TCMFP: a novel herbal formula prediction method based on network target's score integrated with semi-supervised learning genetic algorithms.

Traditional Chinese medicine (TCM) has accumulated thousands years of knowledge in herbal therapy, but the use of herbal formulas is still characterized by reliance on personal experience. Due to the complex mechanism of herbal actions, it is challenging to discover effective herbal formulas for diseases by integrating the traditional experiences and modern pharmacological mechanisms of multi-target interactions. In this study, we propose a herbal formula prediction approach (TCMFP) combined therapy experience of TCM, artificial intelligence and network science algorithms to screen optimal herbal formula for diseases efficiently, which integrates a herb score (Hscore) based on the importance of network targets, a pair score (Pscore) based on empirical learning and herbal formula predictive score (FmapScore) based on intelligent optimization and genetic algorithm. The validity of Hscore, Pscore and FmapScore was verified by functional similarity and network topological evaluation. Moreover, TCMFP was used successfully to generate herbal formulae for three diseases, i.e. the Alzheimer's disease, asthma and atherosclerosis. Functional enrichment and network analysis indicates the efficacy of targets for the predicted optimal herbal formula. The proposed TCMFP may provides a new strategy for the optimization of herbal formula, TCM herbs therapy and drug development.

Strengthening through adversity: The hormesis model in developmental psychopathology.

BACKGROUND: Employing a developmental psychopathology framework, we tested the utility of the hormesis model in examining the strengthening of children and youth through limited levels of adversity in relation to internalizing and externalizing outcomes within a brain-by-development context. METHODS: Analyzing data from the Adolescent Brain and Cognitive Development study (N = 11,878), we formed latent factors of threat, deprivation, and unpredictability. We examined linear and nonlinear associations between adversity dimensions and youth psychopathology symptoms and how change of resting-state functional connectivity (rsFC) in the default mode network (DMN) from Time 1 to Time 5 moderates these associations. RESULTS: A cubic association was found between threat and youth internalizing problems; low-to-moderate family conflict levels reduced these problems. Deprivation also displayed a cubic relation with youth externalizing problems, with moderate deprivation levels associated with fewer problems. Unpredictability linearly increased both problem types. Change in DMN rsFC significantly moderated the cubic link between threat levels and internalizing problems, with declining DMN rsFC levels from Time 1 to Time 5 facilitating hormesis. Hormetic effects peaked earlier, emphasizing the importance of sensitive periods and developmental timing of outcomes related to earlier experiences. CONCLUSIONS: Strengthening through limited environmental adversity is crucial for developing human resilience. Understanding this process requires considering both linear and nonlinear adversity-psychopathology associations. Testing individual differences by brain and developmental context will inform preventive intervention programming.

Identification of the susceptible genes and mechanism underlying the comorbid presence of coronary artery disease and rheumatoid arthritis: a network modularization analysis.

OBJECTIVE: The comorbidities of coronary artery disease (CAD) and rheumatoid arthritis (RA) are mutual risk factors, which lead to higher mortality, but the biological mechanisms connecting the two remain unclear. Here, we aimed to identify the risk genes for the comorbid presence of these two complex diseases using a network modularization approach, to offer insights into clinical therapy and drug development for these diseases. METHOD: The expression profile data of patients CAD with and without RA were obtained from the GEO database (GSE110008). Based on the differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) was used to construct a gene network, detect co-expression modules, and explore their relation to clinical traits. The Zsummary index, gene significance (GS), and module membership (MM) were utilized to screen the important differentiated modules and hub genes. The GO and KEGG pathway enrichment analysis were applied to analyze potential mechanisms. RESULT: Based on the 278 DEGs obtained, 41 modules were identified, of which 17 and 24 modules were positively and negatively correlated with the comorbid occurrence of CAD and RA (CAD&RA), respectively. Thirteen modules with Zsummary < 2 were found to be the underlying modules, which may be related to CAD&RA. With GS ≥ 0.5 and MM ≥ 0.8, 49 hub genes were identified, such as ADO, ABCA11P, POT1, ZNF141, GPATCH8, ATF6 and MIA3, etc. The area under the curve values of the representative seven hub genes under the three models (LR, KNN, SVM) were greater than 0.88. Enrichment analysis revealed that the biological functions of the targeted modules were mainly involved in cAMP-dependent protein kinase activity, demethylase activity, regulation of calcium ion import, positive regulation of tyrosine, phosphorylation of STAT protein, and tissue migration, etc. CONCLUSION: Thirteen characteristic modules and 49 susceptibility hub genes were identified, and their corresponding molecular functions may reflect the underlying mechanism of CAD&RA, hence providing insights into the development of clinical therapies against these diseases.

