Children's Ability to Recognize Visually Occluded Stimuli

The purpose of this research was to study children's ability to recognize partially occluded images. Tasks were constructed which consisted of occluded images from video games, trademarks, and household objects. The tasks were administered to third and sixth grade students at two elementary schools in Arlington, Texas. The researcher discovered no significant differences between the scores of males and females except for the males' higher score on the video game task

Behavioral, Cognitive, and Socioemotional Pathways from Early Childhood Adversity to BMI: Evidence from Two Prospective, Longitudinal Studies

Childhood adversity is associated with higher adult weight, but few investigations prospectively test mechanisms accounting for this association. Using two socioeconomically high-risk prospective longitudinal investigations, the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA; N = 267; 45.3% female) and the Fragile Families and Child Wellbeing Study (FFCWS; n = 2,587; 48.5% female), pathways between childhood adversity and later body mass index (BMI) were tested using impulsivity, emotion dysregulation, and overeating as mediators. Childhood adversity from 0 to 5 years included four types of adversities: greater unpredictability, threat/abuse, deprivation/neglect, and low socioeconomic status. Parents reported on child impulsivity, emotion dysregulation, and overeating. Height and weight were self-reported and measured at 32 and 37 years in MLSRA and at 15 years in FFCWS. FFCWS results indicated that threat, deprivation, and low socioeconomic status predicted greater impulsivity and emotion dysregulation at 5 years, which in turn predicted greater overeating at 9 years and higher BMI z-score at 15 years. Early unpredictability in FFCWS predicted higher BMI through greater impulsivity but not emotion dysregulation at age 5. MLSRA regression results replicated the threat/abuse → emotion dysregulation → overeating → higher BMI pathway. These findings suggest that different dimensions of early adversity may follow both similar and unique pathways to predict BMI

Unidirectional Cross-Activation of GRPR by MOR1D Uncouples Itch and Analgesia Induced by Opioids

SummarySpinal opioid-induced itch, a prevalent side effect of pain management, has been proposed to result from pain inhibition. We now report that the μ-opioid receptor (MOR) isoform MOR1D is essential for morphine-induced scratching (MIS), whereas the isoform MOR1 is required only for morphine-induced analgesia (MIA). MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, relaying itch information. We show that morphine triggers internalization of both GRPR and MOR1D, whereas GRP specifically triggers GRPR internalization and morphine-independent scratching. Providing potential insight into opioid-induced itch prevention, we demonstrate that molecular and pharmacologic inhibition of PLCβ3 and IP3R3, downstream effectors of GRPR, specifically block MIS but not MIA. In addition, blocking MOR1D-GRPR association attenuates MIS but not MIA. Together, these data suggest that opioid-induced itch is an active process concomitant with but independent of opioid analgesia, occurring via the unidirectional cross-activation of GRPR signaling by MOR1D heterodimerization

Effects of subsequent systemic anticancer medication following first-line lenvatinib: a post hoc responder analysis from the phase 3 REFLECT study in unresectable hepatocellular carcinoma

Introduction: Understanding the relationship between subsequent-line therapies and overall survival (OS) is important for maximizing OS for patients with hepatocellular carcinoma. Objective: In this post hoc analysis, we investigated OS in lenvatinib- and sorafenib-treated patients from the REFLECT study, who then received subsequent anticancer medication during the survival follow-up period. Methods: The follow-up period commenced at the first off-treatment visit after stopping the study medication and continued until study termination, withdrawal of consent, or death. OS and objective response rate were calculated for patients who did or did not receive poststudy anticancer medication for both treatment arms, as well as for the overall cohort. We investigated the subset of patients who responded to first-line treatment and subsequently received anticancer medication. Results: The OS for patients initially randomized to first-line lenvatinib (versus first-line sorafenib) and who then received any subsequent anticancer medication was 20.8 vs. 17.0 months (hazard ratio [HR] 0.87; 95% CI 0.67–1.14). The OS for patients who initially received first-line lenvatinib (versus first-line sorafenib) and who did not receive any subsequent anticancer medication was 11.5 vs. 9.1 months (HR 0.90; 95% CI 0.75–1.09). Responders to first-line lenvatinib who received subsequent medication had a median OS of 25.7 months (95% CI 18.5–34.6); responders to first line-sorafenib who received subsequent medication had a median OS of 22.3 months (95% CI 14.6–not evaluable). Conclusions: In this post hoc analysis of all patients in the REFLECT study who received subsequent anticancer medication, OS was increased compared with patients who did not receive any subsequent anticancer medication. In a subset analysis of responders who had received subsequent anticancer medication, use of first-line lenvatinib led to a slightly longer median OS; more research is needed on the benefits of using first-line lenvatinib compared with sorafenib

