Mitochondrial-derived microproteins: from discovery to function.

Given the uniqueness of the mitochondria, and the fact that they have their own genome, mitochondrial-derived microproteins (MDPs) are similar to, but different from, nuclear-encoded microproteins. The discovery of an increasing number of microproteins from this organelle and the importance of mitochondria to cellular and organismal health make it a priority to study this novel class of proteins in search of possible therapeutic targets and cures. In this review, we discuss the history of MDP discovery, describe the function of each MDP, and conclude with future goals and techniques to help discover more MDPs.

Ethanol abolishes ventilatory long-term facilitation and blunts the ventilatory response to hypoxia in female rats.

Obstructive sleep apnea (OSA) is a breathing disorder in which airway obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures can induce intermittent hypoxemia and lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia treatment (IH), which consists of alternating exposure to hypoxic and normal air, can induce a long-lasting increase in breathing motor outputs called long term facilitation (LTF).

Tumor-Associated Edema in Children with Kaposi Sarcoma: 14 Years' Experience at Kamuzu Central Hospital, Lilongwe, Malawi.

Background/objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS.

Productive mRNA Chromatin Escape is Promoted by PRMT5 Methylation of SNRPB.

Protein Arginine Methyltransferase 5 (PRMT5) regulates RNA splicing and transcription by symmetric dimethylation of arginine residues (Rme2s/SDMA) in many RNA binding proteins. However, the mechanism by which PRMT5 couples splicing to transcriptional output is unknown. Here, we demonstrate that a major function of PRMT5 activity is to promote chromatin escape of a novel, large class of mRNAs that we term Genomically Retained Incompletely Processed Polyadenylated Transcripts (GRIPPs).

Language to Support Dignity for Children With Advanced Cancer and Their Families.

Background And Objectives: Conversations about dignity are fundamental to person-centered care in pediatrics, yet practical language strategies to promote and support dignity remain understudied. To address this gap, we aimed to identify and characterize language used by pediatric oncologists to recognize and affirm dignity across advancing illness.

Methods: In this longitudinal prospective study, we audio-recorded serial disease reevaluation encounters between pediatric oncologists, children with cancer, and families across 24 months or until the child's death.

Dignity in the Pediatric Population: A Systematic Review.

Context: Children are a uniquely vulnerable patient population with restricted abilities for self-advocacy and autonomy, risking infringement upon their dignity. Yet the concept of dignity in pediatrics remains underexplored relative to the adult literature and other outcome measures.

Objectives: To characterize how dignity is defined, evaluated, and/or measured in pediatrics.

Exploring Pediatric Code Status, Advance Care Planning, and Mode of Death Disparities at End of Life.

Context: Children from marginalized groups are at risk for worse medical outcomes, yet little is known about their end of life experiences.

Objective: We examine the characteristics of deceased children with a focus on race, ethnicity, and preferred language.

Methods: We conducted a cross-sectional study of patients who died at Texas Children's Hospital from 2018 to 2019.

RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC).

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work.

Prognostic Impact of Sinus Rhythm in Atrial Fibrillation Patients: Separating Rhythm Outcomes From Randomized Strategy Findings From the CABANA Trial.

Background: Clinically detected atrial fibrillation (AF) is associated with a significant increase in mortality and other adverse cardiovascular events. Since the advent of effective methods for AF rhythm control, investigators have attempted to determine how much these adverse prognostic AF effects could be mitigated by the restoration of sinus rhythm (SR) and whether the method used mattered.

Methods: The CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) randomized 2204 AF patients to ablation versus drug therapy, of which 1240 patients were monitored in follow-up using the CABANA ECG rhythm monitoring system.

Remote Monitoring and Data Collection for Decentralized Clinical Trials.

Importance: Less than 5% of patients with cancer enroll in a clinical trial, partly due to financial and logistic burdens, especially among underserved populations. The COVID-19 pandemic marked a substantial shift in the adoption of decentralized trial operations by pharmaceutical companies.

Objective: To assess the current global state of adoption of decentralized trial technologies, understand factors that may be driving or preventing adoption, and highlight aspirations and direction for industry to enable more patient-centric trials.

Novel Integration of a Health Equity Immersion Curriculum in Medical Training.

Health disparities education is an integral and required part of medical professional training, and yet existing curricula often fail to effectively denaturalize injustice or empower learners to advocate for change. We discuss a novel collaborative intervention that weds the health humanities to the field of health equity. We draw from the health humanities an intentional focus retraining provider imaginations by centering patient narratives; from the field of health equity, we draw the linkage between stigmatized social identities and health disparities.

Regional differences in outcomes with ablation versus drug therapy for atrial fibrillation: Results from the CABANA trial.

Background: The finding of unexpected variations in treatment benefits by geographic region in international clinical trials raises complex questions about the interpretation and generalizability of trial findings. We observed such geographical variations in outcome and in the effectiveness of atrial fibrillation (AF) ablation versus drug therapy in the Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. This paper describes these differences and investigates potential causes.

Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease.

BACKGROUNDKaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.

Contrasting Experimental Rodent Aftercare With Human Clinical Treatment for Cervical Spinal Cord Injury: Bridging the Translational "Valley of Death".

More than half of all spinal cord injuries (SCIs) occur at the cervical level and often lead to life-threatening breathing motor dysfunction. The C2 hemisection (C2Hx) and high cervical contusion mouse and rat models of SCI are widely utilized both to understand the pathological effects of SCI and to develop potential therapies. Despite rigorous research effort, pre-clinical therapeutics studied in those animal models of SCI sometimes fail when evaluated in the clinical setting.

Factors influencing treatment decision-making for cancer patients in low- and middle-income countries: A scoping review.

Purpose: In this scoping review, we evaluated existing literature related to factors influencing treatment decision-making for patients diagnosed with cancer in low- and middle-income countries, noting factors that influence decisions to pursue treatment with curative versus non-curative intent. We identified an existing framework for adult cancer developed in a high-income country (HIC) context and described similar and novel factors relevant to low-and middle-income country settings.

Methods: We used scoping review methodology to identify and synthesize existing literature on factors influencing decision-making for pediatric and adult cancer in these settings.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19.

Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

Design, Setting, And Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia.

Medicare characteristics, treatment, cost and survival in triple class exposed relapsed or refractory multiple myeloma.

This study describes real-world treatment patterns of Medicare beneficiaries with relapsed or refractory multiple myeloma (RRMM) who are triple class exposed (TCE). Retrospective analysis of Medicare fee for service claims to identify a cohort age >65 with RRMM + TCE, 1 January 2016 to 30 June 2019. Initiation of a new treatment regimen (TCE1), healthcare resource utilization, cost and mortality.

Factors associated with antiretroviral therapy adherence among adolescents living with HIV in the era of isoniazid preventive therapy as part of HIV care.

High levels of adherence to antiretroviral therapy (ART) are essential to promoting viral suppression and consequential good treatment outcomes. Adolescents living with HIV (ALHIV) in sub-Saharan Africa are less adherent to ART compared to adults, leading to lower rates of viral suppression and immunological recovery. We conducted a mixed-method study utilizing a convergent parallel approach to explore factors associated with ART adherence among ALHIV in the era of isoniazid preventive therapy (IPT) as part of HIV care.

Global caregiver perspectives on COVID-19 immunization in childhood cancer: A qualitative study.

Introduction: SARS-CoV-2 has led to an unprecedented pandemic where vulnerable populations, such as those with childhood cancer, face increased risk of morbidity and mortality. COVID-19 vaccines are a critical intervention to control the pandemic and ensure patient safety. This study explores global caregiver's perspectives related to COVID-19 immunization in the context of pediatric cancer management.

AMPK activation by metformin protects against pulmonary hypertension in rats and relaxes isolated human pulmonary artery.

Pulmonary hypertension (PH) is associated with pulmonary vasoconstriction and endothelial dysfunction leading to impaired nitric oxide (NO) and prostacyclin (PGI) pathways. Metformin, the first line treatment for type 2 diabetes and AMP-activated protein kinase (AMPK) activator, has been recently highlighted as a potential PH treatment. AMPK activation has been reported to improve endothelial function by enhancing endothelial NO synthase (eNOS) activity and to have relaxant effects in blood vessels.

Effects of Ablation Versus Drug Therapy on Quality of Life by Sex in Atrial Fibrillation: Results From the CABANA Trial.

Background Women with atrial fibrillation (AF) demonstrate more AF-related symptoms and worse quality of life (QOL). Whether increased use of ablation in women reduces sex-related QOL differences is unknown. Sex-related outcomes for ablation versus drug therapy was a prespecified analysis in the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial.

The Increased Clinical and Economic Burden of Hyperkalemia in Medicare Patients Admitted to Long-Term Care Settings.

Introduction: Older patients are at increased risk for hyperkalemia (HK). This study describes the prevalence, recurrence, and clinical and economic burden of HK in Medicare patients admitted to a long-term care (LTC) setting.

Methods: Retrospective cohort study using 100% Medicare Fee-for-Service (FFS) claims identified patients aged ≥ 65 years with index admission between 2017 and 2019 to a LTC setting (skilled nursing, home health, inpatient rehabilitation, or long-term acute care).

Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.

The prevalence of type 2 diabetes in North West London (NWL) is relatively high compared to other parts of the United Kingdom with outcomes suboptimal. This presents a need for more effective strategies to identify people living with type 2 diabetes who need additional support. An emerging subset of web-based interventions for diabetes self-management and population management has used artificial intelligence and machine learning models to stratify the risk of complications from diabetes and identify patients in need of immediate support.

Divergent clinical presentations and outcomes among children and adolescents with Kaposi sarcoma in Malawi and Tanzania.

Objectives: The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV-8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric-specific approach.

Methods: The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease.