Long-term, continuous, subcutaneous levodopa/carbidopa infusion with ND0612 in Parkinson's disease: 3-year outcomes from the open-label BeyoND study.

Introduction: ND0612 is being investigated as a continuous, subcutaneous levodopa/carbidopa infusion, in combination with oral levodopa/carbidopa, for motor fluctuations in Parkinson's disease (PD). One-year data from the ongoing BeyoND study (NCT02726386) showed that the ND0612 regimen was safe and well tolerated and provided a sustained ≥2-h improvement in daily Good ON-time through 12 months of treatment.

Methods: We describe 3-year safety and efficacy outcomes for participants who completed 12 months of ND0612 treatment in the core study period and entered the extension phase.

Global natural history infrastructure requires international solidarity, support, and investment in local capacity.

Amid global challenges like climate change, extinctions, and disease epidemics, science and society require nuanced, international solutions that are grounded in robust, interdisciplinary perspectives and datasets that span deep time. Natural history collections, from modern biological specimens to the archaeological and fossil records, are crucial tools for understanding cultural and biological processes that shape our modern world. At the same time, natural history collections in low and middle-income countries are at-risk and underresourced, imperiling efforts to build the infrastructure and scientific capacity necessary to tackle critical challenges.

Extracorporeal Life Support Organization 2024 Guideline for Early Rehabilitation or Mobilization of Adult Patients on Extracorporeal Membrane Oxygenation.

This Extracorporeal Life Support Organization guideline describes early rehabilitation or mobilization of patients on extracorporeal membrane oxygenation (ECMO). The guideline describes useful and safe practices put together by an international interprofessional team with extensive experience in the field of ECMO and ECMO rehabilitation or mobilization. The guideline is not intended to define the delivery of care or substitute sound clinical judgment.

Current Evidence on the Care of Young Infants With Hypothermia in the Emergency Department.

The presence of hypothermia among young infants in the emergency department may be a sign of serious or invasive bacterial infections, or invasive herpes simplex viral infection. However, hypothermia may also occur due to a variety of other infectious and noninfectious conditions or environmental exposure. In some settings, hypothermia may represent a protective, energy-conserving response to illness.

Viewing Asilomar from the Global South.

To many in the scientific community, the 1975 Asilomar Conference on Recombinant DNA stands as a singular achievement. This experiment in governance seemed to demonstrate that citizens could trust scientists to anticipate their fields' risks and propose sensible ways to regulate themselves. Over the past half-century, similar efforts have been made to govern controversial areas of research, from geoengineering to artificial intelligence.

Distinguishing classes of neuroactive drugs based on computational physicochemical properties and experimental phenotypic profiling in planarians.

Mental illnesses put a tremendous burden on afflicted individuals and society. Identification of novel drugs to treat such conditions is intrinsically challenging due to the complexity of neuropsychiatric diseases and the need for a systems-level understanding that goes beyond single molecule-target interactions. Thus far, drug discovery approaches focused on target-based in silico or in vitro high-throughput screening (HTS) have had limited success because they cannot capture pathway interactions or predict how a compound will affect the whole organism.

Cardiac MRI in Heart Transplantation: Approaches and Clinical Insights.

Orthotopic heart transplant (OHT) is a well-established therapy for end-stage heart failure that leads to improved long-term survival rates, with careful allograft surveillance essential for optimizing clinical outcomes after OHT. Unfortunately, complications can arise after OHT that can compromise the success of the OHT. Cardiac MRI is continually evolving, with a range of advanced techniques that can be applied to evaluate allograft structure and function.

Graph contrastive learning of subcellular-resolution spatial transcriptomics improves cell type annotation and reveals critical molecular pathways.

Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.

Learning too much from too little: False face stereotypes emerge from a few exemplars and persist via insufficient sampling.

Face stereotypes are prevalent, consequential, yet oftentimes inaccurate. How do false first impressions arise and persist despite counter-evidence? Building on the overgeneralization hypothesis, we propose a domain-general cognitive mechanism: insufficient statistical learning, or Insta-learn. This mechanism posits that humans are quick statistical learners but insufficient samplers.

A Statistically-Robust Model of the Axomyelin Unit under Normal Physiologic Conditions with Application to Disease States.

Despite tremendous progress in characterizing the myriad cellular structures in the nervous system, a full appreciation of the interdependent and intricate interactions between these structures is as yet unfulfilled. Indeed, few more so than the interaction between the myelin internode and its ensheathed axon. More than a half-century after the ultrastructural characterization of this axomyelin unit, we lack a reliable understanding of the physiological properties, the significance and consequence of pathobiological processes, and the means to gauge success or failure of interventions designed to mitigate disease.

A plasmid with the gene enhances the fitness of strains under laboratory conditions.

Antimicrobial resistance (AMR) is a major threat to global public health that continues to grow owing to selective pressure caused by the use and overuse of antimicrobial drugs. Resistance spread by plasmids is of special concern, as they can mediate a wide distribution of AMR genes, including those encoding extended-spectrum -lactamases (ESBLs). The CTX-M family of ESBLs has rapidly spread worldwide, playing a large role in the declining effectiveness of third-generation cephalosporins.

Plasmids encode and can mobilize onion pathogenicity in Pantoea agglomerans.

