Miracle-dz/UniFAR-FTUs huggingface dataset:
Less is more: Removing a modality of an expected olfactory‐visual stimulation enhances brain activation

In recent years, multisensory integration of visual and olfactory stimuli has extensively been explored resulting in the identification of responsible brain areas. As the experimental designs of previous research often include alternating presentations of unimodal and bimodal stimuli, the conditions cannot be regarded as completely independent. This could lead to effects of an expected but surprisingly missing sensory modality. In our experiment, we used a common functional magnetic resonance imaging (fMRI) study design with alternating strong unimodal and bimodal olfactory‐visual food stimuli, in addition to a slight overhang of the bimodal stimuli in an effort to examine the effects of removing a visual or olfactory congruent stimulus for older people (41–83 years). Our results suggest that the processing of olfactory and visual stimuli stays intact over a wide age‐range and that the utilization of strong stimuli does not lead to superadditive multisensory integration in accordance with the principle of inverse effectiveness. However, our results demonstrate that the removal of a stimulus modality leads to an activation of additional brain areas. For example, when the visual stimulus modality is missing, the right posterior superior temporal gyrus shows higher activation, whereas the removal of the olfactory stimulus modality leads to higher activation in the amygdala/hippocampus and the postcentral gyrus. These brain areas are related to attention, memory, and the search of the missing stimulus. Consequently, careful attention must be paid to the design of a valid, multimodal sensory experiment while also controlling for cognitive expectancy effects that might confound multimodal results.
Multicenter Evaluation of the Acuitas AMR Gene Panel for Detection of an Extended Panel of Antimicrobial Resistance Genes among Bacterial Isolates

The Acuitas antimicrobial resistance (AMR) gene panel is a qualitative, multiplex, nucleic acid‐based in vitro diagnostic test for the detection and differentiation of 28 antimicrobial resistance markers associated with not susceptible results (NS; i.e., intermediate or resistant) to one or more antimicrobial agents among cultured isolates of select Enterobacterales, Pseudomonas aeruginosa, and Enterococcus faecalis. This study was conducted at four sites and included testing of 1,224 deidentified stocks created from 584 retrospectively collected isolates and 83 prospectively collected clinical isolates. ABSTRACT The Acuitas antimicrobial resistance (AMR) gene panel is a qualitative, multiplex, nucleic acid‐based in vitro diagnostic test for the detection and differentiation of 28 antimicrobial resistance markers associated with not susceptible results (NS; i.e., intermediate or resistant) to one or more antimicrobial agents among cultured isolates of select Enterobacterales, Pseudomonas aeruginosa, and Enterococcus faecalis. This study was conducted at four sites and included testing of 1,224 deidentified stocks created from 584 retrospectively collected isolates and 83 prospectively collected clinical isolates. The Acuitas results were compared with a combined reference standard including whole-genome sequencing, organism identification, and phenotypic antimicrobial susceptibility testing. The positive percent agreement (PPA) for FDA-cleared AMR targets ranged from 94.4% for MCR-1 to 100% for armA, CTX-M-2, DHA, IMP, OXA-9, SHV, vanA, and VEB. The negative percent agreement (NPA) for the majority of targets was ≥99%, except for AAC, AAD, CMY-41, P. aeruginosa gyrA mutant, Sul1, Sul2, and TEM targets (range, 96.5% to 98.5%). Three AMR markers did not meet FDA inclusion criteria (GES, SPM, and MCR-2). For each organism, 1 to 22 AMR targets met the minimum reportable PPA/NPA and correlated with ≥80% positive predictive value with associated NS results for at least one agent (i.e., the probability of an organism carrying an AMR marker testing NS to the associated agent). We demonstrate that the Acuitas AMR gene panel is an accurate method to detect a broad array of AMR markers among cultured isolates. The AMR markers were further associated with expected NS results for specific agent-organism combinations.
The brain state of motor imagery is reflected in the causal information of functional near-infrared spectroscopy

