Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Spatiotemporal evolution and transmission dynamics of Alpha and Delta SARS-CoV-2 variants contributing to sequential outbreaks in Cambodia during 2021.

Background: Tracking the emergence, introduction and spread of SARS-CoV-2 variants of concern are essential for informing public health strategies. In 2021, Cambodia faced two major epidemic waves of SARS-CoV-2 triggered by the successive rise of the Alpha and Delta variants.

Methods: Phylodynamic analysis of 1,163 complete SARS-CoV-2 genomes from Cambodia, along with global sequences, were conducted between February and September 2021 to infer viral introductions, molecular epidemiology and population dynamics.

To eat or not to eat oats: factors associated with oats consumption using the I-Change model.

A suboptimal diet is responsible for more deaths worldwide than any other risk. A dietary factor that needs more attention is whole-grain consumption because of its proven health, nutritional, and environmental benefits. Despite these benefits, the daily whole-grain and dietary fibre intake by Dutch residents is low and the reasons for this low consumption are unknown.

Improved resolution of avian influenza virus using Oxford Nanopore R10 sequencing chemistry.

Unlabelled: Highly pathogenic avian influenza viruses continue to pose global risks to One Health, including agriculture, public, and animal health. Rapid and accurate genomic surveillance is critical for monitoring viral mutations, tracing transmission, and guiding interventions in near real-time. Oxford Nanopore sequencing holds promise for real-time influenza genotyping, but data quality from R9 chemistry has limited its adoption due to challenges resolving low-complexity regions such as the biologically critical hemagglutinin cleavage site, a homopolymer of basic amino acids that distinguish highly pathogenic strains.

Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells.

The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Monitoring of controlled ovarian stimulation in IVF.

Since the inception of in vitro fertilization (IVF), monitoring of controlled ovarian stimulation (COS) has traditionally involved numerous appointments for ultrasound and laboratory testing to guide medication use and dosing, determine trigger timing, and allow for measures to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Recent advances in the field of assisted reproductive technology (ART) have called into question the timing and frequency of COS monitoring appointments, as discussed in this commentary.

[IN VITRO FERTILIZATION (IVF) TREATMENTS IN MACCABI HEALTHCARE SERVICES 2015-2020].

Background: Previously, we have summarized IVF treatment outcomes for the years 2007-2014. In 2014, the Ministry of Health (MOH) recommended that infertile patients above 39 years of age can be offered IVF as a first line treatment, given the natural age-related decrease in ovarian reserve.

Objectives: The purpose of the current publication is to summarize IVF treatment outcomes for the years 2015-2020, and to explore possible changes in IVF treatments following the MOH statement.

Ideal frozen embryo transfer regime.

Purpose Of Review: This review aims to compare evidence on four criteria (embryo implantation, obstetric outcomes, patient convenience, and IVF-unit efficiency) by analyzing published research on different endometrial preparation methods for frozen embryo transfer (FET).

Recent Findings: While the artificial-FET cycle provides advantages in scheduling and implantation, it falls short in ensuring optimal obstetric outcomes. In contrast, natural-FET ensures embryo implantation conditions if ovulation is correctly identified.

LH supplementation in IVF: human nature, politics, and elephants in the room.

Luteinizing hormone (LH) is present throughout the natural follicular phase. However, the debate is still not settled on whether LH is needed during ovarian stimulation in IVF. This commentary looks at the evolution of this debate, mentioning three elephants in the room that were ignored by the Pharma industry, professional organizations, and clinicians alike: 1.

A Deep Learning Framework with Explainability for the Prediction of Lateral Locoregional Recurrences in Rectal Cancer Patients with Suspicious Lateral Lymph Nodes.

Malignant lateral lymph nodes (LLNs) in low, locally advanced rectal cancer can cause (ipsi-lateral) local recurrences ((L)LR). Accurate identification is, therefore, essential. This study explored LLN features to create an artificial intelligence prediction model, estimating the risk of (L)LR.

Time-sensitive assessment of luteal phase progesterone after HCG ovulation triggering: another brick off the wall?

In recent years, there has been growing interest in understanding the dynamics of progesterone levels during the luteal phase after HCG-triggered ovulation. Recent studies have provided data showing a deviation from the natural ovulatory cycle, with peak progesterone concentrations occurring earlier and declining steadily thereafter, demonstrating that a fall in progesterone concentration early in the luteal phase was associated with lower rates of ongoing pregnancy. These findings highlight the importance of changes in progesterone concentration, rather than absolute concentrations, in determining optimal endometrial conditions.

A Look inside the Replication Dynamics of SARS-CoV-2 in Blyth's Horseshoe Bat () Kidney Cells.

Bats are considered the natural reservoir of numerous emerging viruses such as severe acute respiratory syndrome coronaviruses (SARS-CoVs). There is a need for immortalized bat cell lines to culture and investigate the pathogenicity, replication kinetics, and evolution of emerging coronaviruses. We illustrate the susceptibility and permissiveness of a spontaneously immortalized kidney cell line (Rhileki) from Blyth's horseshoe bat () to SARS-CoV-2 virus, including clinical isolates, suggesting a possible virus-host relationship.

The awareness of radiologists for the presence of lateral lymph nodes in patients with locally advanced rectal cancer: a single-centre, retrospective cohort study.

Objectives: Enlarged lateral lymph nodes (LLNs) are associated with increased (lateral) local recurrence rates. Size and anatomical location should therefore always be reported by radiologists and discussed during multidisciplinary meetings. The objective was to investigate how often LLNs are mentioned in MRI reports in a tertiary referral centre.

Prospective analysis of clinically significant prostate cancer detection with [F]DCFPyL PET/MRI compared to multiparametric MRI: a comparison with the histopathology in the radical prostatectomy specimen, the ProStaPET study.

Purpose: Multiparametric magnetic resonance imaging (mpMRI) is a well-established imaging method for localizing primary prostate cancer (PCa) and for guiding targeted prostate biopsies. [F]DCFPyL positron emission tomography combined with MRI (PSMA-PET/MRI) might be of additional value to localize primary PCa. The aim of this study was to assess the diagnostic performance of [F]DCFPyL-PET/MRI vs.

Work hours and overtime of nurses working in Cambodian hospitals.

Aim: To examine the nature and prevalence of Cambodian nurses' work hours and overtime and related factors BACKGROUND: The chronic shortage of nursing workforce is a major cause of overtime among nurses.

Introduction: Nursing shortage and working overtime among nurses negatively affect nurse and patient outcomes, but nurses' work hours and overtime in Cambodia have not been comprehensively examined.

Methods: A multicenter cross-sectional study was conducted in four Cambodian hospitals.

Indeterminate Liver Lesions in Patients With Early Stage Rectal Cancer: Can They Be Ignored?

Purpose: Small, hypoattenuating, indeterminate liver lesions are often encountered during staging computed tomography (CT) in patients with early-stage rectal cancer. This study aimed to determine the incidence and prognostic significance of these lesions.

Methods And Materials: A single institution's colorectal cancer (CRC) database was searched for patients with early-stage rectal cancer, defined as a cT1-2N0 tumor on magnetic resonance imaging (MRI).

Time, time, time: see what governs the luteal phase endocrinology.

Two modes of ovulation trigger are used in IVF: hCG, acting on ovarian LH receptors, and GnRH agonist, eliciting pituitary LH and FSH surges. These two modes are evaluated herein, focusing on how they serve specific time-sensitive events crucial for achieving embryo implantation and pregnancy. hCG trigger is associated with significant timing deviation from physiology.

Dealing with indeterminate pulmonary nodules in colorectal cancer patients; a systematic review.

Introduction: Indeterminate pulmonary nodules (IPNs) are frequently encountered on staging computed tomography (CT) in colorectal cancer (CRC) patients and they create diagnostic dilemmas. This systematic review and pooled analysis aims to estimate the incidence and risk of malignancy of IPNs and provide an overview of the existing literature on IPNs in CRC patients.

