Combining machine learning with structure-based protein design to predict and engineer post-translational modifications of proteins.

Post-translational modifications (PTMs) of proteins play a vital role in their function and stability. These modifications influence protein folding, signaling, protein-protein interactions, enzyme activity, binding affinity, aggregation, degradation, and much more. To date, over 400 types of PTMs have been described, representing chemical diversity well beyond the genetically encoded amino acids. Such modifications pose a challenge to the successful design of proteins, but also represent a major opportunity to diversify the protein engineering toolbox. To this end, we first trained artificial neural networks (ANNs) to predict eighteen of the most abundant PTMs, including protein glycosylation, phosphorylation, methylation, and deamidation. In a second step, these models were implemented inside the computational protein modeling suite Rosetta, which allows flexible combination with existing protocols to model the modified sites and understand their impact on protein stability as well as function. Lastly, we developed a new design protocol that either maximizes or minimizes the predicted probability of a particular site being modified. We find that this combination of ANN prediction and structure-based design can enable the modification of existing, as well as the introduction of novel, PTMs. The potential applications of our work include, but are not limited to, glycan masking of epitopes, strengthening protein-protein interactions through phosphorylation, as well as protecting proteins from deamidation liabilities. These applications are especially important for the design of new protein therapeutics where PTMs can drastically change the therapeutic properties of a protein. Our work adds novel tools to Rosetta's protein engineering toolbox that allow for the rational design of PTMs.

The remote work of child protection professionals during COVID-19: A scoping review and thematic analysis.

BACKGROUND: The COVID-19 pandemic created new challenges and barriers for the work of child protection professionals (CPPs) and intensified existing hardships for families and children, increasing the risk of child maltreatment. As new restrictions and precautions were implemented by governments worldwide to stop the virus from spreading, CPPs had to adapt to a new reality of working remotely. However, limited research has investigated how remote work impacted CPPs and child protection work and how CPPs handled this alternative work style. OBJECTIVE: This review aims to address gaps in the research to reveal the creative and effective approaches CPPs developed to overcome the challenges presented by COVID-19, defined as the 'positive legacy' of CPPs, particularly in adapting to remote work challenges. METHOD: This review was conducted using a scoping review, followed by two rounds of thematic analysis. The scoping review was conducted in six languages: Hebrew, Arabic, French, Portuguese, Spanish, and English. RESULTS: The first round of thematic analysis found 18 articles relevant to this review. The second round extracted two main themes: 1) the challenges of remote work and 2) overcoming the challenges of no contact. CONCLUSIONS: The findings of this review may be used to inform future strategies for child protection during a pandemic. They also provide an opportunity to rethink the relationship child protection work has with technology to systematically reform current and future protection policies and practices, including outside of a pandemic.

What was missed in child protection responses during COVID-19? Perceptions of professionals from various countries.

BACKGROUND: The COVID-19 pandemic increased the likelihood of child maltreatment and made already difficult circumstances for children and their families much worse. This increased the significance of the child protection system's role in responding to child maltreatment and ensuring children's rights, including their right to a safe life without violence. Unfortunately, accumulating evidence has indicated that the rates of child maltreatment increased during the pandemic. OBJECTIVE: The current study sought to identify the gaps within child protection responses in various countries during the COVID-19 pandemic and to discover how we can respond to crises in the future while preserving children's rights, including their right to protection from maltreatment. METHOD: Five focus groups with a total of 47 professionals working with children from various countries were conducted via Zoom and analyzed using a thematic approach. RESULTS: Three main themes were identified: 1) gaps in policies, 2) gaps in practice, and 3) professionals' messages to improve policy and practice. CONCLUSIONS: This study emphasizes what was missed in child protection policy and practice, highlighting the continuous neglect of children's needs and voices within policies, practices and guidelines worldwide during the pandemic. Professionals' recommendations for policy and practice are also discussed.

Experiences and responses of child protection professionals during COVID-19: Lessons learned from professionals around the globe.

