BACKGROUND:Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder with hyperphagia, hypothalamic dysfunction, and severe behavioral dysregulation. Empirical descriptions of integrated inpatient treatment models remain limited. We examined multidomain outcomes during interdisciplinary inpatient stabilization in PWS. METHODS:This exploratory retrospective cohort included nine adolescents and young adults with genetically confirmed PWS admitted for severe behavioral dysregulation to a specialized interdisciplinary inpatient program. Behavioral, functional, anthropometric, and fasting metabolic outcomes were assessed at admission and discharge; medication profiles were recorded descriptively and three-month follow-up obtained via caregiver interview. Within-subject change was analyzed with Wilcoxon signed-rank tests. RESULTS:Token engagement increased (median 8 percentage points, p < 0.05) and aggression resolved: every patient had incidents in the first week, none in the final week (p = 0.004). Agitation showed a non-significant decrease (p = 0.063, floor effect) and global behavioral disturbance was non-significant (p = 0.24). Walk distance and functional independence improved (both p < 0.05). Weight decreased 73 lbs (1.2% per week) and BMI by 11.9 kg/m2 (both p < 0.05), with improvements in triglycerides, HbA1c, HDL, LDL, and total cholesterol (all p < 0.05). No behavioral-metabolic correlations survived false discovery rate adjustment. At three months, 89% remained in the community without rehospitalization and 77% rated global well-being as good or excellent. CONCLUSIONS:Structured interdisciplinary inpatient treatment for severe behavioral dysregulation in PWS was associated with multidomain improvement across behavioral, functional, and cardiometabolic domains. Behavioral and metabolic changes were not directly coupled; causality cannot be inferred. These findings support prospective investigation of integrated treatment models.
The purpose of the present study was to investigate the effects of a sleep treatment package on the frequency of night awakenings, bedtime resistance, and caregiver stress with the caregivers of three child participants diagnosed with Prader-Willi syndrome (PWS) using a multiple baseline across subjects design. During baseline, child participants were not exposed to any procedure. During intervention, caregivers implemented a treatment package including graduated extinction, bedtime routines, and bedtime fading without response cost. All interventions were previously successful with children diagnosed with autism spectrum disorder but had not been attempted with this population. Correct responding was defined as zero instances of night awakenings, zero instances of bedtime resistance (different for each child participant) and decreases in caregiver-reported stress. In addition, social validity was assessed using a Likert-style questionnaire. The results show that the treatment package had varying success across all participants, with the most success being for reducing behaviors at bedtime. These results will provide further understanding of the effect behavior-analytic approaches can have on children diagnosed with Prader-Willi syndrome, increasing the number of applications of applied behavior analysis and the supports available for caregivers of children diagnosed with PWS.
Rapid and reliable identification of multivariate geochemical anomalies is critical for delineating prospective mineralized zones and reducing uncertainty in mineral exploration targeting. Extended isolation forest (EIF) is a powerful unsupervised ensemble learning algorithm that efficiently isolates anomalies from high-dimensional geochemical datasets using randomly oriented hyperplane partitions. Previous studies have demonstrated the effectiveness of EIF in multivariate geochemical anomaly detection and mineral potential modeling. However, its performance can be significantly affected by stochastic variability arising from random partitioning and random subsampling during isolation tree construction, which may result in unstable anomaly patterns and inconsistent exploration targets in complex geological environments. To mitigate this limitation, we developed a robust unsupervised framework for the identification of multivariate geochemical anomalies associated with gold mineralization in the Southwestern Yilgarn Craton, Australia. The proposed framework integrates robust factor analysis (RFA), a Jaccard-based stability index and EIF to enhance the reliability and reproducibility of anomaly detection. RFA was first applied to compositional soil geochemical data to identify the most significant pathfinder elements associated with gold mineralization, which were subsequently used as input variables for the EIF model. The model was then optimized using a Jaccard-based stability criterion to ensure consistent anomaly detection across repeated independent runs. Model performance was assessed using area under the receiver operating characteristic curve (AUC). The obtained AUC value of 0.82 indicates strong predictive capacity, confirming that the generated anomaly map effectively delineates mineralization-related geochemical patterns and provides a reliable proxy for mineral prospectivity mapping. Overall, the proposed framework offers a robust and reproducible unsupervised approach for multivariate geochemical anomaly detection with strong applicability in both greenfield and brownfield mineral exploration settings.
Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder classically defined by hyperphagia and obesity. However, its profound psychiatric phenotype offers a unique genetic framework for understanding major mental illnesses. This review positions PWS as a potentially informative biological model for psychosis and obsessive-compulsive disorder (OCD), bridging the gap between 15q11-q13 imprinting defects and neural circuit dysfunction. We synthesize evidence demonstrating that psychosis in PWS is not a uniform trait but is disproportionately linked to the maternal uniparental disomy (mUPD) subtype. This genotype-phenotype correlation suggests that overexpression of maternally imprinted genes and loss of paternal expression disrupt cortical excitatory-inhibitory balance, resembling the "schizophrenia-bipolar" genomic architecture. Furthermore, synthesized evidence characterizes the repetitive, ritualistic behaviors in PWS not merely as behavioral challenges, but as a developmentally arrested OCD-spectrum phenotype driven by distinct serotonergic-oxytocinergic imbalances and hypothalamic-limbic dysconnectivity. Mechanistic insights from preclinical models of MAGEL2, SNORD116, and NDN deficiency are integrated with clinical findings to highlight shared neurobiological substrates. Finally, we outline a roadmap for precision psychiatry in PWS, emphasizing the necessity of pharmacogenomics in antipsychotic management and the potential of targeted circuit-based therapeutics. By deconstructing the psychiatric comorbidities of PWS, we provide a framework for translating genomic architecture into mechanistic understanding and targeted treatment for complex neuropsychiatric disorders.
This study examined interoception and mindfulness as related processes in eating behaviors in a non-clinical population. The aim was to identify interoceptive sensibility and mindfulness clusters using a person-centered approach and to examine their associations with eating behaviors, eating disorder risk, body mass index, and psychological distress. An online survey was conducted in a French community sample of 381 adults. Participants completed validated self-report measures assessing interoceptive sensibility, mindfulness, eating behaviors, and psychological distress. Cluster analysis identified four distinct groups reflecting different combinations of interoceptive sensibility and mindfulness. Profiles characterized by higher mindfulness consistently showed more adaptive eating patterns, including lower emotional and external eating and greater reliance on internal cues, regardless of interoceptive levels. In contrast, clusters with lower mindfulness showed higher levels of emotional eating and psychological distress. Within these low mindfulness profiles, high interoception was associated with lower depressive symptoms, lower eating disorder risk, and normal-weight status. These findings suggest that mindfulness was consistently associated with adaptive eating and psychological outcomes across profiles, whereas interoceptive sensibility further differentiated outcomes among profiles characterized by lower mindfulness. Overall, the results highlight the importance of considering both interoceptive sensibility and mindfulness jointly to better understand variability in eating behaviors and psychological distress.
BACKGROUND:Research on the association between sugar-sweetened beverages (SSBs) and depression has advanced, but most studies are cross-sectional and focus on adults. This meta-analysis assesses their association in youth using observational data. METHODS:We searched Ovid Cochrane, Ovid Embase, Ovid Medline, and PsycINFO databases up until December 2024 for relevant studies. Two reviewers performed data extraction and assessed the risk of bias. A random-effects model calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to explore heterogeneity. RESULTS:A total of 19 articles with 26 independent studies were included, totaling 275,168 participants with an average age of 16.1 years (range 11-25). Overall, a statistically significant pooled estimate was observed in youth (OR = 1.28, 95%CI = 1.16-1.41; I2 = 94.3%). When separated by study design, cross-sectional studies yielded a statistically significant pooled estimate with considerable heterogeneity (OR = 1.33, 95%CI = 1.18-1.50, I2 = 94.5%), whereas the pooled estimate from cohort studies was not statistically significant (OR = 1.13, 95%CI = 0.97-1.31, I2 = 69.1%), consistent across both adolescents and young adults. Results from subgroup analyses revealed that region, measurement of exposure, type of outcome, and follow-up period (for cohort studies only) may be the sources of heterogeneity (all Pinteraction< 0.05). CONCLUSION:Despite an overall association between SSBs and depression, separate analysis by study design has yielded inconsistent findings, with a statistically significant estimate found in cross-sectional but not in cohort studies. Future research should focus on longitudinal studies with longer follow-up periods.
