Miracle-dz/UniFAR-FTUs huggingface dataset:
Co-Adaptive Control of Bionic Limbs via Unsupervised Adaptation of Muscle Synergies

Objective: In this work, we present a myoelectric interface that extracts natural motor synergies from multi-muscle signals and adapts in real-time with new user inputs. With this unsupervised adaptive myocontrol (UAM) system, optimal synergies for control are continuously co-adapted with changes in user motor control, or as a function of perturbed conditions via online non-negative matrix factorization guided by physiologically informed sparseness constraints in lieu of explicit data labelling. Methods: UAM was tested in a set of virtual target reaching tasks completed by able-bodied and amputee subjects. Tests were conducted under normative and electrode perturbed conditions to gauge control robustness with comparisons to non-adaptive and supervised adaptive myocontrol schemes. Furthermore, UAM was used to interface an amputee with a multi-functional powered hand prosthesis during standardized Clothespin Relocation Tests, also conducted in normative and perturbed conditions. Results: In virtual tests, UAM effectively mitigated performance degradation caused by electrode displacement, affording greater resilience over an existing supervised adaptive system for amputee subjects. Induced electrode shifts also had negligible effect on the real world control performance of UAM with consistent completion times (23.91$\pm$1.33 s) achieved across Clothespin Relocation Tests in the normative and electrode perturbed conditions. Conclusion: UAM affords comparable robustness improvements to existing supervised adaptive myocontrol interfaces whilst providing additional practical advantages for clinical deployment. Significance: The proposed system uniquely incorporates neuromuscular control principles with unsupervised online learning methods and presents a working example of a freely co-adaptive bionic interface.
Meta-Analyses of Reading Intervention Studies Including Students With Learning Disabilities: A Methodological Review

Learning disabilities (LD) may affect a range of academic skills but are most often observed in reading. Researchers and policymakers increasingly recommend addressing reading difficulties encountered by students with LD using evidence-based practices, or interventions validated through multiple, high-quality research studies. A valuable tool in identifying evidence-based practices is the meta-analysis, which entails statistically aggregating the results obtained through primary studies. Specific methods used in meta-analyses have the potential to influence their findings, with ramifications for research and practice. This review assessed the methodological features of the systematic reviews and analytic procedures featured in meta-analyses of reading intervention studies that included students with LD written between 2000 and 2020. Identified articles (N = 23) suggest that meta-analyses have become more prevalent and transparent over time, notwithstanding issues related to publication bias and the opacity of coding procedures. A discussion of implications follows a description of results.
Incorporating affect into the design of 1-d rotary physical controls

The visceral emotional reactions that users have to technologies is increasingly understood to be important in terms of safety, performance, and pleasure in its own right. This thesis systematically explores users's emotional (affect) reactions to everyday physical manual controls, in order to inform a design process that considers appropriate affective response as well as performance relationships. Design of both mechanical and emerging mechatronic physical controls are addressed. This novel design process includes parameterizing second order (inertial) dynamics using a system identification technique, and rendering models on a custom force-feedback knob. Next, this thesis explores biometric and self-reported measures of the affective responses elicited by these dynamics, and an iterative prototyping tool for rapid refinement of the "feel" of physical controls. This research impacts use of the passive physical interfaces such as mechanical knobs and sliders that are already ubiquitous in our everyday environments, as well as the active physical controls that are emerging in embedded computing environments such as cars, games, and medical devices.
Synergistic effect of the novel β-lactamase inhibitor BLI-489 combined with imipenem or meropenem against diverse carbapenemase-producing carbapenem-resistant Enterobacterales.

