Correlation-driven nonequilibrium exciton site transition in a WSe2/WS2 moiré supercell.

Moiré superlattices of transition metal dichalcogenides offer a unique platform to explore correlated exciton physics with optical spectroscopy. Whereas the spatially modulated potentials evoke that the exciton resonances are distinct depending on a site in a moiré supercell, there have been no clear demonstration how the moiré excitons trapped in different sites dynamically interact with the doped carriers; so far the exciton-electron dynamic interactions were presumed to be site-dependent. Thus, the transient emergence of nonequilibrium correlations are open questions, but existing studies are limited to steady-state optical measurements. Here we report experimental fingerprints of site-dependent exciton correlations under continuous-wave as well as ultrashort optical excitations. In near-zero angle-aligned WSe2/WS2 heterobilayers, we observe intriguing polarization switching and strongly enhanced Pauli blocking near the Mott insulating state, dictating the dominant correlation-driven effects. When the twist angle is near 60°, no such correlations are observed, suggesting the strong dependence of atomic registry in moiré supercell configuration. Our studies open the door to largely unexplored nonequilibrium correlations of excitons in moiré superlattices.

Conceptualizing Family Caregivers' Use of Community Support Services: A Scoping Review.

BACKGROUND AND OBJECTIVES: Only a fraction of the 53 million caregivers in the United States use available formal community services. This scoping review synthesized the literature on the barriers and facilitators of community support service utilization by adult caregivers of a family member or friend with an illness, disability, or other limitation. RESEARCH DESIGN AND METHODS: We searched PubMed, CINAHL, PsycInfo, and Web of Science for quantitative and qualitative articles assessing barriers and facilitators of caregivers' access to and utilization of resources, following Preferred Reporting Items for Systematic Review and Meta-Analysis scoping review guidelines. Thematic analysis, drawing on an initial conceptualization, informed key insights around caregivers' resource navigation process. RESULTS: The review provides support for individual factors affecting service use. Notably, some factors-such as time restrictions and increased caregiving demands-appear to function as barriers to accessing services even as they increase caregivers' need for support. Additionally, contextual barriers including cultural factors and support of friends/family can affect caregivers' access to resources. Finally, experience with health systems and structures and the intersection with other factors can affect service utilization. DISCUSSION AND IMPLICATIONS: Suboptimal access to and utilization of community support services can be addressed at both the person and system level to mitigate potential inequities. Ensuring that caregivers are aware of, eligible for, and have the capacity and support to access the appropriate resources at the right time is essential for improving caregiver outcomes, reducing burnout, and supporting continued care.

Immunoglobulin G4-related hypertrophic pachymeningitis with an isolated scalp mass mimicking a brain tumor: a case report and literature review.

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disorder associated with fibroinflammatory conditions that can affect multiple organs. Hallmark histopathological findings of IgG4-RD include lymphocytic infiltration of IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. However, little is known about central nervous system involvement of IgG4-RD. Hypertrophic pachymeningitis (HP) has recently been reported as a manifestation of IgG4-RD, which may have previously been demonstrated in a significant percentage of idiopathic cases. Herein, we report a rare case of a 63-year-old male who presented with a scalp mass that mimicked a brain tumor. He was diagnosed with IgG4-related HP (IgG4-RP) after surgery. This case suggests that awareness of a possibility of IgG4-RP in patients with isolated scalp masses, even in the absence of systemic symptoms, is crucial. A combination of careful history taking, evaluation of serum IgG4-levels and imaging as an initial work-up, followed by tissue biopsy, is important for the differential diagnosis of IgG4-RP, malignancy, and other infectious diseases.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Korean guidelines for the management of gout.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Hydrogen Production from Barley Straw and Miscanthus by the Hyperthermophilic Bacterium, Cadicellulosirupter bescii.

