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The neurotoxins of Costridiurn botulinum and tetanus bind to gangliosides as a first step of their toxin activity. Identifying suitable receptors that compete with gangliosides could prevent toxin binding to the neuronal cells. A possible ganglioside-binding site of the botulinum neurotoxin B (BoNT/B) has already been proposed and evidence is now presented for a drug binding to botulinum neurotoxin B from structural studies. Doxorubicin, a well known DNA intercalator, binds to the neurotoxin at the receptor-binding site proposed earlier. The structure of the BoNT/B-doxorubicin complex reveals that doxorubicin has interactions with the neurotoxin similar to those of sialyllactose. The aglycone moiety of the doxorubicin stacks with tryptophan 1261 and interacts with histidine 1240 of the binding domain. Here, the possibility is presented of designing a potential antagonist for these neurotoxins from crystallo- graphic analysis of the neurotoxin-doxorubicin complex, which will be an excellent lead compound. [ABSTRACT FROM AUTHOR]

The objective of this life cycle environmental cost analysis (LCECA) model is to include eco-costs into the total cost of the products. Eco-costs are both the direct and indirect costs of the environmental impacts caused by the product in its entire life cycle. Subsequently, this LCECA model identifies the feasible alternatives for cost-effective, eco-friendly parts/products. This attempts to incorporate costing into the life cycle assessment (LCA) practice. Ultimately, it aims to reduce the total cost with the help of green or eco-friendly alternatives in all the stages of the life cycle of any product. The new category of eco-costs of the cost breakdown structure includes eight eco-costs, namely cost of effluent/waste treatment, cost of effluent/waste control, cost of waste disposal, cost of implementation of environmental management systems, costs of eco-taxes, costs of rehabilitation (in case of environmental accidents), cost savings of renewable energy utilization, and cost savings of recycling and reuse strategies. Development of a suitable cost model and the identification of the feasible alternatives are performed simultaneously. Various checklists based on multiple environmental criteria will be used to ensure the eco-friendly nature of the alternatives. On the basis of the calculated environmental impact indices (EII), priorities will be made for the selection of suitable alternatives. The mathematical model of LCECA aims to define the relationships between the total cost of products and the various eco-costs concerned with the life cycle of the products, and determine quantitative expressions between the above-said costs. A computational LCECA model has been developed to compare the eco-costs of the alternatives. This model will include a break-even analysis to evaluate the alternatives, and sensitivity analysis and risk analysis modules. This model aims at a cost-effective, eco-friendly product as an end result. This LCECA model will be compatible with the existing LCA software tools. [ABSTRACT FROM AUTHOR]

Background and Objectives: The improvement in the reaction time is important, as it is the indicator of the performance in sports and in professional persons. Therefore, there is a need for techniques or courses that can improve the reaction time. Yoga was found to cause a better improvement in the health of the individuals with and without ailments. Hence, this study intended to show its utility as a short course for improving the reaction time. Methods: 25 male healthy volunteers who were aged between 18 and 25 years were selected. The Auditory Reaction Time (ART), the Visual Reaction Time (VRT) and the Cutaneous Reaction Time (CRT) were assessed before and after the yoga sessions. Results: There was a reduction in the alert responses of ART, VRT and CRT for both the sides. The decrease was statistically significant (P<0.05). The random responses did not show a significant improvement. RT had no correlation with the age, height or the weight. Conclusion: A short course of yoga has a beneficial effect on the reaction time and it can be used as a tool for improving the reaction time. [ABSTRACT FROM AUTHOR]

Single crystals of the outer surface protein C (OspC) from Borrelia burgdorferi HB19 have been obtained by the vapor-diffusion method. These crystals belong to space group P21, with unit-cell parameters a = 66.218, b = 46.113, c = 112.079 Å, β = 99.30°, and diffract to at least 2.2 Å resolution. Native data have been collected from flash-frozen crystals at the National Synchrotron facility of Brookhaven National Laboratory. There are two dimers per asymmetric unit, related by a non-crystallographic twofold axis and a pseudo-translational symmetry. [ABSTRACT FROM AUTHOR]

