based on machine vision. In order to address the abovementioned issues, this paper proposes a deep vehicle detection algorithm based on the dual-vehicle deformable part model. The deep learning framework can be used for vehicle detection to solve the problem related to incomplete design and other issues. In this paper, the deep model is used for vehicle detection that consists of feature extraction, deformation processing, occlusion processing, and classifier training using the back propagation (BP) algorithm to enhance the potential synergistic interaction between various parts and to get more comprehensive vehicle characteristics. The experimental results have shown that proposed algorithm is superior to the existing detection algorithms in detection of partially shielded vehicles, and it ensures high detection efficiency while satisfying the real-time requirements of safe driving assistance technology.
Monocytes/Macrophages promote vascular CXCR4 expression via the ERK pathway in hepatocellular carcinoma

ABSTRACT We recently identified CXCR4 as a novel vascular marker for vessel sprouting in hepatocellular carcinoma (HCC) tissues. Thus, CXCR4+ endothelial cells (ECs) could serve as a potential predictor for patients who may benefit from sorafenib treatment; however, the mechanism that regulates vascular CXCR4 expression in HCC remains largely unknown. Here, we revealed a large number of monocytes/macrophages (Mo/Mφ) to be selectively enriched in the perivascular areas of CXCR4+ vessels in HCC samples. The depletion of Mo/Mφ with gadolinium chloride (GdCl3) or zoledronic acid (ZA) treatment significantly reduced vascular CXCR4 expression in HCC tumors. This phenomenon was also confirmed in CCR2-KO mice, which exhibited reduced infiltration of inflammatory Mo/Mφ in tumor tissues. Mechanistic studies revealed that inflammatory cytokines derived from tumor conditioned Mo/Mφ, especially TNF-α, could up-regulate CXCR4 expression on ECs. TNF-α-induced activation of the Raf-ERK pathway, but not Notch signaling, was responsible for the expression of CXCR4. Moreover, the combination treatment of sorafenib with ZA was associated with improved anti-tumor efficacy by significantly reducing vascular CXCR4 expression. These findings revealed that Mo/Mφ could regulate CXCR4 expression in the tumor vasculature. Thus, the inhibition of Mo/Mφ inflammation might enhance the treatment efficacy of sorafenib in HCC.
T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma

Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, T-cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amid immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM. Experimental Design: Tumor-infiltrating and peripheral blood lymphocytes (TILs and PBLs) were isolated from patients with GBM. Levels of exhaustion-associated inhibitory receptors and poststimulation levels of the cytokines IFNγ, TNFα, and IL2 were assessed by flow cytometry. T-cell receptor Vβ chain expansion was also assessed in TILs and PBLs. Similar analysis was extended to TILs isolated from intracranial and subcutaneous immunocompetent murine models of glioma, breast, lung, and melanoma cancers. Results: Our data reveal that GBM elicits a particularly severe T-cell exhaustion signature among infiltrating T cells characterized by: (1) prominent upregulation of multiple immune checkpoints; (2) stereotyped T-cell transcriptional programs matching classical virus-induced exhaustion; and (3) notable T-cell hyporesponsiveness in tumor-specific T cells. Exhaustion signatures differ predictably with tumor identity, but remain stable across manipulated tumor locations. Conclusions: Distinct cancers possess similarly distinct mechanisms for exhausting T cells. The poor TIL function and severe exhaustion observed in GBM highlight the need to better understand this tumor-imposed mode of T-cell dysfunction in order to formulate effective immunotherapeutic strategies targeting GBM. Clin Cancer Res; 24(17); 4175–86. ©2018 AACR. See related commentary by Jackson and Lim, p. 4059
Facial first impressions and partner preference models: Comparable or distinct underlying structures?

