Detecting adolescent depression through passive monitoring of linguistic markers in smartphone communication.

BACKGROUND: Cross sectional studies have identified linguistic correlates of major depressive disorder (MDD) in smartphone communication. However, it is unclear whether monitoring these linguistic characteristics can detect when an individual is experiencing MDD, which would facilitate timely intervention. METHODS: Approximately 1.2 million messages typed into smartphone social communication apps (e.g. texting, social media) were passively collected from 90 adolescents with a range of depression severity over a 12-month period. Sentiment (i.e. positive vs. negative valence of text), proportions of first-person singular pronouns (e.g. 'I'), and proportions of absolutist words (e.g. 'all') were computed for each message and converted to weekly aggregates temporally aligned with weekly MDD statuses obtained from retrospective interviews. Idiographic, multilevel logistic regression models tested whether within-person deviations in these linguistic features were associated with the probability of concurrently meeting threshold for MDD. RESULTS: Using more first-person singular pronouns in smartphone communication relative to one's own average was associated with higher odds of meeting threshold for MDD in the concurrent week (OR = 1.29; p = .007). Sentiment (OR = 1.07; p = .54) and use of absolutist words (OR = 0.99; p = .90) were not related to weekly MDD. CONCLUSIONS: Passively monitoring use of first-person singular pronouns in adolescents' smartphone communication may help detect MDD, providing novel opportunities for early intervention.

Childhood trauma predicts blunted error monitoring in adulthood: An event-related potential study.

Abuse and neglect have detrimental consequences on emotional and cognitive functioning during childhood and adolescence, including error monitoring, which is a critical aspect of cognition that has been implicated in certain internalizing and externalizing psychopathologies. It is unclear, however, whether (a) childhood trauma has effects on error monitoring and, furthermore whether, (b) error monitoring mediates the relation between childhood trauma and psychopathology in adulthood. To this end, in a large sample of young adults (ages 18-30) who were oversampled for psychopathology (N = 390), the present study assessed relations between childhood trauma and error-related negativity (ERN), which is a widely used neurophysiological indicator of error monitoring. Cumulative childhood trauma predicted ERN blunting, as did two specific types of traumas: sexual abuse and emotional neglect. Furthermore, the ERN partially mediated the effects of cumulative childhood trauma and emotional neglect on externalizing-related symptoms. Future studies should further examine the relations between childhood trauma and error monitoring in adulthood, which can help to inform intervention approaches.

A prospective study of the relative contribution of adolescent peer support quantity and quality to depressive symptoms.

BACKGROUND: During adolescence, peer support has an increasingly important role in identity formation and well-being. Prior research has identified that lack of social support from peers in adolescence is a potent risk factor for depression. Two ways that social support has been operationalized is by the number of one's friends (i.e., 'quantity') and perception of one's network (i.e., 'quality'). Typically, these aspects of peer support are assessed separately. METHODS: Using data from the National Longitudinal Study of Adolescent to Adult Health (N = 3,857), this study sought to test whether (1) adolescent depression relates to having fewer friends versus lower quality friendships, (2) these aspects of adolescent peer support prospectively predict depression in adulthood, (3) gender moderates the effects of peer support on depression, and (4) these aspects of peer support buffer the effects of stressful life events on depression. RESULTS: Peer support quality uniquely predicted depression in adolescence and adulthood among both males and females. The effect of peer support quality on depressive symptoms, however, was greater for females than males. By contrast, peer support quantity did not uniquely predict depression for males or females. CONCLUSIONS: Qualitative aspects of adolescent peer support uniquely contribute to mental health not only in adolescence, but in adulthood as well. Potential processes through which peer support relates to depression are discussed, as well as implications for treatment.

Transient presence of stomatocytes: A clue to the diagnosis of overhydrated hereditary stomatocytosis in a child with beta-thalassemia.

BACKGROUND: Overhydrated hereditary stomatocytosis (OHSt) is a rare disorder characterized by abnormalities in erythrocytic volume homeostasis. Early and accurate diagnosis is essential for appropriate management and genetic counseling. METHODS: We present the case of a child with beta-thalassemia and a history of multiple blood transfusions. Clinical presentation, laboratory findings, and genetic testing were reviewed. Peripheral blood smear examination and genetic analysis were performed. RESULTS: The patient was admitted with severe anemia, and peripheral blood smear examination revealed the presence of up to 50% stomatocytes. Laboratory investigations showed abnormalities in red blood cell parameters, including decreased hemoglobin levels and increased mean corpuscular volume. Genetic testing identified a heterozygous mutation in the RHAG gene, confirming the diagnosis of OHSt. The presence of stomatocytes in the peripheral blood smear was transient, correlating with episodes of hemolysis and its control.

What you want may not be what you like: A test of the aberrant salience hypothesis in schizophrenia risk.

Motivational abnormalities represent a key area of dysfunction in individuals with, or at risk for, schizophrenia and severely limit broad domains of functioning in these populations. The aberrant salience hypothesis posits that motivational abnormalities are the result of an over-attribution of salience to nonpleasurable stimuli but an under-attribution of salience to pleasurable ones. Consequently, people "want" what they do not "like" but do not "want" what they "like." However, it is unclear how this hypothesis manifests in schizophrenia risk beyond monetary rewards. The current research provided a multimodal investigation of the aberrant salience hypothesis in people with elevated psychotic-like experiences (PLEs) who are at risk for developing psychosis. Study 1 examined the link between liking and incentive salience using a neurobiological indicator of incentive salience (contingent negative variation/CNV) in 23 PLEs and 21 Control participants. The PLEs group showed diminished CNV reactivity to pleasant (vs. neutral) social images, which was driven by an augmented response to neutral stimuli. Study 2 examined liking, incentive salience, and conscious wanting experience using a psychological indicator of incentive salience (positive spontaneous thoughts/PSTs) in 38 PLEs and 246 Control participants. The PLEs group showed diminished correspondence between liking, PSTs, and conscious wanting across diverse reward contexts. Collectively, individuals with PLEs over-attribute salience to neutral stimuli and, to a lesser degree, under-attribute salience to rewards. Findings of the current research support abnormal salience attribution as a trait-like feature implicated in the pathophysiology and development of schizophrenia and provide valuable insights on research and treatment of this illness.

Graphene oxide conjugated with polymers: a study of culture condition to determine whether a bacterial growth stimulant or an antimicrobial agent?

BACKGROUND: The results showed that the deciding factor is the culture medium in which the bacteria and the graphene oxide (GO) are incubated at the initial manipulation step. These findings allow better use of GO and GO-based materials more and be able to clearly apply them in the field of biomedical nanotechnology. RESULTS: To study the use of GO sheets applied in the field of biomedical nanotechnology, this study determines whether GO-based materials [GO, GO-polyoxyalkyleneamine (POAA), and GO-chitosan] stimulate or inhibit bacterial growth in detail. It is found that it depends on whether the bacteria and GO-based materials are incubated with a nutrient at the initial step. This is a critical factor for the fortune of bacteria. GO stimulates bacterial growth and microbial proliferation for Gram-negative and Gram-positive bacteria and might also provide augmented surface attachment for both types of bacteria. When an external barrier that is composed of GO-based materials forms around the surface of the bacteria, it suppresses nutrients that are essential to microbial growth and simultaneously produces oxidative stress, which causes bacteria to die, regardless of whether they have an outer-membrane-Gram-negative-bacteria or lack an outer-membrane-Gram-positive-bacteria, even for high concentrations of biocompatible GO-POAA. The results also show that these GO-based materials are capable of inducing reactive oxygen species (ROS)-dependent oxidative stress on bacteria. Besides, GO-based materials may act as a biofilm, so it is hypothesized that they suppress the toxicity of low-dose chitosan. CONCLUSION: Graphene oxide is not an antimicrobial material but it is a general growth enhancer that can act as a biofilm to enhance bacterial attachment and proliferation. However, GO-based materials are capable of inducing ROS-dependent oxidative stress on bacteria. The applications of GO-based materials can clearly be used in antimicrobial surface coatings, surface-attached stem cells for orthopedics, antifouling for biocides and microbial fuel cells and microbial electro-synthesis.

Severe sexual abuse in childhood and altered neurophysiological response to reward in female adults.

BACKGROUND: A relatively understudied but growing body of research indicates that individuals with a history of childhood trauma exhibit altered reward processing in adulthood. Research to date has focused on adversity broadly, with studies typically finding evidence of blunted response to rewards in adults with a history of childhood trauma. OBJECTIVE: Given the role of reward processing in risk for psychopathology and the particularly pathogenic nature of sexual abuse (SA), the present study sought to assess whether adults with a history of severe childhood SA exhibit altered neurophysiological response to rewards. PARTICIPANTS AND SETTING: Female adults (N = 105) were included from two study sites that used the same measures of childhood trauma (Childhood Trauma Questionnaire, CTQ), reward processing (Doors Task), and psychopathology (SCID). METHODS: Based on participants' CTQ and SCID responses, three groups were created: Severe SA (n = 36), Clinical Match (with comparable lifetime psychopathology but no-to-minimal SA history; n = 35), and Healthy Controls (n = 34). Group differences in RewP amplitude were assessed. RESULTS: The Severe SA group exhibited larger reward positivity (RewP) amplitude to monetary rewards than the Clinical Match and Healthy Control groups (partial ƞ2 = 0.06, p = .047). This effect remained after covarying for severity of other forms of childhood trauma. CONCLUSIONS: Our study found that severe SA in childhood was related to a heightened response to reward in adulthood. Furthermore, this was not attributable to the severity of other forms of early trauma or comorbid psychopathology. Future studies are needed to identify how heightened reward processing following severe childhood SA may be implicated in the onset and course of psychopathology.

Cognitive inflexibility and heightened error monitoring are related to lower sexual functioning.

Sexual functioning is an important predictor of well-being and relationship satisfaction. Previous research indicates that several aspects of cognitive function are related to sex-related behaviors and functioning among individuals with sex-related disorders, neurological disorders, and in older adults; however, this has been relatively underexamined in younger populations. To examine this, the present study assessed whether behavioral and/or neurophysiological measures of cognitive function are associated with sexual functioning in a community sample of young 489 adults (64 % female) ages 18-30. Cognitive flexibility (n = 460) and inhibition (n = 466) were measured using neuropsychological assessment (D-KEFS), and conflict monitoring and error monitoring were measured by event-related potentials (conflict N2: n = 394; error-related negativity: n = 389). After separately testing relations between the different measures of cognitive function and sexual functioning, we assessed whether results (1) remained after covarying for externalizing and internalizing dimensions (PID-5; n = 489) or (2) varied by gender. Finally, we tested whether any aspects of cognitive function were unique predictors of sexual functioning. Cognitive flexibility and error monitoring (i.e., error-related negativity) were both significantly related to sexual functioning among males and females, such that poorer cognitive flexibility and heightened error monitoring were related to lower sexual functioning. No significant effects emerged for inhibition or conflict monitoring. In a multiple regression model, cognitive flexibility and error monitoring each accounted for a unique portion of variance in sexual functioning beyond other aspects of cognitive function and psychopathology-related traits. Results suggest that cognitive function is a meaningful correlate of sexual functioning in young adulthood, which should be considered further in future research.

The effects of family support and smartphone-derived homestay on daily mood and depression among sexual and gender minority adolescents.

Sexual and gender minority (SGM) adolescents are at elevated risk for depression. This risk is especially pronounced among adolescents whose home environment is unsupportive or nonaffirming, as these adolescents may face familial rejection due to their identity. Therefore, it is critical to better understand the mechanisms underlying this risk by probing temporally sensitive associations between negative mood and time spent in potentially hostile home environments. The current study included adolescents (N = 141; 43% SGM; 13-18 years old), oversampled for depression history, who completed clinical interviews assessing lifetime psychiatric history and depression severity as well as self-report measures of social support. Participants also installed an app on their personal smartphones, which assessed their daily mood and geolocation-determined mobility patterns over a 6-month follow-up period. Over the 6-month follow-up period, SGM adolescents reported elevated depression severity and lower daily mood relative to non-SGM youth. Interestingly, SGM adolescents who reported low family support experienced lower daily mood than non-SGM adolescents, particularly on days when they spent more time at home. Current findings reinforce evidence for disparities in depression severity among SGM adolescents and highlight family support as a key factor. Specifically, more time spent in home environments with low family support was associated with worse mood among SGM adolescents. These results underscore the need for clinical interventions to support SGM youth, particularly interventions that focus on familial relationships and social support within the home environment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Urbanization, Human Inequality, and Material Consumption.

Global material consumption needs to be reduced to be within its planetary boundary. Urbanization and human inequality are two profound economic-social phenomena, which have potential impacts on material consumption. This paper aims to empirically explore how urbanization and human inequality affect material consumption. For this aim, four hypotheses are proposed and the coefficient of human inequality and material footprint per capita are employed to measure comprehensive human inequality and consumption-based material consumption, respectively. Based on an unbalanced panel data set of around 170 countries from 2010 to 2017, the regression estimations demonstrate that: (1) urbanization reduces material consumption; (2) human inequality increases material consumption; (3) the interaction effect between urbanization and human inequality reduces material consumption; (4) urbanization reduces human inequality, which explains why the interaction effect works; (5) urbanization makes more sense for reducing material consumption if the extents of human inequality are larger and the positive impacts of human inequality on material consumption are weakened if the extents of urbanization are larger. It is concluded that promoting urbanization and reducing human inequality are compatible with both ecological sustainability and social fairness. This paper contributes to understanding and achieving the absolute decoupling between economic-social development and material consumption.

Preliminary evidence that individuals with remitted alcohol use disorder and major depressive disorder exhibit enhanced neural responses to reward: An EEG study.

INTRODUCTION: Disruptions in neural responses to reward are implicated in risk for Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD). It is not clear whether these findings extend to those in remission from AUD and MDD, a critical question as studies of remission can (a) rule out effects due to current symptoms, and (b) can reveal potential trait-like differences. METHODS: Individuals with and without remitted AUD (rAUD) and/or rMDD (rMDD) were drawn from a larger study to create four groups: rAUD (n = 54), rMDD (n = 66), rAUD + rMDD (n = 53), and a community control group (CCG; n = 81). Participants completed a validated monetary reward task during electroencephalogram (EEG). Multilevel models examined group differences in event-related potentials and time-frequency indices of reward and loss responsiveness, namely, reward positivity (RewP), feedback negativity (FN), reward-related delta power, and loss-related theta power. RESULTS: Analyses revealed that the rAUD + rMDD group had significantly higher reward-related delta activity than the three other groups (p-values < 0.01), which did not differ from each other. Sensitivity analyses revealed this relationship fell just above the threshold set for significance after controlling for residual current MDD and AUD symptoms (p =.05). There were no other group differences or significant interactions (p-values > 0.05). CONCLUSIONS: To our knowledge, this is the first study to show that individuals with remitted AUD and MDD demonstrate increased sensitivity to rewards compared to individuals with remitted AUD alone, MDD alone, and without AUD or MDD. These findings suggest heightened motivational salience to reward might be an important factor in comorbid AUD and MDD.

Pregnant woman with acute promyelocytic leukemia delivers healthy twins and is cured successfully: A case report.

Acute promyelocytic leukemia (APL) during pregnancy is rare and difficult to treat. To the best of our knowledge, there is little precedent for successful treatment with combined chemotherapeutic agents without affecting delivery. The present study reported the case of a 31-year-old woman pregnant with twins who presented to the antenatal service at 13-week gestational age with complaints of vaginal bleeding, lower abdominal pain, bleeding gums and skin ecchymosis, and was eventually diagnosed with APL. After treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO)-based induction regimen, the patient achieved a complete remission (CR) and delivered two healthy male infants at 34 weeks of gestation. The use of ATRA and ATO for the treatment of APL is controversial due to teratogenic effects and lethal retinoic acid syndrome. However, the patient demonstrated that the chemotherapy regimen with ATRA and ATO during the second and third trimesters can result in a sustainable remission and successful pregnancy outcome.

