ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma.

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG.

Cellular density and variability in laryngeal and pharyngeal squamous cell carcinoma using confocal laser endomicroscopy.

Objective: Confocal laser endomicroscopy (CLE) allows the visualization of epithelium in a thousand-fold magnification. This study analyzes the architectural differences at the cellular level of the mucosa and squamous cell carcinoma (SCC).

Patients And Methods: A total of 60 CLE sequences recorded in 5 patients with SCC undergoing laryngectomy between October 2020 and February 2021 were analyzed.

Electromagnetic Induction for Treatment of Unspecific Back Pain: A Prospective Randomized Sham-Controlled Clinical Trial.

Objective: To evaluate the effects of high-energy pulsed electromagnetic fields on unspecific back pain.

Methods: A prospective, randomized, sham-controlled clinical trial with repeated measurements was performed. The study included 5 visits (V0 to V4) with 3 interventions during V1, V2 and V3.

Gender minority stress in transgender people: a major role for social network.

Background: Gender minority individuals, on average, experience higher rates of mental health problems. Mounting work suggests that gender minority stress (GMS) contributes to mental health outcomes in transgender/gender-nonconforming individuals.

Aim: We assessed whether GMS decreased in transgender people after initiating gender-affirming hormone therapy (GAHT), and we identified social predictors and hormonal associations for GMS at 2 time points.

Evaluating preclinical evidence for clinical translation in childhood brain tumours: Guidelines from the CONNECT, PNOC, and ITCC brain networks.

Clinical outcomes for many childhood brain tumours remain poor, despite our increasing understanding of the underlying disease biology. Advances in molecular diagnostics have refined our ability to classify tumour types and subtypes, and efforts are underway across multiple international paediatric neuro-oncology consortia to take novel biological insights in the worst prognosis entities into innovative clinical trials. Whilst for the first time we are designing such studies on the basis of disease-specific biological data, the levels of preclincial evidence in appropriate model systems on which these trials are initiated is still widely variable.

How to measure children's feet: 3D foot scanning compared with established 2D manual or digital methods.

Background: In infants and young children, a wide heterogeneity of foot shape is typical. Therefore, children, who are additionally influenced by rapid growth and maturation, are a very special cohort for foot measurements and the footwear industry. The importance of foot measurements for footwear fit, design, as well as clinical applications has been sufficiently described.

Yeast Puf3p-mediated mRNA decay is regulated by carbon source-specific differential interaction of Puf3p with Pop2p and Yak1p.

Puf3p regulates the stability of nuclear-encoded mRNAs acting in mitochondrial biogenesis and function in Saccharomyces cerevisiae. This work identifies the phosphorylation of Pop2p, a component of the deadenylase complex, as being critical for adapting Puf3p-mediated mRNA decay upon carbon source alterations. We demonstrate that the Puf3p-Pop2p association diminishes in mitochondria-reliant conditions and establish Yak1p, a kinase that phosphorylates Pop2p at threonine 97, as a new player in Puf3p-mediated regulation of mRNA decay.

History and current status of clinical studies using human pluripotent stem cells.

The Human Pluripotent Stem Cell Registry established a database of clinical studies using human pluripotent stem cells (PSCs) as starting material for cell therapies. Since 2018, we have observed a switch toward human induced pluripotent stem cells (iPSCs) from human embryonic stem cells. However, rather than using iPSCs for personalized medicines, allogeneic approaches dominate.

Multi-omic and spatial dissection of immunotherapy response groups in non-small cell lung cancer.

The composition and activation status of the cellular milieu contained within the tumour microenvironment (TME) is becoming increasingly recognized as a driving factor for immunotherapy response. Here, we employed multiplex immunohistochemistry (mIHC), and digital spatial profiling (DSP) to capture the targeted immune proteome and transcriptome of tumour and TME compartments from an immune checkpoint inhibitor (ICI)-treated (n = 41) non-small cell lung cancer (NSCLC) patient cohort. We demonstrate by mIHC that the interaction of CD68 macrophages with PD1 , FoxP3 cells is enriched in ICI refractory tumours (p = 0.

Zfp580 inactivation as a new therapeutic target to enhance recovery after stroke in mice.

Paracrine cerebral Interleukin 6 (Il6) is relevant for stroke recovery, but systemic Il6 elevation may worsen outcome. Hence, paracrine Il6 response modulation within the neurovascular unit has emerged as an attractive therapeutic approach. Lithium modulates Il6 responses and improves stroke outcome.

