Current progress of cerebral organoids for modeling Alzheimer's disease origins and mechanisms.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease that has emerged as a leading risk factor for dementia associated with increasing age. Two-dimensional (2D) cell culture and animal models, which have been used to analyze AD pathology and search for effective treatments for decades, have significantly contributed to our understanding of the mechanism of AD. Despite their successes, 2D and animal models can only capture a fraction of AD mechanisms due to their inability to recapitulate human brain-specific tissue structure, function, and cellular diversity.

Vascular stiffening in aging females with a hypertension-induced HIF2A gain-of-function mutation.

Pulmonary arterial hypertension (PAH) is more prevalent in females than males; the causes of this sex difference have not been adequately explored. Gain-of-function (GOF) mutations in hypoxia-inducible factor 2α (HIF2A) lead to PAH and thrombotic consequences in patients and mice. Additionally, multiple emerging studies suggest that elevated systemic arterial stiffening (SAS) occurs in PAH; this could have critical prognostic value.

Development of nintedanib nanosuspension for inhaled treatment of experimental silicosis.

Silicosis is an irreversible and progressive fibrotic lung disease caused by massive inhalation of crystalline silica dust at workplaces, affecting millions of industrial workers worldwide. A tyrosine kinase inhibitor, nintedanib (NTB), has emerged as a potential silicosis treatment due to its inhibitory effects on key signaling pathways that promote silica-induced pulmonary fibrosis. However, chronic and frequent use of the oral NTB formulation clinically approved for treating other fibrotic lung diseases often results in significant side effects.

Inclusion of hearing and vision impairments in cognitive training interventions.

Introduction: Cognitive training can potentially reduce risk of cognitive decline and dementia in older adults. To support implementation of cognitive training in the broader population of older adults, it is critical to evaluate intervention implementation and efficacy among representative samples, particularly those at highest risk of cognitive decline. Hearing and vision impairments are highly prevalent among older adults and confer increased risk of cognitive decline/dementia.

Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy with a high rate of recurrence and a dismal 5-year survival rate. Contributing to the poor prognosis of PDAC is the lack of early detection, a complex network of signaling pathways and molecular mechanisms, a dense and desmoplastic stroma, and an immunosuppressive tumor microenvironment. A recent shift toward a neoadjuvant approach to treating PDAC has been sparked by the numerous benefits neoadjuvant therapy (NAT) has to offer compared with upfront surgery.

Use of Elamipretide in patients assigned treatment in the compassionate use program: Case series in pediatric patients with rare orphan diseases.

Several mitochondrial diseases are caused by pathogenic variants that impair membrane phospholipid remodeling, with no FDA-approved therapies. Elamipretide targets the inner mitochondrial membrane where it binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and ATP production. In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age.

Acute vasoreactivity testing during right heart catheterization in chronic thromboembolic pulmonary hypertension: Results from the pulmonary vascular disease phenomics study.

Chronic thromboembolic pulmonary hypertension (CTEPH) is believed to involve both vascular obstruction and vasoconstriction; hence, pulmonary vasodilators such as riociguat may be beneficial. Acute vasoreactivity testing (AVT) is seldom performed routinely in CTEPH patients, so there is limited understanding of the frequency and significance of an acute vasodilator response. Systematic vasodilator testing with oxygen (O) and oxygen plus inhaled nitric oxide (O + iNO) was performed as part of the Pulmonary Vascular Disease Omics (PVDOMICS) NHLBI project, providing an opportunity to examine AVT responses in CTEPH.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Weight changes following antidiabetic mediation use: Real-world evidence from health system data.

Objective: Newer antidiabetic medications such as sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) result in weight loss in clinical trials. However, the real-world effectiveness remains unclear. The magnitude of weight change associated with antidiabetic medication using real-world data was examined.

Clinical significance of pulmonary hypertension in interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute's innovative drug development initiative-Group 3 pulmonary hypertension.

Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area.

Thromboprophylaxis in people hospitalized with COVID-19: Assessing intermediate or standard doses in a retrospective cohort study.

Background And Objectives: Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID-19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses.

Methods: We studied electronic health records from 50 091 adults hospitalized with COVID-19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.

Downregulating EVA1C exerts the potential to promote neuron growth after neonatal hypoxic-ischemic encephalopathy injury associated with alternative splicing.

Neonatal hypoxic-ischemic encephalopathy (NHIE) is one of the major diseases in newborns during the perinatal stage, which globally is the main reason for children's morbidity and mortality. However, the mechanism of NHIE still remains poorly clear. In this study, the 7-day-old rats were subjected to hypoxic-ischemia (HI), then brain damage was detected.

New weapons to fight malaria transmission: A historical view.

The stagnation of our fight against malaria in recent years, mainly due to the development of mosquito insecticide resistance, argues for the urgent development of new weapons. The dramatic evolution of molecular tools in the last few decades led to a better understanding of parasite-mosquito interactions and coalesced in the development of novel tools namely, mosquito transgenesis and paratransgenesis. Here we provide a historical view of the development of these new tools and point to some remaining challenges for their implementation in the field.

Age-specific differences in the magnitude of malaria-related anemia during low and high malaria seasons in rural Zambian children.

Background: Malaria causes anemia by destruction of red blood cells and inhibition of erythropoiesis.

Objective: We assessed whether the magnitude of the malaria-specific effect on anemia differs by age, during low and high malaria seasons.

Method: In rural Zambian children participating in a pro-vitamin A efficacy trial, we estimated differences in the prevalence of anemia (defined as hemoglobin < 110 g/L for children < 60 months.

CAR-T-OPENIA: Chimeric antigen receptor T-cell therapy-associated cytopenias.

Chimeric antigen receptor (CAR) T-cell is the most recent version in the evolution of cellular therapy with promising responses, which has revolutionized the management of some hematological malignancies in the current times. As the clinical use has progressed rather rapidly since the first approval in 2017, toxicities beyond cytokine release syndrome and immune effector cell-associated neurological syndrome have surfaced. Cytopenias are common in <30 days ("early"), 30-90 days ("short-term") as well as >90 days ("prolonged"); and have clinical implications to patient care as well as resource utilization.

Two diverse carriers are better than one: A case study in α-particle therapy for prostate specific membrane antigen-expressing prostate cancers.

Partial and/or heterogeneous irradiation of established (i.e., large, vascularized) tumors by α-particles that exhibit only a 4-5 cell-diameter range in tissue, limits the therapeutic effect, since regions not being hit by the high energy α-particles are likely not to be killed.

Proteomics discovery of pulmonary hypertension biomarkers: Insulin-like growth factor binding proteins are associated with disease severity.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by sustained elevations of pulmonary artery pressure. To date, we lack circulating, diagnostic, and prognostic markers that correlate to clinical and functional parameters. In this study, we performed mass spectrometry-based proteomics analysis to identify circulating biomarkers of PAH.

Hepatoma-derived growth factor is associated with pulmonary vascular remodeling and PAH disease severity and survival.

Hepatoma-derived growth factor (HDGF) was previously shown to be associated with increased mortality in a small study of idiopathic and connective tissue disease-associated pulmonary arterial hypertension (PAH). In this study, we measured serum HDGF levels in a large multicenter cohort (total 2017 adult PAH-Biobank enrollees), we analyzed the associations between HDGF levels and various clinical measures using linear or logistic regression models. Higher HDGF levels were found to be significantly associated with worse pulmonary hemodynamics, prostacyclin treatment; among PAH subtypes, higher HDGF levels were most associated with portopulmonary hypertension (beta = 0.

Ventricular mass discriminates pulmonary arterial hypertension as redefined at the Sixth World Symposium on Pulmonary Hypertension.

Cardiac magnetic resonance (CMR) measures of right ventricular (RV) mass, volumes, and function have diagnostic and prognostic value in pulmonary arterial hypertension (PAH). We hypothesized that RV mass-based metrics would discriminate incident PAH as redefined by the lower mean pulmonary arterial pressure (mPAP) threshold of >20 mmHg at the Sixth World Symposium on Pulmonary Hypertension (6th WSPH). Eighty-nine subjects with suspected PAH underwent CMR imaging, including 64 subjects with systemic sclerosis (SSc).

Environmental air pollution and chronic rhinosinusitis: A systematic review.

Objective: Chronic rhinosinusitis (CRS) is a highly prevalent and burdensome disease. The pathophysiology is not fully elucidated, but environmental pollutants have been suggested to impact the inflammatory component of the disease process. This review aims to summarize the role of environmental pollution in CRS onset and disease severity.

Applications of ambient ionization mass spectrometry in 2021: An annual review.

Ambient ionization mass spectrometry (AIMS) has revolutionized the field of analytical chemistry, enabling the rapid, direct analysis of samples in their native state. Since the inception of AIMS almost 20 years ago, the analytical community has driven the further development of this suite of techniques, motivated by the plentiful advantages offered in addition to traditional mass spectrometry. Workflows can be simplified through the elimination of sample preparation, analysis times can be significantly reduced and analysis remote from the traditional laboratory space has become a real possibility.