The Value of Necrotic Area Features in Contrast-Enhanced Ultrasound for Distinguishing Between Benign and Malignant Subpleural Pulmonary Lesions.

Objective: To analyze Necrotic Area Features of subpleural pulmonary lesions (SPLs) demonstrated by contrast-enhanced ultrasound (CEUS) and investigate their value in differentiating between malignant and benign SPLs.

Methods: Patients with SPLs who underwent CEUS at our hospital from January to May 2021. The following patient information was recorded: (i) age, (ii) sex, (iii) lesion size, (iv) lesion location, (v) size of necrotic areas and (vi) necrotic area morphology, including sieve-like necrosis, necrotic area with septal enhancement, necrotic area with annular enhancement margins, and necrotic area with burr-like enhancement margins.

Women may not benefit from repeated frozen embryo transfers: a retrospective analysis of the cumulative live birth rate of 43 972 women.

Study Question: Which specific groups of women would not benefit from repeated frozen embryo transfers (FETs)?

Summary Answer: Women over 45 years of age should stop treatment after three FET attempts due to the absence of further benefits, while women aged 40-45 years and those with a diminished ovarian reserve and other causes of infertility have a lower chance of improving their cumulative live birth rate (CLBR) within five FET cycles and experience fewer advantages from repeated transfers.

What Is Known Already: In real-life scenarios of ART, women who fail to achieve a live birth often choose to undergo repeated FETs via the freeze-all strategy.

Study Design Size Duration: This retrospective study included 43 972 women who underwent 86 496 oocyte retrieval cycles and 82 022 FET cycles between January 2010 and March 2023 under the freeze-all strategy.

Mucosal Healing Among Black and White Patients With Inflammatory Bowel Disease.

Introduction: Crohn's disease and ulcerative colitis are characterized by chronic inflammation of the gastrointestinal tract. Mucosal healing (MH) is a therapeutic goal in patients with inflammatory bowel disease (IBD). Current data suggest that Black patients may experience worse clinical outcomes than White patients with IBD.

Enzyme-Instructed Photoactivatable Supramolecular Antigens on Cancer Cell Membranes for Precision-Controlled T-Cell-Based Cancer Immunotherapy.

Cancer immunotherapies based on cytotoxic CD8 T lymphocytes (CTLs) are highly promising for cancer treatment. The specific interaction between T-cell receptors and peptide-MHC-I complexes (pMHC-I) on cancer cell membranes critically determines their therapeutic outcomes. However, the lack of appropriate endogenous antigens for MHC-I presentation disables tumor recognition by CTLs.

An esophagectomy surgical Apgar score-based nomogram-a risk-based postoperative triage system: a phase II randomised trial.

Background: The esophagectomy surgical Apgar score (eSAS) has been found to be a predictor of postoperative complications in esophagectomy. In our previous study, we built a graphic nomogram based on eSAS and demonstrated that it can effectively predict the risk of major morbidity after esophagectomy. In this study, we aimed to assess the benefits of using an eSAS-based nomogram model as a postoperative risk-based triage system for patients undergoing esophagectomy.

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).

An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis.

Background: The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production.

Olgotrelvir, a dual inhibitor of SARS-CoV-2 M and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19.

Background: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance.

Methods: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (M), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells.

Findings: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115.

Protein Tyrosine Phosphatase SHP2 in Macrophages Acts as an Antiatherosclerotic Regulator in Mice.

Background: Macrophages have versatile roles in atherosclerosis. SHP2 (Src homology 2 containing protein tyrosine phosphatase 2) has been demonstrated to play a critical role in regulating macrophage activation. However, the mechanism of SHP2 regulation of macrophage function in an atherosclerotic microenvironment remains unknown.

Coating-Free Culture Medium for Establishing and Maintaining Human Induced Pluripotent Stem Cells.

Cell expansion of human pluripotent stem cells (hPSCs) commonly depends on Matrigel as a coating matrix on two-dimensional (2D) culture plates and 3D microcarriers. However, the xenogenic Matrigel requires sophisticated quality-assurance processes to meet clinical requirements. In this study, we develop an innovative coating-free medium for expanding hPSCs.

Improved pharmacokinetics of HIV-neutralizing VRC01-class antibodies achieved by reduction of net positive charge on variable domain.

