Tackling microbial iron homeostasis: novel antimicrobial strategies.

The escalating threat of antimicrobial resistance demands innovative therapeutic strategies beyond classical targets. Recent insights into the mechanisms of bacterial iron acquisition - ranging from siderophores and heme uptake to ferrous iron transport - have enabled new approaches to impair pathogen growth and virulence. These pathways are increasingly being harnessed for therapeutic gain.

Insights from the first 820 patients from the Brazilian Multicenter Registry of Hereditary Angioedema: the key role of genetic testing and targeted therapies.

Background: Hereditary angioedema (HAE) is a rare autosomal dominant disorder with a prevalence of 1:50,000 individuals. Delayed diagnosis and deaths from asphyxia still occur.

Objective: To identify knowledge and management gaps regarding clinical, genetic, and therapeutic aspects of HAE in Brazil, aiming to improve patient care and outcomes.

Dynamic control of electron correlations in photodoped charge-transfer insulators.

The electronic properties of correlated insulators are governed by the strength of Coulomb interactions, enabling the control of electronic conductivity with external stimuli. This work highlights that the strength of electronic correlations in nickel oxide (NiO), a prototypical charge-transfer insulator, can be coherently reduced by tuning the intensity of an optical pulse excitation. This weakening of correlations persists for hundreds of picoseconds and exhibits a recovery time independent of photodoping density across two orders of magnitude.

Phylodynamic estimation of the within-host evolutionary rate of extended-spectrum beta-lactamase-producing Enterobacterales.

Despite their clinical relevance, the within-host evolution of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales is still poorly understood. To estimate the within-host evolutionary rates of ESBL-producing and species complex, we fitted phylodynamic models to genomic sequence data of longitudinally collected rectal swabs from 63 colonized hospital patients. We estimated an average within-host evolutionary rate of 7.

Persistent progression independent of relapse activity in multiple sclerosis.

Patients with relapsing-remitting multiple sclerosis (RRMS) may experience disability progression independent of relapse activity (PIRA), which can be an early sign of secondary progressive MS (SPMS). We defined persistent PIRA as ongoing sustained disability over the entire available follow-up period. However, PIRA events can regress over time.

Multi-system benefits of non-invasive spinal cord stimulation following cervical spinal cord injury: a case study.

Unlabelled: Cervical spinal cord injury (SCI) impairs sensorimotor and autonomic functions. We investigated the effects of lumbosacral transcutaneous spinal cord stimulation (tSCS) on urinary bladder, bowel, and sexual function as well as cardiovascular and sensorimotor functions in one individual with chronic clinically motor-complete cervical SCI, 11 years post-injury. Following 30 sessions of lumbosacral tSCS, the individual presented with improved urinary bladder compliance as well as anorectal function in parallel with mitigation of the severity of autonomic dysreflexia during filling cystometry and anorectal manometry.

Using adaptive optics to assess hyporeflective clump speed and size in age-related macular degeneration in the PINNACLE Study. (PINNACLE Study Report 6).

Background/objectives: Hyporeflective clumps (HRC) are a common finding in adaptive optics ophthalmoscopy (AOO) of age-related macular degeneration (AMD). They appear on optical coherence tomography (OCT) as hyperreflective foci (HRF) or abutting the retinal pigment epithelium (RPE) layer as RPE thickening. The cellular origin of HRF is debated between migrated RPE cells and mononuclear phagocytes (MP).

Pragmatic evidence and the nature of randomized trials.

Pragmatic trials are increasingly gaining recognition. However, what pragmatic trials are is frequently misunderstood. They are frequently described superficially by their manifestation and surface only, as studies conducted in "real world" settings, having wide inclusion criteria, and less complicated study procedures.

Entangled cellular and molecular relationships at the sensory neuron-cancer interface.

Peripheral sensory neurons, once regarded merely as a passive route for nociceptive signals, are now acknowledged as active participants in solid tumor progression. This review explores how sensory neurons influence and are influenced by the tumor microenvironment (TME) through both chemical and electrical signaling, underscoring their pivotal role in the emerging field of cancer neuroscience. We summarize recent findings indicating that cancer-neuron interactions vary among different organs and experimental models, highlighting the ways in which various tumors recruit and reprogram sensory neurons to establish mutual communication loops that foster malignancy.

