Assessing the economic impact and healthcare resource utilization of inpatient pneumococcal disease among adults: a French national claims database study.

Introduction: Pneumococcal diseases (PD) caused by include invasive PD (IPD) and non-bacteremia pneumococcal pneumonia (NBPP). Current French vaccination guidelines FOCUS on patients with underlying medical conditions (UMC) who are at a higher risk of PD. This study describes the healthcare resource utilization (HCRU) and economic burden of inpatient PD in French adults, to inform vaccination guidelines, especially among vulnerable subpopulations at increased risk of PD.

Expanding vaccination competencies to community pharmacists: modelling the organizational and economic impacts of new human papilloma virus (HPV) vaccine pathways in France.

Background: The vaccine coverage rate (VCR) for human papillomavirus (HPV) in France is one of the lowest in Europe, well below the target of 80% announced in the French Cancer Plan 2021-2030. The extension of vaccination competencies (prescription and administration) to new health care providers, such as community pharmacists (CPs), was a decisive step by the French Health Authority (HAS) in 2022 to simplify access to vaccination and improve the VCR. This research assessed the economic and organizational impacts (OIs) of the extension of vaccination competencies in France.

Human Papillomavirus (HPV) vaccination coverage among French adolescents: A claims data study.

Background: The French cancer control strategy 2021-2030 aims to achieve 80 % human papillomavirus (HPV) vaccination coverage. Since 2021, HPV vaccination is also recommended for boys aged 11-14 years, with a catch-up vaccination recommended for unvaccinated adolescents aged ≤19 years. The PAPILLON study used claims data to monitor the evolution of HPV Vaccination Coverage Rate (VCR) in the French population.

The mutation R107Q alters mtSSB ssDNA compaction ability and binding dynamics.

Mitochondrial single-stranded DNA-binding protein (mtSSB) is essential for mitochondrial DNA (mtDNA) replication. Recently, several mtSSB variants have been associated with autosomal dominant mitochondrial optic atrophy and retinal dystrophy. Here, we have studied at the molecular level the functional consequences of one of the most severe mtSSB variants, R107Q.

Facilitating human papillomavirus vaccination pathways by extending vaccination competencies to community pharmacists: A cross-sectional survey on the acceptability and expectations among healthcare professionals and parents.

Background: Human papillomavirus (HPV) vaccination coverage rate (VCR) remains low in France (37.4% in girls in 2021). The French health authority recommended in 2022 to extend vaccination competencies to additional healthcare providers (HCPs), including community pharmacists (CPs).

How to Quantify DNA Compaction by TFAM with Acoustic Force Spectroscopy and Total Internal Reflection Fluorescence Microscopy.

Mitochondrial transcription factor A (TFAM) plays a key role in the organization and compaction of the mitochondrial genome. However, there are only a few simple and accessible methods available to observe and quantify TFAM-dependent DNA compaction. Acoustic Force Spectroscopy (AFS) is a straightforward single-molecule force spectroscopy technique.

Disease causing mutation (P178L) in mitochondrial transcription factor A results in impaired mitochondrial transcription initiation.

Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression, and packaging of mitochondrial DNA (mtDNA). Recently, a pathogenic homozygous variant in TFAM (P178L) has been associated with a severe mtDNA depletion syndrome leading to neonatal liver failure and early death. We have performed a biochemical characterization of the TFAM variant P178L in order to understand the molecular basis for the pathogenicity of this mutation.

Seismic tremor reveals active trans-crustal magmatic system beneath Kamchatka volcanoes.

The occurrence and the style of volcanic eruptions are largely controlled by the ways in which magma is stored and transported from the mantle to the surface through the crust. Nevertheless, our understanding of the deep roots of volcano-magmatic systems remains very limited. Here, we use the sources of seismovolcanic tremor to delineate the active part of the magmatic system beneath the Klyuchevskoy Volcanic Group in Kamchatka, Russia.

The Health Professional's View on the Inclusion of Age in the Recommendations for Pneumococcal Vaccination: Results of a Cross-Sectional Survey in France.

Elderly people are at high risk for pneumococcal infections. However, older age is not an eligibility factor for pneumococcal vaccination in France. Adults with certain co-morbidities or immunocompromised states are eligible for vaccination, which leaves adults aged ≥65 years without comorbidities at-risk for pneumococcal infections.

Real-world effectiveness of pembrolizumab in advanced melanoma: analysis of a French national clinicobiological database.

To describe real-world pembrolizumab administration and outcomes for advanced melanoma in France. Using the MelBase longitudinal database, this multicenter historical-prospective study examined treatment and outcomes of patients with nonuveal, unresectable stage III/IV melanoma initiating pembrolizumab from April 2016 to September 2017, with follow-up to September 2019. Kaplan-Meier time-to-event analyses were conducted.

Real-world cost-effectiveness of etonogestrel implants compared to long-term and short term reversible contraceptive methods in France.

Background: To estimate the cost-effectiveness (CE) of etonogestrel implants compared to other long-term and short-term reversible contraceptive methods available in France.

Research Design And Methods: A 6-year Markov model compared effectiveness between the implant and six other contraceptive methods in sexually active, not-pregnancy-seeking French females of reproductive age. Contraception efficacy, switch rates and outcomes were based on French current medical practice.

Organization of DNA in Mammalian Mitochondria.

As with all organisms that must organize and condense their DNA to fit within the limited volume of a cell or a nucleus, mammalian mitochondrial DNA (mtDNA) is packaged into nucleoprotein structures called nucleoids. In this study, we first introduce the general modes of DNA compaction, especially the role of the nucleoid-associated proteins (NAPs) that structure the bacterial chromosome. We then present the mitochondrial nucleoid and the main factors responsible for packaging of mtDNA: ARS- (autonomously replicating sequence-) binding factor 2 protein (Abf2p) in yeast and mitochondrial transcription factor A (TFAM) in mammals.

Structural basis for adPEO-causing mutations in the mitochondrial TWINKLE helicase.

TWINKLE is the helicase involved in replication and maintenance of mitochondrial DNA (mtDNA) in mammalian cells. Structurally, TWINKLE is closely related to the bacteriophage T7 gp4 protein and comprises a helicase and primase domain joined by a flexible linker region. Mutations in and around this linker region are responsible for autosomal dominant progressive external ophthalmoplegia (adPEO), a neuromuscular disorder associated with deletions in mtDNA.

Reslizumab Compared with Benralizumab in Patients with Eosinophilic Asthma: A Systematic Literature Review and Network Meta-Analysis.

Background: The interaction of IL-5 with its receptor on eosinophils increases the activation and maintenance of eosinophils; blocking this interaction reduces asthma symptoms in patients with the eosinophilic phenotype. Reslizumab, which binds to IL-5, and benralizumab, which targets the IL-5 receptor α subunit, have not been compared in head-to-head trials.

Objective: To indirectly compare reslizumab with benralizumab in similar patient populations using a network meta-analysis.

The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair.

EXD2 is a recently identified exonuclease that has been implicated in nuclear double-strand break repair. Given our long standing interest in mitochondrial DNA maintenance and indications that EXD2 could also be a mitochondrial protein we sought to determine its cellular localization and possible mitochondrial associated functions. Our results show that EXD2 indeed shows mitochondrial localization, but, surprisingly, is found predominantly associated with the mitochondrial outer-membrane.

In vitro-reconstituted nucleoids can block mitochondrial DNA replication and transcription.

The mechanisms regulating the number of active copies of mtDNA are still unclear. A mammalian cell typically contains 1,000-10,000 copies of mtDNA, which are packaged into nucleoprotein complexes termed nucleoids. The main protein component of these structures is mitochondrial transcription factor A (TFAM).

The UbL protein UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes.

UBTD1 is a previously uncharacterized ubiquitin-like (UbL) domain containing protein with high homology to the mitochondrial Dc-UbP/UBTD2 protein. Here we show that UBTD1 and UBTD2 belong to a family of proteins that is conserved through evolution and found in metazoa, funghi, and plants. To gain further insight into the function of UBTD1, we screened for interacting proteins.

STED nanoscopy combined with optical tweezers reveals protein dynamics on densely covered DNA.

Dense coverage of DNA by proteins is a ubiquitous feature of cellular processes such as DNA organization, replication and repair. We present a single-molecule approach capable of visualizing individual DNA-binding proteins on densely covered DNA and in the presence of high protein concentrations. Our approach combines optical tweezers with multicolor confocal and stimulated emission depletion (STED) fluorescence microscopy.

A toolbox for generating single-stranded DNA in optical tweezers experiments.

Essential genomic transactions such as DNA-damage repair and DNA replication take place on single-stranded DNA (ssDNA) or require specific single-stranded/double-stranded DNA (ssDNA/dsDNA) junctions (SDSJ). A significant challenge in single-molecule studies of DNA-protein interactions using optical trapping is the design and generation of appropriate DNA templates. In contrast to dsDNA, only a limited toolbox is available for the generation of ssDNA constructs for optical tweezers experiments.

Protein sliding and DNA denaturation are essential for DNA organization by human mitochondrial transcription factor A.

Mitochondria organize their genome in protein-DNA complexes called nucleoids. The mitochondrial transcription factor A (TFAM), a protein that regulates mitochondrial transcription, is abundant in these nucleoids. TFAM is believed to be essential for mitochondrial DNA compaction, yet the exact mechanism has not been resolved.

The mitochondrial DNA helicase TWINKLE can assemble on a closed circular template and support initiation of DNA synthesis.

Mitochondrial DNA replication is performed by a simple machinery, containing the TWINKLE DNA helicase, a single-stranded DNA-binding protein, and the mitochondrial DNA polymerase γ. In addition, mitochondrial RNA polymerase is required for primer formation at the origins of DNA replication. TWINKLE adopts a hexameric ring-shaped structure that must load on the closed circular mtDNA genome.