Loss of Cpt1a results in elevated glucose-fueled mitochondrial oxidative phosphorylation and defective hematopoietic stem cells.

Hematopoietic stem cells (HSCs) rely on self-renewal to sustain stem cell potential and undergo differentiation to generate mature blood cells. Mitochondrial fatty acid β-oxidation (FAO) is essential for HSC maintenance. However, the role of Carnitine palmitoyl transferase 1a (CPT1A), a key enzyme in FAO, remains unclear in HSCs.

When midwives ask permission to discuss weight with pregnant women with high body weight: a qualitative study.

Background: In 2021, 15% of pregnant women in Denmark had a Body Mass Index (BMI) of 30 kg/m or more, which is associated with complications for both mothers and children. Healthcare professionals often feel insecure when discussing weight with pregnant women with high body weight, and people with high body weight are exposed to stigmatisation. To counter this, different tools have been developed to support respectful weight-related conversations, often recommending asking permission to talk about weight.

Professionals' perspectives on caring for cancer patients with pre-existing severe mental disorders.

Introduction: Cancer trajectories among patients with pre-existing severe mental disorders (SMD) are challenging and these pateints' prognosis is poor. This study aimed at exploring barriers in cancer trajectories among patients with pre-existing SMD as experienced by Danish healthcare professionals.

Methods: Semi-structured interviews were conducted with healthcare professionals who were sampled by purposive sampling.

Direct Salmonella injection into enteroid cells allows the study of host-pathogen interactions in the cytosol with high spatiotemporal resolution.

Intestinal epithelial cells (IECs) play pivotal roles in nutrient uptake and in the protection against gut microorganisms. However, certain enteric pathogens, such as Salmonella enterica serovar Typhimurium (S. Tm), can invade IECs by employing flagella and type III secretion systems (T3SSs) with cognate effector proteins and exploit IECs as a replicative niche.

Managing the new wave of weight loss medication in general practice: A qualitative study.

In early 2023, a new type of weight loss medication, Wegovy (semaglutide), was made available in Denmark. Both subsequent media coverage and public demand were huge. Wegovy is only available by prescription, primarily via general practitioners.

A comprehensive analysis of pneumococcal two-component system regulatory networks.

Two-component systems are key signal-transduction systems that enable bacteria to respond to a wide variety of environmental stimuli. The human pathogen, (pneumococcus) encodes 13 two-component systems and a single orphan response regulator, most of which are significant for pneumococcal pathogenicity. Mapping the regulatory networks governed by these systems is key to understand pneumococcal host adaptation.

ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline.

H3K9 trimethylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2).

ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline.

H3K9 tri-methylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2).

Communication about weight-related issues with adult patients with obesity in general practice: A scoping review.

Background: Primary care providers see patients with obesity in general practice every day but may be challenged regarding communication about obesity. The research question of this study is: how do general practitioners and general practice staff and adult patients with obesity communicate about weight-related issues?

Methods: A scoping review approach was used, searching PubMed, Scopus and CINAHL for peer-reviewed studies - of both quantitative and/or qualitative study designs, and published between 2001 and 2021.

Results: Twenty articles were included.

Perceptions, behaviours and potential barriers to effective obesity care. Results from the ACTION-DK study.

Aim: Weight bias, stigma and discrimination are pervasive in the health care system and society and may result in biased treatment of people living with obesity (PwO). We aimed to identify perceptions, attitudes and potential barriers that exist between people with obesity and health care professionals (HCPs) in Denmark.

Methods: The ACTION-DK survey was a cross-sectional, non-interventional, descriptive study conducted in Denmark.

How doctors build community and socialize into a clinical department through morning reports. A positioning theory study.

Phenomenon: The morning report is one of the longest surviving hospital practices. Most studies of the morning report focus on the effectiveness of formal medical training, while focus on social and communicative aspects is rarer. This study explores the social interactions and communication in morning reports, examining the ways in which they contribute to the construction of professional identity and socialization into the community of the clinical department.

Barriers in cancer trajectories of patients with pre-existing severe mental disorders-A systematic review.

Background: Patients with pre-existing severe mental disorders are significantly less likely to receive guideline-recommended cancer treatment and seems to have a significantly lower rate of cancer survival compared to patients with cancer without mental disorders.

Aim: To perform a systematic review on barriers at patient-, provider- and system-levels in cancer trajectories of patients with pre-existing severe mental disorders.

Method: A systematic review was performed following the PRISMA guidelines (PROSPERO ID: CRD42022316020).

Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability.

MYC-driven medulloblastomas are highly aggressive childhood brain tumors, however, the molecular and genetic events triggering MYC amplification and malignant transformation remain elusive. Here we report that mutations in CTDNEP1, a CTD nuclear-envelope-phosphatase, are the most significantly enriched recurrent alterations in MYC-driven medulloblastomas, and define high-risk subsets with poorer prognosis. Ctdnep1 ablation promotes the transformation of murine cerebellar progenitors into Myc-amplified medulloblastomas, resembling their human counterparts.

A novel cancer risk prediction score for the natural course of FA patients with biallelic BRCA2/FANCD1 mutations.

Biallelic germline mutations in BRCA2 occur in the Fanconi anemia (FA)-D1 subtype of the rare pediatric disorder, FA, characterized clinically by severe congenital abnormalities and a very high propensity to develop malignancies early in life. Clinical and genetic data from 96 FA-D1 patients with biallelic BRCA2 mutations were collected and used to develop a new cancer risk prediction score system based on the specific mutations in BRCA2. This score takes into account the location of frameshift/stop and missense mutations relative to exon 11 of BRCA2, which encodes the major sites for interaction with the RAD51 recombinase, and uses the MaxEnt and HBond splicing scores to analyze potential splice site perturbations.

Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation.

Meiotic sex chromosome inactivation (MSCI) is an essential process in the male germline. While genetic experiments have established that the DNA damage response (DDR) pathway directs MSCI, due to limitations to the experimental systems available, mechanisms underlying MSCI remain largely unknown. Here we establish a system to study MSCI ex vivo, based on a short-term culture method, and demonstrate that active DDR signaling is required both to initiate and maintain MSCI via a dynamic and reversible process.

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This review focuses on communication about weight-related issues with patients with obesity in general practice. Primary care providers still lack knowledge and tools to address and communicate about the topic of weight and weight-related issues - with focus on minimizing stigmatization and a person centered approach. A few communication tools on the topic have been developed but it seems that the use of those is limited, suggesting an urgent need for making a fast, easy and simple tool for the use in general practice.

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Obesity stigma refers to the pervasive sociocultural disapproval and prejudice against people with obesity which is associated with different negative traits. The stigmatisation of people with obesity manifests itself in different social areas, both privately and publicly, including in the health care system, often resulting in negative physical, social, and psychological consequences for people with obesity. Consequently, it is imperative that healthcare professionals seek to avoid and take action against this type of stigmatisation, e.

Identification of new RAD51D-regulating microRNAs that also emerge as potent inhibitors of the Fanconi anemia/homologous recombination pathways.

The Fanconi anemia (FA) and homologous recombination (HR) pathways, which partially overlap and include RAD51 and its paralogs, are key for the repair of different types of DNA damage, such as DNA interstrand crosslinks. First, to broadly assess the impact of microRNA-mediated regulation, we examined microRNA expression profiles in five isogenic fibroblast cell pairs, either deficient in DNA repair due to germline mutations in FANCA, FANCB, FANCC, FANCI or BRIP1/FANCJ or proficient due to correction with retroviral vectors. In each pair, we observed lower abundance of specific microRNAs in the FA-deficient cells.

Head and Neck Cancer Susceptibility and Metabolism in Fanconi Anemia.

Fanconi anemia (FA) is a rare inherited, generally autosomal recessive syndrome, but it displays X-linked or dominant negative inheritance for certain genes. FA is characterized by a deficiency in DNA damage repair that results in bone marrow failure, and in an increased risk for various epithelial tumors, most commonly squamous cell carcinomas of the head and neck (HNSCC) and of the esophagus, anogenital tract and skin. Individuals with FA exhibit increased human papilloma virus (HPV) prevalence.

What works in appraisal meetings for newly graduated doctors? - and what doesn't?

Background: In Denmark a national formal advisory program (NFAP) is mandatory in Postgraduate Medical Education (PGME). According to this, an educational advisor is assigned to each doctor in every clinical rotation to guide and oversee the work and learning progress of the trainee. This study explores why newly graduated trainees evaluated the appraisal meetings in the advisory program as either beneficial (successes) or not beneficial (non-successes).

Meiotic sex chromosome inactivation and the XY body: a phase separation hypothesis.

In mammalian male meiosis, the heterologous X and Y chromosomes remain unsynapsed and, as a result, are subject to meiotic sex chromosome inactivation (MSCI). MSCI is required for the successful completion of spermatogenesis. Following the initiation of MSCI, the X and Y chromosomes undergo various epigenetic modifications and are transformed into a nuclear body termed the XY body.

Ambivalence and moral dilemmas in women's lived experiences of obesity and pregnancy: Qualitative insights for maternal lifestyle interventions.

Background: Maternal obesity is a global health concern that is associated with significant effects on both short- and long-term health of both mother and child. However, maternal lifestyle interventions tend to focus solely on diet and physical activity in ways that disembody and disengage the social context in which women live their lives.

Aims: The aim of this study was to explore the lived experiences of maternal obesity and delve into how experiences of the body and motherhood affect women's motivation for participating in a postpartum lifestyle intervention.

Understanding BRCA2 Function as a Tumor Suppressor Based on Domain-Specific Activities in DNA Damage Responses.

is an essential genome stability gene that has various functions in cells, including roles in homologous recombination, G2 checkpoint control, protection of stalled replication forks, and promotion of cellular resistance to numerous types of DNA damage. Heterozygous mutation of is associated with an increased risk of developing cancers of the breast, ovaries, pancreas, and other sites, thus acts as a classic tumor suppressor gene. However, understanding function as a tumor suppressor is severely limited by the fact that ~70% of the encoded protein has not been tested or assigned a function in the cellular DNA damage response.

RNF8 is not required for histone-to-protamine exchange in spermiogenesis†.

While an E3 ubiquitin ligase, RNF8, was initially reported to be required for histone-to-protamine exchange in spermiogenesis, we subsequently demonstrated that RNF8 is not involved in this process. Nevertheless, reflecting a lingering misunderstanding in the field, a growing number of studies have continued to postulate a requirement for RNF8 in the histone-to-protamine exchange. For example, a recent study claimed that a mouse PIWI protein, MIWI, controls RNF8-mediated histone-to-protamine exchange.

The p.Ser64Leu and p.Pro104Leu missense variants of PALB2 identified in familial pancreatic cancer patients compromise the DNA damage response.

PALB2 has been identified as a breast and pancreatic cancer susceptibility gene. Utilizing a targeted sequencing approach, we discovered two novel germline missense PALB2 variants c.191C>T and c.