Given the frequency of relationships nowadays initiated online, where impressions from face photographs may influence relationship initiation, it is important to understand how facial first impressions might be used in such contexts. We therefore examined the applicability of a leading model of verbally expressed partner preferences to impressions derived from real face images and investigated how the factor structure of first impressions based on potential partner preference-related traits might relate to a more general model of facial first impressions. Participants rated 1,000 everyday face photographs on 12 traits selected to represent (Fletcher, et al. 1999, Journal of Personality and Social Psychology, 76, 72) verbal model of partner preferences. Facial trait judgements showed an underlying structure that largely paralleled the tripartite structure of Fletcher et al.'s verbal preference model, regardless of either face gender or participant gender. Furthermore, there was close correspondence between the verbal partner preference model and a more general tripartite model of facial first impressions derived from a different literature (Sutherland et al., 2013, Cognition, 127, 105), suggesting an underlying correspondence between verbal conceptual models of romantic preferences and more general models of facial first impressions.
Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer

The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre‐diagnostically. We assessed the association of antibody responses to SGG proteins in pre‐diagnostic serum samples with CRC risk in a case–control study nested within a prospective cohort. Pre‐diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04–1.77). Positivity for two or more proteins of a previously identified SGG 6‐marker panel with greater CRC‐specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44–3.27). In this prospective nested case–control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification.
Do subjective assessments of running patterns reflect objective parameters?

Abstract Running patterns are often categorized into subgroups according to common features before data analysis and interpretation. The Volodalen® method is a simple field-based tool used to classify runners into aerial or terrestrial using a 5-item subjective rating scale. We aimed to validate the Volodalen® method by quantifying the relationship between its subjective scores and 3D biomechanical measures. Fifty-four runners ran 30 s on a treadmill at 10, 12, 14, 16, and 18 km h−1 while their kinematics were assessed subjectively using the Volodalen® method and objectively using 3D motion capture. For each runner and speed, two researchers scored the five Volodalen® items on a 1-to-5 scale, which addressed vertical oscillation, upper-body motion, pelvis and foot position at ground contact, and footstrike pattern. Seven 3D biomechanical parameters reflecting the subjective items were also collected and correlated to the subjective scores. Twenty-eight runners were classified as aerial and 26 as terrestrial. Runner classification did not change with speed, but the relative contribution of the biomechanical parameters to the subjective classification was speed dependent. The magnitude of correlations between subjective and objective measures ranged from trivial to very large. Five of the seven objective parameters significantly differed between aerial and terrestrial runners, and these parameters demonstrated the strongest correlations to the subjective scores. Our results support the validity of the Volodalen® method, whereby the visual appreciation of running gait reflected quantifiable objective parameters. Two minor modifications to the method are proposed to simplify its use and improve agreement between subjective and objective measures.
Brain volumetric correlates of inhibition and cognitive flexibility 16 years following childhood traumatic brain injury

Executive functions (EFs), such as inhibition and cognitive flexibility, are essential for everyday functioning, including regulation of socially appropriate emotional responses. These skills develop during childhood and continue maturing into early adulthood. The current study aimed to investigate the very long‐term impact of childhood traumatic brain injury (TBI) on inhibition and cognitive flexibility, and to examine whether global white matter is associated with these abilities. Twenty‐eight young adult survivors of childhood TBI (mean age at 16‐year follow‐up = 21.67 years, SD = 2.70) and 16 typically developing controls (TDCs), group‐matched for age, sex, and socioeconomic status, completed tests of inhibition and cognitive flexibility and underwent structural MRI. Survivors of childhood TBI did not significantly differ from TDCs on EF or white matter volume. However, the relationship between EF and white matter volume differed between survivors of TBI and TDCs. Survivors of TBI did not mimic the brain behavior relationship that characterized EF in TDCs. The inverse brain behavior relationship, exhibited by childhood TBI survivors, suggests disruptions in the whole brain underpinning EF following childhood TBI.
Accurate prediction and elucidation of drug resistance based on the robust and reproducible chemoresponse communities

