Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.

Cancer is a complex disease characterized by specific "mission-critical" events that drive the uncontrolled growth and spread of tumor cells and their offspring. These events are essential for the advancement of the disease. One of the main contributors to these events is dysregulation of cell death pathways-such as apoptosis, necroptosis, ferroptosis, autophagy, pyroptosis, cuproptosis, parthanatos and-allows cancer cells to avoid programmed cell death and continue proliferating unabated.

Insomnia and Chronic Pain Mediate the Relationship Between Traumatic Brain Injury and Reduced Positive Airway Pressure Adherence Among Veterans.

Objective: To examine whether co-morbid insomnia, post-traumatic stress disorder (PTSD), depression, and chronic pain mediate the relationship between traumatic brain injury (TBI) and positive airway pressure (PAP) treatment adherence.

Setting: One Veterans Health Administration (VHA) sleep medicine site.

Participants: Veterans (n = 8836) who were prescribed a modem-enabled PAP device.

Karius testing in the identification of infective endocarditis presenting with acute ischaemic stroke.

Our case highlights an atypical presentation of endocarditis with acute ischaemic stroke in a male patient in his 60s. The patient had undergone a congenital bicuspid aortic valve replacement with a bioprosthetic valve and an ascending aortic root graft with a pacemaker. He experienced intermittent fevers, chills and malaise over 15 months leading up to his presentation.

Workflow for predictive risk assessments of UVCBs: cheminformatics library design, QSAR, and read-across approaches applied to complex mixtures of metal naphthenates.

Substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) are commonly found in the environment. However, assessing their human toxicological risk is challenging due to their variable composition and many constituents. Metal naphthenate salts are one such category of UVCBs that are the reaction products of naphthenic acids with metals to form complex mixtures.

Somatic mitochondrial DNA mutations are a source of heterogeneity among primary leukemic cells.

Somatic mitochondrial DNA (mtDNA) mutations are prevalent in tumors, yet defining their biological significance remains challenging due to the intricate interplay between selective pressure, heteroplasmy, and cell state. Utilizing bulk whole-genome sequencing data from matched tumor and normal samples from two cohorts of pediatric cancer patients, we uncover differences in the accumulation of synonymous and nonsynonymous mtDNA mutations in pediatric leukemias, indicating distinct selective pressures. By integrating single-cell sequencing (SCS) with mathematical modeling and network-based systems biology approaches, we identify a correlation between the extent of cell-state changes associated with tumor-enriched mtDNA mutations and the selective pressures shaping their distribution among individual leukemic cells.

Democratising artificial intelligence in healthcare: community-driven approaches for ethical solutions.

The rapid advancement and widespread adoption of artificial intelligence (AI) has ushered in a new era of possibilities in healthcare, ranging from clinical task automation to disease detection. AI algorithms have the potential to analyse medical data, enhance diagnostic accuracy, personalise treatment plans and predict patient outcomes among other possibilities. With a surge in AI's popularity, its developments are outpacing policy and regulatory frameworks, leading to concerns about ethical considerations and collaborative development.

Protein Tyrosine Phosphatase regulation by Reactive Oxygen Species.

Protein Tyrosine Phosphatases (PTPs) help to maintain the balance of protein phosphorylation signals that drive cell division, proliferation, and differentiation. These enzymes are also well-suited to redox-dependent signaling and oxidative stress response due to their cysteine-based catalytic mechanism, which requires a deprotonated thiol group at the active site. This review focuses on PTP structural characteristics, active site chemical properties, and vulnerability to change by reactive oxygen species (ROS).

Psychological and psychosocial determinants of COVID related face covering behaviours: A systematic review.

Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures.

Psychological and psychosocial determinants of COVID-related handwashing behaviours: A systematic review.

Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures.

Optimization of stimulated rotational Raman scattering over vibrational scattering in a hydrogen-filled fiber.

We present the first, to the best of our knowledge, investigation of the gain competition between rotational and vibrational stimulated Raman scattering (SRS) in the transient regime for a hydrogen (H)-filled antiresonant fiber (ARF) with the aim of generating multispectral emission composed of only rotational SRS. We show numerically and experimentally that purely rotational emission requires optimization of ARF length and spectral transmission, pump power and polarization, and H pressure. In this work, the H-filled ARF is pumped by 40 kW, 7 ns pulses at λ = 1.

Short-Term Morbidity and Mortality after Distal Femur Open Reduction Internal Fixation in the Geriatric Population.

Objective: Distal femur fractures remain a significant cause of morbidity and mortality for elderly patients. There is a lack of large population studies investigating short-term outcomes after distal femur c in elderly patients. The purpose of this study is to assess the incidence of and risk factors for various short-term outcomes after distal femur open reduction internal fixation (ORIF) in the geriatric population.

Hospital admissions among patients with Comorbid Substance Use disorders: a secondary analysis of predictors from the NavSTAR Trial.

Background: Individuals with substance use disorders (SUDs) frequently use acute hospital services. The Navigation Services to Avoid Rehospitalization (NavSTAR) trial found that a patient navigation intervention for hospitalized patients with comorbid SUDs reduced subsequent inpatient admissions compared to treatment-as-usual (TAU).

