Programmable trans-splicing riboregulators for complex cellular logic computation.

Synthetic genetic circuits program the cellular input-output relationships to execute customized functions. However, efforts to scale up these circuits have been hampered by the limited number of reliable regulatory mechanisms with high programmability, performance, predictability and orthogonality. Here we report a class of split-intron-enabled trans-splicing riboregulators (SENTRs) based on de novo designed external guide sequences.

Nuclear Medicine Imaging in Epilepsy.

Approximately one-third of patients with focal epilepsy have medically refractory focal epilepsy (MRFE), which significantly impacts their quality of life. Once a seizure focus is identified and determined to be in the noneloquent cortex, it can be surgically resected with the goal of freedom from seizures and minimal neurocognitive deficit. During noninvasive (phase I) presurgical planning, functional (nuclear) imaging and structural imaging are complementary in the accurate localization of the epileptogenic zone (EZ).

Longitudinal CT Radiomics to Predict Progression-free Survival in Patients with Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy.

Rationale And Objectives: To develop and validate a radiomics signature, utilizing baseline and restaging CT, for preoperatively predicting progression-free survival (PFS) after neoadjuvant chemotherapy (NAC) in locally advanced gastric cancer (LAGC).

Methods: A total of 316 patients with LAGC who received NAC followed by gastrectomy were retrospectively included in this single-center study; these patients were split into two cohorts, one for training (n = 243) and the other for validation (n = 73), based on the different districts of our hospital. A total of 1316 radiomics features were extracted from the volume of interest of the gastric-cancer lesion on venous phase CT images.

Flexible progestin-primed ovarian stimulation versus a GnRH antagonist protocol in predicted suboptimal responders undergoing freeze-all cycles: a randomized non-inferiority trial.

Study Question: Are live birth rates (LBRs) per woman following flexible progestin-primed ovarian stimulation (fPPOS) treatment non-inferior to LBRs per woman following the conventional GnRH-antagonist protocol in expected suboptimal responders undergoing freeze-all cycles in assisted reproduction treatment?

Summary Answer: In women expected to have a suboptimal response, the 12-month likelihood of live birth with the fPPOS treatment did not achieve the non-inferiority criteria when compared to the standard GnRH antagonist protocol for IVF/ICSI treatment with a freeze-all strategy.

What Is Known Already: The standard PPOS protocol is effective for ovarian stimulation, where medroxyprogesterone acetate (MPA) is conventionally administered in the early follicular phase for ovulatory suppression. Recent retrospective cohort studies on donor cycles have shown the potential to prevent premature ovulation and maintain oocyte yields by delaying the administration of MPA until the midcycle (referred to as fPPOS), similar to GnRH antagonist injections.

Isolation, Structure Elucidation, and Bioactivity Evaluation of Two Alkaloids From H. Stem: A Traditional Medicinal Spice and Its Chemico-Pharmacological Aspects.

Bangladesh is endowed with an abundance of excellent medicinal plant resources. A well-known traditional medicinal plant H. from the Piperaceae family is rich in bioactive phytochemicals that have antidiarrheal, antimicrobial, analgesic, antioxidant, anticancer, and cytotoxic effects.

Flaxseed Linusorb Alleviates Collagen-Induced Rheumatoid Arthritis in Rats via Inhibiting the TLR4/NF-κb/MAPK Signal Pathway and Modulating Gut Microbiota.

Flaxseed linusorb (FL) has gradually garnered widespread attention in recent years because of its intriguing bioactivities like anti-inflammation, antimelanogenesis, and even anticancer effects. Based on its proven anti-inflammatory activity and mechanism, it is supposed that FL may also exhibit an effect in treating and preventing rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) rat models were established to investigate the potential therapeutic effect of FL, which were intervened with FL via gavage (50 and 100 mg/kg B.

Definitive Evidence for the Identification and Function of Renin-Expressing Cholinergic Neurons in the Nucleus Ambiguus.

Background: The importance of the brain renin-angiotensin system in cardiovascular function is well accepted. However, not knowing the precise source of renin in the brain has been a limitation toward a complete understanding of how the brain renin-angiotensin system operates.

Methods: Highly sensitive in situ hybridization techniques and conditional knockout mice were used to address the location and function of renin in the brainstem.

Structure-guided development of selective caseinolytic protease P agonists as antistaphylococcal agents.

Methicillin-resistant Staphylococcus aureus is a ubiquitous pathogen, posing a serious threat to human health worldwide. Thus, there is a high demand for antibiotics with distinct targets. Caseinolytic protease P (ClpP) is a promising target for combating staphylococcal infections; however, selectively activating S.

Comparative mitochondrial proteomic: PGAM5-mediated necroptosis through excessive mitophagy in sheep livers under molybdenum and cadmium co-exposure.

Accumulation of excessive molybdenum (Mo) and cadmium (Cd) in the environment poses detrimental effects on organisms. The precise mechanisms of hepatotoxicity that are involved with mitochondria, resulting from the co-exposure to Mo and Cd, remain poorly understood and elusive. To fill the gap, a total of 24 sheep were stratified into two groups: control group and Mo + Cd group (45 mg Mo·kg⁻¹·B.