Transcriptomic analysis reveals the role of Glycolysis pathway in Litopenaeus vannamei during DIV1 infection.

In recent years, shrimp farming has experienced significant losses due to the emergence of DIV1 (Decapod iridescent virus 1), an infectious virus with a high fatality rate among shrimp. In this study, we conducted transcriptomic analyses on shrimp Litopenaeus vannamei hemocytes following DIV1 infection and focused on the function of genes in the Glycolysis pathway during DIV1 infection. A total of 2197 differentially expressed genes (DEGs) were identified, comprising 1506 up-regulated genes and 691 down-regulated genes. These genes were primarily associated with Phagosome, ECM-Receptor Interaction, Drug Metabolism-Other Enzymes, and the AGE-RAGE signaling pathway in diabetic complications. KEGG pathway enrichment analysis of the DEGs revealed a noteworthy correlation with metabolic pathways, with a specific focus on glucose metabolism. Specifically, the Glycolysis/Gluconeogenesis pathway exhibited significant upregulation following DIV1 infection. In line with this, we observed an augmented accumulation of glycolytic-related metabolites in the hemolymph following DIV1 challenge along with upregulation of the relative mRNA expression of several glycolytic-related genes. Moreover, we found that the inhibition of lactate dehydrogenase (LDH) activity through RNAi or the use of an inhibitor resulted in reduced lactate production, effectively safeguarding shrimp from DIV1 infection. These findings not only provide a comprehensive dataset for further investigation into DIV1 pathogenesis but also offer valuable insights into the immunometabolism mechanisms that govern shrimp responses to DIV1 infection.

Biological sensitivity to context as a dyadic construct: An investigation of child-parent RSA synchrony among low-SES youth.

Parenting behaviors are significantly linked to youths' behavioral adjustment, an association that is moderated by youths' and parents' self-regulation. The biological sensitivity to context theory suggests that respiratory sinus arrhythmia (RSA) indexes youths' varying susceptibility to rearing contexts. However, self-regulation in the family context is increasingly viewed as a process of "coregulation" that is biologically embedded and involves dynamic Parent×Child interactions. No research thus far has examined physiological synchrony as a dyadic biological context that may moderate associations between parenting behaviors and preadolescent adjustment. Using a two-wave sample of 101 low-socioeconomic status (SES) families (children and caretakers; mean age 10.28 years), we employed multilevel modeling to examine dyadic coregulation during a conflict task, indicated by RSA synchrony, as a moderator of the linkages between observed parenting behaviors and preadolescents' internalizing and externalizing problems. Results showed that high dyadic RSA synchrony resulted in a multiplicative association between parenting and youth adjustment. High dyadic synchrony intensified the relations between parenting behaviors and youth behavior problems, such that in the context of high dyadic synchrony, positive and negative parenting behaviors were associated with decreased and increased behavioral problems, respectively. Parent-child dyadic RSA synchrony is discussed as a potential biomarker of biological sensitivity in youth.

Improving Children's Expressive Language and Auditory Comprehension Through Responsive Caregiving: Evidence from a Randomized Controlled Trial of a Strength-Based Video-Coaching Intervention.