The amino-acid composition of the immunoglobulin variable region has been observed to impact antibody pharmacokinetics (PK). Here, we sought to improve the PK of the broad HIV-1-neutralizing VRC01-class antibodies, VRC07-523LS and N6LS, by reducing the net positive charge in their variable domains. We used a structure-guided approach to generate a panel of antibody variants incorporating select Arg or Lys substituted to Asp, Gln, Glu, or Ser.

Endothelial TIE1 Restricts Angiogenic Sprouting to Coordinate Vein Assembly in Synergy With Its Homologue TIE2.

Background: Vascular growth followed by vessel specification is crucial for the establishment of a hierarchical blood vascular network. We have shown that TIE2 is required for vein development while little is known about its homologue TIE1 (tyrosine kinase with immunoglobulin-like and EGF [epithelial growth factor]-like domains 1) in this process.

Methods: We analyzed functions of TIE1 as well as its synergy with TIE2 in the regulation of vein formation by employing genetic mouse models targeting , , and , together with in vitro cultured endothelial cells to decipher the underlying mechanism.

Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

Background: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking.

Methods: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy.

Slow TCA flux and ATP production in primary solid tumours but not metastases.

Tissues derive ATP from two pathways-glycolysis and the tricarboxylic acid (TCA) cycle coupled to the electron transport chain. Most energy in mammals is produced via TCA metabolism. In tumours, however, the absolute rates of these pathways remain unclear.

Cancer fitness genes: emerging therapeutic targets for metastasis.

Development of cancer therapeutics has traditionally focused on targeting driver oncogenes. Such an approach is limited by toxicity to normal tissues and treatment resistance. A class of 'cancer fitness genes' with crucial roles in metastasis have been identified.

Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers.

Stage I non-small cell lung cancer (NSCLC) presents diverse outcomes. To identify molecular features leading to tumor recurrence in early-stage NSCLC, we perform multiregional whole-exome sequencing (WES), RNA sequencing, and plasma-targeted circulating tumor DNA (ctDNA) detection analysis between recurrent and recurrent-free stage I NSCLC patients (CHN-P cohort) who had undergone R0 resection with a median 5-year follow-up time. Integrated analysis indicates that the multidimensional clinical and genomic model can stratify the prognosis of stage I NSCLC in both CHN-P and EUR-T cohorts and correlates with positive pre-surgical deep next generation sequencing (NGS) ctDNA detection.

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial.

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost.

Second Heart Field-Derived Cells Contribute to Angiotensin II-Mediated Ascending Aortopathies.

Background: The ascending aorta is a common location for aneurysm and dissection. This aortic region is populated by a mosaic of medial and adventitial cells that are embryonically derived from either the second heart field (SHF) or the cardiac neural crest. SHF-derived cells populate areas that coincide with the spatial specificity of thoracic aortopathies.

Pharmacological disruption of the MTDH-SND1 complex enhances tumor antigen presentation and synergizes with anti-PD-1 therapy in metastatic breast cancer.

Despite increased overall survival rates, curative options for metastatic breast cancer remain limited. We have previously shown that metadherin (MTDH) is frequently overexpressed in poor prognosis breast cancer, where it promotes metastasis and therapy resistance through its interaction with staphylococcal nuclease domain-containing 1 (SND1). Through genetic and pharmacological targeting of the MTDH-SND1 interaction, we reveal a key role for this complex in suppressing antitumor T cell responses in breast cancer.

Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis.

Metastatic breast cancer is a leading health burden worldwide. Previous studies have shown that metadherin (MTDH) promotes breast cancer initiation, metastasis and therapy resistance; however, the therapeutic potential of targeting MTDH remains largely unexplored. Here, we used genetically modified mice and demonstrate that genetic ablation of Mtdh inhibits breast cancer development through disrupting the interaction with staphylococcal nuclease domain-containing 1 (SND1), which is required to sustain breast cancer progression in established tumors.

CaMKII Serine 280 O-GlcNAcylation Links Diabetic Hyperglycemia to Proarrhythmia.

[Figure: see text].

pHLIP ICG for delineation of tumors and blood flow during fluorescence-guided surgery.

Fluorescence imaging has seen enduring use in blood flow visualization and is now finding a new range of applications in image-guided surgery. In this paper, we report a translational study of a new fluorescent agent for use in surgery, pHLIP ICG, where ICG (indocyanine green) is a surgical fluorescent dye used widely for imaging blood flow. We studied pHLIP ICG interaction with the cell membrane lipid bilayer, the pharmacology and toxicology in vitro and in vivo (mice and dogs), and the biodistribution and clearance of pHLIP ICG in mice.