Correlated variability and its attentional modulation depend on anatomical connectivity.

Visual cortical neurons show variability in their responses to repeated presentations of a stimulus and a portion of this variability is shared across neurons. Attention may enhance visual perception by reducing shared spiking variability. However, shared variability and its attentional modulation are not consistent within or across cortical areas, and depend on additional factors such as neuronal type. A critical factor that has not been tested is actual anatomical connectivity. We measured spike count correlations among pairs of simultaneously recorded neurons in the primary visual cortex (V1) for which anatomical connectivity was inferred from spiking cross-correlations. Neurons were recorded in monkeys performing a contrast-change discrimination task requiring covert shifts in visual spatial attention. Accordingly, spike count correlations were compared across trials in which attention was directed toward or away from the visual stimulus overlapping recorded neuronal receptive fields. Consistent with prior findings, attention did not significantly alter spike count correlations among random pairings of unconnected V1 neurons. However, V1 neurons connected via excitatory synapses showed a significant reduction in spike count correlations with attention. Interestingly, V1 neurons connected via inhibitory synapses demonstrated high spike count correlations overall that were not modulated by attention. Correlated variability in excitatory circuits also depended upon neuronal tuning for contrast, the task-relevant stimulus feature. These results indicate that shared variability depends on the type of connectivity in neuronal circuits. Also, attention significantly reduces shared variability in excitatory circuits, even when attention effects on randomly sampled neurons within the same area are weak.

Nitrogen fertilization and soil nitrogen cycling: Unraveling the links among multiple environmental factors, functional genes, and transformation rates.

Anthropogenic nitrogen (N) inputs substantially influence the N cycle in agricultural ecosystems. However, the potential links among various environmental factors, nitrogen functional genes, and transformation rates under N fertilization remain poorly understood. Here, we conducted a five-year field experiment and collected 54 soil samples from three 0-4 m boreholes across different treatments: control, N-addition (nitrogen fertilizer) and NPK-addition (combined application of nitrogen, phosphorus and potassium fertilizers) treatments. Our results revealed pronounced variations in soil physiochemical parameters, metal concentrations and antibiotic levels under both N and NPK treatments. These alternations induced significant shifts in bacterial and fungal communities, altered NFG abundance and composition, and greatly enhanced rates of nitrate reduction processes. Notably, nutrients, antibiotics and bacteria exerted a more pronounced influence on NFGs and nitrate reduction under N treatment, whereas nutrients, metals, bacteria and fungi had a significant impact under NPK treatment. Furthermore, we established multidimensional correlations between nitrate reduction gene profiles and the activity rates under N and NPK treatments, contrasting with the absence of significant relationships in the control treatment. These findings shed light on the intricate relationships between microbial genetics and ecosystem functions in agricultural ecosystem, which is of significance for predicting and managing metabolic processes effectively.

Role of socioeconomic factors and interkingdom crosstalk in the dental plaque microbiome in early childhood caries.

Early childhood caries (ECC) is influenced by microbial and host factors, including social, behavioral, and oral health. In this cross-sectional study, we analyze interkingdom dynamics in the dental plaque microbiome and its association with host variables. We use 16S rRNA and ITS1 amplicon sequencing on samples collected from preschool children and analyze questionnaire data to examine the social determinants of oral health. The results indicate a significant enrichment of Streptococcus mutans and Candida dubliniensis in ECC samples, in contrast to Neisseria oralis in caries-free children. Our interkingdom correlation analysis reveals that Candida dubliniensis is strongly correlated with both Neisseria bacilliformis and Prevotella veroralis in ECC. Additionally, ECC shows significant associations with host variables, including oral health status, age, place of residence, and mode of childbirth. This study provides empirical evidence associating the oral microbiome with socioeconomic and behavioral factors in relation to ECC, offering insights for developing targeted prevention strategies.

Digital Maturity as a Predictor of Quality and Safety Outcomes in US Hospitals: Cross-Sectional Observational Study.

BACKGROUND: This study demonstrates that digital maturity contributes to strengthened quality and safety performance outcomes in US hospitals. Advanced digital maturity is associated with more digitally enabled work environments with automated flow of data across information systems to enable clinicians and leaders to track quality and safety outcomes. This research illustrates that an advanced digitally enabled workforce is associated with strong safety leadership and culture and better patient health and safety outcomes. OBJECTIVE: This study aimed to examine the relationship between digital maturity and quality and safety outcomes in US hospitals. METHODS: The data sources were hospital safety letter grades as well as quality and safety scores on a continuous scale published by The Leapfrog Group. We used the digital maturity level (measured using the Electronic Medical Record Assessment Model [EMRAM]) of 1026 US hospitals. This was a cross-sectional, observational study. Logistic, linear, and Tweedie regression analyses were used to explore the relationships among The Leapfrog Group's Hospital Safety Grades, individual Leapfrog safety scores, and digital maturity levels classified as advanced or fully developed digital maturity (EMRAM levels 6 and 7) or underdeveloped maturity (EMRAM level 0). Digital maturity was a predictor while controlling for hospital characteristics including teaching status, urban or rural location, hospital size measured by number of beds, whether the hospital was a referral center, and type of hospital ownership as confounding variables. Hospitals were divided into the following 2 groups to compare safety and quality outcomes: hospitals that were digitally advanced and hospitals with underdeveloped digital maturity. Data from The Leapfrog Group's Hospital Safety Grades report published in spring 2019 were matched to the hospitals with completed EMRAM assessments in 2019. Hospital characteristics such as number of hospital beds were obtained from the CMS database. RESULTS: The results revealed that the odds of achieving a higher Leapfrog Group Hospital Safety Grade was statistically significantly higher, by 3.25 times, for hospitals with advanced digital maturity (EMRAM maturity of 6 or 7; odds ratio 3.25, 95% CI 2.33-4.55). CONCLUSIONS: Hospitals with advanced digital maturity had statistically significantly reduced infection rates, reduced adverse events, and improved surgical safety outcomes. The study findings suggest a significant difference in quality and safety outcomes among hospitals with advanced digital maturity compared with hospitals with underdeveloped digital maturity.

Syndromic epidermolysis bullosa simplex subtype due to mutations in the KLHL24 gene: series of case reports in Russian families.

Objective: Epidermolysis bullosa simplex (EBS) is a common, well-characterized type of epidermolysis bullosa. However, some rare syndromic EBS phenotypes are not well described. The accumulation of clinical descriptions of patients with syndromic subtypes of EBS is important for understanding the natural history of the disease and assessing genotype-phenotype correlations. Case summary: We present a series of case reports of the syndromic subtype of EBS associated with mutations in the KLHL24 gene in seven patients from four unrelated families. The clinical features of this rare phenotype in children and adult patients are described in detail. In two families, we revealed pathogenic variant c.1A > G (p.Met1?) in the KLHL24 gene. The third family had c.3G > A (p.Met1?) mutation, and the fourth family had a novel de novo variant c.23del (p.Arg8AsnfsTer2). Conclusion: The description of the clinical manifestations of the disease in two generations of EBS families with different genetic variants allows the assessment and prediction of the natural course and severity of the disease in these families, the risk of complications, and the planning of the amount of medical care necessary.

Novel mutation patterns in children with steroid-resistant nephrotic syndrome.

Background: Idiopathic nephrotic syndrome (NS) in children poses treatment challenges, with a subset developing steroid-resistant nephrotic syndrome (SRNS). Genetic factors play a role, yet data on paediatric SRNS genetics in India are scarce. We conducted a prospective study using whole-exome sequencing to explore genetic variants and their clinical correlations. Methods: A single-centre prospective study (October 2018-April 2023) enrolled children with SRNS, undergoing renal biopsy and genetic testing per institutional protocol. Clinical, histological, and genetic data were recorded. DNA isolation and next-generation sequencing were conducted for genetic analysis. Data collection included demographics, clinical parameters, and kidney biopsy findings. Syndromic features were evaluated, with second-line immunosuppressive therapy administered. Patient and renal outcomes are presented for patients with and without genetic variants. Results: A total of 680 paediatric NS patients were analysed, with 121 (17.8%) having SRNS and 96 consent to genetic analysis. 69 (71.9%) had early SRNS, 27 (28.1%) late. Among participants, 62 (64.58%) had reportable genetic variants. The most common were in COL4A genes, with 20 (31.7%) positive. Renal biopsy showed focal segmental glomerulosclerosis in 31/42 (74%) with variants, 16/28 (57.1%) without variants. Second-line immunosuppressions varied, with CNIs the most common. Outcomes varied, with partial or complete remission achieved in some while others progressed to ESRD. Conclusion: The study underscores the importance of genetic analysis in paediatric SRNS, revealing variants in 65.7% of cases. COL4A variants were predominant. Variants correlated with varied renal outcomes, highlighting potential prognostic implications. These findings emphasize the value of personalized approaches and further research in managing paediatric SRNS.

A cross-sectional study on metoprolol concentrations in various biological samples and their inter-correlations.

BACKGROUND: Concentrations of metoprolol in exhaled breath condensate (EBC) have not been investigated. Herein, we aim to determine the metoprolol levels in EBC, plasma, and urine samples. METHODS: Biological samples were collected from 39 patients receiving metoprolol. Metoprolol was determined using liquid chromatography mass spectrometery. The obtained metoprolol levels in biological fluids were investigated for possible inter-correlations. RESULTS: Acceptable linearity was obtained with coefficient of determinations equal to 0.9998, 0.9941, and 0.9963 for EBC, plasma, and urine samples, respectively. The calibration curves were linear in the ranges of 0.6-500, 0.4-500, and 0.7-10,000 µg·L- 1 regarding EBC, plasma, and urine samples, respectively. The detection and quantification limits were (0.18, 0.12, and 0.21 µg·L- 1) and (0.60, 0.40, and 0.70 µg·L- 1) for EBC, plasma, and urine samples, respectively. The relative standard deviations for the intra- and inter-day replications were obtained between 5.2 and 6.1 and 3.3-4.6%, respectively. The obtained mean metoprolol levels in EBC, plasma, and urine samples of 39 patients were 5.35, 70.76, and 1943.1 µg·L- 1. There were correlations between daily dose and plasma and urinary concentrations of metoprolol in the investigated samples, whereas no significant correlation was observed for daily dose and EBC levels. The correlation among plasma-urine levels was significant, however, the non-significant correlation was obtained between plasma and EBC concentrations. CONCLUSION: Metoprolol levels varied widely due to the metabolic pattern of the Azeri population, different dosages received by the patients, formulation effects, age, sex, and interactions with the co-administered drugs. A poor correlation of EBC-plasma concentrations and a significant correlation of plasma-urine concentrations were observed. Further investigations are required to provide the updated services to personalized medicine departments.

Assessing spatial distribution of bioindicator elements in various cutaneous tumors using correlative imaging with laser-ablation-based analytical methods.

Correlative imaging of cutaneous tumors provides additional information to the standard histopathologic examination. However, the joint progress in the establishment of analytical techniques, such as Laser-Induced Breakdown Spectroscopy (LIBS) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in clinical practice is still limited. Their combination provides complementary information as it is also shown in our study in terms of major biotic (Ca, Mg, and P) and trace (Cu and Zn) elements. To elucidate changes in the elemental composition in tumors, we have compiled a set of malignant tumors (Squamous Cell Carcinoma, Basal Cell Carcinoma, Malignant Melanoma, and Epithelioid Angiosarcoma), one benign tumor (Pigmented Nevus) and one healthy-skin sample. The data processing was based on a methodological pipeline involving binary image registration and affine transformation. Thus, our paper brings a feasibility study of a practical methodological concept that enables us to compare LIBS and LA-ICP-MS results despite the mutual spatial distortion of original elemental images. Moreover, we also show that LIBS could be a sufficient pre-screening method even for a larger number of samples according to the speed and reproducibility of the analyses. Whereas LA-ICP-MS could serve as a ground truth and reference technique for preselected samples.

Longitudinal variation of correlations between different components of assessment within a medical school.

BACKGROUND: An assessment program should be inclusive and ensure that the various components of medical knowledge, clinical skills, and professionalism are assessed. The level and the variation over time in the strength of the correlation between these components of assessment is still a matter of study. Based on the meaningful learning theory and the integrated learning theory, we hypothesize that these components increase their connections during the medical school course. METHODS: This is a retrospective cohort study that analyzed data collected for a 10-year period in one medical school. We included students from the 3rd to 6th year of medical school from 2011 to 2021. Three assessment components were addressed: Knowledge, Clinical Skills, and Professionalism. For data analysis, Pearson correlation coefficients (R) and R2 were calculated to study the correlation between variables and a z-test on Fisher's r-to-z was used to determine the differences between correlation coefficients. RESULTS: 949 medical students were included in the study. The correlation between Clinical Skills and Professionalism showed a medium to strong association (Pearson's R ranging from 0.485 to 0.734), while the correlation between Knowledge and Professionalism was weaker but exhibited a steady evolution with Pearson's R fluctuating between 0.075 and 0.218. The Knowledge and Clinical Skills correlation became statistically significant from 2013 onwards and peaking at Pearson's R of 0.440 for the cohort spanning 2016-2019. We also revealed a strengthening of correlations between Professionalism and Clinical Skills from the beginning to the end of clinical training, but not with the knowledge component. CONCLUSIONS: This analysis contributes to our understanding of the dynamics of correlations of different assessment components within an institution and provides a framework for how they interact and influence each other. TRIAL REGISTRATION: This study was not a clinical trial, but a retrospective observational study, without health care interventions. Nevertheless, we provide herein the number of the study as submitted to the Ethics committee - CEICVS 146/2021.

HRV and EEG correlates of well-being using ultra-short, portable, and low-cost measurements.

Wearable electroencephalography (EEG) and electrocardiography (ECG) devices may offer a non-invasive, user-friendly, and cost-effective approach for assessing well-being (WB) in real-world settings. However, challenges remain in dealing with signal artifacts (such as environmental noise and movements) and identifying robust biomarkers. We evaluated the feasibility of using portable hardware to identify potential EEG and heart-rate variability (HRV) correlates of WB. We collected simultaneous ultrashort (2-min) EEG and ECG data from 60 individuals in real-world settings using a wrist ECG electrode connected to a 4-channel wearable EEG headset. These data were processed, assessed for signal quality, and analyzed using the open-source EEGLAB BrainBeats plugin to extract several theory-driven metrics as potential correlates of WB. Namely, the individual alpha frequency (IAF), frontal and posterior alpha asymmetry, and signal entropy for EEG. SDNN, the low/high frequency (LF/HF) ratio, the Poincaré SD1/SD2 ratio, and signal entropy for HRV. We assessed potential associations between these features and the main WB dimensions (hedonic, eudaimonic, global, physical, and social) implementing a pairwise correlation approach, robust Spearman's correlations, and corrections for multiple comparisons. Only eight files showed poor signal quality and were excluded from the analysis. Eudaimonic (psychological) WB was positively correlated with SDNN and the LF/HF ratio. EEG posterior alpha asymmetry was positively correlated with Physical WB (i.e., sleep and pain levels). No relationships were found with the other metrics, or between EEG and HRV metrics. These physiological metrics enable a quick, objective assessment of well-being in real-world settings using scalable, user-friendly tools.

Associations between oxygen saturation Index and oxygenation index in neonates with congenital diaphragmatic hernia.

Objective: To explore the relationship between Oxygenation Index (OI) and Oxygen Saturation Index (OSI) among infants with Congenital Diaphragmatic Hernia (CDH), both within the first 24 h after birth and in extended observations in those who survived until their surgical intervention. Methods: Seven- years retrospective review of CDH cases at a single Level III neonatal intensive care unit. The correlations of various combinations of OI-OSI pairs were assessed using the Spearman's rho Correlation Coefficient. Additionally, during the initial 24 h, the correlations between admission (first), best (lowest), highest, and mean OI and OSI values were determined. The predictive ability of the first 24 h oxygen and oxygen saturation indices for mortality and other adverse outcomes were assessed using the Area Under the Curve (AUC) analysis. Results: Thirty-seven infants with CDH were included in the analysis. A strong correlation was observed between all pairs of OI/OSI (2,289) (Spearman's rho = 0.843), matched pairs of Postductal OI/OSI (1,232 pairs) (Spearman's rho = 0.835) and the unmatched pairs of Postductal OI and Preductal OSI (1,057 pairs) (Spearman's rho = 0.852). Using the regression equations for all pairs, matched and unmatched OI/OSI pairs, we deduced that for clinically pertinent OI thresholds of 10, 15, 20 and 40, the corresponding OSI values were 5, 8, 11, and 23, respectively. Furthermore, in the first 24 h, strong correlations were evident between OI/OSI: at admission (Spearman's rho = 0.783), best OI/OSI (Spearman's rho = 0.848), and highest OI/OSI (Spearman's rho = 0.921). The most robust correlation was observed between the mean OI/OSI with a Spearman's rho of 0.928. First (AUC = 0.849), best (AUC = 0.927), highest (AUC = 0.942) and mean day 1 OI (AUC = 0.946) were all predictive of mortality. Similarly, first (AUC = 1.00), best (AUC = 0.989), highest (AUC = 1.00) and the mean OSI in day 1 (AUC = 0.978) were all predictive of mortality. All of the OIs and OSIs in day 1 except for the admission OSI (AUC = 0.683) were predictive of pulmonary hypertension. Additionally, all of OI and OSI indices in the first 24-hour except for the best day 1 OI (AUC = 0.674) were predictive of the need for rescue HFOV. Conclusion: There were a strong correlation between the OI and OSI in infants with CDH. Oxygenation indices and OSI in the first 24 h were predictive of mortality and other adverse outcomes in infants with CDH.

Effects of inbreeding on reproductive success in endangered North Atlantic right whales.

Only approximately 356 North Atlantic right whales (Eubalaena glacialis) remain. With extremely low levels of genetic diversity, limited options for mates, and variation in reproductive success across females, there is concern regarding the potential for genetic limitations of population growth from inbreeding depression. In this study, we quantified reproductive success of female North Atlantic right whales with a modified de-lifing approach using reproductive history information collected over decades of field observations. We used double-digest restriction site-associated sequencing to sequence approximately 2% of the genome of 105 female North Atlantic right whales and combined genomic inbreeding estimates with individual fecundity values to assess evidence of inbreeding depression. Inbreeding depression could not explain the variance in reproductive success of females, however we present evidence that inbreeding depression may be affecting the viability of inbred fetuses-potentially lowering the reproductive success of the species as a whole. Combined, these results allay some concerns that genetic factors are impacting species survival as genetic diversity is being retained through selection against inbred fetuses. While still far fewer calves are being born each year than expected, the small role of genetics underlying variance in female fecundity suggests that variance may be explained by external factors that can potentially be mitigated through protection measures designed to reduce serious injury and mortality from human activities.

Genome-wide association studies of lifetime and frequency cannabis use in 131,895 individuals.

Cannabis is one of the most widely used drugs globally. Decriminalization of cannabis is further increasing cannabis consumption. We performed genome-wide association studies (GWASs) of lifetime (N=131,895) and frequency (N=73,374) of cannabis use. Lifetime cannabis use GWAS identified two loci, one near CADM2 (rs11922956, p=2.40E-11) and another near GRM3 (rs12673181, p=6.90E-09). Frequency of use GWAS identified one locus near CADM2 (rs4856591, p=8.10E-09; r2 =0.76 with rs11922956). Both traits were heritable and genetically correlated with previous GWASs of lifetime use and cannabis use disorder (CUD), as well as other substance use and cognitive traits. Polygenic scores (PGSs) for lifetime and frequency of cannabis use associated cannabis use phenotypes in AllofUs participants. Phenome-wide association study of lifetime cannabis use PGS in a hospital cohort replicated associations with substance use and mood disorders, and uncovered associations with celiac and infectious diseases. This work demonstrates the value of GWASs of CUD transition risk factors.

Network meta-analysis made simple: a composite likelihood approach.

Network meta-analysis, also known as mixed treatments comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis. Despite the growing popularity of network metaanalysis within comparative effectiveness research, it comes with potential challenges. For example, within-study correlations among treatment comparisons are rarely reported in the published literature. Yet, these correlations are pivotal for valid statistical inference. As demonstrated in earlier studies, ignoring these correlations can inflate mean squared errors of the resulting point estimates and lead to inaccurate standard error estimates. This paper introduces a composite likelihood-based approach that ensures accurate statistical inference without requiring knowledge of the within-study correlations. The proposed method is computationally robust and efficient, with substantially reduced computational time compared to the state-of-the-science methods implemented in R packages. The proposed method was evaluated through extensive simulations and applied to two important applications including a network meta-analysis comparing interventions for primary open-angle glaucoma, and another comparing treatments for chronic prostatitis and chronic pelvic pain syndrome.

The adipokine profile in the plasma and anterior pituitary of pigs during the estrous cycle.

Adipokines play crucial roles in both reproductive and energy metabolic processes. This study aimed to compare the hormonal plasma profile of adiponectin, apelin, vaspin, chemerin, resistin, visfatin, and adipolin, and the expression of their receptors in the anterior pituitary (AP) between normal-weight Large White (LW) and fat Meishan (MS) pigs during different phases of the estrous cycle. We measured adipokine levels in the plasma and assessed their gene expression in the AP. We used Pearson's correlation analysis to examine potential links between adipokines levels, their receptors, and metabolic parameters (body weight; backfat thickness) and reproductive parameters (pituitary weight; age at puberty; levels of gonadotropins, steroid hormones; and gene expression of gonadotropin-releasing hormone receptor and gonadotropins in AP). The plasma levels of the evaluated adipokines fluctuated with phase and breed, except for visfatin and adipolin. Moreover, adipokine expression in AP varied significantly between breeds and estrous cycle phases, except for resistin receptor CAP1. Notably, we observed a positive correlation between plasma levels of adiponectin and its transcript in the AP only in MS pigs. Apelin gene expression correlated negatively with its receptor in MS, while we observed a breed-dependent correlation between chemerin gene expression and its receptor CMKLR1. We identified significant positive or negative correlations between adipokines or their receptor levels in plasma and AP as well as metabolic or reproductive parameters, depending on the breed. In conclusion, we have demonstrated breed-specific and estrous cycle-dependent regulation of adipokines in AP, underscoring their potential impact on metabolic and reproductive processes in swine.

Exploiting multivariate network meta-analysis: A calibrated Bayesian composite likelihood inference.

Multivariate network meta-analysis has emerged as a powerful tool in evidence synthesis by incorporating multiple outcomes and treatments. Despite its advantages, this method comes with methodological challenges, such as the issue of unreported within-study correlations among treatments and outcomes, which potentially lead to misleading conclusions. In this paper, we proposed a calibrated Bayesian composite likelihood approach to overcome this limitation. The proposed method eliminated the need to specify a full likelihood function while allowing for the unavailability of within-study correlations among treatments and outcomes. Additionally, we developed a hybrid Gibbs sampler algorithm along with the Open-Faced Sandwich post-sampling adjustment to enable robust posterior inference. Through comprehensive simulation studies, we demonstrated that the proposed approach yielded unbiased estimates while maintaining coverage probabilities close to the nominal level. Furthermore, we implemented the proposed method on two real-world network meta-analysis datasets; one comparing treatment procedures for the root coverage and another comparing treatments for anaemia in chronic kidney disease patients.

GBA1-Associated Parkinson's Disease Is a Distinct Entity.

GBA1-associated Parkinson's disease (GBA1-PD) is increasingly recognized as a distinct entity within the spectrum of parkinsonian disorders. This review explores the unique pathophysiological features, clinical progression, and genetic underpinnings that differentiate GBA1-PD from idiopathic Parkinson's disease (iPD). GBA1-PD typically presents with earlier onset and more rapid progression, with a poor response to standard PD medications. It is marked by pronounced cognitive impairment and a higher burden of non-motor symptoms compared to iPD. Additionally, patients with GBA1-PD often exhibit a broader distribution of Lewy bodies within the brain, accentuating neurodegenerative processes. The pathogenesis of GBA1-PD is closely associated with mutations in the GBA1 gene, which encodes the lysosomal enzyme beta-glucocerebrosidase (GCase). In this review, we discuss two mechanisms by which GBA1 mutations contribute to disease development: 'haploinsufficiency,' where a single functional gene copy fails to produce a sufficient amount of GCase, and 'gain of function,' where the mutated GCase acquires harmful properties that directly impact cellular mechanisms for alpha-synuclein degradation, leading to alpha-synuclein aggregation and neuronal cell damage. Continued research is advancing our understanding of how these mechanisms contribute to the development and progression of GBA1-PD, with the 'gain of function' mechanism appearing to be the most plausible. This review also explores the implications of GBA1 mutations for therapeutic strategies, highlighting the need for early diagnosis and targeted interventions. Currently, small molecular chaperones have shown the most promising clinical results compared to other agents. This synthesis of clinical, pathological, and molecular aspects underscores the assertion that GBA1-PD is a distinct clinical and pathobiological PD phenotype, necessitating specific management and research approaches to better understand and treat this debilitating condition.

Lithium in Drinking Water and its Potential Impact on Mental Health: A Review.

This review explores the relationship between lithium in drinking water and mental health, a subject that has garnered increasing attention in investigations. Lithium, a metal with a well-established role in psychiatric medications, is found in trace amounts in drinking water, and studies suggest its potential correlations with lower rates of suicide and certain psychiatric disorders. However, these correlations do not imply causation, necessitating an examination of the underlying mechanisms. Lithium concentrations in drinking water vary globally, presenting challenges in establishing a universal threshold for "high" or "low" levels. Additionally, the optimal dosage for potential mental health benefits remains uncertain. Lithium is not considered an essential nutrient, and supplementation should be approached with caution due to possible toxicity risks, emphasizing the importance of medical supervision. The lack of causation and ongoing need for further investigation underscores the importance of cautious interpretation and transparent communication in navigating this evolving field.

Gamma amplitude-envelope correlations are strongly elevated within hyperexcitable networks in focal epilepsy.

Methods to quantify cortical hyperexcitability are of enormous interest for mapping epileptic networks in patients with focal epilepsy. We hypothesize that, in the resting state, cortical hyperexcitability increases firing-rate correlations between neuronal populations within seizure onset zones (SOZs). This hypothesis predicts that in the gamma frequency band (40-200 Hz), amplitude envelope correlations (AECs), a relatively straightforward measure of functional connectivity, should be elevated within SOZs compared to other areas. To test this prediction, we analyzed archived samples of interictal electrocorticographic (ECoG) signals recorded from patients who became seizure-free after surgery targeting SOZs identified by multiday intracranial recordings. We show that in the gamma band, AECs between nodes within SOZs are markedly elevated relative to those elsewhere. AEC-based node strength, eigencentrality, and clustering coefficient are also robustly increased within the SOZ with maxima in the low-gamma band (permutation test Z-scores > 8) and yield moderate discriminability of the SOZ using ROC analysis (maximal mean AUC ~ 0.73). By contrast to AECs, phase locking values (PLVs), a measure of narrow-band phase coupling across sites, and PLV-based graph metrics discriminate the seizure onset nodes weakly. Our results suggest that gamma band AECs may provide a clinically useful marker of cortical hyperexcitability in focal epilepsy.

Insulator-transition-induced Degradation of Pyrochlore Ruthenates in Electrocatalytic Oxygen Evolution and Stabilization through Doping.

Ru-based pyrochlores (e.g., Y2Ru2O7-d) are promised to replace IrO2 in polymer electrolyte membrane (PEM) electrolyzers. It is significant to reveal the cliff attenuation on the oxygen evolution reaction (OER) performance of these pyrochlores. In this work, we monitor the structure changes and electrochemical behavior of Y2Ru2O7-d over the OER process, and it is found that the reason of decisive OER inactivation is derived from an insulator transition occurred within Y2Ru2O7-d due to its inner ²perfecting² lattice induced by continuous atom rearrangement. Therefore, a stabilization strategy of the Ir-substituted Y2Ru2O7-d is proposed to alleviate this undesirable behavior. The double-exchange interaction between Ru and Ir in [RuO6] and [IrO6] octahedra leads the charge redistribution with simultaneous spin configuration adjustment. The electronic state in newly formed octahedrons centered with Ru 4d3 (with the state of eg'2--a1g-1 eg0) and Ir 5d6 (eg'4a1g-2 eg0) relieves the uneven electron distributions in [RuO6] orbital. The attenuated Jahn-Teller effect alleviates atom rearrangement, represented as the mitigation of insulator transition, surface reconstruction, and metal dissolution. As results, the Ir-substituted Y2Ru2O7-d presents the greatly improved OER stability and PEM durability. This study unveils the OER degradation mechanism and stabilization strategy for material design of Ru-based OER catalysts for electrochemical applications.