A network-based systems genetics framework identifies pathobiology and drug repurposing in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments only manage symptoms and lack the ability to slow or prevent disease progression. We utilized a systems genetics approach to identify potential risk genes and repurposable drugs for PD.

Structure-guided insights into TIR-mediated bacterial and eukaryotic immunity.

Within the course of evolution, TIR (Toll/interleukin-1 receptor) domains acquired a myriad of functional specificities. This has significantly added to their well-established roles in innate immune signaling. These additional functions include nicotinamide adenine dinucleotide (NAD)(P) hydrolase, RNA/DNA nuclease (in plants), CN (cyclic nucleotide) cyclase, and base exchanger activities.

SyncGenie: A programmable event synchronization device for neuroscience research.

In neuroscience, accurately correlating brain activity with stimuli and other events requires precise synchronization between neural data and event timing. To achieve this, purpose-built synchronization devices are often used to detect events. This paper introduces SyncGenie, a programmable synchronization device designed for a range of uses in neuroscience research-primarily as a "trigger box" to align neurophysiological data with physical stimulus events, among other possibilities.

An integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis.

Human endogenous retroviruses (HERVs) occupy a large portion of the human genome. Most HERVs are transcriptionally silent, but they can be reactivated during pathological states such as viral infection and certain cancers. The HERV-K HML-2 clade includes elements that recently integrated have in the human germ line and often contain intact open reading frames that possibly support peptide and protein expression.

SMC translocation is unaffected by an excess of nucleoid associated proteins in vivo.

Genome organization is important for DNA replication, gene expression, and chromosome segregation. In bacteria, two large families of proteins, nucleoid-associated proteins (NAPs) and SMC complexes, play important roles in organizing the genome. NAPs are highly abundant DNA-binding proteins that can bend, wrap, bridge, and compact DNA, while SMC complexes load onto the chromosome, translocate on the DNA, and extrude DNA loops.

Prediction of response to anti-HER2 therapy using a multigene assay.

HER2-positive breast cancer (BC), which constitutes 13-15% of cases, shows variable response to anti-HER2 therapies. HER2-positivity, defined as protein overexpression (immunohistochemistry (IHC) score 3+) or equivocal expression (IHC 2+) with evidence of HER2 gene amplification, determines the eligibility to anti-HER2 therapy. MammaTyper® assay (Cerca Biotech GmbH) is a RT-qPCR BC subtyping platform based on the mRNA expression of ERBB2, ESR1, PGR, and MKI67.

The Impact of COVID-19 on the Division of Household Labor Among Women Physicians and Advanced Practice Providers.

Background: COVID-19 increased the burden of childcare on parents, leaving women vulnerable to increased disparities in the division of domestic labor. Women healthcare workers may be at heightened risk of worsening gender parity in the workplace as a result.

Objective: To examine the impact of the COVID-19 pandemic on gender parity in the division of household responsibilities among women healthcare workers.

Simplifying clinical use of TCGA molecular subtypes through machine learning models.

In this issue of Cancer Cell, Ellrott et al. present machine learning models to classify samples into The Cancer Genome Atlas molecular subtypes using compact sets of genomic features. These validated, ready-to-use models are publicly available, although some clinical hurdles need to be cleared before they are fully implemented.

Nucleic acid recognition during prokaryotic immunity.

Parasitic elements often spread to hosts through the delivery of their nucleic acids to the recipient. This is particularly true for the primary parasites of bacteria, bacteriophages (phages) and plasmids. Although bacterial immune systems can sense a diverse set of infection signals, such as a protein unique to the invader or the disruption of natural host processes, phage and plasmid nucleic acids represent some of the most common molecules that are recognized as foreign to initiate defense.

Adjuvant radiation therapy is not associated with a survival benefit after R0 resection in non-metastatic adrenocortical carcinoma.

The benefit of adjuvant radiation therapy (RT) in adrenocortical carcinoma (ACC) is not well characterized for those who undergo initial R0 surgical resection. Patients in the NCDB who underwent R0 resection were placed into two cohorts - those who underwent adjuvant RT and those who did not. 388 patients were identified with 51 receiving RT.

Centering historically minoritized populations to design effective messages about an evidence-based policy to advance social equity.

Researchers have raised concerns that messages describing racial disparities in social outcomes can reduce or polarize support for public policies to address inequality. We questioned this assumption by testing the impact of carefully crafted messages about child tax credit (CTC) expansion. We conducted two randomized message trials, study 1 using Prolific's nonprobability panel ( = 1,402) and study 2 using SSRS's Opinion Panel, a web-based probability sample of US adults ( = 4,483).

Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning.

Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species.

The immunology of stroke and dementia.

Ischemic stroke and vascular cognitive impairment, caused by a sudden arterial occlusion or more subtle but protracted vascular insufficiency, respectively, are leading causes of morbidity and mortality worldwide with limited therapeutic options. Innate and adaptive immunity have long been implicated in neurovascular injury, but recent advances in methodology and new experimental approaches have shed new light on their contributions. A previously unappreciated dynamic interplay of brain-resident, meningeal, and systemic immune cells with the ischemic brain and its vasculature has emerged, and new insights into the frequent overlap between vascular and Alzheimer pathology have been provided.

Randomized clinical trial of a digital integrative medicine intervention among patients undergoing active cancer treatment.

Exercise and mindfulness-based interventions have growing evidence for managing fatigue and comorbid symptoms; however, packaging them in a cohesive digital way for patients undergoing cancer treatment has not been evaluated. We conducted a randomized controlled trial to assess the impact of a 12 week digital integrative medicine program, Integrative Medicine at Home (IM@Home), versus enhanced usual care on fatigue severity (primary outcome), comorbid symptoms and acute healthcare utilization (secondary outcomes), in 200 patients with solid tumors experiencing fatigue during treatment. Fatigue severity decreased more in IM@Home than in the control (1.

Reanalysis of Samburupithecus reveals similarities to nyanzapithecines.

Samburupithecus kiptalami is an ape found in Late Miocene deposits (ca. 9.5 Ma) of northern Kenya.

Cross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles.

Therapeutic monoclonal antibodies (mAbs) against SARS-CoV-2 become obsolete as spike substitutions reduce antibody binding. To induce antibodies against conserved receptor-binding domain (RBD) regions for protection against SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD-nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles.

Automatic medical imaging segmentation via self-supervising large-scale convolutional neural networks.

Purpose: This study aims to develop a robust, large-scale deep learning model for medical image segmentation, leveraging self-supervised learning to overcome the limitations of supervised learning and data variability in clinical settings.

Methods And Materials: We curated a substantial multi-center CT dataset for self-supervised pre-training using masked image modeling with sparse submanifold convolution. We designed a series of Sparse Submanifold U-Nets (SS-UNets) of varying sizes and performed self-supervised pre-training.

inDrops-2: a flexible, versatile and cost-efficient droplet microfluidic approach for high-throughput scRNA-seq of fresh and preserved clinical samples.

The expansion of single-cell analytical techniques has empowered the exploration of diverse biological questions at the individual cells. Droplet-based single-cell RNA sequencing (scRNA-seq) methods have been particularly widely used due to their high-throughput capabilities and small reaction volumes. While commercial systems have contributed to the widespread adoption of droplet-based scRNA-seq, their relatively high cost limits the ability to profile large numbers of cells and samples.

Preanalytical Considerations of Handling Suspected Creutzfeldt-Jakob Disease Specimens Within the Clinical Pathology Laboratories: A Survey-Based Approach.

Creutzfeldt-Jakob disease (CJD) is a rare, fatal, and transmissible neurodegenerative disorder caused by prion proteins. Handling specimens from individuals with suspected or confirmed cases presents a safety challenge to hospital workers including clinical laboratory staff. As no national guidelines exist, the clinical pathology laboratory must establish protocols for handling these specimens to ensure sufficient protective measures.

Abnormal p53 High-Grade Endometrioid Endometrial Cancer: A Systematic Review and Meta-Analysis.

Objective: Our primary objective was to evaluate the oncologic outcomes of patients with abnormal p53 FIGO grade 3 (high-grade) endometrioid endometrial cancer. As secondary objectives, we determined the global prevalence of abnormal p53 in grade 3 endometrioid endometrial carcinomas and the geographical variations.

Methods: The following electronic databases were searched: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science.

Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.

IL-21 shapes the B cell response in a context-dependent manner.

The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1 B cells.

Long-Term Results of Pars Plana Vitrectomy with Internal Limiting Membrane Peeling for Vitreomacular Traction Syndrome: A Prospective Investigation in Central Asian Population.

There is a lack of research on the clinical characteristics of vitreomacular traction (VMT) in the Central Asian population, which evaluates the visual recovery and macular hole closure outcomes of pars plana vitrectomy (PPV) with membrane peel in this population. This long-term prospective cohort study, conducted at the Kazakh Eye Research Institute from June 2015 to December 2021 with a follow-up period until December 2022, included 1574 patients (1784 eyes) with VMT syndrome. Among the eyes, 724 (40.

Benign Soft Tissue Lesions Responsible for Pain: When and How Should the IR Intervene.

In most of the cases Interventional Radiology techniques and therapies are proposed for the management of symptomatic soft tissue benign tumors responsible for pain and/or compression symptoms aiming to offer a curative intent by means of tumor necrosis with subsequent symptoms' management and improvement of life quality. The ablative therapies include chemical, thermal and non-thermal approaches while, trans-arterial (chemo)embolization also has a distinct role. Adjunct ancillary techniques should be performed whenever necessary to increase efficacy and safety and avoid or reduce complications.