Previous studies have primarily investigated the adverse effects of insulin resistance (IR) on cognitive function in schizophrenia (SZ) patients. IR is typically assessed based on fasting insulin (FINS) and fasting blood glucose (FBG) levels. This study revealed that first-episode, drug-naïve (FEND) SZ patients had normal FBG levels, with no significant difference from healthy controls, while significantly elevated FINS levels, indicating that IR in FEND SZ patients may be predominantly driven by increased FINS. This study primarily investigated the association between FINS levels and cognitive impairment in FEND SZ patients. This cross-sectional research recruited 466 FEND SZ patients. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was utilized to evaluate participants' neurocognitive performance, and measured the levels of FINS, FBG, and glycated hemoglobin. The link between FINS and cognitive performance was evaluated using multiple linear regression and smoothing curve fitting methods. After adjusting for relevant confounding factors, FINS were negatively correlated with immediate memory (β = -7.77), attention (β = -9.09), delayed memory (β = -13.02), and total RBANS scores (β = -5.21) (all p < 0.001). Quartile analysis revealed that elevated FINS were linked to decreased cognitive function scores. (all p < 0.001). In FEND SZ patients, higher FINS levels are associated with more severe cognitive impairment, suggesting that FINS may be indicative of evaluating cognitive impairment as a potential biomarker. Measurement of pre-treatment FINS at the initial clinical visit is of important clinical value for guiding therapeutic interventions to improve insulin sensitivity and, consequently, patients' cognitive function.
Introduction Emotional disorders (ED) such as depression and anxiety are the most prevalent worldwide and are often addressed in primary care (PC). Stressful events can cause people to activate adaptive or maladaptive cognitive emotion regulation strategies (CERS). The type of CERS used by an individual with an ED may influence clinical outcomes, quality of life (QoL), and functioning, although the precise effects are not well-understood. The aim of this study was to determine whether CERS are significant predictors of clinical symptoms, QoL, and functioning in PC patients with EDs. Method This study included 685 patients referred for psychological therapy within the PsicAP-CV clinical trial. All data were obtained from self-report measures. Correlation analyses and hierarchical multiple linear regression models were performed, with sociodemographic variables entered in the first step and CERS in the second step. Results Sociodemographic variables explained 4% to 20% of variance. The addition of CERS increased the explained variance to 13%-40%, indicating that CERS is a significant predictor of clinical symptoms, QoL, and functioning in these patients. The use of adaptive CERS was associated with fewer clinical symptoms and better QoL and functioning. By contrast, maladaptive CERS were associated with higher levels of anxiety and depression and poorer QoL and functioning. Discussion Emotion regulation could be a relevant transdiagnostic construct to be considered in the therapeutic context, both in the prevention and treatment of anxiety and depression.
Schizophrenia (SZ) and bipolar disorder (BD) are major psychiatric conditions that show both overlapping and distinct clinical features. The hippocampus, a structure central to multiple cognitive functions including episodic memory, is altered in both disorders. Rather than functioning as a single unit, the hippocampus contains subregions with distinct connectivity patterns that may help clarify similarities and differences between these disorders. The present study directly compared hippocampal functional connectivity in SZ and BD using six well-validated hippocampal seeds (bilateral anterior, mid, and posterior segments) across two experimental contexts: resting state and memory tasks and examined associations with clinical and cognitive measures. Relative to healthy controls, both clinical groups showed significant connectivity alterations. The right posterior hippocampal parcel exhibited hyperconnectivity with the right inferior temporal gyrus in SZ only. The right mid hippocampal parcel showed hypoconnectivity with the left middle temporal gyrus and right superior temporal gyrus, a pattern shared by both clinical groups. Finally, the right anterior hippocampal parcel demonstrated hypoconnectivity with the left middle temporal gyrus that was specific to SZ at rest but shared by both disorders during the memory condition. Overall, these findings reveal both shared and disorder-specific patterns of hippocampal dysconnectivity, with two connectivity clusters showing significant associations with mnemonic performance.