OBJECTIVES To investigate the antibacterial activity of the novel β-lactamase inhibitor BLI-489 combined with imipenem or meropenem against diverse carbapenemase-producing carbapenem-resistant Enterobacterales (CRE) in vivo and in vitro. METHODS Twenty-five CRE strains, including Klebsiella pneumoniae (n = 10), Escherichia coli (n = 6) and Enterobacter cloacae (n = 9), were used in chequerboard assays to evaluate the synergistic effect of BLI-489 combined with imipenem or meropenem. A cytotoxicity test was used to detect the toxicity of BLI-489 monotherapy or combination therapy. Three isolates producing class A, B and D carbapenemases, respectively, were selected to further confirm the synergistic effect in vitro by time-kill assays and in vivo by the Galleria mellonella infection model. RESULTS Chequerboard assays demonstrated that BLI-489 combined with imipenem had a synergistic effect on 7/10, 7/9 and 5/6 of carbapenem-resistant K. pneumoniae, E. cloacae and E. coli, respectively, while BLI-489 and meropenem had a synergistic effect on 8/10, 9/9 and 6/6 of the isolates, respectively. No cytotoxicity was observed when BLI-489 was used alone or in combination with imipenem or meropenem at the test concentrations. In the time-kill assays, combination therapy had a synergistic effect on DC5114 carrying blaKPC-2, FK8401 carrying blaNDM-5 and CG996 carrying blaOXA-23. The synergistic effect in vivo was confirmed by the G. mellonella infection model. CONCLUSIONS The novel β-lactamase inhibitor BLI-489 possesses a synergistic effect against diverse carbapenemase-producing CRE combined with imipenem or meropenem.
Biophysical Modeling of Dopaminergic Denervation Landscapes in the Striatum Reveals New Therapeutic Strategy

Abstract Parkinson’s disease (PD) results from a loss of dopaminergic neurons. What triggers the break-down of neuronal signaling, and how this might be compensated, is not understood. The age of onset, progression and symptoms vary between patients, and our understanding of the clinical variability remains incomplete. In this study, we investigate this, by characterizing the dopaminergic landscape in healthy and denervated striatum, using biophysical modeling. Based on currently proposed mechanisms, we model three distinct denervation patterns, and show how this affect the dopaminergic network. Depending on the denervation pattern, we show how local and global differences arise in the activity of striatal neurons. Finally, we use the mathematical formalism to suggest a cellular strategy for maintaining normal dopamine (DA) signaling following neuronal denervation. This strategy is characterized by dual enhancement of both the release and uptake capacity of DA in the remaining neurons. Overall, our results derive a new conceptual framework for the impaired dopaminergic signaling related to PD and offers testable predictions for future research directions.
NETMAGE: A human disease phenotype map generator for the network-based visualization of phenome-wide association study results

Abstract Background Disease complications, the onset of secondary phenotypes given a primary condition, can exacerbate the long-term severity of outcomes. However, the exact cause of many of these cross-phenotype associations is still unknown. One potential reason is shared genetic etiology—common genetic drivers may lead to the onset of multiple phenotypes. Disease-disease networks (DDNs), where nodes represent diseases and edges represent associations between diseases, can provide an intuitive way of understanding the relationships between phenotypes. Using summary statistics from a phenome-wide association study (PheWAS), we can generate a corresponding DDN where edges represent shared genetic variants between diseases. Such a network can help us analyze genetic associations across the diseasome, the landscape of all human diseases, and identify potential genetic influences for disease complications. Results To improve the ease of network-based analysis of shared genetic components across phenotypes, we developed the humaN disEase phenoType MAp GEnerator (NETMAGE), a web-based tool that produces interactive DDN visualizations from PheWAS summary statistics. Users can search the map by various attributes and select nodes to view related phenotypes, associated variants, and various network statistics. As a test case, we used NETMAGE to construct a network from UK BioBank (UKBB) PheWAS summary statistic data. Our map correctly displayed previously identified disease comorbidities from the UKBB and identified concentrations of hub diseases in the endocrine/metabolic and circulatory disease categories. By examining the associations between phenotypes in our map, we can identify potential genetic explanations for the relationships between diseases and better understand the underlying architecture of the human diseasome. Our tool thus provides researchers with a means to identify prospective genetic targets for drug design, using network medicine to contribute to the exploration of personalized medicine.
Gynephilic Men’s and Androphilic Women’s Visual Attention Patterns: The Effects of Gender and Sexual Activity Cues

