Short- and long-term outcomes in isolated vs. hybrid thoracoscopic ablation in patients with atrial fibrillation: a systematic review and reconstructed individual patient data meta-analysis.

Aims: Both isolated thoracoscopic and hybrid thoracoscopic atrial fibrillation (AF) ablation techniques have demonstrated favourable outcomes in the management of patients with (long-standing) persistent AF, as compared with catheter ablation. However, it is currently unknown whether there is a difference in short- and long-term outcomes when comparing these two minimally invasive surgical AF ablation procedures. Therefore, a systematic review and meta-analysis were performed to investigate these two techniques, with a specific emphasis on long-term freedom from atrial tachyarrhythmias (ATAs).

Temporary sinus node dysfunction following ablation of atrial fibrillation in patients with aberrancy of the sinus node artery: a case series.

Objectives: Our goal was to investigate sinus node dysfunction (SND) as a rare complication following surgical and catheter atrial fibrillation (AF) ablation in patients with an aberrant sinus node artery (SNA).

Methods: We used a retrospective analysis of 3 patients with an aberrant SNA who underwent different AF ablation procedures: 1 concomitant to aortic valve replacement, 1 thoracoscopic hybrid AF ablation and 1 catheter AF ablation.

Results: All patients experienced temporary SND perioperatively.

Determining recommended acceptable intake limits for N-nitrosamine impurities in pharmaceuticals: Development and application of the Carcinogenic Potency Categorization Approach (CPCA).

N-Nitrosamine impurities, including nitrosamine drug substance-related impurities (NDSRIs), have challenged pharmaceutical industry and regulators alike and affected the global drug supply over the past 5 years. Nitrosamines are a class of known carcinogens, but NDSRIs have posed additional challenges as many lack empirical data to establish acceptable intake (AI) limits. Read-across analysis from surrogates has been used to identify AI limits in some cases; however, this approach is limited by the availability of robustly-tested surrogates matching the structural features of NDSRIs, which usually contain a diverse array of functional groups.

Retreatment with HBV siRNA Results in Additional Reduction in HBV Antigenemia and Immune Stimulation in the AAV-HBV Mouse Model.

Background And Aims: Treatment with siRNAs that target HBV has demonstrated robust declines in HBV antigens. This effect is also observed in the AAV-HBV mouse model, which was used to investigate if two cycles of GalNAc-HBV-siRNA treatment could induce deeper declines in HBsAg levels or prevent rebound, and to provide insights into the liver immune microenvironment.

Methods: C57Bl/6 mice were transduced with one of two different titers of AAV-HBV for 28 days, resulting in stable levels of HBsAg of about 10 or 10 IU/mL.

Hybrid atrial fibrillation ablation.

In this state-of-the art review on hybrid atrial fibrillation (AF) ablation, we briefly focus on the pathophysiology of AF, the rationale for the hybrid approach, its technical aspects and the efficacy and safety outcomes after hybrid AF ablation, both from meta-analyses and randomized control trial data. Also, we performed a systematic search to provide a provisional overview of real-world hybrid AF ablation efficacy and safety outcomes. Furthermore, we give an insight into the 'Maastricht approach', an approach that allows us to tailor the ablation procedure to the individual patient.

Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels.

Background: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination.

Mastering the learning curve of endoscopic mitral valve surgery.

Endoscopic mitral valve surgery is a challenging procedure. Surgical volume is mandatory to achieve sufficient proficiency and superior results. To this date the learning curve has proven to be challenging.

The use of recovery animals in nonclinical safety assessment studies with monoclonal antibodies: further 3Rs opportunities remain.

Assessment of reversibility from nonclinical toxicity findings in animals with potential adverse clinical impact is required during pharmaceutical development, but there is flexibility around how and when this is performed and if recovery animals are necessary. For monoclonal antibodies (mAbs) and in accordance with ICH S6(R1) if inclusion of recovery animals is warranted, this need only occur in one study. Data on study designs for first-in-human (FIH)-enabling and later-development toxicity studies were shared from a recent collaboration between the NC3Rs, EPAA, Netherlands Medicines Evaluation Board (MEB) and 14 pharmaceutical companies.

Re-evaluating the need for chronic toxicity studies with therapeutic monoclonal antibodies, using a weight of evidence approach.

To support registration of monoclonal antibodies (mAbs) for chronic indications, 6-month toxicity studies have historically been conducted. Experience with mAb development has shown a relatively benign and well-understood safety profile for this class, with most toxicity findings anticipated based on pharmacology. We evaluated whether a 6-month toxicity study is necessary to assess the long-term safety of mAbs.

Benthic studies adjacent to Sakhalin Island, Russia, 2015 I: benthic biomass and community structure in the nearshore gray whale feeding area.

Okhotsk or western gray whales feed in summer along the northeastern coast of Sakhalin Island, Russia, a region with oil and gas extraction facilities. Seismic surveys increased sound levels in the nearshore feeding area in 2015 for part of the summer, potentially displacing whales from preferred foraging habitat or reducing foraging efficiency. Since lost foraging opportunities might lead to vital rate effects on this endangered species, detailed benthic surveys were conducted to characterize benthic community biomass patterns and spatial and temporal differences.

