Harnessing the power of genomics in hypertension: tip of the iceberg?

Despite the blaze of advancing knowledge on its complex genetic architecture, hypertension remains an elusive condition. Genetic studies of blood pressure have yielded bitter-sweet results thus far with the identification of more than 2,000 genetic loci, though the candidate causal genes and biological pathways remain largely unknown. The era of big data and sophisticated statistical tools has propelled insights into pathophysiology and causal inferences.

Challenges and Opportunities in Implementing a Multicomponent Dementia Caregiver Program in a Complex Healthcare System.

The Tailored Activity Program (TAP), an intervention for people living with dementia (PLWD) and their caregivers, has been shown to reduce behavioral symptoms for PLWD and caregiver burden. While TAP is proven as an evidence-based practice (EBP), it has yet to be implemented at scale. The Department of Veterans Affairs (VA) has prioritized the Age-Friendly Health System (AFHS) initiative, providing an opportunity to test implementation of TAP in a complex healthcare system.

Activin A activation of Smad3 mitigates innate inflammation in mouse models of psoriasis and sepsis.

Phosphorylation of Smad3 is a critical mediator of TGF-β signaling, which plays an important role in regulating innate immune responses. However, whether Smad3 activation can be regulated in innate immune cells in TGF-β-independent contexts remains poorly understood. Here, we show that Smad3 is activated through the phosphorylation of its C-terminal residues (pSmad3C) in murine and human macrophages in response to bacterial and viral ligands, which is mediated by Activin A in a TGF-β independent manner.

Hematophagy generates a convergent genomic signature in mosquitoes and sandflies.

Blood-feeding (hematophagy) is widespread across Diptera (true flies), yet the underlying genetic basis remains poorly understood. Using phylogenomics, we show that four gene families associated with neuromodulation, immune responses, embryonic development, and iron metabolism have undergone independent expansions within mosquitoes and sandflies. Our findings illuminate the underlying genetic basis for blood-feeding adaptations in these important disease vectors.

Constructing future behavior in the hippocampal formation through composition and replay.

The hippocampus is critical for memory, imagination and constructive reasoning. Recent models have suggested that its neuronal responses can be well explained by state spaces that model the transitions between experiences. Here we use simulations and hippocampal recordings to reconcile these views.

Sensorineural and peripheral vascular responses induced by exposure to high-frequency vibration.

Background: Dentists, dental hygienist, and veterinary technicians using drills, scalers and polishers are at risk of developing sensorineural deficits in the fingers and hands. The goal of this study was to determine whether exposure to high-frequency vibration contributed to changes in sensory function.

Methods: The tails of rats were exposed to vibration at 1250 Hz (constant acceleration of 49 m/s2) for 4 hours per day, for 10 days.

Estimated Effectiveness of Nirsevimab Against Respiratory Syncytial Virus.

Importance: Nirsevimab, a long-acting monoclonal antibody, demonstrated efficacy against respiratory syncytial virus (RSV)-associated lower respiratory tract infections (LRTI) in clinical trials. Postlicensure monitoring is essential to confirm these benefits in clinical settings.

Objective: To estimate the effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization.

Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant.

Successful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T-cell-mediated post-transplant complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free/relapse-free survival for post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus/methotrexate (Tac/MTX), but did not improve overall survival. To compare T-cell biology between GVHD prophylaxis regimens, 324 patients were co-enrolled onto BMT CTN 1801 ( NCT03959241 ).

Distinct prelimbic cortex ensembles encode response execution and inhibition.

Learning when to initiate or withhold actions is essential for survival and requires integration of past experiences with new information to adapt to changing environments. While stable prelimbic cortex (PL) ensembles have been identified during reward learning, it remains unclear how they adapt when contingencies shift. Does the same ensemble adjust its activity to support behavioral suppression upon reward omission, or is a distinct ensemble recruited for this new learning? We used single-cell calcium imaging to longitudinally track PL neurons in rats across operant food reward Training, Extinction and Reinstatement, trained rat-specific decoders to predict trial-wise behavior, and implemented an deletion approach to characterize ensemble contributions to behavior.

Decoding the Nature of the Peritrich Stalk: A Distinctive Organelle in a Large Group of Ciliated Unicellular Eukaryotes.

Ciliates represent a diverse assemblage of ancient single-celled eukaryotes characterized by diverse morphological features. Among certain sessilid peritrich ciliates, an exceptional morphological structure known as the stalk has been documented since the pioneering work of Antonie van Leeuwenhoek in the 17th century. This study conducts a comparative genomic analysis of three sessile peritrich species-Epistylis sp.

Reduced temporal and spatial stability of neural activity patterns predict cognitive control deficits in children with ADHD.

This study investigates the neural underpinnings of cognitive control deficits in attention-deficit/hyperactivity disorder (ADHD), focusing on trial-level variability of neural coding. Using fMRI, we apply a computational approach to single-trial neural decoding on a cued stop-signal task, probing proactive and reactive control within the dual control model. Reactive control involves suppressing an automatic response when interference is detected, and proactive control involves implementing preparatory strategies based on prior information.

Sex differences in auditory function of the desert locust.

Age-related auditory decline manifests across the animal kingdom, from humans and mice to zebrafish and insects. Sex differences in auditory decline are established for humans, but there is now evidence in mice and even zebrafish. Here, we found sex differences in auditory decline in an insect, the Desert Locust and investigated its biological basis.

GoldPolish-target: targeted long-read genome assembly polishing.

Background: Advanced long-read sequencing technologies, such as those from Oxford Nanopore Technologies and Pacific Biosciences, are finding a wide use in de novo genome sequencing projects. However, long reads typically have higher error rates relative to short reads. If left unaddressed, subsequent genome assemblies may exhibit high base error rates that compromise the reliability of downstream analysis.

Trend and Provider- and Organizational-Level Factors Associated With Early Palliative Care Billing Among Patients Diagnosed With Distant-Stage Cancers in 2010-2019 in the United States.

Purpose: Early integration of specialized palliative care (PC) is recommended by clinical guidelines for advanced-stage cancers, but real-world evidence of its use is limited. We examined the recent trend of early PC billing among Medicare beneficiaries with distant-stage cancers and associated provider- and organization-level factors.

Methods: Using SEER-Medicare data, we identified Medicare Fee-For-Service beneficiaries 65.

A Posterior Approach for Combined Targeting of the Centromedian Nucleus and Pulvinar for Responsive Neurostimulation.

Background And Objectives: Neuromodulation for the treatment of epilepsy is a growing field, and several thalamic nuclei (including the anterior nucleus, centromedian nucleus [CM], and pulvinar) have been implicated and targeted. Although an anterior trajectory approach to the CM is conventionally used, we report on a novel posterior trajectory which can be useful when the conventional anterior approach is surgically challenging, or where dual CM and pulvinar coverage is desired.

Methods: Clinical and imaging data were retrospectively collected from 7 patients with at least 1 posterior trajectory CM lead and 4 patients with at least 1 anterior trajectory CM lead.

Demographics and Trends in Outpatient Surgery for Laryngeal Cancer: 2016-2021.

Objective: To analyze the utilization patterns of outpatient laryngoscopic excision procedures for laryngeal cancer in the United States, examining procedural costs and patient demographics to identify disparities in healthcare access.

Study Design: Retrospective cohort study.

Setting: National Ambulatory Surgery Sample database of major ambulatory surgeries in the United States, 2016-2021.

Substance Use and Pain Curriculum Innovation: Establishing a Student-Faculty Partnership for Curricular Change.

Problem: The opioid overdose crisis had progressed broadly in the United States, with an 21% increase from 2016 to 2017, and specifically in Massachusetts, with a peak rate of 1,374 deaths in 2016. In 2016, students and faculty at Harvard Medical School (HMS) established the Substance Use and Pain Curriculum Committee (SUPCC) to expand substance use and pain education. However, faculty capacity, financial resources, and administrative support were insufficient to implement changes across all phases of the medical school curriculum.

Deucravacitinib in plaque psoriasis: Four-year safety and efficacy results from the Phase 3 POETYK PSO-1, PSO-2 and long-term extension trials.

Background: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy.

Objectives: To evaluate the safety and efficacy of deucravacitinib through 4 years in the Phase 3 POETYK PSO-1, PSO-2 and long-term extension (LTE) trials in psoriasis.

Methods: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily (QD) or apremilast 30 mg twice daily.

Effectiveness of Adalimumab Biosimilars and Originator for Psoriasis.

Importance: The uncertainties about the real-world effectiveness of adalimumab biosimilars limit their widespread adoption for psoriasis.

Objective: To compare the effectiveness of adalimumab biosimilars Amjevita and Imraldi with Humira for psoriasis.

Design, Setting, And Participants: An emulation of 2 targeted pragmatic clinical trials was conducted using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective pharmacovigilance registry tracking individuals receiving biologic and conventional systemic treatments for psoriasis in the UK and the Republic of Ireland.

Population Pharmacokinetic-Pharmacodynamic (popPK/PD) Relationship of Orismilast, A Potent and Selective PDE4B/D Inhibitor, in Atopic Dermatitis.

Introduction: Orismilast is a novel oral selective inhibitor of phosphodiesterase 4B and 4D subtypes (PDE4B/D) in clinical development for treatment of atopic dermatitis (AD) and other inflammatory skin conditions. Herein, we describe a pharmacokinetic/pharmacodynamic (PK/PD) analysis comparing predicted exposure data of orismilast and apremilast in AD patients and place these data in the context of their IL-13 secretion data generated in a human whole-blood assay.

Methods: A PK/PD assessment of orismilast and apremilast in AD was performed.

Realization of a Photoelectrochemical Cascade for the Generation of Methanol: A Liquid Solar Fuel.

Biochemical networks use reaction cascades to selectively reduce CO using energy from sunlight, but can similar selectivity be achieved by applying a cascade approach to an engineered system? Here, we report the design and implementation of a two-step photoelectrochemical (PEC) cascade to a liquid solar fuel: reduction of CO to CO and subsequent reduction of CO to methanol. The potentials required to perform the reductions were generated using custom-made III-V-based three-terminal tandem (3TT) solar cells. Cobalt phthalocyanine immobilized on multiwalled carbon nanotubes (CoPc/MWCNT) catalyzed both reactions.

Predicting Heart Rate Variability from Heart Rate and Step Count for University Student Weekdays.

University students have high prevalence of stress and anxiety, which may be amenable to in-the-moment interventions supported by wearable devices that measure heart rate variability (HRV). However, for low-cost devices that are convenient to wear, heart rate (HR) and step count are more readily available than HRV. We investigated the performance of machine learning models trained to estimate HRV from HR and step count based on 201 hours of data from 14 participants undertaking normal university weekday activities.

Estimating the serotype-specific association between the concentration of vaccine-induced serum antibodies and protection against pneumococcal colonization.

Background: Pneumococcal conjugate vaccines (PCVs) offer indirect protection by reducing pneumococcal colonization in the vaccinated children and thus transmission. As higher-valency PCVs may trigger a weaker immune response, it is important to understand how differences in immunogenicity between PCVs translate to effectiveness against colonization.

Methods: We estimated the serotype-specific relationship between the concentration of vaccine-induced serum immunoglobulin G (IgG) and protection against colonization using a hierarchical Bayesian model with the longitudinal data from a randomized controlled trial in Israel.

Are Elbow Osteochondritis Dissecans Lesions Different for Gymnasts and Baseball Players?

Objective: Gymnasts and baseball players have different mechanisms of loading their elbows, and there is little data comparing osteochondritis dissecans (OCD) lesions between these 2 sports. Our objective is to compare the clinical and imaging characteristics of elbow OCD lesions between weight-bearing and throwing athletes.

Design: Review from 2015 to 2022.

Parenteral nutritional support in surgical patients: expert consensus statements regarding intravenous lipid emulsions containing omega-3 fatty acids.

Objectives: The International Lipids in Parenteral Nutrition (PN) Summit was convened to offer practical guidance and expert consensus opinion regarding the use of intravenous lipid emulsions (ILEs) in various clinical settings. Herein, we briefly review aspects from this summit that are of particular importance for surgical/hospitalized patients.

Methods: Summit participants identified and discussed new evidence, data, and analyses, that potentially influence the benefits and risks of ILEs in PN or their use in clinical practice.