Room-Temperature Anode-Less All-Solid-State Batteries via the Conversion Reaction of Metal Fluorides.

All-solid-state batteries (ASSBs) that employ anode-less electrodes have drawn attention from across the battery community because they offer competitive energy densities and a markedly improved cycle life. Nevertheless, the composite matrices of anode-less electrodes impose a substantial barrier for lithium-ion diffusion and inhibit operation at room temperature. To overcome this drawback, here, the conversion reaction of metal fluorides is exploited because metallic nanodomains formed during this reaction induce an alloying reaction with lithium ions for uniform and sustainable lithium (de)plating. Lithium fluoride (LiF), another product of the conversion reaction, prevents the agglomeration of the metallic nanodomains and also protects the electrode from fatal lithium dendrite growth. A systematic analysis identifies silver (I) fluoride (AgF) as the most suitable metal fluoride because the silver nanodomains can accommodate the solid-solution mechanism with a low nucleation overpotential. AgF-based full cells attain reliable cycling at 25 °C even with an exceptionally high areal capacity of 9.7 mAh cm-2 (areal loading of LiNi0.8 Co0.1 Mn0.1 O2  = 50 mg cm-2 ). These results offer useful insights into designing materials for anode-less electrodes for sulfide-based ASSBs.

A Comprehensive Review of Neuromuscular Manifestations of COVID-19 and Management of Pre-Existing Neuromuscular Disorders in Children.

Since the emergence of SARS-CoV-2, several studies have been published describing neuromuscular manifestations of the disease, as well as management of pre-existing pediatric neuromuscular disorders during the COVID-19 pandemic. These disorders include muscular dystrophies, myasthenic syndromes, peripheral nerve disorders, and spinal muscular atrophy. Such patients are a vulnerable population due to frequent complications such as scoliosis, cardiomyopathy, and restrictive lung disease that put them at risk of severe complications of COVID-19. In this review, neuromuscular manifestations of COVID-19 in children and the management of pre-existing pediatric neuromuscular disorders during the COVID-19 pandemic are discussed. We also review strategies to alleviate pandemic-associated disruptions in clinical care and research, including the emerging role of telemedicine and telerehabilitation to address the continued special needs of these patients.

A Pediatric Case of Sensory Predominant Guillain-Barré Syndrome Following COVID-19 Vaccination.

Over six billion doses of Coronavirus Disease 2019 (COVID-19) vaccines have been administered worldwide. Amidst the global COVID-19 vaccination campaign, vaccine-related side effects are of ongoing concern and investigation. According to the Centers for Disease Control and Prevention (CDC) and the United States Department of Health and Human Services, three main conditions in adults have surfaced in association with receiving the COVID-19 vaccines. These include thrombosis with thrombocytopenia syndrome (TTS), a rare syndrome involving venous or arterial thrombosis and thrombocytopenia, Guillain-Barre syndrome (GBS), and myocarditis. While a number of GBS cases in adults have been published, to our knowledge, only one pediatric case of COVID-19 vaccine-related GBS has been reported. Herein we describe a case of sensory predominant GBS following the Pfizer-BioNTech COVID-19 vaccine in a 16-year-old female presenting with bilaterally ascending upper and lower extremity numbness and paresthesia.

Metformin as a Treatment Strategy for Sjögren's Syndrome.

Sjögren's syndrome (SS), a chronic inflammatory disease involving the salivary and lacrimal glands, presents symptoms of sicca as well as systemic manifestations such as fatigue and musculoskeletal pain. Only a few treatments have been successful in management of SS; thus treatment of the disease is challenging. Metformin is the first-line agent for type 2 diabetes and has anti-inflammatory potential. Its immunomodulatory capacity is exerted via activation of 5' adenosine monophosphate-activated protein kinase (AMPK). Metformin inhibits mitochondrial respiratory chain complex I which leads to change in adenosine mono-phosphate (AMP) to adenosine tri-phosphate (ATP) ratio. This results in AMPK activation and causes inhibition of mammalian target of rapamycin (mTOR). mTOR plays an important role in T cell differentiation and mTOR deficient T cells differentiate into regulatory T cells. In this manner, metformin enhances immunoregulatory response in an individual. mTOR is responsible for B cell proliferation and germinal center (GC) differentiation. Thus, reduction of B cell differentiation into antibody-producing plasma cells occurs via downregulation of mTOR. Due to the lack of suggested treatment for SS, metformin has been considered as a treatment strategy and is expected to ameliorate salivary gland function.

