Artificial Intelligence for early detection of lung cancer in General Practitioners' clinical notes.

Background: The journey of more than 80% of patients diagnosed with lung cancer starts in general practice. About 75% of patients are diagnosed in an advanced stage (3 or 4), leading to more than 80% mortality within one year at present. The long-term data in general practitioners' records might contain hidden information that could be used for earlier case-finding of patients with cancer.

VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.

Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau () tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors of , and uncover that loss of Core Binding Factor β (CBF-β) causes cell death in -null ccRCC cell lines and impairs tumour establishment and growth . This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) in -null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-β.

Factors influencing the implementation of the CombiConsultation in Dutch clinical practice: a mixed-methods study.

Objective: The CombiConsultation is an innovative concise clinical pharmacy service by the community pharmacist for patients with a chronic condition. We aimed to identify relevant factors influencing the implementation of the CombiConsultation in Dutch clinical practice.

Methods: A mixed-methods study involving interviews and a questionnaire.

Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.

The ubiquitination and proteasome-mediated degradation of Hypoxia Inducible Factors (HIFs) is central to metazoan oxygen-sensing, but the involvement of deubiquitinating enzymes (DUBs) in HIF signalling is less clear. Here, using a bespoke DUBs sgRNA library we conduct CRISPR/Cas9 mutagenesis screens to determine how DUBs are involved in HIF signalling. Alongside defining DUBs involved in HIF activation or suppression, we identify USP43 as a DUB required for efficient activation of a HIF response.

Hypoxia drives HIF2-dependent reversible macrophage cell cycle entry.

Low-oxygen conditions (hypoxia) have been associated primarily with cell-cycle arrest in dividing cells. Macrophages are typically quiescent in G0 but can proliferate in response to tissue signals. Here we show that hypoxia (1% oxygen tension) results in reversible entry into the cell cycle in macrophages.

The transition of general practice into an academic discipline: tracing the origins through the first four professors in general practice/family medicine.

Being the 'mother' of most clinical specialties, general practice is as old as medicine itself. However, as a recognized academic discipline within medical schools, general practice has a relatively short life span. A decisive step forward was taken in 1956 when the University of Edinburgh established its Department of General Practice, and appointed the world's inaugural professor in the field in 1963.

Effectiveness of a guided online primary care intervention for fear of cancer recurrence: A randomised controlled trial.

Objective: Fear of Cancer Recurrence (FCR) is highly prevalent among cancer survivors and leads to decreased quality of life and increased healthcare costs. We assessed the effectiveness of a guided online primary care intervention for FCR, compared to waiting list.

Methods: In this RCT, participants were recruited online and randomised 1:1.

A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis.

Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen for sterol production has resulted in a shared transcriptional response, resembling prolyl hydroxylation of Hypoxia Inducible Factors (HIFs) in metazoans. Whether an analogous metazoan pathway exists is unknown.

Patients' views on the decision to investigate cancer symptoms in older adults: a qualitative interview study in primary care.

Background: Cancer is predominantly a disease of older adults. To date there has been little research on the experiences of older adults or their views on the diagnostic pathway.

Aim: To gain an improved understanding of the views and experiences of older adults on all aspects of cancer investigation.

Barriers and facilitators for the implementation of the CombiConsultation by general practitioners, pharmacists and practice nurses: a qualitative interview study.

Background: The CombiConsultation is a consultation with the pharmacist for patients with a chronic condition, aligned with the periodic consultation with the practice nurse or general practitioner. Implementation requires adjustments in the working methods of these healthcare providers and therefore behavioural changes.

Aim: The aim of this study was to identify the barriers and facilitators that determine the behavioural changes by pharmacists, general practitioners and practice nurses required for the implementation of the CombiConsultation.

A histone deacetylase 3 and mitochondrial complex I axis regulates toxic formaldehyde production.

Cells produce considerable genotoxic formaldehyde from an unknown source. We carry out a genome-wide CRISPR-Cas9 genetic screen in metabolically engineered HAP1 cells that are auxotrophic for formaldehyde to find this cellular source. We identify histone deacetylase 3 (HDAC3) as a regulator of cellular formaldehyde production.

The CombiConsultation for patients with diabetes, COPD and cardiovascular diseases: Evaluation of interventions and personal health-related goals.

Background: The CombiConsultation is a consultation with the community pharmacist for patients with diabetes, COPD and/or cardiovascular disease (CVD), aligned with the annual or quarterly consultation with the practice nurse (PN) or general practitioner (GP). The consultation is focused on the personal health-related goals of the patient.

Objectives: To assess the number and types of personal health-related goals, drug-related problems (DRPs) and interventions identified by pharmacists during a CombiConsultation and to investigate which patients can benefit most from such consultation.

Effectiveness of a blended multidisciplinary intervention for patients with moderate medically unexplained physical symptoms (PARASOL): A cluster randomized clinical trial.

Introduction: In patients with moderate Medically Unexplained Physical Symptoms (MUPS), interventions focusing on both physical and psychological aspects are recommended. A proactive, blended and integrated physical therapy and mental health nurse intervention (PARASOL) might reduce complaints, stimulate self-management and prevent chronicity.

Objective: To investigate short- and long-term effectiveness of the PARASOL intervention compared to usual care on subjective symptom impact and quality of life in patients with moderate MUPS.

Impact of the COVID-19 Outbreak-Delayed Referral of Colorectal and Lung Cancer in Primary Care: A National Retrospective Cohort Study.

The Coronavirus disease 2019 (COVID-19) outbreak impacted health care. We investigated its impact on the time to referral and diagnosis for symptomatic cancer patients in The Netherlands. We performed a national retrospective cohort study utilizing primary care records linked to The Netherlands Cancer Registry.

Cancer detection during the COVID-19 pandemic-Experiences in primary care and recommendations for the future.

Background: To describe general practitioners (GPs) experiences with the impact COVID-19 on the duration of cancer detection.

Methods: Cross-sectional survey study among Dutch GPs.

Results: Fifty-eight GPs participated.

Patient-reported needs for coping with worry or fear about cancer recurrence and the extent to which they are being met: a survey study.

Purpose: Many cancer patients and survivors experience fear or worry about cancer recurrence (FCR). Evidence suggests support for FCR is their largest unmet need. We aimed to assess which types of support are needed, which providers are preferred and to what extent patients' needs are being met.

Cluster analysis of functional independence in community-dwelling older people.

Background: The concept of Functional Independence (FI), defined as 'functioning physically safe and independent from other persons, within one's context", plays an important role in maintaining the functional ability to enable well-being in older age. FI is a dynamic and complex concept covering four clinical outcomes: physical capacity, empowerment, coping flexibility, and health literacy. As the level of FI differs widely between older adults, healthcare professionals must gain insight into how to best support older people in maintaining their level of FI in a personalized manner.

The Impact of the COVID Pandemic on the Incidence of Presentations with Cancer-Related Symptoms in Primary Care.

In the Netherlands, the onset of the coronavirus pandemic saw shifts in primary health service provision away from physical consultations, cancer-screening programs were temporarily halted, and government messaging focused on remaining at home. In March and April 2020, weekly cancer diagnoses decreased to 73% of their pre-COVID levels, and 39% for skin cancer. This study aims to explore the effect of the COVID pandemic on patient presentations for cancer-related symptoms in primary care in The Netherlands.

Mental Health Morbidities and Time to Cancer Diagnosis Among Adults With Colon Cancer in England.

Importance: Mental health morbidity (MHM) in patients presenting with possible cancer symptoms may be associated with prediagnostic care and time to cancer diagnosis.

Objective: To compare the length of intervals to cancer diagnosis by preexisting MHM status in patients who presented with symptoms of as-yet-undiagnosed colon cancer and evaluate their risk of emergency cancer diagnosis.

Design, Setting, And Participants: This cohort study was conducted using linked primary care data obtained from the population-based Clinical Practice Research Datalink, which includes primary care practices in England, linked to cancer registry and hospital data.

Who are the patients being offered the faecal immunochemical test in routine English general practice, and for what symptoms? A prospective descriptive study.

Objectives: The faecal immunochemical test (FIT) was introduced to triage patients with lower-risk symptoms of colorectal cancer (CRC) in English primary care in 2018. While there is growing evidence on its utility to triage patients in this setting, evidence is still limited on how official FIT guidance is being used, for which patients and for what symptoms. We aimed to investigate the use of FIT in primary care practice for lower-risk patients who did not immediately meet criteria for urgent referral.

The evolution and co-evolution of a primary care cancer research network: From academic social connection to research collaboration.

Academic networks are expected to enhance scientific collaboration and thereby increase research outputs. However, little is known about whether and how the initial steps of getting to know other researchers translates into effective collaborations. In this paper, we investigate the evolution and co-evolution of an academic social network and a collaborative research network (using co-authorship as a proxy measure of the latter), and simultaneously examine the effect of individual researcher characteristics (e.