Dissection of Progressive Disease Patterns for a Modified Classification for Immunotherapy.

Importance: Progressive disease (PD) in patients treated with immune checkpoint inhibitors (ICIs) varies widely in outcomes according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Efforts to modify RECIST for ICI treatment have not resolved the heterogeneity in PD patterns, posing a clinical challenge.

Mechanisms of sterilizing immunity provided by an HIV-1 neutralizing antibody against mucosal infection.

Broadly neutralizing antibodies (bnAbs) against HIV-1 have been shown to protect from systemic infection. When employing a novel challenge virus that uses HIV-1 Env for entry into target cells during the first replication cycle, but then switches to SIV Env usage, we demonstrated that bnAbs also prevented mucosal infection of the first cells. However, it remained unclear whether antibody Fc-effector functions contribute to this sterilizing immunity.

Disturbed spatial WNT activation - a potential driver of the reticularized skin phenotype in Systemic Sclerosis (SSc).

Objectives: Little is known on the mechanisms necessary to maintain the physiological adult human skin integrity. This study aims to quantitatively describe anatomical changes in systemic sclerosis (SSc)-skin compared to controls and investigate the underlying mechanisms.

Methods: Skin morphology was histologically assessed in twenty-three SSc-patients, eighteen controls and fifteen patients with hypertrophic scars.

Heterozygous UBR5 variants result in a neurodevelopmental syndrome with developmental delay, autism, and intellectual disability.

E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the presence of autism, epilepsy, and, in some probands, a movement disorder.

Single Particle Dynamics at the Free Surface of Imidazolium-Based Ionic Liquids.

In this work, we carry out a systematic computer simulation investigation of the single particle dynamics at the free surface of imidazolium-based room temperature ionic liquids by applying intrinsic surface analysis. Besides assessing the effect of the potential model and temperature, we focus in particular on the effect of changing the anion type, and, hence, their shape and size. Further, we also address the role of the length of the cation alkyl chains, known to protrude into the vapor phase, on the surface dynamics of the ions.

Lead-Free Perovskite CsAgNaBiInCl Microcrystals for Scattering-Fluorescent Luminescent Solar Concentrators.

In recent years, luminescent solar concentrators (LSCs) have gained a renaissance as a pivotal transparent photovoltaic (PV) for building-integrated photovoltaics (BIPVs). However, most of the studies focused on light-selective LSCs, and less attention was paid to the utilization of the full solar spectrum. In this study, a lead-free microcrystal CsAgNaBiInCl (CANBIC) perovskite phosphor is demonstrated to have bifunctional effects of luminescent down-shifting (LDS) and light scattering for the fabrication of LSCs, realizing light response from ultraviolet (UV) to NIR regions by an edge-mounted Si solar cell.

Dermal penetration of 2-phenoxyethanol in humans: in vivo metabolism and toxicokinetics.

2-Phenoxyethanol (PhE) is an amphiphilic organic compound frequently used as a broad-spectrum preservative in cosmetic products and other consumer goods. PhE is also used as a biocidal component in occupational settings. A previous volunteer study by our working group following oral exposure to PhE showed that PhE is almost completely taken up into the human body followed by an extensive metabolization and fast urinary elimination.

Iron redox effect on the structure and viscosity of a sodium silicate glass and melt.

The viscosity of silicate melts is one of the most important physical properties for understanding high-temperature phenomena in magmatic systems and material processing. The effects of composition and temperature on viscosity have long been elucidated. Although iron ions are the main components of magmatic systems, their influence on viscosity remains unclear because the behavior of iron is complicated; iron ions have two redox states, Fe3+ and Fe2+.

Harnessing multimodal approaches for depression detection using large language models and facial expressions.

Detecting depression is a critical component of mental health diagnosis, and accurate assessment is essential for effective treatment. This study introduces a novel, fully automated approach to predicting depression severity using the E-DAIC dataset. We employ Large Language Models (LLMs) to extract depression-related indicators from interview transcripts, utilizing the Patient Health Questionnaire-8 (PHQ-8) score to train the prediction model.

is implicated in central nervous system, orofacial and maxillofacial anomalies.

Background: Previous studies in mouse, and zebrafish embryos show strong expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 ( in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.

Methods: Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies.

π-Lewis Base Activation of Carbonyls and Hexafluorobenzene.

We report hitherto elusive side-on η2-bonded palladium(0) carbonyl (anthraquinone, benzaldehyde) and arene (benzene, hexa-fluorobenzene) palladium(0) complexes and present the catalytic hydrodefluorination of hexafluorobenzene by cyclohexene. The comparison with respective cyclohexene, pyridine and tetrahydrofuran complexes reveals that the experimental ligand binding strengths follow the order THF < C6H6 < C6F6 < cyclohexene < pyridine < benzaldehyde < anthraquinone. To understand this surprising order, the complexes' electronic structures were elucidated by nuclear magnetic resonance (NMR), single crystal X-Ray diffraction (sc-XRD), ultraviolet/visible (UV/Vis) electronic absorption, infrared (IR) vibrational, Pd L3-edge X-ray absorption (XAS), and X-ray photoelectron (XP) spectroscopic techniques, complemented by Density Functional Theory (DFT) calculations including energy decomposition (EDA-NOCV) and effective oxidation state (EOS) analyses.

iKNOW-Supporting the counseling of women with hereditary risk of breast and ovarian cancer with digital technologies: A randomized controlled trial.

Purpose: We developed the online-based counseling tool iKNOW for women with a pathogenic germline variant in to improve risk understanding and quality of life.

Methods: With a randomized controlled trial, we investigated the efficacy of iKNOW with regard to risk understanding (primary endpoint), quality of life, risk perception, and anxiety (secondary endpoints). Self-report questionnaires were administered to  = 217 women with a pathogenic variant in before counseling (T0), immediately after (T1), 4 weeks after (T2), and 6 months after (T3).

Cross-reactivity of anti-modified protein antibodies in rheumatoid arthritis.

This review comprehensively discusses the cross-reactivity of autoantibodies against modified proteins (AMPAs), the hallmark of rheumatoid arthritis (RA). We found that regardless of tissue sources, subtypes, or isotypes of B cells, AMPAs show high cross-reactivity within and across antigens undergoing citrullination, carbamylation, lysine-acetylation or ornithine-acetylation. The cross-reactive patterns of AMPAs display clonal and individual heterogeneity.

Utilizing machine learning-based QSAR model to overcome standalone consensus docking limitation in beta-lactamase inhibitors screening: a proof-of-concept study.

In virtual drug screening, consensus docking is a standard in-silico approach consisting of a combined result from optimized docking experiments, a minimum of two results combination. Therefore, consensus docking is subjected to a lower success rate than the best docking method due to its mathematical nature, an unavoidable limitation. This study aims to overcome this drawback via random forest, an ensemble machine learning model.

Tracking of spaceflight-induced bone remodeling reveals a limited time frame for recovery of resorption sites in humans.

Mechanical unloading causes bone loss, but it remains unclear whether disuse-induced changes to bone microstructure are permanent or can be recovered upon reloading. We examined bone loss and recovery in 17 astronauts using time-lapsed high-resolution peripheral quantitative computed tomography and biochemical markers to determine whether disuse-induced changes are permanent. During 6 months in microgravity, resorption was threefold higher than formation.

The discharge characteristics of motor units innervating functionally paralyzed muscles.

For individuals with motor complete spinal cord injury (SCI), previous works have shown that spared motor neurons below the injury level can still be voluntarily controlled. In this study, we investigated the behavior of these neurons after SCI by analyzing neural and spatial properties of individual motor units using high-density surface electromyography (HDsEMG) and ultrasound imaging. The dataset for this study is based on motor unit data from our previous work (Oliveira .

A Network Biology-Guided Investigation of the Long Noncoding RNAs' Role in Glaucoma.

Glaucoma is a group of eye diseases characterized by progressive harm to the optic nerve that often results in loss of vision and blindness. Recent studies suggest that deregulation in the expression of a particular type of RNAs named long noncoding RNAs (lncRNAs) can impact the development of glaucoma and, hence, are promising targets for drug discovery. LncRNAs are transcripts with a length longer than 200 nucleotides that are not translated into proteins.

A Practical Guideline for MicroRNA Sequencing Data Analysis in Chronic Lymphocytic Leukemia.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. They have been associated with several diseases and cancers, including chronic lymphocytic leukemia (CLL). CLL is the most common form of adult leukemia, and its pathogenesis is driven by the deletion of miRNAs, such as the miR-15a/16-1 cluster.

The Role of Non-coding RNAs in Tumorigenesis, Diagnosis/Prognosis, and Therapeutic Strategies for Cutaneous Melanoma.

RNA is a substance with various biological functions. It serves as blueprint for proteins and shuttles information from the genes to the protein factories of the cells. However, these factories-the ribosomes-are also composed mainly of RNA, whose purpose is not storing information but enzymatic action.

Overview of the Different Classes of Small RNAs During B-Cell Development.

B lymphocytes (B cells) are a type of white blood cell that play an essential role in the adaptive immune response. They are derived from pluripotent hematopoietic stem cells and undergo several developmental stages in the bone marrow and secondary lymphoid organs to become effector cells. B cells can act as antigen-presenting cells, secrete cytokines, generate immunological memory as memory B cells, and produce and secrete high-affinity antibodies as plasma B cells.

Odor prediction of whiskies based on their molecular composition.

Aroma compositions are usually complex mixtures of odor-active compounds exhibiting diverse molecular structures. Due to chemical interactions of these compounds in the olfactory system, assessing or even predicting the olfactory quality of such mixtures is a difficult task, not only for statistical models, but even for trained assessors. Here, we combine fast automated analytical assessment tools with human sensory data of 11 experienced panelists and machine learning algorithms.

Prosody-focused feedback enhances the efficacy of anti-depressive self-statements in depressed individuals - A randomized controlled trial.

This study was aimed to evaluate whether the efficacy of invoking anti-depressive self-statements to cope with depressed mood can be enhanced for depressed individuals by systematically guiding them to amplify the expression of conviction in their voice. Accordingly, we recruited N = 144 participants (48 clinically depressed individuals, 48 sub-clinically depressed individuals, and 48 non-depressed individuals). Participants were randomly assigned to an experimental or control condition.

Using normalisation process theory to identify factors facilitating the scaling up of parenting programs for immigrant parents.

Objective: As most studies focus on the initial adaptation of culturally tailored parenting programs in real-world settings, scalability and sustainability remain understudied. In this study, we used normalization process theory (NPT) as a conceptual framework to identify and understand the contextual factors impacting the scalability and sustainability of a culturally tailored parenting program, Ladnaan, in three Swedish municipalities.

Method: Nineteen managers, coordinators, and group leaders completed a survey and participated in individual or focus group interviews.

Patient perspectives on the use of digital medical devices and health data for AI-driven personalised medicine in Parkinson's Disease.

Introduction: Parkinson's Disease (PD) affects around 8.5 million people currently with numbers expected to rise to 12 million by 2040. PD is characterized by fluctuating motor and non-motor symptoms demanding accurate monitoring.