Young children from low-SES backgrounds are at higher risk for delayed language development, likely due to differences in their home language environment and decreased opportunities for back and forth communicative exchange. Intervention strategies that encourage reciprocal caregiver-child interactions may effectively promote young children's language development and enhance optimal language outcomes. The Filming Interactions to Nurture Development (FIND) program is a brief strength-based video-coaching intervention designed to promote increased back and forth ("serve and return") interactions between caregivers and their children. The current study used data from a randomized controlled trial (RCT) to examine the effectiveness of the FIND program in improving auditory comprehension and expressive communication skills among children from low-SES backgrounds. The current study used a pretest-posttest design to evaluate intervention effects from an RCT with 91 low-SES families. Families with children aged 4 to 36 months old (41.8% female) were randomly assigned to an active control or FIND intervention group. Children's auditory comprehension and expressive communication were assessed using the Preschool Language Scales, Fifth Edition (PLS-5) during both pre- and post-intervention sessions. Children in the FIND intervention group showed significantly increased expressive communication skills and a non-significant increase in auditory comprehension skills across the intervention period. In contrast, children in the active control group showed non-significant changes in expressive communication and a statistically significant decline in auditory comprehension abilities between pre- and post-intervention assessments. All analyses controlled for sex, age, and home language. This study provides preliminary evidence that the FIND intervention promotes the development of expressive and receptive language skills among young children in high-stress, low-SES environments.

The COVID-19 Pandemic Impact on Households of Young Children With Special Healthcare Needs.

OBJECTIVE: This study examined how the COVID-19 pandemic differently affected households of children with versus without special healthcare needs. We compared caregivers' and children's emotional well-being (Aim 1), the utilization of preventive healthcare services for young children (Aim 2), and the promotive effects of social support on well-being outcomes (Aim 3) during the pandemic between the two groups. METHODS: Data were drawn from an ongoing, large, longitudinal, and national survey that assessed the pandemic impact on households of young children (0-5). Analyses for Aims 1 and 2 were based on 10,572 households, among which 10.96% had children with special healthcare needs. Analyses for Aim 3 were based on a subsample of 821 families, among which 12.54% had children with special healthcare needs. RESULTS: Caregivers of children with special healthcare needs exhibited more emotional distress and reported higher levels of household children's behavioral problems during the pandemic. The percentages of missed preventive healthcare visits and vaccinations were also higher in families of children with special healthcare needs due to structural barriers. Lastly, emotional social support was indirectly related to children's decreased behavioral problems through caregivers' reduced emotional distress, only among households of children without special healthcare needs. In other words, social support alone was not sufficient in promoting caregivers' and children's better well-being outcomes among households of children with special healthcare needs. CONCLUSIONS: The pandemic has caused extensive burdens on families of children with special healthcare needs. Actions from policymakers and early intervention service providers are urgently needed to mitigate these impacts.

Combined effects of S-metolachlor and benoxacor on embryo development in zebrafish (Danio rerio).

It is necessary to study the combined toxicity of an herbicide and its safener because the two are often used in combination. S-metolachlor and its safener benoxacor have been detected in aquatic environments and can individually damage the oxidative stress system in zebrafish embryos (Danio rerio). However, only their separate toxicity in zebrafish (Danio rerio) embryo development has been reported. This study assessed the combined toxicity of benoxacor and S-metolachlor in zebrafish embryo development, including acute toxicity, developmental toxicity, oxidative damage, and cell apoptosis. The 96-h LC50 values were higher in mixtures of benoxacor and S-metolachlor than in benoxacor alone. The treatments included S-metolachlor, Mix-1 (0.1 mg/L benoxacor + 0.1 mg/L S-metolachlor), Mix-2 (0.1 mg/L benoxacor + 0.3 mg/L S-metolachlor) and benoxacor alone. Embryos exposed to Mix-1 and Mix-2 had lower developmental toxicities, superoxide dismutase (SOD) activity, osx and cat expression levels than those exposed to benoxacor alone. Moreover, glutathione S-transferase (GST), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) activities, and the expressions of tbx16, nrf2, bcl2, and caspase9 were higher in the mixtures than in the benoxacor group. High-throughput RNA sequencing revealed that benoxacor had a greater effect on gene regulation than Mix-1 and Mix-2. The malformation rate, different enrichment gene numbers, and gene expression levels of hatched embryos were higher in Mix-1 than in Mix-2. The results indicate that a mixture of S-metolachlor and benoxacor has antagonistic effects in the early stage of embryo development. The mixtures can break the reactive oxygen species balance, causing abnormal cell apoptosis and developmental malformation in embryos. Besides investigating the combined toxicity of benoxacor and S-metolachlor in zebrafish embryo development, this study provides a risk assessment basis for a herbicide combined with its safener.

[Historical evolution of Xuanfu Daizhe Decoction].

Xuanfu Daizhe Decoction, first seen in Zhang Zhongjing's Treatise on Cold Damage Diseases, was composed of seven medicinal materials: Inulae Flos, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma Recens, Haematitum, Pinelliae Rhizoma and Jujubae Fructus. It was used to treat gastric fullness and hardness and belching due to the wrong treatment of typhoid fever and sweating. With detailed records and description in ancient medical books, Xuanfu Daizhe Decoction was widely adopted in clinical practice by physicians of later generations, which expanded its main therapeutic functions. By comprehensive collation of ancient and modern literature on Xuanfu Daizhe Decoction, this paper systematically explored the historical evolution of the prescription from the source, composition, dosage, processing, clinical application, function interpretation and decocting method. It was found that the composition and processing method of the prescription in the past dynasties were relatively consistent, and there was a gradual decrease in dosage in clinical application. In ancient times, Xuanfu Daizhe Decoction was mainly used to treat nausea, vomiting, hiccups, constipation, etc., while modern clinicians mainly used it for digestive diseases such as reflux esophagitis and gastritis. Through the analysis and textual research, the composition, dosage, processing, function evolution and decocting method of this prescription were determined, which provided reference for the research and development of compound preparations of Xuanfu Daizhe Decoction.

Firm parenting and youth adjustment: Stress reactivity and dyadic synchrony of respiratory sinus arrhythmia.

Parental behaviors are potent risk and protective factors for youth development of externalizing problems. Firm control is a parenting strategy that is inconsistently linked to youth adjustment, possibly due to variations in individual biological contexts. Growing research shows that dyadic coregulation of the autonomic nervous system (e.g., parent-child physiological synchrony) is a neurobiological mechanism that links parenting to youth adjustment. However, physiological synchrony may be context-dependent (e.g., adaptive in positive interactions, maladaptive in negative interactions). We aimed to test the role of dyadic synchrony in respiratory sinus arrhythmia (RSA) during parent-child conflict as a mediator between parent firm control and youth's externalizing problems. To capture youth's stress reactivity, we also tested how galvanic skin response reactivity (GSR-R) moderated this indirect path. The sample included 101 dyads of low socioeconomic-status at-risk preadolescents and parents. Results indicated that youth higher levels of GSR-R significantly intensified the link between parent firm control and dyadic RSA synchrony during conflict. Dyadic RSA synchrony further predicted youth increased in externalizing problems. Overall, results suggest that when parents employ firm control parenting with highly reactive teens, dyadic RSA synchrony elevates, potentially modeling less optimal coping with conflict for the youth, which is associated with increased externalizing problems.

Assessing the toxicity of three "inert" herbicide safeners toward Danio rerio: Effects on embryos development.

Recent studies indicated that 'inert ingredients' exert negative effects on the environment. Herbicide safeners are classed as 'inert ingredients', which increase the selectivity and detoxification of herbicides. However, little attention has been focused on the environmental behavior of herbicide safeners. AD-67 (AD), fenclorim (FM), and flurazole (FZ) are three commercially available herbicide safeners. In this study, zebrafish embryos were used as a model to investigate the potential developmental toxicity of these three safeners. The results showed that AD, FM, and FZ 96 h-LC50 values were 2.52, 1.26, and 2.01 mg/L, respectively. Significant decreased body lengths were observed in embryos after 96 h of exposure to 0.2 mg/L FM and FZ. Hatching rates significantly increased at 24 h and decreased at 96 h in all treatment groups (0.02 mg/L AD, 0.2 mg/L AD, 0.02 mg/L AD, 0.2 mg/L FZ, as well as 0.01 and 0.1 mg/L FM). No significant (p > 0.05) changes in heartbeat numbers (60 s), but clearly increased malformation rates were observed in response to safeners exposure. Furthermore, embryos showed signs of oxidative stress, such as decreased activities of superoxide dismutase, altered activities of glutathione reductase and catalase and cell apoptosis. The gene transcription related to body malformation (egf, krt 17, and tbx 16) and cell apoptosis (bcl 2 and bax) changed in treated groups. These genes have been connected to potential toxicological mechanisms. These results indicate that the herbicide safeners AD, FM, and FZ induced developmental toxicities in zebrafish embryos. This study is the first report of the toxicity of safeners in the development of zebrafish embryos. The results may be useful for assessing the risk of herbicides safeners in the aquatic ecosystem.

Improving Caregiver Self-Efficacy and Children's Behavioral Outcomes via a Brief Strength-Based Video Coaching Intervention: Results from a Randomized Controlled Trial.

Many existing preventive intervention programs focus on promoting responsive parenting practices. However, these parenting programs are often long in duration and expensive, and meta-analytic evidence indicates that families facing high levels of adversity typically benefit less. Moreover, due to a lack of specification and evaluation of conceptual models, the mechanisms underlying program-related changes in caregivers and their children often remain unclear. The current study aimed to test the effectiveness of a video feedback parenting intervention program, Filming Interactions to Nurture Development (FIND), in improving caregivers' self-efficacy and reducing children's behavioral problems. Data derived from a randomized controlled trial using pretest-posttest design with low-income families reporting high levels of stress (N = 91, children aged 4 to 36 months old, 41.8% female). Families were randomly assigned to an active control or FIND intervention group. Results indicated that caregivers in the FIND group exhibited significant improvement in self-report sense of parenting competence and self-efficacy in teaching tasks. These program impacts were particularly pronounced among caregivers who experience high levels of childhood adversity. Findings provide preliminary support for the FIND conceptual model. Specifically, caregivers' improved self-efficacy in teaching tasks was linked to children's reduced internalizing and externalizing problems (notably, direct FIND intervention effects on children's behavioral outcomes were not observed). Overall, results support the effectiveness of FIND in enhancing caregivers' sense of parenting competence and potentially promoting optimal child development.

Physiological Stress Response Reactivity Mediates the Link Between Emotional Abuse and Youth Internalizing Problems.

Youth who are raised in emotionally abusive families are more likely to have poor mental health outcomes such as depression and anxiety. However, the mechanisms of this association are unclear. The present study utilized a longitudinal sample of low-SES youth (N = 101, MageT1 = 10.24) to examine stress response reactivity (i.e. vagal withdrawal, sympathetic activation, and hypothalamic-pituitary-adrenal [HPA] axis activation) as mediators between emotional abuse and prospective youth internalizing symptoms. Results indicated that blunted HPA reactivity to a laboratory social stress task mediated the association between emotional abuse and youth internalizing symptoms. Emotional abuse was also associated with blunted parasympathetic nervous system activity (i.e. less vagal withdrawal than average). In sum, emotional abuse is a potent risk factor for youth internalizing symptoms, and this link may be mediated via dysregulation in physiological stress response systems. Primary prevention of childhood emotional abuse and secondary prevention programs that target self-regulation skills may reduce rates of youth internalizing symptoms and disorders.

[An optimization method of weighted network module partition based on TCM theory of "monarch, minister, assistant and guide"].

