Miracle-dz/UniFAR-FTUs huggingface dataset:
Tangent Space Features-Based Transfer Learning Classification Model for Two-Class Motor Imagery Brain-Computer Interface

The performance of a brain-computer interface (BCI) will generally improve by increasing the volume of training data on which it is trained. However, a classifier's generalization ability is often negatively affected when highly non-stationary data are collected across both sessions and subjects. The aim of this work is to reduce the long calibration time in BCI systems by proposing a transfer learning model which can be used for evaluating unseen single trials for a subject without the need for training session data. A method is proposed which combines a generalization of the previously proposed subject-specific "multivariate empirical-mode decomposition" preprocessing technique by taking a fixed band of 8-30Hz for all four motor imagery tasks and a novel classification model which exploits the structure of tangent space features drawn from the Riemannian geometry framework, that is shared among the training data of multiple sessions and subjects. Results demonstrate comparable performance improvement across multiple subjects without subject-specific calibration, when compared with other state-of-the-art techniques.
Development and External Validation of a mpMRI- and ISUP-Based Add-on Prediction Tool to Identity Prostate Cancer Candidates for Pelvic Lymph Node Dissection.

PURPOSE To expand the current prediction tools for lymph node invasion (LNI) in prostate cancer (PCa) patients with today's state-of-the-art available tumor information, including multiparametric MRI (mpMRI)-based tumor (T) staging and detailed biopsy information. MATERIALS AND METHODS PCa patients with registered ISUP-based biopsy information and mpMRI information, who underwent a radical prostatectomy with extended pelvic LN dissection, were selected. A LNI prediction tool was developed in 420 patients and externally validated in 187 patients. A concordance index was estimated to quantify the discriminative performance of the model. RESULTS In the development cohort, a median of 21 LN was removed per patient. Seventy one patients (16.9%) were diagnosed with LNI. Statistically significant predictors of LNI were the iPSA value, mpMRI-based T-stage, maximum tumor-length-in-one-core (mm) and ISUP grade group corresponding to the maximum tumor-involvement-in-one-core. The predictive accuracy of this LNI prediction tool was 79.7% after 5-fold internal cross validation and 72.5% at external validation. CONCLUSIONS We report a contemporary, externally validated prediction tool for the presence of LNI in PCa patients. This prediction tool answers to the paradigm shift from systematic biopsies towards targeted biopsies by incorporating additional core-specific biopsy information instead of the percentage of positive cores. This new tool will also overcome stage migration, which is a potential risk when mpMRI information is used in digital rectal exam based nomograms.
Robots and Tools for Remodeling Bone

The field of robotic surgery has progressed from small teams of researchers repurposing industrial robots, to a competitive and highly innovative subsection of the medical device industry. Surgical robots allow surgeons to perform tasks with greater ease, accuracy, or safety, and fall under one of four levels of autonomy; active, semi-active, passive, and remote manipulator. The increased accuracy afforded by surgical robots has allowed for cementless hip arthroplasty, improved postoperative alignment following knee arthroplasty, and reduced duration of intraoperative fluoroscopy among other benefits. Cutting of bone has historically used tools such as hand saws and drills, with other elaborate cutting tools now used routinely to remodel bone. Improvements in cutting accuracy and additional options for safety and monitoring during surgery give robotic surgeries some advantages over conventional techniques. This article aims to provide an overview of current robots and tools with a common target tissue of bone, proposes a new process for defining the level of autonomy for a surgical robot, and examines future directions in robotic surgery.
Intertwined metal homeostasis, oxidative and biotic stress responses in the Arabidopsis frd3 mutant.

FRD3 (FERRIC REDUCTASE DEFECTIVE 3) plays a major role in iron (Fe) and zinc (Zn) homeostasis in Arabidopsis. It transports citrate, which enables metal distribution in the plant. A frd3 mutant is dwarf and chlorotic and displays constitutive Fe deficiency response and strongly altered metal distribution in tissues. Here, we have examined the interaction between Fe and Zn homeostasis in a frd3 mutant exposed to varying Zn supply. Detailed phenotyping using transcriptomic, ionomic, histochemical and spectroscopic approaches revealed the full complexity of the frd3 mutant phenotype, which resulted from altered transition metal homeostasis, manganese toxicity, oxidative and biotic stress responses. The cell wall played a key role in these processes, as a site for Fe and hydrogen peroxide accumulation, and displayed modified structure in the mutant. Finally, we showed that Zn excess interfered with these mechanisms and partially restored root growth of the mutant, without reverting the Fe deficiency response. In conclusion, the frd3 mutant molecular phenotype is more complex than previously described, and illustrates how the response to metal imbalance depends on multiple signaling pathways.
Comparative Proteomic Analysis Reveals Key Proteins Linked to the Accumulation of Soluble Sugars and Organic Acids in the Mature Fruits of the Wild Malus Species

Soluble sugars and organic acids are the main determinants of fruit organoleptic quality. To investigate the genes responsible for the soluble sugar and organic acid contents of apple fruits, a label-free proteomic analysis involving liquid chromatography (LC)-mass spectrometry (MS)/MS was conducted with the fruits of two Malus species, M. sargentii and M. niedzwetzkyana, which exhibit significant differences in soluble sugar and organic acid contents. A total of 13,036 unique peptides and 1,079 differentially-expressed proteins were identified. To verify the LC-MS/MS results, five candidate proteins were further analyzed by parallel reaction monitoring. The results were consistent with the LC-MS/MS data, which confirmed the reliability of the LC-MS/MS analysis. The functional annotation of the differentially-expressed proteins, based on the gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, revealed that they were mainly related to biological processes and cellular components. Additionally, the main enriched KEGG pathways were related to metabolic processes. Moreover, 31 proteins involved in soluble sugar metabolism, organic acid metabolism, and H+-transport were identified. The results of this study may be useful for the comprehensive characterization of the complex mechanism regulating apple fruit-soluble sugar and organic acid contents.
Clostridium perfringens epsilon toxin induces blood brain barrier permeability via caveolae-dependent transcytosis and requires expression of MAL

Clostridium perfringens epsilon toxin (ETX) is responsible for causing the economically devastating disease, enterotoxaemia, in livestock. It is well accepted that ETX causes blood brain barrier (BBB) permeability, however the mechanisms involved in this process are not well understood. Using in vivo and in vitro methods, we determined that ETX causes BBB permeability in mice by increasing caveolae-dependent transcytosis in brain endothelial cells. When mice are intravenously injected with ETX, robust ETX binding is observed in the microvasculature of the central nervous system (CNS) with limited to no binding observed in the vasculature of peripheral organs, indicating that ETX specifically targets CNS endothelial cells. ETX binding to CNS microvasculature is dependent on MAL expression, as ETX binding to CNS microvasculature of MAL-deficient mice was not detected. ETX treatment also induces extravasation of molecular tracers including 376Da fluorescein salt, 60kDA serum albumin, 70kDa dextran, and 155kDA IgG. Importantly, ETX-induced BBB permeability requires expression of both MAL and caveolin-1, as mice deficient in MAL or caveolin-1 did not exhibit ETX-induced BBB permeability. Examination of primary murine brain endothelial cells revealed an increase in caveolae in ETX-treated cells, resulting in dynamin and lipid raft-dependent vacuolation without cell death. ETX-treatment also results in a rapid loss of EEA1 positive early endosomes and accumulation of large, RAB7-positive late endosomes and multivesicular bodies. Based on these results, we hypothesize that ETX binds to MAL on the apical surface of brain endothelial cells, causing recruitment of caveolin-1, triggering caveolae formation and internalization. Internalized caveolae fuse with early endosomes which traffic to late endosomes and multivesicular bodies. We believe that these multivesicular bodies fuse basally, releasing their contents into the brain parenchyma.
AZD4573 Is a Highly Selective CDK9 Inhibitor That Suppresses MCL-1 and Induces Apoptosis in Hematologic Cancer Cells

