Assessing Human Lung Pharmacokinetics Using Exhaled Breath Particles.

It remains challenging to quantify lung pharmacokinetics (PK) of a drug administered and targeted to act in the lung. Exhaled breath particles (PEx), which are generated when collapsed distal airways reopen during inhalation, offer a noninvasive way to access undiluted epithelial lining fluid (ELF). Therefore, it was the aim of this study to investigate whether PK data can be derived from PEx.

Starch intake and caries increment: A longitudinal study in Finnish adults.

Objective: To evaluate whether changes in starch intake (in terms of amount and food sources) were associated with increments in dental caries among adults.

Design: This is an 11-year longitudinal study (2000-2011) with duplicate assessments for all variables. A 128-item FFQ was used to estimate intake of starch (g/d) and six starch-rich food groups (potatoes, potato products, roots and tubers, pasta, wholegrains and legumes).

Starch intake and changes in dental caries among adults: A longitudinal study in Finland.

Objective: To evaluate the association between starch intake (amount and type) and changes in dental caries among adults over 11 years.

Methods: Data from 1679 adults, aged 30 years and over, who participated in three consecutive surveys in Finland were pooled for analysis. Participants completed a validated semi-structured 128-item food frequency questionnaire at baseline, from which total starch intake (g/day and % energy intake) and the intake (g/day) of seven food groups high in starch (potatoes, potato products, roots and tubers, refined grains, pasta, wholegrains, and legumes) were estimated.

ALT levels, alcohol use, and metabolic risk factors have prognostic relevance for liver-related outcomes in the general population.

Background & Aims: A new nomenclature and subclassification for steatotic liver disease (SLD) was recently introduced. We validated the prognostic value of SLD subclasses in a Finnish population-based cohort and explored the impact of metabolic risk factors and alcohol consumption on liver-related outcomes and death.

Methods: The study included 23,910 individuals (47% men, mean age 50.

Patient-derived organoids in precision cancer medicine.

Organoids are three-dimensional (3D) cultures, normally derived from stem cells, that replicate the complex structure and function of human tissues. They offer a physiologically relevant model to address important questions in cancer research. The generation of patient-derived organoids (PDOs) from various human cancers allows for deeper insights into tumor heterogeneity and spatial organization.

Is Starch Intake Associated With Periodontal Status? An 11-Year Longitudinal Analysis Among Finnish Adults.

Aim: To evaluate the association between baseline starch intake (amount and sources) and changes in periodontal status over 11 years in adults.

Methods: Adults aged 30-82 years, who participated in the Finnish Health 2000 survey and were re-examined in 2004/2005 and/or 2011 were included in the study. The consumption of total starch and six relevant food groups (potatoes, fried potatoes, roots and tubers, pasta, wholegrains and legumes) over the past year was determined at baseline with a validated food frequency questionnaire.

Prenatal and Postnatal Exposure to Antibiotics and the Risk of Type 1 Diabetes in Finnish Children: A Registry-based Study.

Objective: To study whether prenatal and postnatal exposure to antibiotics is associated with the risk of type 1 diabetes in childhood.

Study Design: This case cohort study included 2869 children diagnosed with type 1 diabetes by the end of 2009 who were born between January 1, 1996, and December 31, 2008, in Finland and a reference cohort (n = 74 263) representing 10% of each birth cohort. Exposure to antibiotics was assessed in different time periods.

Alterations in bile acid kinetics after bariatric surgery in patients with obesity with or without type 2 diabetes.

Background: Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking.

Methods: In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort.

Physical Fitness as a Predictor of Disability Retirement: A 9-Year Register Linked Follow-Up Study.

Background: To prospectively examine the association between physical fitness and risk of disability retirement in a large population-based cohort.

Methods: This study utilized data from Health 2011 survey Physical Activity subsample (n = 4898), combined with information on disability retirement derived from 2 national registers. In total, 2455 individuals aged 18-74 years underwent the physical fitness test protocol concerning measures of cardiorespiratory fitness, muscle strength, and balance.

Cytokine release syndrome after treatment with immune checkpoint inhibitors: an observational cohort study of 2672 patients from Karolinska University Hospital in Sweden.

Immune checkpoint inhibitors (ICIs) are linked to diverse immune-related adverse events (irAEs). Rare irAEs surface first in clinical practice. Here, we systematically studied the rare irAE, cytokine-release syndrome (CRS), in a cohort of 2672 patients treated with ICIs at Karolinska University Hospital in Stockholm, Sweden.

Joint associations of leisure time physical activity and screen sitting time with long-term sickness absence due to mental and musculoskeletal diseases: a registry linked follow-up study.

Objectives: To examine joint associations of leisure-time physical activity (LTPA) and screen sitting time with subsequent sickness absence among the adult population.

Study Design: Registry linked follow-up study.

Methods: A representative sample of Finnish adults (n = 10,300) were asked to fill out a questionnaire for the FinHealth 2017 survey.

Production of deoxycholic acid by low-abundant microbial species is associated with impaired glucose metabolism.

Alterations in gut microbiota composition are suggested to contribute to cardiometabolic diseases, in part by producing bioactive molecules. Some of the metabolites are produced by very low abundant bacterial taxa, which largely have been neglected due to limits of detection. However, the concentration of microbially produced metabolites from these taxa can still reach high levels and have substantial impact on host physiology.

Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis.

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells.

A phenotypic screening approach to target p60AmotL2-expressing invasive cancer cells.

Background: Tumor cells have the ability to invade and form small clusters that protrude into adjacent tissues, a phenomenon that is frequently observed at the periphery of a tumor as it expands into healthy tissues. The presence of these clusters is linked to poor prognosis and has proven challenging to treat using conventional therapies. We previously reported that p60AmotL2 expression is localized to invasive colon and breast cancer cells.

Association between physical fitness and perceived work ability among Finnish population: a cross-sectional study.

Objective: This cross-sectional study aims to examine association between different components of physical fitness and perceived work ability among working age population.

Methods: The population-based study sample included 2050 participants aged 18-74 from the Finnish national Health 2011 study. Physical fitness was assessed by the single leg stand test, the modified push-up test, the vertical jump test and the six-minute walk test, and perceived work ability was assessed via interview.

Work ability trends 2000-2020 and birth-cohort projections until 2040 in Finland.

To examine age-group and birth-cohort trends in perceived work ability in Finland in 2000-2020 and make projections of perceived work ability up to 2040 based on the observed birth-cohort development. Ten population-representative cross-sectional surveys conducted in Finland between 2000 and 2020 were used (overall = 61,087, range 817-18,956). Self-reported estimates of current work ability in relation to the person's lifetime best on a scale from zero to ten (0-10) were classified into three groups: limited (0-5), intermediate (6-7), and good (8-10).

Serum ferritin level is associated with liver fibrosis and incident liver-related outcomes independent of genotype in the general population.

Background & Aims: Hyperferritinemia reflects iron accumulation in the body and has been associated with metabolic disturbances and alcohol use, and is also a common finding in individuals diagnosed with liver disease. The major genetic regulator of iron metabolism is the gene.

Methods: The aim of this this study was to investigate the association between serum ferritin and liver fibrosis using the enhanced liver fibrosis (ELF) test, and the association between ferritin and liver-related outcomes in a Finnish population-based cohort of 6194 individuals (45% male, mean [± standard deviation] age, 52.

Natural killer cells drive 4-1BBL positive uveal melanoma towards EMT and metastatic disease.

Background: Inflammation in the eye is often associated with aggravated ocular diseases such as uveal melanoma (UM). Poor prognosis of UM is generally associated with high potential of metastatic liver dissemination. A strong driver of metastatic dissemination is the activation of the epithelial-mesenchymal transition (EMT) regulating transcription factor ZEB1, and high expression of ZEB1 is associated with aggressiveness of UM.

Inhibition of ERO1a and IDO1 improves dendritic cell infiltration into pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and treatment resistant cancers. Due to its desmoplastic and hypoxic nature along with an abundance of myeloid cell infiltration and scarce T cell infiltration, PDAC is considered a cold tumor.

Methods: Here we sought to investigate myeloid cell infiltration and composition in PDAC spheroids by targeting the hypoxia-associated pathways endoplasmic reticulum oxidoreductase 1 alpha (ERO1a) and indoleamine 2,3-dioxygenase 1 (IDO1).

Erratum to: "Enhanced Liver Fibrosis® test predicts liver-related outcomes in the general population" (JHEP Reports 2023; 5: 100765).

[This corrects the article DOI: 10.1016/j.jhepr.

Deciphering the Role of p60AmotL2 in Epithelial Extrusion and Cell Detachment.

Preserving an accurate cell count is crucial for maintaining homeostasis. Apical extrusion, a process in which redundant cells are eliminated by neighboring cells, plays a key role in this regard. Recent studies have revealed that apical extrusion can also be triggered in cells transformed by oncogenes, suggesting it may be a mechanism through which tumor cells escape their microenvironment.

Waist-hip ratio is superior to BMI in predicting liver-related outcomes and synergizes with harmful alcohol use.

Background: Obesity is associated with liver disease, but the best obesity-related predictor remains undefined. Controversy exists regarding possible synergism between obesity and alcohol use for liver-related outcomes (LRO). We assessed the predictive performance for LROs, and synergism with alcohol use, of abdominal obesity (waist-hip ratio, WHR), and compared it to overall obesity (body mass index, BMI).

Combined use of the ELF test and CLivD score improves prediction of liver-related outcomes in the general population.

Background And Aims: Effective and feasible population screening strategies are needed for the early detection of individuals at high risk of future severe liver-related outcomes. We evaluated the predictive performance of the combination of liver fibrosis assessment, phenotype profile, and genetic risk.

Methods: Data from 5795 adults attending the Finnish Health 2000 Survey were linked with healthcare registers for liver-related outcomes (hospitalization, hepatocellular cancer, and death).