[Donor DNA Modification with Cas9 Targeting Sites Improves the Efficiency of MTC34 Knock-in into the CXCR4 Locus].

To successfully apply the genome editing technology using the CRISPR/Cas9 system in the clinic, it is necessary to achieve a high efficiency of knock-in, which is insertion of a genetic construct into a given locus of the target cell genome. One of the approaches to increase the efficiency of knock-in is to modify donor DNA with the same Cas9 targeting sites (CTS) that are used to induce double-strand breaks (DSBs) in the cell genome (the double-cut donor method). Another approach is based on introducing truncated CTS (tCTS), including a PAM site and 16 proximal nucleotides, into the donor DNA.

[Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line].

The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human CXCR4 locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus.

Aortic pressures within a giant right coronary artery aneurysm.

Background: Giant coronary artery aneurysms are rare conditions with potentially devastating consequences. We report a case of the largest documented giant right coronary artery (RCA) aneurysm to date.

Case Presentation: A 57-year-old male patient visited our outpatient clinic for abdominal pain and exertional dyspnea.

Evaluation of the Effect of Risankizumab on the Pharmacokinetics of Cytochrome P450 Substrates in Patients with Moderately to Severely Active Ulcerative Colitis or Crohn's Disease.

Background And Objective: The objective of this study was to characterize the effects of risankizumab on the pharmacokinetics of cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A substrates in patients with moderately to severely active Crohn's disease (CD) or ulcerative colitis (UC) using a cocktail approach.

Methods: Patients with CD or UC (n = 20) received single doses of probe substrates for CYP1A2 (caffeine 100 mg), CYP2C9 (warfarin 10 mg), CYP2C19 (omeprazole 20 mg), CYP2D6 (metoprolol 50 mg), and CYP3A (midazolam 2 mg) before and after intravenous infusions of risankizumab 1800 mg once every 4 weeks for four doses. Serial blood samples were collected for determination of concentrations of the CYP probe drugs and metabolites with and without risankizumab.

Broth microdilution protocol for determining antimicrobial susceptibility of Legionella pneumophila to clinically relevant antimicrobials.

Currently there is no detailed, internationally agreed protocol defined to evaluate antimicrobial susceptibility testing (AST) for Legionella pneumophila (required to establish epidemiological cut-off value or "ECOFF" boundaries); therefore, antimicrobial resistance in these isolates cannot be defined. AST methods utilising media containing activated charcoal as an ingredient, to enable Legionella growth, are unreliable as noted in an internationally authored opinion paper and a new gold standard is required. Here we define a detailed protocol for broth microdilution (BMD) using defined cell culture collection-deposited control reference strains (Philadelphia-1 and Knoxville-1) as well as two accessible reference strains with moderately (lpeAB-carrying) and markedly (23S rRNA mutation-carrying) elevated azithromycin minimum inhibitory concentration (MIC).

Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis.

Background: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages.

Methods: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%.

Detection and quantification of SARS-CoV-2 in wastewater using a mobile laboratory setting.

This study evaluated a point-of-care device for wastewater-based epidemiology (WBE) of SARS-CoV-2 circulation. WBE is a critical tool but faces challenges such as laboratory infrastructure, sample transport, skilled personnel, and time-consuming methods. Currently, a rapid, portable solution for wastewater surveillance is lacking.

Psychological Distress, Resources, and Coping Strategies Among Evacuees and Non-Evacuees From an Armed Conflict Zone: A Network Analysis.

This study focuses on two groups: evacuees from Israel's southern and northern frontline communities following the October 7th Hamas attack, and individuals from regions not directly threatened. Using network analysis, we identified key associations and central nodes related to stress indicators (i.e.

A novel minimally invasive neurosurgical cranial fixation device for improved accuracy of intraventricular catheter placement: an experimental animal study.

Background: External ventricular drain (EVD) insertion is one of the most commonly performed neurosurgical procedures. Herein, we introduce a new concept of a cranial fixation device for insertion of EVDs, that reduces reliance on freehand placement and drilling techniques and provides a simple, minimally invasive approach that provides strong fixation to minimal thickness skulls.

Methods: An experimental device for catheter insertion and fixation was designed and tested in both ex-vivo and in-vivo conditions to assess accurate cannulation of the ventricle and to test the strength of fixation to the skull.

Trends and changes in the relationship between quality and price in tenders for healthcare services in the Israeli health system, 2013-2023.

Background And Objectives: Public healthcare systems face constraints in financial and professional resources. The Mandatory Tenders Law 5752 - 1992 stipulates that before entering into a contract for the supply of a service or product, public authorities and government corporations must undergo a public tender process. The authors sought to identify and contextualize the trends observed in tenders for healthcare services over the past decade amid increasingly stringent resource constraints.

The impact of a fracture liaison service with in-hospital anti-osteoporosis treatment on subsequent hip fracture and mortality rates-a single-center retrospective study.

Unlabelled: The implementation of an in-hospital fracture liaison service facilitated prompt initiation of anti-osteoporosis treatment following a hip fracture (HF), increasing follow-up and treatment rates. This led to a 48% reduction in the risk of subsequent HF and a 29% decrease in mortality rates.

Purpose: To demonstrate the impact of an institutional fracture liaison service (FLS) which allowed in-hospital anti-osteoporosis treatment following hip fracture (HF) on subsequent HF and mortality rate.

Revisiting medical oaths: how student-driven ethical codes reflect changing values.

Background: Medical oaths and ethical codes play a crucial role in guiding physicians through their professional responsibilities. This study extends prior research on ethical codes created by students at the Medical School for International Health (MSIH) by analysing codes from the years 2007 to 2022.

Objective: The objective of this study is to evaluate changes in the ethical principles emphasised by MSIH students over time and to compare these with previous cohorts.

A neurocognitive pathway for engineering artificial touch.

Artificial haptics has the potential to revolutionize the way we integrate physical and virtual technologies in our daily lives, with implications for teleoperation, motor skill acquisition, rehabilitation, gaming, interpersonal communication, and beyond. Here, we delve into the intricate interplay between the somatosensory system and engineered haptic inputs for perception and action. We critically examine the sensory feedback's fidelity and the cognitive demands of interfacing with these systems.

Ethnic Disparities in Chronic Diseases: Comparison Between Arabs and Jews in Israel.

Background: The lifestyle of the Arab population in Israel has changed in the last few decades, and modernization and urbanization have impacted the prevalence of chronic diseases.

Objectives: To investigate the prevalence of chronic diseases in the Arab population compared to the Jewish population in Israel.

Methods: This retrospective study included Arab and Jewish people insured by Israel's largest health maintenance organization.

Classifying vocal responses of broilers to environmental stressors via artificial neural network.

Detecting early-stage stress in broiler farms is crucial for optimising growth rates and animal well-being. This study aims to classify various stress calls in broilers exposed to cold, heat, or wind, using acoustic signal processing and a transformer artificial neural network (ANN). Two consecutive trials were conducted with varying amounts of collected data, and three ANN models with the same architecture but different parameters were examined.

Nephrocalcinosis tendency does not worsen under burosumab treatment for X-linked hypophosphatemic rickets: a multicenter pediatric study.

Background: X-linked hypophosphatemic rickets (XLH) is associated with uninhibited FGF23 activity, which leads to phosphaturia, hypophosphatemia and depressed active vitamin D (1,25OH2D) levels. Conventional treatment with phosphate supplements and vitamin D analogs may lead to hypercalciuria (HC), nephrocalcinosis (NC) and hyperparathyroidism. We investigated the effects of burosumab treatment, an anti-FGF23 monoclonal antibody recently approved for XLH, on these complications.

Arabidopsis ubiquitin ligase PUB41 positively regulates ABA-mediated seed dormancy and drought response.

Unlabelled: Seed germination is a tightly regulated, non-reversible developmental process, and it is crucial to prevent premature germination under conditions that may not allow the plant's life cycle to be completed. The plant hormone ABA is the key regulator of seed dormancy and inhibition of germination. ABA is also involved in the plant response to drought.

In COVID-19 Patients Supported with Extracorporeal Membrane Oxygenation, Intensive Care Unit Mortality Is Associated with the Blood Transfusion Rate.

: The COVID-19 pandemic markedly increased the number of patients with infection-related acute respiratory distress syndrome who required extracorporeal membrane oxygenation (ECMO) and multiple blood transfusions. This study aimed to assess a potential correlation between the daily rate of transfused blood products and the intensive care unit (ICU) outcome of ECMO-supported COVID-19 patients. : Data were retrieved from the electronic databases of three Israeli tertiary care centers.

Outcomes and Prognosis of COVID-19-Induced Adult Respiratory Distress Syndrome Patients Treated with Prolonged Veno-Venous Extracorporeal Membrane Oxygenation: A Retrospective Multicenter Study.

Predicting whether extracorporeal membrane oxygenation (ECMO) treatment duration affects prognosis is important both medically and economically. : We conducted a retrospective, multicenter study to better understand the outcomes of patients treated with veno-venous (VV) ECMO over a prolonged duration, analyzing data from the Israel ECMO registry. The study included all adult patients treated with VV-ECMO due to COVID-19-induced respiratory failure.

Perioperative Lung Ultrasound Findings in Elective Intra-Abdominal Surgery: Associations with Postoperative Pulmonary Complications.

For patients undergoing abdominal surgery, postoperative pulmonary complications (PPCs) are a major source of morbidity and mortality. The use of point-of-care ultrasonography (POCUS), and specifically POCUS of the lungs, has seen many advancements in recent years. We hypothesize that perioperative lung ultrasonography can be used as a predictor for PPCs.