Assessing arthropod diversity metrics derived from stream environmental DNA: spatiotemporal variation and paired comparisons with manual sampling.

Background: Benthic invertebrate (BI) surveys have been widely used to characterize freshwater environmental quality but can be challenging to implement at desired spatial scales and frequency. Environmental DNA (eDNA) allows an alternative BI survey approach, one that can potentially be implemented more rapidly and cheaply than traditional methods.

Methods: We evaluated eDNA analogs of BI metrics in the Potomac River watershed of the eastern United States.

Precision based approach to tailoring radiotherapy in the multidisciplinary management of pediatric central nervous system tumors.

Modern day survivorship from childhood malignancies is estimated to be over 80%. However, central nervous system tumors remain the leading cause of cancer mortality in children and is the most common solid tumor in this population. Improved survivorship is, in part, a result of improved multidisciplinary care, often with a combination of surgery, radiation therapy, and systemic therapy.

The influence of obstructive sleep apnea and continuous positive airway pressure on the nasal microbiome.

Objective: The aim of this study was to investigate the influence of obstructive sleep apnea and continuous positive airway pressure on the nasal microbiome.

Patients And Methods: Endonasal swabs from the olfactory groove of 22 patients with moderate and severe obstructive sleep apnea (OSA) and a control group of 17 healthy controls were obtained at the Department of Otorhinolaryngology of the Friedrich-Alexander-Universität Erlangen-Nürnberg. 16S rRNA gene sequencing was performed to further evaluate the endonasal microbiome.

A scoping review of intimate partner violence in hospitalized patients.

Background: Despite the high prevalence and significant health effects of intimate partner violence (IPV), little is known about its associations with hospitalization.

Objective: To perform a scoping review of how IPV impacts hospitalization rates, characteristics, and outcomes in adult patients.

Data Sources: A search of four databases (MEDLINE, Embase, Web of Science, and CINAHL) using a combination of terms including hospitalized patients and IPV revealed 1608 citations.

mRNA aggregates harness danger response for potent cancer immunotherapy.

Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of 'onion-like' multi-lamellar RNA-LP aggregates (LPA).

Fibroblastic reticular cells provide a supportive niche for lymph node-resident macrophages.

The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models.

The Fragile X Protein Family in Amyotrophic Lateral Sclerosis.

The fragile X protein (FXP) family comprises the multifunctional RNA-binding proteins FMR1, FXR1, and FXR2 that play an important role in RNA metabolism and regulation of translation, but also in DNA damage and cellular stress responses, mitochondrial organization, and more. FMR1 is well known for its implication in neurodevelopmental diseases. Recent evidence suggests substantial contribution of this protein family to amyotrophic lateral sclerosis (ALS) pathogenesis.

Splenic stromal niches in homeostasis and immunity.

The spleen is a gatekeeper of systemic immunity where immune responses against blood-borne pathogens are initiated and sustained. Non-haematopoietic stromal cells construct microanatomical niches in the spleen that make diverse contributions to physiological spleen functions and regulate the homeostasis of immune cells. Additional signals from spleen autonomic nerves also modify immune responses.

Effect of postoperative systemic prednisolone on short-term and long-term outcomes in chronic rhinosinusitis with nasal polyps: A multi-centered randomized clinical trial.

Introduction: The objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures.

Methods: This was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids.

Prevalence and Causes of Diagnostic Errors in Hospitalized Patients Under Investigation for COVID-19.

Background: The COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs).

Pruritus in cutaneous graft-versus-host disease: A systematic review.

Pruritus is a common symptom of cutaneous graft-versus-host disease (GVHD) following haematopoietic stem cell transplantation (HSCT). However, little is known about its prevalence, pathophysiology, perceptual characteristics, impact on quality of life and response to antipruritic therapies. The aim of this review was to determine the current knowledge on pruritus in cutaneous GVHD.

What works in medication reconciliation: an on-treatment and site analysis of the MARQUIS2 study.

Background: The second Multicenter Medication Reconciliation Quality Improvement Study demonstrated a marked reduction in medication discrepancies per patient. The aim of the current analysis was to determine the association of patient exposure to each system-level intervention and receipt of each patient-level intervention on these results.

Methods: This study was conducted at 17 North American Hospitals, the study period was 18 months per site, and sites typically adopted interventions after 2-5 months of preintervention data collection.