Gray whale density during seismic surveys near their Sakhalin feeding ground.

Oil and gas development off northeastern Sakhalin Island, Russia, has exposed the western gray whale population on their summer-fall foraging grounds to a range of anthropogenic activities, such as pile driving, dredging, pipeline installation, and seismic surveys. In 2015, the number of seismic surveys within a feeding season surpassed the level of the number and duration of previous seismic survey activities known to have occurred close to the gray whales' feeding ground, with the potential to cause disturbance to their feeding activity. To examine the extent that gray whales were potentially avoiding areas when exposed to seismic and vessel sounds, shore-based teams monitored the abundance and distribution of gray whales from 13 stations that encompassed the known nearshore feeding area.

Seismic surveys near gray whale feeding areas off Sakhalin Island, Russia: assessing impact and mitigation effectiveness.

In 2015, two oil and gas companies conducted seismic surveys along the northeast coast of Sakhalin Island, Russia, near western gray whale (Eschrichtius robustus) feeding areas. This population of whales was listed as Critically Endangered at the time of the operations described here but has been reclassified as Endangered since 2018. The number and duration of the 2015 seismic surveys surpassed the level of previous seismic survey activity in this area, elevating concerns regarding disturbance of feeding gray whales and the potential for auditory injury.

Benthic studies adjacent to Sakhalin Island, Russia, 2015 II: energy content of the zoobenthos in western gray whale feeding grounds.

The waters adjacent to the northeastern coast of Sakhalin Island, Russia, are an important feeding ground for the endangered western gray whale. Data on the energy available to foraging whales from their prey resources is required for researchers interested in modeling the bioenergetics of whale foraging, but little energy content information is available for the benthic prey communities of gray whales in this region. In this study, we describe the energy density (ED), biomass, and total energy availability (ED × biomass) of benthic prey sampled from two gray whale foraging areas adjacent to Sakhalin Island: the nearshore and offshore feeding areas.

Complementarity of mDSC, DMA, and DRS Techniques in the Study of and Sub- Transitions in Amorphous Solids: PVPVA, Indomethacin, and Amorphous Solid Dispersions Based on Indomethacin/PVPVA.

Recently, glasses, a subset of amorphous solids, have gained attention in various fields, such as polymer chemistry, optical fibers, and pharmaceuticals. One of their characteristic features, the glass transition temperature () which is absent in 100% crystalline materials, influences several material properties, such as free volume, enthalpy, viscosity, thermodynamic transitions, molecular motions, physical stability, mechanical properties, etc. In addition to , there may be several other temperature-dependent transitions known as sub- transitions (or β-, γ-, and δ-relaxations) which are identified by specific analytical techniques.

Do we still need animals? Surveying the role of animal-free models in Alzheimer's and Parkinson's disease research.

The use of animals in neuroscience and biomedical research remains controversial. Policy is built around the "3R" principle of "Refining, Reducing and Replacing" animal experiments, and across the globe, different initiatives stimulate the use of animal-free methods. Based on an extensive literature screen to map the development and adoption of animal-free methods in Alzheimer's and Parkinson's disease research, we find that at least two in three examined studies rely on animals or on animal-derived models.

Surgical Treatments of Chronic Vulvar Pain After Female Genital Mutilation/Cutting.

Background: Vulvar and in particular clitoral pain can affect women with Female Genital Mutilation/Cutting (FGM/C). To date, there is no comprehensive study on the different available treatments for vulvar pain after FGM/C.

Aim: To study the outcome of surgical treatments of vulvar and/or clitoral pain among women living with FGM/C.

Differential expression of maturation and activation markers on NK cells in patients with active and latent tuberculosis.

NK cells were recently suggested to be important for the initial control of M. tuberculosis infection. The phenotypes of the 3 main NK blood subsets, CD56 , CD56 , and CD56 cells, were characterized by flow cytometry in a cohort of 81 prospectively enrolled subjects (21 untreated patients with active tuberculosis -aTB-, 35 latently TB infected -LTBI- subjects, and 25 non-infected controls), using 9 different mAbs added to whole blood.

Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function.

Deficiency of the serine hydrolase prolyl endopeptidase-like (PREPL) causes a recessive metabolic disorder characterized by neonatal hypotonia, feeding difficulties, and growth hormone deficiency. The pathophysiology of PREPL deficiency and the physiological substrates of PREPL remain largely unknown. In this study, we connect PREPL with mitochondrial gene expression and oxidative phosphorylation by analyzing its protein interactors.

Coding-Complete Sequences of Recombinant Lumpy Skin Disease Viruses Collected in 2020 from Four Outbreaks in Northern Vietnam.

(LSDV) causes a severe, systemic, and economically important disease in cattle. Here, we report coding-complete sequences of recombinant LSDVs from four outbreaks in October and November 2020 in northeastern Vietnam.

The Importance of Quality Control of LSDV Live Attenuated Vaccines for Its Safe Application in the Field.

Vaccination is an effective approach to prevent, control and eradicate diseases, including lumpy skin disease (LSD). One of the measures to address farmer hesitation to vaccinate is guaranteeing the quality of vaccine batches. The purpose of this study was to demonstrate the importance of a quality procedure via the evaluation of the LSD vaccine, Lumpivax (Kevevapi).