ABSTRACT Men and women differ in the degree of specificity of sexual response and differences in attention to sexual cues may be a mechanism underlying these gendered patterns. The majority of previous research has examined attention using static images, which differ considerably from the dynamic videos used in studies of sexual response. To test attention as a potential mechanism involved in gendered sexual response, we used eye-tracking to examine visual attention patterns of 33 gynephilic men and 36 androphilic women to videos depicting preferred and nonpreferred gender targets engaging in varying sexual activities. Specificity of controlled attention was gendered, and this effect differed depending on the intensity of sexual activity cues depicted. Regardless of sexual activity cues, men’s controlled attention was gender-specific toward preferred targets. Sexual activity cues did, however, impact the degree to which women’s controlled attention was gender-specific. Specifically, women’s attention was gender-specific to low-intensity stimuli but nonspecific for masturbation and same-sex dyadic stimuli. Women’s attention was gender-specific for mixed-sex dyadic stimuli, but with greater attention directed toward nonpreferred gender targets. Overall, contextual cues impact women’s attention to a greater degree than men’s. Potential explanations for these findings and implications of stimulus selection for sexuality research are discussed.
Topological characterization of vortex structures on a transonic compressor stator during the stalling process

Numerical simulations, verified against experimental results, were used to study the stalling process of a transonic compressor. The method of topological analysis was used to study the distribution of the flow field on the blade surface in detail. In this manner, the steady three-dimensional vortex structure of the transonic compressor stator under transition conditions was established, and the mechanism of the stalling process was revealed from the perspective of the vortex structure evolution. The results show that in the process of stalling, as the back pressure increases, the separation areas on the suction side of the stator and the scale and strength of the separation vortex also increase, thereby weakening other vortices and causing a large amount of low-energy fluid to accumulate in the passage. Thus, the passage is blocked, and the through-flow capability of the compressor is reduced. In addition, because of the complex movement of the vortices and the transport of low-energy fluid clusters, the boosting capacity of the compressor is reduced, thus causing the compressor to stall.
Phosphorylation of MdERF17 by MdMPK4 promotes apple fruit peel degreening during light/dark transitions

Abstract As apple fruits (Malus domestica) mature, they accumulate anthocyanins concomitantly with losing chlorophyll (Chl); however, the molecular pathways and events that coordinate Chl degradation and fruit coloration have not been elucidated. We showed previously that the transcription factor ETHYLENE RESPONSE FACTOR17 (MdERF17) modulates Chl degradation in apple fruit peels and that variation in the pattern of MdERF17 serine (Ser) residues is responsible for differences in its transcriptional regulatory activity. Here, we report that MdERF17 interacts with and is phosphorylated by MAP KINASE4 (MdMPK4-14G). Phosphorylation of MdERF17 at residue Thr67 by MdMPK4-14G is necessary for its transcriptional regulatory activity and its regulation of Chl degradation. We also show that MdERF17 mutants with different numbers of Ser repeat insertions exhibit altered phosphorylation profiles, with more repeats increasing its interaction with MdMPK4. MdMPK4-14G can be activated by exposure to darkness and is involved in the dark-induced degreening of fruit peels. We also demonstrate that greater phosphorylation of MdERF17 by MdMPK4-14G is responsible for the regulation of Chl degradation during light/dark transitions. Overall, our findings reveal the mechanism by which MdMPK4 controls fruit peel coloration.
Translating stem cell research into development of cellular drugs—a perspective from manufacture of stem cell products and CMC considerations

The development of human pluripotent stem cell (PSC)‐derived medicinal products has been gathering steam in recent years, but the translation of research protocols into GMP production remains a daunting task. The challenges not only reside with the nature of cellular therapeutics but are also rooted in the general inexperience in industry‐scale production of stem cell products. Manufacturers of PSC‐derived products should be aware of the technical nuances and take a holistic approach toward early planning and engagement with their academic partners. While not all issues will be readily resolved soon, the collective knowledge and consensus by the manufacturers and key stakeholders will help to guide rapid progression of the field.
Neurotensin agonist PD 149163 modulates the neuroinflammation induced by bacterial endotoxin lipopolysaccharide in mice model