Electrophysiological evidence of mal-adaptation to error in remitted depression.

Identifying risk markers for major depressive disorder (MDD) that persist into remission is key to address MDD's high rate of recurrence. Central to MDD recurrence are the disorder's negative information processing biases, such as heightened responses to errors, which may subsequently impair abilities to monitor performance and adjust behaviors based on environmental demands. However, little is known regarding the neurophysiological correlates of post-error adaptation in depression. The current study investigated event-related potentials (ERPs) and behavioral performance following errors from a flanker task in 58 participants with remitted MDD (rMDD) and 118 healthy controls (HC). Specifically, using trial-level data, we tested: (a) the impact of errors on response-locked ERPs of the current and post-error trials (error-related negativity [ERN] and correct response negativity [CRN]) and (b) longer-term adaptation to errors (ERN/CRN) over the course of the task. Compared to HC, rMDD participants showed a larger ERN to the current trial and smaller habituation in ERN over time. On trials immediately following errors, rMDD participants showed slower reaction times that were predicted by the previous-trial ERN amplitude but comparable accuracy to HC, suggesting a deficient ability to disengage from errors and/or a compensatory effort to mitigate accuracy decrements. Critically, this pattern of responding: (a) was concurrently associated with greater levels of anhedonia symptoms, more severe MDD history, and interpersonal impairment (but lower impairment in life activities) and (b) predicted more anhedonia symptoms at one-year follow-up. Collectively, a hyperactive performance monitoring system may be a useful risk marker for future MDD recurrence.

Capturing mood dynamics through adolescent smartphone social communication.

Most adolescents with depression remain undiagnosed and untreated-missed opportunities that are costly from both personal and public health perspectives. A promising approach to detecting adolescent depression in real-time and at a large scale is through their social communication on the smartphone (e.g., text messages, social media posts). Past research has shown that language from online social communication reliably indicates interindividual differences in depression. To move toward detecting the emergence of depression symptoms intraindividually, the present study tested whether sentiment (i.e., words connoting positive and negative affect) from smartphone social communication prospectively predicted daily mood fluctuations in 83 adolescents (Mage = 16.49, 73.5% female) with a wide range of depression severity. Participants completed daily mood ratings across a 90-day period, during which 354,278 messages were passively collected from social communication apps. Greater positive sentiment (i.e., more positive weighted composite valence score and a greater proportion of words expressing positive sentiment) predicted more positive next-day mood, controlling for previous-day mood. Moreover, greater proportions of positive and negative sentiment were, respectively, associated with lower anhedonia and greater dysphoria symptoms measured at baseline. Exploratory analyses of nonaffective linguistic features showed that greater use of social engagement words (e.g., friends and affiliation) and emojis (primarily consisting of hearts) predicted more positive changes in mood. Collectively, findings suggest that language from smartphone social communication can detect mood fluctuations in adolescents, laying the foundation for language-based tools to identify periods of heightened depression risk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Do public employment services affect the self-rated health of migrant workers in China?

Migrant workers greatly contributing to China's industrialization and urbanization are confronted with increasing health risks. This study empirically investigates the effects of public employment services on the self-rated health of migrant workers in Shanghai China, by using data from the National Bureau of Statistics from 2015 to 2020. The estimation results under the Ordered Probit model illustrate that public employment services significantly improve the self-rated health of migrant workers, and vocational training, job development and other related services show an apparently positive correlation with the self-rated health. The marginal effect analysis reveals that public employment services obviously reduce the probability of health satisfaction as "average", "relatively satisfied" and "relatively dissatisfied", which translate into a significant increase in the probability of "very satisfied". The mechanism analysis verifies that public employment services enhance the self-rated health by increasing the proportion of medical insurance and injury insurance of migrant workers. The results are still reliable by adopting the methods of subsample regression, Propensity Score Matching and variable substitution to conduct robustness checks. This study further enriches the literature on public employment services and the health status of migrant workers, and provides policy implications on improving the health status of migrant workers and the public employment service system of China under the impact of the COVID-19 pandemic.

Event-related potentials to acoustic startle probes during unpredictable threat are associated with individual differences in intolerance of uncertainty.

Individual differences in sensitivity to unpredictable threat may be a critical mechanism for internalizing psychopathology phenotypes. The present study examined whether the startle probe-elicited N100 and P300 during unpredictable threat - two event-related potentials indexing early and elaborative attentional processing of unpredictable threat - may be endophenotypes for internalizing psychopathology, including fear and distress/misery disorders and intolerance of uncertainty (IU), a clinical trait that is transdiagnostically associated with internalizing disorders. A large sample of adult siblings (N = 375) completed the no, predictable, and unpredictable threat task, during which the N100 and P300 were recorded. Relative to the no threat condition, N100 was more strongly enhanced in anticipation of unpredictable than predictable threat while P300 was suppressed to both predictable and unpredictable threat. While neither N100 enhancement nor P300 suppression to unpredictable threat was associated with fear or distress/misery disorders, they were negatively linked to inhibitory IU (a facet of IU). Thus, individuals high in inhibitory IU showed reduced attentional engagement with the threatening context when it was unpredictable. Further, N100 enhancement and, to a lesser degree, P300 suppression to unpredictable threat showed familial aggregation - a key criterion for determining whether a biomarker is an endophenotype. In sum, N100 enhancement and P300 suppression to unpredictable threat may be endophenotypes for dimensional measures of internalizing psychopathology.

Isolated myeloid sarcoma with pericardial and pleural effusions as first manifestation: A case report.

RATIONALE: Myeloid sarcoma (MS) involves the proliferation of extramedullary blasts from 1 or more myeloid lineages, replacing the original tissue structures, and these neoplasias are called granulocytic sarcoma, chloroma, or extramedullary myeloid neoplasms. These tumors develop in lymphoid organs, bones, skin, soft tissues, various mucous membranes, organs, and the central nervous system. MS is rare in non-leukemic patients, while MS patient with effusion as the first manifestation is even rare. PATIENT CONCERNS: We report the case of 44-year-old woman with abdominal pain, diarrhea, and vomiting. DIAGNOSIS: Ultrasound examination and computed tomography of the chest revealed large pericardial effusions and bilateral pleural effusions. Cytomorphological examination of the pericardial and pleural effusion, flow cytometry, and immunohistochemical markers suggested myeloid tumor cells. However, concurrent peripheral blood and bone marrow examinations showed no evidence of acute myeloid leukemia. The patient was eventually diagnosed with isolated MS. INTERVENTIONS AND OUTCOMES: After chemotherapy with pirarubicin + cytarabine and high-dose cytarabine + etoposide, the pericardial effusion and pleural effusion were absorbed, and the mediastinal mass significantly shrunk. One year after patient gave up treatment, acute myeloid leukemia (AML) was confirmed by bone marrow examinations. CONCLUSION: The early manifestations of the patient lacked specificity and were highly susceptible to misdiagnosis. Cytomorphology and flow cytology indicated important directions for the diagnosis of the disease in the early stage. Administration of chemotherapy regimen containing cytarabine could prolong disease-free survival and time before progress to AML.

Exposure-response analyses of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma.

BACKGROUND: Exposure-response analyses were conducted to explore the relationship between selected efficacy and safety endpoints and serum phosphate (PO4) concentrations, a potential biomarker of efficacy and safety, in locally advanced or metastatic urothelial carcinoma patients with FGFR alterations treated with erdafitinib. METHODS: Data from two dosing regimens of erdafitinib in a phase 2 study (NCT02365597), 6 and 8-mg/day with provision for pharmacodynamically guided titration per serum PO4 levels, were analyzed using Cox proportional hazard or logistic regression models. Efficacy endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Safety endpoints were adverse events typical for FGFR inhibitors. RESULTS: Exposure-efficacy analyses on 156 patients (6-mg = 68; 8-mg = 88) showed that patients with higher serum PO4 levels within the first 6 weeks showed better OS (hazard ratio 0.57 [95% CI 0.46-0.72] per mg/dL of PO4; p = 0.01), PFS (hazard ratio 0.80 [0.67-0.94] per mg/dL of PO4; p = 0.01), and ORR (odds ratio 1.38 [1.02-1.86] per mg/dL of PO4; p = 0.04). Exposure-safety analyses on 177 patients (6-mg = 78; 8-mg = 99) showed that the incidence of selected adverse events associated with on-target off-tumor effects significantly rose with higher PO4. CONCLUSIONS: The exploratory relationship between serum PO4 levels and efficacy/safety outcomes supported the use of pharmacodynamically guided dose titration to optimize erdafitinib's therapeutic benefit/risk ratio. CLINICAL TRIAL REGISTRATION NUMBER: NCT02365597.

Erdafitinib's effect on serum phosphate justifies its pharmacodynamically guided dosing in patients with cancer.

A population pharmacokinetic (PK)-pharmacodynamic (PD) model was developed using data from 345 patients with cancer. The population PK-PD model evaluated the effect of erdafitinib total and free plasma concentrations on serum phosphate concentrations after once-daily oral continuous (0.5-12 mg) and intermittent (10-12 mg for 7 days on/7 days off) dosing, and investigated the potential covariates affecting erdafitinib-related changes in serum phosphate levels. Phosphate is used as a biomarker for erdafitinib's efficacy and safety: increases in serum phosphate were observed after dosing with erdafitinib, which were associated with fibroblast growth factor receptor target engagement via inhibition of renal fibroblast growth factor 23-mediated signaling. PK-PD model-based simulations were performed to assess the approved PD-guided dosing algorithm of erdafitinib (8 mg once-daily continuous dosing, with up-titration to 9 mg based on phosphate levels [<5.5 mg/dl] and tolerability at 14-21 days of treatment). The serum phosphate concentrations increased after the first dose and reached near maximal level after 14 days of continuous treatment. Serum phosphate increased with erdafitinib free drug concentrations: doubling the free concentration resulted in a 1.8-fold increase in drug-related phosphate changes. Dose adjustment after at least 14 days of dosing was supported by achievement of >95% maximal serum phosphate concentration. The peak-to-trough fluctuation within a dosing interval was limited for serum phosphate concentrations (5.68-5.65 mg/dl on Day 14), supporting phosphate monitoring at any time relative to dosing. Baseline phosphate was higher in women, otherwise, none of the investigated covariate-parameter relationships were considered clinically relevant. Simulations suggest that the starting dose of 8-mg with up-titration to 9-mg on Days 14-21 maximized the number of patients within the target serum phosphate concentrations (5.5-7 mg/dl) while limiting the number of treatment interruptions. The findings from the PK-PD model provided a detailed understanding of the erdafitinib concentration-related phosphate changes over time, which supports erdafitinib's dosing algorithm.

An Effortful Approach to Social Affiliation in Schizophrenia: Preliminary Evidence of Increased Theta and Alpha Connectivity during a Live Social Interaction.

People with schizophrenia often experience a profound lack of motivation for social affiliation-a facet of negative symptoms that detrimentally impairs functioning. However, the mechanisms underlying social affiliative deficits remain poorly understood, particularly under realistic social contexts. Here, we investigated subjective reports and electroencephalography (EEG) functional connectivity in schizophrenia during a live social interaction. Individuals with schizophrenia (n = 16) and healthy controls (n = 29) completed a face-to-face interaction with a confederate while having EEG recorded. Participants were randomly assigned to either a Closeness condition designed to elicit feelings of closeness through self-disclosure or a Small-Talk condition with minimal disclosure. Compared to controls, patients reported lower positive emotional experiences and feelings of closeness across conditions, but they showed comparably greater subjective affiliative responses for the Closeness (vs. Small-Talk) condition. Additionally, patients in the Closeness (vs. Small-Talk) condition displayed a global increase in connectivity in theta and alpha frequency bands that was not observed for controls. Importantly, greater theta and alpha connectivity was associated with greater subjective affiliative responding, greater negative symptoms, and lower disorganized symptoms in patients. Collectively, findings indicate that patients, because of pronounced negative symptoms, utilized a less efficient, top-down mediated strategy to process social affiliation.