The Mount Sinai Resilience Scale (MSRS) assesses cognitive, behavioral, and emotional resilience processes, yet the interrelationships among these processes, including which are most central and most strongly associated with mental health outcomes, remain poorly characterized. This study used network analysis to characterize the structure of MSRS-assessed resilience processes and their associations with clinical outcomes in a population-based sample of U.S. adults (N = 1794) enriched for elevated perceived stress and trauma exposure. Participants completed the MSRS and validated measures of depressive, anxiety, and posttraumatic stress disorder (PTSD) symptoms and well-being. Regularized Gaussian graphical models were estimated to characterize network structure and centrality, with clinical outcomes incorporated as nodes to identify unique associations with individual MSRS items. The network demonstrated moderate density (157 of 276 possible edges), reflecting widespread conditional associations among resilience processes. Engagement in meaningful activities, perceived positive impact of spirituality, and active emotional recovery demonstrated the highest centrality, while emotional awareness and directly facing fears also showed high expected influence. Staying hopeful about the future, directly facing fears, and engaging in meaningful activities were consistently associated with lower depressive, anxiety, and PTSD symptoms and higher well-being. Forgiveness was positively associated with PTSD symptoms, suggesting a more complex role in trauma-related adaptation. Overall, MSRS resilience processes were organized around interconnected domains of meaning, spirituality, and emotional regulation. Hope, behavioral approach to feared experiences, and engagement in meaningful activities emerged as resilience processes with consistent associations across multiple mental health outcomes, highlighting their potential relevance for resilience-focused interventions.
Among people with bipolar I disorder (BD), cannabis use disorder (CUD) is highly comorbid and correlated with poorer clinical outcomes, including increased suicidal behaviors and decreased quality-of-life (QoL). However, research on different levels of CUD severity and their links to suicidal behaviors and QoL are underexplored. Using data from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III), this study examined the relationships between DSM-5 CUD severity and lifetime suicide attempts or health-related QoL in participants with and without lifetime bipolar I disorder (ns = 753 and 35,556, respectively). A logistic regression model, adjusted for sex, age, and race/ethnicity, indicated the rate of lifetime suicide attempts was 16.65% (95% CI [13.17, 20.83]) in people without BD and with severe CUD compared to 33.71% (95% CI [21.64, 48.36]) in people with BD and severe CUD. Additionally, an adjusted linear regression model showed that mental health QoL significantly declined in individuals without BD from those with no CUD symptoms (M = 51.49, 95% CI [51.33, 51.65]) to severe CUD (M = 45.28, 95% CI [44.35, 46.21]), whereas the mental health QoL for individuals with BD did not significantly vary across CUD severity. Physical health QoL was not significantly different across BD status nor CUD severity. Overall, these findings suggest that CUD severity is significantly associated with altered outcomes on lifetime suicide attempts and mental health QoL depending on lifetime BD status; however, BD may still play a more prominent role in mental health outcomes, regardless of CUD severity.
Water conservancy and hydropower projects enhance regional climate resilience and watershed water security yet inevitably trigger large-scale involuntary reservoir resettlement. As representative involuntarily displaced populations, reservoir resettlees' social identity directly impacts local social stability and regional sustainable socioeconomic development. Based on a ten-year longitudinal qualitative investigation including in-depth interviews and participant observation in Village Y of Wuxikou Reservoir, Jiangxi Province, this paper divides the entire resettlement process into three stages: relocation, stabilization and development. From the dual perspectives of host community identity and out-groups identity, this study explores the dynamic evolutionary rules of resettlees' social identity. The results indicate that resettlees sequentially develop alienated identity, superficial adaptive identity and segregated identity across different phases. On this basis, the core concept of differential identity is proposed, which features a dual structure of vertical temporal differentiation and horizontal spatial differentiation. This paper expands the applicable scope and explanatory power of the “differential mode of association” and social identity theory in involuntary resettlement contexts. Grounding on the differential identity framework, this paper puts forward targeted integrated governance solutions to break intergroup segregation, facilitate cross-group integration and build resilient resettlement communities consistent with Sustainable Development Goals (SDGs) 11 and 13.
The discrimination of ore deposit types is primarily based on geological, geochemical, and isotopic characteristics. Conventionally, these types are identified using specific element diagrams. However, traditional geochemical methods often fail to determine scheelite deposit types of the complex Xuefengshan Sb-Au-W metallogenic belt in China, where mineralization resulted from the superposition of multiphase geological events. Machine learning (ML) methods, have been increasingly applied to identify deposit genesis by establishing relationships between deposit characteristics and genetic types using extensive datasets. However, inaccurate data labels, the limitations of single models, and poor model interpretability lead to decreased accuracy. This study proposes a ML framework based on interpretable ensemble learning. We collects geochemical element data from typical orogenic and magmatic-hydrothermal scheelite deposits globally. Deep clustering is used to filter data and overcome the subjectivity of original data labels. An ensemble learning model is used to construct a classifier to improve the model's robustness and generalization ability. An interpretable model is introduced to analyze the contribution of individual feature elements, revealing the metallogenic genesis. This method demonstrates high accuracy on the test set. According to this method, the scheelite deposit type of the Xuefengshan metallogenic belt is primarily magmatic-hydrothermal in origin, with orogenic superposition. This helps resolve a long-standing controversy in the region and establishes a repeatable and interpretable new paradigm for ML-based discrimination of ore deposit genetic types.
Though volcanogenic massive sulfide (VMS) deposits are major global sources of indium (In), the physicochemical mechanisms and key factors controlling its significant enrichment remain poorly understood. To address the issue, this study investigates the Tiemurt VMS Pb-Zn-Cu deposit, utilizing detailed petrography, in-situ LA-ICP-MS analysis, and thermodynamic modeling to reveal the In enrichment mechanisms in VMS deposits. Petrographic observations identified two distinct generations of sphalerite corresponding to different mineralization stages. The early-stage sphalerite (Sp1) is euhedral-subhedral, associated with pyrite, and displays darker colors (red to brown), whereas the late-stage sphalerite (Sp2) is anhedral, intimately intergrown with chalcopyrite, and shows lighter colors (mainly yellow). The trace element results demonstrate that Sp1 has a significantly higher In content (average 317 ppm) than Sp2 (average 220 ppm). Additionally, In concentrations positively correlate with Fe contents. Because Fe is the primary chromophore that darkens sphalerite, this strong coupled enrichment mechanism allows macroscopic sphalerite color (red > brown > yellow) to serve as a reliable indicator for In concentration. Crystallization temperatures calculated using the GGIMFis thermometer range from 344 to 382 °C for Sp1 and 312 to 355 °C for Sp2, indicating a cooling trend during fluid evolution. Thermodynamic modeling data showed that in the early-stage hydrothermal fluids (≥360 °C), Zn2+ preferentially complexes with Cl−, leaving InCl2+ or In3+ as unstable species, and In efficiently precipitates into Sp1 under the environment of log fO2 = −32 to −26 and pH = 6–8. As the fluids cool at ~340 °C, weakened Zn2+ competition allows In3+ to form stable InCl3, and In precipitates into Sp2 under the conditions of log fO2 = −42 to −32 and pH = 5.5–11. We therefore conclude that the key factor controlling the difference in In content between Sp1 and Sp2 is the precipitation mechanism rather than migration capacity. This may be different from the In enrichment mechanism associated with magmatic hydrothermal systems, where In is mainly present as InCl3 complexes with strong migration capacity. These new findings enable us to understand how the physicochemical conditions of fluids control the enrichment of In in VMS deposits, and also highlight that the color of sphalerite can be used to target potential In resources in PbZn deposits.
