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.

Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond.

Objectives: To study neutrophil gelatinase-associated lipocalin (NGAL) levels in peripheral blood in SLE, and to propose a mechanism by which neutrophils secrete NGAL on stimulation with immune complexes (IC).

Methods: NGAL was measured by ELISA in two independent Swedish SLE cohorts acting as exploratory and validation cohort (n=124 and n=308, respectively), disease controls (n=38) and healthy controls (n=77). NGAL levels were measured in supernatant from IC-stimulated neutrophils in the presence or absence of a toll-like receptor 8 inhibitor (TLR8i).

Nurses' experiences of text-based digital triage at primary healthcare centres in Sweden: a qualitative interview study.

Background: Telehealth services are becoming increasingly popular at primary healthcare centres. Some examples include text-based digital triage and health guidance using chats, emails, images and pre-filled forms. Telephone-based communication has until recent years been the predominant means for triage and health guidance, but now includes written communication via computer or smartphone.

A prospective observational study on persistent postoperative pediatric pain, 4P: The study protocol.

Background: Access to adequate pain treatment is a fundamental right, yet international data suggest that a considerable number of children experience acute and persistent pain. Little is known about the occurrence of both acute and persistent pain in children. The incidence of persistent postoperative pain in children is an unexplored area but international studies suggest that many children experience long-term pain after surgery, with a major impact on daily life.

An Activin Receptor-Like Kinase 1-governed monocytic lineage shapes an immunosuppressive landscape in breast cancer metastases.

The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.

Fracture liaison service (FLS) is associated with lower subsequent fragility fracture risk and mortality: NoFRACT (the Norwegian capture the fracture initiative).

Unlabelled: Subsequent fracture rates and associated mortality were compared before and after the introduction of fracture liaison service (FLS). In 100,198 women and men, FLS was associated with 13% and 10% lower risk of subsequent fragility fractures and 18% and 15% lower mortality. The study suggests that FLS may prevent fractures.

Treatment of bile acid diarrhea with GLP-1 receptor agonists: A Promising Yet Understudied Approach.

Bile acid diarrhea (BAD) is a chronic and socially debilitating disease characterized by abdominal pain, diarrhea, urgency, and fecal incontinence. Recently, in a six-week randomized controlled trial (RCT), we showed that the glucagon-like peptide 1 receptor agonist (GLP-1RA) liraglutide is superior to bile acid sequestration (considered standard-of-care) using colesevelam in reducing BAD symptoms. The emergence of new, more potent, and longer-acting GLP-1RAs has spurred an interest in these treatments in BAD management.

Revising the null model in language evolution research.

We comment on the consequences of the target article for language evolution research. We propose that the default assumption should be that of language-readiness in extinct hominins, and the integration of different types of available evidence from multiple disciplines should be used to assess the likely extent of the realization of this readiness. The role of archaeological evidence should be reconsidered.

Prospective validation study of a combined urine and plasma test for predicting high-grade prostate cancer in biopsy naïve men.

Objective: Early and accurate diagnosis of prostate cancer (PC) is crucial for effective treatment. Diagnosing  clinically insignificant cancers can lead to overdiagnosis and overtreatment, highlighting the importance of accurately selecting patients for further evaluation based on improved risk prediction tools. Novel biomarkers offer promise for enhancing this diagnostic process.

Validation of a Coarse-Grained Martini 3 Model for Molecular Oxygen.

Molecular oxygen (O) is essential for life, and continuous effort has been made to understand its pathways in cellular respiration with all-atom (AA) molecular dynamics (MD) simulations of, e.g., membrane permeation or binding to proteins.

Effects of therapy in experimental models of Peyronie's disease: a scoping review.

Background: Peyronie's disease (PD) is a fibrotic disorder affecting the penile tunica albugínea, with unclear pathophysiology despite centuries of recognition.

Aim: This scoping review maps the effects of interventions in basic PD research, synthesizing evidence from in vivo and in vitro studies to guide future investigation.