Methods: This secondary analysis extends previous findings from the NavSTAR trial by examining whether selected patient characteristics independently predicted hospital service utilization and moderated the effect of the NavSTAR intervention.

Cell Senescence-Independent Changes of Human Skin Fibroblasts with Age.

Skin ageing is defined, in part, by collagen depletion and fragmentation that leads to a loss of mechanical tension. This is currently believed to reflect, in part, the accumulation of senescent cells. We compared the expression of genes and proteins for components of the extracellular matrix (ECM) as well as their regulators and found that in vitro senescent cells produced more matrix metalloproteinases (MMPs) than proliferating cells from adult and neonatal donors.

Shoulder Pain in a Pediatric Throwing Athlete.

Pediatric avulsion fractures most commonly occur at sites of secondary ossification and are often associated with chronic stress from repetitive movements. Because of a variety of risk factors, youth athletes place higher stress on ossification centers, and their activities may predispose them to injury. This case report describes a 12-year-old female softball player who presented with pain at the distal acromion, worsened by her overhead throwing motion.

Allostery in Protein Tyrosine Phosphatases is Enabled by Divergent Dynamics.

Dynamics-driven allostery provides important insights into the working mechanics of proteins, especially enzymes. In this study, we employ this paradigm to answer a basic question: in enzyme superfamilies, where the catalytic mechanism, active sites, and protein fold are conserved, what accounts for the difference in the catalytic prowess of the individual members? We show that when subtle changes in sequence do not translate to changes in structure, they do translate to changes in dynamics. We use sequentially diverse PTP1B, TbPTP1, and YopH as representatives of the conserved protein tyrosine phosphatase (PTP) superfamily.

Development of a Discharge Counseling and Medication Reconciliation Process for Pediatric Patients Within a Large, Academic Health System.

Objective: This study aims to characterize the impact of a pharmacist-driven discharge medication reconciliation and counseling program targeting high-risk pediatric patients to mitigate barriers in transitions of care.

Methods: This was a single-center quality improvement initiative including high-risk pediatric patients within a large academic medical center. Pharmacy, medical, and information technology team members developed a scoring system to identify patients at high risk of hospital readmission that resulted in a trigger tool built within the electronic medical record (EMR).

The Lived Experiences of Pregnant and Parenting Women in Recovery Toward Medication Treatment for Opioid Use Disorder.

Background: Maternal misuse of prescription opioids and illicit drugs such as, heroin and non-pharmaceutical fentanyl analogs has increased in the last 2 decades and one in 5 women reported misuse of opioids. Medications for opioid use disorder (MOUD) are recommended for treating pregnant women with opioid use disorder (OUD). MOUD is effective in reducing cravings and negative outcomes, yet treatment is underutilized and varies in integration and intensity of resources across health systems.

Nurse and Social Worker Palliative Telecare Team and Quality of Life in Patients With COPD, Heart Failure, or Interstitial Lung Disease: The ADAPT Randomized Clinical Trial.

Importance: Many patients with chronic obstructive pulmonary disease (COPD), heart failure (HF), and interstitial lung disease (ILD) endure poor quality of life despite conventional therapy. Palliative care approaches may benefit this population prior to end of life.

Objective: Determine the effect of a nurse and social worker palliative telecare team on quality of life in outpatients with COPD, HF, or ILD compared with usual care.

Polysubstance use and post-discharge mortality risk among hospitalized patients with opioid use disorder.

Polysubstance use is becoming increasingly common and presents several harms. This study aimed to examine the association of comorbid cocaine, alcohol (binge drinking), and sedative use with mortality among hospitalized patients with opioid use disorder (OUD). A subsample of adult medical/surgical hospital patients with OUD who were seen by a hospital addiction consultation service in Baltimore City and enrolled in a randomized trial of a patient navigation intervention were included in this study ( = 314; 45 % female; 48 % White; mean age = 44).

Immunity-linked genes are stimulated by a membrane stress pathway linked to Golgi function and the ARF-1 GTPase.

Infection response and other immunity-linked genes (ILGs) were first named in -based expression after pathogen challenge, but many are also up-regulated when lipid metabolism is perturbed. Why pathogen attack and metabolic changes both increase ILGs is unclear. We find that ILGs are activated when phosphatidylcholine (PC) levels change in membranes of secretory organelles in .

Rise of the Virtual Nurse.

As the process of providing health care becomes increasingly complex and the foundation of the nursing profession changes, nursing leaders will need to think differently about how to support their colleagues more efficiently and effectively. The role of the virtual nurse is expanding as part of the effort to address these complexities and develop innovative solutions. Although more work is necessary to define best practices in the variations of virtual nursing, current examples have had a positive impact on nursing and patient care.

Crystal Structures Reveal Hidden Domain Mechanics in Protein Kinase A (PKA).

Cyclic-AMP-dependent protein kinase A (PKA) is a critical enzyme involved in various signaling pathways that plays a crucial role in regulating cellular processes including metabolism, gene transcription, cell proliferation, and differentiation. In this study, the mechanisms of allostery in PKA were investigated by analyzing the vast repertoire of crystal structures available in the RCSB database. From existing structures of murine and human PKA, we elucidated the conformational ensembles and protein dynamics that are altered in a ligand-dependent manner.

Disease-specific loss of microbial cross-feeding interactions in the human gut.

Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases.