Lipopeptide-mediated Cas9 RNP delivery: A promising broad therapeutic strategy for safely removing deep-intronic variants in .

Deep-intronic (DI) variants represent approximately 10%-12% of disease-causing genetic defects in -associated Stargardt disease (STGD1). Although many of these DI variants are amenable to antisense oligonucleotide-based splicing-modulation therapy, no treatment is currently available. These molecules are mostly variant specific, limiting their applicability to a broader patient population.

Innovative all-in-one exome sequencing strategy for diagnostic genetic testing in male infertility: Validation and 10-month experience.

Background: Current guidelines indicate that patients with extreme oligozoospermia or azoospermia should be tested for chromosomal imbalances, azoospermia factor (AZF) deletions and/or CFTR variants. For other sperm abnormalities, no genetic diagnostics are recommended.

Objectives: To determine whether exome sequencing (ES) with combined copy number variant (CNV) and single nucleotide variant (SNV) analysis is a reliable first-tier method to replace current methods (validation study), and to evaluate the diagnostic yield after 10 months of implementation (evaluation study).

Detection of DNA Contamination in Prenatal Samples from Whole Exome Sequencing Data.

Background: Maternal cell contamination (MCC) in prenatal samples poses a risk for misdiagnosis, and therefore, testing for contamination is necessary during genetic analysis of prenatal specimens. MCC testing is currently performed as a method separate from the diagnostic method. With the increasing application of whole exome sequencing (WES) in prenatal diagnosis, we sought to develop a method to estimate the level of contamination from WES data, aiming to eliminate the need for a separate MCC test.

Impressive clinical improvement and disappearance of neuropathic pain in an adult patient with hypophosphatasia treated with asfotase alfa.

Hypophosphatasia (HPP) is a rare disorder, resulting from loss-of-function variants of the ALPL gene encoding non-tissue specific alkaline phosphatase (TNSALP). Presentation varies largely, with increased severity usually occurring with earlier disease onset. Here we describe the clinical improvement of a 57-year-old woman with childhood onset HPP, after initiating treatment with asfotase alfa (Strensiq®).

Detection and attribution of an anomaly in terrestrial photosynthesis in Europe during the COVID-19 lockdown.

Carbon dioxide (CO) uptake by plant photosynthesis, referred to as gross primary production (GPP) at the ecosystem level, is sensitive to environmental factors, including pollutant exposure, pollutant uptake, and changes in the scattering of solar shortwave irradiance (SW) - the energy source for photosynthesis. The 2020 spring lockdown due to COVID-19 resulted in improved air quality and atmospheric transparency, providing a unique opportunity to assess the impact of air pollutants on terrestrial ecosystem functioning. However, detecting these effects can be challenging as GPP is influenced by other meteorological drivers and management practices.

Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes.

Dysregulation of Wingless and Int-1 (Wnt) signaling has been strongly associated with development and progression of osteoarthritis (OA). Here, we set out to investigate the independent effects of either mechanical stress (MS) or inflammation on Wnt signaling in human neocartilage pellets, and to relate this Wnt signaling to OA pathophysiology. OA synovium-conditioned media (OAS-CM) was collected after incubating synovium from human end-stage OA joints for 24 h in medium.

All-in-one whole exome sequencing strategy with simultaneous copy number variant, single nucleotide variant and absence-of-heterozygosity analysis in fetuses with structural ultrasound anomalies: A 1-year experience.

Objective: We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result.

Methods: After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis.

CCN4/WISP1 Promotes Migration of Human Primary Osteoarthritic Chondrocytes.

Objectives: Previously, we have shown the involvement of cellular communication network factor 4/Wnt-activated protein Wnt-1-induced signaling protein 1 (CCN4/WISP1) in osteoarthritic (OA) cartilage and its detrimental effects on cartilage. Here, we investigated characteristics of CCN4 in chondrocyte biology by exploring correlations of CCN4 with genes expressed in human OA cartilage with functional follow-up.

Design: Spearman correlation analysis was performed for genes correlating with using our previously established RNA sequencing dataset of human preserved OA cartilage of the RAAK study, followed by a pathway enrichment analysis for genes with ρ ≥|0.

Coronary Intravascular Lithotripsy.

Coronary artery calcification is strongly associated with adverse cardiac events and can impede the success of percutaneous coronary intervention (PCI) due to challenges with delivery of equipment and expansion of stents. Current treatment modalities for mitigation of coronary calcification have limitations and inherent risk of complications. Coronary intravascular lithotripsy (IVL) is a novel technique to modify coronary artery calcification via acoustic pressure waves.

A human 3D neo-cartilage model to explore the response of OA risk genes to hyper-physiological mechanical stress.

Objective: Due to the complexity and heterogeneity of osteoarthritis (OA) pathophysiology, studying the interaction between intrinsic molecular changes in chondrocytes after hyper-physiological mechanical stress (MS) and aberrant signalling of OA risk genes remains a challenge. In this study we set out to set up an 3D neo cartilage pellet model that enables us to explore the responses of OA risk genes to hyper-physiological MS.

Design: Human primary chondrocyte neo-cartilage pellets were exposed for 2 days to 2 ​× ​10 ​min of hyper-physiological dynamic MS attained by a 20% strain and a frequency of 5 ​Hz.

Effect of Pasteurization by Moderate Intensity Pulsed Electric Fields (PEF) Treatment Compared to Thermal Treatment on Quality Attributes of Fresh Orange Juice.

Novel pulsed electric field (PEF) process conditions at moderate electric field strength and long pulse duration have recently been established to obtain microbial inactivation. In this study, the effect of these PEF conditions ( = 0.9 and 2.

Toward Detection of the Molecular Parity Violation in Chiral Ru(acac) and Os(acac).

We present a theory-experiment investigation of the helically chiral compounds Ru(acac) and Os(acac) as candidates for next-generation experiments for detection of molecular parity violation (PV) in vibrational spectra. We used relativistic density functional theory calculations to identify optimal vibrational modes with expected PV effects exceeding by up to 2 orders of magnitude the projected instrumental sensitivity of the ultrahigh resolution experiment under construction at the Laboratoire de Physique des Lasers in Paris. Preliminary measurements of the vibrational spectrum of Ru(acac) carried out as the first steps toward the planned experiment are presented.

Automated Evolutionary Engineering of Yeasts.

Evolutionary engineering of microbes provides a powerful tool for untargeted optimization of (engineered) cell factories and identification of genetic targets for further research. Directed evolution is an intrinsically time-intensive effort, and automated methods can significantly reduce manual labor. Here, design considerations for various evolutionary engineering methods are described, and generic workflows for batch-, chemostat-, and accelerostat-based evolution in automated bioreactors are provided.

Effects of High-Pressure Processing, UV-C Irradiation and Thermoultrasonication on Donor Human Milk Safety and Quality.

Holder pasteurization (HoP) is the current recommended treatment for donor human milk. Although this method inactivates microbial contaminants, it also negatively affects various milk components. High-pressure processing (HPP, 400, 500, and 600 MPa), ultraviolet-C irradiation (UV-C, 2,430, 3,645, and 4,863 J/L) and thermoultrasonication (TUS, 1,080 and 1,620 kJ/L) were investigated as alternatives to thermal pasteurization (HoP).

Diaphragmatic dysfunction in neuromuscular disease, an MRI study.

The aim of this exploratory study was to evaluate diaphragmatic function across various neuromuscular diseases using spirometry-controlled MRI. We measured motion of the diaphragm relative to that of the thoracic wall (cranial-caudal ratio vs. anterior posterior ratio; CC-AP ratio), and changes in the diaphragmatic curvature (diaphragm height and area ratio) during inspiration in 12 adults with a neuromuscular disease having signs of respiratory muscle weakness, 18 healthy controls, and 35 adult Pompe patients - a group with prominent diaphragmatic weakness.

Deceleration and Trapping of SrF Molecules.

We report on the electrostatic trapping of neutral SrF molecules. The molecules are captured from a cryogenic buffer-gas beam source into the moving traps of a 4.5-m-long traveling-wave Stark decelerator.

Systematic study and uncertainty evaluation of P, T-odd molecular enhancement factors in BaF.

A measurement of the magnitude of the electric dipole moment of the electron (eEDM) larger than that predicted by the Standard Model (SM) of particle physics is expected to have a huge impact on the search for physics beyond the SM. Polar diatomic molecules containing heavy elements experience enhanced sensitivity to parity (P) and time-reversal (T)-violating phenomena, such as the eEDM and the scalar-pseudoscalar (S-PS) interaction between the nucleons and the electrons, and are thus promising candidates for measurements. The NL-eEDM collaboration is preparing an experiment to measure the eEDM and S-PS interaction in a slow beam of cold BaF molecules [P.

Human Milk from Previously COVID-19-Infected Mothers: The Effect of Pasteurization on Specific Antibodies and Neutralization Capacity.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), many put their hopes in the rapid availability of effective immunizations. Human milk, containing antibodies against syndrome coronavirus 2 (SARS-CoV-2), may serve as means of protection through passive immunization. We aimed to determine the presence and pseudovirus neutralization capacity of SARS-CoV-2 specific IgA in human milk of mothers who recovered from COVID-19, and the effect of pasteurization on these antibodies.

Health congruence paradox in older adults: Contribution of cognition and relational visits.

The health congruence paradox can have important implications for those working with older adults as older adults' health understanding may be vague or directed toward health concerns other than those medically identified. Objective health was measured as diagnosed conditions from medical records. Two measures of subjective health were obtained through relational visits of university students, 1) health concerns older adults reported on a visit survey, 2) health concerns students reported during casual conversation.

A supersonic laser ablation beam source with narrow velocity spreads.

A supersonic beam source for SrF and BaF molecules is constructed by combining the expansion of carrier gas (a mixture of 2% SF and 98% argon) from an Even-Lavie valve with laser ablation of a barium/strontium metal target at a repetition rate of 10 Hz. Molecular beams with a narrow translational velocity spread are produced at relative values of Δv/v = 0.053(11) and 0.

Temperature and presence of ethanol affect accumulation of intracellular trehalose in Lactobacillus plantarum WCFS1 upon pulsed electric field treatment.

Pulsed electric field (PEF) treatment can be used to increase intracellular small molecule concentrations in bacteria, which can lead to enhanced robustness of these cells during further processing. In this study we investigated the effects of the PEF treatment temperature and the presence of 8% (v/v) ethanol in the PEF medium on cell survival, membrane fluidity and intracellular trehalose concentrations of Lactobacillus plantarum WCFS1. A moderate PEF treatment temperature of 21 °C resulted in a high cell survival combined with higher intracellular trehalose concentrations compared to a treatment at 10 and 35 °C.

Radial vs. Femoral Access for Percutaneous Coronary Artery Intervention in Patients With ST-Elevation Myocardial Infarction.

Background: We aimed to compare the safety and efficacy of transradial vs transfemoral access for coronary angiography and intervention in patients presenting with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock.

Methods: PubMed, Embase and Cochrane Central were searched for randomized controlled trials (RCTs) comparing outcomes of STEMI patients who underwent transradial angiography (TRA) compared to transfemoral angiography (TFA). Our outcomes of interest were major adverse cardiac events (MACE), all-cause mortality, severe bleeding, access site bleeding, myocardial infarction, stroke, and major vascular complications.

Comparing thermal inactivation to a combined process of moderate heat and high pressure: Effect on ascospores in strawberry puree.

High pressure processing is a mild preservation process that inactivates pathogenic and spoilage micro-organisms in food products, but preserves the fresh characteristics of a product. Compared to untreated product, an enhanced shelf life is obtained during refrigerated storage. Knowledge on the use of high pressure pasteurisation aimed for ambient storage is limited.