The disease-gene-drug multi-level network constructed by network pharmacology can predict drug targets and has been widely used in the study of material basis and mechanism of action of Chinese medicinal prescriptions. However, most of the current studies have normalized the efficacies of Chinese herbal medicines in the compounds during the construction of the network. There is also a lack of in-depth exploration of the mechanism of synergy among multiple components. This study proposed a network module partition method based on group collaboration and the pharmacological network was weighed according to the traditional Chinese medicine(TCM) theory of "monarch, minister, assistant and guide". Taking the Tanyu Tongzhi Prescription as an example, we constructed its pharmacological network for the treatment of myocardial ischemia-reperfusion injury. The group collaboration module in the network was identified and the network changes before and after the weighting were compared based on the network topology analysis to explore a new method to find the core nodes of the network as well as the core drugs that affected the efficacy of the compounds. The results showed that the module partition method based on group collaboration could be used to identify and partition group collaboration mo-dules in pharmacological networks of compounds. The proposed weighted network based on the TCM theory of "monarch, minister, assistant, and guide" could identify and partition the modules based on the characteristics of the pharmacological network. The identification and partition results of modules of Tanyu Tongzhi Prescription in the weighted network were superior to those in the unweighted network. The weighted closeness centrality(WCC) evaluation method was conducive to finding key nodes and relations in the network as compared with traditional methods, thereby providing a basis for analyzing the core components of drugs and extracting more accurate drug components and targets.

[Hotspots and trends of Ophiopogonis Radix based on CiteSpace knowledge map].

Ophiopogonis Radix is an important Yin-nourishing drug in traditional Chinese medicine(TCM), with the effects of nourishing Yin, promoting fluid production, clearing away heart-fire, and relieving restlessness. It is widely used in clinical practice due to its multiple chemical components and pharmacological effects. The technique "mapping knowledge domains" is an effective tool to quantitatively and objectively visualize the development frontiers and trends of certain disciplines. In this study, TCM research papers related to Ophiopogonis Radix were retrieved from Web of Science(WoS) and CNKI, and the research institutions, journals, and keywords involved were visualized and analyzed using the scientometric software CiteSpace. The co-occurrence network of related research on Ophiopogonis Radix was constructed, and the Ophiopogonis Radix-disease-target network was plotted using Cytoscape 3.8.2. The hot topics in Chinese and English papers were analyzed and the shortcomings in the research on Ophiopogonis Radix were summed up. Furthermore, the development trends were discussed. A total of 1 403 Chinese papers and 292 English papers were included in this study. The analysis of research institutions showed that Beijing University of Chinese Medicine and China Pharmaceutical University were the two research institutions with the largest numbers of papers published. The analysis of journals showed that Hebei Journal of Traditional Chinese Medicine and Journal of Asian Natural Products Research were the two journals with the highest numbers of papers concerning Ophiopogonis Radix. The keyword analysis showed that the research contents of Chinese papers focused on the analysis of medication regularity and clinical observation trials, while the English papers focused on component analysis and pharmacological investigation. Data mining and apoptosis-based pharmacological mechanism might be the research trends in the future.

[Textual research principles and suggestions on function and indication of ancient classical formulas].

Indication and functions is an important key information in the research and development of the ancient classical formulas, which directly affects the clinical positioning of the compound formulas and their reasonable, effective and safe use after marke-ting. It is also the embodiment of the ultimate vitality of ancient classical formulas. Due to the particularity of ancient classical formulas, it is of great significance to accurately define and describe the functions and indications of classical formulas to exert their unqiue advantages. Based on the analysis of the provenances, classification of clinical indications, and functions of 100 prescriptions in the Catalogue of Ancient Classical Formulas(First Batch), this paper summarized the incompleteness, irregularity and inconsistency in the original text, the differences in terminology between ancient and modern times, and the evolution of the meanings of prescriptions in different dynasties. In addition, under the guidance of the general principle of textual researh on ancient classical formulas, which is to inherit the essence, make the past serve the present, link up the past and the present, and bulid consensus, this paper proposed the following ideas: respecting the original meanings and provenances of ancient classical formulas, taking full consideration of the development and evolution, serving the current clinical application and health needs, accurately linking up the ancient and modern terminologies, standardizing the expression of traditional Chinese medicine(TCM) terminology, highlighting the characteristics of TCM, attaching importance to the textual research principles and suggestions of post-marketing evidence-based and clinical positioning research, so as to determine the the functions and indications of the ancient classical formulas in a scientific, standardized and reasonable way and better guide the clinical application of the classical formulas.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Developmental pathways from child maltreatment to adolescent suicide-related behaviors: The internalizing and externalizing comorbidity hypothesis.