This work aimed to evaluate the feasibility of biohydrogen production from Barley Straw and Miscanthus. The primary obstacle in plant biomass decomposition is the recalcitrance of the biomass itself. Plant cell walls consist of cellulose, hemicellulose, and lignin, which make the plant robust to decomposition. However, the hyperthermophilic bacterium, Caldicellulosiruptor bescii, can efficiently utilize lignocellulosic feedstocks (Barley Straw and Miscanthus) for energy production, and C. bescii can now be metabolically engineered or isolated to produce more hydrogen and other biochemicals. In the present study, two strains, C. bescii JWCB001 (wild-type) and JWCB018 (ΔpyrFA Δldh ΔcbeI), were tested for their ability to increase hydrogen production from Barley Straw and Miscanthus. The JWCB018 resulted in a redirection of carbon and electron (carried by NADH) flow from lactate production to acetate and hydrogen production. JWCB018 produced ~54% and 63% more acetate and hydrogen from Barley Straw, respectively than its wild-type counterpart, JWCB001. Also, 25% more hydrogen from Miscanthus was obtained by the JWCB018 strain with 33% more acetate relative to JWCB001. It was supported that the engineered C. bescii, such as the JWCB018, can be a parental strain to get more hydrogen and other biochemicals from various biomass.

Permeability of Fresh and Frozen Porcine and Human Gingiva and the Effect of Storage Duration.

The gingiva is the target site for some topical drugs, but the permeability of human gingiva has not been systematically evaluated. Pigs are a common animal model for in vitro membrane transport studies. The objectives of this study were to: (a) determine the permeability coefficients of freshly excised human gingiva using model permeants, (b) compare the permeability coefficients of fresh human gingiva with those of fresh porcine gingiva, (c) evaluate the effect of freezing duration on the permeability of porcine gingiva, and (d) compare the permeability coefficients of fresh and cadaver (frozen) human gingiva. A goal was to examine the feasibility of using porcine gingiva as a surrogate for human gingiva. The potential of using frozen tissues in permeability studies of gingiva was also examined. Fresh and frozen porcine gingiva, fresh human gingiva, and frozen cadaver human gingiva were compared in the transport study with model polar and lipophilic permeants. The fresh porcine and human tissues showed similarities in the "permeability coefficient vs. octanol-water distribution coefficient" relationship. The porcine gingiva had a lower permeability than that of the human, with a moderate correlation between the permeability of the fresh porcine and fresh human tissues. The permeability of the porcine tissues for the model polar permeants increased significantly after the tissues were frozen in storage. Moreover, the frozen human cadaver tissue could not be utilized due to the high and indiscriminating permeability of the tissue for the permeants and large tissue sample-to-sample variabilities.

Melanin Treatment Effect of Vacuoles-Zinc Oxide Nanoparticles Combined with Ascorbic Acid.

Currently, ascorbic acid (AA) is widely used as a skin whitening material, but, AA, an unstable hydrophilic molecule, cannot penetrate the skin easily, due to the hydrophobic character of the stratum corneum. Therefore, we conjugated AA with hydrated zinc oxide-an inorganic matrix with positive surface charge, to improve the stability of AA. The metal-conjugated-ascorbic acid (ZnAA) was then combined with yeast vacuole through the vacuolar membrane proteins that relate to metal transportation to create an enhanced vacuole that contained ZnAA. The characteristics of vacuole with ZnAA (ZnAA_Vac) were next examined by various tests that included X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Field emission scanning electron microscopy (FE-SEM), and energy-dispersive X-ray (EDX) analysis. Furthermore, the ability of ZnAA_Vac to degrade melanin was confirmed in both melanoma cell line B16F10, and the artificial human skin MelanoDerm. The results showed that ZnAA_Vac possessed a higher depigmenting effect than the wild-type vacuole or ascorbic acid by reducing 75% of melanin color. Interestingly, ZnAA_Vac was found to be harmless, and did not cause any cytotoxicity to the cells. Overall, ZnAA_Vac is expected to provide a robust, harmless, and effective whitening agent for the skin.

Comprehensive Characterization of Mutant Pichia stipitis Co-Fermenting Cellobiose and Xylose through Genomic and Transcriptomic Analyses.

