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ObjectiveThis study investigates the efficacy and feasibility of electrical stimulation (E-Stim) on sensory fibers of the plantar region during hemodialysis sessions, aiming to improve mobility in patients with diabetes by providing a connection between E-Stim and enhanced mobility with minimal patient effort required.Research design and methodsParticipants age ≥18 years with diabetes undergoing hemodialysis and able to walk at least 10 m with or without aid were recruited and divided into an intervention group receiving 1-h intradialytic E-Stim three times a week and a control group using an identical nonfunctional device for 12 weeks. Gait, physical activity, patient-reported outcomes, and the technology acceptance model were assessed to evaluate the intervention's effectiveness and acceptance.ResultsOut of 117 initial participants, 97 completed the study. Significant improvements were observed in the intervention group compared with the control group in gait performance (stride time at dual-task and fast walking), physical activity (stand to walk and sit to stand), quality of life, plantar numbness, and cognitive function after 12 weeks. The intervention group showed that magnitudes of improvement on gait performance and physical activity metrics were associated with enhancements in quality of life and cognitive function, respectively. The intervention group also reported higher usefulness and usage satisfaction, with a greater willingness to continue using E-Stim at home.ConclusionsThe 12-week intradialytic E-Stim intervention is a feasible and effective method to enhance gait performance, physical activity level, cognitive function, and other patient-reported outcomes in patients undergoing hemodialysis, representing a practical, low-risk therapy option for those unable to engage in traditional exercise programs.

Although evidence exists for a causal association between 25-hydroxyvitamin D (25(OH)D) serum levels, and multiple sclerosis (MS), the role of variation in vitamin D receptor (VDR) binding in MS is unknown. Here, we leveraged previously identified variants associated with allele imbalance in VDR binding (VDR-binding variant; VDR-BV) in ChIP-exo data from calcitriol-stimulated lymphoblastoid cell lines and 25(OH)D serum levels from genome-wide association studies to construct genetic instrumental variables (GIVs). GIVs are composed of one or more genetic variants that serve as proxies for exposures of interest. Here, GIVs for both VDR-BVs and 25(OH)D were used in a two-sample Mendelian Randomization study to investigate the relationship between VDR binding at a locus, 25(OH)D serum levels, and MS risk. Data for 13,598 MS cases and 38,887 controls of European ancestry from Kaiser Permanente Northern California, Swedish MS studies, and the UK Biobank were included. We estimated the association between each VDR-BV GIV and MS. Significant interaction between a VDR-BV GIV and a GIV for serum 25OH(D) was evidence for a causal association between VDR-BVs and MS unbiased by pleiotropy. We observed evidence for associations between two VDR-BVs (rs2881514, rs2531804) and MS after correction for multiple tests. There was evidence of interaction between rs2881514 and a 25(OH)D GIV, providing evidence of a causal association between rs2881514 and MS. This study is the first to demonstrate evidence that variation in VDR binding at a locus contributes to MS risk. Our results are relevant to other autoimmune diseases in which vitamin D plays a role.

INTRODUCTION: The chromosome 22q11.2 deletion syndrome (22q11.2DS) is characterized by a well-defined microdeletion and is associated with a wide range of brain-related phenotypes including schizophrenia spectrum disorders (SCZ), autism spectrum disorders (ASD), anxiety disorders and attention deficit disorders (ADHD). The typically deleted region in 22q11.2DS contains multiple genes which haploinsufficiency has the potential of altering the protein and the metabolic profiles. OBJECTIVES: Alteration in metabolic processes and downstream protein pathways during the early brain development may help to explain the increased prevalence of the observed neurodevelopmental phenotypes in 22q11.2DS. However, relatively little is known about the correlation of dysregulated protein/metabolite expression and neurobehavioral impairments in individuals who developed them over time. METHODS: In this study, we performed untargeted metabolic and proteomic analysis in plasma samples derived from 30 subjects including 16 participants with 22q11.2DS and 14 healthy controls (TD) enrolled in a longitudinal study, aiming to identify a metabolic and protein signature informing about the underlying mechanisms involved in disease development and progression. The metabolic and proteomic profiles were also compared between the participants with 22q11.2DS with and without various comorbidities, such as medical involvement, psychiatric conditions, and autism spectrum disorder (ASD) to detect potential changes among multiple specimens, collected overtime, with the aim to understand the basic underlying mechanisms involved in disease development and progression. RESULTS: We observed a large number of statistically significant differences in metabolites between the two groups. Among them, the levels of taurine and arachidonic acid were significantly lower in 22q11.2DS compared to the TD group. In addition, we identified 16 proteins that showed significant changes in expression levels (adjusted P

We began our tenure as editors-in-chief of the Asian Pacific American Law Journal’s (APALJ) Volume 28 in the journal’s tiny office in the back corner of the law school sitting among stacks of publications from the past three decades. Since its founding, APALJ has stood apart in its mission of elevating authentic perspectives on issues at the heart of the Asian American community. It is this mission that shapes our volume; the articles published within draw on stories often overlooked in critiquing established ways of thinking and engaging in a radical imagination of what Asian America could be.

Calcium carbonate (CaCO3) is abundant on Earth, is a major component of marine biominerals and thus of sedimentary and metamorphic rocks and it plays a major role in the global carbon cycle by storing atmospheric CO2 into solid biominerals. Six crystalline polymorphs of CaCO3 are known-3 anhydrous: calcite, aragonite, vaterite, and 3 hydrated: ikaite (CaCO3·6H2O), monohydrocalcite (CaCO3·1H2O, MHC), and calcium carbonate hemihydrate (CaCO3·½H2O, CCHH). CCHH was recently discovered and characterized, but exclusively as a synthetic material, not as a naturally occurring mineral. Here, analyzing 200 million spectra with Myriad Mapping (MM) of nanoscale mineral phases, we find CCHH and MHC, along with amorphous precursors, on freshly deposited coral skeleton and nacre surfaces, but not on sea urchin spines. Thus, biomineralization pathways are more complex and diverse than previously understood, opening new questions on isotopes and climate. Crystalline precursors are more accessible than amorphous ones to other spectroscopies and diffraction, in natural and bio-inspired materials.

Abstract Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4+ T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4+ T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4+ T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4+ T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4+ T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults.

Abstract This paper introduces the DERCo (Dublin EEG-based Reading Experiment Corpus), a language resource combining electroencephalography (EEG) and next-word prediction data obtained from participants reading narrative texts. The dataset comprises behavioral data collected from 500 participants recruited through the Amazon Mechanical Turk online crowd-sourcing platform, along with EEG recordings from 22 healthy adult native English speakers. The online experiment was designed to examine the context-based word prediction by a large sample of participants, while the EEG-based experiment was developed to extend the validation of behavioral next-word predictability. Online participants were instructed to predict upcoming words and complete entire stories. Cloze probabilities were then calculated for each word so that this predictability measure could be used to support various analyses pertaining to semantic context effects in the EEG recordings. EEG-based analyses revealed significant differences between high and low predictable words, demonstrating one important type of potential analysis that necessitates close integration of these two datasets. This material is a valuable resource for researchers in neurolinguistics due to the word-level EEG recordings in context.

Yersinochloa nianheana sp. nov. from Vietnam is described and illustrated. It is found in southern Vietnam, where it occurs at an elevation of 1400–1500 m in Voi Mountain, Duc Trong District, Lam Dong Province. This new species is distinguished from a similar species, Yersinochloa dalatensis, by culm nodes with a thick swollen patella, culm leaf blades erect, auricles conspicuous, margins bearing long hairs, palea dorsal view showing rachilla extension and rudimentary floret at the apex and lodicules purple gradually towards the top. Besides that, the species is distinguished from Yersinochloa nghiana by the leaf blades without being swollen at the base, the prophyllate bud 2-keeled, lodicules purple at ½ upper parts and unbifid at the base.

Abstract Neonatal intensive care unit (NICU), particularly in treating developmental and epileptic encephalopathy (DEE) and metabolic epilepsy (ME), requires a deep understanding of their complex etiologies and treatment responses. After excluding treatable cases such as infectious or autoimmune encephalitis, our focus shifted to a more challenging subgroup of 59 patients for in-depth genetic analysis using exome sequencing (ES). The ES analysis identified 40 genetic abnormalities, significantly including de novo variants. Notably, we found structural variation as duplications in regions 2q24.3, including SCN1A and SCN2A were observed in 7 cases. These genetic variants, impacting ion channels, glucose transport, transcription regulation, and kinases, play a crucial role in determining medication efficacy. More than one-third (34.2%) of patients with DEE had an unfavorable response to anti-seizure medications (ASMs) in the chronic phase. However, since the ketogenic supplementary diet showed a positive effect, more than three-quarters (80%) of these drug-resistant patients improved during a 3-month follow-up. In contrast, the ME had a lower adverse reaction rate of 9.1% (2/22) to specialized medications, yet there were 5 fatalities and 10 cases with unidentified genetic etiologies. This study suggests the potential of categorizing drug-resistant variants and that a ketogenic diet could be beneficial in managing DEE and ME. It also opens new perspectives on the mechanisms of the ketogenic diet on the discovered genetic variants.

Abstract Background Many Australian adults are not receiving timely or effective diabetes management to prevent or delay the onset of diabetes related complications. Integrated care, a worldwide trend in healthcare reform, aims to reduce the fragmented delivery of health services and improve outcomes. This study aimed to test whether a specialist-led integrated model of care provided to a small subset of patients in general practices leads to spillover clinical improvements in all patients of the practice with type 2 diabetes. Methods Seventy-two general practice sites (clusters) in New South Wales, Australia received the Diabetes Alliance intervention, creating a non-randomised open cohort stepped wedge trial. The intervention comprised of case conferencing, delivered directly to a small proportion of adults with type 2 diabetes (n = 1,072) of the general practice sites; as well as practice feedback, education and training. Spillover clinical improvements were assessed on all adults with type 2 diabetes within the general practice sites (n = 22,706), using practice level data recorded in the MedicineInsight electronic database, compared before and after the intervention. Outcome measures included frequency of diabetes screening tests in line with the Annual Cycle of Care, and clinical results for weight, blood pressure, HbA1c, lipids, and kidney function. Results Compared to before Diabetes Alliance, the odds of all practice patients receiving screening tests at or above the recommended intervals were significantly higher for all recommended tests after Diabetes Alliance (odds ratio range 1.41–4.45, p

This paper describes the research protocol for the Educational and Developmental Gains in Early Childhood (EDGE) Study, which will examine the implementation of two years of funded kindergarten prior to the first year of school in Victoria, Australia. EDGE will examine whether children's language, cognitive, social-emotional, and behavioural outcomes are improved after two years of kindergarten compared to one year. The experiences of (and impacts on) teachers, service leaders, and families will also be examined. The study includes a cross-sectional cohort of 95 early childhood education and care (ECEC) services, and an embedded longitudinal observational cohort of children attending these services. Case studies of 15-20 ECEC services will also be collected, in addition to interviews with policy stakeholders.

In this paper, we report the initial stages of Response to Intervention (RTI) implementation in one school that participated in the Getting it Right from the Start (GIRFTS) pilot study. Implementation of an RTI framework for oral language and reading was supported by teacher professional learning and a dedicated Implementation Support Partner (ISP). Participants were interviewed to explore their perceptions of the change process and identify barriers and enablers to implementation. Thematic analysis was used to identify factors that supported the implementation of RTI, including strategic collegial relationships, teacher motivation, and a desire to achieve consistency of assessment and instruction. The ISP was seen as a crucial coaching role for keeping implementation on track, providing feedback and advice, and helping teachers translate professional learning into their school context. This study highlights some key factors that schools and policy-makers should focus on to promote successful early implementation of RTI approaches.

Objective: Understanding how children cope is an important factor in investigating the impact of adversity on child development. With children increasingly experiencing adverse situations -- such as the COVID-19 pandemic -- having methods of assessing coping strategies is an essential step in supporting self-regulation development. Parent report is a common method of measuring child outcomes, as parents observe children across a range of settings. Thus, the goal of this study was to investigate the reliability and validity of the KidCOPE-Parent form -- an adaptation of the original KidCOPE self-report. Methods: A sample of 253 children, aged 6-7 years old, across 19 government and catholic schools in Melbourne, Victoria. Results: Findings indicate that a two-factor model best fits the data, with the KidCOPE-P demonstrating moderately acceptable reliability and validity. There were some differences in mean scores reported between males and females for items relating to problem-solving, social support, and resignation coping strategies. Conclusion: Overall, the KidCOPE-P is moderately suitable for assessing children's coping strategies, as observed by a parent. Future research is needed to replicate these findings and continue to explore the KidCOPE-P's reliability as a parent-report measure of child coping strategies.

ObjectiveWe undertook this study to estimate changes in cell-specific DNA methylation (DNAm) associated with methotrexate (MTX) response using whole blood samples collected from rheumatoid arthritis (RA) patients before and after initiation of MTX treatment.MethodsPatients included in this study were from the Rheumatoid Arthritis Medication Study (n = 66) and the University of California San Francisco Rheumatoid Arthritis study (n = 11). All patients met the American College of Rheumatology RA classification criteria. Blood samples were collected at baseline and following treatment. Disease Activity Scores in 28 joints using the C-reactive protein level were collected at baseline and after 3-6 months of treatment with MTX. Methylation profiles were generated using the Illumina Infinium HumanMethylation450 and MethylationEPIC v1.0 BeadChip arrays using DNA from whole blood. MTX response was defined using the EULAR response criteria (responders showed good/moderate response; nonresponders showed no response). Differentially methylated positions were identified using the Limma software package and Tensor Composition Analysis, which is a method for identifying cell-specific differential DNAm at the CpG level from tissue-level ("bulk") data. Differentially methylated regions were identified using Comb-p software.ResultsWe found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell-specific differential global methylation associated with MTX response. After correction for multiple testing, 1 differentially methylated position was associated with differential DNAm between responders and nonresponders at baseline in CD4+ T cells, CD8+ T cells, and natural killer cells. Thirty-nine cell-specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples.ConclusionWe identified cell-specific changes in DNAm that were associated with MTX treatment response in RA patients. Future studies of DNAm and MTX treatment response should include measurements of DNAm from sorted cells.