Implementation of the EU's Health Technology Assessment regulation: where does existing methods guidance require concretization and what are the relevant methodological options?

Objectives: The EUnetHTA Core Model is well-established in the HTA community. Some recommendations of corresponding guidance documents leave room for alternative methodological choices. Considering the new HTA regulation (HTAR), we aimed to identify needs for concretization (NCs) in EUnetHTA guidance and provide indicative methodological options.

iPSC-Derived Epithelial, Mesenchymal, Endothelial, and Immune Cell Co-Culture to Model Airway Barrier Integrity in Lung Health and Disease.

Human lung tissue is composed of an interconnected network of epithelium, mesenchyme, endothelium, and immune cells from the upper airway of the nasopharynx to the smallest alveolar sac. Interactions between these cells are crucial in lung development and disease, acting as a barrier against harmful chemicals and pathogens. Current in vitro co-culture models utilize immortalized cell lines with different biological backgrounds, which may not accurately represent the cellular milieu or interactions of the lung.

In vivo treatment with a non-aromatizable androgen rapidly alters the ovarian transcriptome of previtellogenic secondary growth coho salmon (Onchorhynchus kisutch).

Recent evidence suggests that androgens are a potent driver of growth during late the primary stage of ovarian follicle development in teleosts. We have previously shown that the non-aromatizable androgen, 11-ketotestosterone (11-KT), both advances ovarian follicle growth in vivo and dramatically alters the primary growth ovarian transcriptome in coho salmon. Many of the transcriptomic changes pointed towards 11-KT driving process associated with the transition to a secondary growth phenotype.

Several common methods of making vesicles (except an emulsion method) capture intended lipid ratios.

Unlabelled: Researchers choose different methods of making giant unilamellar vesicles in order to satisfy different constraints of their experimental designs. A challenge of using a variety of methods is that each may produce vesicles of different lipid compositions, even if all vesicles are made from a common stock mixture. Here, we use mass spectrometry to investigate ratios of lipids in vesicles made by five common methods: electroformation on indium tin oxide slides, electroformation on platinum wires, gentle hydration, emulsion transfer, and extrusion.

Digital Health Applications (DiHA): Approaches to develop a reimbursement process for the statutory health insurance in Austria.

Purpose: To elaborate a concept for implementing digital health applications (DiHA), including prioritisation criteria (PC) for the Austrian context and an overview of available prioritised DiHAs.

Methods: Based on European DiHA-listings and input by Austrian experts, a categorised meta-directory of DiHAs was created. PC were developed to reflect, inter alia, the provisions of the Austrian General Insurance Act, and were applied to the meta-directory to identify DiHAs potentially relevant for the Austrian statutory health insurance.

Inferring light responses of primate retinal ganglion cells using intrinsic electrical signatures.

. Retinal implants are designed to stimulate retinal ganglion cells (RGCs) in a way that restores sight to individuals blinded by photoreceptor degeneration. Reproducing high-acuity vision with these devices will likely require inferring the natural light responses of diverse RGC types in the implanted retina, without being able to measure them directly.

Wearable cardioverter defibrillator for preventing sudden cardiac death in patients at risk: An updated systematic review of comparative effectiveness and safety.

Objectives: To synthesise the available evidence of wearable cardioverter defibrillator (WCD) therapy as an add-on measure to optimal medical therapy (OMT) or as a replacement of hospital stay.

Methods: An update systematic review (SR) of comparative effectiveness and safety of WCD therapy was conducted. We included randomised controlled trials (RCT), prospective comparative studies and prospective uncontrolled studies with at least 100 patients.

Ripples at edges of blooming lilies and torn plastic sheets.

Ripples arise at edges of petals of blooming Lilium casablanca flowers and at edges of torn plastic sheets. In both systems, ripples are a consequence of excess length along the edge of a sheet. Through the use of time-lapse videos of blooming lilies and published images of torn plastic sheets, we find that ripples in both systems are well described by the scaling relationship a∝w(L-w), where a is amplitude, w is wavelength, and L is arc length.

Reimbursement decisions for medical services in Austria: an analysis of influencing factors for the hospital individual services catalogue between 2008 and 2020.

Objectives: To (1) describe the (evidence-based) reimbursement process of hospital individual services, (2) evaluate the accordance between evidence-based recommendations and reimbursement decision of individual services and (3) elaborate potential aspects that play a role in the decision-making process in Austria.

Method: The reimbursement process is described based on selected relevant sources such as official documents. Evidence-based recommendations and subsequent reimbursement decisions for the annual maintenance of the hospital individual service catalogue in Austria between 2008 and 2020 were analysed using a mixed methods approach, encompassing descriptive statistics and a focus group with Austrian decision makers.

Allelic diversification after transposable element exaptation promoted as the master sex determining gene of sablefish.

Concepts of evolutionary biology suggest that morphological change may occur by rare punctual but rather large changes, or by more steady and gradual transformations. It can therefore be asked whether genetic changes underlying morphological, physiological, and/or behavioral innovations during evolution occur in a punctual manner, whereby a single mutational event has prominent phenotypic consequences, or if many consecutive alterations in the DNA over longer time periods lead to phenotypic divergence. In the marine teleost, sablefish (), complementary genomic and genetic studies led to the identification of a sex locus on the Y Chromosome.

Extracorporeal Cytokine Adsorption Therapy As a Preventive Measure in Cardiac Surgery and As a Therapeutic Add-On Treatment in Sepsis: An Updated Systematic Review of Comparative Efficacy and Safety.

Objectives: Evaluating whether there is a clinical benefit of using extracorporeal cytokine adsorption therapy in two indications.

Design: Systematic review.

Setting: Search on four databases, Medline, Embase, The Cochrane Library, and the European Network for Health Technology Assessment planned and ongoing projects database.

Steering New Drug Discovery Campaigns: Permeability, Solubility, and Physicochemical Properties in the bRo5 Chemical Space.

An increasing number of drug discovery programs concern compounds in the beyond rule of 5 (bRo5) chemical space, such as cyclic peptides, macrocycles, and degraders. Recent results show that common paradigms of property-based drug design need revision to be applied to larger and more flexible compounds. A virtual event entitled "Solubility, permeability and physico-chemical properties in the bRo5 chemical space" was organized to provide preliminary guidance on how to make the discovery of oral drugs in the bRo5 space more effective.

Comparative Effectiveness and Safety of Allografts and Autografts in Posterior Cruciate Ligament Reconstruction Surgery: A Systematic Review.

Purpose: To evaluate the evidence of the effectiveness and safety of allografts compared to autografts in posterior cruciate ligament reconstruction.

Methods: Four electronic databases were systematically searched for eligible randomized controlled studies. Crucial effectiveness outcomes included patient-reported function, activity level and symptoms, clinical knee stability, health-related quality of life, and patient satisfaction.

Allograft for Anterior Cruciate Ligament Reconstruction (ACLR): A Systematic Review and Meta-Analysis of Long-Term Comparative Effectiveness and Safety. Results of a Health Technology Assessment.

Purpose: To evaluate whether allograft anterior cruciate ligament reconstruction (ACLR) is superior or inferior to autograft ACLR or conservative management in terms of effectiveness and safety.

Methods: A systematic review of the evidence for allograft ACLR was conducted. Randomized controlled trials with a minimum mean follow-up time of 5 years were included.

Strong population differentiation in lingcod () is driven by a small portion of the genome.

Delimiting intraspecific genetic variation in harvested species is crucial to the assessment of population status for natural resource management and conservation purposes. Here, we evaluated genetic population structure in lingcod (), a commercially and recreationally important fishery species along the west coast of North America. We used 16,749 restriction site-associated DNA sequencing (RADseq) markers, in 611 individuals collected from across the bulk of the species range from Southeast Alaska to Baja California, Mexico.

Vanishing Bile Duct Syndrome Preceding the Diagnosis of Hodgkin Lymphoma.

Vanishing bile duct syndrome is an acquired liver disease characterized by the progressive destruction and loss of intrahepatic bile ducts. It usually signifies end-stage cholestatic liver disease and is characterized by ductopenia on liver biopsy specimen. We present a case of vanishing bile duct syndrome as the presenting symptom in a patient with Hodgkin lymphoma with subsequent improvement after adequate treatment of the lymphoma.

Inference of nonlinear receptive field subunits with spike-triggered clustering.

Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. We present a method for maximum likelihood estimation of subunits by soft-clustering spike-triggered stimuli, and demonstrate its effectiveness in visual neurons.

Updating the portfolio of physicochemical descriptors related to permeability in the beyond the rule of 5 chemical space.

Beyond rule of 5 (bRo5) molecules are attracting significant interest in modern drug discovery mostly because many novel targets require large and more flexible structures. The main aim of this paper is the identification of ad hoc bRo5 physicochemical descriptors of ionization, lipophilicity, polarity and chameleonicity and their measurement. We used different methods to collect ionization (pK measures and log k'80 PLRP-S trends), lipophilicity (in octanol/water, in apolar systems and in biomimetic environments), polarity (Δlog P, EPSA and Δlog K) and chameleonicity (ChameLogD) descriptors for 26 bRo5 drugs.

An update on retinal prostheses.

Retinal prostheses are designed to restore a basic sense of sight to people with profound vision loss. They require a relatively intact posterior visual pathway (optic nerve, lateral geniculate nucleus and visual cortex). Retinal implants are options for people with severe stages of retinal degenerative disease such as retinitis pigmentosa and age-related macular degeneration.

Cardiac remodeling in response to embryonic crude oil exposure involves unconventional NKX family members and innate immunity genes.

Cardiac remodeling results from both physiological and pathological stimuli. Compared with mammalian hearts, fish hearts show a broader array of remodeling changes in response to environmental influences, providing exceptional models for dissecting the molecular and cellular bases of cardiac remodeling. We recently characterized a form of pathological remodeling in juvenile pink salmon () in response to crude oil exposure during embryonic cardiogenesis.

Unusual Physiological Properties of Smooth Monostratified Ganglion Cell Types in Primate Retina.

The functions of the diverse retinal ganglion cell types in primates and the parallel visual pathways they initiate remain poorly understood. Here, unusual physiological and computational properties of the ON and OFF smooth monostratified ganglion cells are explored. Large-scale multi-electrode recordings from 48 macaque retinas revealed that these cells exhibit irregular receptive field structure composed of spatially segregated hotspots, quite different from the classic center-surround model of retinal receptive fields.

Temporal Dynamics of DNA Methylation Patterns in Response to Rearing Juvenile Steelhead () in a Hatchery versus Simulated Stream Environment.

Genetic selection is often implicated as the underlying cause of heritable phenotypic differences between hatchery and wild populations of steelhead trout () that also differ in lifetime fitness. Developmental plasticity, which can also affect fitness, may be mediated by epigenetic mechanisms such as DNA methylation. Our previous study identified significant differences in DNA methylation between adult hatchery- and natural-origin steelhead from the same population that could not be distinguished by DNA sequence variation.

Actor-partner examination of daily parenting stress and couple interactions in the context of child autism.

Parents of children with autism spectrum disorder (ASD) are at risk for poor couple relationship quality. The goal of the current study was to understand actor and partner associations between daily level of parenting stress and perceived couple interactions using a 14-day daily diary in 186 families of children with ASD. A comparison group of 182 families of children without a neurodevelopmental disability was included to determine if actor and partner associations differed in a context of child ASD.