The increasing global energy demand and the depletion of conventional fossil fuel supplies, coupled with greenhouse gas emissions from excessive fossil fuel use, open the door for consideration of renewable energy sources. Among these, biodiesel has arisen as a sustainable and feasible alternative, providing environmental and economic advantages by reducing dependence on finite fossil fuel resources. This study focuses on biodiesel production from Madhuca indica seed oil using three catalysts: HCl, KOH, and dolomite. The optimum reaction parameters were methanol:oil molar ratio 20:1, catalyst weight percentage 5% and reaction temperature 60 °C. The reaction duration for each catalyst was 20 h for acid-catalyzed (HCl) process, 2 h for alkali-catalyzed (KOH) process, and 10 h for dolomite-based reaction. The biodiesel yields for acid, alkali, and dolomite catalysts are 94%, 96%, and 93%, respectively. According to the techno-economic study conducted with Aspen Plus, the payback periods for transesterification based on acid, alkali, and dolomite would be 3.66, 5.42, and 2.96 years, respectively. These results demonstrate the economic viability of dolomite as a green catalyst with competitive biodiesel yields and the shortest payback period., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable (manuscript does not report on or involve the use of any animal or human data or tissue). Ethical responsibilities: I wish to state that all the authors mutually agree that it should be submitted to Environmental Science and Pollution Research. I wish to state that the present work is the original work of the authors. I wish to state that the manuscript was not previously submitted to Environmental Science and Pollution Research. Results were presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Authors adhere to discipline-specific rules for acquiring, selecting, and processing data. Consent for publication: All authors agreed to publish their data prior in Environmental Science and Pollution Research and have not submitted the data in any form to any journal. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Physical activity guidelines targeting different populations with and without chronic diseases or disabilities are required to meet the diverse functional and physiological needs experienced by different subgroups of people to achieve optimal health benefits. As the importance of physical activity guidelines in promoting optimal health and well-being becomes increasingly recognised, there is a critical need for their systematic evaluation to ensure they remain effective, applicable and aligned with evolving health needs and scientific insights. This study aims to systematically review, critically evaluate, and compare global physical activity and sedentary behaviour guidelines on frequency, intensity, time, and type of exercise for adults, pregnant and postpartum women, and people living with chronic conditions and/or disabilities. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols checklist. We will search the Allied and Complementary Medicine Database, APA PsycInfo, Cumulative Index of Nursing and Allied Health Literature, Cochrane Library, Education Resources Information Center, Google Scholar, MEDLINE, PubMed, Scopus, SPORTDiscus, Web of Science and grey literature databases from 2010 to October 2024. Two reviewers will independently select guidelines, extract data and assess methodological quality using the Appraisal of Guidelines for Research and Evaluation II Instrument . Key recommendations will be summarised and classified as 'strong' and 'conditional' based on established criteria. A comprehensive evaluation of current guidelines will identify their differences and similarities and reveal their relevance in practical settings. The findings will guide healthcare professionals, researchers and policymakers in implementing evidence-based recommendations for managing physical activity and sedentary behaviour in targeted populations. Additionally, we will highlight current knowledge gaps and potential shortcomings in existing guidelines. PROSPERO registration number: CRD42023491339., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Due to neofunctionalization, a single fold can be identified in multiple proteins that have distinct molecular functions. Depending on the time that has passed since gene duplication and the number of mutations, the sequence similarity between functionally divergent proteins can be relatively high, eroding the value of sequence similarity as the sole tool for accurately annotating the function of uncharacterized homologs. Here, we combine bioinformatic approaches with targeted experimentation to reveal a large multifunctional family of putative enzymatic and nonenzymatic proteins involved in heme metabolism. This family (homolog of HugZ (HOZ)) is embedded in the "FMN-binding split barrel" superfamily and contains separate groups of proteins from prokaryotes, plants, and algae, which bind heme and either catalyze its degradation or function as nonenzymatic heme sensors. In prokaryotes these proteins are often involved in iron assimilation, whereas several plant and algal homologs are predicted to degrade heme in the plastid or regulate heme biosynthesis. In the plant Arabidopsis thaliana, which contains two HOZ subfamilies that can degrade heme in vitro (HOZ1 and HOZ2), disruption of AtHOZ1 (AT3G03890) or AtHOZ2A (AT1G51560) causes developmental delays, pointing to important biological roles in the plastid. In the tree Populus trichocarpa, a recent duplication event of a HOZ1 ancestor has resulted in localization of a paralog to the cytosol. Structural characterization of this cytosolic paralog and comparison to published homologous structures suggests conservation of heme-binding sites. This study unifies our understanding of the sequence-structure-function relationships within this multilineage family of heme-binding proteins and presents new molecular players in plant and bacterial heme metabolism., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Subarachnoid block is the most common anesthetic technique for patients having corrective hip surgeries. However, adequate positioning for a successful subarachnoid block is a major challenge in this particular population of patients, owing to the site of fracture. Regional anesthesia, in the form of nerve blocks, is an effective means of alleviating such constraints and gives an added benefit of prolonged postoperative analgesia. The pericapsular nerve group (PENG) block and the fascia iliaca compartment block (FICB), under ultrasonography guidance, are a few examples of the commonly performed peripheral nerve blocks in such settings. However, the landmark-based techniques of nerve blockade still hold good in many resource poor settings, given the lack of ultrasonography facilities., Aim: To compare the ease of spinal positioning using the patient sitting satisfaction score between the landmark-guided FICB and PENG block., Materials and Methods: This study was done on 80 patients of the American Society of Anesthesiology (ASA) grade I or II with intertrochanteric fractures of the hip joint scheduled for proximal femoral nailing. Patients were allocated into two groups of 40 each through computer generated random numbers, to receive 30 ml of 0.5% ropivacaine via the landmark-guided technique of FICB in Group F and peripheral nerve stimulator assisted landmark-guided PENG block in Group P, 30 minutes prior to spinal positioning. Time to passive leg raise (PLR) to 15 degrees and time to PLR to 30 degrees with a standard goniometer guidance at visual analogue scale (VAS) score < 4 and ease of spinal positioning through the sitting satisfaction score at the 30th minute were assessed. Any adverse effects and events of failure were noted. The duration of postoperative analgesia was measured through the time to the first dose of paracetamol on arrival at the post-anesthesia care unit., Results: Statistical analysis was done using JASP version (0.18.3.0) using the independent samples t-test and significance was taken when p value was < 0.001. The time to PLR to 15 degrees and 30 degrees were achieved faster in the patients who received the PENG block in comparison to the patients who received the FICB, and the average patient sitting satisfaction score was significantly higher in Group P as compared to Group F (p < 0.001). While the overall amount of analgesics used in both groups was similar, the overall period of postoperative analgesia was prolonged in Group F compared to Group P (p < 0.001)., Conclusion: The landmark guided PENG block is feasible and superior to the landmark-guided FICB for preoperative positioning and analgesia. The FICB provides a longer duration of postoperative analgesia for patients with intertrochanteric fractures., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. SRM Medical College Hospital - Institutional Ethics Committee - Students issued approval SRMIEC-ST0922-196. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Pavithra et al.)

Background: Cutibacterium acnes, a common anaerobic platelet concentrate (PC) contaminant, has been associated with rare mild adverse transfusion reactions and is often considered a harmless commensal. Notably, C. acnes can cause chronic infections and has been shown to induce the release of proinflammatory cytokines by immune cells. Since elevated concentrations of proinflammatory factors in PCs have been linked to noninfectious adverse reactions, this study aimed to assess whether C. acnes could elicit the release and accumulation of proinflammatory factors during PC storage, thereby enhancing the risk of such reactions., Study Design/methods: Four ABO-matched buffy coat PCs were pooled and split into six units, each were inoculated with either saline (negative control), a Staphylococcus aureus isolate (positive control, 30 colony forming units [CFU]/unit), or four C. acnes PC isolates (10 CFU/mL) and stored at 20-24°C with agitation. Bacterial counts, platelet activation, and concentration of proinflammatory factors were assessed on days 0, 3, and 5. N = 3., Results: C. acnes counts remained stable, while S. aureus proliferated reaching 10 8 CFU/mL by the end of PC storage. By day 5, no significant differences in platelet activation or proinflammatory cytokine profiles were observed in C. acnes-contaminated PCs compared to the negative control (p > .05), while there was a significant increase (p ≤ .05) in sCD40L concentration (day 3), and platelet activation and IL-8 concentration (day 5) in S. aureus-contaminated units., Discussion: C. acnes contamination does not promote the accumulation of proinflammatory factors in the absence of proliferation during storage and may not enhance the risk of inflammatory reactions when transfused to patients., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background and Aim: The aim of this study is to compare the effect of different lubricating agents used with the i-gel® laryngeal mask airway on the incidence of postoperative sore throat., Materials and Methods: After obtaining institutional ethics approval, this prospective trial was conducted on 150 patients who were scheduled for minor surgical procedures. The study population was placed in three groups of 50 each, after randomization with computer-generated random numbers, based on the lubricant used (Group LJ: with lignocaine jelly as the lubricant, Group WJ: with water-based jelly as a lubricant, Group NS: with 0.9% normal saline as a lubricant). The time taken to secure the airway (from insertion to the first end-tidal carbon dioxide (ETCO 2 ) tracing and five-point auscultation) and the number of attempts were noted. During extubation, blood staining was noted. In the postoperative period, sore throat was monitored with the numerical rating scale for the first 24 hours. Postoperative hoarseness of voice, cough and difficulty in swallowing were the other parameters noted. The results were entered in a standard spread sheet. Statistical analysis was done using JASP version 0.18.3.0 using the independent samples t-test and the Chi-square test for quantitative variables., Results: All three groups were comparable in terms of demography (p > 0.05). The time taken to insertion, number of attempts and securing of the airway were also comparable amongst the three groups (p > 0.05). Blood staining during LMA removal was comparable between the three groups (p > 0.05). In the postoperative period, sore throat was comparable between the three groups (p > 0.05). The incidence of hoarseness of voice in the postoperative period however was more significant in Group LJ when compared to the other two (p < 0.05). Postoperative swallowing discomfort was also significantly higher in Group LJ than in the other two groups (p < 0.05)., Conclusion: We conclude that lignocaine jelly, water-based jelly and normal saline used as lubricating agents on the i-gel airway did not show a difference in the incidence of postoperative sore throat. Lignocaine jelly was associated with a higher incidence of hoarseness of voice and swallowing discomfort when compared to the other lubricants., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. SRM Medical College Hospital Institutional Ethics Committee issued approval 8469(A)/IEC/2022. This double-blind trial was registered with the Clinical Trial Registry of India (CTRI/2023/02/049480). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Balachandran et al.)

reasoning is a key ability for an intelligent system. Large language models (LMs) achieve above-chance performance on abstract reasoning tasks but exhibit many imperfections. However, human abstract reasoning is also imperfect. Human reasoning is affected by our real-world knowledge and beliefs, and shows notable "content effects"; humans reason more reliably when the semantic content of a problem supports the correct logical inferences. These content-entangled reasoning patterns are central to debates about the fundamental nature of human intelligence. Here, we investigate whether language models-whose prior expectations capture some aspects of human knowledge-similarly mix content into their answers to logic problems. We explored this question across three logical reasoning tasks: natural language inference, judging the logical validity of syllogisms, and the Wason selection task. We evaluate state of the art LMs, as well as humans, and find that the LMs reflect many of the same qualitative human patterns on these tasks-like humans, models answer more accurately when the semantic content of a task supports the logical inferences. These parallels are reflected in accuracy patterns, and in some lower-level features like the relationship between LM confidence over possible answers and human response times. However, in some cases the humans and models behave differently-particularly on the Wason task, where humans perform much worse than large models, and exhibit a distinct error pattern. Our findings have implications for understanding possible contributors to these human cognitive effects, as well as the factors that influence language model performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background and Objectives: Platelet concentrates (PC) are stored at 20-24°C to maintain platelet functionality, which may promote growth of contaminant bacteria. Alternatively, cold storage of PC limits bacterial growth; however, data related to proliferation of psychotrophic species in cold-stored PC (CSP) are scarce, which is addressed in this study., Materials and Methods: Eight laboratories participated in this study with a pool/split approach. Two split PC units were spiked with ~25 colony forming units (CFU)/PC of Staphylococcus aureus, Klebsiella pneumoniae, Serratia liquefaciens, Pseudomonas fluorescens and Listeria monocytogenes. One unit was stored under agitation at 20-24°C/7 days while the second was stored at 1-6°C/no agitation for 21 days. PC were sampled periodically to determine bacterial loads. Five laboratories repeated the study with PC inoculated with lyophilized inocula (~30 CFU/mL) of S. aureus and K. pneumoniae., Results: All species proliferated in PC stored at 20-24°C, reaching concentrations of ≤10 9  CFU/mL by day 7. Psychrotrophic P. fluorescens and S. liquefaciens proliferated in CSP to ~10 6  CFU/mL and ~10 5  CFU/mL on days 10 and 17 of storage, respectively, followed by L. monocytogenes, which reached ~10 2  CFU/mL on day 21. S. aureus and K. pneumoniae did not grow in CSP., Conclusion: Psychrotrophic bacteria, which are relatively rare contaminants in PC, proliferated in CSP, with P. fluorescens reaching clinically significant levels (≥10 5  CFU/mL) before day 14 of storage. Cold storage reduces bacterial risk of PC to levels comparable with RBC units. Safety of CSP could be further improved by implementing bacterial detection systems or pathogen reduction technologies if storage is beyond 10 days., (© 2024 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background: Caring for a child with long-term functional limitations can have a negative impact on the physical and psychological well-being of the caregiver. Family-centered care (FCC) interventions have the potential to empower caregivers and contribute to their well-being. This systematic review aimed to synthesize existing evidence on the effectiveness of FCC interventions in improving the well-being of caregivers of children with cerebral palsy (CP), and identify the key components of such interventions that are most commonly practiced and deemed effective., Methods: This review systematically searched seven databases for randomized controlled trials that evaluated the effectiveness of any FCC intervention on the well-being of caregivers of children with or at risk of CP. We used the Cochrane RoB 2.0 tool to assess risk of bias and Critical Appraisal Skills Programme (CASP) checklist for critical appraisal. Due to high heterogeneity of studies, narrative synthesis was used to summarize the data., Results: The review consists of 11 studies which were categorized into five sections based on the components of FCC intervention provided in each individual study: 1. Information provision, and Enabling and partnership (n= 5); 2. Information provision, and Respectful and supportive care (n= 1); 3. Enabling and partnership (n= 2); 4. Enabling and partnership, and Respectful and supportive care (n= 2); 5. Information provision, Enabling and partnership and Respectful and supportive care (n= 1). Risk of bias was low in four studies, unclear in two studies, and high in five studies., Conclusion: FCC interventions were found to be effective in improving caregivers' satisfaction with attainment of child and caregiver goals. Evidence from multiple studies does not strongly support the effectiveness of FCC interventions on caregiver's mental health, parenting and personal outcomes. Limited evidence precludes a conclusion on the effectiveness of the components of FCC on well-being of caregivers of children with CP., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Poojari DP et al.)

