Integration of therapeutic cargo into the human genome with programmable type V-K CAST.

CRISPR-associated (Cas) transposases (CAST) are RNA-guided systems capable of programmable integration of large segments of DNA without creating double-strand breaks. Engineered Cascade CAST function in human cells but are challenging to deploy due to the complexity of the targeting components. Unlike Cascade, which require three Cas proteins, type V-K CAST require a single Cas12k effector for targeting.

The Landmark Series: Management of Primary Hyperparathyroidism.

Surgery is the only definitive treatment for primary hyperparathyroidism (PHPT). The surgical management of PHPT has evolved over the past several decades in response to the continually growing body of evidence supporting its effectiveness in both symptomatic and asymptomatic disease. As imaging modalities for localization, operative approach, and intraoperative adjuncts, such as intraoperative parathyroid hormone testing, have been optimized, careful evaluation of the timing of parathyroidectomy in relationship to the disease's natural history has been pursued to limit the detrimental end-organ effects of untreated PHPT.

Burden of prolonged treatment delay among patients with common cancers in the Philippines.

Purpose: Prolonged treatment delay often leads to adverse cancer prognosis. However, the demographic and clinical predictors of higher treatment delay burden in the Philippines have not been thoroughly evaluated.

Methods: We conducted a population-based retrospective cohort study on patients diagnosed with common cancers who received cancer treatment, to quantify the burden of prolonged treatment delay in the Philippines among this population.

3D convolutional deep learning for nonlinear estimation of body composition from whole body morphology.

Body composition prediction from 3D optical imagery has previously been studied with linear algorithms. In this study, we present a novel application of deep 3D convolutional graph networks and nonlinear Gaussian process regression for human body shape parameterization and body composition estimation. We trained and tested linear and nonlinear models with ablation studies on a novel ensemble body shape dataset containing 4286 scans.

Trends in anti-seizure medication spending by Medicare Part D and Medicaid from 2012 to 2022.

Objectives: The rising cost of anti-seizure medications (ASMs) in the United States (US) is a major concern for patients, healthcare providers, insurance payors, and policymakers. We aim to describe and analyze the spending trends on ASMs in the Medicare Part D (MPD) and Medicaid population in the US.

Methods: A retrospective study was conducted on the databases of MPD and Medicaid Spending by Drug from 2012 to 2022, which was published by the Centers for Medicare and Medicaid Services (CMS).

Laser Upcycling of Hemoglobin Protein Biowaste into Engineered Graphene Aerogel Architectures for 3D Supercapacitors.

Graphene aerogels (GAs) with engineered architectures are a promising material for applications ranging from filtration to energy storage/conversion. However, current preparation approaches involve the combination of multiple intrinsically-different methodologies to achieve graphene-synthesis and architecture-engineering, complicating the entire procedure. Here, a novel approach to prepare GAs with engineered architectures based on the laser-upcycling of protein biowaste, hemoglobin, is introduced.

Digital phenotyping from wearables using AI characterizes psychiatric disorders and identifies genetic associations.

Psychiatric disorders are influenced by genetic and environmental factors. However, their study is hindered by limitations on precisely characterizing human behavior. New technologies such as wearable sensors show promise in surmounting these limitations in that they measure heterogeneous behavior in a quantitative and unbiased fashion.

Enhancing representativeness of patient-reported outcomes in routine radiation oncology care: a quality improvement protocol to address non-response.

Introduction: Non-response significantly undermines the representativeness of patient-reported outcome (PRO) data, thereby compromising its utility for facilitating high-value, equitable, patient-centred care in cancer clinics. Quality improvement studies are needed to assess the representativeness of PRO data collected in routine care, identify the underlying causes of non-response and develop novel methods to ensure data representativeness. Using a multilevel framework and a mixed-methods approach, we have three aims: (1) characterise the non-response of the Global-10 across clinic, provider and patient levels; (2) identify multilevel causes of non-response and potential strategies to improve representativeness in PRO collection; and (3) develop effective modifications to missing-data methods to enhance the representativeness of pre-existing PRO data.

Variation in commercial prices for thyroidectomy and parathyroidectomy at US hospitals.

Background: The 2021 Hospital Price Transparency Rule mandated hospitals to publicly disclose their service prices to improve competition and lower healthcare costs. Our aim was to characterize commercial price variation for thyroidectomy and parathyroidectomy.

Methods: We performed a national cross-sectional study of hospital price variation in 2022 and 2023 using the Turquoise Health dataset.

Diblock Copolymer Targeted Lipid Nanoparticles: Next-Generation Nucleic Acid Delivery System Produced by Confined Impinging Jet Mixers.

