Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens.

Background: Heightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load ("blips") during ART are associated with increases in inflammation.

A Pooled Analysis of Eight Clinical Studies Suggests a Link Between Influenza-Like Symptoms and Pharmacodynamics of the Toll-Like Receptor-7 Agonist Vesatolimod.

Introduction: Vesatolimod is a Toll-like receptor-7 (TLR7) agonist in clinical development as part of a combination regimen for human immunodeficiency virus (HIV) cure. Influenza-like symptoms associated with TLR7-mediated immune activation have been reported in clinical trials of vesatolimod. Therefore, a broader understanding of the safety profile of vesatolimod and association with dose and mechanism of action will help inform future clinical studies.

The Surprise Question and Health-Related Quality of Life in Patients on Hemodialysis: A Cross-Sectional Multicenter Study.

Background: The Surprise Question (SQ) is a common method aimed at identifying frail patients who need serious illness conversations to integrate a palliative approach. However, little is known about whether the SQ identifies patients on hemodialysis who perceive that they are declining or have low health-related quality of life (HRQoL)-important aspects when considering the need for serious illness conversations.

Objective: To explore how nurses and physicians' responses to the SQ are associated with patients' self-reported HRQoL.

HIV rebound in HIV controllers is associated with a specific fecal microbiome profile.

HIV infection is associated with gut dysbiosis, and microbiome variability may affect HIV control when antiretroviral therapy (ART) is stopped. The TLR7 agonist, vesatolimod, was previously associated with a modest delay in viral rebound following analytical treatment interruption in HIV controllers (HCs). Using a retrospective analysis of fecal samples from HCs treated with vesatolimod or placebo (NCT03060447), people with chronic HIV (CH; NCT02858401) or without HIV (PWOH), we examined fecal microbiome profile in HCs before/after treatment, and in CH and PWOH.

Effects and considerations of multiplexing ForenSeq Kintelligence libraries with a negative control.

The negative template control or negative amplification control has been an essential component of the forensic DNA analysis workflow that helps monitor contamination. As such, the inclusion of a negative control in forensic DNA analysis has been a requirement for all laboratories audited under the FBI's Quality Assurance Standards. As massively parallel sequencing (MPS) becomes more conventional in forensic laboratories, considerations for the inclusion of a negative control in every sequencing run can be evaluated.

Safety, pharmacodynamics, and antiviral activity of selgantolimod in viremic patients with chronic hepatitis B virus infection.

Background & Aims: Novel finite therapies for chronic hepatitis B (CHB) are needed, since lifelong treatment is usually required with current available oral antivirals. This phase II study (NCT03615066) evaluated the safety, pharmacodynamics, and antiviral activity of selgantolimod (a Toll-like receptor 8 agonist [TLR8]) with tenofovir alafenamide (TAF).

Methods: Viremic patients with CHB not receiving treatment were stratified by HBeAg status and randomized 2:2:1 to TAF 25 mg/day with selgantolimod 3 mg orally once weekly (QW), selgantolimod 1.

Liver stiffness measurement as a noninvasive method for the diagnosis of liver cirrhosis in patients with chronic hepatitis D virus infection.

Background: Noninvasive tests (NITs) have been proposed as an alternative to liver biopsy for diagnosing liver cirrhosis. The evidence of NIT performance in patients with chronic hepatitis D (CHD) is limited.

Aims: To evaluate the diagnostic performance of liver stiffness measurement (LSM) and other NITs in CHD patients.

Safety and efficacy of the oral TLR8 agonist selgantolimod in individuals with chronic hepatitis B under viral suppression.

Background & Aims: Selgantolimod (GS-9688) is a Toll-like receptor 8 (TLR8) agonist that suppresses HBV in vitro. In a phase II study, we evaluated the safety and efficacy of weekly selgantolimod treatment in virally suppressed individuals with chronic HBV taking oral antiviral treatment.

Methods: Forty-eight patients were randomized into two cohorts (hepatitis B e antigen [HBeAg]-positive and -negative [n = 24 each]) to receive oral selgantolimod 3 mg, 1.

Sensory deprivation arrests cellular and synaptic development of the night-vision circuitry in the retina.

Experience regulates synapse formation and function across sensory circuits. How inhibitory synapses in the mammalian retina are sculpted by visual cues remains unclear. By use of a sensory deprivation paradigm, we find that visual cues regulate maturation of two GABA synapse types (GABA and GABA receptor synapses), localized across the axon terminals of rod bipolar cells (RBCs)-second-order retinal neurons integral to the night-vision circuit.

Predicting the dengue cluster outbreak dynamics in Yogyakarta, Indonesia: a modelling study.

Background: Human mobility and climate conditions are recognised key drivers of dengue transmission, but their combined and individual role in the local spatiotemporal clustering of dengue cases is not well understood. This study investigated the effects of human mobility and weather conditions on dengue risk in an urban area in Yogyakarta, Indonesia.

Methods: We established a Bayesian spatiotemporal model for neighbourhood outbreak prediction and evaluated the performances of two different approaches for constructing an adjacency matrix: one based on geographical proximity and the other based on human mobility patterns.

Efficacy of antiviral therapy and host-virus interactions visualised using serial liver sampling with fine-needle aspirates.

Background & Aims: Novel therapies for chronic hepatitis B (CHB), such as RNA interference, target all viral RNAs for degradation, whereas nucleoside analogues are thought to block reverse transcription with minimal impact on viral transcripts. However, limitations in technology and sampling frequency have been obstacles to measuring actual changes in HBV transcription in the liver of patients starting therapy.

Methods: We used elective liver sampling with fine-needle aspirates (FNAs) to investigate the impact of treatment on viral replication in patients with CHB.

European projections of West Nile virus transmission under climate change scenarios.

West Nile virus (WNV), a mosquito-borne zoonosis, has emerged as a disease of public health concern in Europe. Recent outbreaks have been attributed to suitable climatic conditions for its vectors favoring transmission. However, to date, projections of the risk for WNV expansion under climate change scenarios is lacking.

Discrepancy in responses to the surprise question between hemodialysis nurses and physicians, with focus on patient clinical characteristics: A comparative study.

Introduction: The surprise question (SQ) "Would I be surprised if this patient died within the next xx months" can be used by different professions to foresee the need of serious illness conversations in patients approaching end of life. However, little is known about the different perspectives of nurses and physicians in responses to the SQ and factors influencing their appraisals. The aim was to explore nurses' and physicians' responses to the SQ regarding patients on hemodialysis, and to investigate how these answers were associated with patient clinical characteristics.

Mitochondrial N-formyl methionine peptides contribute to exaggerated neutrophil activation in patients with COVID-19.

Neutrophil dysregulation is well established in COVID-19. However, factors contributing to neutrophil activation in COVID-19 are not clear. We assessed if N-formyl methionine (fMet) contributes to neutrophil activation in COVID-19.

[ C]PBB3 binding in Aβ(-) or Aβ(+) corticobasal syndrome.

Corticobasal syndrome (CBS) is associated with 4-repeat tauopathy and/or Alzheimer's disease pathologies. To examine tau and amyloid-β (Aβ) deposits in CBS patients using positron emission tomography (PET). Eight CBS patients and three healthy individuals lacking amyloid pathology underwent PET with [ C]PBB3 for tau imaging, and [ C]AZD2184 for Aβ.

Prognostic value of severe acute respiratory syndrome coronavirus-2 viral load and antibodies in patients hospitalized with COVID-19.

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and anti-SARS-CoV-2 antibodies in coronavirus disease 2019 (COVID-19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double-blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID-19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA.

β2-Adrenoreceptor Agonists, Montelukast, and Parkinson Disease Risk.

Objective: This study was undertaken to examine the association between montelukast use, β2-adrenoreceptor (β2AR) agonist use, and later Parkinson disease (PD).

Methods: We ascertained use of β2AR agonists (430,885 individuals) and montelukast (23,315 individuals) from July 1, 2005 to June 30, 2007, and followed 5,186,886 PD-free individuals from July 1, 2007 to December 31, 2013 for incident PD diagnosis. We estimated hazard ratios and 95% confidence intervals using Cox regressions.

Assessing the national burden of allergic asthma by web-search data, pollen counts, and drug prescriptions in Germany and Sweden.

Background: Asthma and its main phenotype allergic asthma are prevalent, chronic, and complex diseases affecting 4% of the population. One main trigger for allergic asthma exacerbations is pollen. Online health information search behavior by people is increasing, and analysis of web-search data can provide valuable insight into disease burden and risk factors of a population.

Single-cell quantification and dose-response of cytosolic siRNA delivery.

Endosomal escape and subsequent cytosolic delivery of small interfering RNA (siRNA) therapeutics is believed to be highly inefficient. Since it has not been possible to quantify cytosolic amounts of delivered siRNA at therapeutic doses, determining delivery bottlenecks and total efficiency has been difficult. Here, we present a confocal microscopy-based method to quantify cytosolic delivery of fluorescently labeled siRNA during lipid-mediated delivery.

Nowcasting COVID-19 Statistics Reported with Delay: A Case-Study of Sweden and the UK.

The COVID-19 pandemic has demonstrated the importance of unbiased, real-time statistics of trends in disease events in order to achieve an effective response. Because of reporting delays, real-time statistics frequently underestimate the total number of infections, hospitalizations and deaths. When studied by event date, such delays also risk creating an illusion of a downward trend.