The development of a yeast strain capable of fermenting mixed sugars efficiently is crucial for producing biofuels and value-added materials from cellulosic biomass. Previously, a mutant Pichia stipitis YN14 strain capable of co-fermenting xylose and cellobiose was developed through evolutionary engineering of the wild-type P. stipitis CBS6054 strain, which was incapable of cofermenting xylose and cellobiose. In this study, through genomic and transcriptomic analyses, we sought to investigate the reasons for the improved sugar metabolic performance of the mutant YN14 strain in comparison with the parental CBS6054 strain. Unfortunately, comparative wholegenome sequencing (WGS) showed no mutation in any of the genes involved in the cellobiose metabolism between the two strains. However, comparative RNA sequencing (RNA-seq) revealed that the YN14 strain had 101.2 times and 5.9 times higher expression levels of HXT2.3 and BGL2 genes involved in cellobiose metabolism, and 6.9 times and 75.9 times lower expression levels of COX17 and SOD2.2 genes involved in respiration, respectively, compared with the CBS6054 strain. This may explain how the YN14 strain enhanced cellobiose metabolic performance and shifted the direction of cellobiose metabolic flux from respiration to fermentation in the presence of cellobiose compared with the CBS6054 strain.

Effects of Engineered Saccharomyces cerevisiae Fermenting Cellobiose through Low-Energy-Consuming Phosphorolytic Pathway in Simultaneous Saccharification and Fermentation.

Until recently, four types of cellobiose-fermenting Saccharomyces cerevisiae strains have been developed by introduction of a cellobiose metabolic pathway based on either intracellular ß-glucosidase (GH1-1) or cellobiose phosphorylase (CBP), along with either an energy-consuming active cellodextrin transporter (CDT-1) or a non-energy-consuming passive cellodextrin facilitator (CDT-2). In this study, the ethanol production performance of two cellobiose-fermenting S. cerevisiae strains expressing mutant CDT-2 (N306I) with GH1-1 or CBP were compared with two cellobiose-fermenting S. cerevisiae strains expressing mutant CDT-1 (F213L) with GH1-1 or CBP in the simultaneous saccharification and fermentation (SSF) of cellulose under various conditions. It was found that, regardless of the SSF conditions, the phosphorolytic cellobiose-fermenting S. cerevisiae expressing mutant CDT-2 with CBP showed the best ethanol production among the four strains. In addition, during SSF contaminated by lactic acid bacteria, the phosphorolytic cellobiose-fermenting S. cerevisiae expressing mutant CDT-2 with CBP showed the highest ethanol production and the lowest lactate formation compared with those of other strains, such as the hydrolytic cellobiose-fermenting S. cerevisiae expressing mutant CDT-1 with GH1-1, and the glucose-fermenting S. cerevisiae with extracellular ß-glucosidase. These results suggest that the cellobiose-fermenting yeast strain exhibiting low energy consumption can enhance the efficiency of the SSF of cellulosic biomass.

Permeability of Buccal Mucosa.

The buccal mucosa provides an alternative route of drug delivery that can be more beneficial compared to other administration routes. Although numerous studies and reviews have been published on buccal drug delivery, an extensive review of the permeability data is not available. Understanding the buccal mucosa barrier could provide insights into the approaches to effective drug delivery and optimization of dosage forms. This paper provides a review on the permeability of the buccal mucosa. The intrinsic permeability coefficients of porcine buccal mucosa were collected. Large variability was observed among the published permeability data. The permeability coefficients were then analyzed using a model involving parallel lipoidal and polar transport pathways. For the lipoidal pathway, a correlation was observed between the permeability coefficients and permeant octanol/water partition coefficients (Kow) and molecular weight (MW) in a subset of the permeability data under specific conditions. The permeability analysis suggested that the buccal permeation barrier was less lipophilic than octanol. For the polar pathway and macromolecules, a correlation was observed between the permeability coefficients and permeant MW. The hindered transport analysis suggested an effective pore radius of 1.5 to 3 nm for the buccal membrane barrier.

Verification of Blood-Brain Barrier Disruption Based on the Clinical Validation Platform Using a Rat Model with Human Skull.

Methods to improve drug delivery efficiency through blood-brain barrier disruption (BBBD) based on microbubbles and focused ultrasound (FUS) are continuously being studied. However, most studies are being conducted in preclinical trial environments using small animals. The use of the human skull shows differences between the clinical and preclinical trials. BBBD results from preclinical trials are difficult to represent in clinical trials because various distortions of ultrasound by the human skull are excluded in the former. Therefore, in our study, a clinical validation platform based on a preclinical trial environment, using a human skull fragment and a rat model, was developed to induce BBBD under conditions similar to clinical trials. For this, a human skull fragment was inserted between the rat head and a 250 kHz FUS transducer, and optimal ultrasound parameters for the free field (without human skull fragment) and human skull (with human skull fragment) were derived by 300 mVpp and 700 mVpp, respectively. BBBD was analyzed according to each case using magnetic resonance images, Evans blue dye, cavitation, and histology. Although it was confirmed using magnetic resonance images and Evans blue dye that a BBB opening was induced in each case, multiple BBB openings were observed in the brain tissues. This phenomenon was analyzed by numerical simulation, and it was confirmed to be due to standing waves owing to the small skull size of the rat model. The stable cavitation doses (SCDh and SCDu) in the human skull decreased by 13.6- and 5.3-fold, respectively, compared to those in the free field. Additionally, the inertial cavitation dose in the human skull decreased by 1.05-fold compared to that of the free field. For the histological analysis, although some extravasated red blood cells were observed in each case, it was evaluated as recoverable based on our previous study results. Therefore, our proposed platform can help deduct optimal ultrasound parameters and BBBD results for clinical trials in the preclinical trials with small animals because it considers variables relevant to the human skull.

Localized Modification of Water Molecule Transport After Focused Ultrasound-Induced Blood-Brain Barrier Disruption in Rat Brain.

Interstitial solutes can be removed by various overlapping clearance systems, including blood-brain barrier (BBB) transport and glymphatic clearance. Recently, focused ultrasound (FUS)-induced BBB disruption (BBBD) has been applied to visualize glymphatic transport. Despite evidence that FUS-BBBD might facilitate glymphatic transport, the nature of fluid movement within the sonication region is yet to be determined. In this study, we sought to determine whether FUS-BBBD may facilitate the local movement of water molecules. Two different FUS conditions (0.60-0.65 MPa and 0.75-0.80 MPa) were used to induce BBBD in the caudate-putamen and thalamus regions of healthy Sprague-Dawley rats. The water diffusion caused by FUS-BBBD was analyzed using the apparent diffusion coefficient (ADC), axial diffusivity, radial diffusivity (RD), and fractional anisotropy, obtained at 5 min, 24 and 48 h, as well as the water channel expression of aquaporin-4 (AQP-4) immunostaining at 48 h after FUS-induced BBBD. In addition, hematoxylin and eosin histopathology and Fluoro-Jade C (FJC) immunostaining were performed to analyze brain damage. The signal changes in ADC and RD in the sonication groups showed significant and transient reduction at 5 min, with subsequent increases at 24 and 48 h after FUS-induced BBBD. When we applied higher sonication conditions, the ADC and RD showed enhancement until 48 h, and became comparable to contralateral values at 72 h. AQP-4 expression was upregulated after FUS-induced BBBD in both sonication conditions at 48 h. The results of this study provide preliminary evidence on how mechanical forces from FUS alter water dynamics through diffusion tensor imaging (DTI) measures and AQP4 expression.

How do spouses of cancer survivors engage with mental healthcare? An exploratory analysis of visit characteristics.

