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Introduction Pulmonary lymphangitis carcinomatosa is a rare and severe manifestation of metastatic disease that causes pulmonary symptoms and radiologic patterns similar to interstitial lung diseases.Case presentation We report a case of a 78-year-old woman who presented to our department with insidiously developed symptoms of fatigue, dry cough, and severe dyspnea for 3 months. Chest radiography showed bilateral interstitial changes. On suspicion of interstitial lung disease, bronchoscopy and transbronchial cryobiopsy were carried out. Surprisingly, histopathological investigation revealed pulmonary lymphangitis carcinomatosa originating from primary breast adenocarcinoma.Conclusion To achieve an accurate diagnosis and prevent delay of initiation of proper treatment a thorough diagnostic approach is necessary. In case of doubt, biopsy should be performed to secure clarification. In this case report we discuss the diagnostic value of transbroncial cryobiopsy for this purpose.

This qualitative study explored the experiences of individuals testing a novel internet-delivered acceptance and commitment therapy program (iACT) for patients with mild and moderate depressive disorder. Twelve participants, consisting of one male and 11 females with a history of depression but not currently depressed were recruited. Individual semi-structured interviews were conducted after 14 days of access to the iACT without therapist guidance. By using reflexive thematic analysis three key themes reflecting important aspects of the participants' experiences were created. ‘Theme 1: I would have been too ill to benefit from the program’ points to generally positive sentiments about the program among participants but raised concerns about treatment adherence during a depressive episode. ‘Theme 2: It has the potential to fill gaps in healthcare services’ highlighted the program's perceived role as a supplement to current health services rather than as a standalone intervention. ‘Theme 3: It is not perfect for anyone’ underscored the participants different views on how their personal needs would be met by this program and the lack of tailoring to individual preferences. These findings provide valuable insights for refining future internet-delivered intervention development targeting patients with depression or other mental health challenges.

Various stakeholders, such as modelers, policy makers, farmers, and environmental regulators need reliable soil bulk density and coarse fragment content data. These two soil parameters are necessary to calculate soil carbon and nutrients stocks, to estimate water availability for plants, or to assess soil compaction. However, measuring these two parameters is labor intensive and time consuming. Therefore, many agricultural and environmental studies often miss these two soil parameters. Here, we provide four datasets, one with bulk density and coarse fragment contents of topsoil and subsoil, measured in two campaigns of the French Soil Quality Monitoring Network (RMQS for its acronym in French), a second one with the average values for bulk density and coarse fragments of the two campaigns at 0–30 cm and 30–50 cm. The third and the fourth ones are the raw data needed to calculate the two first datasets divided by campaign. In addition, the R script for calculating the depth-weighted values per soil layer is provided

Abstract Background Human genetic contribution to HIV progression remains inadequately explained. The type 1 interferon (IFN) pathway is important for host control of HIV and variation in type 1 IFN genes may contribute to disease progression. This study assessed the impact of variations at the gene and pathway level of type 1 IFN on HIV-1 viral load (VL). Methods Two cohorts of antiretroviral (ART) naïve participants living with HIV (PLWH) with either early (START) or advanced infection (FIRST) were analysed separately. Type 1 IFN genes (n = 17) and receptor subunits (IFNAR1, IFNAR2) were examined for both cumulated type 1 IFN pathway analysis and individual gene analysis. SKAT-O was applied to detect associations between the genotype and HIV-1 study entry viral load (log10 transformed) as a proxy for set point VL; P-values were corrected using Bonferroni (P G) was associated with study entry VL (p = 0.0020, beta = 0.32; G associated with higher study entry VL than A) in single SNP association analyses. The findings were not reproduced in FIRST participants. Conclusion Across 19 type 1 IFN genes, only IFNW1 was associated with HIV-1 study entry VL in a cohort of ART-naïve individuals in early stages of their infection, however, this was no longer significant in sensitivity analyses that controlled for population structures using LME.

