Single cells tell it all.

A new single-cell atlas of gene expression provides insights into the patterning of the neural plate of mice.

Elevation of NT-proBNP Levels in Pediatric and Young Adult Hematopoietic Stem Cell Transplant Patients with Endotheliopathy.

Background/objectives: Hematopoietic stem cell transplantation (HSCT) in pediatric and young adult (YA) patients can lead to endotheliopathy, such as thrombotic microangiopathy (TMA), sinusoidal obstruction syndrome (SOS), and diffuse alveolar hemorrhage (DAH). Natriuretic peptides have been studied as markers of endotheliopathy and critical illness. We hypothesized that an elevation in NT-proBNP was associated with the development of endotheliopathy (DAH, SOS, or TMA) in the first 100 days following HSCT in pediatric and YA patients.

Activation of Heme Metabolism Promotes Tissue Health After Intraarticular Injury or Surgical Exposure.

Posttraumatic osteoarthritis (PTOA) is a well-recognized public health burden without any disease modifying treatment. This occurs despite noted advances in surgical care in the past 50 years. Mitochondrial oxidative damage pathways initiate PTOA after severe injuries like intraarticular fracture that often require surgery and contribute to PTOA after less severe injuries that may or may not require surgery like meniscal injuries.

White matter variations in congenital adrenal hyperplasia: possible implications for glucocorticoid treatment.

Congenital adrenal hyperplasia has been reported to manifest with white matter aberrations. However, many previous studies included only small samples, restricted their analyses to females, lacked a control group and/or did not correct for brain size. Here, we examined the largest sample to date, comprising 53 male and female participants with congenital adrenal hyperplasia, who were matched with 53 male and female controls in terms of sex, age, education, and verbal intelligence.

Effects of Congenital Adrenal Hyperplasia (CAH) and Biological Sex on Brain Size.

Congenital Adrenal Hyperplasia (CAH) has been reported to involve structural alterations in some brain regions. However, it remains to be established whether there is also an impact on the size of the brain as a whole. Here, we compiled the largest CAH sample to date (n = 53), matched pair-wise to a control group (n = 53) on sex, age, and verbal intelligence.

The association between infant non-nutritive suck and oral motor development.

This study investigated if non-nutritive suck (NNS) at 3 months is related to subsequent oral motor and motor skills using caregiver-reported scores on the Child Oral and Motor Proficiency Scale (ChOMPS) at 12 months in a cohort of 69 full-term infants and their caregivers. Longer NNS burst durations were associated with lower oral motor coordination and total ChOMPS scores. More NNS cycles per minute was associated with lower complex motor movement scores.

AI-based IsAb2.0 for antibody design.

Therapeutic antibody design has garnered widespread attention, highlighting its interdisciplinary importance. Advancements in technology emphasize the critical role of designing nanobodies and humanized antibodies in antibody engineering. However, current experimental methods are costly and time-consuming.

CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma.

Novel chimeric antigen receptor (CAR) T-cell approaches are needed to improve therapeutic efficacy in solid tumors. High-risk neuroblastoma is an aggressive pediatric solid tumor that expresses cell-surface GPC2 and GD2 with a tumor microenvironment infiltrated by CD16a-expressing innate immune cells. Here we engineer T-cells to express a GPC2-directed CAR and simultaneously secrete a bispecific innate immune cell engager (BiCE) targeting both GD2 and CD16a.

A reciprocal relationship between mitochondria and lipid peroxidation determines the chondrocyte intracellular redox environment.

In orthopedic research, many studies have applied vitamin E as a protective antioxidant or used tert-butyl hydroperoxide to induce oxidative injury to chondrocytes. These studies often support the hypothesis that joint pathology causes oxidative stress and increased lipid peroxidation that might be prevented with lipid antioxidants to improve cell survival or function and joint health; however, lipid antioxidant supplementation was ineffective against osteoarthritis in clinical trials and animal data have been equivocal. Moreover, increased circulating vitamin E is associated with increased rates of osteoarthritis.

JAK Inhibitors in Cytokine Storm Syndromes.