Child maltreatment is a robust risk factor for suicidal ideation and behaviors during adolescence. Elevations in internalizing and externalizing symptomology have been identified as two distinct developmental pathways linking child maltreatment and adolescent risk for suicide. However, recent research suggests that the co-occurrence of internalizing and externalizing symptomology may form a distinct etiological pathway for adolescent risk behaviors. Using the Longitudinal Studies on Child Abuse and Neglect (LONGSCAN) sample (N = 1,314), the present study employed a person-centered approach to identify patterns of concurrent change in internalizing and externalizing psychopathology over five time points from early childhood to adolescence in relation to previous experiences of child maltreatment and subsequent suicidal ideation and behaviors. Results indicated four distinct bivariate externalizing and internalizing growth trajectories. Group membership in a heightened comorbid internalizing and externalizing symptom trajectory mediated the association between childhood abuse and adolescent suicidal ideation and suicidal behaviors. These findings suggest that the concurrent development of externalizing and internalizing symptoms in childhood and adolescence may constitute a unique developmental trajectory that confers risk for suicide-related outcomes.

Heart Rate Variability Reactivity Moderates the Indirect Link Between Child Maltreatment and Young Adult Alcohol Use Problems Via Depressive Symptoms.

BACKGROUND AND OBJECTIVES: Young adults with childhood maltreatment (CM) histories are particularly vulnerable to depressive symptoms and alcohol use problems. Research suggests that maltreated youth may misuse alcohol in part to alleviate depressive symptoms. However, many youths with depressive symptoms exercise self-control and abstain from heavy alcohol use. The present study aimed to examine the influence of heart rate variability reactivity (HRV-R), a psychophysiological biomarker of self-regulation, in the indirect link between CM and alcohol-use problems via depressive symptoms among low socioeconomic-status rural young adults. METHODS: Two waves of data were collected from a community sample of 225 low socioeconomic-status nonmetropolitan young adults (Mage = 21.56, 52.9% female). HRV data were obtained with an electrocardiogram during a social stress task. CM was assessed through the Childhood Trauma Questionnaire. Alcohol use problems were measured using the Alcohol Use Disorders Identification Test. RESULTS: The indirect effect of CM on alcohol use problems via elevated depressive symptoms was positive and significant (α × ß = .159, P < .001). Self-regulation, indicated by high HRV-R (ie, vagal withdrawal), was found to significantly buffer the link between depressive symptoms and alcohol use problems (ß = .193, P = .022). DISCUSSION AND CONCLUSIONS: Adequate self-regulation capacities can protect maltreated youths from self-medicating alcohol use problems. SCIENTIFIC SIGNIFICANCE: This study will advance researchers' understanding of the development of alcohol use problems through unwrapping the risk and protective mechanisms underlying the association between young adults' early life stress and alcohol use behaviors. (Am J Addict 2020;29:141-150).

Child Maltreatment and Resilience: The Promotive and Protective Role of Future Orientation.

Maltreatment is associated with risk for a wide range of socio-emotional and behavioral problems in adolescence. Despite this risk, many maltreated youth adjust well through the process of resilience. Extant research demonstrates that future orientation is linked to reduced risks for maladjustment in adolescence. Few studies, however, have tested the protective and promotive role of future orientation using positive and negative developmental outcomes among maltreated youth. The present study aimed to investigate the promotive and moderating role of future orientation among a longitudinal sample of maltreated and demographically comparable non-maltreated youth (N = 1354, 51.5% female, 53.2% African American). Data collected from Time 1 (Mage = 4.56, SDage = 0.70) to Time 8 (Mage = 18.514, SDage = 0.615) were used. Compared to the non-maltreated youth, maltreated youth showed increased delinquent behaviors and reduced self-esteem. In addition, future orientation significantly predicted higher levels of social competence and attenuated the adverse effects of maltreatment on youth delinquency and substance use. The findings highlight the role of future orientation in the development of resilience among maltreated youth, bearing significant contributions to prevention and intervention programs designed to protect youth against risks linked to child maltreatment and promote their positive development.