Injuries and anatomical variations of the female genitalia.

Background: Female genital injuries are often underreported or misinterpreted, particularly in cases of sexual violence. Until now, most research has focused on injuries caused by sexual intercourse, while injuries arising from everyday activities or anatomical variations have received less attention. This study aims to document genital injuries in healthy women, regardless of sexual assault, in order to contribute to an understanding of genital injury patterns and improve forensic interpretation.

Informing Facility Selection Through a Web-Based User Ratings System: Protocol for a Randomized Controlled Trial Among Mothers in Urban Lao People's Democratic Republic.

Background: Despite the increasing options for public and private health care providers in the Lao People's Democratic Republic (Lao PDR), choosing a high-quality provider or facility is difficult because timely and reliable information about providers is not readily available. Additionally, only 28% described their most recent visit to a health care provider as high quality, suggesting that while options for care are expanding, people may need support in finding providers that meet their quality needs. To inform efforts to improve access to high-quality care, evidence is needed on mechanisms that empower people to identify and use such care.

Deep Learning Modeling to Differentiate Multiple Sclerosis From MOG Antibody-Associated Disease.

Background And Objectives: Multiple sclerosis (MS) is common in adults while myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is rare. Our previous machine-learning algorithm, using clinical variables, ≤6 brain lesions, and no Dawson fingers, achieved 79% accuracy, 78% sensitivity, and 80% specificity in distinguishing MOGAD from MS but lacked validation. The aim of this study was to (1) evaluate the clinical/MRI algorithm for distinguishing MS from MOGAD, (2) develop a deep learning (DL) model, (3) assess the benefit of combining both, and (4) identify key differentiators using probability attention maps (PAMs).

Effectiveness of the national HIV pre-exposure prophylaxis (PrEP) programme among female sex workers in Rwanda: a retrospective cohort study.

Background: In 2018, Rwanda incorporated oral pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine (Truvada) into national HIV guidelines as part of a comprehensive HIV prevention programme for female sex workers (FSWs). This study assessed the impact of PrEP on HIV incidence among FSWs in urban Rwanda.

Methods: We conducted a retrospective cohort study among HIV-negative FSWs aged≥18 years at 20 health facilities in Kigali from January 2019 to October 2021.

Prediction of treatment outcome in patients receiving internet-delivered cognitive behavioural therapy for depressive and anxiety symptoms: a machine learning analysis of data from a healthcare-embedded longitudinal study.

Background: Digital therapeutics (DTx) show promise in bridging mental healthcare gaps. However, treatment selection often relies on availability and trial-and-error, prolonging suffering and increasing costs. Personalised prediction models could help identify individuals benefiting most from specific DTx.

Retrospective use of the PRECIS-2 trial design tool to assess design choices in randomised controlled trials; An empirical review.

Introduction: The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) tool has been widely used to help investigators design randomised trials, facilitating the task of aligning design choices with an explanatory or pragmatic primary trial intention. PRECIS-2 is increasingly being used to retrospectively assess the degree of pragmatism or explanatoriness among published trials within reviews. There is little information on the interrater reliability of the tool and no consensus on the preferred method of achieving an accurate and reliable judgement of trial 'pragmatism' when using PRECIS-2 retrospectively.

Preventing CpG hypermethylation in oocytes safeguards mouse development.

Except for regulatory CpG-island sequences, genomes of most mammalian cells are widely DNA-methylated. In oocytes, though, DNA methylation (DNAme) is largely confined to transcribed regions. The mechanisms restricting de novo DNAme in oocytes and their relevance thereof for zygotic genome activation and embryonic development are largely unknown.

Prospects of Nanoscience with Nanocrystals: 2025 Edition.

Nanocrystals (NCs) of various compositions have made important contributions to science and technology, with their impact recognized by the 2023 Nobel Prize in Chemistry for the discovery and synthesis of semiconductor quantum dots (QDs). Over four decades of research into NCs has led to numerous advancements in diverse fields, such as optoelectronics, catalysis, energy, medicine, and recently, quantum information and computing. The last 10 years since the predecessor perspective "Prospect of Nanoscience with Nanocrystals" was published in ACS Nano have seen NC research continuously evolve, yielding critical advances in fundamental understanding and practical applications.

