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Despite the increasing interest in using microbial-based technologies to support human space exploration, many unknowns remain not only on bioprocesses but also on microbial survivability and genetic stability under non-Earth conditions. Here the desert cyanobacterium Chroococcidiopsis sp. CCMEE 029 was investigated for robustness of the repair capability of DNA lesions accumulated under Mars-like conditions (UV radiation and atmosphere) simulated in low Earth orbit using the EXPOSE-R2 facility installed outside the International Space Station. Genomic alterations were determined in a space-derivate of Chroococcidiopsis sp. CCMEE 029 obtained upon reactivation on Earth of the space-exposed cells. Comparative analysis of whole-genome sequences showed no increased variant numbers in the space-derivate compared to triplicates of the reference strain maintained on the ground. This result advanced cyanobacteria-based technologies to support human space exploration.

Purpose To assess the potential role of computed tomography (CT) texture analysis (CTTA) in identifying vulnerable patients with carotid artery atherosclerosis. Methods In this case-control pilot study, 12 patients with carotid atherosclerosis and a subsequent history of transient ischemic attack or stroke were age and sex matched with 12 control cases with asymptomatic carotid atherosclerosis (follow-up time 103.58 ± 9.2 months). CTTA was performed using a commercially available research software package (TexRAD) by an operator blinded to clinical data. CTTA comprised a filtration-histogram technique to extract features at different scales corresponding to spatial scale filter (fine = 2 mm, medium = 3 mm, coarse = 4 mm), followed by quantification using histogram-based statistical parameters: mean, kurtosis, skewness, entropy, standard deviation, and mean value of positive pixels. A single axial slice was selected to best represent the largest cross-section of the carotid bifurcation or the greatest degree of stenosis, in presence of an atherosclerotic plaque, on each side. Results CTTA revealed a statistically significant difference in skewness between symptomatic and asymptomatic patients at the medium (0.22 ± 0.35 vs − 0.18 ± 0.39, p < 0.001) and coarse (0.23 ± 0.22 vs 0.03 ± 0.29, p = 0.003) texture scales. At the fine-texture scale, skewness (0.20 ± 0.59 vs − 0.18 ± 0.58, p = 0.009) and standard deviation (366.11 ± 117.19 vs 300.37 ± 82.51, p = 0.03) were significant before correction. Conclusion Our pilot study highlights the potential of CTTA to identify vulnerable patients in stroke and TIA. CT texture may have the potential to act as a novel risk stratification tool in patients with carotid atherosclerosis.

Mitochondrial dysfunction has pleiotropic effects and is frequently caused by mitochondrial DNA mutations. However, factors such as significant variability in clinical manifestations make interpreting the pathogenicity of variants in the mitochondrial genome challenging. Here, we present APOGEE 2, a mitochondrially-centered ensemble method designed to improve the accuracy of pathogenicity predictions for interpreting missense mitochondrial variants. Built on the joint consensus recommendations by the American College of Medical Genetics and Genomics/Association for Molecular Pathology, APOGEE 2 features an improved machine learning method and a curated training set for enhanced performance metrics. It offers region-wise assessments of genome fragility and mechanistic analyses of specific amino acids that cause perceptible long-range effects on protein structure. With clinical and research use in mind, APOGEE 2 scores and pathogenicity probabilities are precompiled and available in MitImpact. APOGEE 2’s ability to address challenges in interpreting mitochondrial missense variants makes it an essential tool in the field of mitochondrial genetics. APOGEE 2 is a machine-learning tool for assessing the fragility of the mitochondrial genome, evaluating genetic variant pathogenicity and ultimately enhancing our understanding of the clinical heterogeneity of mitochondrial genetic diseases.

Desert strains of the genus Chroococcidiopsis are among the most desiccation-resistant cyanobacteria capable of anhydrobiosis. The accumulation of two sugars, sucrose and trehalose, facilitates the entrance of anhydrobiotes into a reversible state of dormancy by stabilizing cellular components upon water removal. This study aimed to evaluate, at the atomistic level, the role of trehalose in desiccation resistance by using as a model system the 30S ribosomal subunit of the desert cyanobacterium Chroococcidiopsis sp. 029. Molecular dynamic simulations provided atomistic evidence regarding its protective role on the 30S molecular structure. Trehalose forms an enveloping shell around the ribosomal subunit and stabilizes the structures through a network of direct interactions. The simulation confirmed that trehalose actively interacts with the 30S ribosomal subunit and that, by replacing water molecules, it ensures ribosomal structural integrity during desiccation, thus enabling protein synthesis to be carried out upon rehydration.

ObjectivesTo assess the intraoperative neuroimaging findings in patients treated with transcranial MR-guided focused ultrasound (tcMRgFUS) thalamotomy using 1.5T equipment in comparison with the 48-h follow-up.MethodsFifty prospectively enrolled patients undergoing unilateral tcMRgFUS thalamotomy for either medication-refractory essential tremor (n = 39) or Parkinson tremor (n = 11) were included. Two radiologists evaluated the presence and size of concentric lesional zones (zone I, zone II, and zone III) on 2D T2-weighted sequences acquired intraoperatively after the last high-energy sonication and at 48 h. Sonication parameters including number of sonications, delivered energy, and treatment temperatures were also recorded. Differences in lesion pattern and size were assessed using the McNemar test and paired t test, respectively.ResultsZones I, II, and III were visualized in 34 (68%), 50 (100%), and 44 (88%) patients, and 31 (62%), 50 (100%), and 45 (90%) patients after the last high-energy sonication for R1 and R2, respectively. All three concentric zones were visualized intraoperatively in 56–58% of cases. Zone I was significantly more commonly visualized at 48 h (p < 0.001). Diameter of zones I and II and the thickness of zone III significantly increased at 48 h (p < 0.001). Diameters of zones I and II measured intraoperatively demonstrated significant correlation with thermal map temperatures (p ≤ 0.001). Maximum temperature significantly correlated with zone III thickness at 48 h. A threshold of 60.5° had a sensitivity of 56.5–66.7% and a specificity of 70.5–75.5% for thickness > 6 mm at 48 h.ConclusionsIntraoperative imaging may accurately detect typical lesional findings, before completing the treatment. These imaging characteristics significantly correlate with sonication parameters and 48-h follow-up.Key Points• Intraoperative T2-weighted images allow the visualization of the zone I (coagulation necrosis) in most of the treated patients, while zone II (cytotoxic edema) is always detected.• Lesion size depicted with intraoperative transcranial MRgFUS imaging correlates well with procedure parameters.• Intraoperative transcranial MRgFUS imaging may have a significant added value for treating physicians.

Background Active upper extremity (UE) assistive devices have the potential to restore independent functional movement in individuals with UE impairment due to neuromuscular diseases or injury-induced chronic weakness. Academically fabricated UE assistive devices are not usually optimized for activities of daily living (ADLs), whereas commercially available alternatives tend to lack flexibility in control and activation methods. Both options are typically difficult to don and doff and may be uncomfortable for extensive daily use due to their lack of personalization. To overcome these limitations, we have designed, developed, and clinically evaluated the NuroSleeve, an innovative user-centered UE hybrid orthosis. Methods This study introduces the design, implementation, and clinical evaluation of the NuroSleeve, a user-centered hybrid device that incorporates a lightweight, easy to don and doff 3D-printed motorized UE orthosis and a functional electrical stimulation (FES) component. Our primary goals are to develop a customized hybrid device that individuals with UE neuromuscular impairment can use to perform ADLs and to evaluate the benefits of incorporating the device into occupational therapy sessions. The trial is designed as a prospective, open-label, single-cohort feasibility study of eight-week sessions combined with at-home use of the device and implements an iterative device design process where feedback from participants and therapists informs design improvement cycles. Results All participants learned how to independently don, doff, and use the NuroSleeve in ADLs, both in clinical therapy and in their home environments. All participants showed improvements in their Canadian Occupational Performance Measure (COPM), which was the primary clinical trial outcome measure. Furthermore, participants and therapists provided valuable feedback to guide further development. Conclusions Our results from non-clinical testing and clinical evaluation demonstrate that the NuroSleeve has met feasibility and safety goals and effectively improved independent voluntary function during ADLs. The study’s encouraging preliminary findings indicate that the NuroSleeve has met its technical and clinical objectives while improving upon the limitations of the existing UE orthoses owing to its personalized and flexible approach to hardware and firmware design. Trial Registration: ClinicalTrials.gov identifier: NCT04798378, https://clinicaltrials.gov/ct2/show/NCT04798378 , date of registration: March 15, 2021.

The prevalence and impact of imaging findings detected during screening procedures in patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy for functional neurological disorders has not been assessed yet. This study included 90 patients who fully completed clinical and neuroradiological screenings for tcMRgFUS in a single-center. The presence and location of preoperative imaging findings that could impact the treatment were recorded and classified in three different groups according to their relevance for the eligibility and treatment planning. Furthermore, tcMRgFUS treatments were reviewed to evaluate the number of transducer elements turned off after marking as no pass regions the depicted imaging finding. A total of 146 preoperative imaging findings in 79 (87.8%) patients were detected in the screening population, with a significant correlation with patients’ age (rho = 483, p < 0.001). With regard of the group classification, 119 (81.5%), 26 (17.8%) were classified as group 1 or 2, respectively. One patient had group 3 finding and was considered ineligible. No complications related to the preoperative imaging findings occurred in treated patients. Preoperative neuroradiological findings are frequent in candidates to tcMRgFUS and their identification may require the placement of additional no-pass regions to prevent harmful non-targeted heating.

The concept of ideal tumor surgery is to remove the neoplastic tissue without damaging adjacent normal structures. High-intensity focused ultrasound (HIFU) was developed in the 1940s as a viable thermal tissue ablation approach. In clinical practice, HIFU has been applied to treat a variety of solid benign and malignant lesions, including pancreas, liver, prostate, and breast carcinomas, soft tissue sarcomas, and uterine fibroids. More recently, magnetic resonance guidance has been applied for treatment monitoring during focused ultrasound procedures (magnetic resonance–guided focused ultrasound, MRgFUS). Intraoperative magnetic resonance imaging provides the best possible tumor extension and dynamic control of energy deposition using real-time magnetic resonance imaging thermometry. We introduce the fundamental principles and clinical indications of the MRgFUS technique; we also report different treatment options and personal outcomes.

Intracortical Brain-computer interfaces (iBCIs) are a promising technology to restore function after stroke. It remains unclear whether iBCIs will be able to use the signals available in the neocortex overlying stroke affecting the underlying white matter and basal ganglia. Here, we decoded both local field potentials (LFPs) and spikes recorded from intracortical electrode arrays in a person with chronic cerebral subcortical stroke performing various tasks with his paretic hand, with and without a powered orthosis. Analysis of these neural signals provides an opportunity to explore the electrophysiological activities of a stroke affected brain and inform the design of medical devices that could restore function. The frequency domain analysis showed that as the distance between an array and the stroke site increased, the low frequency power decreased, and high frequency power increased. Coordinated cross-channel firing of action potentials while attempting a motor task and cross-channel simultaneous low frequency bursts while relaxing were also observed. Using several offline analysis techniques, we propose three features for decoding motor movements in stroke-affected brains. Despite the presence of unique activities that were not reported in previous iBCI studies with intact brain functions, it is possible to decode motor intents from the neural signals collected from a subcortical stroke-affected brain.

Transcutaneous spinal cord stimulation (tSCS) is a promising non-invasive method to improve motor function in individuals with spinal cord injury (SCI) by enhancing spinal reflex pathways. This study aimed to investigate the effects of different tSCS electrode placement montages and targeted spinal levels on neurophysiological responses such as spinally evoked motor responses (sEMRs), dorsal root reflex activation, and muscle recruitment in individuals with SCI and healthy controls to optimize stimulation strategies for motor recovery. Five participants (three individuals with SCI and two controls) underwent transcutaneous spinal cord stimulation using various electrode montages, target spinal level stimulation, and single- and paired-pulse paradigms. Electromyographic responses were analyzed to determine sEMR threshold, amplitudes, and paired-pulse attenuation. Different spinal levels and spatial configurations of electrode placements influenced the sEMR threshold and incidence of sEMR across all participants. Paired-pulse analysis showed more pronounced second-pulse attenuation in SCI participants (48 ± 36%) than in controls (12 ± 20%, p = 0.0425), with distinct trends observed across montages and muscle groups. These findings suggest that spinal level, electrode configuration, and paired-pulse effects are key factors in personalizing tSCS, informing the development of patient-centered therapeutic strategies. Future studies with larger and more diverse cohorts are needed to validate and expand these findings.