Uncovering latent infections in kidneys: A novel molecular approach for differential detection.

Leptospirosis, a re-emerging zoonotic disease caused by spp., poses significant global health and veterinary challenges. Long-term colonization of renal tubules by in asymptomatic hosts highlights the need for sensitive detection methods.

Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.

This Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise, we identified , a highly brain penetrant and selective mGlu NAM which displayed moderate potency against both human and rat mGlu.

Application of deep learning reconstruction in abdominal magnetic resonance cholangiopancreatography for image quality improvement and acquisition time reduction.

Purpose: To compare deep learning (DL)-based and conventional reconstruction through subjective and objective analysis and ascertain whether DL-based reconstruction improves the quality and acquisition speed of clinical abdominal magnetic resonance imaging (MRI).

Methods: The 124 patients who underwent abdominal MRI between January and July 2021 were retrospectively studied. For each patient, two-dimensional axial T-weighted single-shot fast spin-echo MRI images with or without fat saturation were reconstructed using DL-based and conventional methods.

Discovery of VU6016235: A Highly Selective, Orally Bioavailable, and Structurally Distinct Tricyclic M Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM).

Herein, we report structure-activity relationship (SAR) studies to develop novel tricyclic M PAM scaffolds with improved pharmacological properties. This endeavor involved a "tie-back" strategy to replace a 5-amino-2,4-dimethylthieno[2,3-]pyrimidine-6-carboxamide core, which led to the discovery of two novel tricyclic cores. While both tricyclic cores displayed low nanomolar potency against both human and rat M and were highly brain-penetrant, the 2,4-dimethylpyrido[4',3':4,5]thieno[2,3-]pyrimidine tricycle core provided lead compound, , with an overall superior pharmacological and drug metabolism and pharmacokinetics (DMPK) profile, as well as efficacy in a preclinical antipsychotic animal model.

Discovery of VU6008677: A Structurally Distinct Tricyclic M Positive Allosteric Modulator with Improved CYP450 Profile.

This Letter details our efforts to develop novel tricyclic muscarinic acetylcholine receptor subtype 4 (M) positive allosteric modulator (PAM) scaffolds with improved pharmacological properties. This endeavor involved a "tie-back" strategy to replace the 3-amino-5-chloro-4,6-dimethylthieno[2,3-]pyridine-2-carboxamide core, which led to the discovery of two novel tricyclic cores: an 8-chloro-9-methylpyrido[3',2':4,5]thieno[3,2-]pyrimidin-4-amine core and 8-chloro-7,9-dimethylpyrido[3',2':4,5]furo[3,2-]pyrimidin-4-amine core. Both tricyclic cores displayed low nanomolar potency against human M and greatly reduced cytochrome P450 inhibition when compared with parent compound .

Higher Plasma -Inositol in Pregnancy Associated with Reduced Postpartum Blood Loss: Secondary Analyses of the NiPPeR Trial.

We previously reported that a combined -inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of -inositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section.

Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer.

Background: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC.

Objective: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.

Clinical, Cultural, Computational, and Regulatory Considerations to Deploy AI in Radiology: Perspectives of RSNA and MICCAI Experts.

The Radiological Society of North of America (RSNA) and the Medical Image Computing and Computer Assisted Intervention (MICCAI) Society have led a series of joint panels and seminars focused on the present impact and future directions of artificial intelligence (AI) in radiology. These conversations have collected viewpoints from multidisciplinary experts in radiology, medical imaging, and machine learning on the current clinical penetration of AI technology in radiology and how it is impacted by trust, reproducibility, explainability, and accountability. The collective points-both practical and philosophical-define the cultural changes for radiologists and AI scientists working together and describe the challenges ahead for AI technologies to meet broad approval.

IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial.

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l at baseline were randomized to receive clazakizumab (2.

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.

The ASCENT Trial: a phase 2 study of induction and consolidation afatinib and chemoradiation with or without surgery in stage III EGFR-mutant NSCLC.

Background: The role of tyrosine kinase inhibitors (TKIs) in early-stage and metastatic oncogene-driven non-small cell lung cancer (NSCLC) is established, but it remains unknown how best to integrate TKIs with concurrent chemoradiotherapy (cCRT) in locally advanced disease. The phase 2 ASCENT trial assessed the efficacy and safety of afatinib and cCRT with or without surgery in locally advanced epidermal growth factor receptor (EGFR)-mutant NSCLC.

Patients And Methods: Adults ≥18 years with histologically confirmed stage III (AJCC 7th edition) NSCLC with activating EGFR mutations were enrolled at Mass General and Dana-Farber/Brigham Cancer Centers, Boston, Massachusetts.

Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights.

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume.

Subtype Identification of Surgically Curable Primary Aldosteronism During Treatment With Mineralocorticoid Receptor Blockade.

Background: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment.

Methods: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers.

Synthetic PET from CT improves diagnosis and prognosis for lung cancer: Proof of concept.

[F]Fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are indispensable components in modern medicine. Although PET can provide additional diagnostic value, it is costly and not universally accessible, particularly in low-income countries. To bridge this gap, we have developed a conditional generative adversarial network pipeline that can produce FDG-PET from diagnostic CT scans based on multi-center multi-modal lung cancer datasets (n = 1,478).

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up).

Characterizing the D-Amino Acid Position in Peptide Epimers by Using Higher-Energy Collisional Dissociation Tandem Mass Spectrometry: A Case Study of Liraglutide.

D-amino acid-containing peptides (DAACPs) occur in biological and artificial environments. Since the importance of DAACPs has been recognized, various mass spectrometry-based analytical approaches have been developed. However, the capability of higher-energy collisional dissociation (HCD) fragmentation to characterize DAACP sites has not been evaluated.

A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD.

Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients. Here we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs in ALS-FTD, including in presymptomatic C9orf72 mutation carriers.

Heat Transfer Performance of a 3D-Printed Aluminum Flat-Plate Oscillating Heat Pipe Finned Radiator.

As electronic components progressively downsize and their power intensifies, thermal management has emerged as a paramount challenge. This study presents a novel, high-efficiency finned heat exchanger, termed Flat-Plate Oscillating Heat Pipe Finned Radiator (FOHPFR), which employs arrayed flat-plate oscillating heat pipes (OHP) as heat dissipation fins. Three-dimensional (3D)-printed techniques allow the internal microchannels of the FOHPFR to become rougher, providing excellent surface wettability and capillary forces, which in turn significantly improves the device's ability to dissipate heat.

Decompressive craniectomy versus craniotomy for acute subdural hematoma: Updated meta-analysis of real-world clinical outcome after RESCUE-ASDH trial.

Introduction: The Randomized Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation of Acute Subdural Hematoma trial found that disability and quality-of-life outcomes were similar between craniotomy and decompressive craniectomy for traumatic acute subdural hematoma (ASDH), contrasting previous literature. This meta-analysis aimed to validate the applicability of RESCUE-ASDH results using real-world data in ASDH patients.

Methods: We searched Chocrane, Embase, and MEDLINE for relevant articles reporting clinical outcomes of craniotomy and decompressive craniectomy.

A Deep Learning Decision Support Tool to Improve Risk Stratification and Reduce Unnecessary Biopsies in BI-RADS 4 Mammograms.

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset.

Materials And Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016.