Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS

Chimeric Antigen Receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs) are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR) to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV) infection in pigtail macaques. CAR-containing cells persisted for more than 2 years without any measurable toxicity and were capable of multilineage engraftment. Combination antiretroviral therapy (cART) treatment followed by cART withdrawal resulted in lower viral rebound in CAR animals relative to controls, and demonstrated an immune memory-like response. We found CAR-expressing cells in multiple lymphoid tissues, decreased tissue-associated SHIV RNA levels, and substantially higher CD4/CD8 ratios in the gut as compared to controls. These results show that HSPC-derived CAR T-cells are capable of long-term engraftment and immune surveillance. This study demonstrates for the first time the safety and feasibility of HSPC-based CAR therapy in a large animal preclinical model.
The Freezing Threshold for k-Colourings of a Random Graph

We determine the exact value of the freezing threshold, rfk, for k-colourings of a random graph when k≥ 14. We prove that for random graphs with density above rfk, almost every colouring is such that a linear number of vertices are frozen, meaning that their colour cannot be changed by a sequence of alterations whereby we change the colours of o(n) vertices at a time, always obtaining another proper colouring. When the density is below rfk, then almost every colouring is such that every vertex can be changed by a sequence of alterations where we change O(log n) vertices at a time. Frozen vertices are a key part of the clustering phenomena discovered using methods from statistical physics. The value of the freezing threshold was previously determined by the nonrigorous cavity method.
Directional analysis of images with Gabor wavelets

The paper presents a new scheme for analysis of linear directional components in images by using a multiresolution representation based on Gabor wavelets. A dictionary of Gabor filters with varying tuning frequency and orientation, specifically designed in order to reduce the redundancy in the wavelet-based representation, is applied to the given image. The filter responses for different scales and orientation are analyzed by using the Karhunen-Loeve (KL) transform and Otsu's (1979) method of thresholding. The KL transform is applied to select the principal components of the filter responses, preserving only the most relevant directional elements appearing at all scales. The first N principal components, thresholded by using Otsu's method, are used to reconstruct the magnitude and phase of the directional components of the image. Rose diagrams computed from the phase images are used for quantitative and qualitative analysis of the oriented patterns. The proposed scheme is applied to the analysis of asymmetry between left and right mammograms. For this purpose, a set of three features is extracted from the Rose diagrams and used in a parametric statistical classifier. A total of 80 images from 20 normal cases, 14 asymmetric cases, and 6 distortion cases from the Mini-MIAS database were used to evaluate the scheme using the leave-one-out methodology, resulting in an average diagnostic accuracy of 72.5%.
Supporting a Healthy Culture: Results of the Practice Environment Scale, Australia in a Magnet®Designated Hospital

The Magnet Recognition Program® requires evidence that nursing practice environments support staff to provide optimal care, access professional development opportunities, and participate in hospital affairs. The research presented in this article aimed to assess clinical nurses’ work environment at a recently designated, private Magnet® hospital in Sydney, Australia. Authors compare results with baseline data collected for a gap analysis before application for recognition. The outcomes challenge previously reported data suggesting that hospitals on the journey to Magnet recognition outperform already designated hospitals in this respect.
Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury

Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and latent TGFβ binding protein 4 (LTBP4). We now evaluated the functional effect of these modifiers in the context of muscle injury and repair to elucidate their mechanisms of action. We found that excess osteopontin exacerbated sarcolemmal injury, and correspondingly, that loss of osteopontin reduced injury extent both in isolated myofibers and in muscle in vivo. We found that ablation of osteopontin was associated with reduced expression of TGFβ and TGFβ-associated pathways. We identified that increased TGFβ resulted in reduced expression of Anxa1 and Anxa6, genes encoding key components of the muscle sarcolemma resealing process. Genetic manipulation of Ltbp4 in dystrophic muscle also directly modulated sarcolemmal resealing, and Ltbp4 alleles acted in concert with Anxa6, a distinct modifier of muscular dystrophy. These data provide a model in which a feed forward loop of TGFβ and osteopontin directly impacts the capacity of muscle to recover from injury, and identifies an intersection of genetic modifiers on muscular dystrophy.
High spatial resolution imaging of the segregation of reactive elements to oxide grain boundaries in alumina scales

Abstract Although it is well established that reactive elements such as yttrium and hafnium can segregate to oxide/metal interfaces and oxide grain boundaries in thermally grown oxides, their distribution and role at these sites are less certain. For example, their effect on oxide growth, scale plasticity and spallation is still debated. It has also been reported that hafnium and yttrium rich oxide particles can be present within growing alumina scales and that the growth or shrinkage of these particles can affect the Y and Hf distributions in the aluminium oxide grain boundaries in their vicinity. Hence, we now report the use of very high spatial resolution imaging in the SuperSTEM electron microscope to investigate the distribution of Y and Hf in aluminium oxide grain boundaries at the atomic level. The oxide scales studied were detached from Fe – 20Cr – 5Al alloy substrates doped with Y and Hf, which had been oxidised for up to 100 h at 1250°C in laboratory air. The scales were ion beam thinned prior to examination in the STEM, and a series of tilting experiments and through focal series were used to map out the distributions of the reactive elements. The influence of electron beam/sample interactions was also studied and some evidence for the movement of Hf and Y atoms along the grain boundaries to the surfaces of the thin oxide foils is also reported.
Rapid and Accurate Sequencing of Enterovirus Genomes Using MinION Nanopore Sequencer.

OBJECTIVE Knowledge of an enterovirus genome sequence is very important in epidemiological investigation to identify transmission patterns and ascertain the extent of an outbreak. The MinION sequencer is increasingly used to sequence various viral pathogens in many clinical situations because of its long reads, portability, real-time accessibility of sequenced data, and very low initial costs. However, information is lacking on MinION sequencing of enterovirus genomes. METHODS In this proof-of-concept study using Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) strains as examples, we established an amplicon-based whole genome sequencing method using MinION. We explored the accuracy, minimum sequencing time, discrimination and high-throughput sequencing ability of MinION, and compared its performance with Sanger sequencing. RESULTS Within the first minute (min) of sequencing, the accuracy of MinION was 98.5% for the single EV71 strain and 94.12%-97.33% for 10 genetically-related CA16 strains. In as little as 14 min, 99% identity was reached for the single EV71 strain, and in 17 min (on average), 99% identity was achieved for 10 CA16 strains in a single run. CONCLUSION MinION is suitable for whole genome sequencing of enteroviruses with sufficient accuracy and fine discrimination and has the potential as a fast, reliable and convenient method for routine use.
Cardiotoxicity associated with carfilzomib: systematic review and meta-analysis

Abstract Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using ‘R’ software with metaphor package. A total of 4164 patients with various malignancies were included. The overall estimated cumulative incidence of cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade (≥ grade 3) toxicity, which seems higher than other PIs. Compared to control group, the odds of developing cardiotoxicity due to carfilzomib was significantly higher with OR of 2.03 (95% CI: 1.19–3.46, p = .010) and 2.04 (95% CI: 1.31–3.17, p = .002) for all-grades and high grades, respectively. Concomitant immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory agents, respectively (p = .033)). There was no variation in the incidence of cardiotoxicity among newly diagnosed versus RRMM (p = .38), and high versus standard dose carfilzomib (p = .86).
A multi-branch convolutional neural network for detecting double JPEG compression

Detection of double JPEG compression is important to forensics analysis. A few methods were proposed based on convolutional neural networks (CNNs). These methods only accept inputs from pre-processed data, such as histogram features and/or decompressed images. In this paper, we present a CNN solution by using raw DCT (discrete cosine transformation) coefficients from JPEG images as input. Considering the DCT sub-band nature in JPEG, a multiple-branch CNN structure has been designed to reveal whether a JPEG format image has been doubly compressed. Comparing with previous methods, the proposed method provides end-to-end detection capability. Extensive experiments have been carried out to demonstrate the effectiveness of the proposed network.
Self-aligned double patterning-aware detailed routing with double via insertion and via manufacturability consideration

In 10nm technology node, self-aligned double patterning (SA DP) and triple patterning lithography (TPL) allow us to achieve minimum wiring pitch of around 45nm. While metal layers can be printed by SADP, via layer manufacturing requires TPL to maintain design rules. SADP-aware detailed routing is proposed to ensure decomposability of metal layer patterns. However, its routing solution does not automatically guarantee TPL decomposable via layers. Vias have an inherently low reliability and via failure causes a great yield loss. Double via insertion (DVI) is an effective means to increase yield by reducing via failures. With the restriction of SADP design rules and consideration of TPL decomposability for via layers, DVI becomes a more challenging problem. In this paper, we consider DVI and via layer TPL manufacturability simultaneously in SADP-aware detailed routing. The experimental results demonstrate our router can obtain 100% routability and TPL decomposable via layers with reduced dead via count.
Efficacy of Cognitive Training in Older Adults with and without Subjective Cognitive Decline Is Associated with Inhibition Efficiency and Working Memory Span, Not with Cognitive Reserve

The present study explores the role of cognitive reserve, executive functions, and working memory (WM) span, as factors that might explain training outcomes in cognitive status. Eighty-one older adults voluntarily participated in the study, classified either as older adults with subjective cognitive decline or cognitively intact. Each participant underwent a neuropsychological assessment that was conducted both at baseline (entailing cognitive reserve, executive functions, WM span and depressive symptomatology measures, as well as the Mini-Mental State Exam regarding initial cognitive status), and then 6 months later, once each participant had completed the training program (Mini-Mental State Exam at the endpoint). With respect to cognitive status the training program was most beneficial for subjective cognitive decline participants with low efficiency in inhibition at baseline (explaining a 33% of Mini-Mental State Exam total variance), whereas for cognitively intact participants training gains were observed for those who presented lower WM span.
Adaptive Fault-Tolerant Attitude Tracking Control of Spacecraft With Prescribed Performance

The science objectives of a spacecraft mission place stringent performance requirements on the spacecraft attitude control system. However, it remains an open problem how to guarantee consistent control performance necessary to meet these requirements, especially in the event of actuator faults and input saturation. Motivated by this fact, in this paper, we address the problem of attitude tracking control with prescribed performance guarantees for a rigid spacecraft subject to unknown but constant inertia parameters, unexpected disturbances, actuator faults, and input saturation. First, certain performance functions specified a priori by the designer are adopted to impose desired performance metrics on the attitude tracking errors. Then, the original attitude tracking error dynamics with performance constraints is transformed into an equivalent “state-constrained” one whose robust stabilization is shown to be sufficient to solve the stated problem via a novel error transformation. Subsequently, based on the transformed system, an adaptive fault-tolerant controller is derived by incorporating backstepping control, the barrier Lyapunov function, and Nussbaum gains. It is proved that the designed controller is able to guarantee the satisfaction of the prespecified constraints on the transformed errors, as well as the boundedness of all other closed-loop signals, without resorting to a judicious selection of the control parameters. Finally, the effectiveness of the proposed control scheme is evaluated by means of simulation experiments carried out on a microsatellite.
The long-term effects of the health coaching self-management program for nursing-home residents

Background and aims Little is known about whether a self-management program for nursing-home residents (NHR) with cognitive impairment is likely to have an impact on the care of this growing population. This study aimed to evaluate the effects of the health-coaching self-management program for NHR (HCSMP-NHR) on 1) self-efficacy and goal attainment scaling (GAS), 2) health status and quality of life (QoL) among older people, including those with cognitive impairment, in Korean nursing homes. Methods This was a cluster-randomized controlled trial. Participants in the intervention group (n=43, mean age =80.91±7.65 years) received the HCSMP-NHR intervention, composed of group health education and individual coaching, for 8 weeks. Conventional care was provided to the conventional group (n=47, mean age =80.19±7.53 years) during the same period. The effects of the HCSMP-NHR were measured three times: at baseline, week 9, and week 20. Results The intervention group showed better results for self-efficacy (P=0.007), health distress (P=0.007), depression (P<0.001), and QoL (P=0.04) at week 9. Mean GAS score of the intervention group gradually increased from −0.38 to 0.74. The time × group interaction showed that the intervention group had significant improvements in QoL (P=0.047), and significant reductions in health distress (P=0.016) and depression (P<0.001), while showing no deterioration in shortness of breath (P<0.001). Conclusion Our study findings indicate that the HCSMP-NHR improved self-efficacy and GAS and enhanced the health status and QoL of NHR with chronic conditions who also had mild-to-moderate cognitive impairment. Moreover, these effects were successfully maintained over the 5 months of the trial. Further research is needed to establish the optimum intervention period and to assess the possibility of nationwide implementation of the HCSMP-NHR.
Anterior Cruciate Ligament Injuries in the Young Athlete: Evaluation and Treatment

Injuries to the pediatric and adolescent athlete are becoming more common as increasing numbers of this patient population are participating in year-round sporting activities. As these figures continue to rise, there have been an escalating number of patients with both traumatic and nontraumatic, sports-related knee injuries presenting to orthopedic surgeons for evaluation. Anterior cruciate ligament injuries in these patients, specifically in the skeletally immature, represent a complex problem. Treatment of these patients requires a thorough understanding of anatomy and physiology of the pediatric patient, the natural history of this injury, and knowledge of the potential complications of surgical intervention. This review will address these topics and will describe the presentation, diagnosis, and most commonly used surgical techniques currently being used with these patients. Future directions and advances in care of these injuries will also be discussed.
A new structure of a magnetorheological brake with the waveform boundary of a rotary disk

This paper presents a novel magnetorheological (MR) brake design incorporating a rotary disk with a waveform boundary that generates a resistance force based on the effects of a material deformation process. This force is transmitted from an external agent and creates the necessary energy for breaking the structure of the hardened MR fluid. Its minimum destructive ability is proportional to the variable stiffness of an MR fluid in a magnetic field. In this design, the waveform wall of a rotary disk crushes the particles chains (fibrils) of the MR fluid together instead of breaking them via strain in a conventional MR brake. The resistance forces and braking torques generated by this crush action are stronger than those produced by strain action. To verify our proposed MR brake, the proposed and conventional MR brakes are designed using similar magnetic circuits and material parameters. We compared the performance of our novel MR brake to the performance of a conventional MR brake, and demonstrated that the measured resistance torque of the proposed MR brake is approximately 600% greater than resistance torques generated by conventional brakes.
Evolutionary trade-offs between reproduction and dispersal in populations at expanding range boundaries

During recent climate warming, some species have expanded their ranges northwards to keep track of climate changes. Evolutionary changes in dispersal have been demonstrated in these expanding populations and here we show that increased dispersal is associated with reduced investment in reproduction in populations of the speckled wood butterfly, Pararge aegeria. Evolutionary changes in flight versus reproduction will affect the pattern and rate of expansion at range boundaries in the future, and understanding these responses will be crucial for predicting the distribution of species in the future as climates continue to warm.
High-Order Affinity Extension of Normalized Cut and Its Applications

In the normalized cut (Ncut) process, it is crucial to construct an appropriate affinity matrix. The affinity matrix is generally limited to pairwise similarity relations. However, in practice, it is necessary to use high-order affinities in several computer vision applications such as motion segmentation. In this paper, by using high-order singular value decomposition techniques, we derive a high-order affinity model directly from the Ncut relaxation formula, called high-order normalized cut (HNcut). However, in practice, it cannot directly utilize the high-order affinity matrix because of the computational resources required. To address this issue, we adopt and improve various techniques to make the proposed method more practical such as sampling strategy. Finally, we analyze the upper error bound of our algorithm based on matrix perturbation theory. To demonstrate the performance of our HNcut, we compare it with some existing algorithms for the motion segmentation and face clustering problems.
Sexual Orientation Disparities in the Use of Emerging Drugs

ABSTRACT Background: Prescription drug, e-cigarette, smokeless tobacco, and synthetic marijuana use has risen dramatically in the United States over the past decade. Objectives: This paper investigates the use of risky substances among adolescents, and examines disparities between sexual minority (i.e., mostly heterosexual and lesbian, gay, bisexual; LGB) and heterosexual adolescents in use of novel and emerging substances. Given the public health risk and the imminence of these substances in the media, emerging drug use was examined in a county wide sample of adolescents in a Southern state. Methods: A probability sample of middle and high school students (N = 3012; ages 11–18) using random cluster methods was obtained in a mid-sized school district in the Southeastern United States. Results: LGB adolescents reported higher past-30 day and lifetime use of cigarettes (AORs =2.77, 2.90, respectively), smokeless tobacco (lifetime only: AOR = 1.88), e-cigarettes (lifetime only; AOR = 1.92), alcohol (AORs = 1.7, 2.20), marijuana (AORs = 3.02, 3.06), synesthetic marijuana (AORs = 3.77, 2.48), and prescription drugs (AORs = 3.82, 2.55). Adolescents who self-identified as “mostly heterosexual” reported higher lifetime cigarette use, and past 30-day use of e-cigarettes and prescription drugs as compared with heterosexual adolescents. Conclusions: Our results are notable given the dearth of data documenting use of increasingly emerging or “trendy” substances such as prescription drugs. More research is needed to understand the underlying cause of these disparities, and efforts should be targeted toward this population to reduce negative outcomes from misuse.