Supplemental Digital Content is available in the text. Background Brain–computer interface (BCI) is a promising neurorehabilitation strategy for ameliorating post-stroke function disorders. Physiological changes in the brain, such as functional near-infrared spectroscopy (fNIRS) dedicated to exploring cerebral circulatory responses during neurological rehabilitation tasks, are essential for gaining insights into neurorehabilitation mechanisms. However, the relationship between the neurovascular responses in different brain regions under rehabilitation tasks remains unknown. Objective The present study explores the fNIRS interactions between brain regions under different motor imagery (MI) tasks, emphasizing functional characteristics of brain network patterns and BCI motor task classification. Methods Granger causality analysis (GCA) is carried out for oxyhemoglobin data from 29 study participants in left- and right-hand MI tasks. Results According to research findings, homozygous and heterozygous states in the two brain connectivity modes reveal one and nine channel pairs, respectively, with significantly different (P < 0.05) GC values under the left- and right-hand MI tasks in the population. With reference to the total 10 channel pairs of causality differences between the two brain working states, a support vector machine is used to classify the two tasks with an overall accuracy of 83% for five-fold cross-validation. Conclusion As demonstrated in the present study, fNIRS offers causality patterns in different brain states of MIBCI motor tasks. The research findings show that fNIRS causality can be used to assess different states of the brain, providing theoretical support for its application to neurorehabilitation assessment protocols to ultimately improve patients’ quality of life. Video Abstract: http://links.lww. com/WNR/A653.
Standardized Integration of Person-Generated Data Into Routine Clinical Care

Person-generated data (PGD) are a valuable source of information on a person’s health state in daily life and in between clinic visits. To fully extract value from PGD, health care organizations must be able to smoothly integrate data from PGD devices into routine clinical workflows. Ideally, to enhance efficiency and flexibility, such integrations should follow reusable processes that can easily be replicated for multiple devices and data types. Instead, current PGD integrations tend to be one-off efforts entailing high costs to build and maintain custom connections with each device and their proprietary data formats. This viewpoint paper formulates the integration of PGD into clinical systems and workflow as a PGD integration pipeline and reviews the functional components of such a pipeline. A PGD integration pipeline includes PGD acquisition, aggregation, and consumption. Acquisition is the person-facing component that includes both technical (eg, sensors, smartphone apps) and policy components (eg, informed consent). Aggregation pools, standardizes, and structures data into formats that can be used in health care settings such as within electronic health record–based workflows. PGD consumption is wide-ranging, by different solutions in different care settings (inpatient, outpatient, consumer health) for different types of users (clinicians, patients). The adoption of data and metadata standards, such as those from IEEE and Open mHealth, would facilitate aggregation and enable broader consumption. We illustrate the benefits of a standards-based integration pipeline for the illustrative use case of home blood pressure monitoring. A standards-based PGD integration pipeline can flexibly streamline the clinical use of PGD while accommodating the complexity, scale, and rapid evolution of today’s health care systems.
Nurses' awareness and adherence with national ethical guidelines for research in North India

Background: A large number of nurse researchers do not adhere to ethical standards while performing the research. Moreover, there is far less data on knowledge of existing national ethical guidelines. This study was, therefore, done to assess awareness and adherence to current national ethical guidelines among nursing students and faculty members. Methods: A cross-sectional descriptive study was done among nursing faculty members and theses carried out by postgraduate nursing students between 2012 and 2017. Using the convenience sampling technique, seven states of North India were selected. In each of the selected seven states, one government and one private nursing college was selected. Thus, a sample of 14 nursing colleges was selected. Then, using simple random sampling, a total of 140 nursing faculty members and 280 postgraduate nursing theses were selected from all the chosen institutes to be part of the study. Data analysis was done using descriptive statistics. Ethical considerations: The study has been approved by the institutional ethical committee (ECR/737/Inst/UK/2018/RR-18). In addition, written permission from the head of each nursing institute was obtained before conducting the study. After participants read the Participation Information Sheet, they were asked for written informed consent before data collection. Confidentiality of the information and anonymity of the participants were maintained throughout the study. Results: The majority (81.8%) of the participants were females. It was found that compared to private nurses, government college nurses were more adhered to the research guidelines on research project approval (68.6% vs 22.1%), informed consent guidelines (74.3% vs 25%), providing patient information sheets (55.7% vs 10%), maintaining information confidentiality (82.9% vs 72.1%), maintaining anonymity (76.4% vs 22.9%) and obtaining custodian permission (97.8 vs 89.3%). It was also shown that nurses were more aware of the informed consent process domain (4.3 ± 0.3) followed by the general ethical principles domain (3.8 ± 0.8). Conclusion: Government college nurses adhered more to the research guidelines as compared to those employed in private settings. Most of the faculty members were not part of any clinical trials and had no research ethics training at all. Therefore, it is needed to provide an instructional programme to raise awareness of the research ethical standards.
A neural network model of when to retrieve and encode episodic memories

