Factors Influencing Real-World Use of the More-Affected Upper Limb After Stroke: A Scoping Review.

IMPORTANCE: Current interventions are limited in improving use of the more-affected upper limb in real-world daily occupations and functional independence poststroke. A comprehensive understanding of the factors influencing real-world upper limb use is required to develop interventions to improve functional independence poststroke. OBJECTIVE: To systematically review the factors that influence real-world use of the more-affected upper limb poststroke. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, and the Physiotherapy Evidence Database for English-language articles from 2012 to 2023. STUDY SELECTION AND DATA COLLECTION: Of 774 studies, we included 33 studies that had participants at least age 18 yr who exhibited upper limb impairments poststroke, objectively measured real-world upper limb use using a movement sensor, and measured factors affecting upper limb use. Two reviewers independently screened the abstracts. FINDINGS: The results were categorized by International Classification of Functioning, Disability and Health domains. Prominent factors were upper limb impairment; motor ability; functional independence; task type; hand dominance; stroke-related factors, including time since stroke; and perception of use of the more-affected upper limb. CONCLUSIONS AND RELEVANCE: Existing interventions primarily focus on upper limb impairments and motor ability. Our findings suggest that interventions should also incorporate other factors: task type (unilateral vs. bilateral), hand dominance, self-efficacy, and perception of more-affected limb use as active ingredients in improving real-world use of the more-affected upper limb poststroke. We also provide recommendations to use behavioral activation theory in designing an occupation-focused intervention to augment self-efficacy and confidence in use of the more-affected upper limb in daily occupations. Plain-Language Summary: In order to develop interventions to improve functional independence poststroke, occupational therapy practitioners must have a comprehensive understanding of the factors that influence real-world more-affected upper limb use. The study findings provide a set of distinct factors that practitioners can target separately or in combination to improve real-world use of the more-affected upper limb poststroke.

Corticospinal excitability during motor preparation of upper extremity reaches reflects flexor muscle synergies: A novel principal component-based motor evoked potential analyses.

Background: Previous research has shown that noninvasive brain stimulation can be used to study how the central nervous system (CNS) prepares the execution of a motor task. However, these previous studies have been limited to a single muscle or single degree of freedom movements (e.g., wrist flexion). It is currently unclear if the findings of these studies generalize to multi-joint movements involving multiple muscles, which may be influenced by kinematic redundancy and muscle synergies. Objective: The objective of this study was to characterize corticospinal excitability during motor preparation in the cortex prior to functional upper extremity reaches. Methods: 20 participants without neurological impairments volunteered for this study. During the experiment, the participants reached for a cup in response to a visual "Go Cue". Prior to movement onset, we used transcranial magnetic stimulation (TMS) to stimulate the motor cortex and measured the changes in motor evoked potentials (MEPs) in several upper extremity muscles. We varied each participant's initial arm posture and used a novel synergy-based MEP analysis to examine the effect of muscle coordination on MEPs. Additionally, we varied the timing of the stimulation between the Go Cue and movement onset to examine the time course of motor preparation. Results: We found that synergies with strong proximal muscle (shoulder and elbow) components emerged as the stimulation was delivered closer to movement onset, regardless of arm posture, but MEPs in the distal (wrist and finger) muscles were not facilitated. We also found that synergies varied with arm posture in a manner that reflected the muscle coordination of the reach. Conclusions: We believe that these findings provide useful insight into the way the CNS plans motor skills.

Recovery of Function After Acquired Neurological Injury.

The articles in this Special Issue on Recovery of Function After Neurological Injury include an impressive range of clinical diagnoses, scientific approaches, and theoretical frameworks that demonstrate the breadth and depth of occupational therapy in the restoration of function after neurological injury. An emerging theme throughout is the need for the profession of occupational therapy to identify and use more efficient methods for diagnosing and treating people with neurological injuries to improve their quality of life and the impact of care.

Medical emergencies in a dental school clinic - A 12-year review and lessons learned.

PURPOSE: The aims of this study were to estimate the type and frequency of different medical emergencies that occurred over the study period (twelve years) and discuss the lessons learned and the modifications made in the curriculum to better equip dental students and faculty in their management. MATERIALS AND METHODS: A retrospective study was conducted to evaluate all medical emergencies that needed activation of the response team at our school from 2008 to 2020. RESULTS: The emergency response system was activated 250 times during the 12-year period. There were 132 medical emergencies in the pre-doctoral clinic and 105 events in the post-doctoral clinic (p 0.0680). Most of the emergencies occurred in patients between 45 and 64 years of age. Syncope occurs most often followed by adverse cardiovascular, respiratory, anxiety, and hypoglycemic events. CONCLUSIONS: Medical emergencies occurring in a dental school provide a unique opportunity for students to gain experience in their management. The key lies in preparing the students and faculty to prevent them from occurring, but should these occur, then they should be able to promptly recognize symptoms and institute prompt intervention.

A soybean trypsin inhibitor reduces the resistance to transgenic maize in a population of Spodoptera frugiperda (Lepidoptera: Noctuidae).

Lepidopteran pests have been successfully managed by the adoption of insect resistant transgenic plants expressing Cry and/or Vip insecticidal proteins derived from Bacillus thuringiensis (Bt plants). Among such pests, Spodoptera frugiperda (Smith, 1797) (Lepidoptera: Noctuidae) is highlighted for its destructive potential in maize crops and for cases of field-evolved resistance to Bt plants. Cry insecticidal proteins expressed in Bt plants are known for their interaction with insect midgut receptors and subsequent midgut cell disruption that leads to target pest death. In the midgut of lepidopteran larval pests such as S. frugiperda, serine proteases are important in dietary protein digestion and activation or degradation of insecticidal proteins. This work was conducted to evaluate if the use of a soybean trypsin inhibitor (SBTI) could disrupt the development of a Bt-susceptible and a Bt-resistant population of S. frugiperda ingesting Bt (expressing Cry1F, Cry1A.105, and Cry2Ab2 Cry proteins) and non-Bt maize plants. The SBTI was produced and purified using recombinant expression in E. coli followed by purification in Ni-Sepharose. Bioassays using non-Bt maize leaves indicated that the development of susceptible and resistant populations of S. frugiperda was not influenced by the ingestion of SBTI. However, when the resistant population consumed Bt maize plants amended with SBTI, high mortality along with a reduction in larval weight and reduced activity of digestive trypsins were observed. Although the mode of action was not elucidated, it is possible that the consumption of SBTI increased susceptibility to Bt maize in the resistant population of S. frugiperda.

Novel insecticidal proteins from ferns resemble insecticidal proteins from Bacillus thuringiensis.

Lepidopterans affect crop production worldwide. The use of transgenes encoding insecticidal proteins from Bacillus thuringiensis (Bt) in crop plants is a well-established technology that enhances protection against lepidopteran larvae. Concern about widespread field-evolved resistance to Bt proteins has highlighted an urgent need for new insecticidal proteins with different modes or sites of action. We discovered a new family of insecticidal proteins from ferns. The prototype protein from Pteris species (Order Polypodiales) and variants from two other orders of ferns, Schizaeales and Ophioglossales, were effective against important lepidopteran pests of maize and soybean in diet-based assays. Transgenic maize and soybean plants producing these proteins were more resistant to insect damage than controls. We report here the crystal structure of a variant of the prototype protein to 1.98 Å resolution. Remarkably, despite being derived from plants, the structure resembles the 3-domain Cry proteins from Bt but has only two out of three of their characteristic domains, lacking the C-terminal domain which is typically required for their activities. Two of the fern proteins were effective against strains of fall armyworm that were resistant to Bt 3-domain Cry proteins Cry1Fa or Cry2A.127. This therefore represents a novel family of insecticidal proteins that have the potential to provide future tools for pest control.

Performance of cotton expressing Cry1Ac, Cry1F and Vip3Aa19 insecticidal proteins against Helicoverpa armigera, H. zea and their hybrid progeny, and evidence of reduced susceptibility of a field population of H. zea to Cry1 and Vip3Aa in Brazil.

The genetically modified cotton DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 expressing Cry1Ac, Cry1F and Vip3Aa19 from Bacillus thuringiensis Berliner (Bt) has been cultivated in Brazil since the 2020/2021 season. Here, we assessed the performance of DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 cotton expressing Cry1Ac, Cry1F and Vip3Aa19 against Helicoverpa armigera (Hübner), Helicoverpa zea (Boddie), and their hybrid progeny. We also carried out evaluations with DAS-21023-5 × DAS-24236-5 cotton containing Cry1Ac and Cry1F. In leaf-disk bioassays, DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 was effective in controlling neonates from laboratory colonies of H. armigera, H. zea and the hybrid progeny (71.9%-100% mortality). On floral bud bioassays using L2 larvae, H. zea presented complete mortality, whereas H. armigera and the hybrid progeny showed <55% mortality. On DAS-21023-5 × DAS-24236-5 cotton, the mortality of H. armigera on leaf-disk and floral buds ranged from 60% to 73%, whereas mortality of hybrids was <46%. This Bt cotton caused complete mortality of H. zea larvae from a laboratory colony in the early growth stages, but mortalities were <55% on advanced growth stages and on floral buds. In field studies conducted from 2014 to 2019, DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 cotton was also effective at protecting plants against H. armigera. In contrast, a population of H. zea collected in western Bahia in 2021/2022 on Bt cotton expressing Cry1 and Vip3Aa proteins, showed 63% mortality after 30 d, with insects developing into fifth and sixth instars, on DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 cotton. We conclude that H. armigera, H. zea, and their hybrid progeny can be managed with DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 cotton; however we found the first evidence in Brazil of a significant reduction in the susceptibility to DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 cotton of a population of H. zea collected from Bt cotton in Bahia in 2021/2022.

Structural journey of an insecticidal protein against western corn rootworm.

The broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action. Using an integrative structural biology approach, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at high resolution. We discovered an assembly inhibition mechanism, a molecular switch that activates pre-pore oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings demonstrate not only the utility of Mpf2Ba1 in the development of biotechnology solutions for protecting maize from WCR to promote food security, but also uncover previously unknown mechanistic principles of bacterial MACPF assembly.

Muscle Coordination Matters: Insights into Motor Planning using Corticospinal Responses during Functional Reaching.

The central nervous system (CNS) moves the human body by forming a plan in the primary motor cortex and then executing this plan by activating the relevant muscles. It is possible to study motor planning by using noninvasive brain stimulation techniques to stimulate the motor cortex prior to a movement and examine the evoked responses. Studying the motor planning process can reveal useful information about the CNS, but previous studies have generally been limited to single degree of freedom movements ( e.g., wrist flexion). It is currently unclear if findings in these studies generalize to multi-joint movements, which may be influenced by kinematic redundancy and muscle synergies. Here, our objective was to characterize motor planning in the cortex prior to a functional reach involving the upper extremity. We asked participants to reach for a cup placed in front of them when presented with a visual "Go Cue". Following the go cue, but prior to movement onset, we used transcranial magnetic stimulation (TMS) to stimulate the motor cortex and measured the changes in the magnitudes of evoked responses in several upper extremity muscles (MEPs). We varied each participant's initial arm posture to examine the effect of muscle coordination on MEPs. Additionally, we varied the timing of the stimulation between the go cue and movement onset to examine the time course of changes in the MEPs. We found that the MEPs in all proximal (shoulder and elbow) muscles increased as the stimulation was delivered closer to movement onset, regardless of arm posture, but MEPs in the distal (wrist and finger) muscles were not facilitated or even inhibited. We also found that facilitation varied with arm posture in a manner that reflected the coordination of the subsequent reach. We believe that these findings provide useful insight into the way the CNS plans motor skills.

Multiscale deep learning framework captures systemic immune features in lymph nodes predictive of triple negative breast cancer outcome in large-scale studies.

The suggestion that the systemic immune response in lymph nodes (LNs) conveys prognostic value for triple-negative breast cancer (TNBC) patients has not previously been investigated in large cohorts. We used a deep learning (DL) framework to quantify morphological features in haematoxylin and eosin-stained LNs on digitised whole slide images. From 345 breast cancer patients, 5,228 axillary LNs, cancer-free and involved, were assessed. Generalisable multiscale DL frameworks were developed to capture and quantify germinal centres (GCs) and sinuses. Cox regression proportional hazard models tested the association between smuLymphNet-captured GC and sinus quantifications and distant metastasis-free survival (DMFS). smuLymphNet achieved a Dice coefficient of 0.86 and 0.74 for capturing GCs and sinuses, respectively, and was comparable to an interpathologist Dice coefficient of 0.66 (GC) and 0.60 (sinus). smuLymphNet-captured sinuses were increased in LNs harbouring GCs (p < 0.001). smuLymphNet-captured GCs retained clinical relevance in LN-positive TNBC patients whose cancer-free LNs had on average ≥2 GCs, had longer DMFS (hazard ratio [HR] = 0.28, p = 0.02) and extended GCs' prognostic value to LN-negative TNBC patients (HR = 0.14, p = 0.002). Enlarged smuLymphNet-captured sinuses in involved LNs were associated with superior DMFS in LN-positive TNBC patients in a cohort from Guy's Hospital (multivariate HR = 0.39, p = 0.039) and with distant recurrence-free survival in 95 LN-positive TNBC patients of the Dutch-N4plus trial (HR = 0.44, p = 0.024). Heuristic scoring of subcapsular sinuses in LNs of LN-positive Tianjin TNBC patients (n = 85) cross-validated the association of enlarged sinuses with shorter DMFS (involved LNs: HR = 0.33, p = 0.029 and cancer-free LNs: HR = 0.21 p = 0.01). Morphological LN features reflective of cancer-associated responses are robustly quantifiable by smuLymphNet. Our findings further strengthen the value of assessment of LN properties beyond the detection of metastatic deposits for prognostication of TNBC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Quantification of subtype purity in Luminal A breast cancer predicts clinical characteristics and survival.

PURPOSE: PAM50 profiling assigns each breast cancer to a single intrinsic subtype based on a bulk tissue sample. However, individual cancers may show evidence of admixture with an alternate subtype that could affect prognosis and treatment response. We developed a method to model subtype admixture using whole transcriptome data and associated it with tumor, molecular, and survival characteristics for Luminal A (LumA) samples. METHODS: We combined TCGA and METABRIC cohorts and obtained transcriptome, molecular, and clinical data, which yielded 11,379 gene transcripts in common and 1,178 cases assigned to LumA. We used semi-supervised non-negative matrix factorization (ssNMF) to compute the subtype admixture proportions of the four major subtypes-pLumA, pLumB, pHER2, and pBasal-for each case and measured associations with tumor characteristics, molecular features, and survival. RESULTS: Luminal A cases in the lowest versus highest quartile for pLumA transcriptomic proportion had a 27% higher prevalence of stage > 1, nearly a threefold higher prevalence of TP53 mutation, and a hazard ratio of 2.08 for overall mortality. We found positive associations between pHER2 and HER2 positivity by IHC or FISH; between pLumB and PR negativity; and between pBasal and younger age, node positivity, TP53 mutation, and EGFR expression. Predominant basal admixture, in contrast to predominant LumB or HER2 admixture, was not associated with shorter survival. CONCLUSION: Bulk sampling for genomic analyses provides an opportunity to expose intratumor heterogeneity, as reflected by subtype admixture. Our results elucidate the striking extent of diversity among LumA cancers and suggest that determining the extent and type of admixture holds promise for refining individualized therapy. LumA cancers with a high degree of basal admixture appear to have distinct biological characteristics that warrant further study.

Efficient quality control of whole slide pathology images with human-in-the-loop training.

Histopathology whole slide images (WSIs) are being widely used to develop deep learning-based diagnostic solutions, especially for precision oncology. Most of these diagnostic softwares are vulnerable to biases and impurities in the training and test data which can lead to inaccurate diagnoses. For instance, WSIs contain multiple types of tissue regions, at least some of which might not be relevant to the diagnosis. We introduce HistoROI, a robust yet lightweight deep learning-based classifier to segregate WSI into 6 broad tissue regions-epithelium, stroma, lymphocytes, adipose, artifacts, and miscellaneous. HistoROI is trained using a novel human in-the-loop and active learning paradigm that ensures variations in training data for labeling efficient generalization. HistoROI consistently performs well across multiple organs, despite being trained on only a single dataset, demonstrating strong generalization. Further, we have examined the utility of HistoROI in improving the performance of downstream deep learning-based tasks using the CAMELYON breast cancer lymph node and TCGA lung cancer datasets. For the former dataset, the area under the receiver operating characteristic curve (AUC) for metastasis versus normal tissue of a neural network trained using weakly supervised learning increased from 0.88 to 0.92 by filtering the data using HistoROI. Similarly, the AUC increased from 0.88 to 0.93 for the classification between adenocarcinoma and squamous cell carcinoma on the lung cancer dataset. We also found that the performance of the HistoROI improves upon HistoQC for artifact detection on a test dataset of 93 annotated WSIs. The limitations of the proposed model are analyzed, and potential extensions are also discussed.

Population genomics of fall armyworm by genotyping-by-sequencing: Implications for pest management.

The fall armyworm (FAW), Spodoptera frugiperda, is a significant pest of many crops in the world and it is native to the Americas, where the species has shown the ability to rapidly evolve resistance to insecticides and transgenic plants. Despite the importance of this species, there is a gap in the knowledge regarding the genetic structure of FAW in South America. Here, we examined the genetic diversity of FAW populations across a wide agricultural area of Brazil and Argentina using a Genotyping-by-Sequencing (GBS) approach. We also characterized samples by their host strain based on mitochondrial and Z-linked genetic markers. The GBS methodology enabled us to discover 3309 SNPs, including neutral and outlier markers. Data showed significant genetic structure between Brazil and Argentina populations, and also among the Argentinian ecoregions. Populations inside Brazil showed little genetic differentiation indicating high gene flow among locations and confirming that structure is related to the presence of corn and rice strains. Outlier analysis indicated 456 loci putatively under selection, including genes possibly related to resistance evolution. This study provides clarification of the population genetic structure of FAW in South America and highlights the importance of genomic research to understand the risks of spread of resistance genes.

A phase II study to evaluate the efficacy of low-dose rasburicase (1.5mg) in adolescent and adult acute leukemia and high-grade lymphomas with tumor lysis syndrome.

The FDA recommended dose of rasburicase 0.2 mg/kg/day till the resolution of TLS or up to 5 days, might be in excess and is prohibitively expensive. The quality of evidence supporting low dose rasburicase is limited. The objective is to study the plasma uric acid response rate. This is a single center, non-randomised phase II study. Duration is 10 June 2017 till 30 July 2019. Study setting is at Adult Hematolymphoid Unit, Tata Memorial Center. Participants are patients with acute leukemia and high-grade lymphomas aged >/=18 years, with ECOG PS of 0-3, with either laboratory or clinical TLS. Rasburicase was administered at fixed-dose of 1.5 mg. The subsequent doses (1.5 mg each dose) were administered only if plasma UA levels did not decline by >50% on day 2, at the physician's discretion. We demonstrate that a low-dose rasburicase strategy leads to rapid and sustained reductions of uric acid in about 52% patients.

Control of paretic and non-paretic upper extremity during bimanual reaching after stroke.

Most actions of daily life engage the two upper extremities (UEs) in a highly coordinated manner. While it is recognized that bimanual movements are impaired post-stroke, understanding how the paretic and non-paretic UE contributes to this impairment is important for future interventions. We investigated kinetic and kinematics at the shoulder, elbow, and wrist joints in the paretic and non-paretic UE in 8 individuals with chronic stroke and non-dominant UE in 8 healthy controls during unimanual and bimanual tasks. Kinematic analysis revealed little effect of stroke. However, kinetic analysis revealed that during unimanual movements, joint control was impaired during unimanual and bimanual movements in both UEs, although to a lesser extent in the non-paretic than paretic UE. During bimanual movements, joint control did not change in the paretic UE, and it further deteriorated in the non-paretic UE compared with the unimanual movements. Our findings suggest that a single session of bimanual task performance does not improve joint control of the paretic UE and it impairs control of the non-paretic UE, making it more like that of the paretic UE.

Unsupervised learning framework for temperature compensated damage identification and localization in ultrasonic guided wave SHM with transfer learning.

Damage localization algorithms for ultrasonic guided wave-based structural health monitoring (GW-SHM) typically utilize manually-defined features and supervised machine learning on data collected under various conditions. This scheme has limitations that affect prediction accuracy in practical settings when the model encounters data with a distribution different from that used for training, especially due to variation in environmental factors (e.g., temperature) and types of damages. While deep learning based models that overcome these limitations have been reported in literature, they typically comprise of millions of trainable parameters. As an alternative, we propose an unsupervised approach for temperature-compensated damage identification and localization in GW-SHM systems based on transferring learning from a convolutional auto encoder (TL-CAE). Remarkably, without using signals corresponding to the damages during training (unsupervised), our method demonstrates more accurate damage detection and localization as well as robustness to temperature variations than supervised approaches reported on the publicly available Open Guided Waves (OGW) dataset. Additionally, we have demonstrated reduction in number of trainable parameters using transfer learning (TL) to leverage similarities between time-series among various sensor paths. It is also worth noting that the proposed framework uses raw time-domain signals, without any pre-processing or knowledge of material properties. It should therefore be scalable and adaptable for other materials, structures, damages, and temperature ranges, should more data become available in the future. We present an extensive parametric study to demonstrate feasibility of the proposed method.