A Unified Approach to Health Data Exchange: A Report From the US DHHS.

Importance: Health information technology, such as electronic health records (EHRs), has been widely adopted, yet accessing and exchanging data in the fragmented US health care system remains challenging. To unlock the potential of EHR data to improve patient health, public health, and health care, it is essential to streamline the exchange of health data. As leaders across the US Department of Health and Human Services (DHHS), we describe how DHHS has implemented fundamental building blocks to achieve this vision.

A 2024 Update on US FDA Implementation of Partial Area Under the Curve Into Bioavailability and Bioequivalence Assessments.

Comparisons of maximum drug concentration (C) and total area under the concentration vs. time curve (AUC) may be inadequate for bioavailability (BA)/bioequivalence (BE) assessments in cases where the shape of the pharmacokinetic (PK) profile of a drug impacts the clinical performance. In such cases, partial area under the concentration vs.

Ascitic fluid amylase-to-serum amylase ratio to predict pancreatic duct leaks causing ascites.

Objectives: Pancreatic duct leaks can cause ascites, and fluid amylase can be used as a marker to suggest pancreatic duct leak; however, there is no reference parameter or cutoff value for diagnosis. We assessed whether a novel ratio of ascitic fluid to serum amylase can reliably predict pancreatic leaks and need for endoscopic retrograde cholangiopancreatography (ERCP).

Materials And Methods: Patients who had fluid amylase from ascitic fluid and serum amylase within one week of confirmed pancreatic leaks via ERCP were included along with appropriate medical and surgical controls.

Living in Historically Redlined Neighborhoods and the Cognitive Function of Black and White Adults.

Objectives: We determined if living in historically redlined neighborhoods was associated with level and change in cognitive functioning and if this association differed for Black and White older adults.

Methods: We linked the Health and Retirement Study 1998-2018 data to redlining scores from the Historic Redlining Indicator data. Our sample included adults aged 50 years and older (24,230 respondents, 129,618 person-period observations).

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Response to neoadjuvant chemotherapy leads to better survival outcomes in upper tract urothelial carcinoma.

Objectives: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for patients with high-risk upper tract urothelial carcinoma (UTUC) using a large, well-curated multi-institutional database.

Patients And Methods: This study was a multi-institutional retrospective analysis conducted by the UTUC Collaborative Network (UCAN), combining data from 2276 patients with UTUC who underwent radical nephroureterectomy at seven high-volume tertiary care centres in the United States. The UCAN data were analysed to evaluate the impact of response to NAC on survival outcomes in patients with UTUC.

Bridging Therapies-Ex Vivo Liver Xenoperfusion and the Role of Machine Perfusion: An Update.

Advancements in xenotransplantation intersecting with modern machine perfusion technology offer promising solutions to patients with liver failure providing a valuable bridge to transplantation and extending graft viability beyond current limitations. Patients facing acute or acute chronic liver failure, post-hepatectomy liver failure, or fulminant hepatic failure often require urgent liver transplants which are severely limited by organ shortage, emphasizing the importance of effective bridging approaches. Machine perfusion is now increasingly used to test and use genetically engineered porcine livers in translational studies, addressing the limitations and costs of non-human primate models.

Integrating malaria vaccine and CRISPR/Cas9 gene drive: a comprehensive strategy for accelerated malaria eradication.

Malaria remains a significant public health challenge, particularly in low- and middle-income countries, despite ongoing efforts to eradicate the disease. Recent advancements, including the rollout of malaria vaccines, such as RTS,S/AS01 and R21/Matrix-M™, offer new avenues for prevention. However, the rise of resistance to anti-malarial medications necessitates innovative strategies.

The Role of Social Deficits in the Link Between Social Gambling Motives and Problem Gambling.

In comparison to other motives for gambling, social motives (e.g., gambling for social interaction) are often suggested to be the least problematic and, in some cases, even a protective factor for problem gambling.

Exploration of linear and interpretable models for quantification of cell parameters via contactless short-wave infrared hyperspectral sensing.

The development of optical sensors for label-free quantification of cell parameters has numerous uses in the biomedical arena. However, using current optical probes requires the laborious collection of sufficiently large datasets that can be used to calibrate optical probe signals to true metabolite concentrations. Further, most practitioners find it difficult to confidently adapt black box chemometric models that are difficult to troubleshoot in high-stakes applications such as biopharmaceutical manufacturing.

Large donor CRISPR for whole-CDS replacement of cell adhesion molecule LRRTM2.

The cell adhesion molecule Leucine-Rich Repeat Transmembrane neuronal protein 2 (LRRTM2) is crucial for synapse development and function. However, our understanding of its endogenous trafficking has been limited due to difficulties in manipulating its coding sequence (CDS) using standard genome editing techniques. Instead, we replaced the entire LRRTM2 CDS by adapting a two-guide CRISPR knock-in method, enabling complete control of LRRTM2.