Materials And Methods: EMBASE, Pubmed and the Cochrane database were searched for papers published between January 2005 and April 2020.

The exogenous progesterone-free luteal phase: two pilot randomized controlled trials in IVF patients.

Research Question: Is the reproductive outcome similar after gonadotrophin-releasing hormone agonist (GnRHa) trigger followed by luteal human chorionic gonadotrophin (HCG) boluses compared with HCG trigger and a standard luteal phase support (LPS)?

Design: Two open-label pilot randomized controlled trials (RCT) with 250 patients from 2014 to 2019, with a primary outcome of ongoing pregnancy per embryo transfer. Patients with ≤13 follicles on the trigger day were randomized (RCT 1) to: Group A (n = 65): GnRHa trigger followed by a bolus of 1500 IU HCG s.c.

Suboptimal response to GnRH agonist trigger: causes and practical management.

Purpose Of Review: GnRH agonist products are used extensively worldwide to trigger ovulation and final oocyte maturation in in vitro fertilization cycles. The purpose of this article is to outline possible causes for a suboptimal response to the GnRH agonist trigger.

Recent Findings: Risk factors for such a suboptimal response include prolonged hormonal contraceptive use, previous GnRHa-induced pituitary downregulation, a hypogonadotropic/hypogonadal condition, patient error, environmental conditions that may damage the GnRHa product used, GnRH and luteinizing hormone (LH) receptors polymorphisms, low baseline LH and low endogenous serum LH levels on trigger day as well as low BMI.

Reduced FSH and LH action: implications for medically assisted reproduction.

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play complementary roles in follicle development and ovulation via a complex interaction in the hypothalamus, anterior pituitary gland, reproductive organs, and oocytes. Impairment of the production or action of gonadotropins causes relative or absolute LH and FSH deficiency that compromises gametogenesis and gonadal steroid production, thereby reducing fertility. In women, LH and FSH deficiency is a spectrum of conditions with different functional or organic causes that are characterized by low or normal gonadotropin levels and low oestradiol levels.

IVF and the exogenous progesterone-free luteal phase.

Purpose Of Review: In a conventional IVF cycle, final oocyte maturation and ovulation is triggered with a bolus of hCG, followed by progesterone-based luteal support that spans several weeks if pregnancy is achieved. This article summarizes several approaches of the exogenous progesterone-free luteal support in IVF.

Recent Findings: Triggering ovulation with GnRH agonist may serve as an alternative to hCG, with well established advantages.

In situ detection of protein interactions for recombinant therapeutic enzymes.

Despite their therapeutic potential, many protein drugs remain inaccessible to patients since they are difficult to secrete. Each recombinant protein has unique physicochemical properties and requires different machinery for proper folding, assembly, and posttranslational modifications (PTMs). Here we aimed to identify the machinery supporting recombinant protein secretion by measuring the protein-protein interaction (PPI) networks of four different recombinant proteins (SERPINA1, SERPINC1, SERPING1, and SeAP) with various PTMs and structural motifs using the proximity-dependent biotin identification (BioID) method.

GnRH agonist triggering followed by 1500 IU of HCG 48 h after oocyte retrieval for luteal phase support.

Research Question: Gonadotrophin releasing hormone (GnRH) agonist trigger after GnRH antagonist-based ovarian stimulation protocol for IVF is gaining popularity, because it prevents ovarian hyperstimulation syndrome and allows for near physiological LH and FSH surges. A small dose of HCG (1500 IU) on the day of oocyte retrieval, followed by daily progesterone administration, is currently the preferred way to secure adequate luteal support after GnRH agonist trigger. In the present study, the possibility that a bolus of 1500 IU HCG, given 2 days after oocyte retrieval, may be sufficient to sustain adequate luteal support without additional progesterone treatment was questioned.