Nonregistration, Discontinuation, and Nonpublication of Randomized Trials: A Systematic Review.

Importance: Previous work found that 25% to 30% of randomized clinical trials (RCTs) with protocols approved in 2012 or between 2000 and 2003 were discontinued prematurely, most commonly due to inadequate participant recruitment. To minimize research waste, RCTs should be registered and their results made available.

Objectives: To assess the fate of RCTs approved by ethics committees in 2016 in terms of nonregistration, discontinuation, and nonpublication, and to examine RCT characteristics associated with discontinuation due to poor recruitment and nonpublication of RCT results.

Disrupting Siglec-mediated interactions to develop immunotherapies for cancer treatment.

Introduction: Recent advances in cancer immunotherapy have improved patient outcomes, even in advanced stages of the disease. However, the effectiveness of current cancer immunotherapies remains limited to a small subset of patients because of resistance and an immunosuppressive tumor microenvironment.

Areas Covered: Research performed during the last years have identified immunosuppressive interactions between sialic acid-containing glycans and sialic acid-binding immunoglobulin-like lectin (Siglec) receptors as a potential new, targetable pathway to overcome resistance to immunotherapy.

Implantable Light-Powered Human Designer Cells for Electrical Energy Generation.

Herein, an implantable, miniature biohybrid device has been developed that utilizes light-dependent ion-gradient formation by genetically engineered human designer cells, expressing light-activated ion channels and proton pumps to generate electrical potential and deliver electrical energy. These designer cells are cultured in custom-designed polycarbonate chambers, connected by electrodes and separated from an ion reservoir by a proton-selective Nafion membrane. Upon illumination, the light-activated channels and pumps on the designer cells establish a sustained proton gradient across the Nafion membrane, which drives an electrical current in the external circuit.

Comparing Imaging Depth of Intravital Lung Imaging Using Perfluorocarbon-Based Liquid Ventilation With Tissue Clearing for Deep-Tissue Imaging.

Intravital lung imaging has been employed to study physiological and pathophysiological processes related to nanoparticle deposition in the alveolar lung, particularly in the context of air pollution and drug delivery. However, optical imaging depth is limited, often attributed to the refractive index (RI) mismatch at the alveolar air-tissue interface. To investigate this, we evaluated two complementary strategies.

A roadmap for navigating child health research data sharing across Canada and beyond - building on UCAN CAN-DU.

Background: Sharing health data within and across jurisdictions is important for research and improving healthcare quality; however, researchers, governments and funders must balance the benefits of data sharing with data privacy. Though frameworks exist to guide data sharing it can be difficult to translate these into practice. Therefore, our aim was to create a practical example of data sharing for researchers in pediatric rheumatology.

Prevalence and risk factors of mental health symptoms of individuals in different detention settings: a cross-sectional study.

Background: The prevalence of mental health symptoms is substantially higher in incarcerated individuals than in the general public. However, little is known how different types of incarceration, including pre-trial and correctional detention as well as detention exclusively for deportation proceedings (administrative detention), are associated with mental health symptoms. We aimed to investigate the prevalence of mental health symptoms in this vulnerable population and examine the impact of different types of detention as well as risk factors on their mental health symptoms.

The Prevalence of Potential Drug-Drug-Gene Interactions: A Descriptive Study Using Swiss Claims Data.

Purpose: We aimed to determine the prevalence of interactions between PGx drugs metabolized by CYP2C9, CYP2C19, and CYP2D6 and drugs that act as inhibitors or inducers of those enzymes in the Swiss population.

Patients And Methods: We defined concomitant use of PGx drugs and inhibitors/inducers as instances where a claim of a PGx drug and a claim of an inducer or inhibitor concerning the same enzyme were made within a specified temporal window, either ± 5 days or ± 30 days. We assessed concomitant drug use between 2017 and 2021, using claims data from a Swiss insurance company (Helsana).