OBJECTIVE: To better understand how cancer caregivers engage with mental healthcare, this exploratory study sought to assess the distribution and correlates of visit characteristics for mental health-related medical care among spouses of cancer survivors. METHODS: Using nationally representative data from the Medical Expenditures Panel Survey, we assessed the proportion of caregivers who received a mental health-related prescription or psychotherapy visit across care settings (office based, outpatient hospital, emergency room, or inpatient visit), provider type (psychiatric, primary care, other specialty, or other), and visit purpose (regular checkup, diagnosis and treatment, follow-up, psychotherapy, other), and the health condition(s) associated with the visit. Logistic and multinomial regressions assessed the predisposing, enabling, need, and survivor characteristics associated with the visit characteristics. RESULTS: A plurality of spouses of cancer survivors accessed mental healthcare through an office-based visit (90%) with a primary care provider (47%). One third accessed treatment as part of a regular check-up (32%). Several factors were associated with visit characteristics, notably the cancer survivor's health status and healthcare utilization. CONCLUSIONS: The findings provide an important reminder of the often-invisible mental health burden experienced by cancer caregivers and confirm the importance of routine primary care as a doorway to mental healthcare. Assessing how the care recipient's care needs and caregiving itself may act as barriers to specialty care will be a critical future research trajectory.

Role of cancer survivor health and health service use in spouses' use of mental health-related care.

BACKGROUND: Spouses of cancer survivors are at an increased risk of poor mental health outcomes but are known to underuse supportive services. The objective of the current study was to determine how the health and health care use of cancer survivors were associated with depression and anxiety-related health care use in their spouses. METHODS: The current observational study used data from the Medical Expenditure Panel Survey to identify married individuals with a cancer-related medical event or disability ("cancer survivors"), and linked health and health care use data across spousal dyads. Spouses reporting a prescription for an antidepressant or antianxiety medication or any psychotherapy were flagged as having used mental health care. Correlates of use were assessed, with a focus on the health and health care use of the cancer survivor. RESULTS: Greater than 25% of the spouses of cancer survivors used mental health care over the approximately 2.5 years of follow-up. Controlling for their own predisposing, enabling, and need characteristics, spouses were found to be less likely to use mental health care if the cancer survivor reported more health conditions or elevated depressed mood compared with dyads in which the survivor reported low distress and depression. Spouses were nearly 3 times more likely to use mental health care if the cancer survivor themselves had used mental health care (odds ratio, 2.98; 95% confidence interval, 2.17-4.09). CONCLUSIONS: The findings of the current study enhance understanding of how health outcomes are intertwined in families with cancer, and reinforce the importance of a family-centered approach to cancer care that facilitates psychosocial care. LAY SUMMARY: The health and well-being of cancer survivors and their spouses are intertwined. The results of the current study demonstrated that this interrelationship extends to mental health care related to depression and anxiety. Spouses of cancer survivors were found to be less likely to receive mental health care when the survivor had more health care needs. Spouses were nearly 3 times more likely to receive care if the survivor also was receiving mental health care. Caregiving spouses may face more challenges finding the time, money, or energy to engage in their own self-care. However, providing supportive care to one partner may help the other partner access care as well.

Outcomes and Risk Factors of Systolic Pulmonary Artery Pressure Progression in Patients with Systemic Rheumatic Diseases: Follow-up Results from a Korean Registry.

