Scaffold-enabled high-resolution cryo-EM structure determination of RNA.

Cryo-EM structure determination of protein-free RNAs has remained difficult with most attempts yielding low to moderate resolution and lacking nucleotide-level detail. These difficulties are compounded for small RNAs as cryo-EM is inherently more difficult for lower molecular weight macromolecules. Here we present a strategy for fusing small RNAs to a group II intron that yields high resolution structures of the appended RNA.

Creating codes of ethics for public health professionals and institutions.

Background: The World Health Organization and the Association of Schools of Public Health in the European Region called for the professionalization of the public health workforce, including the creation of codes of ethics. In this article, the Public Health Ethics and Law Network provides guidance on creating such codes, based on values and principles commonly identified for public health.

Methods: Our interest was in codes addressing public health broadly rather than disciplines within public health.

Durability of response of UGN-101: Longitudinal follow up of multicenter study.

Purpose: UGN-101, a reverse thermal mitomycin gel for upper tract instillation, recently became the first FDA approved treatment for upper tract urothelial carcinoma (UTUC). However, the durability of UGN-101 treatment has not been well described. Here we present long term outcomes from our multi-institutional cohort for patients who initially responded to treatment.

Predicting 90-day return to the emergency department in orthopaedic trauma patients in the Southeastern USA: a machine-learning approach.

Introduction: Return-to-acute-care metrics, such as early emergency department (ED) visits, are key indicators of healthcare quality, with ED returns following surgery often considered avoidable and costly events. Proactively identifying patients at high risk of ED return can support quality improvement efforts, allowing interventions to target vulnerable patients. With its predictive capabilities, machine learning (ML) has shown potential in forecasting various clinical outcomes but remains underutilised in orthopaedic trauma.

Effects of estradiol administration on brain activation and anhedonia in perimenopausal women: A pharmaco-fMRI study.

Background: Half of perimenopausal women experience depressive symptoms, including anhedonia. Anhedonia is associated with dysregulation of the frontostriatal circuit. Both the frontrostriatal circuit and depression may be regulated by the reproductive hormone estradiol (E2).

An in-depth review of AI-powered advancements in cancer drug discovery.

The convergence of artificial intelligence (AI) and genomics is redefining cancer drug discovery by facilitating the development of personalized and effective therapies. This review examines the transformative role of AI technologies, including deep learning and advanced data analytics, in accelerating key stages of the drug discovery process: target identification, drug design, clinical trial optimization, and drug response prediction. Cutting-edge tools such as DrugnomeAI and PandaOmics have made substantial contributions to therapeutic target identification, while AI's predictive capabilities are driving personalized treatment strategies.

There is no "I" in team: Implications for academic radiology.

All of us must find the right balance between team science and fostering leadership with dynamic colleagues. That dichotomy was well-encapsulated in a famous exchange between basketball players Shaquille O'Neal and Kobe Bryant regarding there "being no 'I' in team". In our view, there is nothing more satisfying than collaborating with a team of people and publishing impactful papers or making key discoveries.

Mouse models of Kaposi sarcoma-associated herpesvirus (KSHV).

Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is a prerequisite for the development of several human cancers, including Kaposi sarcoma and primary effusion lymphoma. Efficient long-term infection with KSHV and subsequent virally induced cell transformation is limited to humans, resulting in a lack of small animal models for KSHV-driven malignancies. Various attempts to create a mouse model for KSHV include infection of humanized mice, generating transgenic mice that ectopically express viral proteins, and grafting KSHV-infected tumor, primary, or immortalized cells onto immunodeficient mice.

Assessment of Malaria Rapid Diagnostic Tests and Histidine-Rich Protein 2 Deletions among Asymptomatic Children and Adults in Bagamoyo, Tanzania.

Malaria rapid diagnostic tests (mRDTs) that detect histidine-rich protein 2 (HRP2) remain the mainstay of falciparum malaria diagnosis in Sub-Saharan Africa. Understanding their test characteristics when used for surveillance in asymptomatic populations is important. We explored the rate of false-positive and false-negative mRDT results among asymptomatic persons >5 years old screened for malaria at schools and clinics in the rural Bagamoyo District using 18S ribosomal RNA real-time polymerase chain reaction (qPCR) as the reference test.

Multi-modal investigation reveals pathogenic features of diverse DDX3X missense mutations.

De novo mutations in the RNA binding protein DDX3X cause neurodevelopmental disorders including DDX3X syndrome and autism spectrum disorder. Amongst ~200 mutations identified to date, half are missense. While DDX3X loss of function is known to impair neural cell fate, how the landscape of missense mutations impacts neurodevelopment is almost entirely unknown.

A human pathogenic hantavirus circulates and is shed in taxonomically diverse rodent reservoirs.

Background: Orthohantaviruses are negative-sense RNA viruses that can cause hantavirus cardiopulmonary syndrome (HCPS) in humans. In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of HCPS, with a fatality rate of 36% and most cases occuring in the southwestern states. The western deer mouse, Peromyscus sonoriensis, is the primary reservoir for SNV; however, it remains unclear if alternative reservoirs exist.

Pitch Types and Their Influence on Elbow Varus Torque and Spin Rate in Professional Baseball Pitchers.