Heme has a critical role in the chemical framework of the cell as an essential protein cofactor and signaling molecule that controls diverse processes and molecular interactions. Using a phylogenomics-based approach and complementary structural techniques, we identify a family of dimeric hemoproteins comprising a domain of unknown function DUF2470. The heme iron is axially coordinated by two zinc-bound histidine residues, forming a distinct two-fold symmetric zinc-histidine-iron-histidine-zinc site. Together with structure-guided in vitro and in vivo experiments, we further demonstrate the existence of a functional link between heme binding by Dri1 (Domain related to iron 1, formerly ssr1698) and post-translational regulation of succinate dehydrogenase in the cyanobacterium Synechocystis, suggesting an iron-dependent regulatory link between photosynthesis and respiration. Given the ubiquity of proteins containing homologous domains and connections to heme metabolism across eukaryotes and prokaryotes, we propose that DRI (Domain Related to Iron; formerly DUF2470) functions at the molecular level as a heme-dependent regulatory domain., (© 2024. The Author(s).)

Background: Microbial screening of platelet concentrates (PC) with automated culture methods is widely implemented to reduce septic transfusion reactions. Herein, detection of bacterial contamination in PC was compared between units prepared in plasma and a mix of plasma and platelet additive solution (PAS) and between the BACT/ALERT 3D and next generation BACT/ALERT VIRTUO systems., Study Design/methods: Double apheresis units were split into single units, diluted in either PAS (PAS-PC) or plasma (plasma-PC), and tested for in vitro quality and sterility prior to spiking with ~30 CFU/unit of Staphylococcus epidermidis, Staphylococcus aureus, Serratia marcescens, and Klebsiella pneumoniae or ~10 CFU/mL of Cutibacterium acnes. Spiked PC were sampled for BACT/ALERT testing (36 and 48 h post-spiking) and colony counts (24, 36, and 48 h post-spiking). Times to detection (TtoD) and bacterial loads were compared between PC products and BACT/ALERT systems (N = 3)., Results: Bacterial growth was similar in plasma-PC and PAS-PC. No significant differences in TtoD were observed between plasma-PC and PAS-PC at the 36-h sampling time except for S. epidermidis which grew faster in plasma-PC and C. acnes which was detected earlier in PAS-PC (p < .05). Detection of facultative bacteria was 1.3-2.2 h sooner in VIRTUO compared with 3D (p < .05) while TtoD for C. acnes was not significantly different between the two systems., Discussion: Comparable bacterial detection was observed in plasma-PC and PAS-PC with PC sampling performed at 36-h post blood collection. PC sampling at ≤36 h could result in faster detection of facultative pathogenic organisms with the VIRTUO system and improved PC safety., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Molecular genetic understanding of flowering time regulation is crucial for sorghum development. GRAIN NUMBER, PLANT HEIGHT AND HEADING DATE 7 (SbGhd7) is one of the six classical loci conferring photoperiod sensitivity of sorghum flowering. However, its functions remain poorly studied. The molecular functions of SbGhd7 were characterized. The gene regulatory network controlled by SbGhd7 was constructed and validated. The biological roles of SbGhd7 and its major targets were studied. SbGhd7 overexpression (OE) completely prevented sorghum flowering. Additionally, we show that SbGhd7 is a major negative regulator of flowering, binding to the promoter motif TGAATG(A/T)(A/T/C) and repressing transcription of the major florigen FLOWERING LOCUS T 10 (SbFT10) and floral activators EARLY HEADING DATE (SbEhd1), FLAVIN-BINDING, KELCH REPEAT, F-BOX1 (SbFKF1) and EARLY FLOWERING 3 (SbELF3). Reinforcing the direct effect of SbGhd7, SbEhd1 OE activated the promoters of three functional florigens (SbFT1, SbFT8 and SbFT10), dramatically accelerating flowering. Our studies demonstrate that SbGhd7 is a major repressor of sorghum flowering by directly and indirectly targeting genes for flowering activation. The mechanism appears ancient. Our study extends the current model of floral transition regulation in sorghum and provides a framework for a comprehensive understanding of sorghum photoperiod response., (© 2024 The Authors New Phytologist © 2024 New Phytologist Foundation.)

Background1: Despite a growing interest in gaming rehabilitation for upper limb (UL) recovery post-stroke, studies investigating the effects of game-based rehabilitation incorporating functional games are lacking., Objective: To investigate the efficacy of an intensive, functional, gamified rehabilitation program compared to task-based training on UL motor function in acute/sub-acute stroke survivors., Methods: This randomized, multicenter, single-blind, clinical trial comprises 120 participants with unilateral stroke who were randomized to receive either gamified training (n = 64) using the ArmAble™ [experimental group (EG)] or task-based training (n = 56) in conjunction with conventional therapy for 2 hours per day, 6 days per week for 2 weeks, followed by UL rehabilitation for another 4 weeks at home. Primary outcomes evaluated by a blinded assessor included the Fugl-Meyer Assessment-Upper Extremity (FM-UE), and Action Research Arm Test (ARAT). Data were analyzed using a linear mixed-effect regression model., Results: The mean (standard deviation) age of the participants was 54.4 ± 11.7 years (78.1% men) in the EG and 57.7 ± 10.9 years (73.2% men) in the comparator group (CG). The median (interquartile range) time since stroke was 30.0 (54.0) days in the EG and 22.5 (45.0) days in the CG. Following the 2-week intervention, a statistically significant improvement was observed in the EG for the FM-UE [between-group mean differences (95% confidence interval): -3.9 (-6.5, -1.3); P  = .003]; but not for the ARAT [-2.9 (-5.8, 0.0); P  = .051]. Gains at 6 weeks were significantly greater in the EG for both FM-UE [-3.9 (-6.5, -1.3); P  = .003]; and ARAT [-3.0 (-5.9, -0.0); P  = .046]., Conclusion: Gamified rehabilitation using the ArmAble™ device has shown immediate and short-term improvement in UL function after acute/sub-acute stroke., Clinical Trials Registry Number: CTRI/2020/09/027651., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