Effectiveness of the Interdisciplinary Home-bAsed Reablement Programme (I-HARP) on improving functional independence of people living with dementia: a multicentre, pragmatic, randomised, open-label, controlled trial.

Background: We investigated the effectiveness of an Interdisciplinary Home-bAsed Reablement Programme (I-HARP) on improving functional independence, health and well-being of people with dementia, family carer outcomes and costs.

Method: A multicentre pragmatic parallel-arm randomised controlled trial compared I-HARP to usual care in community-dwelling people with mild to moderate dementia and their family carers in Sydney, Australia (2018-2022). I-HARP is a 4-month, home-based, dementia rehabilitation model delivered by an interdisciplinary team.

Cerebral blood volume index in the era of thrombectomy-treated large and medium vessel ischemic strokes.

The cerebral blood volume index (CBV index) is a perfusion-based marker of collateral status. Several real-world data analyses from observational stroke cohorts have established relationships between this parameter and a range of favorable and unfavorable stroke outcomes. In this review, an overview is provided of the CBV index, within the context of thrombectomy-treated large vessel and medium vessel occlusion ischemic strokes.

Single-cell RNA flow cytometry to assess intratumoral production of cytokines/chemokines.

The tumor microenvironment (TME) consists of complex interactions between cellular and extracellular components, among which the immune system is known to play an integral role in disease progression and response to therapy. Cytokines and chemokines are cell signaling proteins used by immune cells to communicate with each other as well as with other cell types in the body. These proteins control systemic and local immune responses and levels of cytokines/chemokines in the TME have been associated with tumor outcomes.

Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.

We report the discovery of small molecules that target the RNA tertiary structure of self-splicing group II introns and display potent antifungal activity against yeasts, including the major public health threat . High-throughput screening efforts against a yeast group II intron resulted in an inhibitor class which was then synthetically optimized for enhanced inhibitory activity and antifungal efficacy. The most highly refined compounds in this series display strong, gene-specific antifungal activity against .

Investigating Subpopulation Dynamics in Clonal CHO-K1 Cells with Single-Cell RNA Sequencing.

Chinese Hamster Ovary (CHO) cells produce monoclonal antibodies and other biotherapeutics at industrial scale. Despite their ubiquitous nature in the biopharmaceutical industry, little is known about the behaviors of individual transfected clonal CHO cells. Most CHO cells are assessed on their stability, their ability to produce the protein of interest over time.

Endo-Bentall Repair: Early Results and Feasibility of a Physician-Constructed Endo-Bentall Device.

Objective: We present our experience with endovascular Bentall procedure (Endo-Bentall) using a modular valve conduit (Endo-Bentall) in high-risk patients with aortic root pathologies.

Methods: The physician constructed Endo-Bentall device is composed of a self-expanding transcatheter aortic valve (TAVR), aortic endovascular stent graft (TEVAR), and two wire-reinforced fenestrations for coronary artery stenting. The TAVR valve is sutured into an appropriately sized TEVAR graft.

From Zone -1 to Zone 3: Feasibility and Safety of Complex Endovascular Aortic Repairs in Type A Aortic Dissection.

Objective: Over 30% of patients presenting with acute type A aortic dissection (ATAAD) are considered high - risk or inoperable. This study aims to investigate the early and mid-term outcomes of complex endovascular aortic repair of aortic root, ascending aorta, and aortic arch among patients with ATAAD.

Methods: From January 2018 to January 2023, 29 patients who were considered high risk for open operation underwent endovascular aortic repair.

AN IMMUNOHISTOCHEMICAL AND MOLECULAR GENETIC STUDY OF 60 COLORECTAL CARCINOMA BRAIN METASTASES IN PURSUIT OF PREDICTIVE BIOMARKERS FOR CANCER THERAPY.

Colorectal carcinoma brain metastases (n=60) were studied using next-generation sequencing and immunohistochemistry. RAS and BRAF mutations were detected in 58.2% and 7.

Immunogenicity and safety of a monovalent omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose in US adults: interim analysis of a single-arm phase 2/3 study.

Background: Authorities globally recommended a monovalent omicron XBB.1.5-based COVID-19 vaccine for the 2023-24 season.

Forest restoration improves habitat and water quality in tropical streams: A multiscale landscape assessment.

Forest restoration has been a common practice to safeguard water quality and stream health but it is unclear to which extent and pace forest restoration recovers stream ecosystem structure and functions. Also, stream health might be affected by the forest restoration type and the quality of the interventions. Here, we sought to evaluate the recovery of stream habitat and water quality through forest restoration in catchments dominated by pasturelands, and explored the relationship between landscape structure and stream ecosystem recovery.

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies - A stakeholder meeting report.

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.

Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement.

Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.

Guidelines to minimize risk when dry needling the rectus capitus posterior major muscle.

Background: Headache disorders are prevalent often leading to disability. The rectus capitus posterior major muscle (RCPMaj) may contribute to headache symptoms via nociceptive convergence and myodural bridging.

Objectives: To establish guidelines for needle length and needle angle to mitigate risks during dry needling RCPMaj.