Organizational Governance of Emerging Technologies: AI Adoption in Healthcare

Private and public sector structures and norms refine how emerging technology is used in practice. In healthcare, despite a proliferation of AI adoption, the organizational governance surrounding its use and integration is often poorly understood. What the Health AI Partnership (HAIP) aims to do in this research is to better define the requirements for adequate organizational governance of AI systems in healthcare settings and support health system leaders to make more informed decisions around AI adoption. To work towards this understanding, we first identify how the standards for the AI adoption in healthcare may be designed to be used easily and efficiently. Then, we map out the precise decision points involved in the practical institutional adoption of AI technology within specific health systems. Practically, we achieve this through a multi-organizational collaboration with leaders from major health systems across the United States and key informants from related fields. Working with the consultancy IDEO.org, we were able to conduct usability-testing sessions with healthcare and AI ethics professionals. Usability analysis revealed a prototype structured around mock key decision points that align with how organizational leaders approach technology adoption. Concurrently, we conducted semi-structured interviews with 89 professionals in healthcare and other relevant fields. Using a modified grounded theory approach, we were able to identify 8 key decision points and comprehensive procedures throughout the AI adoption lifecycle. This is one of the most detailed qualitative analyses to date of the current governance structures and processes involved in AI adoption by health systems in the United States. We hope these findings can inform future efforts to build capabilities to promote the safe, effective, and responsible adoption of emerging technologies in healthcare

X-linked Severe Combined Immunodeficiency Syndrome: The First Korean Case with γc Chain Gene Mutation and Subsequent Genetic Counseling

X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening immune disorder, caused by mutations in the γc chain gene, which encodes an essential component of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. A 13-month-old boy with recurrent infections who had reduced serum immunoglobulin levels and decreased numbers of CD3, CD16/56 cells was evaluated for γc chain gene mutation and protein expression. The patient had a C-to-T point mutation at nucleotide position 690, one of the hot spots, resulting in a single amino acid substitution of cysteine for arginine (R226C), as determined by direct sequencing and PCR-RFLP. The patient's mother was a heterozygous carrier. Percutaneous umbilical cord blood sampling was performed at the 6-month of gestation in a subsequent pregnancy. As the immunophenotype of the fetus showed an identical pattern, the pregnancy was terminated and genetic analysis of the abortus confirmed recurrence. This is the first report of the molecular diagnosis of X-SCID in Korea. Genetic analysis of the γc chain gene is useful for definite diagnosis and genetic counseling for X-SCID

Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC (Pdx1-Cre, LSL-KrasG12D/+, LSL-Trp53R172H/+) and poorly metastatic KPflC (Pdx1-Cre, LSL-KrasG12D/+, Trp53fl/+) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KPflC, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs). Using biomechanical assessments, second harmonic generation imaging, and birefringence analysis, we show that NID2 reduction by CRISPR interference (CRISPRi) in CAFs reduces stiffness and matrix remodeling in three-dimensional models, leading to impaired cancer cell invasion. Intravital imaging revealed improved vascular patency in live NID2-depleted tumors, with enhanced response to gemcitabine/Abraxane. In orthotopic models, NID2 CRISPRi tumors had less liver metastasis and increased survival, highlighting NID2 as a potential PDAC cotarget

An Investigation of Young Children's Awareness of Line and Line Quality in Art and Graphic Reproductions

The purpose of this study was to determine whether kindergarten children possess the ability to recognize, match, and discuss lines and line qualities. Using graphics and art reproductions, three matching tasks were constructed which examined young children's awareness of the line qualities of length, width, straightness, direction, movement, and uniformity. Graphics and art reproductions were also used to construct two tracing tasks employed to examine young children's awareness of actual and implied lines. The tasks were administered to 69 kindergarten students from four elementary schools in a public school district in the north central Texas area

Behaviour of Over-reinforced High-Strength Concrete Beams Confined with Post-Tensioned Steel Straps: an experimental investigation

This study examines the flexural behaviour of High-Strength Concrete (HSC) beams confined using an innovative Steel Strapping Tensioning Technique (SSTT) able to provide active confinement. Twelve overreinforced HSC beams (fc=50 or 80 MPa) were designed to fail prematurely by concrete crushing at midspan. The midspan of eight of such beams was confined externally using the SSTT with different steel strap confinement ratios, which aimed to delay concrete crushing. The test results are discussed in terms of the failure modes, load-deflection response, and observed concrete and tensile reinforcement strains. Whilst unconfined beams failed in a brittle manner with no post-peak deflection, the steel straps were very effective at enhancing the post-peak deformation of the SSTT-confined beams by up to 126%. Moreover, for the beams tested in this study, the use of the SSTT led to failures after yielding of the tensile reinforcement. The proposed SSTT can be used to confine HSC elements where ductility is required