bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Feasibility of the ABCs of SLEEPING Mobile Application: Exploring Implementation, Acceptability, and Limited Efficacy
Authors: Jemcov Anastasija , Keys Elizabeth , Corkum Penny 
Published: August 2021

Objective: Behaviourally based sleep problems are common among school-age children. Due to a number of barriers, few children receive evidence-based behavioural interventions for their sleep problems. The ABCs of SLEEPING mobile application was developed to provide parents with individualized and prioritized evidence-based sleep recommendations. Method: The current study assessed the feasibility of the intervention using a cohort pretest posttest design. Acceptability was assessed by collecting parent ratings of satisfaction/suitability and qualitative feedback through open-ended questions. Implementation was assessed weekly for 4 weeks to examine if the intervention was used as intended. Preliminary-efficacy was explored by assessing changes in children’s sleep and bedtime behaviours using parent report. Results: Parents generally reported satisfaction with the each of the three intervention components (questionnaire, report, and tips) and suitability of the tips for their child’s age and sleep problems. Descriptive statistics of the implementation data revealed parents did not use the intervention as much as intended. Content analysis of the qualitative data indicated that some changes to the intervention are needed (e.g., reminders to implement). Statistically significant evidence for preliminary-efficacy was found based on parent-reported questionnaires, but sleep was not normalized. Conclusion: The results indicate that while the ABCs of SLEEPING mobile application was found to have a moderate level of feasibility, it is not yet ready for large-scale testing. Future research should focus on modifying the intervention to imbed features to support implementation of the intervention. Implications for Impact Statement In this study we describe the feasibility testing of a smartphone-application designed to improve access to individualized information about sleep and healthy sleep practices entitled “ The ABCs of SLEEPING.” Our results demonstrated its acceptability and preliminary efficacy; however, the app was not implemented daily as intended. This research also demonstrates the importance of evaluating interventions for the end-user.
“Quiero Soy Un Niño!”: Family-Based Treatment of a Mexican American Child with Gender Dysphoria and Disruptive Behaviors
Authors: Christian-Brandt Allison S. , Philpott Jaqueline , Edwards-Leeper Laura 
Published: August 2021

Objective: Research among transgender and gender nonconforming (TGNC) youth is growing, but sparse among prepubertal children. Given that TGNC youth experience higher rates of psychological difficulties than peers, and family support of gender identity serves as a protective factor, experts have called for gender-affirmative psychological services as part of comprehensive gender care. However, research on evidence-based practices for TGNC youth is lacking, particularly among young children. The present case report seeks to add the literature on culturally-responsive, family-based treatment for TGNC children. Method: Authors describe adapting positive attending and relationship-enhancement skills from behavioral parent training for six-year-old “Dani,” a Mexican American child referred to treatment for ADHD symptoms, who also exhibited behavioral issues in the context of gender dysphoria. Treatment adaptations included adjunctive parent and child sessions for gender psychoeducation and support, exclusion of a limit-setting phase, and applying positive parenting skills to affirmation of Dani’s gender identity and expression. Services were also tailored for the family’s cultural values and level of acculturation. Results: As parents’ use of positive attending skills increased alongside support for Dani’s diverse gender expression in the first phase of treatment, disruptive behaviors markedly decreased. In the second phase of treatment, family understanding and communication regarding gender was enhanced, while parent distress related to Dani’s gender dysphoria reduced. Conclusions: Continued research on affirmative interventions provided in a culturally-responsive manner, such as described in this case report, are imperative, given the negative psychological outcomes among TGNC youth and the significant health service disparities among this underserved, vulnerable population. Implications for Impact Statement The present case study describes adapting positive attending and relationship-enhancement skills from traditional behavioral parent training to provide culturally-responsive, gender-affirmative therapy with the family of a young Mexican American child with ADHD, disruptive behaviors, and gender dysphoria.
From Planning to Implementation: Creating and Adapting Universal Screening Protocols to Address Caregiver Mental Health and Psychosocial Complexity
Authors: Buchholz Melissa , Ashby Bethany , Costello Lisa , Ehmer Amy , Serrano Verenea , von Schulz Jonna , Wolcott Catherine , Talmi Ayelet 
Published: August 2021