OBJECTIVES: This study aims to investigate the outcomes and risk factors associated with the progression of systolic pulmonary artery pressure (sPAP) in patients with systemic rheumatic diseases. PATIENTS AND METHODS: A total of 532 patients (73 males, 459 females; median age 49 years; interquartile range (IQR), 36 to 62 years) registered with the Registry of Pulmonary Hypertension Associated with Rheumatic Diseases were included. Mortality curves were constructed using the Kaplan- Meier method and comparisons were performed using the log-rank test. A paired t-test was performed to evaluate the patients with markedly elevated sPAP between baseline and follow-up. RESULTS: The average follow-up duration was 31 months (IQR, 9 to 60 months). Of the patients, 196 had follow-up echocardiographs at least one year later. We defined the sPAP over 60 mmHg as markedly elevated. Patients in the increased sPAP above 60 mmHg at follow-up and persistently markedly elevated sPAP were associated with worse outcomes in all-cause mortality and pulmonary arterial hypertension-related mortality (p<0.001). In patients with systemic sclerosis, the majority of patients remained static within their pressure group or rose progressively: the patients with markedly elevated sPAP at follow-up were higher than those at baseline (32% versus 15%, p<0.01). In patients with mixed connective tissue disease (MCTD) or rheumatoid arthritis (RA), the majority of patients remained static within their pressure group or gradually improved: the patients with markedly elevated sPAP at follow-up were lower than those at baseline (RA=14% versus 29%, MCTD=5% versus 16%, p<0.05). CONCLUSION: Persistently high sPAP or increase of sPAP over 60 mmHg at follow-up was associated with increased mortality. There were some differences in the progression of sPAP according to the underlying rheumatic diseases.

Diminished Expression of P-glycoprotein Using Focused Ultrasound Is Associated With JNK-Dependent Signaling Pathway in Cerebral Blood Vessels.

MRI-guided focused ultrasound (MRgFUS) combined with microbubbles (MBs) is a promising technology that can facilitate drug delivery through a temporarily disrupted blood-brain barrier (BBB) and induce the down-regulation of P-glycoprotein (P-gp) expression on the blood vessels. Despite the increasing evidence regarding the down-regulation of P-gp expression after MRgFUS BBB disruption (BBBD), its underlying molecular events remain unclear. The aim of this study was to evaluate the underlying mechanism of FUS BBBD-mediated P-gp down-regulation. While our results showed down-regulation of P-gp at 24 h post-BBBD in transcriptional and translational levels, restoration to the normal expression appeared at different time points for transcriptional (72 h) and translational (120 h) levels. In addition, the signaling molecule, JNK, was significantly activated in the cerebral blood vessels at 24 h post-BBBD. Although P-gp levels were significantly decreased, the expression levels of proteins involved in the integrity of blood vessels, such as Glut1, ZO-1 and occludin, were not decreased at 24 h post-BBBD. Our study suggests that the JNK signaling pathway is involved in the regulation of FUS-induced P-gp expression, without affecting vessel integrity, and a detailed regulatory mechanism can provide the basis for clinical application of FUS to the treatment of neurological disease.

Viral Effects of a dsRNA Mycovirus (PoV-ASI2792) on the Vegetative Growth of the Edible Mushroom Pleurotus ostreatus.

A double-stranded RNA (dsRNA) mycovirus was detected in malformed fruiting bodies of Pleurotus ostreatus strain ASI2792, one of bottle cultivated commercial strains of the edible oyster mushroom. The partial RNA-dependent RNA polymerase (RdRp) gene of the P. ostreatus ASI2792 mycovirus (PoV-ASI2792) was cloned, and a cDNA sequences alignment revealed that the sequence was identical to the RdRp gene of a known PoSV found in the P. ostreatus strain. To investigate the symptoms of PoV-ASI2792 infection by comparing the isogenic virus-free P. ostreatus strains with a virus-infected strain, isogenic virus-cured P. ostreatus strains were obtained by the mycelial fragmentation method for virus curing. The absence of virus was verified with gel electrophoresis after dsRNA-specific virus purification and Northern blot analysis using a partial RdRp cDNA of PoV-ASI2792. The growth rate and mycelial dry weight of virus-infected P. ostreatus strain with PoV-ASI2792 mycovirus were compared to those of three virus-free isogenic strains on 10 different media. The virus-cured strains showed distinctly higher mycelial growth rates and dry weights on all kinds of experimental culture media, with at least a 2.2-fold higher mycelial growth rate on mushroom complete media (MCM) and Hamada media, and a 2.7-fold higher mycelial dry weight on MCM and yeastmalt-glucose agar media than those of the virus-infected strain. These results suggest that the infection of PoV mycovirus has a deleterious effect on the vegetative growth of P. ostreatus.