BACKGROUND: COVID-19 significantly worsened already challenging circumstances for children and their families and globally increased the likelihood of child maltreatment. This risk heightened the urgency of child protection professionals in preventing child maltreatment and defending children's rights. The vast and growing body of research on protecting children from child maltreatment during COVID-19 has emphasized practitioners' tremendous difficulty in this arena. OBJECTIVE: The current international study sought to identify the experiences and responses of child protection professionals to child maltreatment during COVID-19. PARTICIPANTS AND SETTING: Five real-time, virtual focus groups were conducted among professionals who work with children from countries around the globe. METHOD: Reflexive thematic analysis was employed to analyze the focus group transcripts. RESULTS: The participants identified their experiences and challenges in performing their role of protecting children. Additionally, they shared context-adapted and innovative responses to child maltreatment, while emphasizing self-care and their mental health. CONCLUSIONS: The results highlighted that child protection was significantly more challenging during the COVID-19 pandemic. Furthermore, they underlined the importance of establishing practices and policies for child protection in crisis times as well as ensuring both children's and professionals' well-being and mental health.

Examining resilience among child protection professionals during COVID-19: A global comparison across 57 countries.

BACKGROUND: The COVID-19 pandemic led to numerous challenges for child protection professionals (CPPs). However, limited research has investigated the interwoven concepts of coping, resilience, and mental distress among CPPs during COVID-19 on a global scale. OBJECTIVES: This study aimed to explore CPPs' practice, resilience, and mental distress during COVID-19, the relationship between their resilience and mental distress, the global stability of the Multi-System Model of Resilience (MSMR), and how CPPs' resilience varied according to the Human Development Index (HDI). METHODS: Data were collected from 420 CPPs in 57 countries across five continents between July and September 2021. Participants completed an online questionnaire on demographics, resilience, mental distress, coping, and perceptions of child protection during the pandemic in their native languages. The analyses compared the countries grouped according to HDI using means comparisons, correlations, and multiple linear regressions. A two-path analysis was also performed to identify variables associated with behavioral resilience engagement and mental distress. RESULTS: The findings indicated that CPPs' perceptions of COVID-19's impact on child maltreatment varied in correlation with their country's HDI. There were also significant HDI-based differences regarding the perceived opportunity to engage in resilient behavior and its helpfulness. Years of professional experience, internal resilience, and external resilience were shown to be significant predictors of mental distress among CPPs during the pandemic, and resilience mediated how years of experience predicted mental distress. CONCLUSIONS: This study emphasized the importance of experience and internal resilience for CPPs' psychological well-being. It also provides empirical evidence to support the MSMR theory on a global scale. Additionally, it demonstrates how the perceived changes in child maltreatment during COVID-19 may be associated with regional HDI. Lastly, the opportunities CPPs had to engage in resilient behavior and how much this helped them was associated with regional HDI, but not in the way originally predicted. Study results also hold implications for how practice and policy may be altered to help CPPs cope better during times of crisis and generally.

Association between longitudinal patterns of child maltreatment experiences and adolescent substance use.

BACKGROUND: Although there is a well-established link between child maltreatment and adolescent substance use, it remains unclear if and how longitudinal patterns of maltreatment experiences are associated with substance use in adolescence. OBJECTIVE: The purpose of the study was to examine how distinct patterns of longitudinal maltreatment experiences are associated with adolescent substance use. PARTICIPANTS AND SETTING: The participants were 899 adolescents from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). METHODS: We conducted repeated measures latent class analysis (RMLCA) to identify patterns of physical abuse, sexual abuse, and neglect from birth to age 17 and their relations to tobacco, alcohol, and marijuana use at age 18. RESULTS: RMLCA identified three physical abuse classes (Stable low physical abuse; School age peak physical abuse; Physical abuse primarily in infancy/toddlerhood), two sexual abuse classes (Stable no/low sexual abuse; School age peak sexual abuse), and three neglect classes (High neglect in childhood; Neglect primarily in infancy/toddlerhood; Neglect primarily at school age). Adolescents in the school age peak physical abuse class showed greater alcohol, cigarette, and marijuana use, compared to other physical abuse classes. Similarly, adolescents in the school age peak sexual abuse class showed greater substance use than those in the stable no/low sexual abuse class. Lastly, adolescents in the neglect primarily in infancy/toddlerhood class showed significantly less substance use than those in the other two neglect classes. CONCLUSIONS: Findings highlight the importance of early intervention and ongoing maltreatment prevention.

