Association between diffusion tensor imaging measurements and cognitive performances in people with multiple sclerosis: A systematic review and meta-analysis.

Background: Alterations in structural connectivity of brain networks have been linked to complex cognitive functions in people with multiple sclerosis (PwMS). However, a definitive consensus on the optimal diffusion tensor imaging (DTI) markers as indicators of cognitive performance remains incomplete and inconclusive. This systematic review and meta-analysis aimed to explore the evidence on the correlation between DTI metrics and cognitive functions in PwMS.

Endoscopic Ultrasound-Guided Treatments for Pancreatic Cancer: Understanding How Endoscopic Ultrasound Has Revolutionized Management of Pancreatic Cancer.

Pancreatic cancer is associated with high rates of morbidity and mortality. Endoscopic ultrasound (EUS)-guided biopsy has become the standard diagnostic modality per the guidelines. The use of EUS has been growing for providing various treatments in patients with pancreatic cancers: biliary and gallbladder drainage for those with malignant biliary obstruction, gastroenterostomy for malignant gastric outlet obstruction, celiac plexus/ganglia neurolysis for pain control, radiofrequency ablation, placement of fiducial markers, and injection of local chemotherapeutic agents.

A Brief History of Ferritin, an Ancient and Versatile Protein.

Ferritin, a highly conserved iron storage protein, is among the earliest proteins that have been purified, named, and characterized due to its unique properties that continue to captivate researchers. Ferritin is composed of 24 subunits that form an almost spherical shell delimiting a cavity where thousands of iron atoms can be stored in a nontoxic ferric form, thereby preventing cytosolic iron from catalyzing oxidative stress. Mitochondrial and extracellular ferritin have also been described and characterized, with the latter being associated with several signaling functions.

Novel Inhibitors for MDM2-MDM4 E3 Ligase Potently Induce p53-Indepedent Apoptosis in Drug-Resistant Leukemic Cells.

MDM2 and MDM4 are major negative regulators of tumor suppressor p53. Beyond regulating p53, MDM2 possesses p53-independent activity in promoting cell cycle progression and tumorigenesis via its RING domain ubiquitin E3 ligase activity. MDM2 and MDM4 form heterodimer polyubiquitin E3 ligases via their RING domain interaction.

Protein dynamics underlies strong temperature dependence of heat receptors.

Ion channels are generally allosteric proteins, involving specialized stimulus sensor domains conformationally linked to the gate to drive channel opening. Temperature receptors are a group of ion channels from the transient receptor potential family. They exhibit an unprecedentedly strong temperature dependence and are responsible for temperature sensing in mammals.

Advancing the Mechanosensitivity of Atropisomeric Diarylethene Mechanophores through a Lever-Arm Effect.

Understanding structure-mechanical activity relationships (SMARs) in polymer mechanochemistry is essential for the rational design of mechanophores with desired properties, yet SMARs in noncovalent mechanical transformations remain relatively underexplored. In this study, we designed a subset of diarylethene mechanophores based on a lever-arm hypothesis and systematically investigated their mechanical activity toward a noncovalent-yet-chemical conversion of atropisomer stereochemistry. Results from Density functional theory (DFT) calculations, single-molecule force spectroscopy (SMFS) measurements, and ultrasonication experiments collectively support the lever-arm hypothesis and confirm the exceptional sensitivity of chemo-mechanical coupling in these atropisomers.

Voices of Nanomedicine: Blueprint Guidelines for Collaboration in Addressing Global Unmet Medical Needs.

The "" under this Perspective underline the importance of interdisciplinary collaboration and partnerships across several disciplines, such as medical science and technology, medicine, bioengineering, and computational approaches, in bridging the gap between research, manufacturing, and clinical applications. Effective communication is key to bridging team gaps, enhancing trust, and resolving conflicts, thereby fostering teamwork and individual growth toward shared goals. Drawing from the success of the COVID-19 vaccine development, we advocate the application of similar collaborative models in other complex health areas such as nanomedicine and biomedical engineering.

Safety concerns associated with the use of benzodiazepines during MRI.

Magnetic resonance imaging (MRI) is a powerful diagnostic tool that uses strong magnetic fields and radio waves to create detailed images of the body's internal structures. This article examines the challenges associated with MRI, particularly focusing on patient anxiety and claustrophobic reactions that can lead to aborted scans. It discusses the use of anxiolytics, especially benzodiazepines, to manage these issues, while highlighting the potential risks of respiratory depression and other adverse outcomes in select patient populations.

Msh2-Msh3 DNA-binding is not sufficient to promote trinucleotide repeat expansions in Saccharomyces cerevisiae.

Mismatch repair (MMR) is a highly conserved DNA repair pathway that recognizes mispairs that occur spontaneously during DNA replication and coordinates their repair. In Saccharomyces cerevisiae, Msh2-Msh3 and Msh2-Msh6 initiate MMR by recognizing and binding insertion deletion loops (in/dels) up to ∼ 17 nucleotides (nt.) and base-base mispairs, respectively; the two complexes have overlapping specificity for small (1-2 nt.

Safety and Effectiveness of a New 532 nm, Long Pulse-Duration, Variable Pulse Structure Laser for Treatment of Poikiloderma of Civatte.

Background: Poikiloderma of Civatte is a benign skin condition characterized by reticulate erythema and hyperpigmentation in sun-exposed areas, predominantly on the neck, cheeks, and chest. Chronic UV exposure leads to vascular proliferation and red cell extravasation resulting in hemosiderin and melanin deposition. While many light-based modalities have been utilized to treat the disorder, the significant vascularity makes it ideally suited for treatment with vascular lasers.

Meta-Analysis of the Input and Disposition of Various Dosage Forms of Methylprednisolone in Healthy Subjects Utilizing a Physiologically Based Pharmacokinetic Model.

The study quantitatively analyzes and compares the pharmacokinetics (PK) of methylprednisolone (MPL) in humans upon administration of various dosage forms. The PK parameters and profiles of MPL in healthy subjects were collected from 22 literature sources. A minimal physiologically based pharmacokinetic (mPBPK) model consisting of blood and two tissue (lumped liver and kidney, remainder) compartments with nonlinear tissue partitioning was applied to describe MPL disposition.

Development of a portable SERS tool to evaluate the effectiveness of washing methods to remove pesticide residue from fruit surface.

Background: Pesticides are widely used in agriculture to control pests and enhance crop yields. However, post-harvest, there are growing concerns about the potential health risks posed by pesticide residues on produce surfaces. Analyzing these residues is challenging due to their typically low concentrations and the potential interference from the complex matrix of the produce's surface.

Superstable lipid vacuoles endow cartilage with its shape and biomechanics.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis.

A Systematic Review of Cancer-Related Trauma and Growth in Caregivers Across the Lifespan.

Background: Family members can be required to take on the role of "caregiver" at any stage of life, causing disruption and psychological distress. This review sought to describe the traumatic impact (i.e.

Gene regulation by convergent promoters.

Convergent transcription, that is, the collision of sense and antisense transcription, is ubiquitous in mammalian genomes and believed to diminish RNA expression. Recently, antisense transcription downstream of promoters was found to be surprisingly prevalent. However, functional characteristics of affected promoters are poorly investigated.

Development and optimization of an mRNA-vectored single-chain IgA1 isotype monoclonal antibody with potential to treat or prevent dengue virus infection.

Dengue virus (DENV) is a rapidly expanding infectious disease threat that causes an estimated 100 million symptomatic infections every year. A barrier to preventing DENV infections with traditional vaccines or prophylactic monoclonal antibody (mAb) therapies is the phenomenon of Antibody-Dependent Enhancement (ADE), wherein sub-neutralizing levels of DENV-specific IgG antibodies can enhance infection and pathogenesis rather than providing protection from disease. Fortunately, IgG is not the only antibody isotype capable of binding and neutralizing DENV, as DENV-specific IgA1 isotype mAbs can bind and neutralize DENV while without exhibiting any ADE activity.

Design of Cell-Penetrating Domain Antibodies via a Genetically Encoded β-Lactam Amino Acid.

Domain antibodies such as monobodies provide an attractive immunoglobin fold for evolving high-affinity protein binders targeting the intracellular proteins implicated in cell signalling. However, it remains a challenge to endow cell permeability to these small and versatile protein binders. Here, we report a streamlined approach combining orthogonal crosslinking afforded by a genetically encoded β-lactam-lysine (BeLaK) and genetic supercharging to generate cell-penetrating monobodies.

A Rare Case of Chronic Lymphocytic Leukemia Transforming Into Waldenström Macroglobulinemia During Ibrutinib Therapy.

Chronic lymphocytic leukemia (CLL) can rarely transform into Waldenström macroglobulinemia (WM), posing diagnostic and therapeutic challenges. The diagnosis of WM requires bone marrow infiltration by lymphoplasmacytic cells and the presence of IgM gammopathy. Immunophenotypic markers include FMC7+, CD19+, CD20+, and CD138+.

Denovo variants in POGZ and YY1 genes: The novel mega players for neurodevelopmental syndromes in two unrelated consanguineous families.

Novel denovo variants of exome sequences are major cause of pathogenic neurodevelopmental disorders with a dominant genetic mechanism that emphasize their heterogeneity and complex phenotypes. White Sutton syndrome and Gabriele-de-Vries syndrome are congenital neuro-impairments with overlap of severe intellectual disability, microcephaly, convulsions, seizures, delayed development, dysmorphism of faces, retinal diseases, movement disorders and autistic traits. POGZ gene codes for pogo transposable element-derived zinc-finger protein and YY1 gene regulates transcription, chromatin, and RNA-binding proteins that have been associated with White Sutton and Gabriele-de-Vries syndromes, in recent data.

A small cavity for detecting sound-induced flow.

A study is presented of a method for creating an acoustic flow sensor that is generally compatible with current silicon microfabrication processes. An aim of this effort is to obtain a design consisting of a minimal departure from the existing designs employed in mass-produced silicon microphones. Because the primary component in all of these microphones is the cavity behind the pressure-sensing diaphragm, we begin with a study of the acoustic particle velocity within a cavity in a planar surface.

Global Challenges in the Access of Endovascular Treatment for Acute Ischemic Stroke (Global MT Access).

Background: Mechanical thrombectomy (MT) is the standard of care for eligible acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) since 2015.

Aim: Our aim was to determine the key challenges for MT implementation and access worldwide.

Methods: We conducted an international online survey consisting of 37 questions, distributed through the World Stroke Organization network, and as invited by co-authors between December 2022 and March 2023.

Semisynthesis of Alkaloid Derivatives: Pyranoacridone-Hydroxamic Acid Cytotoxic Conjugates with HDAC and Topoisomerase II α Dual Inhibitory Activity.

Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from des--methylacronycine () and noracronycine () pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an cytotoxicity assay, KT32 () with noracronycine () as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC values of 1.

Experimental Myopia Results in Peripapillary Ganglion Cell and Astrocyte Reorganization with No Functional Implications During Early Development.

Myopic eye growth induces mechanical stretch, which can lead to structural and functional retinal alterations. Here, we investigated the effect of lens-induced myopic growth on the distribution of retinal ganglion cells (RGCs), glial fibrillary acidic protein (GFAP) expression and intensity, and peripapillary retinal nerve fiber layer (ppRNFL) thickness in common marmosets () induced with myopia continuously for six months, using immunohistochemistry and spectral-domain optical coherence tomography. We also explored the relationship between cellular structural parameters and the photopic negative response (PhNR) using full-field electroretinography.

Genetic Heterogeneity in Four Probands Reveals , , and Related Neurodevelopmental Disorders.

: Neurodevelopmental disorders of genetic etiology are a highly diverse set of congenital recurrent complications triggered by irregularities in the basic tenets of brain development. : We present whole exome sequencing analysis and expression characteristics of the probands from four unrelated Pakistani consanguineous families with facial dysmorphism, neurodevelopmental, ophthalmic, auditory, verbal, psychiatric, behavioral, dental, and skeletal manifestations otherwise unexplained by clinical spectrum. : Whole exome sequencing identifies a novel, bi-allelic, missense variant in the gene [NM_152419.