Objective: Children are accompanied to primary care settings by caregivers who present with their own mental health and psychosocial distress. Primary care is an optimal place to identify negative impacts on child health. Clinics with integrated behavioral health (IBH) clinicians are well-positioned to implement and respond to caregiver screenings. Methods: Universal screening to address perinatal mood and anxiety disorders (PMADs) and psychosocial distress was implemented in 3 primary care clinics within 1 hospital system. Pediatric psychologists supported implementation across all clinics. Screening frequencies, average scores of elevated screeners, and most common treatment recommendations made by IBH clinicians were extracted from medical records. Results: Universal caregiver screening effectively identified mental health and psychosocial concerns and was a driver of increased behavioral health access in pediatric primary care. A total of 6,080 caregivers were screened over 3 years. Results showed 10% and 16.4% of caregivers had elevated PMADs screening results, 33% to 46% identified social determinants of health needs, and 6.6% to 11.5% identified mental health concerns. Responses to screeners including follow up with the IBH team, brief interventions, and caregiver referral to mental health services. Conclusions: Caregiver screening is an essential component of comprehensive well-child care. Without universal screening processes, caregiver mental health and psychosocial concerns may go undetected and unaddressed. Implications for Impact Statement This paper describes the importance of screening caregivers for behavioral health concerns and psychosocial adversity during pediatric primary care visits. The role of pediatric psychologists in developing universal screening protocols is described. Results indicate that caregiver screening yields increased behavioral health involvement.
Introduction to the Special Interest Issue on Parent/Guardian Interventions in Pediatric Psychology: The Role of the Pediatric Psychologist Working with Caregivers as the Target of Intervention
Authors: Kahhan Nicole A. , Junger Katherine W. 
Published: August 2021

Objective: There is a complex and bidirectional relationship between parent/guardian wellbeing and child physical and mental health. The role of a pediatric psychologist in this relationship has historically emphasized working with the parent as an agent of change to disseminate evidence-based skills and techniques toward improving child functioning. Increasingly, the role a pediatric psychologist can play in directly impacting the health and wellbeing of the parent/guardian of the identified patient is being explored, especially with expanded integration of behavioral health into primary care and medical home models that approach child health through a holistic, preventative lens. Furthermore, parents of children with acute/chronic illness are at increased risk of mental health concerns themselves; thus, considering parent functioning as its own outcome when working with pediatric patients may confer additional benefits in optimizing family adjustment. Method: Articles inclusive of topics on screening, early intervention, treatment, and program development targeting the parent/guardian of pediatric patients were considered for this issue. Results: This Special Issue includes 10 articles highlighting novel interventions targeting parent well-being in primary care and medical subspecialty settings using a range of service delivery modalities. Additionally, this issue explores the ethical, logistical, and systems considerations that can pose challenges to responding to parent mental health needs within the pediatric health care system, which pediatric psychology as a field is still learning to negotiate. Conclusions: This issue highlights clinical practice approaches and novel research in which the primary target of intervention is the caregiver of a pediatric patient. Implications for Impact Statement The aim of this Special Issue is to contribute to the research base for pediatric psychology providers with regards to models and methodology for parent/guardian specific screening and intervention in the pediatric health care system. Ethical issues in addressing caregivers as the primary point of intervention also are explored while promoting a holistic family care model.
Organizational principles of amygdalar input-output neuronal circuits
Authors: Huang Limeng , Chen Yiwen , Jin Sen , Lin Li , Duan Shumin , Si Ke , Gong Wei , Julius Zhu J. 
Published: August 2021