Pantoea agglomerans is one of four Pantoea species reported in the USA to cause bacterial rot of onion bulbs. However, not all P. agglomerans strains are pathogenic to onion.

A Qualitative Meta-Synthesis of Women's Experiences of Internalized Sociocultural Sexual Pressure.

Sexual coercion occurs when a person applies pressure to force another person to have unwanted sex. Yet, sociocultural expectations may also impact women's sexual consent/refusal behaviors in the absence of partner pressure. We conducted a qualitative meta-synthesis to investigate factors contributing to incongruent sexual decision-making (i.

Selective Neurectomy with Regenerative Peripheral Nerve Interface Surgery for Facial Synkinesis.

Selective neurectomy (SN) typically leaves cut nerve endings to be either free-floating or buried in facial muscles. Regenerative peripheral nerve interfaces (RPNIs) use autologous skeletal muscle grafts to provide a nonfacial muscle target for reinnervation. To evaluate the effectiveness of RPNI surgery with SN for improving postoperative facial function through botulinum toxin use and facial movement metrics.

Sickle Cell Trait Does Not Cause "Sickle Cell Crisis" Leading to Exertion-Related Death: A Systematic Review.

Globally, an estimated 300 million individuals have sickle cell trait (SCT), the carrier state for sickle cell disease. While sickle cell disease (SCD) is associated with increased morbidity and shortened lifespan, SCT has a lifespan comparable to that of the general population. However, "sickle cell crisis" has been used as a cause of death for decedents with SCT in reports of exertion-related death in athletes, military personnel, and individuals in police custody.

clustur: an R package for clustering features using sparse distance matrices.

The clustur R package implements the clustering algorithms found in the mothur software package for assigning 16S rRNA gene sequences to operational taxonomic units (OTUs). Making these algorithms accessible through the R ecosystem will foster their further development, broader application, and integration within other R packages.

Distribution of early-branching Cyanobacteriia and the potential habitats that gave rise to the earliest oxygenic phototrophs.

The evolution of oxygenic photosynthesis in the Cyanobacteria was one of the most transformative events in Earth history, eventually leading to the oxygenation of Earth's atmosphere. However, it is difficult to understand how the earliest Cyanobacteria functioned or evolved on early Earth in part because we do not understand their ecology, including the environments in which they lived. Here, we use a cutting-edge bioinformatics tool to survey nearly 500,000 metagenomes for relatives of the taxa that likely bookended the evolution of oxygenic photosynthesis to identify the modern environments in which these organisms live.

Mentorship in Plastic Surgery: A Systematic Review of the Current Literature and Elucidation of Recurring Themes.

Background: Mentorship is an integral part of developing competent, passionate, and successful plastic surgeons and is an important element of surgeons' wellness. Although mentorship programs have been described in the literature, this study aimed to elucidate the specific qualities of an effective mentor in plastic surgery.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses methodology was utilized to conduct a systematic review of the literature.

Associations of neighbourhood food retail with disability and death in older adults: Cardiovascular Health Study.

Background: A healthier diet is associated with lower chronic disease burden, but the impact of neighbourhood food environments on disability and death in older adults is not known.

Methods: In the Cardiovascular Health Study, a cohort study of adults aged 65+, we calculated study years until death (years of life (YOL)), study years without activities of daily living (ADL) difficulty (years of able life; YoAL) and percent of study years without ADL difficulty (compression of disability). Linear regression quantified associations of food establishments within 5 km of baseline home address (as a z-score) with each outcome, adjusted for sociodemographic characteristics.

Mineralized tissue loss at the femoral ACL enthesis in young male ACL-injured patients.

Purpose: Primary anterior cruciate ligament (ACL) reconstruction graft failure remains a significant health concern in young patients. Despite the high incidence of poor graft integration in these patients and the resulting high failure rate, little consideration has been given to the quality of the bone into which the graft is anchored at reconstruction. Therefore, we investigated post ACL injury mineralized tissue changes in the ACL femoral entheses of young males and compared them to changes previously reported for young females.

Challenges and Recommendations for Proxy Reporting in Aging Research: A Brief Commentary.

The US has an aging population that is under-represented in research. Many older adults face barriers to research participation, such as mobility issues, comorbidities, and declining physical and cognitive health, which make it harder for them to understand study processes and give informed consent. Proxies can be family members, paid or unpaid caregivers, or healthcare providers who provide health information for older adults.

Comparative main effects, mediators, and moderators of cognitive behavioral therapy, acceptance and commitment therapy, and emotional awareness and expression therapy for chronic spinal pain: Randomized controlled trial rationale and protocol.

Background: Chronic spinal (back/neck) pain is common and costly. Psychosocial treatments are available but have modest effects. Knowledge of treatment mechanisms (mediators and moderators) can be used to enhance efficacy.

Assessing the Impact of Patient-Specific Instrumentation and Fixation on Accuracy and Radiation Exposure in a Cadaveric Model of Medial Opening-Wedge High Tibial Osteotomy.

Background: Traditional freehand techniques in high tibial osteotomy (HTO) have been shown to lack precision and accuracy. Patient-specific instrumentation (PSI) and fixation created from cross-sectional imaging have recently been introduced to address this problem.

Purpose/hypothesis: The purpose of the study was to compare traditional freehand techniques versus PSI in a human cadaveric model of HTO.