Do quality of life and work productivity change in early axial spondyloarthritis and non-axial spondyloarthritis patients after two years?

Objective: To compare health-related quality of life (HRQoL) and work productivity in axial spondyloarthritis (axSpA) and non-axSpA patients with chronic back pain of < 2 years (2 y).

Methods: Baseline and 2 y data of patients included in the SPondyloArthritis Caught Early cohort were analyzed. HRQoL was assessed by the physical (PCS) and mental component summary (MCS) scores of the 36-Item Short-Form Health Survey; and presenteeism, absenteeism, work productivity loss (WPL) and activity impairment (AI) by the Work Productivity and Activity Impairment questionnaire.

Various repair events following CRISPR/Cas9-based mutational correction of an infertility-related mutation in mouse embryos.

Purpose: Unpredictable genetic modifications and chromosomal aberrations following CRISPR/Cas9 administration hamper the efficacy of germline editing. Repair events triggered by double-strand DNA breaks (DSBs) besides non-homologous end joining and repair template-driven homology-directed repair have been insufficiently investigated in mouse. In this work, we are the first to investigate the precise repair mechanisms triggered by parental-specific DSB induction in mouse for paternal mutational correction in the context of an infertility-related mutation.

Pronuclear transfer rescues poor embryo development of -grown secondary mouse follicles.

Study Question: Is pronuclear transfer (PNT) capable of restoring embryo developmental arrest caused by cytoplasmic inferiority of -grown (IVG) mouse oocytes?

Summary Answer: PNT to matured cytoplasm significantly improved embryo development of IVG mouse oocytes, leading to living, fertile offspring.

What Is Known Already: follicle culture has been considered as a fertility preservation option for cancer patients. Studies describing the culture of human follicles remain scarce, owing to low availability of tissue.

Consensus on the definitions and descriptions of the domains of the OMERACT Core Outcome Set for shared decision making interventions in rheumatology trials.

Objective: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions.

Methods: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions.

Retained chromosomal integrity following CRISPR-Cas9-based mutational correction in human embryos.

Human germline gene correction by targeted nucleases holds great promise for reducing mutation transmission. However, recent studies have reported concerning observations in CRISPR-Cas9-targeted human embryos, including mosaicism and loss of heterozygosity (LOH). The latter has been associated with either gene conversion or (partial) chromosome loss events.

Cathepsin-L Secreted by High-Quality Bovine Embryos Exerts an Embryotrophic Effect In Vitro.

While human in vitro embryo production is generally performed individually, animal models have shown that culturing embryos in groups improves blastocyst yield and quality. Paracrine embryotrophins could be responsible for this improved embryo development, but their identity remains largely unknown. We hypothesize that supplementation of embryotrophic proteins to a culture medium could be the key to improve individual embryo production.

Characterization of ovarian tissue oocytes from transgender men reveals poor calcium release and embryo development, which might be overcome by spindle transfer.

Study Question: Can spindle transfer (ST) overcome inferior embryonic development of in vitro matured ovarian tissue oocytes (OTO-IVM) originating from testosterone-treated transgender men?

Summary Answer: ST shows some potential to overcome the embryo developmental arrest observed in OTO-IVM oocytes from transgender men.

What Is Known Already: OTO-IVM is being applied as a complementary approach to increase the number of oocytes/embryos available for fertility preservation during ovarian tissue cryopreservation in cancer patients. OTO-IVM has also been proposed for transgender men, although the potential of their oocytes remains poorly investigated.

Assisted oocyte activation does not overcome recurrent embryo developmental problems.

Study Question: Can recurrent embryo developmental problems after ICSI be overcome by assisted oocyte activation (AOA)?

Summary Answer: AOA did not improve blastocyst formation in our patient cohort with recurrent embryo developmental problems after ICSI.

What Is Known Already: The use of AOA to artificially induce calcium (Ca2+) rises by using Ca2+ ionophores (mainly calcimycin and ionomycin) has been reported as very effective in overcoming fertilization failure after ICSI, especially in patients whose Ca2+ dynamics during fertilization are deficient. However, there is only scarce and contradictory literature on the use of AOA to overcome embryo developmental problems after ICSI, and it is not clear whether abnormal Ca2+ patterns during fertilization disturb human preimplantation embryo development.

The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency.

Early during preimplantation development and in heterogeneous mouse embryonic stem cells (mESC) culture, pluripotent cells are specified towards either the primed epiblast or the primitive endoderm (PE) lineage. Canonical Wnt signaling is crucial for safeguarding naive pluripotency and embryo implantation, yet the role and relevance of canonical Wnt inhibition during early mammalian development remains unknown. Here, we demonstrate that transcriptional repression exerted by Wnt/TCF7L1 promotes PE differentiation of mESCs and in preimplantation inner cell mass.

Serial measurement of circulating calprotectin as a prognostic biomarker in COVID-19 patients in intensive care setting.

Objectives: Circulating calprotectin (cCLP) has been shown to be a promising prognostic marker for COVID-19 severity. We aimed to investigate the prognostic value of serial measurements of cCLP in COVID-19 patients admitted to an intensive care unit (ICU).