AbstractThe amygdala, one of the most studied brain structures, integrates brain-wide heterogeneous inputs and governs multidimensional outputs to control diverse behaviors central to survival, yet how amygdalar input-output neuronal circuits are organized remains unclear. Using a simplified cell-type- and projection-specific retrograde transsynaptic tracing technique, we scrutinized brain-wide afferent inputs of four major output neuronal groups in the amygdalar basolateral complex (BLA) that project to the bed nucleus of the stria terminals (BNST), ventral hippocampus (vHPC), medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), respectively. Brain-wide input-output quantitative analysis unveils that BLA efferent neurons receive a diverse array of afferents with varied input weights and predominant contextual representation. Notably, the afferents received by BNST-, vHPC-, mPFC- and NAc-projecting BLA neurons exhibit virtually identical origins and input weights. These results indicate that the organization of amygdalar BLA input-output neuronal circuits follows the input-dependent and output-independent principles, ideal for integrating brain-wide diverse afferent stimuli to control parallel efferent actions. The data provide the objective basis for improving the virtual reality exposure therapy for anxiety disorders and validate the simplified cell-type- and projection-specific retrograde transsynaptic tracing method.
Glucose-sensitive acetylation of Seryl tRNA synthetase regulates lipid synthesis in breast cancer
Authors: Zhao Jin , Bai Hangming , Li Xiaoyu , Yan Jie , Zou Gengyi , Wang Longlong , Li Xiru , Liu Ze , Xiang Rong , Yang Xiang-Lei , Shi Yi 
Published: August 2021

AbstractAbnormally enhanced de novo lipid biosynthesis has been increasingly realized to play crucial roles in the initiation and progression of varieties of cancers including breast cancer. However, the mechanisms underlying the dysregulation of lipid biosynthesis in breast cancer remain largely unknown. Here, we reported that seryl tRNA synthetase (SerRS), a key enzyme for protein biosynthesis, could translocate into the nucleus in a glucose-dependent manner to suppress key genes involved in the de novo lipid biosynthesis. In normal mammary gland epithelial cells glucose can promote the nuclear translocation of SerRS by increasing the acetylation of SerRS at lysine 323. In SerRS knock-in mice bearing acetylation-defective lysine to arginine mutation, we observed increased body weight and adipose tissue mass. In breast cancer cells the acetylation and nuclear translocation of SerRS are greatly inhibited. Overexpression of SerRS, in particularly the acetylation-mimetic lysine to glutamine mutant, dramatically inhibits the de novo lipid synthesis and hence greatly suppresses the proliferation of breast cancer cells and the growth of breast cancer xenografts in mice. We further identified that HDAC4 and HDAC5 regulated the acetylation and nuclear translocation of SerRS. Thus, we identified a SerRS-meditated inhibitory pathway in glucose-induced lipid biosynthesis, which is dysregulated in breast cancer.
Sleep disturbances are associated with cortical and subcortical atrophy in alcohol use disorder
Authors: Zhang Rui , Tomasi Dardo , Manza Peter , Shokri-Kojori Ehsan , Demiral Sukru B. , Feldman Dana E. , Kroll Danielle S. , Biesecker Catherine L. , McPherson Katherine L. , Wang Gene-Jack , Wiers Corinde E. , Volkow Nora D. 
Published: August 2021

