A pen device for injection of recombinant human growth hormone: a European usability engineering study.

Objective: The Aluetta™ reusable pen device and instructions for use (IFU) for growth hormone (r-hGH; Saizen®, Merck KGaA, Darmstadt, Germany) administration were tested for Human-Factors Usability, to ensure it could be used safely and effectively by the intended users in the intended use environment.

Research Design And Methods: Usability testing was conducted under simulated conditions in three groups of participants: pediatric or adult patients with growth hormone deficiency (GHD), participants without GHD, and healthcare professionals (HCPs). The testing comprised a 45-minute training session, a 2-hour testing session, and a participant-feedback session.

Mutagenicity- and pollutant-emission factors of pellet-fueled gasifier cookstoves: Comparison with other combustion sources.

Emissions from solid-fuel burning cookstoves are associated with 3 to 4 million premature deaths annually and contribute significantly to impacts on climate. Pellet-fueled gasifier stoves have some emission factors (EFs) approaching those of gas-fuel (liquid petroleum gas) stoves; however, their emissions have not been evaluated for biological effects. Here we used a new International Organization for Standardization (ISO) testing protocol to determine pollutant- and mutagenicity-EFs for a stove designed for pellet fuel, the Mimi Moto, and for two other forced-draft stoves, Xunda and Philips HD4012, burning pellets of hardwood or peanut hulls.

MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer.

In microorganisms, evolutionarily conserved mechanisms facilitate adaptation to harsh conditions through stress-induced mutagenesis (SIM). Analogous processes may underpin progression and therapeutic failure in human cancer. We describe SIM in multiple in vitro and in vivo models of human cancers under nongenotoxic drug selection, paradoxically enhancing adaptation at a competing intrinsic fitness cost.

Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response.

Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): results in the pre-specified subgroup with heart failure.

Aims: The AMBER trial demonstrated that concomitant use of patiromer enabled the more persistent use of spironolactone by reducing the risk of hyperkalaemia in patients with resistant hypertension and advanced chronic kidney disease. We report herein the pre-specified subgroup analysis in patients with heart failure (HF).

Methods And Results: Participants were randomly assigned (1:1) to receive either placebo or patiromer (8.

Multiplex digital spatial profiling of proteins and RNA in fixed tissue.

Digital Spatial Profiling (DSP) is a method for highly multiplex spatial profiling of proteins or RNAs suitable for use on formalin-fixed, paraffin-embedded (FFPE) samples. The approach relies on (1) multiplexed readout of proteins or RNAs using oligonucleotide tags; (2) oligonucleotide tags attached to affinity reagents (antibodies or RNA probes) through a photocleavable (PC) linker; and (3) photocleaving light projected onto the tissue sample to release PC oligonucleotides in any spatial pattern across a region of interest (ROI) covering 1 to ~5,000 cells. DSP is capable of single-cell sensitivity within an ROI using the antibody readout, with RNA detection feasible down to ~600 individual mRNA transcripts.

Impact of checkpoint blockade on cancer vaccine-activated CD8+ T cell responses.

Immune and molecular profiling of CD8 T cells of patients receiving DC vaccines expressing three full-length melanoma antigens (MAs) was performed. Antigen expression levels in DCs had no significant impact on T cell or clinical responses. Patients who received checkpoint blockade before DC vaccination had higher baseline MA-specific CD8 T cell responses but no evidence for improved functional responses to the vaccine.

It is not just about the frontal plane: sagittal parameters impact curve progression in AIS patients undergoing brace treatment.

Study Design: Retrospective cohort study.

Objectives: The purpose of this study was to explore the association between pre-brace and in-brace sagittal parameters and curve progression. To date, there has been no published research focused on spinopelvic sagittal parameters and bracing outcomes in AIS.

Anxiety and Stress Alter Decision-Making Dynamics and Causal Amygdala-Dorsolateral Prefrontal Cortex Circuits During Emotion Regulation in Children.

Background: Anxiety and stress reactivity are risk factors for the development of affective disorders. However, the behavioral and neurocircuit mechanisms that potentiate maladaptive emotion regulation are poorly understood. Neuroimaging studies have implicated the amygdala and dorsolateral prefrontal cortex (DLPFC) in emotion regulation, but how anxiety and stress alter their context-specific causal circuit interactions is not known.

Assessment of Language Abilities in Minority Adolescents and Young Adults With Autism Spectrum Disorder and Extensive Special Education Needs: A Pilot Study.

Purpose Little is known about the language abilities of adolescents and young adults with autism spectrum disorder (ASD) despite the importance of language in their other life outcomes. Even less is known about the language abilities of racial/ethnic minorities with ASD and extensive special education needs. These gaps limit our understanding of adolescents and young adults with ASD.

Ratcheting quasi-ballistic electrons in silicon geometric diodes at room temperature.

Ratcheting effects play an important role in systems ranging from mechanical socket wrenches to biological motor proteins. The underlying principle is to convert a fluctuating, unbiased force into unidirectional motion. Here, we report the ratcheting of electrons at room temperature using a semiconductor nanowire with precisely engineered asymmetry.

Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death.

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Effects of Delayed Newborn Bathing on Breastfeeding, Hypothermia, and Hypoglycemia.

Objective: To determine whether delaying the newborn bath by 24 hours increases the prevalence of breastfeeding initiation and exclusive breastfeeding at discharge in healthy full-term and late preterm newborns (34 0/7-36 6/7 weeks gestation) and to examine the effect of delayed newborn bathing on the incidences of hypothermia and hypoglycemia.

Design: Pre-post implementation, retrospective, cohort study.

Setting: Provincial children's hospital with an average of 2,500 births per year.

Potential for Resting-State fMRI of the Amygdala in Elucidating Neural Mechanisms of Adaptive Self-Regulatory Strategies: A Systematic Review.

Evolutionary-developmental theories consider the evolved mechanisms underlying adaptive behavioral strategies shaped in response to early environmental cues. Identifying neural mechanisms mediating processes of conditional adaptation in humans is an active area of research. Resting-state functional magnetic resonance imaging (RS-fMRI) captures functional connectivity theorized to represent the underlying functional architecture of the brain.

B cells and tertiary lymphoid structures promote immunotherapy response.

Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity, although these have been less well-studied in ICB treatment.

Tertiary lymphoid structures improve immunotherapy and survival in melanoma.

Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored.

Crystal structure and Hirshfeld surface analysis of ()-3-(3-iodo-phen-yl)-1-(4-iodo-phen-yl)prop-2-en-1-one.

The title compound, CHIO, is a halogenated chalcone formed from two iodine substituted rings, one -substituted and the other -substituted, linked through a prop-2-en-1-one spacer. In the mol-ecule, the mean planes of the 3-iodo-phenyl and the 4-iodo-phenyl groups are twisted by 46.51 (15)°.

Effortful Control Development in the Face of Harshness and Unpredictability.

Using psychosocial acceleration theory, this multimethod, multi-reporter study examines how early adversity adaptively shapes the development of a self-regulation construct: effortful control. Investigation of links between early life harshness and unpredictability and the development of effortful control could facilitate a nuanced understanding of early environmental effects on cognitive and social development. Using the Building Strong Families national longitudinal data set, aspects of early environmental harshness and early environmental unpredictability were tested as unique predictors of effortful control at age 3 using multiple regression.

Mothers' perspectives on challenging behaviours in their children with fragile X syndrome.

Background: Individuals with intellectual and developmental disabilities are more likely to engage in problem behaviours than peers with typical development. The purpose of this study was to provide descriptive and qualitative information about problem behaviours in children with fragile X syndrome (FXS) and how families respond to these behaviours.

Method: We examined interview responses from 53 mothers of 9-year-old children with FXS.

Phase Ib/II trial testing combined radiofrequency ablation and ipilimumab in uveal melanoma (SECIRA-UM).

Approximately, 50% of patients with uveal melanoma develop distant metastasis for which no standard therapy is established. In contrast to cutaneous melanoma, the anti-CTLA-4 antibody ipilimumab showed no clinical activity in uveal melanoma. Liver directed therapies improve local control, but fail to show overall survival (OS) benefit.

Partial FMRP expression is sufficient to normalize neuronal hyperactivity in Fragile X neurons.

Fragile X syndrome (FXS) is the most common genetic form of intellectual disability caused by a CGG repeat expansion in the 5'-UTR of the Fragile X mental retardation gene FMR1, triggering epigenetic silencing and the subsequent absence of the protein, FMRP. Reactivation of FMR1 represents an attractive therapeutic strategy targeting the genetic root cause of FXS. However, largely missing in the FXS field is an understanding of how much FMR1 reactivation is required to rescue FMRP-dependent mutant phenotypes.