A Comprehensive Review of Neurologic Manifestations of COVID-19 and Management of Pre-existing Neurologic Disorders in Children.

Since the first reports of SARS-CoV-2 infection from China, multiple studies have been published regarding the epidemiologic aspects of COVID-19 including clinical manifestations and outcomes. The majority of these studies have focused on respiratory complications. However, recent findings have highlighted the systemic effects of the virus, including its potential impact on the nervous system. Similar to SARS-CoV-1, cellular entry of SARS-CoV-2 depends on the expression of ACE2, a receptor that is abundantly expressed in the nervous system. Neurologic manifestations in adults include cerebrovascular insults, encephalitis or encephalopathy, and neuromuscular disorders. However, the presence of these neurologic findings in the pediatric population is unclear. In this review, the potential neurotropism of SARS-CoV-2, known neurologic manifestations of COVID-19 in children, and management of preexisting pediatric neurologic conditions during the COVID-19 pandemic are discussed.

Recurrent Superior Vena Cava Syndrome in a Patient with Sarcoidosis and Pancreatic Adenocarcinoma: A Case Report and Literature Review.

Background: Superior vena cava (SVC) syndrome may result from extravascular compression or intravascular obstruction such as thrombosis. Recurrent venous thrombosis is typically associated with a hypercoagulable state such as malignancy, and inheritable or acquired coagulopathy. Sarcoidosis is a derangement of the immune system, and it has been associated with malignant diseases and hypercoagulation. The association of pancreatic cancer and sarcoidosis with SVC syndrome has not been reported previously. Here, we present a case of recurrent venous thrombosis causing SVC syndrome in a patient with pancreatic ductal adenocarcinoma and underlying thoracic sarcoidosis. Methods: The patient's electronic health record was retrospectively analyzed. Results: A 66-year-old woman with pancreatic adenocarcinoma was treated with neoadjuvant chemotherapy followed by Whipple procedure, before developing tumor recurrence in the liver. Her treatment course was complicated with repeated incidents of venous thrombosis in the presence of a central venous catheter leading to recurrent SVC syndrome, which resolved with anti-coagulation. Conclusions: This case raises a plausible inter-relationship between sarcoidosis, pancreatic cancer, and hypercoagulable state. We suggest that patients with multiple risk factors for developing venous thrombosis should be carefully monitored for any thrombotic event, and they may benefit from prophylactic anti-coagulation.

The roles of iron and HFE genotype in neurological diseases.

Iron accumulation is a recurring pathological phenomenon in many neurological diseases including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and others. Iron is essential for normal development and functions of the brain; however, excess redox-active iron can also lead to oxidative damage and cell death. Especially for terminally differentiated cells like neurons, regulation of reactive oxygen species is critical for cell viability. As a result, cellular iron level is tightly regulated. Although iron accumulation related to neurological diseases has been well documented, the pathoetiological contributions of the homeostatic iron regulator (HFE), which controls cellular iron uptake, is less understood. Furthermore, a common HFE variant, H63D HFE, has been identified as a modifier of multiple neurological diseases. This review will discuss the roles of iron and HFE in the brain as well as their impact on various disease processes.

H63D variant of the homeostatic iron regulator (HFE) gene alters α-synuclein expression, aggregation, and toxicity.

Pathological features of Parkinson's disease include the formation of Lewy bodies containing α-synuclein and the accumulation of iron in the substantia nigra. Previous studies have suggested that iron accumulation contributes to the Parkinson's disease pathology through reactive oxygen species production and accelerated α-synuclein aggregation. This study examines the effects of commonly occurring H63D variant of the homeostatic iron regulatory (HFE) gene on α-synuclein pathology in cell culture and animal models. H63D HFE expression in SH-SY5Y cells lowered endogenous α-synuclein levels and significantly decreased pre-formed fibril-induced α-synuclein aggregation. H63D HFE cells were also protected from pre-formed fibril-induced apoptosis. Autophagic flux, a major pathway for α-synuclein clearance, was increased in H63D HFE cells. Expression of REDD1 was elevated and rapamycin treatment was unable to further induce autophagy, indicating mTORC1 inhibition as the main mechanism of autophagy induction. Moreover, siRNA knockdown of REDD1 in H63D HFE cells decreased autophagic flux and increased the sensitivity to PFF-mediated toxicity. While iron chelator (deferiprone) treatment rescued WT HFE cells from pre-formed fibril toxicity, it exacerbated or was unable to rescue H63D HFE cells. In the in vivo pre-formed fibril intracranial injection model, H67D Hfe (mouse homolog of the human H63D HFE variant) C57BL/6J × 129 mice showed less α-synuclein aggregation and less decline in motor function compared to WT Hfe. Collectively, this study suggests that H63D HFE variant modifies α-synuclein pathology through the induction of autophagy and has the potential to impact the pathogenesis and treatment response in Parkinson's disease.

The Nrf2-mediated defense mechanism associated with HFE genotype limits vulnerability to oxidative stress-induced toxicity.

There is considerable interest in gene and environment interactions in neurodegenerative diseases. The HFE (homeostatic iron regulator) gene variant (H63D) is highly prevalent in the population and has been investigated as a disease modifier in multiple neurodegenerative diseases. We have developed a mouse model to interrogate the impact of this gene variant in a model of paraquat toxicity. Using primary astrocytes, we found that the H67D-Hfe(equivalent of the human H63D variant) astrocytes are less vulnerable than the WT-Hfe astrocytes to paraquat-induced cell death, mitochondrial damage, and cellular senescence. We hypothesized that the Hfe variant-associated protection is a result of the activation of the Nrf2 antioxidant defense system and found a significant increase in Nrf2 levels after paraquat exposure in the H67D-Hfe astrocytes than the WT-Hfe astrocytes. Moreover, decreasing Nrf2 by molecular or pharmaceutical manipulation resulted in increased vulnerability to paraquat in the H67D-Hfe astrocytes. To further elucidate the role of Hfe variant genotype in neuroprotection mediated by astrocytes, we added media from the paraquat-treated astrocytes to differentiated SH-SY5Y neuroblastoma cells and found a significantly larger reduction in the viability when treated with WT-Hfe astrocyte media than the H67D-Hfe astrocyte media possibly due to higher secretion of IL-6 observed in the WT-Hfe astrocytes. To further explore the mechanism of Nrf2 protection, we measured NQO1, the Nrf2-mediated antioxidant, in primary astrocytes and found a significantly higher NQO1 level in the H67D-Hfe astrocytes. To consider the translational potential of our findings, we utilized the PPMI (Parkinson's Progression Markers Initiative) clinical database and found that, consistent with the mouse study, H63D-HFE carriers had a significantly higher NQO1 level in the CSF than the WT-HFE carriers. Consistent with our previous reports on H63D-HFE in disease, these data further suggest that HFE genotype in the human population impacts the antioxidant defense system and can therefore alter pathogenesis.

Mechanical and biocorrosive properties of magnesium-aluminum alloy scaffold for biomedical applications.

This study investigates the morphology, microstructure, compressive behavior, biocorrosion properties, and cytocompatibility of magnesium (Mg)-aluminum (Al) alloy (AE42) scaffolds for their potential use in biodegradable biomedical applications. Mg alloy scaffolds were successfully synthesized via a camphene-based freeze-casting process with precisely controlled heat treatment. The average porosity was approximately 52% and the median pore diameter was ∼13 µm. Salient deformation mechanisms were identified using acoustic emission (AE) signals and adaptive sequential k-means (ASK) analysis. Twinning, dislocation slip, strut bending, and collapse were dominant during compressive deformation. Nonetheless, the overall compressive behavior and deformation mechanisms were similar to those of bulk Mg based on ASK analysis. The corrosion potential of the Mg alloy scaffold (-1.44 V) was slightly higher than that of bulk AE42 (-1.60 V), but the corrosion rate of the Mg alloy scaffold was faster than that of bulk AE42 due to the enhanced surface area of the Mg alloy scaffold. As a result of cytocompatibility evaluation following ISO10993-5, the concentration of the Mg alloy scaffold extract reducing cell growth rate to 50% (IC50) was 10.7%, which is higher (less toxic) than 5%, suggesting no severe inflammation by implantation into muscle.

Efficacy and safety of mycophenolate mofetil and tacrolimus combination therapy in patients with lupus nephritis: a nationwide multicentre study.

OBJECTIVES: Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (TAC) may be an option for lupus nephritis (LN) patients that do not adequately respond to initial treatment. We evaluated the efficacy and safety of the combination treatment of MMF and TAC in LN patients with suboptimal response to prior MMF or TAC treatments. METHODS: In this multicentre study, we retrospectively enrolled 62 patients with class III, IV, or V LN who inadequately responded to MMF or TAC treatment. Those patients were then treated with a combination of MMF and TAC for 6 months. The primary outcome was complete remission (CR) at 6 months, and secondary outcomes included overall response and adverse events. RESULTS: After 6 months of treatment with the drug combination, CR was achieved in 14 of 62 patients (22.6%), and 35 (56.5%) patients responded. A significant reduction in proteinuria and lupus disease activity score was observable after 3 months. After 1 year, the CR rate increased to 36.4% (20 of 55 patients), and the overall response rate (n=38, 69.1%) also increased from 6 months. Twenty-one patients reported 29 adverse events, including severe infection requiring hospitalisation (n=3, 10.3%), infection not requiring hospitalisation (n=2, 6.9%), and herpes zoster (n=4, 13.8%). CONCLUSIONS: Our findings suggest that a combined MMF and TAC treatment, with a favourable adverse-event profile, may be a beneficial option for LN patients with inadequate response to either MMF or TAC treatments.

Synthesis of nano-scale fast ion conducting cubic Li7La3Zr2O12.

A solution-based process was investigated for synthesizing cubic Li7La3Zr2O12 (LLZO), which is known to exhibit the unprecedented combination of fast ionic conductivity, and stability in air and against Li. Sol-gel chemistry was developed to prepare solid metal-oxide networks consisting of 10 nm cross-links that formed the cubic LLZO phase at 600 ° C. Sol-gel LLZO powders were sintered into 96% dense pellets using an induction hot press that applied pressure while heating. After sintering, the average LLZO grain size was 260 nm, which is 13 times smaller compared to LLZO prepared using a solid-state technique. The total ionic conductivity was 0.4 mS cm(-1) at 298 K, which is the same as solid-state synthesized LLZO. Interestingly, despite the same room temperature conductivity, the sol-gel LLZO total activation energy is 0.41 eV, which 1.6 times higher than that observed in solid-state LLZO (0.26 eV). We believe the nano-scale grain boundaries give rise to unique transport phenomena that are more sensitive to temperature when compared to the conventional solid-state LLZO.

A query result merging scheme for providing energy efficiency in underwater sensor networks.

Underwater sensor networks are emerging as a promising distributed data management system for various applications in underwater environments, despite their limited accessibility and restricted energy capacity. With the aid of recent developments in ubiquitous data computing, an increasing number of users are expected to overcome low accessibility by applying queries to underwater sensor networks. However, when multiple users send queries to an underwater sensor network in a disorganized manner, it may incur lethal energy waste and problematic network traffic. The current query management mechanisms cannot effectively deal with this matter due to their limited applicability and unrealistic assumptions. In this paper, a novel query management scheme involving query result merging is proposed for underwater sensor networks. The mechanism is based on a relational database model and is adjusted to the practical restrictions affecting underwater communication environments. Network simulations will prove that the scheme becomes more efficient with a greater number of queries and a smaller period range.