Child protective services and out-of-home Care for Children during COVID-19: A scoping review and thematic analysis.

BACKGROUND: The COVID-19 pandemic challenged child protection and posed new risks for child maltreatment (CM). Moreover, governmental efforts worldwide prioritized mitigating the spread of the virus over ensuring the welfare and protection of families and children. This neglect caused hardship for many vulnerable children, including those in out-of-home care (OOHC), and challenged the functionality of child protective services (CPS). However, only limited research has investigated the impact of COVID-19 on OOHC and CPS and explored how CPS overcame the challenges of helping children in OOHC. OBJECTIVE: This review aims to address this gap in the research to unveil the 'positive legacy' left by CPS in their work with children in OOHC during COVID-19. METHOD: This review utilized three stages of analysis, including a scoping review followed by two rounds of thematic analysis. The scoping review was carried out in six languages: English, Hebrew, Arabic, French, Portuguese, and Spanish. The first round of thematic analysis found eight relevant articles for this review. The second round of thematic analysis found three themes related to this paper's aim in the context of COVID-19. RESULTS: Three main themes were identified: 1) decision-making and OOHC, 2) difficulties in procedures related to OOHC placement, and 3) handling challenges of OOHC. CONCLUSIONS: The discussion emphasizes the crucial role of preserving children's rights, hearing their voices and needs, and considering their safety and well-being when planning policies and practices to protect them. It also emphasizes society's responsibility to acknowledge contextual factors in child protection.

Childcare Subsidy Employment and Copayment Requirements and Child Maltreatment.

Economic support programs for low-income families may play an important role in preventing child abuse and neglect. In the United States, childcare subsidies are provided to low-income families who meet certain requirements to offset the high cost of childcare. States have flexibility in setting many policies related to the provision of childcare subsidies, which results in a great deal of variation in how the programs operate between states. One policy dimension on which states vary is the number of employment hours required to receive childcare subsidies. A small body of work has begun to investigate the ways in which these state policy variations might relate to child maltreatment. Using 11 years of administrative data from the United States, the current study sought to estimate the relationship between two sources of variation in childcare subsidy policies: employment requirements and copayment size; and child neglect, physical abuse, and emotional abuse substantiations. The study found a nuanced relationship between required employment and neglect substantiations. Specifically, requiring some level of work was not associated with neglect substantiations, but requiring 30 hours of employment was associated with higher rates. The study did not find a relationship between copayment size and maltreatment substantiations.

Material hardship in the postpartum year: Links to child maltreatment.

BACKGROUND: Millions of mothers with young children in the U.S. struggle to afford basic needs. Material hardships such as inadequate food, housing, and medical care increase risk for child maltreatment as mothers face heightened physical and emotional strain. OBJECTIVE: The present study applied a person-centered approach to understand unique subtypes of material hardship experienced by at-risk mothers in the postpartum year, and links from hardship subtypes to subsequent child maltreatment. PARTICIPANTS AND SETTING: The sample included at-risk mothers who gave birth in one of 20 large American cities 1998-2000 and retained custody of their children at age 1 and 3 (N = 3966). METHOD: Latent class analysis (LCA) identified subtypes of material hardship; mean maltreatment scores were estimated across classes. RESULTS: LCA identified four hardship subtypes with differential risks for maltreatment. Compared to "Stable" mothers, "Cost-Burdened" mothers - who displayed high levels of missed rent and utility payments - were significantly more likely to psychological abuse (χ2 = 5.04, p < 0.05) or neglect (χ2 = 4.46, p < 0.05) their children. "Severely Housing Insecure Mothers" - characterized by elevated rates of doubling up, eviction, and homelessness - were significantly more likely to engage in physical assault (χ2 = 16.25, p < 0.001), psychological aggression (χ2 = 11.15, p < 0.01), and neglect (χ2 = 17.55, p < 0.001). CONCLUSIONS: Difficulty maintaining stable and affordable housing is associated with elevated risk of child maltreatment. Efforts to prevent child maltreatment must incorporate access to housing screening and supports, particularly among families with infants.

Our Commitment to Promoting Diversity, Equity, Inclusion, and Justice in Child Maltreatment.

In this commentary, the editorial team of Child Maltreatment extends and expands on APSAC's position on diversity, equity, inclusion, and justice, affirms our commitment and plans for addressing these issues in this publication, and highlights articles in this issue that continue the discussion about race and racism in the child welfare and child protection systems.

The global impact of COVID-19 on child protection professionals: A scoping review and thematic analysis.

BACKGROUND: The COVID-19 pandemic triggered new risks for child maltreatment (CM) and exacerbated existing challenges for families and children, elevating the importance of child protection professionals (CPPs) while also adding barriers to their work. During the pandemic, many CPPs experienced increased workloads, a disrupted work environment, and personal pandemic-related hardships. However, the scope of how COVID-19 impacted CPPs globally, as well as their adopted coping strategies, have not been well explored. OBJECTIVE: This study addresses these gaps in the research by conducting an international scoping review to explore and analyze these topics. METHOD: The scoping review was performed in six languages: English, Hebrew, Arabic, French, Spanish, and Portuguese, across 16 databases. Sixteen manuscripts were included in the final thematic analysis of this review. RESULTS: Two main themes were identified: 1) the impact of COVID-19 on CPPs, and 2) the coping and adaptation strategies employed by CPPs during COVID-19. This review revealed and emphasized the importance of CPPs' resilience during COVID-19, underpinned by the theoretical framework of the social ecology of resilience. CONCLUSIONS: This study highlights the responsibility of social ecologies and organizational structures to create readiness for a rapid response in times of crisis as well as valuable evidence to inform how CPPs, children, and families may be better supported in the event of a future crisis.

Neighborhoods and child abuse: Multiple informant perspectives.

INTRODUCTION: Using data from the nationally representative longitudinal Future of Families and Child Wellbeing Study, the current study sought to examine associations between neighborhood disorder and physical characteristics of the neighborhood at child age three with the likelihood of experiencing physical and psychological abuse and neglect at age five. METHODS: Negative binomial regression and zero inflated negative binomial regression models were used to estimate the associations. RESULTS: Resident perceptions of neighborhood disorder and outside observation of neighborhood physical characteristics were both found to be independently related to the likelihood of physical assault. Resident perceptions were related to psychological aggression. A more positive perception of the neighborhood environment for children (lack of neighborhood disorder) and physical characteristics of the neighborhood were protective against maltreatment. These relationships were not significant for neglect. DISCUSSION: Neighborhood environment is a crucial contributor to maltreatment risk. Findings from the present study showed that multiple perceptions of neighborhood quality were associated with lower risk for child physical assault and psychological aggression. Mothers' perceptions of a more positive neighborhood environment were associated with significantly lower physical assault and psychological aggression scores.

The moderating role of neighborhood social cohesion on the relationship between early mother-child attachment security and adolescent social skills: Brief report.

Background: Social skill is a critical asset for adolescents, and early mother-child attachment is an essential contributor to their development. While less secure mother-child attachment is a known risk factor for adolescent social development, the protective factor of neighborhood context in buffering this risk is still not well understood. Research Design: This study used longitudinal data from the Fragile Families and Child Wellbeing Study (n = 1,876). Adolescent social skills (at age 15) were examined as a function of early attachment security and neighborhood social cohesion (age 3). Results: Children with higher mother-child attachment security at age three had higher adolescent social skills at age 15. The findings show that there was an interaction effect such that neighborhood social cohesion buffered the relationship between mother-child attachment security and adolescent social skills. Conclusion: Our study highlights that early mother-child attachment security can be promotive for cultivating adolescent social skills. Furthermore, neighborhood social cohesion can be protective among children with lower mother-child attachment security.

