Comparisons of three different modes of digital mirror therapy for post-stroke rehabilitation: Preliminary results of randomized controlled trial.

Objective: Technologically adapted mirror therapy shows promising results in improving motor function for stroke survivors. The treatment effects of a newly developed multi-mode stroke rehabilitation system offering multiple training modes in digital mirror therapy remain unknown. This study aimed to examine the effects of unilateral mirror visual feedback (MVF) with unimanual training (UM-UT), unilateral MVF with bimanual training (UM-BT), and bilateral MVF with bimanual training (BM-BT) on clinical outcomes in stroke survivors, compared to classical mirror therapy (CMT). Methods: Thirty-five participants were randomly assigned to one of four groups receiving fifteen 60-minute training sessions for 3-4 weeks. The Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Chedoke Arm and Hand Activity Inventory (CAHAI), Revised Nottingham Sensory Assessment (rNSA), Motor Activity Log (MAL), and EQ-5D-5L were administered at pre- and post-intervention and at 1-month follow-up. Results: After intervention and follow-up, significant within-group treatment efficacies were found on most primary outcomes of the FMA-UE and CAHAI scores in all four groups. Significant within-group improvements in the secondary outcomes were found on the MAL and EQ-5D-5L index in the UM-BT group, and the rNSA tactile sensation and MAL quality of movement subscales in the BM-BT group. No significant between-group treatment efficacies were found. Conclusions: UM-UT, UM-BT, BM-BT, and CMT led to similar clinical effects on the FMA-UE and can be considered effective alternative interventions for post-stroke upper-limb motor rehabilitation. UM-BT and BM-BT showed within-group improvements in functional performance in the patients' affected upper limbs in real-life activities.

Task-Oriented Training by a Personalized Electromyography-Driven Soft Robotic Hand in Chronic Stroke: A Randomized Controlled Trial.

BACKGROUND: Intensive task-oriented training has shown promise in enhancing distal motor function among patients with chronic stroke. A personalized electromyography (EMG)-driven soft robotic hand was developed to assist task-oriented object-manipulation training effectively. Objective. To compare the effectiveness of task-oriented training using the EMG-driven soft robotic hand. METHODS: A single-blinded, randomized controlled trial was conducted with 34 chronic stroke survivors. The subjects were randomly assigned to the Hand Task (HT) group (n = 17) or the control (CON) group (n = 17). The HT group received 45 minutes of task-oriented training by manipulating small objects with the robotic hand for 20 sessions, while the CON group received 45 minutes of hand-functional exercises without objects using the same robot. Fugl-Meyer assessment (FMA-UE), Action Research Arm Test (ARAT), Modified Ashworth Score (MAS), Box and Block test (BBT), Maximum Grip Strength, and active range of motion (AROM) of fingers were assessed at baseline, after intervention, and 3 months follow-up. The muscle co-contraction index (CI) was analyzed to evaluate the session-by-session variation of upper limb EMG patterns. RESULTS: The HT group showed more significant improvement in FMA-UE (wrist/hand, shoulder/elbow) compared to the CON group (P < .05). At 3-month follow-up, the HT group demonstrated significant improvements in FMA-UE, ARAT, BBT, MAS (finger), and AROMs (P < .05). The HT group exhibited a more significant decrease in muscle co-contractions compared to the CON group (P < .05). CONCLUSIONS: EMG-driven task-oriented training with the personalized soft robotic hand was a practical approach to improving motor function and muscle coordination. CLINICAL TRIAL REGISTRY NAME: Soft Robotic Hand System for Stroke Rehabilitation. CLINICAL TRIAL REGISTRATION-URL: https://clinicaltrials.gov/. UNIQUE IDENTIFIER: NCT03286309.

Comparison of the Radiographic and Clinical Outcomes between the Sinus Tarsi and Extended Lateral Approaches for Intra-Articular Calcaneal Fractures: A Retrospective Study.

