Characterization and Safety Evaluation of Autoclaved Gut Commensal RV-01.

Gut commensals play important roles in maintaining the homeostasis of human health. Previous studies indicated that the abundance of in animal hosts was increased by the administration of prebiotics such as polysaccharides purified from iconic oriental medicinal fungi. Subsequently, was found to exert beneficial effects on the amelioration of multiple chronic inflammation-associated diseases.

Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.

Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.

Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.

Care to Explain? AI Explanation Types Differentially Impact Chest Radiograph Diagnostic Performance and Physician Trust in AI.

Background It is unclear whether artificial intelligence (AI) explanations help or hurt radiologists and other physicians in AI-assisted radiologic diagnostic decision-making. Purpose To test whether the type of AI explanation and the correctness and confidence level of AI advice impact physician diagnostic performance, perception of AI advice usefulness, and trust in AI advice for chest radiograph diagnosis. Materials and Methods A multicenter, prospective randomized study was conducted from April 2022 to September 2022.

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.

Long-term Outcomes of Combined Phacotrabeculectomy Surgery in a Singapore Tertiary Hospital.

Purpose: To describe the long-term outcomes of phacotrabeculectomy from a tertiary glaucoma service in Singapore.

Design: Retrospective case series.

Methods: Seven hundred ninety-six eyes of 698 patients who underwent phacotrabeculectomy surgery at the Singapore National Eye Centre between 2005 and 2007 with a minimum follow-up of three years were included.

Disparities in Emergency Medical Services Use, Prehospital Notification, and Symptom Onset to Arrival in Patients With Acute Stroke.

Background: Disparities in time to hospital presentation and prehospital stroke care may be important drivers in inequities in acute stroke treatment rates, functional outcomes, and mortality. It is unknown how patient-level factors, such as race and ethnicity and county-level socioeconomic status, affect these aspects of prehospital stroke care.

Methods: Cross-sectional study of patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage in the Get With the Guidelines-Stroke registry, presenting from July 2015 to December 2019, with symptom onset ≤24 hours.

MRI Predicts Residual Disease and Outcomes in Watch-and-Wait Patients with Rectal Cancer.

Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT.

Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming.

Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

Blood protein assessment of leading incident diseases and mortality in the UK Biobank.

The circulating proteome offers insights into the biological pathways that underlie disease. Here, we test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and mortality in the UK Biobank (n = 47,600). We report 3,209 associations between 963 protein levels and 21 incident outcomes.

Protocol and rationale of the Australian multicentre registry for serial cardiac computed tomography angiography (ARISTOCRAT): a prospective observational study of the natural history of pericoronary adipose tissue attenuation and radiomics.

Background: Vascular inflammation plays a crucial role in the development of atherosclerosis and atherosclerotic plaque rupture resulting in acute coronary syndrome (ACS). Pericoronary adipose tissue (PCAT) attenuation quantified from routine coronary computed tomography angiography (CCTA) has emerged as a promising non-invasive imaging biomarker of coronary inflammation. However, a detailed understanding of the natural history of PCAT attenuation is required before it can be used as a surrogate endpoint in trials of novel therapies targeting coronary inflammation.

Prevalence and transmission of pretreatment drug resistance in people living with HIV-1 in Shanghai China, 2017-2021.

The implementation of pretreatment drug-resistance (PDR) surveillance among people living with HIV-1 (PLWH) is a top priority in countries using efavirenz (EFV)/nevirapine (NVP) for first-line ART. In this study, we assessed the prevalence of PDR among PLWH in Shanghai, China during 2017-2021, and to reveal PDR transmission between Shanghai and other regions of China. A total of 5050 PLWH not on ART during 2017-2021 were included.

Transcriptomic Analysis Reveals the Flavonoid Biosynthesis Pathway Involved in Rhizome Development in Hua.

Hua () rhizomes are rich in flavonoids and other secondary metabolites, exhibiting remarkable antioxidant, anti-tumor, and immunomodulatory effects. flavonoid-biosynthesis-related genes have been characterized already. However, a comprehensive overview of flavonoid biosynthesis pathways is still absent.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

Introduction: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions.

Methods: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT.

Recurrence Characteristics on Optical Coherence Tomography and Treatments of Reis-Bücklers Corneal Dystrophy After Phototherapeutic Keratectomy or Penetrating Keratoplasty.

Purpose: To evaluate the recurrence characteristics on optical coherence tomography and clinical outcomes after phototherapeutic keratectomy (PTK) or penetrating keratoplasty (PKP) in patients with Reis-Bücklers corneal dystrophy (RBCD).

Design: Retrospective interventional case series.

Methods: Seventeen patients with RBCD (31 eyes, including 6 surgery-naïve eyes and 25 surgical eyes) received 44 surgical interventions from 1996 through 2022.

Rectifying METTL4-Mediated N-Methyladenine Excess in Mitochondrial DNA Alleviates Heart Failure.

Background: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear.

Utilizing Deep Learning and Computed Tomography to Determine Pulmonary Nodule Activity in Patients With Nontuberculous Mycobacterial-Lung Disease.

Purpose: To develop and evaluate a deep convolutional neural network (DCNN) model for the classification of acute and chronic lung nodules from nontuberculous mycobacterial-lung disease (NTM-LD) on computed tomography (CT).

Materials And Methods: We collected a data set of 650 nodules (316 acute and 334 chronic) from the CT scans of 110 patients with NTM-LD. The data set was divided into training, validation, and test sets in a ratio of 4:1:1.

Chinese herb ultrafine powder supplementation improves egg nutritional value and quality in laying hens.

This study evaluates the effects of dietary Chinese herb ultrafine powder (CHUP) supplementation in late-phase laying hens on the quality and nutritional values of eggs. A total of 576 Xinyang black-feather laying hens (300-day-old) were randomly allocated into eight groups for a 120-day feeding trial. Each group contained eight replicates with nine hens per replicate.