The intersection of queer identity and psychedelics has not been thoroughly explored by the research community, historically or in the present day. With growing access to legal psychedelic therapies, it is essential that queer psychedelic experiences are understood sufficiently by clinicians in order to provide the most safe and effective care possible. Psychedelics and queerness are intricately related, and there is strong interest in the use of psychedelics for healing and identity development among queer populations.
View Article and Find Full Text PDFIn recent years, machine learning has transformed many aspects of the drug discovery process, including small molecule design, for which the prediction of bioactivity is an integral part. Leveraging structural information about the interactions between a small molecule and its protein target has great potential for downstream machine learning scoring approaches but is fundamentally limited by the accuracy with which protein-ligand complex structures can be predicted in a reliable and automated fashion. With the goal of finding practical approaches to generating useful kinase-inhibitor complex geometries for downstream machine learning scoring approaches, we present a kinase-centric docking benchmark assessing the performance of different classes of docking and pose selection strategies to assess how well experimentally observed binding modes are recapitulated in a realistic cross-docking scenario.
View Article and Find Full Text PDFBackground: Over the past two decades, the development of internet-based treatments for adolescents with anxiety and depressive disorders has advanced rapidly. To date, adolescents' preferences and perceived barriers for internet-based treatment remain largely unknown, especially in clinical samples. Therefore, this study explored the preferences and perceived barriers of adolescents with anxiety or depression regarding internet-based treatment.
View Article and Find Full Text PDFMetal oxide nanoparticles (MONP/s) induce DNA damage, which is influenced by their physicochemical properties. In this study, the high-throughput CometChip and micronucleus (MicroFlow) assays were used to investigate DNA and chromosomal damage in mouse lung epithelial cells induced by nano and bulk sizes of zinc oxide, copper oxide, manganese oxide, nickel oxide, aluminum oxide, cerium oxide, titanium dioxide, and iron oxide. Ionic forms of MONPs were also included.
View Article and Find Full Text PDFNAA15 is a member of the NatA N-terminal acetyltransferase complex, which also includes the NAA10 enzymatic sub-unit. Individuals with variants in the coding region develop -related neurodevelopmental syndrome, which presents with a wide array of manifestations that affect the heart, brain, musculoskeletal system, and behavioral and cognitive development. We tracked a cohort of 27 participants (9 females and 18 males) over time, each with a pathogenic variant, and administered the Vineland-3 assessment to assess their adaptive functioning.
View Article and Find Full Text PDFLymphatics participate in reverse cholesterol transport, and their presence in the arterial wall of the great vessels and prior experimental results suggest their possible role in the development of atherosclerosis. The aim of this study was to characterize the lymphatic vasculature of the arterial wall in atherosclerosis. Tissue sections and tissue-cleared aortas of wild-type mice unveiled significant differences in the density of the arterial lymphatic network throughout the arterial tree.
View Article and Find Full Text PDFOgden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011, and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time.
View Article and Find Full Text PDFBackground: Depressed patients who have become victim of violence are prone to revictimization. However, no evidence-based interventions aimed at reducing revictimization in this group exist.
Methods: This multicenter randomized controlled trial evaluated the effectiveness of an internet-based emotion regulation training (iERT) added to TAU in reducing revictimization, emotion dysregulation, and depressive symptoms in recently victimized, depressed patients compared to TAU alone.
Objective: Comorbid post-traumatic stress disorder in patients with anorexia nervosa may negatively affect the course of anorexia nervosa treatment, which is already challenging. There are currently no guidelines or recommendations on concurrent treatment approaches for both anorexia nervosa and post-traumatic stress disorder. This systematic scoping review aims to explore the feasibility, acceptability and effectiveness of psychological trauma-focused treatment concurrently offered to underweight patients receiving anorexia nervosa treatment.
View Article and Find Full Text PDFRecent studies have described the importance of lymphatics in numerous organ-specific physiological and pathological processes. The role of meningeal lymphatics in various neurological and cerebrovascular diseases has been suggested. It has also been shown that these structures develop postnatally and are altered by aging and that the vascular endothelial growth factor C (VEGFC)/ vascular endothelial growth factor receptor 3 (VEGFR3) signaling plays an essential role in the development and maintenance of them.
View Article and Find Full Text PDFIn recent years machine learning has transformed many aspects of the drug discovery process including small molecule design for which the prediction of the bioactivity is an integral part. Leveraging structural information about the interactions between a small molecule and its protein target has great potential for downstream machine learning scoring approaches, but is fundamentally limited by the accuracy with which protein:ligand complex structures can be predicted in a reliable and automated fashion. With the goal of finding practical approaches to generating useful kinase:inhibitor complex geometries for downstream machine learning scoring approaches, we present a kinase-centric docking benchmark assessing the performance of different classes of docking and pose selection strategies to assess how well experimentally observed binding modes are recapitulated in a realistic cross-docking scenario.