Despite the recent advances and clinical demonstration of lipid nanoparticles (LNPs) for therapeutic and prophylactic applications, the extrahepatic delivery of nucleic acids remains a significant challenge in the field. This limitation arises from the rapid desorption of lipid-PEG in the bloodstream and clearance to the liver, which hinders extrahepatic delivery. In response, we explore the substitution of lipid-PEG with biodegradable block copolymers (BCPs), specifically poly(ε-caprolactone)--poly(ethylene glycol) (PCL--PEG).

Effects of oral contraceptive pills on brain networks: A replication and extension.

Neuroimaging research has identified significant effects of oral contraceptive pills (OCPs) on brain networks. A wide variety of approaches have been employed, largely in observational samples, with few converging results. This study therefore was designed to test for replication and extend this previous work using a randomized, double-blind, placebo-controlled crossover trial of the effects of OCPs on brain networks.

Synthesizing Lipid Nanoparticles by Turbulent Flow in Confined Impinging Jet Mixers.

Lipid nanoparticles (LNPs) have demonstrated their enormous potential as therapeutic delivery vehicles, as evidenced by the approval and global usage of two COVID-19 messenger RNA (mRNA) vaccines. On a small scale, LNPs are often made using microfluidics; however, the limitations of these devices preclude their use on a large scale. The COVID-19 vaccines are manufactured in large quantities using confined impinging jet (CIJ) turbulent mixers.

A NSQIP-Based Randomized Clinical Trial Evaluating Choice of Prophylactic Antibiotics for Pancreaticoduodenectomy.

Surgical site infection is a common complication following pancreaticoduodenectomy and is a major source of postoperative morbidity. Surgical site infection is more common among patients who undergo preoperative biliary instrumentation, likely because of the introduction of intestinal flora into the normally sterile biliary tree. Frequently, bacterial isolates from surgical site infections after pancreaticoduodenectomy demonstrate resistance to the antibiotic agents typically used for surgical prophylaxis, suggesting that broad-spectrum coverage may be beneficial.

Opportunities to improve the diagnosis and treatment of primary hyperparathyroidism: retrospective cohort study.

Background: Although primary hyperparathyroidism (PHPT) is readily diagnosed biochemically and can be cured with low-risk surgery, it is often underrecognized and undertreated. Our objectives were to characterize, within our health system, how often patients with hypercalcemia were evaluated for PHPT and how often patients with PHPT underwent definitive treatment with parathyroidectomy.

Methods: Ambulatory patients aged 18 years or older seen at our health system between January 2018 and June 2023 with chronic hypercalcemia were identified from the medical record.

SBRT for Pancreatic Cancer: A Radiosurgery Society Case-Based Practical Guidelines to Challenging Cases.

The use of radiation therapy (RT) for pancreatic cancer continues to be controversial, despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control, but currently, no standardized approach exists. Advances in stereotactic body RT, motion management, real-time image guidance, and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates.

Predictors of Neurological Disability at Hospital Discharge for Acyclovir-treated Pediatric Herpes Simplex Virus Encephalitis.

Background: Herpes simplex virus encephalitis (HSE) is a rare but serious neurological infection that causes neurological dysfunction. Research is lacking on the clinical predictors of neurological outcomes and the optimal duration of therapy for pediatric HSE patients. In this study of pediatric HSE patients, we identified factors predicting neurological disability at hospital discharge and examined associations of acyclovir therapy duration with neurological outcomes.

Patient-Reported Outcome Measures Within a National Multispecialty Surgical Quality Improvement Program.

Importance: Patient-reported outcome measures (PROMs) are increasingly recognized for their ability to promote patient-centered care, but concerted health information technology (HIT)-enabled PROM implementations have yet to be achieved for national surgical quality improvement.

Objective: To evaluate the feasibility of collecting PROMs within a national surgical quality improvement program.

Design, Setting, And Participants: This was a pragmatic implementation cohort study conducted from February 2020 to March 2023.

Adding Patient-reported Outcomes to the American College of Surgeons National Surgical Quality Improvement Program: Results of the First 33,842 Patients From 65 Hospitals.

Objective: To investigate the initial set of patient-reported outcomes (PROs) in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and their associations with 30-day surgical outcomes.

Background: PROs provide important information that can be used to improve routine care and facilitate quality improvement. The American College of Surgeons conducted a demonstration project to capture PROs into the NSQIP to complement clinical data.

Restoration of Epicardial Blood Flow After Left Ventricular Unloading With the Impella CP Heart Pump in a Patient With STEMI Treated With Surgical Revascularization.

Left main occlusion presenting as ST-segment elevation myocardial infarction is an exceedingly morbid condition. This article reports a case of cardiac arrest in a patient after a treadmill stress test. Coronary angiography revealed 100% occlusion of the left main coronary artery.