Methods: From November 2020 to May 2021, patients with COVID-19, admitted at the ICU of the OLV Hospital, Aalst, Belgium, were prospectively included.

TEAD4 regulates trophectoderm differentiation upstream of CDX2 in a GATA3-independent manner in the human preimplantation embryo.

Study Question: What is the role of transcriptional-enhanced associate (TEA) domain family member 4 (TEAD4) in trophectoderm (TE) differentiation during human embryo preimplantation development in comparison to mouse?

Summary Answer: TEAD4 regulates TE lineage differentiation in the human preimplantation embryo acting upstream of caudal-type homeobox protein 2 (CDX2), but in contrast to the mouse in a GATA-binding protein 3 (GATA3)-independent manner.

What Is Known Already: Tead4 is one of the earliest transcription factors expressed during mouse embryo preimplantation development and is required for the expression of TE-associated genes. Functional knock-out studies in mouse, inactivating Tead4 by site-specific recombination, have shown that Tead4-targeted embryos have compromised development and expression of the TE-specific Cdx2 and Gata3 is downregulated.

Instrument selection for the ASAS core outcome set for axial spondyloarthritis.

Objectives: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA).

Methods: An international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments' psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS.

CRISPR/Cas gene editing in the human germline.

The ease and efficacy of CRISPR/Cas9 germline gene editing in animal models paved the way to human germline gene editing (HGGE), by which permanent changes can be introduced into the embryo. Distinct genes can be knocked out to examine their function during embryonic development. Alternatively, specific sequences can be introduced which can be applied to correct disease-causing mutations.

Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts.

SignificanceHatching from the zona pellucida is a prerequisite for embryo implantation and is less likely to occur in vitro for reasons unknown. Extracellular vesicles (EVs) are secreted by the embryo into the culture medium. Yet the role that embryonic EVs and their cargo microRNAs (miRNAs) play in blastocyst hatching has not been elucidated, partially due to the difficulties of isolating them from low amounts of culture medium.

Human germline nuclear transfer to overcome mitochondrial disease and failed fertilization after ICSI.

Purpose: Providing additional insights on the efficacy of human nuclear transfer (NT). Here, and earlier, NT has been applied to minimize transmission risk of mitochondrial DNA (mtDNA) diseases. NT has also been proposed for treating infertility, but it is still unclear which infertility indications would benefit.

SPERM FACTORS AND EGG ACTIVATION: Fertilization failure after human ICSI and the clinical potential of PLCZ1.

Two decades have passed since the discovery of phospholipase C zeta (PLCZ1) as the sperm oocyte-activating factor. At present, there is a general consensus that PLCZ1 is responsible for triggering the calcium (Ca2+) oscillations necessary to start the oocyte activation process in mammals. One proof is that abnormal, reduced, or absent PLCZ1 in human spermatozoa leads to fertilization failure (FF) after intracytoplasmic sperm injection (ICSI).

Test-retest reliability of outcome measures: data from three trials in radiographic and non-radiographic axial spondyloarthritis.

Objectives: Aim of this study was to assess test-retest reliability of candidate instruments for the mandatory domains of the Assessment of Spondyloarthritis international Society (ASAS)-Outcome Measures in Rheumatology core set for axial spondyloarthritis (axSpA).

Methods: Screening and baseline data from COAST-V, COAST-X and RAPID-axSpA was used to evaluate test-retest reliability of each candidate instrument for the mandatory domains (disease activity, pain, morning stiffness, fatigue, physical function, overall functioning and health). A maximum time interval of 28 days between both visits was used for inclusion in this study.

Importance of anti-SARS-CoV-2 assay antigenic composition as revealed by the results of the Belgian external quality assessment (EQA) scheme.

We report on sample IS/17575 since it generated highly divergent results in the Belgian SARS-CoV-2 serology external quality assessment scheme. Sample IS/17575 was serum originating from a 30 years old male patient. 124 diagnostic laboratories analysed this sample.

The ASAS-OMERACT core domain set for axial spondyloarthritis.

Background: The current core outcome set for ankylosing spondylitis (AS) has had only minor adaptations since its development 20 years ago. Considering the significant advances in this field during the preceding decades, an update of this core set is necessary.

Objective: To update the ASAS-OMERACT core outcome set for AS into the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA).

Domains to Be Considered for the Core Outcome Set of Axial Spondyloarthritis: Results From a 3-round Delphi Survey.

Objective: Advances in the field of axial spondyloarthritis (axSpA) and the methodology to develop core sets have led the Assessment of SpondyloArthritis international Society (ASAS) group to update the ASAS-Outcomes in Rheumatology (OMERACT) core set. An important aspect was to ensure it would be applicable to the entire spectrum of axSpA. The first step was to define the most relevant disease domains.

Age at onset in axial spondyloarthritis around the world: data from the Assessment in SpondyloArthritis international Society Peripheral Involvement in Spondyloarthritis study.

Objective: Age at onset is useful in identifying chronic back patients at an increased risk of axial SpA (axSpA). However, the majority of data on which the criterion of age at onset <45 years is based originates from Europe. Therefore it is unknown if this criterion applies in other parts of the world.