AbstractSleep disturbances are prominent in patients with alcohol use disorder (AUD) and predict relapse. So far, the mechanisms underlying sleep disruptions in AUD are poorly understood. Because sleep-related regions vastly overlap with regions, where patients with AUD showed pronounced grey matter (GM) reduction; we hypothesized that GM structure could contribute to sleep disturbances associated with chronic alcohol use. We combined sleep EEG recording and high-resolution structural brain imaging to examine the GM-sleep associations in 36 AUD vs. 26 healthy controls (HC). The patterns of GM-sleep associations differed for N3 vs. REM sleep and for AUD vs. HC. For cortical thickness (CT), CT-sleep associations were significant in AUD but not in HC and were lateralized such that lower CT in right hemisphere was associated with shorter N3, whereas in left hemisphere was associated with shorter REM sleep. For the GM density (GMD), we observed a more extensive positive GMD-N3 association in AUD (right orbitofrontal cortex, cerebellum, dorsal cingulate and occipital cortex) than in HC (right orbitofrontal cortex), and the GMD-REM association was positive in AUD (midline, motor and paralimbic regions) whereas negative in HC (the left supramarginal gyrus). GM structure mediated the effect of chronic alcohol use on the duration of N3 and the age by alcohol effect on REM sleep. Our findings provide evidence that sleep disturbances in AUD were associated with GM reductions. Targeting sleep-related regions might improve sleep in AUD and enhance sleep-induced benefits in cognition and emotional regulation for recovery.
An urgent call to raise the bar in oncology
Authors: Schnog John-John B. , Samson Michael J. , Gans Rijk O. B. , Duits Ashley J. 
Published: August 2021

AbstractImportant breakthroughs in medical treatments have improved outcomes for patients suffering from several types of cancer. However, many oncological treatments approved by regulatory agencies are of low value and do not contribute significantly to cancer mortality reduction, but lead to unrealistic patient expectations and push even affluent societies to unsustainable health care costs. Several factors that contribute to approvals of low-value oncology treatments are addressed, including issues with clinical trials, bias in reporting, regulatory agency shortcomings and drug pricing. With the COVID-19 pandemic enforcing the elimination of low-value interventions in all fields of medicine, efforts should urgently be made by all involved in cancer care to select only high-value and sustainable interventions. Transformation of medical education, improvement in clinical trial design, quality, conduct and reporting, strict adherence to scientific norms by regulatory agencies and use of value-based scales can all contribute to raising the bar for oncology drug approvals and influence drug pricing and availability.
Risk of COVID-19 death in cancer patients: an analysis from Guy’s Cancer Centre and King’s College Hospital in London
Authors: Russell Beth , Moss Charlotte L. , Shah Vallari , Ko Thinzar Ko , Palmer Kieran , Sylva Rushan , George Gincy , Monroy-Iglesias Maria J. , Patten Piers , Ceesay Muhammed Mansour , Benjamin Reuben , Potter Victoria , Pagliuca Antonio , Papa Sophie , Irshad Sheeba , Ross Paul , Spicer James , Kordasti Shahram , Crawley Danielle , Wylie Harriet , Cahill Fidelma , Haire Anna , Zaki Kamarul , Sita-Lumsden Ailsa , Josephs Debra , Enting Deborah , Swampillai Angela , Sawyer Elinor , D’Souza Andrea , Gomberg Simon , Harrison Claire , Fields Paul , Wrench David , Rigg Anne , Sullivan Richard , Kulasekararaj Austin ,   Guy’s Cancer Real World Evidence, Jones Eleanor , Seeva Pavetha , Karampera Christina , Devi Aarani , Rahman Fareen , Smith Daniel , Owczarczyk Kasia , Tsotra Eirini , Gousis Charalampos , Lei Mary , Ghosh Sharmistha , Nintos George , Raj Kavita , Gleeson Mary , Bailey Katherine , Dillon Richard , Streetly Matthew , Mera Anca , Timbres Jasmine , Dolly Saoirse , Van Hemelrijck Mieke 
Published: August 2021

AbstractBackgroundUsing an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death.MethodsData on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy’s Cancer Centre and King’s College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality.ResultsThree hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15–3.38)], Asian ethnicity [3.42 (1. 59–7.35)], haematological cancer [2.03 (1.16–3.56)] and a cancer diagnosis for >2–5 years [2.81 (1.41–5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis).ConclusionsFindings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.
Dynamic regulation of mitochondrial-endoplasmic reticulum crosstalk during stem cell homeostasis and aging
Authors: Lin Weiping , Chen Shuxun , Wang Yan , Wang Ming , Lee Wayne Yuk-Wai , Jiang Xiaohua , Li Gang 
Published: August 2021