Methods: In October-November 2023, a systematic search was conducted across PubMed, Embase (Ovid), Science of Web, and Scopus, following SRYCLE's guidelines.

Nonneutralizing antibodies in Nordic persons with moderate hemophilia A and B (the MoHem study).

Background: The impact of nonneutralizing antibodies (NNAs) in moderate hemophilia is elusive.

Objectives: To explore the presence of NNAs in Nordic persons with moderate hemophilia A (MHA) and B (MHB) in relation to treatment modality, clinical outcome, history of inhibitor, and the corresponding factor VIII (FVIII)/factor IX (FIX) gene mutation.

Methods: A cross-sectional multicenter study covering persons with MHA and MHB in Sweden, Finland, and Norway.

Survival and quality of life after first-time diagnosis of brain metastases: a multicenter, prospective, observational study.

Background: A major concern in anticancer treatment (ACT) of brain metastases (BM) is exposing patients with short expected survival to treatments that negatively impact on quality of life (QoL). Such futile ACT at the end of life is time-consuming and burdensome for patients and their families and entails unnecessary healthcare costs. Refraining from ACT is challenging for both physicians and patients.

Effectiveness of nutritional education intervention during pregnancy on birth outcomes in sub-Saharan Africa: a protocol for a systematic review and meta-analysis.

Introduction: Nutritional education intervention during pregnancy is the process of teaching pregnant women about the importance of a healthy diet and how to make healthy food choices. It is an important part of public health and vital to preventing adverse birth outcomes. Therefore, synthesising available evidence on the effect of nutritional education intervention on birth outcomes is essential for decision-making by policymakers and for identifying needed gaps for future research.

Treating shock with norepinephrine administered in midline catheters in an intermediary care unit: a retrospective cohort study.

Objectives: A rising incidence of septic shock as well as recommendations for early vasopressor initiation has increased the number of patients eligible for norepinephrine (NE). Traditionally, NE has been administered through central lines, in intensive care units, due to the risk of extravasation in peripheral lines. The aim of the current study is to determine the rate of complications and patient outcomes when NE is administered through midline catheters (MCs) in intermediary care units (IMCUs).

Design, evaluation, and in vitro-in vivo correlation of self-nanoemulsifying drug delivery systems to improve the oral absorption of exenatide.

The ability to predict the absorption of exenatide (Ex), a GLP-1 analogue, after oral dosing to rats in self-nanoemulsifying drug delivery systems (SNEDDS), using in vitro methods, was assessed. Ex was complexed with soybean phosphatidylcholine (SPC) prior to loading into SNEDDS. A design of experiments (DoE) approach was employed to develop SNEDDS incorporating medium-chain triglycerides (MCT), medium-chain mono- and diglycerides (MGDG), Kolliphor® RH40, and monoacyl phosphatidylcholine.

The Reliability and Validity of Intraoral Photographs in Assessing Orthodontic Treatment Need.

Background: Orthodontic treatment need has commonly been assessed using treatment need indices during clinical examinations or using photographs in combination with plaster casts. Recently, the use of intraoral photographs alone to screen malocclusions has increased.

Objective: This study aimed to validate intraoral photographs for the assessment of orthodontic treatment need.

Insights From Minnesota on Newborn Screening for Adrenoleukodystrophy: A 5-Year Update.

Our objectives are to report on the outcomes of adrenal insufficiency (AI) and cerebral ALD (cALD) in children diagnosed with X-linked adrenoleukodystrophy (ALD) identified by newborn screening (NBS) in Minnesota in the first 5 years following initiation of NBS in 02/2017. A retrospective chart review was conducted for children diagnosed with ALD via Minnesota NBS from 02/06/2017 through 02/06/2022. Data reviewed included newborn screening data, diagnostic very long chain fatty acid levels, ABCD1 molecular testing results, serial measurements of ACTH and cortisol, and serial brain MRI results.

α-Synuclein interaction with POPC/POPS vesicles.

We have investigated the adsorption of the amyloid-forming protein α-Synuclein (αSyn) onto small unilamellar vesicles composed of a mixture of zwitterionic POPC and anionic POPS lipids. αSyn monomers adsorb onto the anionic lipid vesicles where they adopt an α-helical secondary structure. The degree of adsorption depends on the fraction of anionic lipid in the mixed lipid membrane, but one needs to consider the electrostatic shift of the serine p with increasing fraction of POPS.

Variations in linear energy transfer distributions within a European proton therapy planning comparison of paediatric posterior fossa tumours.

Background And Purpose: Radiotherapy for paediatric posterior fossa tumours may cause complications in the brainstem and upper spinal cord due to high doses. With proton therapy (PT) this risk may increase due to higher relative biological effectiveness (RBE) from elevated linear energy transfer (LET). This study assesses variations in LET in the brainstem and spinal cord in proton treatment plans from European centres.

Hiking Trails Facilitate the Spread of a Native High-Arctic Species.

High-Arctic environments are facing an elevated pace of warming and increasing human activities, making them more susceptible to the introduction and spread of alien species. We investigated the role of human disturbance in facilitating the spread of a native plant () in a high-Arctic natural environment close to Isfjord Radio station and along adjacent hiking trails at Kapp Linné, Svalbard. We reconstructed the spatial pattern of the arrival and spread of at Kapp Linné by combining historical records of the species occurrence (1928-2018) with a contemporary survey of the plant abundance along the main hiking trail (2023 survey) and tested the relative effects of altitude and proximity to hiking trails on the species density via a generalised linear model (GLM).

The Association Between Primary Sclerosing Cholangitis and Microscopic Colitis: A Systematic Review.

The association between primary sclerosing cholangitis (PSC) and microscopic colitis (MC) has been explored in limited studies, suggesting potential shared pathophysiological mechanisms. This systematic review aimed to investigate this relationship by analyzing studies identified through comprehensive searches in PubMed, Embase, and the Cochrane Library. Two studies met the inclusion criteria: a case series of 12 patients and a case report, collectively analyzing 13 cases.

Drug use and acute kidney injury: a Drug-Wide Association Study (DWAS) in Denmark and Sweden.

Background: Knowledge of which medications may lead to acute kidney injury (AKI) is limited, relying mostly on spontaneous reporting in pharmacovigilance systems. We here conducted an exploratory drug-wide association study (DWAS) to screen for associations between dispensed drugs and AKI risk.

Methods: Using two large Danish and Swedish data linkages, we identified AKI hospitalizations occurring between April 1997 and December 2021 in Denmark and between March 2007 and December 2021 in Sweden.

Clinical Outcomes and Donor-specific Antibody Rebound 5 y After Kidney Transplant Enabled by Imlifidase Desensitization.

Background: Imlifidase is an IgG-cleaving endopeptidase conditionally approved in Europe for desensitization of highly sensitized patients before kidney transplantation. We present 5-y outcomes and donor-specific antibody (DSA) levels for clinical trial participants from a single site who received imlifidase for desensitization before incompatible transplantation (NCT02790437).

Methods: Imlifidase was administered up to 24 h before living or deceased donor kidney transplantation.

Conceptual and empirical item hierarchies of person-centred outpatient care.

Introduction: The Person-Centred Care instrument for outpatient care (PCCoc) is a 36-item patient-reported experience measure with 4 ordered response categories, that aims to capture the degree of perceived person-centred care (PCC) from a patient perspective among persons with long-term conditions. The PCCoc is based on a framework that conceptualises outpatient PCC from lower to higher levels of perceived PCC, from personalisation via shared decision-making to empowerment, where 35 of the PCCoc items are a part of the framework's hierarchy.

Aim: To investigate to what extent empirical item responses are consistent with the hierarchical PCCoc conceptual framework among persons with long-term conditions in outpatient care.