Background: Elbow injuries are prevalent among professional baseball pitchers as nearly 25% undergo ulnar collateral ligament reconstruction. Pitch type, ball velocity, and spin rate have been previously hypothesized to influence elbow varus torque and subsequent risk of injury, but existing research is inconclusive.

Purpose: To examine elbow varus torque, cumulative torque, and loading rate within professional pitchers throwing fastball, curveball, change-up, and slider pitches, as well as to identify potential influences of ball spin on the elbow.

Randomized phase II study of bevacizumab with weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant/refractory high grade ovarian cancer (NCI trial).

Purpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC).

Early vs. Delayed Switching from Controlled to Assisted Ventilation: A Target Trial Emulation.

Rationale: In critically ill patients receiving invasive mechanical ventilation, switching from controlled to assisted ventilation is a crucial milestone towards ventilator liberation. The optimal timing for switching to assisted ventilation has not been studied.

Objectives: Our objective was to determine whether a strategy of early as compared to delayed switching affects the duration of invasive mechanical ventilation, ICU length of stay, and mortality.

The gendered nature of leader behaviors: Navigating stereotype threat from conservation of resources and gender role perspectives.

Previous research has highlighted the benefits followers gain from their leaders' initiating structure and consideration. Adopting a leader-centric perspective, we propose that leaders' gender influences the impact of these behaviors for leaders themselves. Drawing from conservation of resources and gender role theories, we explain why gender-role-inconsistent leader behaviors (behaviors that go against gender stereotypes, such as initiating structure for women and consideration for men) is detrimental, while engaging in gender-role-consistent leader behaviors (such as initiating structure for men and consideration for women) is beneficial.

Using Transcriptomic Signatures to Elucidate Individual and Mixture Effects of Inorganic Arsenic and Manganese in Human Placental Trophoblast HTR-8/SVneo Cells.

Prenatal exposure to the toxic metal inorganic arsenic (iAs) is associated with adverse pregnancy and fetal growth outcomes. These adverse outcomes are tied to physiological disruptions in the placenta. While iAs co-occurs in the environment with other metals such as manganese (Mn), there is a gap in the knowledge of the effects of metal-mixtures on the placenta.

MRI-assessed Dynamic Hyperinflation Induced by Tachypnea in Chronic Obstructive Pulmonary Disease: The SPIROMICS-HF Study.

Purpose To assess the repeatability of real-time cine pulmonary MRI measures of metronome-paced tachypnea (MPT)-induced dynamic hyperinflation and its relationship with chronic obstructive pulmonary disease (COPD) severity. Materials and Methods SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) (ClinicalTrials.gov identifier no.

Hospital Safety-Net Burden is Associated with Perioperative Outcomes in Primary Total Hip Arthroplasty: A Multistate Retrospective Analysis, 2015-2020.

Total hip arthroplasty (THA) is a widely performed surgical procedure in the United States, but disparities in THA outcomes related to hospital-level factors, such as safety-net burden, are underexplored. This study expands on previous research by analyzing multicenter, multistate data from 2015 to 2020 to investigate the impact of hospital safety-net burden-defined as the proportion of services billed to Medicaid and uninsured patients-on THA outcomes. This study is a retrospective analysis using data from the State Inpatient Databases for Florida, Kentucky, Maryland, New York, Washington, New Jersey, and North Carolina.

Sexual dimorphic effects of a keystone predator on prey communities.

The importance of trait variation has long been recognized in ecological and evolutionary research. The divergence of sexually dimorphic traits (e.g.

Haploid like spermatid generation by transplantation of neonatal mouse testicular tissue into the epididymal fat of castrated adult mouse.

Objective: Many cancer survivors may experience irreversible infertility due to chemotherapy treatment for childhood cancer. In this study, spermatogenesis development was evaluated following the grafting of fresh and frozen-thawed testicular tissue from neonatal mice to the epididymal fat of adult mice.

Methods: After bilateral castration of recipient mice, fresh or frozen-thawed neonatal testis tissues were grafted into the epididymal fat of the mice.

Rome Foundation Working Team Report: Consensus Statement on the Design and Conduct of Behavioural Clinical Trials for Disorders of Gut-Brain Interaction.

Background: Brain-gut behaviour therapies (BGBT) have gained widespread acceptance as therapeutic modalities for the management of disorders of gut-brain interaction (DGBI). However, existing treatment evaluation methods in the medical field fail to capture the specific elements of scientific rigour unique to behavioural trial evaluation.

Aims: To offer the first consensus on the development and testing of BGBT in DGBI.

DIGITAL THERAPEUTIC COMBINING HYPNOSIS AND DIAPHRAGMATIC BREATHING INTERVENTION FOR FUNCTIONAL ABDOMINAL BLOATING (FAB): A FEASIBILITY STUDY.

Background And Aims: Abdominal bloating is a difficult symptom to treat. Hypnotherapy and diaphragmatic intervention have separately shown benefit on bloating in prior work but have not been united into a single intervention. We aimed to obtain data on the potential therapeutic impact of a novel audio-recorded bloating treatment for bloating integrating hypnosis and diaphragmatic breathing, with proposed synergistic effect.