Recent human behavioral and neuroimaging results suggest that people are selective in when they encode and retrieve episodic memories. To explain these findings, we trained a memory-augmented neural network to use its episodic memory to support prediction of upcoming states in an environment where past situations sometimes reoccur. We found that the network learned to retrieve selectively as a function of several factors, including its uncertainty about the upcoming state. Additionally, we found that selectively encoding episodic memories at the end of an event (but not mid-event) led to better subsequent prediction performance. In all of these cases, the benefits of selective retrieval and encoding can be explained in terms of reducing the risk of retrieving irrelevant memories. Overall, these modeling results provide a resource-rational account of why episodic retrieval and encoding should be selective and lead to several testable predictions.
Spatial distribution of beta‐klotho mRNA in the mouse hypothalamus, hippocampal region, subiculum, and amygdala

Beta‐klotho (KLB) is a coreceptor required for endocrine fibroblast growth factor (FGF) 15/19 and FGF21 signaling in the brain. Klb is prominent within the hypothalamus, which is consistent with its metabolic functions, but diverse roles for Klb are now emerging. Central Klb expression is low but discrete and may govern FGF‐targeted sites. However, given its low expression, it is unclear if Klb mRNA is more widespread. We performed in situ hybridization to label Klb mRNA to generate spatial maps capturing the distribution and levels of Klb within the mouse hypothalamus, hippocampal region, subiculum, and amygdala. Semiquantitative analysis revealed that Klb‐labeled cells may express low, medium, or high levels of Klb mRNA. Hypothalamic Klb hybridization was heterogeneous and varied rostrocaudally within the same region. Most Klb‐labeled cells were found in the lateral hypothalamic zone, but the periventricular hypothalamic region, including the suprachiasmatic nucleus, contained the greatest proportion of cells expressing medium or high Klb levels. We also found heterogeneous Klb hybridization in the amygdala and subiculum, where Klb was especially distinct within the central amygdalar nucleus and ventral subiculum, respectively. By contrast, Klb‐labeled cells in the hippocampal region only expressed low levels of Klb and were typically found in the pyramidal layer of Ammon's horn or dentate gyrus. The Klb‐labeled regions identified in this study are consistent with reported roles of Klb in metabolism, taste preference, and neuroprotection. However, additional identified sites, including within the hypothalamus and amygdala, may suggest novel roles for FGF15/19 or FGF21 signaling.
A buckling-sheet ring oscillator for electronics-free, multimodal locomotion

Locomotion of soft robots typically relies on control of multiple inflatable actuators by electronic computers and hard valves. Soft pneumatic oscillators can reduce the demand on controllers by generating complex movements required for locomotion from a single, constant input pressure, but either have been constrained to low rates of flow of air or have required complex fabrication processes. Here, we describe a pneumatic oscillator fabricated from flexible, but inextensible, sheets that provides high rates of airflow for practical locomotion by combining three instabilities: out-of-plane buckling of the sheets, kinking of tubing attached to the sheets, and a system-level instability resulting from connection of an odd number of pneumatic inverters made from these sheets in a loop. This device, which we call a “buckling-sheet ring oscillator” (BRO), directly generates movement from its own interaction with its surroundings and consists only of readily available materials assembled in a simple process—specifically, stacking acetate sheets, nylon film, and double-sided tape, and attaching an elastomeric tube. A device incorporating a BRO is capable of both translational and rotational motion over varied terrain (even without a tether) and can climb upward against gravity and downward against the buoyant force encountered under water. Description The buckling-sheet ring oscillator enables multimodal locomotion from a constant pressure without using electronic controls.
Effects of physical activity as an adjunct treatment on healing outcomes and recurrence of venous leg ulcers: A scoping review

Healing time is protracted and ulcer recurrence is common in patients with venous leg ulcers. Although compression is the mainstay treatment, many patients do not heal timely. Physical activity may be a clinically effective adjunct treatment to compression to improve healing outcomes. This scoping review provides a broad overview of the effect of physical activity as an adjunct treatment to compression on wound healing and recurrence. We followed the six‐step framework developed by Arksey and O'Malley. We searched electronic databases and trial registration websites for relevant studies and ongoing trials. Two authors independently screened and selected articles. Findings were presented in a descriptive statistical narrative summary. We consulted and presented our findings to the wound consumer group to ensure the relevance of our study. Physical activity interventions in 12 out of the 16 eligible studies consisted of only one component, eight studies were resistance exercises, three studies reported ankle and/or foot range of motion exercises, and one study reported aerobic/walking exercises. The remaining four studies involved multicomponent exercise interventions. Resistance exercise combined with ankle and/or foot range of motion exercise minimised ulcer size on day 12 (intervention group: 4.55 ± 1.14 cm2 vs. control group: 7.43 ± 0.56 cm2) and improved calf muscle pump performance on day 8 (ejection fraction: 40%–65%; residual volume fraction: 56%–40%). We identified one study that reported ulcer recurrence rate with no clinical difference in the intervention group versus the control group (i.e., 12% in intervention vs. 5% in control). Our review identified that resistance exercise was the most common type of physical activity intervention trialled in the published literature. Resistance exercise combined with ankle and/or foot range of motion exercise appears to be effective adjunct treatments; however, the overall evidence is still relatively weak as most programmes had a short intervention period which limited clinical outcomes.
Cardamonin attenuates cerebral ischemia/reperfusion injury by activating the HIF‐1α/VEGFA pathway

Cardamonin is a chalcone with neuroprotective activity. The aim of our study was to explore the functions and mechanism of action of cardamonin in ischemic stroke. Oxygen–glucose deprivation and reperfusion (OGD/R)‐induced human brain microvascular endothelial cells (HBMECs) and middle cerebral artery occlusion (MCAO) mouse model were utilized to mimic ischemic stroke. Cell viability was analyzed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide. Permeability was investigated via fluorescein isothiocyanate‐dextran assay. Apoptosis was detected by TdT‐Mediated dUTP Nick End Labeling staining. Hypoxia‐inducible factor (HIF)‐1α and vascular endothelial growth factor A (VEGFA) protein levels were measured using Western blotting. Brain injury was evaluated by 2,3,5‐triphenyltetrazolium chloride staining, neurological score and brain water content. The 37 overlapping targets of ischemic stroke and cardamonin were predicted to be associated with the HIF‐1/VEGFA signaling. Cardamonin alleviated OGD/R‐induced viability reduction and increase of permeability and apoptosis in HBMECs. Cardamonin increased OGD/R‐induced activation of the HIF‐1α/VEGFA pathway. Inhibition of the HIF‐1α/VEGFA signaling using inhibitor relieved the effect of cardamonin on cell viability, permeability and apoptosis in HBMECs under OGD/R. Cardamonin mitigated brain injury and promoted activation of the HIF‐1α/VEGFA signaling in MCAO‐treated mice. Overall, cardamonin protected against OGD/R‐induced HBMEC damage and MACO‐induced brain injury through activating the HIF‐1α/VEGFA pathway.
CRISPR-based gene disruption and integration of high-avidity, WT1-specific T cell receptors improve antitumor T cell function

