Data-driven discovery of cell-type-directed network-correcting combination therapy for Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by heterogeneous molecular changes across diverse cell types, posing significant challenges for treatment development. To address this, we introduced a cell-type-specific, multi-target drug discovery strategy grounded in human data and real-world evidence. This approach integrates single-cell transcriptomics, drug perturbation databases, and clinical records.

Enhanced cellular longevity arising from environmental fluctuations.

Cellular longevity is regulated by both genetic and environmental factors. However, the interactions of these factors in the context of aging remain largely unclear. Here, we formulate a mathematical model for dynamic glucose modulation of a core gene circuit in yeast aging, which not only guided the design of pro-longevity interventions but also revealed the theoretical principles underlying these interventions.

Regulatory systems and requirements for clinical trials of AAV-based gene therapies - Perspectives from six Asian countries or regions: Report from the 6th Asia Partnership Conference of Regenerative Medicine - April 20, 2023.

Gene therapies, which include viral-vector gene delivery, genome editing, and genetically modified cell therapy, are innovative treatments with the potential to address the underlying genetic causes of disorders and to provide life-changing value in terms of curing disease. Although adeno-associated virus (AAV)-based gene therapy is one of the most advanced types of gene therapy, far fewer AAV-based gene therapy studies have been conducted in Asia than in North America and Europe. The 6th Asia Partnership Conference of Regenerative Medicine (APACRM) was held on April 20, 2023 in Tokyo, Japan.

Emergence characteristics comparing endotracheal tube to reinforced laryngeal mask airway during endoscopic sinus surgery - A randomised controlled study.

Background And Aims: During endoscopic sinus surgery, anaesthetic conditions significantly impact the intraoperative surgical field and bleeding during emergence. While the endotracheal tube (ETT) has been traditionally used in sinus surgery, a reinforced laryngeal mask airway (RLMA) that produces less upper airway stimulation may result in smoother emergence.

Methods: A randomised controlled trial of 72 patients undergoing elective sinus surgery was conducted, with the allocation of airway technique to either ETT with a throat pack or RLMA.

Bottom-up data integration in polymer models of chromatin organization.

Cellular functions crucially depend on the precise execution of complex biochemical reactions taking place on the chromatin fiber in the tightly packed environment of the cell nucleus. Despite the availability of large datasets probing this process from multiple angles, bottom-up frameworks that allow the incorporation of the sequence-specific nature of biochemistry in a unified model of 3D chromatin structure remain scarce. Here, we propose Sequence-Enhanced Magnetic Polymer (SEMPER), a novel stochastic polymer model that naturally incorporates observational data about sequence-driven biochemical processes, such as binding of transcription factor proteins, in a 3D model of chromatin structure.

Enhanced cellular longevity arising from environmental fluctuations.

Cellular longevity is regulated by both genetic and environmental factors. However, the interactions of these factors in the context of aging remain largely unclear. Here, we formulate a mathematical model for dynamic glucose modulation of a core gene circuit in yeast aging, which not only guided the design of pro-longevity interventions, but also revealed the theoretical principles underlying these interventions.

Trends in Volume and Charges of Retinal Tear Patients in the Emergency Department.

Purpose: To characterize retinal tears (RTs) and calculate the economic burden of RTs that present to the emergency department (ED) in the US.

Methods: We used a large national ED database to retrospectively analyze RTs that presented to the ED from 2006 to 2019. Using extrapolation methods, national of the RT patient ED volume, demographics, comorbidities, disposition, inpatient (IP) charges, and ED charges were calculated.

Structures of Cancer Antigen Mesothelin and Its Complexes with Therapeutic Antibodies.

Unlabelled: The tumor-associated antigen mesothelin is expressed at high levels on the cell surface of many human cancers, while its expression in normal tissues is limited. The binding of mesothelin to the tumor-associated cancer antigen 125 (CA-125) can lead to heterotypic cell adhesion and tumor metastasis within the pleural and peritoneal cavities. Immunotherapeutic strategies targeting mesothelin are being intensively investigated.

Predictors of inpatient admission likelihood and prolonged length of stay among cerebrovascular disease patients: A nationwide emergency department sample analysis.

Purpose: To examine the hospital- and patient-related factors associated with increased likelihood of inpatient admission and extended hospitalization.

Methods: We applied multivariate logistic regression to a subset of ED hospital and patient characteristics linearly extrapolated from the 2019 National Emergency Department Sample database (n=626,508). Patient characteristics with 10 or fewer ED visits after national extrapolation were not reported in the current study to maintain patient confidentiality, in accordance with the HCUP Data Use Agreement.

Characterization of Human-Induced Neural Stem Cells and Derivatives following Transplantation into the Central Nervous System of a Nonhuman Primate and Rats.

Neural stem cells (NSCs) and derivatives are potential cellular sources to treat neurological diseases. In the current study, we reprogrammed human peripheral blood mononuclear cells into induced NSCs (iNSCs) and inserted GFP gene into the AAVS1 site for graft tracing. Targeted integration of GFP does not affect the proliferation and differentiation capacity of iNSCs.

Virtual Interviewing for Radiology Residency: Pluses, Minuses, and A Review of the Literature.

This article reviews current medical literature to assess the benefits and drawbacks of virtual interviews for radiology residencies as well as the downstream effects of these changes, best practices, and potential future recruitment methods. Topics covered include the effects of remote recruitment in promoting accessibility and applicant diversity and equality as well as fiscal, environmental, and time savings in combination with technical challenges, the complications of over application, challenges in assessment of program culture and location, impact on morale, and hidden financial and emotional costs. Learnings from other medical specialties are highlighted in addition to the process of signaling, guidelines for conducting and participating in virtual interviews, and matters for future consideration.

Carpal Tunnel Syndrome: Pathophysiology and Comprehensive Guidelines for Clinical Evaluation and Treatment.

In carpal tunnel syndrome (CTS), the median nerve is compressed at the level of the carpal tunnel in the wrist. This entrapment manifests as unpleasant symptoms, such as burning, tingling, or numbness in the palm that extends to the fingers. As the disease progresses, afflicted individuals also report decreased grip strength accompanied by hand weakness and restricted movement.

Induced neural stem cells from Macaca fascicularis show potential of dopaminergic neuron specification and efficacy in a mouse Parkinson's disease model.

Induced neural stem cells (iNSCs) can be reprogrammed from somatic cells and have shown potentials in treatment of various neurological diseases/disorders. Obtaining iNSCs of nonhuman primates serves as an important bridge for clinical translation using iNSCs. In the current study, cynomolgus (Macaca fascicularis) bone marrow mesenchymal stromal cells (MSCs) were reprogrammed into iNSCs by transduction of non-integrative Sendai virus encoding transgenes OCT4, SOX2, KLF4 and C-MYC.

Non-Invasive Blood Flow Speed Measurement Using Optics.

Non-invasive measurement of the arterial blood speed gives important health information such as cardio output and blood supplies to vital organs. The magnitude and change in arterial blood speed are key indicators of the health conditions and development and progression of diseases. We demonstrated a simple technique to directly measure the blood flow speed in main arteries based on the diffused light model.

Forty Years Since the Epidemic: Modern Paradigms in HIV Diagnosis and Treatment.

Human immunodeficiency virus (HIV) is a viral infection that, when transmitted through the exchange of certain bodily fluids, destroys various immune cells and contributes to an overall weakened immune system. If left untreated, HIV progresses to acquired immunodeficiency syndrome (AIDS) - a chronic, life-threatening condition that puts patients at risk for opportunistic infections. Since the emergence of HIV nearly a century ago, the world has seen tremendous advances in elucidating its pathology and progression.

A feasibility study for noninvasive measurement of shear wave speed in live zebrafish.

Zebrafish are being increasingly used as animal models for human diseases such as cardiomyopathy and neuroblastoma. Owing to a nearly fully sequenced genome and efficient genetics/chemical genetics, zebrafish open new research opportunities for human diseases research. The purpose of this study was to develop zebrafish ultrasound vibro-elastography (ZUVE) for measuring the shear wave speed of zebrafish.

Frequency- and Power-Dependent Photoresponse of a Perovskite Photodetector Down to the Single-Photon Level.

Organometallic halide perovskites attract strong interests for their high photoresponsivity and solar cell efficiency. However, there was no systematic study of their power- and frequency-dependent photoresponsivity. We identified two different power-dependent photoresponse types in methylammonium lead iodide perovskite (MAPbI) photodetectors.

Room-temperature long-wave infrared detector with thin double layers of amorphous germanium and amorphous silicon.

A longwave-infrared photodetector made of double layers of 100nm amorphous germanium (a-Ge) and 25nm amorphous silicon (a-Si) have been demonstrated. Under room temperature, the device shows the responsivity of 1.7 A/W, detectivity of 6×108 Jones, and noise equivalent power (NEP) of 5pW/√Hz under 5V bias and at 20kHz operation.

TNFα-induced Up-regulation of Affects the Differentiation and Proliferation of Neural Stem Cells.

The molecular mediators underlying the effects of inflammation on neural stem cells (NSCs) are not fully characterized. In this study, we identified as a downstream basic helix-loop-helix (bHLH) transcription factor in NSCs following exposure to TNFα. Under normal conditions, expression is inhibited at post-transcriptional levels by miR-26a, which targets the 3' untranslated region (UTR) of .

A Pilot Study of Wet Lung Using Lung Ultrasound Surface Wave Elastography in an Ex Vivo Swine Lung Model.

Extravascular lung water (EVLW) is a basic symptom of congestive heart failure and other conditions. Computed tomography (CT) is standard to assess EVLW, but it requires ionizing radiation and radiology facilities. Lung ultrasound reverberation artifacts called B-lines have been used to assess EVLW.

Machine Learning Based Real-Time Image-Guided Cell Sorting and Classification.

Cell classification based on phenotypical, spatial, and genetic information greatly advances our understanding of the physiology and pathology of biological systems. Technologies derived from next generation sequencing and fluorescent activated cell sorting are cornerstones for cell- and genomic-based assays supporting cell classification and mapping. However, there exists a deficiency in technology space to rapidly isolate cells based on high content image information.

Dopaminergic precursors differentiated from human blood-derived induced neural stem cells improve symptoms of a mouse Parkinson's disease model.

Autologous neural stem cells (NSCs) may offer a promising source for deriving dopaminergic (DA) cells for treatment of Parkinson's disease (PD). By using Sendai virus, human peripheral blood mononuclear cells (PBMNCs) were reprogrammed to induced NSCs (iNSCs), which were then differentiated to dopaminergic neurons . Whole-genome deep sequencing was performed to search for mutations that had accumulated during the reprogramming and expansion processes.