Cytokine storm syndromes (CSSs) comprise a group of severe and often fatal hyperinflammatory conditions driven by the overproduction of pro-inflammatory cytokines by activated cells of the immune system. Many of the CSS-associated cytokines mediate their downstream effects by signaling through the Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). In addition, several of these cytokines are produced downstream of JAK/STAT pathway activation.

Elp1 function in placode-derived neurons is critical for proper trigeminal ganglion development.

Background: The trigeminal nerve is the largest cranial nerve and functions in somatosensation. Cell bodies of this nerve are positioned in the trigeminal ganglion, which arises from the coalescence of neural crest and placode cells. While this dual cellular origin has been known for decades, the molecular mechanisms controlling trigeminal ganglion development remain obscure.

ECHO+: An Innovative Technology-Enabled Collaborative Learning and Quality Improvement Program Strengthening Rural Primary Care in Arkansas, West Virginia, and Oklahoma.

In this paper, we describe the Project Extension for Community Healthcare Outcomes+ (ECHO+) model and evaluation plan for incorporating changes to primary care delivery, improving patient and clinician outcomes, and making long-term system improvements.

Cortical gyrification in women and men and the (missing) link to prenatal androgens.

Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex-specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range.

Intrapulmonary administration of recombinant activated factor VII in pediatric, adolescent, and young adult oncology and hematopoietic cell transplant patients with pulmonary hemorrhage.

Introduction: Diffuse alveolar hemorrhage (DAH) is a devastating disease process with 50-100% mortality in oncology and hematopoietic cell transplant (HCT) recipients. High concentrations of tissue factors have been demonstrated in the alveolar wall in acute respiratory distress syndrome and DAH, along with elevated levels of tissue factor pathway inhibitors. Activated recombinant factor VII (rFVIIa) activates the tissue factor pathway, successfully overcoming the tissue factor pathway inhibitor (TFPI) inhibition of activation of Factor X.

An examination of the association between infant non-nutritive suck and developmental outcomes at 12 months.

Objective: To determine the association between infant non-nutritive suck (NNS) dynamics at 3 months and developmental outcomes at 12 months of age in full-term infants. We hypothesized that infants with more mature NNS at 3 months, as evidence by shorter burst duration, fewer cycles per burst, cycles per minute, higher amplitude, and more bursts, would have higher (better) scores on the developmental outcomes at 12 months.

Methods: This was a prospective study that utilized objective and self-report measures.

Temporal Tracking of Plasma Cells Using J-chain CreERT2 Reporter System.

Plasma cells (PCs) are essential for humoral immunity, as they are responsible for the production of antibodies and contribute to immunological memory. Despite their importance, differentiating between long-lived and short-lived PCs remains a challenge due to a lack of specific markers to distinguish these populations. Addressing this gap, our study introduces a novel J-chain CreERT2 GFP allele (IgJ) for precise genetic studies of PCs.

Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation.

Primary hemophagocytic lymphohistiocytosis (pHLH) is a life-threatening hyperinflammatory syndrome that develops mainly in patients with genetic disorders of lymphocyte cytotoxicity and X-linked lymphoproliferative syndromes. Previous studies with etoposide-based treatment followed by hematopoetic stem cell transplantation (HSCT) resulted in 5-year survival of 50% to 59%. Contemporary data are lacking.

Preferences for telehealth: A qualitative study with people accessing a new mental health service.

Objectives: To examine preferences for telehealth versus in-person services for people who sought mental health support from an unfamiliar service during the COVID-19 pandemic and to identify the factors that influenced these preferences.

Methods: Data are drawn from semi-structured interviews with 45 participants (32 people who accessed mental health services, 7 informal support people, and 6 people who accessed services themselves as well as identifying as informal supports). Data relating to experiences of telehealth, comparisons with in-person services and preferences were coded inductively and analysed using qualitative content analysis.

Human antibody V domains targeting uPAR as candidate therapeutics for cancers.

The high expression of uPAR has been linked to tumor progression, invasion, and metastasis in several types of cancer. Such overexpression of uPAR makes it a potential target for immunotherapies across common cancers such as breast, colorectal, lung, ovarian cancer, and melanoma. In our study, two high-affinity and specific human V domain antibody candidates, designed as clones 3 and 115, were isolated from a phage-displayed human V antibody library.