The pharmaceutical productivity gap - Incremental decline in R&D efficiency despite transient improvements.

Rising research and development costs, currently exceeding $3.5 billion per novel drug, reflect a five-decade decline in pharmaceutical R&D efficiency. While recent reports suggest a potential turnaround, this review offers a systems-level analysis to explore whether this marks a structural shift or transient reversal.

The influence of the reference level on loudness and preference judgements for spectrally manipulated fan sounds.

Fan sounds are often quantified using A-weighted sound pressure levels, silently acknowledging their limitations to fully capture the perceived unpleasantness. To overcome this limitation, level adjustments are a way to quantify the subjective preference of spectrally different sounds in listening experiments by adjusting the level of a test sound until it is equally preferred to a fixed reference sound. Since equal loudness contours differ, depending on the overall level, level adjustments might vary for different levels of the reference sound.

An Innovative AI-based primer design tool for precise and accurate detection of SARS-CoV-2 variants of concern.

As the COVID-19 pandemic winds down, it leaves behind the serious concern that future, even more disruptive pandemics may eventually surface. One of the crucial steps in handling the SARS-CoV-2 pandemic was being able to detect the presence of the virus in an accurate and timely manner, to then develop policies counteracting the spread. Nevertheless, as the pandemic evolved, new variants with potentially dangerous mutations appeared.

Booster vaccination with Ad26.COV2.S or an Omicron-adapted vaccine in pre-immune hamsters protects against Omicron BA.2.

Since the original outbreak of the SARS-CoV-2 virus, several rapidly spreading SARS-CoV-2 variants of concern (VOC) have emerged. Here, we show that a single dose of Ad26.COV2.

Multispecies probiotics promote perceived human health and wellbeing: insights into the value of retrospective studies on user experiences.

When taking a broader perspective on the societal impact of probiotics, engagement of end-users is important to discover unmet needs, define relevant health benefits and identify key considerations for successful implementation in daily practice. This study therefore takes a retrospective approach and analyses a database of user experiences to review the effects of four multispecies probiotic formulations. The user experiences were analysed in a dependent sample manner (without control group) and complement previous randomised controlled trials that have been performed with the formulations.

Barriers Influencing Vaccine Development Timelines, Identification, Causal Analysis, and Prioritization of Key Barriers by KOLs in General and Covid-19 Vaccine R&D.

A frequently mentioned factor holding back the introduction of new vaccines on the market are their prohibitively long development timelines. These hamper their potential societal benefit and impairs the ability to quickly respond to emerging new pathogens. This is especially worrisome since new pathogens are emerging at all-time high rates of over one per year, and many age-old pathogens are still not vaccine preventable.

A survival of the fittest strategy for the selection of genotypes by which drug responders and non-responders can be predicted in small groups.

Phenotype Prediction Scores (PPS) might be powerful tools to predict traits or the efficacy of treatments based on combinations of Single-Nucleotide Polymorphism (SNPs) in large samples. We developed a novel method to produce PPS models for small samples sizes. The set of SNPs is first filtered on those known to be relevant in biological pathways involved in a clinical condition, and then further filtered repeatedly in a survival strategy to select stabile positive/negative risk alleles.

Lower Respiratory Tract Infection Trends in East and South-East Asia: In the Light of Economic and Health Care Development.

This study explored to what degree economic development and improvement of healthcare are associated with lower respiratory tract infection (LRTI) mortality. A correlation analysis between LRTI mortality and Gross Domestic Product (GDP) per capita, and the Health Access and Quality Index (HAQI), respectively was conducted for 15 countries in East and South-East Asia. The results revealed a dramatic decrease in LRTI mortality in total populations for lower-middle income (LMI) countries but at the same time an increase in upper-middle income (UMI) and high-income (HI) countries.

Probiotics as a treatment for prenatal maternal anxiety and depression: a double-blind randomized pilot trial.

Probiotic use may be an efficacious treatment option to effectively manage symptoms of prenatal maternal anxiety and depression. Our primary aim was to test feasibility and acceptability for a probiotic randomized controlled trial (RCT) in pregnant women with pre-existing symptoms. This double-blind pilot RCT included 40 pregnant women with low-risk pregnancies and elevated depressive symptoms and/or anxiety.

Classification and specific primer design for accurate detection of SARS-CoV-2 using deep learning.

In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from the National Genomics Data Center repository, separating the genome of different virus strains from the Coronavirus family with 98.73% accuracy.

Prevalence of viral respiratory infections amongst asthmatics: Results of a meta-regression analysis.

Viral respiratory infections (VRI) can act as triggers for acute asthma exacerbations and contribute significantly to asthma-related healthcare costs. Knowing the patterns of viruses amongst asthmatics can be useful in treating and preventing these exacerbations and help decrease the burden they impose on patients and healthcare systems. We aimed to quantify the viral prevalence in asthmatics presenting with exacerbations and identify influencing factors.

On the importance of intraindividual variation in nutritional research.

Nutritional intervention studies, like those with pre- and probiotics, are often hampered by low effect sizes, reducing the power to demonstrate potential efficacy. Here, we perform computer simulations of a hypothetical clinical trial using such an intervention in order to elucidate determining factors that can be influenced in order to optimise the statistical power. Our simulations demonstrate that steering the study population towards a low intraindividual variation dramatically improves statistical power.

Quantity vs. quality: an assessment of the current pipeline for rabies.

Objectives: To gain insight in the potential of the current pipeline for rabies to decrease the burden of disease by evaluating its relevance to high-risk countries.

Methods: Rabies-related patent documents and clinical trials were retrieved from Espacenet and the WHO ICTRP, respectively. Data were cleaned, modulated and categorised into a pre-defined set of indicators those were used for (statistical) analyses on the number of patent applications, patent quality and type of stakeholders involved for different geographical areas.

Probiotics in pregnancy: protocol of a double-blind randomized controlled pilot trial for pregnant women with depression and anxiety (PIP pilot trial).

Background: Maternal prenatal depressive or anxiety symptoms are associated with adverse maternal and infant health outcomes. With prevalence rates of maternal prenatal depression and anxiety ranging between 10 and 20%, attempts to identify effective interventions to reduce symptoms are priority. There are indications that probiotics can reduce symptoms of maternal depression or anxiety.

Dealing with the remaining controversies of probiotic safety.

A clear safety profile of probiotics in clinical practice is essential in decision-making for all stakeholders and regulators. Probiotics have been investigated in different target populations, conditions and age groups. This also includes the use of probiotics in critically ill patients.

Towards a rational design of faecal transplant analogues.

Faecal transplants (microbiota transfer) have shown to be promising therapies having a wide range of therapeutic applications. However, current safety considerations hamper further valorisation. As such, well designed faecal transplant analogues provide an interesting alternative to minimize possible safety aspects.

Towards improved process efficiency in vaccine innovation: The Vaccine Innovation Cycle as a validated, conceptual stage-gate model.

Continuing investments in vaccine innovation are insufficiently translated into market entries of novel vaccines. This innovation paradox is in part caused by stakeholders lacking complete understanding of the complex array of steps necessary for vaccine development and collaboration difficulties between the wide variety of stakeholders involved. Models providing cross-domain understanding can improve collaboration but currently lack both comprehensibility and granularity to enable a prioritized view of activities and criteria.

A research agenda to reinforce rabies control: A qualitative and quantitative prioritization.

Background: Despite the existence of safe and effective vaccines, rabies disease still causes an estimated 59,000 human deaths a year in the endemic areas in Asia and Africa. These numbers reflect severe drawbacks regarding the implementation of PrEP and PEP in endemic settings, such as lack of political will and low priority given to rabies. Since these contextual factors have proven to be persistent, there is an urgency to improve current strategies or develop novel approaches in order to control rabies disease in the future.

How ownership rights over microorganisms affect infectious disease control and innovation: A root-cause analysis of barriers to data sharing as experienced by key stakeholders.

Background: Genetic information of pathogens is an essential input for infectious disease control, public health and for research. Efficiency in preventing and responding to global outbreaks relies on timely access to such information. Still, ownership barriers stand in the way of timely sharing of genetic data from pathogens, frustrating efficient public health responses and ultimately the potential use of such resources in innovations.

The mechanistic link between health and gut microbiota diversity.

Although numerous reports link a decreased diversity of the gut microbiota to a declined health status, to date no mechanistic motivation for this exists. Here, we show by applying first principles basic graph theory on small networks that higher diversity within such a network indeed leads to more efficient systems and redundancy. Our results quantitatively support earlier hypothetical considerations on gut microbiota richness with respect to these parameters.

The underexposed role of food matrices in probiotic products: Reviewing the relationship between carrier matrices and product parameters.

Probiotic microorganisms are increasingly incorporated into food matrices in order to confer proposed health benefits on the consumer. It is important that the health benefits, sensory properties, shelf-life and probiotic gastrointestinal tract (GIT) survival of these products are carefully balanced as they determine functionality and drive consumer acceptance. The strain-specific effects of probiotic species are imperative in this process but carrier matrices may play a pivotal role as well.

Barriers to innovation in human rabies prophylaxis and treatment: A causal analysis of insights from key opinion leaders and literature.

Rabies is an essentially 100% fatal, zoonotic disease, caused by Lyssaviruses. Currently, the disease is vaccine-preventable with pre- and post-exposure prophylaxis (PrEP and PEP). Still, rabies virus is estimated to cause up to 60,000 human deaths annually, of which the vast majority occurs in rural Asia and Africa, due to the inaccessibility of prophylaxis and non-existence of treatment.

The moderating role of absorptive capacity and the differential effects of acquisitions and alliances on Big Pharma firms' innovation performance.

In the context of increased pharmaceutical innovation deficits and Big Pharma blockbusters' patent expirations, this paper examines the moderating role of firms' absorptive capacity in external innovation activities of Big Pharma firms. The study indicates a rising interest of Big Pharma in acquisitions of and alliances with biotechnology companies. Unfortunately, this increased interest is not reflected in the number of new drugs generated by Big Pharma.

Functions of CD40 and Its Ligand, gp39 (CD40L).

Initially, a role for the interaction between CD40, expressed on B cells, and gp39 (CD40L), expressed on activated T cells, has been defined in humoral immunity. CD40-CD40L interaction is an essential signal for B cell proliferation, expression of activation markers, immunoglobulin production, and isotype switching. CD40-CD40L interaction is also required for formation of B memory cells and germinal centers, and signaling through CD40 prevents apoptosis of germinal center B cells.