Multifunctional Near Infrared Polymer Dots for Enhanced Synergistic Photodynamic/Photothermal Effect In Vitro.

Synergistic photodynamic/photothermal therapy (PDT/PTT) can be used to target cancer cells by locally generating singlet oxygen species or increasing temperature under laser irradiation. This approach offers higher tumor ablation efficiency, lower therapeutic dose requirements, and reduced side effects compared to single treatment approaches. However, the therapeutic efficiency of PDT/PTT is still limited by the low oxygen levels within the solid tumors caused by abnormal vasculature and altered cancer cell metabolism.

Novel clinical trial designs emerging from the molecular reclassification of cancer.

Next-generation sequencing has revealed the disruptive reality that advanced/metastatic cancers have complex and individually distinct genomic landscapes, necessitating a rethinking of treatment strategies and clinical trial designs. Indeed, the molecular reclassification of cancer suggests that it is the molecular underpinnings of the disease, rather than the tissue of origin, that mostly drives outcomes. Consequently, oncology clinical trials have evolved from standard phase 1, 2, and 3 tissue-specific studies; to tissue-specific, biomarker-driven trials; to tissue-agnostic trials untethered from histology (all drug-centered designs); and, ultimately, to patient-centered, N-of-1 precision medicine studies in which each patient receives a personalized, biomarker-matched therapy/combination of drugs.

A double dissociation between semantic and spatial cognition in visual to default network pathways.

Processing pathways between sensory and default mode network (DMN) regions support recognition, navigation, and memory but their organisation is not well understood. We show that functional subdivisions of visual cortex and DMN sit at opposing ends of parallel streams of information processing that support visually mediated semantic and spatial cognition, providing convergent evidence from univariate and multivariate task responses, intrinsic functional and structural connectivity. Participants learned virtual environments consisting of buildings populated with objects, drawn from either a single semantic category or multiple categories.

Tensor Train Optimization for Conformational Sampling of Organic Molecules.

Exploring the conformational space of molecules remains a challenge of fundamental importance to quantum chemistry: identification of relevant conformers at ambient conditions enables predictive simulations of almost arbitrary properties. Here, we propose a novel approach, called TTConf, to enable conformational sampling of large organic molecules where the combinatorial explosion of possible conformers prevents the use of a brute-force systematic conformer search. We employ tensor trains as a highly efficient dimensionality reduction algorithm, effectively reducing the scaling from exponential to polynomial.

Collagen Alpha 1(XI) Amino-Terminal Domain Modulates Type I Collagen Fibril Assembly.

The amino-terminal domain of collagen α1(XI) plays a key role in controlling fibrillogenesis. However, the specific mechanisms through which various isoforms of collagen α1(XI) regulate this process are not fully understood. We measured the kinetics of collagen type I self-assembly in the presence of specific collagen α1(XI) isoforms.

Computationally Efficient Polarizable MD Simulations: A Simple Water Model for the Classical Drude Oscillator Polarizable Force Field.

An improvement in the computational efficiency of polarizable force field simulations is made through the development of a polarizable Drude water model, SWM3, in combination with the use of Lennard-Jones Particle Mesh Ewald (LJPME) for the treatment of long-range LJ interactions. The experimental bulk properties, density, heat of vaporization, dielectric constant, and self-diffusion constant of the SWM3 model are accurately replicated at ambient condition. The temperature dependence of the bulk properties is also captured except for the density.

Modular Synthesis of Anti-HER2 Dual-Drug Antibody-Drug Conjugates Demonstrating Improved Toxicity.

Antibodies have gained clinical success in the last two decades for the targeted delivery of highly toxic small molecule chemotherapeutics. Yet antibody-drug conjugates (ADCs) often fail in the clinic due to the development of resistance. The delivery of two mechanistically distinct small molecule drugs on one antibody is of increasing interest to overcome these challenges with single-drug ADCs.

A Multipotent PROX1+ Tumor Stem/Progenitor Cell Population Emerges During Intestinal Tumorigenesis and Mediates Radioresistance in Colorectal Cancer.

Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells.

Catalytic Serine Labeling in Nonaqueous, Acidic Media.

Chemoselective modification of alkylalcohols (e.g., serine residues) on proteins has been a daunting challenge especially in aqueous media.

Nanoscale Manipulation of Single-Molecule Conformational Transition through Vibrational Excitation.

Controlling molecular actions on demand is a critical step toward developing single-molecule functional devices. Such control can be achieved by manipulating the interactions between individual molecules and their nanoscale environment. In this study, we demonstrate the conformational transition of a single pyrrolidine molecule adsorbed on a Cu(100) surface, driven by vibrational excitation through tunneling electrons using scanning tunneling microscopy.

Psychological Challenges of Adults With Severe Mental Illness During the COVID-19 Pandemic.

The COVID-19 pandemic was an unprecedented global health crisis. Vulnerable populations with preexisting mental illness have been disproportionately burdened and may experience adverse mental health outcomes related to the COVID-19 pandemic. Our objective was to evaluate the association between COVID-19 diagnosis, known exposure to COVID-19, sheltering in place, symptom severity, psychological distress, and depression severity among adults with severe mental illness (SMI).

Bivalent OX40 Aptamer and CpG as Dual Agonists for Cancer Immunotherapy.

Cancer immunotherapy has revolutionized cancer treatment by harnessing the body's immune system to recognize and attack tumors. Over the past 25 years, the use of blocking antibodies has fundamentally transformed the landscape of cancer therapy. However, despite extensive research, agonist antibodies targeting costimulatory receptors such as ICOS, GITR, OX40, CD27, and 4-1BB have consistently underperformed in clinical trials over the past 15 years, failing to meet the anticipated success.

Which is the most cost-effective antiseizure medication for initial monotherapy for focal epilepsy?

Objective: An increasing number of antiseizure medications (ASMs) are approved for monotherapy for focal epilepsy, but direct comparisons of the lifetime cost-effectiveness of all existing treatment strategies are lacking. This study aims to compare the cost-effectiveness of new ASMs and traditional ASMs as first-line monotherapy for newly diagnosed focal epilepsy.

Method: We used a Markov model to evaluate the lifetime cost-effectiveness of 10 ASMs in the treatment of focal epilepsy, with lacosamide (LCM) as a control, from the perspective of society in the United States.

FLT3 is genetically essential for ITD-mutated leukemic stem cells but dispensable for human hematopoietic stem cells.

Leukemic stem cells (LSCs) fuel acute myeloid leukemia (AML) growth and relapse, but therapies tailored towards eradicating LSCs without harming normal hematopoietic stem cells (HSCs) are lacking. FLT3 is considered an important therapeutic target due to frequent mutation in AML and association with relapse. However, there has been limited clinical success with FLT3 drug targeting, suggesting either that FLT3 is not a vulnerability in LSC, or that more potent inhibition is required, a scenario where HSC toxicity could become limiting.

Aging platelets shift their hemostatic properties to inflammatory functions.

Platelets are crucial players in hemostasis and thrombosis, but also contribute to immune regulation and host defense, using different receptors, signaling pathways and effector functions, respectively. Whether distinct subsets of platelets specialize in these diverse tasks is insufficiently understood. Here, we employed an in vivo pulse-labelling method in Mus musculus models for tracking in vivo platelet ageing and its functional implications.

Sodium-glucose cotransporter 2 inhibitor treatment has differential effects on the incidence of various malignancies: Evidence from a spontaneous adverse reaction database.

Objective: Sodium-glucose cotransporter (SGLT) 2 inhibitors are expected to demonstrate secondary effects against malignancy. However, long-term and large-scale data are required to evaluate the effects of SGLT2 inhibitors on malignancy, which has not been sufficiently studied in clinical practice. This study aimed to evaluate the association between SGLT2 inhibitors and malignancy using the spontaneous adverse reaction database.

CD44-Mediated Metabolic Rewiring is A Targetable Dependency of IDH-Mutant Leukemia.

Recurrent IDH mutations catalyze NADPH-dependent production of oncometabolite R-2HG for tumorigenesis. IDH inhibition provides clinical response in a subset of acute myeloid leukemia (AML) cases; however, most patients develop resistance, highlighting the need for more effective IDH-targeting therapies. By comparing transcriptomic alterations in isogenic leukemia cells harboring CRISPR base-edited IDH mutations, we identify the activation of adhesion molecules including CD44, a transmembrane glycoprotein, as a shared feature of IDH-mutant leukemia, consistent with elevated CD44 expression in IDH-mutant AML patients.

IL-1R1 and IL-18 Signals Regulate Mesenchymal Stromal Cells in an Aged Murine Model of Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are age-related diseases characterized by bone marrow (BM) dysfunction and an increased risk of developing acute leukemia. While there is growing evidence highlighting the crucial role of the BM microenvironment (BMME) in MDS, the specific influence of inflammation on BMME changes, as well as the potential benefits of targeting cytokines therapeutically, remain to be elucidated. We previously found interleukin-1 (IL-1) to be a driver of aging phenotypes of BMME and hematopoietic stem and progenitor cells (HSPCs).

LI-RADS Ultrasound Surveillance Version 2024: Comparison With Version 2017 for Hepatocellular Carcinoma Detection and Risk Factors for Visualization Score C.

The LI-RADS Ultrasound Surveillance algorithm was updated in 2024, incorporating alpha-fetoprotein (AFP) and visualization score of VIS-C into management recommendations after nonpositive results. This study aimed to compare the diagnostic performance of LI-RADS Ultrasound Surveillance version 2017 (v2017) and version 2024 (v2024) for hepatocellular carcinoma (HCC) detection in at-risk patients and to identify predictors of VIS-C on follow-up surveillance examinations. This retrospective analysis included 407 patients (median age, 56 years; 230 male, 177 female) with cirrhosis who underwent rounds of semi-annual surveillance ultrasound as part of a prospective trial from November 2011 to December 2012.

Association of mental health treatment receipt with cancer screening among US adults with a history of anxiety or depression.

Background: Low participation in cancer screening contributes to a disproportionate burden of cancer morbidity and mortality among adults with mental health (MH) disorders like depression and anxiety. It is unknown whether MH treatment affects screening participation in this population.

Methods: Using the 2019 and 2021 National Health Interview Survey, data from screening-eligible respondents with a history of depression or anxiety were analyzed.

A comprehensive review of clinical experiences and extracurricular activities for US premedical students applying to osteopathic medical schools.

Context: The healthcare industry faces a critical shortage of qualified physicians. To address this growing concern, medical schools nationwide are increasing their efforts to recruit and train premedical students to fill this gap. Those efforts include adequately preparing premedical students with the competencies and skills to meet the application requirements and gain acceptance to the medical school of their choosing.

The impact of pediatric post-cardiac arrest care on survival: A multicenter review from the AHA get with the Guidelines®-resuscitation post-cardiac arrest care registry.

Aim: Adherence to post-cardiac arrest care (PCAC) recommendations is associated with improved outcomes for adults. We aimed to describe the survival impact of meeting American Heart Association (AHA) PCAC guidelines in children after cardiac arrest.

Methods: We conducted a retrospective study using Get With The Guidelines® Resuscitation's (GWTG®-R) registry to describe the PCAC of patients ≤ 18 years old who suffered an in-hospital or out-of-hospital cardiac arrest (IHCA or OHCA).

NMR Spectral Editing, Water Suppression, and Dipolar Decoupling in Low-Field NMR Spectroscopy Using Optimal Control Pulses and Multiple-Pulse Sequence.

Spectral dispersion in low-field nuclear magnetic resonance (NMR) can significantly affect NMR spectral analysis, particularly when studying complex mixtures like metabolic profiling of biological samples. To address signal superposition in these spectra, we employed spectral editing with selective excitation pulses, proving it to be a suitable approach. Optimal control pulses were implemented in low-field NMR and demonstrated their capability to selectively excite and eliminate specific amino acids, such as phenylalanine and taurine, either individually or simultaneously.