At Canadian Blood Services, despite the use of 2% chlorhexidine and 70% isopropyl alcohol (standard disinfectant, SD) prior to venipuncture, Cutibacterium acnes evades eradication and is a major contaminant of platelet concentrates (PCs). Since C. acnes forms bacterial aggregates known as biofilms in the sebaceous niches of the skin, this study aimed to assess whether sebum-like components impact disinfectant efficacy against C. acnes leading to its dominance as a PC contaminant. C. acnes mono-species and dual-species biofilms ( C. acnes s and a transfusion-relevant Staphylococcus aureus isolate) were formed in the presence and absence of sebum-like components and exposed to SD, a hypochlorous acid-based disinfectant (Clinisept+, CP), or a combination of both disinfectants to assess disinfectant efficacy. Our data indicate that sebum-like components significantly reduce the disinfectant efficacy of all disinfectant strategies tested against C. acnes in both biofilm models. Furthermore, though none of the disinfectants led to bacterial eradication, the susceptibility of C. acnes to disinfectants was heightened in an isolate-dependent manner when grown in the presence of S. aureus . The reduction of skin disinfection efficacy in the presence of sebum may contribute to the overrepresentation of C. acnes as a PC contaminant and highlights the need for improved disinfection strategies.

Fouling on glass surfaces reduces the solar panel efficiency and increases water consumption for cleaning. Superhydrophobic coatings on glass enable self-cleaning by allowing water droplets to carry away dirt particles. Observing the interaction between charged particles and surfaces provides insights into effective cleaning. Using a high-speed camera and a long-distance objective, we analyzed the in situ deposition of variously functionalized and charged silica dust microparticles on chemically treated glass. The ambient charges for the control, hydrophobic, and positively charged particles were approximately -0.5, -0.13, and +0.5 nC, respectively. We found that a positively charged particle of 2.3 ± 1.2 μm diameter adhered to hydroxylated glass in ∼0.054 s, compared to 0.40 and 0.45 s for quaternary ammonium- and fluorosilane-functionalized hydrophobic glass. Experiments suggest that quaternary ammonium-functionalized glass surfaces are about 77.8% more resistant to soiling than bare surfaces.

Background and Objectives: Platelet concentrates (PCs) contaminated with Cutibacterium acnes are often transfused prior to detection by the BACT/ALERT system. Though C. acnes is implicated in mild transfusion reactions, delayed clinical effects are unknown. This study assessed the ability to enhance C. acnes detection by supplementing culture media with Tween 80 (T80, an oleic acid source) and a commercial nutrient supplement., Materials and Methods: Anaerobic culture bottles (BPN) were supplemented with T80 or oleic acid. T80-supplemented BPN bottles were inoculated with four C. acnes isolates (10 or 100 colony-forming units [CFU]/bottle) or other transfusion-relevant bacteria (10 CFU/bottle). Samples of plasma containing SSP+ (platelet additive solution [PAS]) (PAS-plasma) at different concentrations, plasma-PCs and PAS-PCs, spiked with two C. acnes isolates (10 CFU/bottle), were inoculated into T80-supplemented BPN bottles. Furthermore, plasma-PCs were spiked with C. acnes and tested in BPN bottles supplemented with the BD Difco Supplement VX (BDVx). Bottles were incubated in the BACT/ALERT system and times to detection (TtoD) were compared (N = 3)., Results: A reduction in TtoD of ≤3.5 days was observed for C. acnes in T80-supplemented BPN, while other species did not show the same effect. However, false positives were observed when T80-supplemented BPN was inoculated with PAS-plasma (except for 70% PAS:30% plasma), plasma-PCs or PAS-PCs. Oleic acid supplementation also resulted in false positives. Interestingly, BDVx-supplemented BPN reduced the TtoD of C. acnes in PCs by ≤1.2 days (p < 0.05), with no false-positive results., Conclusion: BDVx supplementation for detection of C. acnes from PCs could result in timely unit retrieval, preventing the transfusion of contaminated products. In clinical settings, T80 supplementation could significantly enhance C. acnes detection from non-blood-derived samples., (© 2023 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Objective: Predicting post-stroke recovery through prediction models is crucial for choosing appropriate treatment options. However, the existing models predominantly incorporate clinical measures although measurement of movement quality using kinematic measures is essential for distinguishing various types of recovery. Thus, this study aimed at determining if, by considering varied aspects of recovery, adding kinematic measurements over clinical measures would better predict upper extremity (UE) motor impairments at three months post-stroke., Materials and Methods: Eighty-nine stroke survivors (58.9 ± 11.8 years) were assessed for clinical predictors between 4 and 7 days, kinematic predictors within 1 month, and the impairment outcome of the Fugl Meyer Assessment of the UE (FM-UE) at three months post-stroke. Significant predictors (p<0.05) with a variation inflation factor (VIF) <10 were selected for model development. After performing further step-wise selection, three models incorporating clinical outcomes, kinematic measurements, and a combination of these two, respectively, were formulated., Results: The clinical model (R 2  = 0.70) included shoulder abduction finger extension (SAFE) scores, the National Institutes of Health Stroke Scale (NIHSS), and the Montreal Cognitive Assessment (MoCA). The kinematic model (R 2  = 0.34) included total displacement, total time, and reaction time. The combined model (R 2  = 0.72) comprised of SAFE score and shoulder flexion. All the models had a minimal mean squared error on cross validation, which indicated a good validity., Conclusion: The performance of clinical and combined prediction models for predicting three-month post-stroke UE motor recovery was nearly similar. However, in order to detect minimal changes over time and to understand all aspects of motor recovery, there is a need to add instrument-based kinematic measures., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Skin flora bacteria, such as Cutibacterium acnes , are the predominant contaminants of blood products used for transfusion. Platelet concentrates (PCs), a therapeutic product used to treat patients with platelet deficiencies, are stored at ambient temperature under agitation, providing ideal conditions for bacterial proliferation. At Canadian Blood Services, PCs are screened for microbial contamination using the automated BACT/ALERT culture system. Positive cultures are processed and contaminating organisms are identified using the VITEK 2 system. Over a period of approximately 2 years, several PC isolates were identified as Atopobium vaginae to a high level of confidence. However, since A. vaginae is associated with bacterial vaginosis and is not a common PC contaminant, a retrospective investigation revealed that in all cases C. acnes was misidentified as A. vaginae . Our investigation demonstrated that the media type used to grow PC bacterial isolates can have a significant impact on the results obtained on the VITEK 2 system. Furthermore, other identification methods such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALD-TOF MS) and PCR amplification of the 16S RNA gene were only partially successful in the identification of C. acnes . Therefore, our findings support a multiphasic approach when PC isolates are identified as A. vaginae by the VITEK 2 system for proper identification of C. acnes using macroscopic, microscopic and other biochemical analyses., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we design a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibits PLpro with k inact /K I  = 9,600 M -1 s -1 , achieves sub-μM EC 50 values against three SARS-CoV-2 variants in mammalian cell lines, and does not inhibit a panel of human deubiquitinases (DUBs) at >30 μM concentrations of inhibitor. An X-ray co-crystal structure of the compound bound to PLpro validates our design strategy and establishes the molecular basis for covalent inhibition and selectivity against structurally similar human DUBs. These findings present an opportunity for further development of covalent PLpro inhibitors., (© 2023. UT-Battelle, LLC.)

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or M pro , is a promising target for the development of novel antiviral therapeutics. Previous X-ray crystal structures of M pro were obtained at cryogenic tem-per-ature or room tem-per-ature only. Here we report a series of high-resolution crystal structures of unliganded M pro across multiple tem-per-atures from cryogenic to physiological, and another at high humidity. We inter-rogate these data sets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a perturbation-dependent conformational landscape for M pro , including a mobile zinc ion inter-leaved between the catalytic dyad, mercurial conformational heterogeneity at various sites including a key substrate-binding loop, and a far-reaching intra-molecular network bridging the active site and dimer inter-face. Our results may inspire new strategies for antiviral drug development to aid preparation for future coronavirus pandemics., (© Ali Ebrahim et al. 2022.)

Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we have designed a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibited PLpro with k inact /K I = 10,000 M - 1 s - 1 , achieved sub-µM EC 50 values against three SARS-CoV-2 variants in mammalian cell lines, and did not inhibit a panel of human deubiquitinases at > 30 µM concentrations of inhibitor. An X-ray co-crystal structure of the compound bound to PLpro validated our design strategy and established the molecular basis for covalent inhibition and selectivity against structurally similar human DUBs. These findings present an opportunity for further development of covalent PLpro inhibitors.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), threatens global public health. The world needs rapid development of new antivirals and vaccines to control the current pandemic and to control the spread of the variants. Among the proteins synthesized by the SARS-CoV-2 genome, main protease (M pro also known as 3CL pro ) is a primary drug target, due to its essential role in maturation of the viral polyproteins. In this study, we provide crystallographic evidence, along with some binding assay data, that three clinically approved anti hepatitis C virus drugs and two other drug-like compounds covalently bind to the M pro Cys145 catalytic residue in the active site. Also, molecular docking studies can provide additional insight for the design of new antiviral inhibitors for SARS-CoV-2 using these drugs as lead compounds. One might consider derivatives of these lead compounds with higher affinity to the M pro as potential COVID-19 therapeutics for further testing and possibly clinical trials., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Objectives: Whole blood (WB) transfusion has regained attention to treat trauma patients. We reported no significant changes in in vitro quality through 21 days of cold storage for leukoreduced WB (LCWB) when time to filtration was extended from 8 to 24 h from collection. This study evaluated the impact of extended WB-hold at room temperature (RT) prior to leukoreduction on proliferation of transfusion-relevant bacteria., Materials and Methods: WB units were spiked with suspensions of Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Listeria monocytogenes prepared in saline solution (SS) or trypticase soy broth (TSB) to a concentration of ~0.2 CFU/ml (N = 6). Spiked units were held at RT for 18-24 h before leukoreduction and cold-stored for 21 days. Bacterial growth was determined on days 2, 7, 14 and 21. In vitro quality of WB inoculated with unspiked diluents was assessed., Results: K. pneumoniae and S. pyogenes proliferated in WB prior to leukoreduction reaching concentrations ≤10 2 CFU/ml. These bacteria, however, did not proliferate during the subsequent cold storage. S. aureus did not survive in WB while L. monocytogenes reached a concentration of ~10 2 CFU/ml by day 21. LCWB in vitro quality was not affected by SS or TSB., Conclusion: Extended WB-hold prior to leukoreduction allowed proliferation of bacteria able to resist immune clearance, although they did not grow to clinically significant levels. While L. monocytogenes proliferated in LCWB, clinically relevant concentrations were not reached by day 21. These data suggest that transfusing LCWB may not pose a significant bacterial contamination safety risk to transfusion patients., (© 2022 International Society of Blood Transfusion.)

Background and Purpose: Measurement of movement quality is essential to distinguish motor recovery patterns and optimize rehabilitation strategies post-stroke. Recently, the Stroke Recovery and Rehabilitation Roundtable Taskforce (SRRR) recommended four kinetic and kinematic performance assays to measure upper extremity (UE) movements and distinguish behavioral restitution and compensation mechanisms early post-stroke. The purpose of this study is to develop and validate a prediction model to analyze the added prognostic value of performance assays over clinical variables assessed up to 1-month post stroke for predicting recovery of UE motor impairment, capacity and quality of movement (QoM) measured at 3 months post-stroke onset., Methods: In this prospective cohort study, 120 stroke survivors will be recruited within seven days post-stroke. Candidate predictors such as baseline characteristics, demographics and performance assays as per SRRR recommendations along with tonic stretch reflex threshold will be measured up to 1-month post-stroke. Upper extremity motor recovery will be evaluated in terms of motor impairment (Fugl-Meyer assessment for UE), UE capacity measured with Action Research Arm Test (ARAT) and QoM (movement smoothness in the form of peak metrics [PM]) assessed with a reach-to-grasp-to-mouth task (mimicking a drinking task) at 3 months post-stroke. Three multivariable linear regression models will be developed to predict factors responsible for the outcomes of Fugl-Meyer assessment for upper extremity (FM-UE), ARAT and movement quality. The developed models will be internally validated using a split-sample method., Discussion: This study will provide a validated prediction model inclusive of clinical and performance assays that may assist in prediction of UE motor recovery. Predicting the amount of recovery and differentiating between behavioral restitution and compensation (as reflected by the FM-UE, QoM and ARAT) would enable us in realistic goal formation and planning rehabilitation. It would also help in encouraging patients to partake in early post-stroke rehabilitation thus improving the recovery potential., (© 2022 John Wiley & Sons Ltd.)

Bovine tropical theileriosis (BTT) is a tick-borne protozoan disease of cattle and responsible for major economic losses to the dairy farmers in India. This report describes diagnosis, genotyping and successful treatment of heavy infection of Theileria annulata in an organized dairy farm at Kattupakkam, Chennai. Four cross bred cows of 2 to 5 years of age showed clinical signs i.e., anorexia, salivation and panting. Clinical examination revealed pyrexia (40.0 °C to 40.1 °C), pale mucus membranes, enlarged prescapular lymph nodes and haemoglobinuria. The peripheral blood smear examination of infected cows revealed presence of piroplasm within the RBCs indicating high parasitemia. Haematology results suggested that decreased levels of Hb, RBC, WBC and PCV in the infected cows when compared with normal reference values. There were increased serum ALT and AST values and reduced serum total protein, albumin, calcium and phosphorous values in the infected cows. Semi-nested PCR using T. annulata specific oligonucleotide primers amplified 199 bp of the partial T. annulata 18S rRNA gene. Presence of four satellite markers TS6, TS8, TS9, and TS12 in the Theileria annulata isolates 1 and 2 indicating that the isolates were the same haplotype and suggested the infection in the farm was due to a single haplotype of T. annulata parasite. Based on the clinical signs, microscopic examination of blood smear and molecular diagnosis, the condition was diagnosed as tropical theileriosis. Infected cows were successfully treated with a single deep intramuscular injection of buparvaquone (Zubion®, INTAS pharmaceuticals LTD, Ahmedabad, India) along with supportive medication., (Copyright © 2021. Published by Elsevier B.V.)

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or M pro , is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of M pro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded M pro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for M pro , including mobile solvent interleaved between the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and a far-reaching intramolecular network bridging the active site and dimer interface. Our results may inspire new strategies for antiviral drug development to counter-punch COVID-19 and combat future coronavirus pandemics., Competing Interests: Declaration of interests The authors declare no competing interests.

Background: Despite proven health benefits of regular participation in physical activities (PA), adults with stroke fail to achieve recommended levels of PA. Sports being an enjoyable activity is more likely to encourage participation. Therefore, the objectives of the present study are i) to develop and test the feasibility of adaptive sports for promoting PA and Quality of Life (QoL) in community-dwelling adults with stroke, and ii) to explore the participants perception and experiences of playing adaptive sports., Methods: Two focus groups were conducted among the eight experts and a person with stroke to develop adaptive sports. To test the feasibility of these adaptive sports, in a multi methods study eighteen community dwelling adults with stroke were recruited. Participants played adaptive sports twice a week for two months in a community center. Participants pre and post intervention PA levels and QoL were measured. Participants were also interviewed at the end of the program to explore their experiences of participation in adaptive sports., Results: At the end of the program retention rate of the participants was 83.33% and there was a significant improvement in PA levels, while the improvement in QoL was not statistically significant. Participants expressed positive experience with the program. There were no adverse events during or after the participation. Health benefits, fitness, and fun were reported as facilitators, while lack of access to the sporting facility and lack of caregiver support were reported as barriers to participation., Conclusion: Adaptive sports appear to be safe, feasible, and well accepted by the adults with stroke., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To evaluate and summarize the level of evidence for the immediate, short-term, and long-term effects of game-based rehabilitation on upper limb function in adults within the first six months following stroke., Introduction: A game-based intervention is a valuable therapeutic tool for incorporating principles of motor learning and neuroplasticity in the rehabilitation of upper limb function post-stroke. Most of the existing reviews on game-based rehabilitation are focused on the chronic phase of stroke. However, as maximum upper limb motor recovery occurs in the first six months after stroke, further exploration of the effects of game-based rehabilitation in this phase is necessary., Inclusion Criteria: We will include randomized clinical trials assessing the immediate, short-term, and long-term effects of game-based rehabilitation on upper limb function in adults within the first six months following stroke., Methods: The systematic review will follow the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) checklist and JBI methodology for systematic reviews of effectiveness. A database-specific search strategy will be used in CINAHL, PubMed, Scopus, Web of Science, ProQuest, PEDro, OT Seeker, and Ovid MEDLINE to identify studies in the English language with no date limit. Two reviewers will independently screen, extract data from, and assess risk of bias in the eligible studies. Meta-analysis and publication bias evaluation will be done when adequate data are available. If a meta-analysis is precluded, then a narrative synthesis will be done. The Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria will be used to assess the certainty of evidence for the outcome measures of interest., Systematic Review Registration Number: PROSPERO CRD42020190100., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

Introduction: Game-based rehabilitation is an emerging therapeutic intervention that allows intensive, repetitive, task-based training to improve upper limb (UL) function following stroke, based on the principles of neuro-plasticity and motor (re)learning. Rehabilitation using commercial gaming system will be motivating, enjoyable, challenging and affordable. Therefore, the present study aims at assessing the effectiveness of an intensive, functional, gamified rehabilitation program using the ArmAble™ device in improving UL motor function in people with stroke., Method: In this single-blinded, multi-centric, randomized clinical trial, 120 adults with acute/sub-acute unilateral stroke will be randomized to receive an intensive, functional, gamified training program using the ArmAble™ or task-based training along with a conventional therapy for 2 h/day, 6 days/week for 2 weeks, followed by a home-based, functional rehabilitation program for another 4 weeks (~30 min/day, 6 days/week). Primary outcomes evaluated by a blinded assessor at the baseline, 2 weeks and 6 weeks' post-intervention will include the Fugl-Meyer assessment - upper extremity and the action research arm test. A linear mixed effect regression model or relevant non-parametric tests will be used to analyze the data for all outcomes. An intention-to-treat analysis will be used with missing data handled by multiple imputation., Discussion: Rehabilitation provided with the ArmAble™ device, if found effective, can be used from the early stages post-stroke to provide intensive, repetitive, gamified training to improve UL motor function., Trial Registration Number: CTRI/2020/09/027651., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Stroke survivors often face difficulty in community ambulation though they attain steady-state walking in clinical setups. Compliance and unpredictability of the environment may alter the muscle activity and challenge the individual's gait. Successful reintegration into the community requires gait assessment and training in a real-life challenging environment. Little is known about the assessment and training of gait in the community environment under challenging mobility dimensions. Hence, we aimed to study the changes that real-life environmental dimensions have on the activity of selected muscles in hemiparetic lower limb and gait velocity in stroke survivors., Methods: An observational cross-sectional study was conducted on 16 ambulatory stroke survivors to assess the hemiparetic lower limb muscle activity during walking in real-life environmental dimensions. Participants were made to walk in the community on a walkway consisting of even surface, ramp, stairs, uneven terrain and obstacles. They were also made to manoeuvre through traffic and pick a load while walking for a distance in the walkway. Muscle activity of Rectus Femoris, Biceps Femoris, Gastrocnemius Medialis and Tibialis Anterior of the paretic lower limb were continuously recorded while walking using wireless surface electromyography. Gait velocity for the entire walkway and level of perceived difficulty while walking in different dimensions were also measured. Paired t-test was used to compare the percentage Maximum Voluntary Contraction (%MVC) of lower limb muscles between even surface and real-life environment dimensions while walking. One sample t-test was used to compare the gait velocity in real-life dimensions versus gait velocity in even surface measured in an earlier study., Results: There was a significant reduction (p < 0.01) in the activity of all four hemiparetic lower limb muscles while walking under the influence of real-life environmental dimensions compared to even surface. Gait velocity (0.33 ± 0.17 m/s) was significantly lower than that is essential to be a community ambulator. The level of perceived difficulty across all dimensions was reported qualitatively with the highest difficulty reported during stair and obstacle clearance., Conclusion: Real-life environmental dimensions lead to the reduction of paretic lower limb muscle activities and gait velocity during walking in community-dwelling stroke survivors. Stroke survivors perceived more difficulty while walking in real-life environment dimensions particularly while negotiating stairs and obstacles., Significance: Knowledge about the influence of real-life environmental dimensions will help the clinicians to target rehabilitation methods to improve walking adaptability., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities., Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity., Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020., Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms., Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes., Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01)., Conclusions and Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

Background: Whole blood (WB) is held at room temperature for not more than 24 hours before blood component manufacturing. The ability of several culture collection, skin-derived, and transfusion-related bacteria to survive in WB stored at 22 ± 2°C for 24 hours was investigated in this study., Study Design and Methods: Twenty-one bacteria of the species Staphylococcus epidermidis, Staphylococcus aureus, Staphylococcus capitis, Streptococcus agalactiae, Serratia liquefaciens, Serratia marcescens, Klebsiella pneumoniae, Escherichia coli, and Yersinia enterocolitica were inoculated into 7-mL aliquots of WB at a concentration of 500 colony-forming units (CFU)/mL. Spiked WB was stored aerobically at 22 ± 2°C, and bacterial viability and growth were monitored at 3, 8, and 24 hours during WB storage. Bacteria that showed decreased viability during WB incubation were further characterized for their sensitivity to plasma factors and neutrophil killing., Results: There were three different scenarios for bacterial behavior during the hold of WB at 22 ± 2°C. Five bacteria proliferated (p < 0.03), 11 remained viable or showed low proliferation, and a third group of five bacteria had decreased or lost viability (p < 0.01). Three of the latter five bacteria were plasma-sensitive while the other two were plasma-resistant but susceptible to neutrophil killing (p = 0.01)., Conclusions: The bactericidal activity of WB can be the result of plasma sensitivity or neutrophil killing. Bacteria with a starting inoculum of 500 CFU/mL, and able to resist WB immune factors, can proliferate to clinically significant levels posing a potential safety risk to transfusion patients. Results of this pilot study should be validated under standard WB collection and storage conditions., (© 2019 AABB.)

Successful navigation can require realizing the current path choice was a mistake and the best strategy is to retreat along the recent path: 'back-track'. Despite the wealth of studies on the neural correlates of navigation little is known about backtracking. To explore the neural underpinnings of backtracking we tested humans during functional magnetic resonance imaging on their ability to navigate to a set of goal locations in a virtual desert island riven by lava which constrained the paths that could be taken. We found that on a subset of trials, participants spontaneously chose to backtrack and that the majority of these choices were optimal. During backtracking, activity increased in frontal regions and the dorsal anterior cingulate cortex, while activity was suppressed in regions associated with the core default-mode network. Using the same task, magnetoencephalography and a separate group of participants, we found that power in the alpha band was significantly decreased immediately prior to such backtracking events. These results highlight the importance for navigation of brain networks previously identified in processing internally-generated errors and that such error-detection responses may involve shifting the brain from default-mode states to aid successful spatial orientation.

Central to the concept of the "cognitive map" is that it confers behavioral flexibility, allowing animals to take efficient detours, exploit shortcuts, and avoid alluring, but unhelpful, paths. The neural underpinnings of such naturalistic and flexible behavior remain unclear. In two neuroimaging experiments, we tested human participants on their ability to navigate to a set of goal locations in a virtual desert island riven by lava, which occasionally spread to block selected paths (necessitating detours) or receded to open new paths (affording real shortcuts or false shortcuts to be avoided). Detours activated a network of frontal regions compared with shortcuts. Activity in the right dorsolateral PFC specifically increased when participants encountered tempting false shortcuts that led along suboptimal paths that needed to be differentiated from real shortcuts. We also report modulation in event-related fields and theta power in these situations, providing insight to the temporal evolution of response to encountering detours and shortcuts. These results help inform current models as to how the brain supports navigation and planning in dynamic environments.

The game of chess is the longest-studied domain in the history of artificial intelligence. The strongest programs are based on a combination of sophisticated search techniques, domain-specific adaptations, and handcrafted evaluation functions that have been refined by human experts over several decades. By contrast, the AlphaGo Zero program recently achieved superhuman performance in the game of Go by reinforcement learning from self-play. In this paper, we generalize this approach into a single AlphaZero algorithm that can achieve superhuman performance in many challenging games. Starting from random play and given no domain knowledge except the game rules, AlphaZero convincingly defeated a world champion program in the games of chess and shogi (Japanese chess), as well as Go., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)