Contextual factors of child behavioral health across developmental stages.

This study examines the relative influence of environmental contexts (family, school, neighborhood) on child behavioral health at ages 3, 5, 9, and 15 years. Path analysis was conducted on a sample of 4,898 urban children from a longitudinal dataset called the Fragile Families and Child Wellbeing Study. Child physical abuse, emotional abuse, maternal depression, substance use, neighborhood social cohesion, neighborhood poverty, school connectedness, and peer bullying had concurrent relationships with child behavior problems at one or more developmental stages. Early childhood abuse (age 3) and school age environmental contexts (age 9) had lasting effects on later behavior problems. Findings underscore the importance of both multilevel contextual factors and developmental timing in determining behavioral health outcomes in children.

QI initiative to reduce the number of inpatient falls in an acute hospital Trust.

Inpatient falls are one of the most frequent concerns to patient safety within the acute hospital environment, equating to 1700 falls per year in an 800-bed general hospital. They are predicted to cost approximately £2600 per patient, however, this estimate does not capture the costs and impact that inpatient falls have on the wider health and social care system. It also does not take into the account loss of confidence and delays in functional recovery.This report shares the learning from a quality improvement (QI) initiative that took place in a District General Hospital (DGH) in the UK. The initiative started in February 2020, was paused November 2020 due to wave 2 of the pandemic and restarted in March 2021. Improvement was achieved in January 2021.Data for falls within the Trust identified that falls were within common cause variation. A system change was needed to achieve an improvement.A QI project was commenced with the aim to achieve a 5% reduction in falls per 1000 bed days in a care of the elderly ward.Two primary drivers were identified: recognising patients at high risk of falls and preventing them from falling. Change ideas to address these primary drivers were tested using Plan Do Study Act (PDSA) cycles. Changes tested included: the development of an assessment tool to identify patients at high risk of falls, use of a wristband to identify patients at high risk of a fall, and increased observation.Change ideas achieved some success with the process measures but did not achieve an improvement with the outcome measures. A Trust wide change idea relating to the falls prevention service did lead to a sustained improvement in falls reduction.The barriers to the improvement included changing Trust priorities during the pandemic, and limited opportunities to fully engage the ward-based team with systems thinking and changing mental models.

Implementation and Mental Health Outcomes of a Service Cascade Linking Child Welfare and Children's Mental Health Systems: A Case Study of the Gateway CALL Demonstration.

The mental health needs of children and youth involved in the child welfare system remain largely unmet. Service cascades are an emerging approach to systematizing mental health screening, assessment, and treatment referral processes. However, evidence is minimal and inconsistent regarding the effectiveness of such approaches for improving mental health service access and outcomes. In an effort to address this gap, this study presents a case-study of the implementation fidelity and treatment outcomes of the Gateway CALL service cascade. Study analyses involved longitudinal data collected as part of a larger evaluation of Gateway CALL. Specifically, descriptive and linear mixed model analyses were conducted to assess the implementation of service cascade components, and changes in mental health outcomes (behavior problems) among 175 children placed out-of-home during the study. Study analyses found that although fidelity was strong early in the service cascade, implementation began to break down once components involved more than one service system (child welfare, mental health). However, results also indicated that parent-reported child behavior problems decreased significantly over time, despite later cascade components being implemented with poor fidelity to the Gateway CALL service model. For children and youth involved in child welfare systems, service cascades like Gateway CALL have the potential to significantly improve both mental health service receipt and outcomes. To maximize the effectiveness of such approaches, later phases of implementation may require increased attention and support, particularly regarding processes and outcomes that cross child welfare and mental health service systems.