Selecting the available treatment for each cancer patient from genomic context is a core goal of precision medicine, but innovative approaches with mechanism interpretation and improved performance are still highly needed. Through utilizing in vitro chemotherapy response data coupled with gene and miRNA expression profiles, we applied a network‐based approach that identified markers not as individual molecules but as functional groups extracted from the integrated transcription factor and miRNA regulatory network. Based on the identified chemoresponse communities, the predictors of drug resistance achieved high accuracy in cross‐validation and were more robust and reproducible than conventional single‐molecule markers. Meanwhile, as candidate communities not only enriched abundant cellular process but also covered a variety of drug enzymes, transporters, and targets, these resulting chemoresponse communities furnished novel models to interpret multiple kinds of potential regulatory mechanism, such as dysregulation of cancer cell apoptosis or disturbance of drug metabolism. Moreover, compounds were linked based on the enrichment of their common chemoresponse communities to uncover undetected response patterns and possible multidrug resistance phenotype. Finally, an omnibus repository named ChemoCommunity (http://www.jianglab.cn/ChemoCommunity/) was constructed, which furnished a user‐friendly interface for a convenient retrieval of the detailed information on chemoresponse communities. Taken together, our method, and the accompanying database, improved the performance of classifiers for drug resistance and provided novel model to uncover the possible regulatory mechanism of individual response to drug.
Geochemistry of Muro Banded Iron-Formation, Central Nigeria

Muro Banded Iron-Formation occurs in the Proterozoic Toto Schist Belt, central Nigeria. It consists preponderantly of oxide facies and minor carbonate facies. The oxide facies is made up of alternating bands of quartz (metachert) with those of hematite + magnetite + martite ± goethite, chlorite, pyrrhotite and garnet. The carbonate facies consists of quartz (metachert) + siderite ± goethite. In the oxide facies the total iron content (Fe2O3t) ranges from 33.95% to 48.08% and the SiO2 content from 50.33% to 64.50%. In the case of the carbonate facies, the Fe2O3t content varies from 15.42% to 20.66% and SiO2 content from 66.84 to 72.86%. The Al2O3 content is generally low ranging from 0.1% to 0.54% in the oxide facies, and 0.24% to 0.31% in the carbonate facies. Chemically, the Muro Iron-Formation is similar to the Lake Superior-type iron-formations in terms of the distribution of the major and trace elements. This taken together with similarities in lithological associations indicates its deposition in similar environments i.e. shallow intra-continental or restricted/barred marine basin. The very low Al2O3 contents indicate minor clastic dilution of the original chemical precipitates.
Liver enzyme normalization predicts success of Hepatitis C oral direct-acting antiviral treatment.

PURPOSE Monitoring of hepatitis C virus (HCV) treatment response is performed by serial HCV RNA measurements; however, this may not be useful for predicting treatment success or failure with oral direct-acting antiviral agent (DAA) therapies. Liver enzyme levels, which are elevated in chronic HCV and tend to decline on therapy, may serve as a more logistically and economically feasible alternative for monitoring treatment response. SOURCE The Ottawa Hospital Viral Hepatitis Clinic patients (n=219), receiving interferon-free oral DAA treatments, were assessed for liver enzymes and HCV RNA levels at baseline, week 4 and ≥12 weeks post-treatment. Suppression cut points used for this analysis were ALT ≤ 40U L-1 and AST ≤ 30U L-1. The primary outcome was week 12 sustained virologic response (SVR). By our analysis, all indicators had strong PPV (>90%) but limited NPV (.
Pseudo almost periodic solutions for CNNs with oscillating leakage coefficients and complex deviating arguments

Abstract In this paper, cellular neural networks with oscillating leakage coefficients and complex deviating arguments are considered. Some criteria are established for the existence of pseudo almost periodic solutions for these models by using the contraction mapping fixed point theorem and inequality analysis technique. The results of this paper are new and complement the previously known ones.
Social-Aware Relay Selection for Device-to-Device Underlaying Cellular Networks