TIA1 Mediates Divergent Inflammatory Responses to Tauopathy in Microglia and Macrophages.

The RNA binding protein TIA1 is known to regulate stress responses. Here we show that TIA1 plays a much broader role in inflammatory cells, being required for the microglial sensome. We crossed TIA1 cKO mice (using a CX3CR1 driven cre element) to PS19 MAPT P301S tauopathy mice.

Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis.

Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis.

Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective.

Intracytoplasmic sperm injection versus conventional in vitro fertilization in infertile couples with normal total sperm count and motility: does sperm morphology matter?

Study Question: Among couples with infertility and normal total sperm count and motility, can sperm morphology be used as a biomarker to identify couples who benefit more from ICSI over conventional IVF (c-IVF) on fertility outcomes?

Summary Answer: Based on this secondary analysis of a large randomized clinical trial (RCT), sperm morphology has limited value as a biomarker to identify couples who benefit more from ICSI over c-IVF on live birth, ongoing pregnancy, clinical pregnancy or total fertilization failure.

What Is Known Already: Our recent RCT showed that ICSI did not result in higher live birth rates in couples with normal total sperm count and motility. It is unclear whether sperm morphology can be used as a biomarker to identify couples who benefit more from ICSI over c-IVF in this population.

Enhancing Lesion Detection in Inflammatory Myelopathies: A Deep Learning-Reconstructed Double Inversion Recovery MRI Approach.

Background And Purpose: The imaging of inflammatory myelopathies has advanced significantly over time, with MRI techniques playing a pivotal role in enhancing lesion detection. However, the impact of deep learning (DL)-based reconstruction on 3D double inversion recovery (DIR) imaging for inflammatory myelopathies remains unassessed. This study aims to compare acquisition time, image quality, diagnostic confidence, and lesion detection rates among sagittal T2WI, standard DIR, and DL -reconstructed DIR in patients with inflammatory myelopathies.

One fresh cleavage-stage single embryo transfer (SET) plus one frozen-thawed blastocyst-stage SET or one fresh cleavage-stage double embryo transfer? A retrospective matched cohort study.

Study Question: Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle?

Summary Answer: In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle.

What Is Known Already: The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies.

Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140  fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13  TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.

Evaluating the Value of Eye-Tracking Augmented Debriefing in Medical Simulation-A Pilot Randomized Controlled Trial.

Introduction: Debriefing after simulation facilitates reflective thinking and learning. Eye-tracking augmented debriefing (ETAD) may provide advantages over traditional debriefing (TD) by leveraging video replay with first-person perspective. This multisite randomized controlled trial compared the impact of ETAD with TD (without eye-tracking and without video) after simulation on 4 outcomes: (1) resident metacognitive awareness (the primary outcome), (2) cognitive load (CL) of residents and debriefers, (3) alignment of resident self-assessment and debriefer assessment scores, and (4) resident and debriefer perceptions of the debriefing experience.

Coupling Habitat Radiomic Analysis with the Diversification of the Tumor ecosystem: Illuminating New Strategy in the Assessment of Postoperative Recurrence of Non-Muscle Invasive Bladder Cancer.

Rationale And Objectives: Non-muscle-invasive bladder cancer (NMIBC) is highly recurrent, with each recurrence potentially progressing to muscle-invasive cancer, affecting patient prognosis. Intratumoral heterogeneity plays a crucial role in NMIBC recurrence. This study investigated a novel habitat-based radiomic analysis for stratifying NMIBC recurrence risk.

Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation.

Background: CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor).

Lower-intensity CPX-351 plus venetoclax induction for adults with newly diagnosed AML unfit for intensive chemotherapy.

Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, a B-cell lymphoma-2 inhibitor. This phase 1b study evaluated lower-intensity CPX-351 combined with venetoclax in adults with acute myeloid leukemia (AML) considered unfit/ineligible for intensive chemotherapy. In a dose-exploration phase using a 3+3 design, patients received stepwise dosing of CPX-351 IV on days 1 and 3 plus venetoclax 400 mg orally on days 2 to 21 per cycle to determine the recommended phase 2 dose (RP2D) for this combination.

Metal-Free CO Prodrugs Activated by Molecular Oxygen Protect against Doxorubicin-Induced Cardiomyopathy in Mice.

Carbon monoxide has been extensively studied for its various therapeutic activities in cell cultures and animal models. Great efforts have been made to develop noninhalational approaches for easy and controlled CO delivery. Herein, we introduce a novel metal-free CO prodrug approach that releases CO under near-physiological conditions.

Vitamin U alleviates AFB-induced hepatotoxicity in pregnant and lactating mice by regulating the Nrf2/Hmox1 pathway.

This study investigated the protective effect of Vitamin U on liver injury induced by aflatoxin B (AFB) in maternal mice. 25 pregnant ICR mice were randomly divided into five groups: the AFB group (AF, 0.3 mg AFB/kg b.

Improving prognostic accuracy in lung transplantation using unique features of isolated human lung radiographs.

Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases.