Highly Pathogenic Avian Influenza (HPAI) H5N1 virus in Finland in 2021-2023 - Genetic diversity of the viruses and infection kinetics in human dendritic cells.

Highly pathogenic avian influenza (HPAI) H5N1 is known for its virulence and zoonotic potential, infecting birds and mammals, thus raising public health concerns. Since 2021 its spread among birds has led to cross-species transmission causing epizootics among mammals, eventually impacting fur animal farms in Finland in 2023. To analyze the infectivity of the Finnish H5N1 isolates in human cells, representatives of diverse H5N1 isolates were selected based on the genetic differences, host animal species, and the year of occurrence.

The comprehensive SARS-CoV-2 'hijackome' knowledge base.

The continuous evolution of SARS-CoV-2 has led to the emergence of several variants of concern (VOCs) that significantly affect global health. This study aims to investigate how these VOCs affect host cells at proteome level to better understand the mechanisms of disease. To achieve this, we first analyzed the (phospho)proteome changes of host cells infected with Alpha, Beta, Delta, and Omicron BA.

Long-term COVID-19 vaccine- and Omicron infection-induced humoral and cell-mediated immunity.

Introduction: Mutations occurring in the spike (S) protein of SARS-CoV-2 enables the virus to evade COVID-19 vaccine- and infection-induced immunity.

Methods: Here we provide a comprehensive analysis of humoral and cell-mediated immunity in 111 healthcare workers who received three or four vaccine doses and were followed up to 12 and 6 months, respectively, after the last vaccine dose. Omicron breakthrough infection occurred in 71% of the vaccinees, enabling evaluation of vaccine- and vaccine/infection-induced hybrid immunity.

Virus-specific Dicer-substrate siRNA swarms inhibit SARS-CoV-2 infection in TMPRSS2-expressing Vero E6 cells.

After 4 years of the COVID-19 pandemic, SARS-CoV-2 continues to circulate with epidemic waves caused by evolving new variants. Although the rapid development of vaccines and approved antiviral drugs has reduced virus transmission and mitigated the symptoms of infection, the continuous emergence of new variants and the lack of simple-use (non-hospitalized, easy timing, local delivery, direct acting, and host-targeting) treatment modalities have limited the effectiveness of COVID-19 vaccines and drugs. Therefore, novel therapeutic approaches against SARS-CoV-2 infection are still urgently needed.

Applying quantum approximate optimization to the heterogeneous vehicle routing problem.

Quantum computing offers new heuristics for combinatorial problems. With small- and intermediate-scale quantum devices becoming available, it is possible to implement and test these heuristics on small-size problems. A candidate for such combinatorial problems is the heterogeneous vehicle routing problem (HVRP): the problem of finding the optimal set of routes, given a heterogeneous fleet of vehicles with varying loading capacities, to deliver goods to a given set of customers.

AGA Clinical Practice Update on Integrating Potassium-Competitive Acid Blockers Into Clinical Practice: Expert Review.

Description: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the available evidence and offer expert Best Practice Advice on the integration of potassium-competitive acid blockers (P-CABs) in the clinical management of foregut disorders, specifically including gastroesophageal reflux disease, Helicobacter pylori infection, and peptic ulcer disease.

Methods: This expert review was commissioned and approved by the AGA Institute Governing Board and CPU Committee to provide timely guidance on a topic of high clinical importance to the AGA membership. This CPU expert review underwent internal peer review by the CPU Committee and external peer review through the standard procedures of Gastroenterology.

Comparison of Los Angeles Grades of Erosive Esophagitis Scored by Local Investigators vs Central Adjudicators in a Clinical Trial.

Approximately 30% of patients with typical gastroesophageal reflux disease (GERD) symptoms have endoscopic evidence of erosive esophagitis (EE). The severity of EE is commonly graded using the Los Angeles (LA) classification system as grade A (minimal) to D (very severe), depending on the extent of endoscopically visible mucosal breaks (Supplementary Figure 1). Accurate grading of EE severity is crucial in clinical trials of medical EE treatments, as EE severity strongly influences both initial rates of healing and the likelihood of recurrence during maintenance treatment.

Vonoprazan is Efficacious for Treatment of Heartburn in Non-erosive Reflux Disease: A Randomized Trial.

Background & Aims: Potassium-competitive acid blockers have documented efficacy for erosive esophagitis. We performed a randomized trial in United States subjects diagnosed with non-erosive reflux disease of vonoprazan vs placebo for 4 weeks, followed by a 20-week active-treatment extension.

Methods: Adult subjects with heartburn ≥4 days/week during screening without erosive esophagitis on endoscopy were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg.

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

Objective: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes.

Design: Difference-in-difference study.

Setting: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls.

Review article: Upper gastrointestinal bleeding - review of current evidence and implications for management.

Background: Acute upper gastrointestinal bleeding (UGIB) is a common emergency requiring hospital-based care. Advances in care across pre-endoscopic, endoscopic and post-endoscopic phases have led to improvements in clinical outcomes.

Aims: To provide a detailed, evidence-based update on major aspects of care across pre-endoscopic, endoscopic and post-endoscopic phases.

AGA Clinical Practice Update on High-Quality Upper Endoscopy: Expert Review.

Description: The purpose of this Clinical Practice Update (CPU) Expert Review is to provide clinicians with guidance on best practices for performing a high-quality upper endoscopic exam.

Methods: The best practice advice statements presented herein were developed from a combination of available evidence from published literature, guidelines, and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out, which aligns with standard processes for American Gastroenterological Association (AGA) Institute CPUs.

Clinical predictive value of renalase in post-ERCP pancreatitis.

Background And Aims: Plasma levels of renalase decrease in acute experimental pancreatitis. We aimed to determine if decreases in plasma renalase levels after ERCP predict the occurrence of post-ERCP pancreatitis (PEP).

Methods: In this prospective cohort study conducted at a tertiary hospital, plasma renalase was determined before ERCP (baseline) and at 30 and 60 minutes after ERCP.

Achieving Value by Risk Stratification With Machine Learning Model or Clinical Risk Score in Acute Upper Gastrointestinal Bleeding: A Cost Minimization Analysis.

Introduction: We estimate the economic impact of applying risk assessment tools to identify very low-risk patients with upper gastrointestinal bleeding who can be safely discharged from the emergency department using a cost minimization analysis.

Methods: We compare triage strategies (Glasgow-Blatchford score = 0/0-1 or validated machine learning model) with usual care using a Markov chain model from a US health care payer perspective.

Results: Over 5 years, the Glasgow-Blatchford score triage strategy produced national cumulative savings over usual care of more than $2.

Trends in Upper Gastrointestinal Bleeding in Patients on Primary Prevention Aspirin: A Nationwide Emergency Department Sample Analysis, 2016-2020.

Background: Recent guidelines do not recommend routine use of aspirin for primary cardiovascular prevention (ppASA) and suggest avoidance of ppASA in older individuals due to bleeding risk. However, ppASA is frequently taken without an appropriate indication. Estimates of the incidence of upper gastrointestinal bleeding due to ppASA in the United States are lacking.

Infectious viruses from transfected SARS-CoV-2 genomic RNA.

SARS-CoV-2 emerged at the end of 2019, and like other novel pathogens causing severe symptoms, WHO recommended heightened biosafety measures for laboratories working with the virus. The positive-stranded genomic RNA of coronaviruses has been known to be infectious since the 1970s, and overall, all experiments with the possibility of SARS-CoV-2 propagation are carried out in higher containment level laboratories. However, as SARS-CoV-2 RNA has been routinely handled in BSL-2 laboratories, the question of the true nature of RNA infectiousness has risen along with discussion of appropriate biosafety measures.

Plasma renalase levels are associated with the development of acute pancreatitis.

Background/objectives: Severe acute pancreatitis is associated with significant morbidity and mortality. Identifying factors that affect the risk of developing severe disease could influence management. Plasma levels of renalase, an anti-inflammatory secretory protein, dramatically decrease in a murine acute pancreatitis model.