The aim of this study was to compare the radiological and functional outcomes of the extended lateral and sinus tarsi approaches for managing displaced intraarticular calcaneal fractures. This retrospective study involved 44 patients with displaced intra-articular calcaneal fractures. The patients were treated with either the extended lateral or sinus tarsi approach and followed up for at least a year. The radiological and clinical outcomes were compared between the approaches. The waiting time for surgery was shorter and the complication rate was lower in the sinus tarsi approach group than in the other group. There were no significant differences in the American Orthopedic Foot and Ankle Society ankle-hindfoot score, Foot Function Index, or visual analog scale score between the groups. In both groups, the radiological outcomes (Böhler angle, calcaneal width, and calcaneal height) were better postoperatively than preoperatively. The sinus tarsi approach is a safe and effective alternative to the extended lateral approach for managing displaced intraarticular calcaneal fractures. It is associated with a lower complication rate and a shorter waiting time for surgery than the extended lateral approach, with similar functional and radiological outcomes.

Polyethylene microplastics induced lipidomic responses in Chironomus tepperi: A two-generational exploration.

Microplastics (MPs) accumulating in freshwater sediment have raised concerns about potential risks to benthic dwelling organisms, yet few studies have examined the long-term impacts caused by MP exposure. This study investigated alterations to lipid profiles in an Australian freshwater invertebrate, Chironomus tepperi, induced by polyethylene MP fragments (1-45 µm) at environmentally relevant concentrations (125, 250, 500 and 1000 MPs/kg sediment), using a two-generational experimental design. In the parental generation, the relative abundance of triacylglycerols, total fatty acids and unsaturated fatty acids exhibited apparent hormetic patterns, with low-concentration stimulation and high-concentration inhibition observed. The overall trend in these lipid classes is consistent with previously observed changes to polar metabolite profiles, indicating that ingestion of MPs could inhibit nutrient assimilation from food leading to disruption of energy availability. In the first filial generation continuously exposed to MPs, however, abundance of cholesterol and total fatty acids increased with increasing exposure concentrations, suggesting different effects on energy metabolism between the parental generation and offspring. No differences in the lipidome were observed in first filial larvae that were not exposed, implying that MPs pose negligible carry-over effects. Overall, the combined results of this study together with a preceding metabolomics study provide evidence of a physical effect of MPs with subsequent impacts to bioenergetics. Nevertheless, future research is required to explore the potential long-term impacts caused by MPs, and to unravel the impacts of the surfactant control as a potential contributor to the observed hormetic response, particularly for studies exploring sub-lethal effects of MP exposure using sensitive omics techniques.

Bioactive Glass and Silica Particles for Skeletal and Cardiac Muscle Tissue Regeneration.

When skeletal and cardiac tissues are damaged, surgical approaches are not always successful and tissue regeneration approaches are investigated. Reports in the literature indicate that silica nanoparticles and bioactive glasses (BGs), including silicate bioactive glasses (e.g., 45S5 BG), phosphate glass fibers, boron-doped mesoporous BGs, borosilicate glasses, and aluminoborates, are promising for repairing skeletal muscle tissue. Silica nanoparticles and BGs have been combined with polymers to obtain aligned nanofibers and to maintain controlled delivery of nanoparticles for skeletal muscle repair. The literature indicates that cardiac muscle regeneration can be also triggered by the ionic products of BGs. This was observed to be due to the release of vascular endothelial growth factor and other growth factors from cardiomyocytes, which regulate endothelial cells to form capillary structures (angiogenesis). Specific studies, including both in vitro and in vivo approaches, are reviewed in this article. The analysis of the literature indicates that although the research field is still very limited, BGs are showing great promise for muscle tissue engineering and further research in the field should be carried out to expand our basic knowledge on the application of BGs in muscle (skeletal and cardiac) tissue regeneration. Impact statement This review highlights the potential of silica particles and bioactive glasses (BGs) for skeletal and cardiac tissue regeneration. These biomaterials create scaffolds triggering muscle cell differentiation. Ionic products from BGs stimulate growth factors, supporting angiogenesis in cardiac tissue repair. Further research is required to expand our know-how on silica particles and BGs in muscle tissue engineering.

Microplastics and other anthropogenic fibres in large apex shark species: Abundance, characteristics, and recommendations for future research.

Microplastics and microfibres are found ubiquitously in global oceans as well as marine organisms from different trophic levels. However, little is known about the presence of microplastics and microfibres in marine megafauna, such as sharks. This study provided the first investigation of the presence of microplastics and other anthropogenic fibres (i.e., cellulose based fibres) in intestine and muscle samples of four large apex shark species in Australian coastal waters. Microplastics and other anthropogenic fibres were found in 82% of the analysed intestine samples. The mean abundance in intestine samples was 3.1 ± 2.6 particles/individual, which corresponded to 0.03 ± 0.02 particles/g of intestine, across all shark species. The size of particles ranged from 190 to 4860 µm in length with 92% being fibrous in shape and the rest fragments. FTIR spectroscopy identified that 70% of fibres were cellulose-based followed by polyethylene terephthalate (PET), while the fragments were polyethylene and polypropylene. In shark muscles, 60% of samples contained microplastics and other anthropogenic fibres, again with the majority being cellulose-based fibres followed by PET fibres. Methodological differences hinder a more comprehensive assessment of microplastic contamination across studies. Additionally, we identified some challenges which should be factored in for future studies looking at the presence of microplastics as well as other anthropogenic fibres in these large marine organisms. Overall, the findings provide first evidence of microplastics and other anthropogenic fibres not only in the intestines, but also in muscle tissues of large apex shark species.

Generation and characterization of ultrabroadband polarization-frequency hyperentangled photons.

We generate ultrabroadband photon pairs entangled in both polarization and frequency bins through an all-waveguided Sagnac source covering the entire optical C- and L-bands (1530-1625 nm). We perform comprehensive characterization of high-fidelity states in multiple dense wavelength-division multiplexed channels, achieving full tomography of effective four-qubit systems. Additionally, leveraging the inherent high dimensionality of frequency encoding and our electro-optic measurement approach, we demonstrate the scalability of our system to higher dimensions, reconstructing states in a 36-dimensional Hilbert space consisting of two polarization qubits and two frequency-bin qutrits. Our findings hold potential significance for quantum networking, particularly dense coding and entanglement distillation in wavelength-multiplexed quantum networks.

Two-mode squeezing over deployed fiber coexisting with conventional communications.

Squeezed light is a crucial resource for continuous-variable (CV) quantum information science. Distributed multi-mode squeezing is critical for enabling CV quantum networks and distributed quantum sensing. To date, multi-mode squeezing measured by homodyne detection has been limited to single-room experiments without coexisting classical signals, i.e., on "dark" fiber. Here, after distribution through separate fiber spools (5 km), -0.9 ± 0.1-dB coexistent two-mode squeezing is measured. Moreover, after distribution through separate deployed campus fibers (about 250 m and 1.2 km), -0.5 ± 0.1-dB coexistent two-mode squeezing is measured. Prior to distribution, the squeezed modes are each frequency multiplexed with several classical signals-including the local oscillator and conventional network signals-demonstrating that the squeezed modes do not need dedicated dark fiber. After distribution, joint two-mode squeezing is measured and recorded for post-processing using triggered homodyne detection in separate locations. This demonstration enables future applications in quantum networks and quantum sensing that rely on distributed multi-mode squeezing.

Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model.

BACKGROUND: Effective therapy for COVID-19 remains limited. Hydroxychloroquine (HCQ) has been considered, but safety and efficacy concerns remain. Chitosan exhibits antiviral and immunomodulatory effects, yet how the combination of HCQ and chitosan performs in treating COVID-19 is unknown. METHODS: Male Syrian hamsters were inoculated intranasally with standardized stocks of the SARS-CoV-2 virus. Hamsters were allocated to saline (PBS), chitosan oligosaccharide (COS), HCQ, or COS + HCQ groups and received corresponding drugs. On days 1, 7, and 14 post-infection, two animals from each group were euthanized for sample collection. Viral loads were measured in lung homogenates. Biochemistry markers, cytokines, and immunoglobulins were analyzed from hamster sera. HCQ concentrations were compared between the blood, bronchoalveolar lavage, and lung tissues. All groups underwent histopathology exams of the lungs. Additional hamsters were treated with the same drugs to assess for toxicities to the heart and liver. RESULTS: Among all groups, viral loads in the COS + HCQ group were the lowest by day 8. The COS + HCQ group produced the highest interleukin (IL)-6 levels on day 4, and the highest IL-10, IgA and IgG levels on day 8. HCQ concentrations were higher in the COS + HCQ group's lungs than the HCQ group, despite having received half the dose of HCQ. Histopathology demonstrated earlier inflammation resolution and swifter viral clearance in the COS + HCQ group. There was no evidence of cardiac or hepatic injury in hamsters that received HCQ. CONCLUSION: In hamsters infected with the SARS-CoV-2 virus, the combination of intranasal COS and HCQ was associated with increased HCQ absorption in the lungs, more effective immune responses, without increasing the risk of hepatic or cardiac injuries.

Metabolomic responses in freshwater benthic invertebrate, Chironomus tepperi, exposed to polyethylene microplastics: A two-generational investigation.

The accumulation of microplastics (MPs) in sediments could pose risks to benthic organisms and their progeny. Here, we examined effects on traditional apical endpoints along with changes to whole body metabolite profiles induced by irregular shaped polyethylene MPs (1-45 µm) at environmentally relevant concentrations (125, 250, 500 and 1000 MPs/kg sediment) in Chironomus tepperi using a two-generation exposure regime. Survival and emergence of C. tepperi were negatively affected in the parental generation at the two highest concentrations, whereas endpoints associated with growth were only impacted at 1000 MPs/kg sediment. Metabolites associated with several amino acid and energy metabolism pathways were present at lower abundances at the highest exposure concentration suggesting an overall impact on bioenergetics which relates to the inhibition of food acquisition or nutrient assimilation caused by ingestion of MPs, rather than a traditional receptor-mediated toxicity response. In contrast, no significant effects on apical endpoints were observed in the continuous exposure of first filial generation, and lactic acid was the only metabolite that differed significantly between groups. Larvae in unexposed conditions showed no differences in survival or metabolite profiles suggesting that effects in the parental generation do not carry over to the next filial generation. The findings provide evidence on the underlying impacts of MP ingestion and potential adaption to MP exposure of C. tepperi.

Microplastics and Tire Wear Particles in Urban Stormwater: Abundance, Characteristics, and Potential Mitigation Strategies.

Stormwater has been identified as a pathway for microplastics (MPs), including tire wear particles (TWPs), into aquatic habitats. Our knowledge of the abundance of MPs in urban stormwater and potential strategies to control MPs in stormwater is still limited. In this study, stormwater samples were collected from microlitter capture devices (inlet and outlet) during rain events. Sediment samples were collected from the material captured in the device and from the inlet and outlet of a constructed stormwater wetland. MP (>25 µm) concentration in stormwater varied across different locations ranging from 3.8 to 59 MPs/L in raw and 1.8 to 32 MPs/L in treated stormwater, demonstrating a decrease after passage through the device (35-88% removal). TWPs comprised ∼95% of all particles, followed by polypropylene (PP) and poly(ethylene terephthalate) (PET). The concentration of TWPs ranged from 2.5 to 58 TWPs/L and 1450 to 4740 TWPs/kg in stormwater and sediment, respectively. A higher abundance of MPs was found in the sediment at the inlet of the constructed wetland compared to the outlet, indicating a potential role of wetlands in removing MPs from stormwater. These findings suggest that both constructed wetlands and microlitter capture devices can mitigate the transport of MPs from stormwater to the receiving waterways.

Integration of statistical shape modeling and alternating interpolation-based model tracking technique for measuring knee kinematics in vivo using clinical interleaved bi-plane fluoroscopy.

Background: A 2D fluoroscopy/3D model-based registration with statistical shape modeling (SSM)-reconstructed subject-specific bone models will help reduce radiation exposure for 3D kinematic measurements of the knee using clinical alternating bi-plane fluoroscopy systems. The current study aimed to develop such an approach and evaluate in vivo its accuracy and identify the effects of the accuracy of SSM models on the kinematic measurements. Methods: An alternating interpolation-based model tracking (AIMT) approach with SSM-reconstructed subject-specific bone models was used for measuring 3D knee kinematics from dynamic alternating bi-plane fluoroscopy images. A two-phase optimization scheme was used to reconstruct subject-specific knee models from a CT-based SSM database of 60 knees using one, two, or three pairs of fluoroscopy images. Using the CT-reconstructed model as a benchmark, the performance of the AIMT with SSM-reconstructed models in measuring bone and joint kinematics during dynamic activity was evaluated in terms of mean target registration errors (mmTRE) for registered bone poses and the mean absolute differences (MAD) for each motion component of the joint poses. Results: The mmTRE of the femur and tibia for one image pair were significantly greater than those for two and three image pairs without significant differences between two and three image pairs. The MAD was 1.16 to 1.22° for rotations and 1.18 to 1.22 mm for translations using one image pair. The corresponding values for two and three image pairs were 0.75 to 0.89° and 0.75 to 0.79 mm; and 0.57 to 0.79° and 0.6 to 0.69 mm, respectively. The MAD values for one image pair were significantly greater than those for two and three image pairs without significant differences between two and three image pairs. Conclusions: An AIMT approach with SSM-reconstructed models was developed, enabling the registration of interleaved fluoroscopy images and SSM-reconstructed models from more than one asynchronous fluoroscopy image pair. This new approach had sub-millimeter and sub-degree measurement accuracy when using more than one image pair, comparable to the accuracy of CT-based methods. This approach will be helpful for future kinematic measurements of the knee with reduced radiation exposure using 3D fluoroscopy with clinically alternating bi-plane fluoroscopy systems.

Use of spatial panel-data models to investigate factors related to incidence of end-stage renal disease: a nationwide longitudinal study in Taiwan.

BACKGROUND: The assumptions of conventional spatial models cannot estimate the responses across space and over time. Here we propose new spatial panel data models to investigate the association between the risk factors and incidence of end-stage renal disease (ESRD). METHODS: A longitudinal (panel data) study was conducted using data from the National Health Insurance Database in Taiwan. We developed an algorithm to identify the patient's residence and estimate the ESRD rate in each township. Corresponding covariates, including patient comorbidities, history of medication use, and socio-environmental factors, were collected. Local Indicators of Spatial Association were used to describe local spatial clustering around an individual location. Moreover, a spatial panel data model was proposed to investigate the association between ESRD incidence and risk factors. RESULTS: In total, 73,995 patients with ESRD were included in this study. The western region had a higher proportion of high incidence rates than the eastern region. The proportion of high incidence rates in the eastern areas increased over the years. We found that most "social environmental factors," except average income and air pollution (PM 2.5 and PM10), had a significant influence on the incidence rate of ESRD when considering spatial dependences of response and explanatory variables. Receiving non-steroidal anti-inflammatory drugs and aminoglycosides within 90 days prior to ESRD had a significant positive effect on the ESRD incidence rate. CONCLUSION: Future comprehensive studies on townships located in higher-risk clusters of ESRD will help in designing healthcare policies for suitable action.

Epigenetic remodeling of the immune landscape in cancer: therapeutic hurdles and opportunities.

The tumor immune microenvironment represents a sophisticated ecosystem where various immune cell subtypes communicate with cancer cells and stromal cells. The dynamic cellular composition and functional characteristics of the immune landscape along the trajectory of cancer development greatly impact the therapeutic efficacy and clinical outcome in patients receiving systemic antitumor therapy. Mounting evidence has suggested that epigenetic mechanisms are the underpinning of many aspects of antitumor immunity and facilitate immune state transitions during differentiation, activation, inhibition, or dysfunction. Thus, targeting epigenetic modifiers to remodel the immune microenvironment holds great potential as an integral part of anticancer regimens. In this review, we summarize the epigenetic profiles and key epigenetic modifiers in individual immune cell types that define the functional coordinates of tumor permissive and non-permissive immune landscapes. We discuss the immunomodulatory roles of current and prospective epigenetic therapeutic agents, which may open new opportunities in enhancing cancer immunotherapy or overcoming existing therapeutic challenges in the management of cancer.

Analysis of the literature shows a remarkably consistent relationship between size and abundance of microplastics across different environmental matrices.

Microplastics come in a variety of shapes, polymer types and sizes. Due to the lack of a harmonised approach to analyse and quantify microplastics, there are huge disparities in size detection limits and size classifications used in the literature. This has caused large variations in reported microplastic data and has made comparing microplastic abundance between studies extremely challenging. Herein, we applied a simple mathematical approach that allows for a meaningful comparison between size and abundance (number of particles) of microplastics irrespective of the size classifications used. This method was validated using two separate datasets (microplastics in air and sediment) and applied to re-analyse 127 publications reporting microplastics in various environmental matrices. We demonstrate a strong negative linear relationship between microplastic concentrations and their sizes with comparable slopes across all matrices. Using this method, it is possible to compare the concentration of microplastics of various sizes between studies. It also allows estimation of the abundance of microplastics of a specific size where data are not available. This enables researchers to predict environmentally relevant concentrations of microplastics (particularly for smaller microplastics) and provide realistic exposure scenarios in future toxicity studies, which will greatly improve our understanding of the risks that microplastics pose to living organisms.

Complete Frequency-Bin Bell Basis Synthesizer.

We report the experimental generation of all four frequency-bin Bell states in a single versatile setup via successive pumping of spontaneous parametric down-conversion with single and dual spectral lines. Our scheme utilizes intensity modulation to control the pump configuration and offers turn-key generation of any desired Bell state using only off-the-shelf telecommunication equipment. We employ Bayesian inference to reconstruct the density matrices of the generated Bell states, finding fidelities ≥97% for all cases. Additionally, we demonstrate the sensitivity of the frequency-bin Bell states to common-mode and differential-mode temporal delays traversed by the photons comprising the state-presenting the potential for either enhanced resolution or nonlocal sensing enabled by our complete Bell basis synthesizer.

Broadband polarization-entangled source for C+L-band flex-grid quantum networks.

The rising demand for transmission capacity in optical networks has motivated steady interest in expansion beyond the standard C-band (1530-1565 nm) into the adjacent L-band (1565-1625 nm) for an approximate doubling of capacity in a single stroke. However, in the context of quantum networking, the L-band has yet to be fully leveraged with the suite of advanced tools for characterization and management available from classical lightwave communications. In this work, we demonstrate an ultrabroadband two-photon source integrating both C- and L-band wavelength-selective switches for complete control of spectral routing and allocation across 7.5 THz in a single setup. Polarization state tomography of all 150 pairs of 25-GHz-wide channels reveals an average fidelity of 0.98 and total distillable entanglement greater than 181 kebits/s. This source is explicitly designed for flex-grid optical networks and can facilitate optimal utilization of entanglement resources across the full C+L-band.

Kinematic strategies for obstacle-crossing in older adults with mild cognitive impairment.

Introduction: Mild cognitive impairment (MCI) is considered a transitional stage between soundness of mind and dementia, often involving problems with memory, which may lead to abnormal postural control and altered end-point control when dealing with neuromechanical challenges during obstacle-crossing. The study aimed to identify the end-point control and angular kinematics of the pelvis-leg apparatus while crossing obstacles for both leading and trailing limbs. Methods: 12 patients with MCI (age: 66.7 ± 4.2 y/o; height: 161.3 ± 7.3 cm; mass: 62.0 ± 13.6 kg) and 12 healthy adults (age: 67.7 ± 2.9 y/o; height: 159.3 ± 6.1 cm; mass: 61.2 ± 12.0 kg) each walked and crossed obstacles of three different heights (10, 20, and 30% of leg length). Angular motions of the pelvis and lower limbs and toe-obstacle clearances during leading- and trailing-limb crossings were calculated. Two-way analyses of variance were used to study between-subject (group) and within-subject (obstacle height) effects on the variables. Whenever a height effect was found, a polynomial test was used to determine the trend. A significance level of α = 0.05 was set for all tests. Results: Patients with MCI significantly increased pelvic anterior tilt, hip abduction, and knee adduction in the swing limb during leading-limb crossing when compared to controls (p < 0.05). During trailing-limb crossing, the MCI group showed significantly decreased pelvic posterior tilt, as well as ankle dorsiflexion in the trailing swing limb (p < 0.05). Conclusion: Patients with MCI adopt altered kinematic strategies for successful obstacle-crossing. The patients were able to maintain normal leading and trailing toe-obstacle clearances for all tested obstacle heights with a specific kinematic strategy, namely increased pelvic anterior tilt, swing hip abduction, and knee adduction during leading-limb crossing, and decreased pelvic posterior tilt and swing ankle dorsiflexion during trailing-limb crossing. The current results suggest that regular monitoring of obstacle-crossing kinematics for reduced toe-obstacle clearance or any signs of changes in crossing strategy may be helpful for early detection of compromised obstacle-crossing ability in patients with single-domain amnestic MCI. Further studies using a motor/cognitive dual-task approach on the kinematic strategies adopted by multiple-domain MCI will be needed for a complete picture of the functional adaptations in such a patient group.

Total Liquid Transfer with Enhanced Contact Line Slippage.

A new surface treatment method is developed to achieve total liquid transfer. The transfer process of a liquid droplet is recorded through high-speed photography and analyzed via image analysis to investigate the hydrodynamic interactions. For a pristine PMMA surface, a viscous and viscoelastic liquid facilitates transfer by increased viscous and inertial forces and delayed liquid bridge breakage but is limited by slow contact line slippage. Hydrophobic surface treatments can increase contact line slippage and the receding angle to achieve transfer ratios up to 98%. However, pinning and contact angle hysteresis from surface roughness features limit liquid transfer, especially for smaller droplets and higher separation velocities. A lubricant-infused surface treatment with PDMS and a thin layer of less viscous silicone oil provides a smooth, homogeneous surface with fast slippage, low contact angle hysteresis, and only a slight oil wetting ridge. Liquid could then transfer at high ratios (∼99.9%), regardless of droplet size and separation velocity. Finally, complete transfer liquid from indented cells is demonstrated to show the potential of this surface modification method for gravure printing.

A missense variant in the nuclear localization signal of DKC1 causes Hoyeraal-Hreidarsson syndrome.

Hoyeraal-Hreidarsson syndrome (HHS) is the most severe form of dyskeratosis congenita (DC) and is caused by mutations in genes involved in telomere maintenance. Here, we identified male siblings from a family with HHS carrying a hemizygous mutation (c.1345C > G, p.R449G), located in the C-terminal nuclear localization signal (NLS) of the DKC1 gene. These patients exhibit progressive cerebellar hypoplasia, recurrent infections, pancytopenia due to bone marrow failure, and short leukocyte telomere lengths. Single-cell RNA sequencing analysis suggested defects in the NLRP3 inflammasome in monocytes and the activation and maturation of NK cells and B cells. In experiments using induced pluripotent stem cells (iPSCs) from patients, DKC1_R449G iPSCs had short telomere lengths due to reduced levels of human telomerase RNA (hTR) and increased cytosolic proportions of DKC1. Treatment with dihydroquinolizinone RG7834 and 3'deoxyanosine cordycepin rescued telomere length in patient-derived iPSCs. Together, our findings not only provide new insights into immunodeficiency in DC patients but also provide treatment options for telomerase insufficiency disorders.