Purpose: Cyclin-dependent kinase 9 (CDK9) is a transcriptional regulator and potential therapeutic target for many cancers. Multiple nonselective CDK9 inhibitors have progressed clinically but were limited by a narrow therapeutic window. This work describes a novel, potent, and highly selective CDK9 inhibitor, AZD4573. Experimental Design: The antitumor activity of AZD4573 was determined across broad cancer cell line panels in vitro as well as cell line- and patient-derived xenograft models in vivo. Multiple approaches, including integrated transcriptomic and proteomic analyses, loss-of-function pathway interrogation, and pharmacologic comparisons, were employed to further understand the major mechanism driving AZD4573 activity and to establish an exposure/effect relationship. Results: AZD4573 is a highly selective and potent CDK9 inhibitor. It demonstrated rapid induction of apoptosis and subsequent cell death broadly across hematologic cancer models in vitro, and MCL-1 depletion in a dose- and time-dependent manner was identified as a major mechanism through which AZD4573 induces cell death in tumor cells. This pharmacodynamic (PD) response was also observed in vivo, which led to regressions in both subcutaneous tumor xenografts and disseminated models at tolerated doses both as monotherapy or in combination with venetoclax. This understanding of the mechanism, exposure, and antitumor activity of AZD4573 facilitated development of a robust pharmacokinetic/PD/efficacy model used to inform the clinical trial design. Conclusions: Selective targeting of CDK9 enables the indirect inhibition of MCL-1, providing a therapeutic option for MCL-1–dependent diseases. Accordingly, AZD4573 is currently being evaluated in a phase I clinical trial for patients with hematologic malignancies (clinicaltrials.gov identifier: NCT03263637). See related commentary by Alcon et al., p. 761
Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH

Non-alcoholic fatty liver diseases (NAFLD) including the severe form with steatohepatitis (NASH) are highly prevalent ailments to which no approved pharmacological treatment exists. Dietary intervention aiming at 10% weight reduction is efficient but fails due to low compliance. Increase in physical activity is an alternative that improved NAFLD even in the absence of weight reduction. The underlying mechanisms are unclear and cannot be studied in humans. Here, a rat NAFLD model was developed that reproduces many facets of the diet-induced NAFLD in humans. The impact of endurance exercise was studied in this model. Male Wistar rats received control chow or a NASH-inducing diet rich in fat, cholesterol, and fructose. Both diet groups were subdivided into a sedentary and an endurance exercise group. Animals receiving the NASH-inducing diet gained more body weight, got glucose intolerant and developed a liver pathology with steatosis, hepatocyte hypertrophy, inflammation and fibrosis typical of NAFLD or NASH. Contrary to expectations, endurance exercise did not improve the NASH activity score and even enhanced hepatic inflammation. However, endurance exercise attenuated the hepatic cholesterol overload and the ensuing severe oxidative stress. In addition, exercise improved glucose tolerance possibly in part by induction of hepatic FGF21 production.
Translating the Chronic Disease Self-Management Program for Community-Dwelling Adults With Developmental Disabilities

Objective: The study was to test the feasibility of supplementary materials (DD-CDSMP) supporting people with developmental disabilities who are aging to participate in the Chronic Disease Self-Management Program (CDSMP). CDSMP is a six-session group intervention designed to increase self-management of chronic health conditions. Method: Supplementary materials were utilized within two CDSMP workshops. Each workshop involved seven to nine persons with developmental disabilities and five to seven staff. Supplementary materials to the existing intervention manual were reviewed using a framework for modifications and adaptions for evidence-based interventions. Process interviews with leaders and participants, pre- and posttests on self-management activity and satisfaction surveys assessed outcomes and feasibility. Results: Classes were successfully held with a 70% completer rate, and all materials proved useful. Discussion: People with developmental disabilities as they age tend to have more comorbid conditions than the general population. Developing and implementing materials and strategies to making self-management more accessible to people with developmental disabilities in mainstream rather than segregated settings will improve the quality of people’s lives.
Systematic Analysis of Alkaline/Neutral Invertase Genes Reveals the Involvement of Smi-miR399 in Regulation of SmNINV3 and SmNINV4 in Salvia miltiorrhiza

Alkaline/neutral invertases (NINVs), which irreversibly catalyze the hydrolysis of sucrose into fructose and glucose, play crucial roles in carbohydrate metabolism and plant development. Comprehensive insights into NINV genes are lacking in Salvia miltiorrhiza, a well-known traditional Chinese medicinal (TCM) plant with significant medicinal and economic value. Through genome-wide prediction, nine putative SmNINV genes, termed SmNINV1-SmNINV9, were identified. Integrated analysis of gene structures, sequence features, conserved domains, conserved motifs and phylogenetic trees revealed the conservation and divergence of SmNINVs. The identified SmNINVs were differentially expressed in roots, stems, leaves, flowers, and different root tissues. They also responded to drought, salicylic acid, yeast extract, and methyl jasmonate treatments. More importantly, computational prediction and experimental validation showed that SmNINV3 and SmNINV4 were targets of Smi-miR399, a conserved miRNA previously shown to affect Pi uptake and translocation through the cleavage of PHOSPHATE2 (PHO2). Consistently, analysis of 43 NINV genes and 26 miR399 sequences from Arabidopsis thaliana, Populus trichocarpa, Manihot esculenta, and Solanum lycopersicum showed that various AtNINV, PtNINV, MeNINV, and SlNINV genes were regulated by miR399. It indicates that the miR399-NINV module exists widely in plants. Furthermore, Smi-miR399 also cleaved SmPHO2 transcripts in S. miltiorrhiza, suggesting the complexity of NINVs, PHO2, and miR399 networks.
Scleroderma Patient-centered Intervention Network—Scleroderma Support group Leader EDucation (SPIN-SSLED) program: non-randomised feasibility trial

Objectives The Scleroderma Patient-centered Intervention Network—Scleroderma Support group Leader EDucation (SPIN-SSLED) Programme was designed to improve confidence and self-efficacy and to reduce burden for support group leaders. Objectives were to (1) evaluate feasibility of programme delivery, including required resources, management issues and scientific aspects (eg, performance of outcome measures) and (2) assess user satisfaction and identify any modifications needed to improve programme content or delivery based on participant feedback. Design Non-randomised feasibility trial. Setting North American patient organisations. Participants Current support group leaders or potential new leaders referred by patient organisations. Intervention The programme included 13 modules delivered live via videoconference over 3 months (April to July 2018) in 60 to 90 min sessions. Outcome measures (1) Elements of feasibility, including enrolment and consent procedures, percentage of referred group leaders who consented to participate, session attendance and technical support requirements; (2) programme usability, understandability, organisation and clarity; (3) leader satisfaction with the programme and (4) planned trial outcome measures, including support group leader self-efficacy, burnout, emotional distress and physical function. Results All 12 referred potential participants consented to enrol, and 10 were included in two training groups of five participants each. Participants attended 95% of sessions. Required technical support was minimal, and videoconferencing technology functioned well. Overall programme satisfaction rating was 9.4/10. Mean item rating on the eight items of the Client Satisfaction Questionnaire-8 was 3.83 (1=low satisfaction; 4=high satisfaction). Pre-post scores on the Scleroderma Support Group Leader Self-efficacy Scale increased by 1.7 SDs (large effect); scores on burnout, emotional distress and physical function improved by 0.44, 0.38 and 0.45 SDs (moderate effects). Conclusion The SPIN-SSLED Programme was feasibly delivered, including management, resource and scientific aspects. Participant satisfaction was high. The programme is ready to be tested in a full-scale randomised controlled trial. Trial registration number NCT03508661
Investigation of a Ventilation System for Energy Efficiency and Indoor Environmental Quality in a Renovated Historical Building: A Case Study

This paper emphasizes the importance of environmental protection regarding the reduction of energy consumption while maintaining living standards. The aim of the research is to observe the effects of mechanical and natural ventilation on energy consumption and building operation as well as indoor environmental quality (IEQ). The results of indoor environmental quality testing show that the mean relative humidity (31%) is in the permissible range (30%–70%); the mean CO2 concentration (1050.5 ppm) is above the recommended value of 1000 ppm according to Pettenkofer; and the mean PM10 concentration (43.5 µg/m3) is under the limit value of 50 µg/m3. A very large positive correlation is found between relative humidity and concentration of CO2 as well as between the concentration of PM5 and the concentration of CO2. The most commonly occurring sick building syndrome (SBS) symptoms are found to be fatigue and the feeling of a heavy head.
The Acetate Pathway Supports Flavonoid and Lipid Biosynthesis in Arabidopsis1[OPEN]

The Arabidopsis acetate or polyketide pathway operates at the interface of central and lipid metabolism as well as supporting the much better studied phenylpropanoid pathway of flavonoid biosynthesis. The phenylpropanoid pathway of flavonoid biosynthesis has been the subject of considerable research attention. By contrast, the proposed polyketide pathway, also known as the acetate pathway, which provides malonyl-CoA moieties for the C2 elongation reaction catalyzed by chalcone synthase, is less well studied. Here, we identified four genes as candidates for involvement in the supply of cytosolic malonyl-CoA from the catabolism of acyl-CoA, based on coexpression analysis with other flavonoid-related genes. Two of these genes, ACC and KAT5, have been previously characterized with respect to their involvement in lipid metabolism, but no information concerning their relationship to flavonoid biosynthesis is available. To assess the occurrence and importance of the acetate pathway, we characterized the metabolomes of two mutant or transgenic Arabidopsis lines for each of the four enzymes of this putative pathway using a hierarchical approach covering primary and secondary metabolites as well as lipids. Intriguingly, not only flavonoid content but also glucosinolate content was altered in lines deficient in the acetate pathway, as were levels of lipids and most primary metabolites. We discuss these data in the context of our current understanding of flavonoids and lipid metabolism as well as with regard to improving human nutrition.
The other student debt crisis: How borrowing to pay for a child's college education relates to parents' mental health at mid-life.

OBJECTIVES More parents are borrowing to help their children pay for college. These loans may be a source of financial stress and worry, which could influence parents' mental health. We determine whether child-related educational debt is associated with worse mental health among parents and if fathers are more sensitive to this debt than mothers, given potential gender differences in financial decision-making and relationships with adult children. METHOD Data come from the National Longitudinal Survey of Youth 1979, a nationally representative sample of persons born between 1957 and 1964. We used the Center for Epidemiologic Studies Depression Scale and the Short Form-12 Mental Health Component Score to assess mental health. We restricted our sample to parents who had at least one biological child attend college and who were interviewed at age 50, when mental health was assessed (n=3,545). RESULTS Among fathers, having any child-related educational debt versus none was associated with fewer depressive symptoms, but having greater amounts of child-related educational debt was associated with more depressive symptoms and worse mental health. No relationship was found for mothers.
Robust Transmit Antenna Design for Performance Improvement of Cell-Edge Users: Approach of NOMA and Outage/Ergodic Capacity Analysis

In this investigation, a wireless sensor network using a non-orthogonal multiple access (NOMA) system is considered in two scenarios related to the number of serving access point/base stations, where two policies provide system performance improvement in two sensors (the near user and the far user). To improve performance efficiency, two robust transmit antenna strategies are designed related to the access point/base station (BS), namely (i) Transmit Antenna Selection (TAS) mode and (ii) two base station (TBS) approach to simultaneously serve NOMA users. First, the TAS scheme is implemented to provide suboptimal outage performance for such NOMA, in which BS equipped at least two antennas while NOMA users are equippeda single antenna. Secondly, the TBS scheme is conducted to enhance the outage performance, especially considering priority evaluation for the far user in user pairs. As an important result, such far users in two proposed schemes are studied by introducing the exact closed-form expression to examine outage behavior. Accordingly, the closed-form expressions regarding ergodic capacity can be further obtained. To corroborate the exactness of these metrics, Monte Carlo simulation is performed. In addition, the proposed schemes exhibit various performance evaluations accompanied by different related parameters such as power allocation factors, the number of transmit antenna, and transmit signal-to-noise ratio (SNR).