T cell receptor (TCR)–based therapy has the potential to induce durable clinical responses in patients with cancer by targeting intracellular tumor antigens with high sensitivity and by promoting T cell survival. However, the need for TCRs specific for shared oncogenic antigens and the need for manufacturing protocols able to redirect T cell specificity while preserving T cell fitness remain limiting factors. By longitudinal monitoring of T cell functionality and dynamics in 15 healthy donors, we isolated 19 TCRs specific for Wilms’ tumor antigen 1 (WT1), which is overexpressed by several tumor types. TCRs recognized several peptides restricted by common human leukocyte antigen (HLA) alleles and displayed a wide range of functional avidities. We selected five high-avidity HLA-A*02:01–restricted TCRs, three that were specific to the less explored immunodominant WT137–45 and two that were specific to the noncanonical WT1−78–64 epitopes, both naturally processed by primary acute myeloid leukemia (AML) blasts. With CRISPR-Cas9 genome editing tools, we combined TCR-targeted integration into the TCR α constant (TRAC) locus with TCR β constant (TRBC) knockout, thus avoiding TCRαβ mispairing and maximizing TCR expression and function. The engineered lymphocytes were enriched in memory stem T cells. A unique WT137–45-specific TCR showed antigen-specific responses and efficiently killed AML blasts, acute lymphoblastic leukemia blasts, and glioblastoma cells in vitro and in vivo in the absence of off-tumor toxicity. T cells engineered to express this receptor are being advanced into clinical development for AML immunotherapy and represent a candidate therapy for other WT1-expressing tumors. Description T cells engineered to express a high-avidity WT1-specific TCR and no competing endogenous TCRs can eliminate cancer cells in vitro and in vivo. Alternative WT1 targets Adoptive cell therapy using T cell receptor (TCR)–modified T cells has shown clinical success. However, it remains a challenge to find TCRs that respond to shared tumor antigens presented in common human leukocyte antigen molecules. To that end, Ruggiero et al. and Lahman et al. identified and tested TCR constructs targeting alternative epitopes in the Wilms’ tumor antigen 1 (WT1) protein. Ruggiero and colleagues identified WT137–45 as a candidate peptide for TCR-based therapies and used CRISPR-Cas9 editing to target WT137–45-specific TCR sequences to the TRAC locus. Lahman and colleagues showed that, whereas a TCR-targeted WT1 epitope was lost because of immunoproteasome down-regulation, WT137–45 retains its expression and could be targeted by T cells expressing TCRs specific to that epitope, even in cancer cells that lose immunoproteasome activity. In both cases, T cells expressing WT137–45-specific TCRs controlled tumor burden in murine models. Thus, WT137–45 represents a candidate target for TCR-based immunotherapies that is resistant to immunoproteasome down-regulation.
Nerve root magnetic stimulation improves locomotor function following spinal cord injury with electrophysiological improvements and cortical synaptic reconstruction

Following a spinal cord injury, there are usually a number of neural pathways that remain intact in the spinal cord. These residual nerve fibers are important, as they could be used to reconstruct the neural circuits that enable motor function. Our group previously designed a novel magnetic stimulation protocol, targeting the motor cortex and the spinal nerve roots, that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury. Here, we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury. Rats underwent surgery to clamp the spinal cord at T10; three days later, the rats were treated with repetitive magnetic stimulation (5 Hz, 25 pulses/train, 20 pulse trains) targeting the nerve roots at the L5–L6 vertebrae. The treatment was repeated five times a week over a period of three weeks. We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord. In addition, the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex. Overall, the results suggest that nerve root magnetic stimulation may be an effective, noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.
Absence of tissue transglutaminase reduces amyloid‐beta pathology in APP23 mice

Alzheimer's disease (AD) is characterised by amyloid‐beta (Aβ) aggregates in the brain. Targeting Aβ aggregates is a major approach for AD therapies, although attempts have had little to no success so far. A novel treatment option is to focus on blocking the actual formation of Aβ multimers. The enzyme tissue transglutaminase (TG2) is abundantly expressed in the human brain and plays a key role in post‐translational modifications in Aβ resulting in covalently cross‐linked, stable and neurotoxic Aβ oligomers.