Abstract Objective The disruption of bidirectional communication between neuroendocrine and immune components by stressors leads to mental problems. The immunomodulation therapy of neuroinflammation-led psychiatric illness is an emerging area of research. Therefore, the present study aimed to evaluate immune modulation efficacy of PD 149163 (PD) against the lipopolysaccharide (LPS)-induced neuroinflammation. Materials and methods The Swiss albino mice (female/12 weeks) were divided into six groups (6 mice/group): (I) Control: 0.9% NaCl; (II) LPS: 1 mg/kg BW, for 5 days; (III) LPS + PD Low: LPS 1 mg/kg BW (for 5 days) after that PD 100 µg/kg BW (for 21 days); (IV) LPS + PD High: LPS 1 mg/kg BW (for 5 days) after that PD 300 µg/kg BW (for 21 days); (V) PD Low: PD 100 µg/kg BW (for 21 days); (VI) PD High: PD 300 µg/kg BW (for 21 days). All treatments were given intraperitoneal. Results The LPS-induced weight loss (body and brain) was normalized to control after PD treatment. The PD enhanced superoxide dismutase (SOD) activity while decreased lipid hydroperoxide (LOOH) level altered in LPS-exposed mice. The significantly increased pro-inflammatory cytokines (IL-6 and TNF-α) in LPS exposure were also decreased by PD. Likewise, the LPS-induced HPA axis activation was stabilized by PD. In the hippocampus, the pyramidal cell layer thickness, pyramidal neurons number and size of CA1 and CA3 regions were reduced along with misalignment, shrinkage, and impairment of cytoarchitecture. In the co-treated group, the LPS-induced hippocampus disruption was reversed after PD exposure. Conclusion We suggested that the PD modulates the LPS-induced neuroinflammation and psychiatric illness in a dose-dependent manner.
Artificial intelligence and suicide prevention: A systematic review

Abstract Background Suicide is one of the main preventable causes of death. Artificial intelligence (AI) could improve methods for assessing suicide risk. The objective of this review is to assess the potential of AI in identifying patients who are at risk of attempting suicide. Methods A systematic review of the literature was conducted on PubMed, EMBASE, and SCOPUS databases, using relevant keywords. Results Thanks to this research, 296 studies were identified. Seventeen studies, published between 2014 and 2020 and matching inclusion criteria, were selected as relevant. Included studies aimed at predicting individual suicide risk or identifying at-risk individuals in a specific population. The AI performance was overall good, although variable across different algorithms and application settings. Conclusions AI appears to have a high potential for identifying patients at risk of suicide. The precise use of these algorithms in clinical situations, as well as the ethical issues it raises, remain to be clarified.
Willingness to Engage in Collective Action After the Police Killing of an Unarmed Black Man: Differential Pathways for Black and White Individuals

Abstract This cross‐sectional survey study examined the underlying psychosocial constructs of Black (n = 163) and White (n = 246) university students' willingness to endorse racially motivated collective action. Consistent with the defensive motivation system model, we expected the police shooting of an unarmed Black American to activate concerns about personal safety, thereby eliciting negative affect, lack of forgiveness of the perpetrator, and motivation to engage in collective action. This path model was expected for both Black and White participants, with stronger associations among Black participants. In the full model, Black participants identified more with the victim and indicated greater personal threat, which led to (1) more negative affect and greater endorsement of collective action and (2) greater avoidance of the shooter and greater endorsement of collective action. In the Black participants model, collective action was explained by identifying with the victim and feeling personally threatened. In the White participants model, collective action was explained by three pathways stemming from identifying with the victim and personal threat, including negative affect, seeking avoidance, and seeking revenge. The results indicate different mechanisms to explain Black and White individuals' motivation to endorse collective action to prevent police‐involved shootings of unarmed Black Americans.
음장 시뮬레이션에 의한 특정 판소리 홀의 음향평가 ( Acoustic Estimation of a Specific PANSORI Hall by the Sound Field Simulation Technique )

한국 민속음악 중의 하나인 판소리는 거의 야외에서 공연되었으나, 현재는 실내에서 공연되는 경우가 더 많 아졌다. 따라서, 판소리가 실내에서 공연되는 경우, 이 판소리가 실내에서는 어떤 청감적 인상을 나타내는지 를 검토하기 위해 몇개의 평정척도표(울림의 길이, 명료도, 전체적 인상등)를 정하여 청감심리평가를 하였다. 본 청감심리평가의 분석결과 울림길이의 경우 판소리는 잔향시간이 0. 6초에서 0.8초의 범위가, 명료도는 0.8 초 전후가, 인상은 1. 0초~1. 2초의 범위가 좋은 홀의 조건으로서 제안할 수가 있게 되었다. 따라서, 판소리의 경우 공연중에 흔히 튀어나오는 `아니리'의 연행이 잘 되게 하기 위해서는 잔향시간이 짧은 쪽의 홀이 좋은 명료도를 갖기 때문에, 잔향시간은 될 수 있는대로, 짧은 쪽이 바람직하다는 것을 알게 되었 다. 또한, 이번의 실험에 의해 임펄스 응답으로 부터는 실내의 음향적 물리량뿐만 아니라 여러가지 청감평가를 위한 시험음을 만들 수 있기 때문에, 이 음향적 신호처리기술의 응용은 실내음향설계에 있어서 매우 유효한 도구로 사용할 수 있다는 것이 검증되었다.
Hexavalent chromium induces hepatocyte apoptosis via regulation of apoptosis signal‐regulating kinase 1/c‐Jun amino‐terminal kinase signaling

With the spread of hexavalent chromium (Cr(VI)) contamination, Cr(VI)‐induced hepatotoxicity has attracted increasing attention in recent years. To date, however, the exact mechanism of Cr(VI) toxicity remains unclear. In this study, we investigated the role of apoptosis signal‐regulating kinase 1 (ASK1)/c‐Jun amino‐terminal kinase (JNK) in Cr(VI)‐induced hepatic toxicity and the possible related mechanisms. AML‐12 hepatocyte cell‐lines were treated with 0, 1, 4, and 16 μmol/Lof Cr(VI) with or without GS‐444271 (an ASK1 inhibitor). Adult male mice were administered with 0, 2, 8, and 32 mg/kg body mass (BM)/day of Cr(VI) for 5 days. The level of hepatocyte apoptosis/proliferation, generation of reactive oxygen species (ROS), and expression levels of mRNAs and proteins related to ASK1/JNK and nuclear factor‐E2‐related factor 2 (Nrf2) signaling were assessed. Results showed that high Cr(VI) exposure induced hepatocyte apoptosis and liver injury by generation of ROS and down‐regulation of Nrf2 signaling. In addition, ASK1/JNK signaling activity was upregulated in the Cr(VI)‐treated group. Furthermore, GS‐444217 treatment significantly rescued Cr(VI)‐induced hepatocyte apoptosis and liver dysfunction in vitro and in vivo by down‐regulation of ASK1/JNK signaling. Thus, ASK1/JNK signaling appears to play an important role in Cr(VI)‐induced hepatocyte apoptosis and liver injury. This study should help improve our understanding of the mechanism of Cr(VI)‐induced liver injury and provide support for future investigations on liver disease therapy.
A critical review of the kinetic direct peptide reactivity assay (kDPRA) for skin sensitizer potency assessment – taking it forward

Abstract It is widely recognized that the ability of chemicals to sensitize, and the potency of those chemicals that are sensitizers, is related to their ability to covalently modify protein in the skin. With the object of putting non-animal-based prediction of skin sensitization on a more quantitative footing, a recent paper describes the development of the kinetic Direct Protein Reactivity Assay (kDPRA), in which a matrix of peptide depletion values for different reaction times and test chemical concentrations is generated and analyzed so as to derive a reactivity parameter, logk max, which is used to classify chemicals into one of two potency categories. The present paper demonstrates that the reaction chemistry is not always consistent with the mathematical analysis of the data matrix and the kDPRA protocol does not identify such cases. Consequently the derived logk max value is not always mechanistically meaningful and its application to predict potency can lead to misleading conclusions. It is shown that by adopting a data analysis protocol based on conventional kinetics practice, the kDPRA can be made to provide more reliably meaningful and more extensive information that can be used for purposes such as potency estimation for deriving No Expected Sensitization Induction Level (NESILs) required for quantitative risk assessment (QRA), deriving quality specifications in terms of acceptable impurity levels, and development of structure-activity relationships. Secondly, the paper addresses applicability domain issues, in particular the problem of deciding whether or not the kDPRA is applicable for a given chemical.