AbstractCellular therapy exerts profound therapeutic potential for curing a broad spectrum of diseases. Adult stem cells reside within a specified dynamic niche in vivo, which is essential for continuous tissue homeostatic maintenance through balancing self-renewal with lineage selection. Meanwhile, adult stem cells may be multipotent or unipotent, and are present in both quiescent and actively dividing states in vivo of the mammalians, which may switch to each other state in response to biophysical cues through mitochondria-mediated mechanisms, such as alterations in mitochondrial respiration and metabolism. In general, stem cells facilitate tissue repair after tissue-specific homing through various mechanisms, including immunomodulation of local microenvironment, differentiation into functional cells, cell “empowerment” via paracrine secretion, immunoregulation, and intercellular mitochondrial transfer. Interestingly, cell-source-specific features have been reported between different tissue-derived adult stem cells with distinct functional properties due to the different microenvironments in vivo, as well as differential functional properties in different tissue-derived stem cell-derived extracellular vehicles, mitochondrial metabolism, and mitochondrial transfer capacity. Here, we summarized the current understanding on roles of mitochondrial dynamics during stem cell homeostasis and aging, and lineage-specific differentiation. Also, we proposed potential unique mitochondrial molecular signature features between different source-derived stem cells and potential associations between stem cell aging and mitochondria–endoplasmic reticulum (ER) communication, as well as potential novel strategies for anti-aging intervention and healthy aging.
LIF/LIFR oncogenic signaling is a novel therapeutic target in endometrial cancer
Authors: Tang Weiwei , Ramasamy Kumaraguruparan , Pillai Sureshkumar M. A. , Santhamma Bindu , Konda Swapna , Pitta Venkata Prabhakar , Blankenship Logan , Liu Junhao , Liu Zexuan , Altwegg Kristin A. , Ebrahimi Behnam , Pratap Uday P. , Li Xiaonan , Valente Philip T. , Kost Edward , Sareddy Gangadhara R. , Vadlamudi Ratna K. , Nair Hareesh B. , Tekmal Rajeshwar R. , Viswanadhapalli Suryavathi 
Published: August 2021

AbstractEndometrial cancer (EC) is the fourth most common cancer in women. Advanced-stage EC has limited treatment options with a poor prognosis. There is an unmet need for the identification of actionable drivers for the development of targeted therapies in EC. Leukemia inhibitory factor receptor (LIFR) and its ligand LIF play a major role in cancer progression, metastasis, stemness, and therapy resistance. However, little is known about the functional significance of the LIF/LIFR axis in EC progression. In this study using endometrial tumor tissue arrays, we identified that expression of LIF, LIFR is upregulated in EC. Knockout of LIFR using CRISPR/Cas9 in two different EC cells resulted in a significant reduction of their cell viability and cell survival. In vivo studies demonstrated that LIFR-KO significantly reduced EC xenograft tumor growth. Treatment of established and primary patient-derived EC cells with a novel LIFR inhibitor, EC359 resulted in the reduction of cell viability with an IC50in the range of 20–100 nM and induction of apoptosis. Further, treatment with EC359 reduced the spheroid formation of EC cancer stem cells and reduced the levels of cancer stem cell markers SOX2, OCT4, NANOG, and Axin2. Mechanistic studies demonstrated that EC359 treatment attenuated the activation of LIF-LIFR driven pathways, including STAT3 and AKT/mTOR signaling in EC cells. Importantly, EC359 treatment resulted in a significant reduction of the growth of EC patient-derived explants ex vivo, EC cell line-derived xenografts, and patient-derived xenografts in vivo. Collectively, our work revealed the oncogenic potential of the LIF/LIFR axis in EC and support the utility of LIFR inhibitor, EC359, as a novel targeted therapy for EC via the inhibition of LIF/LIFR oncogenic signaling.