Mutability and hypermutation antagonize immunoglobulin codon optimality.

The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality.

Clinical Characteristics and Survival Outcomes of Patients With Primary and Secondary Plasma Cell Leukemia According to the 2021 Definition: A Single Center Retrospective Study.

Introduction: Plasma cell leukemia (PCL) is a rare malignancy with poor overall survival (OS). Recently, its diagnostic criteria were revised by lowering the threshold of circulating plasma cells from ≥ 20% to ≥ 5%.

Methods: Between 2010 and 2024, patients with primary PCL (pPCL) and secondary PCL (sPCL) were identified at a tertiary center.

Idiopathic intracranial hypertension in Asians: a retrospective dual-center study.

Background: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF.

Methods: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan.

Antibody modulation of B cell responses-Incorporating positive and negative feedback.

Antibodies are powerful modulators of ongoing and future B cell responses. While the concept of antibody feedback has been appreciated for over a century, the topic has seen a surge in interest due to the evidence that the broadening of antibody responses to SARS-CoV-2 after a third mRNA vaccination is a consequence of antibody feedback. Moreover, the discovery that slow antigen delivery can lead to more robust humoral immunity has put a spotlight on the capacity for early antibodies to augment B cell responses.

Bicolor Tuning and Hyper-Reflective Color Switching Based on Two Stacked Cholesteric Liquid Crystal Cells with Asymmetric Electrothermal Optical Responses.

We propose a double-cell cholesteric liquid crystal (CLC) device composed of a left-handed (LH) CLC cell with a pair of sheet electrodes and a right-handed (RH) CLC cell with a tri-electrode configuration characterized by a sheet electrode on the top and an interdigitated electrode on the bottom substrates. Bi-reflected color tuning and hyper-reflective color switching are revealed from this cell stack via the electrothermal control of the central wavelengths of the LH- and RH-bandgaps by voltage-induced pseudo-dielectric heating. The two CLCs are thermally sensitive and exhibit overlapped bandgaps in the field-off state with nearly identical temperature dependence, resulting in a hyper-reflective color at 720 nm at 23.

Correlation of High-Grade Osteosarcoma Response to Chemotherapy with Enhanced Tissue Immunological Response: Analysis of CD95R, IFN-γ, Catalase, Hsp70, and VEGF.

High-grade osteosarcoma, a primary malignant bone tumour, is experiencing a global increase in reported incidence with varied prevalence. Despite advances in management, which include surgery and neoadjuvant chemotherapy often an unsatisfactory outcome is found due to poor or heterogeneous response to chemotherapy. Our study delved into chemotherapy responses in osteosarcoma patients and associated molecular expressions, focusing on CD95 receptor (CD95R), interferon (IFN)-γ, catalase, heat-shock protein (Hsp)70, and vascular endothelial growth factor (VEGF).

Polymeric Nanoparticles Enable mRNA Transfection and Its Translation in Intervertebral Disc and Human Joint Cells, Except for M1 Macrophages.

Chronic lower back pain caused by intervertebral disc degeneration and osteoarthritis (OA) are highly prevalent chronic diseases. Although pain management and surgery can alleviate symptoms, no disease-modifying treatments are available. mRNA delivery could halt inflammation and degeneration and induce regeneration by overexpressing anti-inflammatory cytokines or growth factors involved in cartilage regeneration.

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.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

Objectives: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam.

Methods: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear.

Multimodal, broadly neutralizing antibodies against SARS-CoV-2 identified by high-throughput native pairing of BCRs from bulk B cells.

TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology to pair B cell receptor heavy and light chains of SARS-CoV-2 spike protein-binding antibodies derived from enriched antigen-specific memory B cells and bulk antibody-secreting cells. We identified approximately 60,000 productive, in-frame, paired antibody sequences, from which 2,093 antibodies were selected for functional evaluation based on abundance, isotype and patterns of somatic hypermutation.

A single ascending dose study of single-stranded oligodeoxyribonucleotide RO7062931 in Chinese healthy volunteers.

RO7062931 is an N-acetylgalactosamine (GalNAc)-conjugated single-stranded oligodeoxyribonucleotide complementary to hepatitis B virus RNA. GalNAc conjugation targets the liver through the asialoglycoprotein receptor (ASGPR). This phase I single ascending dose (SAD) study evaluated the safety, tolerability, and pharmacokinetics of RO7062931 in Chinese healthy volunteers.

Interstitial lung abnormalities in a large clinical lung cancer screening cohort: association with mortality and ILD diagnosis.

Background: Interstitial lung abnormalities (ILA) are CT findings suggestive of interstitial lung disease in individuals without a prior diagnosis or suspicion of ILD. Previous studies have demonstrated that ILA are associated with clinically significant outcomes including mortality. The aim of this study was to determine the prevalence of ILA in a large CT lung cancer screening program and the association with clinically significant outcomes including mortality, hospitalizations, cancer and ILD diagnosis.

SAINT: A Phase I/Expanded Phase II Study Using Safe Amounts of Ipilimumab, Nivolumab and Trabectedin as First-Line Treatment of Advanced Soft Tissue Sarcoma.

Background: This Phase 1/2 study is based on the hypothesis that immune checkpoint inhibitors are more effective when given earlier in the course of the disease for advanced soft tissue sarcoma.

Methods: Phase I endpoints-maximum tolerated dose in previously treated patients; Phase II endpoints-best response, progression free survival and overall survival and incidence of adverse events in previously untreated patients; Phase I treatments-escalating doses of trabectedin (1.0, 1.

Affordable, portable and self-administrable electrical impedance tomography enables global and regional lung function assessment.

Accessibility of diagnostic screening and treatment monitoring devices for respiratory diseases is critical in promoting healthcare and reducing sudden complications and mortality. Spirometry is the standard for diagnosing and monitoring several lung diseases. However, it lacks regional assessment capabilities necessary for detecting subtle regional changes in certain diseases.

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.

Background: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

Introduction: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR.

Methods: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367).

Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial.

To evaluate the insulin-only configuration of the iLet bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). In this multicenter, randomized, controlled trial, 165 youth with T1D (6-17 years old; baseline HbA1c 5.8%-12.

Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

Background: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.

Methods: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring).

Lamin-A/C Is Modulated by the Involvement of Histamine-Mediated Calcium/Calmodulin-Dependent Kinase II in Lung Cancer Cells.

Lamins are nuclear envelope proteins involved in various cellular functions, such as DNA modulation, cellular differentiation, and development. In this study, we investigate the role of histamine in lung cancer biology. Since it is known that lamin-A/C is negatively regulated in lung cancer, we hypothesize that histamine signaling is related to nuclear lamin-A/C regulation and cancer progression.

SARS-CoV-2 Outbreak Dynamics in an Isolated US Military Recruit Training Center With Rigorous Prevention Measures.

Background: Marine recruits training at Parris Island experienced an unexpectedly high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite preventive measures including a supervised, 2-week, pre-entry quarantine. We characterize SARS-CoV-2 transmission in this cohort.

Methods: Between May and November 2020, we monitored 2,469 unvaccinated, mostly male, Marine recruits prospectively during basic training.

Teach 'em young: Influenza vaccines induce broadly neutralizing antibodies in children.

Antibodies against the influenza virus hemagglutinin stalk afford broad protection against antigenically drifted viruses. In this issue of , Yegorov et al. identify that current vaccine formulations induce neutralizing stalk antibodies in children-a highly vulnerable population.

Artificial Intelligence for Detecting and Delineating Margins of Early ESCC Under WLI Endoscopy.

Introduction: Conventional white light imaging (WLI) endoscopy is the most common screening technique used for detecting early esophageal squamous cell carcinoma (ESCC). Nevertheless, it is difficult to detect and delineate margins of early ESCC using WLI endoscopy. This study aimed to develop an artificial intelligence (AI) model to detect and delineate margins of early ESCC under WLI endoscopy.