Primary care in the Nordic countries have many similarities but are also different in crucial ways (Olsen et al. 2016). Among the similarities are that Nordic primary care is tax-based, aims to ensure equal and easy access to care for all citizens, and supply high-quality care at the lowest cost-effective level. Among the differences are the Nordic countries’ way of organizing primary care with respect to remuneration, incentives, and the use of general practitioners (GPs) as gatekeepers. As other countries, the Nordic countries have experienced certain challenges in primary care in recent years. Demands from patients and third-party payers are increasing both with respect to quantity and quality of services expected for provision. Some of the reasons for this are ageing populations, more patients with chronic diseases, and third-party payers aiming to make primary care the main responsible for prevention and treatment of the chronically ill. At the same time, the supply of GPs continues to drop (especially in Denmark and Norway and with Finland as an exception), the share of avoidable hospital admissions of all hospital admissions is still too high, and the same holds for the share of inappropriate antibiotic prescriptions in primary care (OECD 2020). There is therefore still room for improvement, although primary care in the Nordic countries overall tend to be placed in the better half of the distributions compared to other OECD countries. In the 2020 OECD report on the potential of primary health care, several actions were outlined that could help strengthen the efficiency, effectiveness, and access of primary care. To improve the efficiency of primary care, new recruitment and training strategies, better use of digital technology, and providing the right (financial) incentives were pointed out as potential tools. To improve the effectiveness and responsiveness of primary care, reorganization in teams and integrated networks, bundled payments, and improved information systems were pointed out as possible solutions. To improve access and equity in primary care, it was recommended to use technology and mobile clinics to reach rural areas, in occupational health in workplaces, and to revisit the roles of health care professionals (OECD 2020). In this special issue in the Nordic journal of health economics, several studies from the Nordic countries focus on the challenges in Nordic primary care in different ways. The issue includes empirical studies from Sweden, Norway, Denmark, and Finland, as well as a theoretical contribution concerned with recruitment and retention in Nordic primary care. The studies all factor into the recommendations made in the OECD report on how to strengthen primary care. For example, in this special issue we will learn in a study by Glengård that characteristics that can be changed by primary care clinics themselves, such as division of labour and continuity of care are also the most important for patients’ experience of care relative to factors that are out of the primary care clinics’ control. On the positive side, this means that there is scope for improvements while on the negative side, improvements may be difficult due to challenges with GP shortages in Sweden, where the study was conducted. Oxholm and colleagues are also concerned with the GP shortage issue and study the link between work pressure in general practice and job dissatisfaction of GPs. They find that the link between experienced work pressure and job dissatisfaction is stronger for GPs working in areas with an undersupply of GPs and for GPs in singlehanded practices. These areas could therefore be of special interest to policy makers when implementing new incentive schemes and structures affecting GPs’ work pressure. While reorganising primary care may be part of the solution to overcome the challenges in primary care, Aars and Kaarbøe offer insights into the recruitment and retention of GPs in a theoretical model to inform policy decisions. They show that there are conflicting effects as policies that have a positive effect on recruiting and retaining GPs can have a negative effect on GPs’ effort and services and that the effect is sensitive to GPs’ degree of altruism. In a study by Snilsberg, who is concerned with how new team-based primary care delivery models in Norway can be effectively evaluated when there are potential issues with selection bias and small sample sizes, we learn that matching methods can be used to account for these issues and propensity score weighting is suggested. The paper also identifies several important predictors for joining the new primary care delivery models. Holster and colleagues are interested in how occupational healthcare in Finland is used and how the use is associated with other ambulatory service sectors and the distribution of care between these. Interestingly they find that the use of occupational healthcare seems to be associated with higher use of ambulatory care services overall, which suggests that ambulatory care is not allocated according to need. This raises important questions of equality in access to care. Focusing on the challenges in Nordic Primary care from a health economic perspective is a first step towards understanding the mechanisms behind the problems. The health economics discipline and its tools can help uncover the issues and disclose where to set in to solve the problems. It can also explore the potential of the OECD recommendations in more detail and elicit in what areas the greatest potential is for improving efficiency, effectiveness, and equity. Recommendations for important next steps to solve the current issues could be to 1) gain inspiration from countries who (also) have well-run primary health care sectors (here Israel has been enhanced as an interesting example that performs well on a number of indicators (OECD 2012, Barua and Jacques 2018, Rotenberg et al. 2022)) and explore the contexts of these sectors, and 2) join forces with other academic disciplines, e.g. researchers from primary care, public administration, organizational theory etc. to shed light on the topic from different angles using different methods. Finally, it is of utmost importance to inform and guide policy makers about which interventions and organizational changes that are deemed successful and how Nordic primary care could best be improved. It can turn out to be a strength that the covid-19 pandemic has forced the health care system and professionals to adapt quickly to the new situation, to collaborate on the treatment of patients between health care sectors, and to develop and provide technological solutions to consult and treat patients at the distance. The next years will tell whether these rapid changes in primary care have accelerated technological progress and led to permanent changes in behaviour that is assumed to enable the realisation of unexploited potential in Nordic primary care. Health economists can contribute to this understanding by investigating whether such changes provide higher quality of care at a more cost-effective level.