Neighborhood Poverty, Family Economic Well-Being, and Child Maltreatment.

This study sought to understand the relationships between neighborhood poverty, family monetary well-being, and child maltreatment. The specific research questions were as follows: (1) Is neighborhood poverty at age 1 related to child physical abuse, psychological abuse, and neglect at age 5? (2) Are these relationships mediated by family monetary well-being? The study relied on data from three waves (child ages 1, 3, and 5) of the Fragile Families and Child Wellbeing Study, a longitudinal birth-cohort study of 4,898 children from 20 large U.S. cities. Structural equation modeling was employed to examine mediational effects. The study found a lasting impact of neighborhood poverty on child neglect only, and this relationship was fully mediated by family monetary well-being. There was not a significant longitudinal relationship between neighborhood poverty and physical abuse or psychological abuse. Implications from the study suggest that neighborhood disadvantage impacts a families' economic well-being, and that individual-level economic supports may interrupt the pathway from neighborhood poverty to child neglect.

Changes of perceived Neighbourhood environment: A longitudinal study of collective efficacy among vulnerable families.

Neighbourhood level factors are associated with individual's behaviours but limited empirical research investigate the long-term changes of neighbourhood factors, especially neighbourhood collective efficacy. Moreover, the longitudinal effects of neighbourhood structural factors on neighbourhood process factors worth further research. Thus, the current study examined the (1) the long-term trajectory of collective efficacy; (2) whether the time-varying neighbourhood structural factors are associated with collective efficacy over time. Using the four waves of FFCWS data (N = 4898), the current research found that neighbourhood social cohesion and informal social control increased over time, and the changes of neighbourhood structural factors are associated with the changes of collective efficacy over time. Identifying the dynamic changes of neighbourhood factors would benefit the further investigations of the influences of neighbourhood factors on individuals, and the implications of the findings were discussed.

Stabilizing proteins, simplified: A Rosetta-based webtool for predicting favorable mutations.

Many proteins have low thermodynamic stability, which can lead to low expression yields and limit functionality in research, industrial and clinical settings. This article introduces two, web-based tools that use the high-resolution structure of a protein along with the Rosetta molecular modeling program to predict stabilizing mutations. The protocols were recently applied to three genetically and structurally distinct proteins and successfully predicted mutations that improved thermal stability and/or protein yield. In all three cases, combining the stabilizing mutations raised the protein unfolding temperatures by more than 20°C. The first protocol evaluates point mutations and can generate a site saturation mutagenesis heatmap. The second identifies mutation clusters around user-defined positions. Both applications only require a protein structure and are particularly valuable when a deep multiple sequence alignment is not available. These tools were created to simplify protein engineering and enable research that would otherwise be infeasible due to poor expression and stability of the native molecule.

The mediating role of housing insecurity in the relationship between neighborhood social cohesion and child maltreatment among low-income urban families.

BACKGROUND: Child abuse has deleterious impacts for children across their lifespan. Understanding the pathways in which child abuse occurs is critical for targeting prevention efforts. The trust and bonds between neighbors may play a preventive role against child abuse, with parents receiving support from those who are geographically close. Such relationships may guard against housing insecurity, which is related to child abuse. OBJECTIVE: The current study examines the relationships between social cohesion, housing insecurity, and child abuse. PARTICIPANTS AND SETTING: The study relies on data from the Fragile Families and Child Wellbeing Study, a longitudinal birth cohort study of 4898 families from 20 large urban cities. The study focuses on data from waves 3, 4, 5 when focal children were ages 3, 5, and 9 years. METHODS: Structural equation modeling is used to test the mediational relationship between neighborhood social cohesion at age 3, housing insecurity at age 5, and physical and psychological child abuse at age 9. RESULTS: The study found that social cohesion is related to lower levels of physical and psychological abuse, and these pathways are partially mediated through housing insecurity. CONCLUSIONS: The findings underscore the important role of neighborhoods in child maltreatment prevention.