View Article and Find Full Text PDFOrgan-specific lymphatics are essential for the maintenance of healthy organ function and lymphatic dysfunction can lead to the development of various diseases. However, the precise role of those lymphatic structures remains unknown, mainly due to inefficient visualization techniques. Here, we present an efficient approach to visualizing organ-specific lymphatic growth.
View Article and Find Full Text PDFBackground: Dysfunctional emotion regulation (ER) is associated with symptoms of depression and anxiety in adolescents. This pilot study aimed to examine the acceptability and feasibility of a guided internet-based emotion regulation training (ERT) added to cognitive behavioral therapy (CBT). Furthermore, we aimed to examine the feasibility of the randomized study design and to provide a first estimate of the effectiveness of CBT + ERT compared with CBT alone in adolescents with depressive or anxiety disorders.
View Article and Find Full Text PDFBackground: During adolescence, depressive and anxiety disorders are among the most common mental health disorders. Both disorders tend to persist, are predictive for other mental disorders, and are associated with severe impairment in diverse areas. Although Cognitive Behavioral Therapy (CBT) has proven to be an effective treatment, a considerable number of adolescents do not respond to CBT and residual symptoms often remain.
View Article and Find Full Text PDFPrioritizing molecules for synthesis is a key role of computational methods within medicinal chemistry. Multiple tools exist for ranking molecules, from the cheap and popular molecular docking methods to more computationally expensive molecular-dynamics (MD)-based methods. It is often questioned whether the accuracy of the more rigorous methods justifies the higher computational cost and associated calculation time.
View Article and Find Full Text PDFBackground: Depressed patients are prone to violent victimization, and patients who were victimized once are at increased risk to fall victim to violence again. However, knowledge on the context of victimization in depressed patients is lacking, and research identifying targets for prevention is urgently needed.
Methods: This cross-sectional study explored context characteristics, disclosure rates and gender differences regarding violent victimization in 153 recently victimized depressed patients.
As the world continues to face uncertainty due to COVID-19, there is concern for adolescent wellbeing as they attempt to cope with changes to their education and social interactions. Considering the trade-offs between physical distancing and virtual education versus in-person instruction may be particularly pertinent to understanding adolescent loneliness and worries surrounding COVID-19 and their academics. Adolescents ( = 1,708; age = 12.
View Article and Find Full Text PDFThe U.S. is struggling with dual crises of chronic pain and opioid overdoses.
View Article and Find Full Text PDFPIP4K2A is an insufficiently studied type II lipid kinase that catalyzes the conversion of phosphatidylinositol-5-phosphate (PI5P) into phosphatidylinositol 4,5-bisphosphate (PI4,5P). The involvement of PIP4K2A/B in cancer has been suggested, particularly in the context of p53 mutant/null tumors. PIP4K2A/B depletion has been shown to induce tumor growth inhibition, possibly due to hyperactivation of AKT and reactive oxygen species-mediated apoptosis.
View Article and Find Full Text PDFSMYD3 (SET and MYND domain-containing protein 3) is a protein lysine methyltransferase that was initially described as an H3K4 methyltransferase involved in transcriptional regulation. SMYD3 has been reported to methylate and regulate several nonhistone proteins relevant to cancer, including mitogen-activated protein kinase kinase kinase 2 (MAP3K2), vascular endothelial growth factor receptor 1 (VEGFR1), and the human epidermal growth factor receptor 2 (HER2). In addition, overexpression of SMYD3 has been linked to poor prognosis in certain cancers, suggesting SMYD3 as a potential oncogene and attractive cancer drug target.
View Article and Find Full Text PDFAims: This systematic review and meta-analysis assessed the effectiveness of digital interventions addressing depressive symptoms and alcohol use simultaneously among people with co-occurring depression and problematic alcohol use.
Methods: Seven databases were searched for trials evaluating digital interventions aimed at depression and alcohol use. Random-effects meta-analyses were conducted to pool effects on depressive symptoms and alcohol use up to 3-month and 6-month follow-up.
Purpose: 5' adenosine monophosphate-activated kinase (AMPK) is an essential regulator of cellular energy homeostasis and has been associated with different pathologies, including cancer. Precisely defining the biological role of AMPK necessitates the availability of a potent and selective inhibitor.
Methods: High-throughput screening and chemical optimization were performed to identify a novel AMPK inhibitor.