D2D relaying strategy is conceived as an attractive enhancement technique as the complement for D2D communication which can extend the communication range and further improve the system performance. Considering users' selfishness, we establish a new D2D cooperate relaying paradigm by leveraging two social factor: social tie and reputation. Tie strength with the source decides how much power can be provided by relay users. The cooperation probability modeled by the combination of reputation and social tie reflects the user's forwarding willingness. Then we propose two social- aware relay schemes considering the impact of social tie and reputation. Simulations results show that there is a trade-off between the cooperation probability and transmission rate of the potential relay user, the proposed schemes can greatly improve the performance in different cases.
Walking tolerance of patients recovering from hip fracture: a phase I trial

Abstract Purpose: To find out how much physical activity in the form of walking can be tolerated by adults admitted for inpatient rehabilitation after hip fracture. Method: Using a phase I dose–response design, in addition to usual scheduled rehabilitation care participants without cognitive impairment were supervised to walk for a prescribed length of time on 5 consecutive days. Doses started at 3 min and were escalated when three participants successfully completed a dose. Secondary outcomes included physical activity and the Ambulatory Self-Confidence Questionnaire (ASCQ). Results: The maximum tolerated dose of walking for the 13 participants (4 men and 9 women; mean age 81 years, SD 10) was 6 min. At 10 min only 1 of 5 participants was able to complete the dose. The main reason for not tolerating the prescribed dose was fatigue. Participants had relatively low levels of daily physical activity (mean 507 steps/day), and lacked confidence in their walking (ASCQ mean 4.6). Conclusion: Physical activity guidelines for older people are not appropriate for patients in active inpatient rehabilitation recovering from hip fracture where other factors such as fatigue may limit physical activity levels. These results can be taken into account when designing rehabilitation programmes after hip fracture. Implications for Rehabilitation Hip fracture is a common and serious fracture with ongoing disability for which people require inpatient rehabilitation to prepare for return to independent living in the community. The maximum tolerated dose of walking of 6 minutes suggests physical activity guidelines for older people are not applicable for those receiving active inpatient rehabilitation after hip fracture. The maximum tolerated dose of walking of 6 minutes during inpatient rehabilitation suggests rehabilitation programmes be structured to allow adequate time for recovery.
Whole‐exome sequencing identifies a novel mutation of GPD1L (R189X) associated with familial conduction disease and sudden death

Cardiac conduction disease (CCD) is a serious disorder and the leading cause of mortality worldwide. It is characterized by arrhythmia, syncope or even sudden cardiac death caused by the dysfunction of cardiac voltage‐gated channel. Previous study has demonstrated that mutations in genes encoding voltage‐gated channel and related proteins were the crucial genetic lesion of CCD. In this study, we employed whole‐exome sequencing to explore the potential causative genes in a Chinese family with ventricular tachycardia and syncope. A novel nonsense mutation (c.565C>T/p.R189X) of glycerol‐3‐phosphate dehydrogenase‐like (GPD1L) was identified and co‐segregated with the affected family members. GPD1L is a crucial interacting protein of SCN5A, a gene encoded sodium channel α‐subunit Nav1.5 and mainly associated with Brugada syndrome (BrS). The novel mutation (c.565C>T/p.R189X) may result in a premature stop codon at position 189 in exon 4 of the GPD1L gene and lead to functional haploinsufficiency of GPD1L due to mRNA carrying this mutation will be degraded by nonsense‐mediated mRNA decay, which has been confirmed by Western blot in HEK293 cells transfected HIS‐GPD1L plasmid. The levels of GPD1L decreasing may disturb the function of Nav1.5 and induce arrhythmia and syncope in the end. In conclusion, our study not only further supported the important role of GPD1L in CCD, but also expanded the spectrum of GPD1L mutations and will contribute to the genetic diagnosis and counselling of families with CCD.