Periodic ER-plasma membrane junctions support long-range Ca signal integration in dendrites.

Neuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1 μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca channels and ER Ca-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca homeostasis, and local activation of the Ca/calmodulin-dependent protein kinase II.

A Clinical Prediction Model For Short-Term Prognosis In Patients With Non Acute Myocardial Infarction Related Cardiogenic Shock.

Background: While acute myocardial infarction (AMI) is widely recognized as the primary cause of Cardiogenic Shock (CS), Non-AMI related CS has been excluded from the majority of CS studies. Information on its prognostic factors remains largely understudied, and it is necessary to focus on these patients to identify the specific risk factors. In this study, we aimed to build and validate a predictive nomogram and risk classification system.

The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

Accelerated spine MRI with deep learning based image reconstruction: a prospective comparison with standard MRI.

Rationale And Objectives: To evaluate the performance of deep learning (DL) reconstructed MRI in terms of image acquisition time, overall image quality and diagnostic interchangeability compared to standard-of-care (SOC) MRI.

Materials And Methods: This prospective study recruited participants between July 2023 and August 2023 who had spinal discomfort. All participants underwent two separate MRI examinations (Standard and accelerated scanning).

Optimizing the anesthetic care of patients with aromatic l-amino acid decarboxylase deficiency.

Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder that results in a lack of the monoamine neurotransmitters dopamine, serotonin, norepinephrine, and epinephrine. Patients present with a wide spectrum of symptoms, including motor and autonomic dysfunction, hypotonia, and developmental delay, often before the age of one. Until recently, treatment options were limited to symptom control, but the recent approval of the first gene therapy for AADC deficiency in Europe and the UK has provided an alternative to treating symptoms for this disease.

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.

A potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer.

The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms.

Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle.

ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban.

Background: Intracellular Ca cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca-ATPase 2a) is responsible for the sequestration of cytosolic Ca into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear.

Evaluating Educational Outcomes Using Patient Outcomes of New Surgeons Performing Partial Colectomy Compared to Cholecystectomy.

Purpose: Despite ongoing efforts to improve surgical education, surgical residents face gaps in their training. However, it is unknown if differences in the training of surgeons are reflected in the patient outcomes of those surgeons once they enter practice. This study aimed to compare the patient outcomes among new surgeons performing partial colectomy-a common procedure for which training is limited-and cholecystectomy-a common procedure for which training is robust.

Association of obesity and mortality in sepsis patients: A meta-analysis from observational evidence.

The project aims to investigate the correlation between obesity, overweight, or low body weight and the risk of mortality in sepsis patients. We performed a rigorous and thorough search of major electronic databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, from the inception of these databases up to March 28, 2023. The data were analyzed with Stata software (version 16.

Combining Deep Learning and Radiomics for Automated, Objective, Comprehensive Bone Mineral Density Assessment From Low-Dose Chest Computed Tomography.

Rationale And Objectives: To develop an intelligent diagnostic model for osteoporosis screening based on low-dose chest computed tomography (LDCT). The model incorporates automatic deep-learning thoracic vertebrae of cancellous bone (TVCB) segmentation model and radiomics analysis.

Materials And Methods: A total of 442 participants who underwent both LDCT and quantitative computed tomography (QCT) examinations were enrolled and were randomly allocated to the training, internal testing, and external testing cohorts.

Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology.

Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis.

Portable Bulk-Water Disinfection by Live Capture of Bacteria with Divergently Branched Porous Graphite in Electric Fields.

Easy access to clean water is essential to functioning and development of modern society. However, it remains arduous to develop energy-efficient, facile, and portable water treatment systems for point-of-use (POU) applications, which is particularly imperative for the safety and resilience of society during extreme weather and critical situations. Here, we propose and validate a meritorious working scheme for water disinfection via directly capturing and removing pathogen cells from bulk water using strategically designed three-dimensional (3D) porous dendritic graphite foams (PDGFs) in a high-frequency AC field.

High-throughput single nucleus total RNA sequencing of formalin-fixed paraffin-embedded tissues by snRandom-seq.

Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers.

Intensive Blood Pressure Management Preserves Functional Connectivity in Patients with Hypertension from the Systolic Blood Pressure Intervention Randomized Trial.

Background And Purpose: The Systolic Blood Pressure Intervention (SPRINT) randomized trial demonstrated that intensive blood pressure management resulted in slower progression of cerebral white matter hyperintensities, compared with standard therapy. We assessed longitudinal changes in brain functional connectivity to determine whether intensive treatment results in less decline in functional connectivity and how changes in brain functional connectivity relate to changes in brain structure.

Materials And Methods: Five hundred forty-eight participants completed longitudinal brain MR imaging, including resting-state fMRI, during a median follow-up of 3.

A scoping review of portable sensing for out-of-lab anterior cruciate ligament injury prevention and rehabilitation.

Anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) surgery are common. Laboratory-based biomechanical assessment can evaluate ACL injury risk and rehabilitation progress after ACLR; however, lab-based measurements are expensive and inaccessible to most people. Portable sensors such as wearables and cameras can be deployed during sporting activities, in clinics, and in patient homes.

Evolving Use of Regional versus General Anesthesia for the Surgical Repair of Open Globe Injuries.

Purpose: The purpose of the current study is to report outcomes with the evolving use of regional anesthesia with monitored anesthesia care (RA-MAC) vs general anesthesia (GA) in the repair of open globe injuries.

Design: Retrospective, consecutive, comparative, nonrandomized clinical study.

Methods: The study includes 507 eyes of 507 patients with open globe injuries treated with either RA-MAC or GA at a tertiary referral center between 2015 and 2020.