Objectives: Use of opioids can lead to frequent and severe side effects, prompting the exploration of non-pharmacological alternatives, including nudging, to reduce opioid consumption. This review identifies and evaluates patient-targeted nudges to support opioid tapering among adults with chronic non-cancer pain. Methods: We searched EMBASE, MEDLINE, CINAHL, PsycInfo, and Social Science citation index for articles published from 2010 to January 2023. Eligibility criteria were based on the PICOS framework and included original peer-reviewed English language studies on adults with chronic non-cancer pain and interventions aligning with the nudge definition by Thaler and Sunstein. Studies with relevant comparators, measurable outcomes, real-world data, and pre/post-intervention measures were included. Data were manually extracted and reported in a descriptive manner. The process adhered to PRISMA-ScR reporting guidelines. Results: Four of 222 articles fulfilled the inclusion criteria. All included nudges aimed at providing information to support decision-making and behavior change. Three nudge categories were identified: increasing salience, understanding mappings, and feedback. Outcome measures were program-related, focusing on perceptions, knowledge acquisition, engagement metrics, and psychological well-being. Conclusions: There were no statistically significant effects or only small evidence of effects in the program-related outcomes. None of the studies included a control group with standard care or no intervention comparison and none included objective measures of opioid reduction. More studies are needed to draw conclusions on the effectiveness of nudges to support opioid tapering among chronic non-cancer pain patients.

Abstract Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10−8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Abstract Whole genome sequencing (WGS) is becoming the preferred method for molecular genetic diagnosis of rare and unknown diseases and for identification of actionable cancer drivers. Compared to other molecular genetic methods, WGS captures most genomic variation and eliminates the need for sequential genetic testing. Whereas, the laboratory requirements are similar to conventional molecular genetics, the amount of data is large and WGS requires a comprehensive computational and storage infrastructure in order to facilitate data processing within a clinically relevant timeframe. The output of a single WGS analyses is roughly 5 MIO variants and data interpretation involves specialized staff collaborating with the clinical specialists in order to provide standard of care reports. Although the field is continuously refining the standards for variant classification, there are still unresolved issues associated with the clinical application. The review provides an overview of WGS in clinical practice - describing the technology and current applications as well as challenges connected with data processing, interpretation and clinical reporting.

Large donor–acceptor scaffolds derived from polycyclic aromatic hydrocarbons (PAHs) with tunable HOMO and LUMO energies are important for several applications, such as organic photovoltaics. Here, we present a large selection of PAHs based on central indenofluorene (IF) or fluorene cores and containing various dithiafulvene (DTF) donor units that gain aromaticity upon oxidation and a variety of acceptor units, such as vinylic diesters, enediynes, and cross-conjugated radiaannulenes (RAs) that gain aromaticity upon reduction. In some cases, the DTF units are expanded by pyrrolo annelation. The optical and redox properties of these compounds, in some cases carbon-rich, were studied by UV–vis absorption spectroscopy and cyclic voltammetry. Synthetically, the work explores IF diones or fluorenone as central building blocks by subjecting the carbonyl groups to a variety of reactions; that are, phosphite- or Lawesson’s reagent-mediated olefination reactions (to introduce DTF motifs), Ramirez/Corey–Fuchs dibromo-olefinations followed by Sonogashira couplings (to introduce enediynes motifs), and Knoevenagel condensations (to introduce the vinylic diester motif). By a subsequent Glaser–Hay coupling reaction, a RA acceptor unit was introduced to provide a DTF-IF-RA donor–acceptor scaffold with a low-energy charge-transfer absorption and multi-redox behavior.

Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients’ immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.

Background and purpose: In Norway, comprehensive molecular tumour profiling is implemented as part of the public healthcare system. A substantial number of tumours harbour potentially targetable molecular alterations. Therapy outcomes may improve if targeted treatments are matched with actionable genomic alterations. In the IMPRESS-Norway trial (NCT04817956), patients are treated with drugs outside the labelled indication based on their tumours molecular profile. Patients and methods: IMPRESS-Norway is a national, prospective, non-randomised, precision cancer medicine trial, offering treatment to patients with advanced-stage disease, progressing on standard treatment. Comprehensive next-generation sequencing, TruSight Oncology 500, is used for screening. Patients with tumours harbouring molecular alterations with matched targeted therapies available in IMPRESS-Norway, are offered treatment. Currently, 24 drugs are available in the study. Primary study endpoints are percentage of patients offered treatment in the trial, and disease control rate (DCR) defined as complete or partial response or stable disease in evaluable patients at 16 weeks (W16) of treatment. Secondary endpoint presented is DCR in all treated patients. Results: Between April 2021 and October 2023, 1,167 patients were screened, and an actionable mutation with matching drug was identified for 358 patients. By the data cut off 186 patients have initiated treatment, 170 had a minimum follow-up time of 16 weeks, and 145 also had evaluable disease. In patients with evaluable disease, the DCR was 40% (58/145). Secondary endpoint analysis of DCR in all treated patients, showed DCR of 34% (58/170). Interpretation: Precision cancer medicine demonstrates encouraging clinical effect in a subset of patients included in the IMPRESS-Norway trial.

Introduction: The health effects of alcohol are well established but the influence on pulmonary function remains debated. Studies indicate that small amounts of alcohol are beneficial and heavy consumption is harmful, suggesting a U-shaped association. Our objective is to determine whether there is an association between alcohol intake and changes in pulmonary function parameters, exploring the potential protective effect of moderate alcohol consumption and the harm caused by heavy drinking. Methods: A comprehensive search from PubMed, Embase, Cochrane and CINAHL was carried out, and studies were evaluated using the JBI methodological framework for scoping reviews. Two independent reviewers conducted parallel screening and data extraction. A data extraction form was utilised to organise key themes, with qualitative analysis and visual representation of the results. Results: Among 4427 screened abstracts, 179 underwent full-text review, resulting in 30 eligible studies. Of these, 10 showed a negative effect, nine reported no impact, nine exhibited a positive effect and two indicated a nonlinear U-shaped association between alcohol consumption and pulmonary function parameters. Conclusion: While the U-shaped curve hypothesis remains unconfirmed by the current literature, there are notable associations. Heavy alcohol consumption appears to negatively affect pulmonary function, while low to moderate intake shows a positive influence in included studies. However, the diversity in study quality, the nonstandardised alcohol intake quantification and the confounding role of smoking challenge definitive conclusions. The need for consistent, long-term international studies is evident to further explore this relationship while addressing the complex interplay between alcohol and smoking.

Background Ovarian cancer (OC) is the leading cause of death from gynecologic malignancies in the Western world. Contributing factors include a high frequency of late-stage diagnosis, the development of chemoresistance, and the evasion of host immune responses. Currently, debulking surgery and platinum-based chemotherapy are the treatment cornerstones, although recurrence is common. As the clinical efficacy of immune checkpoint blockade is low, new immunotherapeutic strategies are needed. Chimeric antigen receptor (CAR) T cell therapy empowers patients’ own T cells to fight and eradicate cancer, and has been tested against various targets in OC. A promising candidate is the MUC16 ectodomain. This ectodomain remains on the cell surface after cleavage of cancer antigen 125 (CA125), the domain distal from the membrane, which is currently used as a serum biomarker for OC. CA125 itself has not been tested as a possible CAR target. In this study, we examined the suitability of the CA125 as a target for CAR T cell therapy.Methods We tested a series of antibodies raised against the CA125 extracellular repeat domain of MUC16 and adapted them to the CAR format. Comparisons between these candidates, and against an existing CAR targeting the MUC16 ectodomain, identified K101 as having high potency and specificity. The K101CAR was subjected to further biochemical and functional tests, including examination of the effect of soluble CA125 on its activity. Finally, we used cell lines and advanced orthotopic patient-derived xenograft (PDX) models to validate, in vivo, the efficiency of our K101CAR construct.Results We observed a high efficacy of K101CAR T cells against cell lines and patient-derived tumors, in vitro and in vivo. We also demonstrated that K101CAR functionality was not impaired by the soluble antigen. Finally, in direct comparisons, K101CAR, which targets the CA125 extracellular repeat domains, was shown to have similar efficacy to the previously validated 4H11CAR, which targets the MUC16 ectodomain.Conclusions Our in vitro and in vivo results, including PDX studies, demonstrate that the CA125 domain of MUC16 represents an excellent target for treating MUC16-positive malignancies.