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Evidence suggests that testicular cancer (TC) originates from germ cell neoplasia in situ arising during fetal development, implying that prenatal environmental exposures may influence disease risk. We investigated whether maternal place of residence during pregnancy is associated with regional variation in TC incidence. We conducted a nationwide cohort study including 1,342,996 men born in Finland between 1960 and 1999. Participants were followed from birth until diagnosis of TC, death, emigration, or the end of follow-up (2021). A total of 2976 TC cases were identified. Information on municipality of birth was used as a proxy for maternal residence during pregnancy. Incidence rates and cumulative incidence were estimated by birth cohort and age at diagnosis. To examine regional variation, cumulative TC incidence by birth cohort and municipality was modeled using Bayesian hierarchical binomial regression allowing incidence to vary across municipalities. TC incidence increased across birth cohorts, peaking among men born in 1975-1979 (16.8 per 100,000). Cumulative incidence rose in all municipalities, ranging from 67.9 to 132.5 per 100,000 among men born in 1960-1969 and from 283.2 to 327.6 among those born in 1980-1989. Marked geographic clustering was observed. Incidence was consistently elevated among men born in southwestern Finland and remained high throughout the study period. Over successive birth cohorts, an eastward shift in higher incidence was observed. Although direct cohort evidence linking specific environmental exposures to TC remains limited, these findings support the hypothesis that prenatal environmental factors contribute to the pathogenesis of TC and may partly explain regional differences in incidence.

In 1975 clozapine was associated with 8 agranulocytosis deaths in Finland, leading to clozaphobia. In 1989 clozapine was approved in the United States (US) by the Food and Drug Administration (FDA) for treatment-resistant schizophrenia and in 2003 for suicide prevention. The FDA contributed to clozaphobia by focusing on the risk of agranulocytosis while ignoring other risks. On November 19, 2024, an FDA clozapine meeting reported 140,000 annual prescriptions and 0.03% mortality from agranulocytosis, and allowed patients' advocates to argue that the restrictions were costing millions of lives. In June 2025 the package insert eliminated the centralized database and hematological monitoring became "recommended". Four 2025 clozapine articles from this journal are used to initiate a rational discussion on suicide prevention and agranulocytosis risk. Suicide takes 5% of patients with schizophrenia, while long-term treatment with clozapine may prevent up to 80% of these deaths. US prescribers not willing to use clozapine need to consider long-acting injectable antipsychotics unless they want to contribute to the future 194,000 suicide deaths in patients with schizophrenia. For every future increase of 10,000 long-term clozapine prescriptions in schizophrenia, 400 US lives will be saved from suicide, costing 3 from agranulocytosis. More widespread clozapine usage may save an unknown number of lives among other treatment-resistant US psychiatric patients and in other countries. Worldwide, 4 million people with schizophrenia will kill themselves in the coming years; every 10% increase in clozapine usage may lead to saving 320,000 lives at a cost of 2,400 deaths from agranulocytosis.

BackgroundNurse researchers from six participating countries (Great Britain, Australia, New Zealand, USA, Finland and Denmark) collaborated on an international menopause study on nurses.PurposeTo demonstrate an iterative two stage thematic analysis within a qualitative paradigm as it applied to an international menopause study.MethodsUsing an exploratory approach, the Framework Method and Braun and Clarke's thematic analysis were applied to data from 48 participants.ResultsThe Framework method provided an organising structure capturing large amounts of narrative data into a structured matrix. Following detailing of the larger data set into abstracted categories, Braun & Clarke's thematic analysis method enabled researchers to abstract themes into specific narratives reflective of participants voices.ConclusionThe iterative thematic analysis approach enabled nurse researchers to effectively collaborate across different countries, different time-zones and different cultures to synthesise a large body of qualitative data in a systematic, structured approach. This research demonstrates an iterative systematic methodological approach that can be used by nurse researchers analysing data manually where other programmes are not available.

The aim of this review was to identify and examine psychological autopsy studies of physician and nurse suicide, with the overriding goal of better understanding circumstantial and psychological aspects of death. To the best of our knowledge, this represents the first review to examine psychological autopsy studies of physicians and nurses. A variety of search strategies were utilized. A literature search was conducted using medical databases, reference lists from articles were hand-searched, articles from academic websites were hand-searched, and articles from organizational websites were hand-searched. In total, eight psychological autopsy studies on physician suicide and one psychological autopsy study on nurse suicide were included. Physician and nurse suicide decedents from England and Wales, Finland, Thailand, and the United States were examined using psychological autopsy. Sociodemographic characteristics, occupational status, method(s) of suicide, location of suicide, and presence of a suicide note were inconsistently reported. Alternatively, histories, contributing factors, and circumstances preceding death were consistently reported. Specifically, physician and nurse suicide decedents often had history of mental health concerns, psychiatric hospitalization, and suicide attempt(s). Physician and nurse suicide decedents also often experienced current mental health concerns at time of death, particularly depressive disorders. Alcohol and substance use disorder sometimes occurred concomitantly. Taken together, additional research may be important in updating the evidence base. Additional psychological autopsy studies that include physician and nurse suicide decedents from different global regions may also be important in building the evidence base and in determining the generalizability of findings. Collectively, additional research is important, as psychological autopsy studies may provide important implications for research, surveillance, prevention, and intervention.

Bedside teaching is essential to instilling clinical and communication skills, and its benefits to both learners and patients are particularly notable in psychiatry. Bedside rounding has declined in teaching hospitals, however, a trend that may reflect constraints on teaching and clinical time, perceived inefficiency, and awkwardness for trainees. Creating safe and nonpunitive learning environments, maximizing efficiency, and formatting rounds to support learners are strategies that may reduce these barriers. In this column, the authors describe using dialogic practice, a method of communication derived from Finland's Open Dialogue approach, to integrate bedside teaching into psychiatry inpatient rounds. This is the first description of dialogic practice as a teaching tool rather than a clinical approach. In this model, teaching is integrated directly into the patient interview. The attending psychiatrist may step in to make an intervention or teaching point, then hand the interview back to the trainee. The authors demonstrate this method using example cases. The use of dialogic practice, which incorporates multiple voices in each encounter, allows for integrating feedback and teaching into clinical care. Patients benefit by feeling fully included in discussions about their care, while learners receive valuable real-time feedback that they can immediately integrate into the ongoing interview. Dialogic teaching is highly efficient while modeling valuable skills and respecting both the patient and the learner. It must, however, be implemented in a psychologically safe learning environment.

Recent advances in engineering adeno-associated virus (AAV) capsids capable of crossing the blood-brain barrier (BBB) have led to the development of numerous variants aimed at enhancing central nervous system gene delivery. Over the past decade, as new BBB-penetrant capsids were reported or independently identified through our own capsid library screening, we systematically evaluated their performance in adult marmosets, using a standardized experimental framework. Here, we present a cross-comparison of eleven AAV variants, predominantly AAV9-derived, alongside native AAV9 following systemic administration. Whole-brain reporter expression was quantitatively assessed using uniform imaging and analysis pipelines to enable relative comparison across animals. Under these conditions, most previously reported and newly identified BBB-penetrant variants-including those obtained through our own screening efforts-did not exhibit brain transduction levels clearly distinguishable from those of AAV9 based on whole-brain fluorescence intensity. In contrast, VCAP-102 consistently produced markedly higher brain-wide reporter expression across animals, accompanied by substantially increased vector genome copy numbers in the marmoset cortex, with most GFP-positive cells corresponding to neurons. These findings provide a systematic benchmark for evaluating BBB-penetrant AAV capsids in non-human primates and identify VCAP-102 as a highly efficient vector for systemic brain gene delivery.

Anatomical variants of the anterior cerebral artery (ACA) may increase technical complexity during endovascular treatment of distal ACA aneurysms (DACA). However, their impact on treatment outcomes remains unclear. This study evaluated whether ACA variants influence angiographic and clinical outcomes following endovascular treatment. A retrospective multicenter analysis was conducted using data from the CRETA Registry, including patients with ruptured and unruptured DACA treated endovascularly. Patients were grouped according to ACA anatomy (variant vs. conventional). Outcomes were compared after propensity score matching (PSM) to adjust for confounders including age, aneurysm rupture status, dome-to-neck ratio, branch origin, and treatment type. The primary outcome was aneurysm occlusion at last follow-up based on the Raymond-Roy classification. Secondary outcomes included ischemic and hemorrhagic complications, vasospasm, and clinical outcome measured by the modified Rankin Scale (mRS). After PSM, 128 patients were included (64 per group). Among patients with available imaging follow-up (54 in the conventional group and 55 in the variant group), adequate occlusion rates were comparable between the variant and conventional ACA groups (81.5% vs. 85.5%; p = 0.600). No significant differences were observed in ischemic or hemorrhagic complications, vasospasm, or long-term clinical outcomes. Sensitivity analyses confirmed the robustness of the findings. ACA anatomical variants do not adversely affect the safety or efficacy of endovascular treatment for DACA. With appropriate anatomical assessment and treatment selection, endovascular therapy remains effective even in the presence of complex ACA configurations.

Incendiary weapons (IW) have been used in 21st-century armed conflicts, causing severe burn injuries with lifelong physical and psychological consequences. Existing international law has shortcomings that have undermined its ability to adequately address the human cost of IW. While the harm from IW has been reported, limited standardized clinical data on their medical effects, in addition to high-quality evidence on treatment protocols, exist. No structured assessment of existing literature on this topic exists. This review seeks to address this gap. A scoping review was conducted to evaluate existing literature and identify evidence gaps regarding the medical effects and management of IW injuries in 21st-century armed conflict. A systematic search strategy was performed using standardized inclusion criteria. A standardized extraction form was used to capture data elements for description in both peer-reviewed and grey literature. Our search identified 14,050 records for screening across peer-reviewed and grey literature that were narrowed to 56 included reports. A total of 5565 patients were specifically reported to be affected by IW across 26 countries; however, there was a lack of homogeneous reporting across all categories of interest. Available reports described severe and multidimensional injuries with lack of consensus regarding both diagnosis and treatment of IW injuries. Available data regarding IW use, injury, and treatment are heterogeneous, limiting epidemiological analysis to inform care and practice guidelines. The described injuries raise the need for standardized data collection and focused training on IW care in conflict settings. Global databases to strengthen the evidence base on IW casualties are needed to enhance policy efforts, diagnosis and treatment standards, and trainings, which will in turn improve clinical performance.

To evaluate the prevalence of comorbidities preceding the diagnosis of psoriatic arthritis (PsA) compared with the general population. We identified all adult patients granted a special reimbursement (SR) for disease-modifying anti-rheumatic drugs for PsA between 2002 and 2014 from the Finnish Social Insurance Institution register (N&#x2009;=&#x2009;6077). Three general population controls were matched to each case. Visits to specialized medical care (Classification of Disease 10th revision coded), and prescription drug purchases categorized by Anatomical Therapeutic Chemical codes were collected for cases and controls between 2000 and 2014. We evaluated the period from 24 months before to 3 months after the index date (ID), defined as the date when the SR was granted. SRs granted for other chronic diseases prior to the ID were additionally collected. PsA patients had three times more visits to specialized medical care and increased overall drug use compared with controls. Based on SRs valid at the time of PsA diagnosis, new-onset PsA patients had significantly higher prevalence of diabetes mellitus (women: 11% vs. 7%; men: 14% vs. 10%; all p&#x2009;<&#x2009;0.001), cardiovascular diseases (women: 19% vs. 14%; men: 23% vs. 18%; all p&#x2009;<&#x2009;0.001), and obstructive lung diseases (women: 12% vs. 7%; men: 8% vs. 6%; all p&#x2009;<&#x2009;0.001) compared with controls. PsA patients demonstrate increased morbidity already at the time of PsA diagnosis. Screening for comorbidities should therefore be considered when joint disease is clinically apparent.

To provide a comprehensive analysis regarding outcomes of repeated screening and detection of low-grade versus high-grade cancer from the European Randomised Study of Screening for Prostate Cancer (ERSPC). This study analysed men aged 55-69&#x2009;years at random across the ERSPC trial centres except France. Men in the screening arm were classified as ever-attenders (who attended at least one screening cycle) or non-attenders (who did not attend a specific screening cycle). Cancer detection rates (CDRs) were calculated by age group and centre across three screening cycles. A secondary analysis incorporated interval prostate cancer (PCa) cases-those diagnosed outside the screening protocol-among both ever-attenders and non-attenders. Incidence data from the control arm were included for comparison. Based on screen-detected cases, CDRs were consistently higher for low-grade than for intermediate- and high-grade cases across all centres and screening cycles. Trends in CDRs for high-grade cases varied by centre: CDRs decreased from the first to the second cycle and increased again during the third cycle in most centres, whereas CDRs increased in Spain with each successive screening cycle. The ERSPC data show a decreasing detection rate for low-grade cancer and substantial variation in the detection rate for intermediate- and high-grade cancer between centres across repeated screening rounds. Increasing interval and non-attender cancers indicate diminishing effectiveness of uniform screening schedules. These findings support personalised screening approaches and improved strategies to maintain participation.

The intestinal epithelial lining is highly dynamic, with size and cellular composition adapting to nutrient status. This requires regulation of intestinal stem cell (ISC) proliferation and enterocyte (EC) size. How the intestinal absorptive area matches physiological nutrient conditions remains unclear. Here, we show that the Nuclear Factor Y (NF-Y) transcription factor plays a role in this process. NF-Y loss-of-function (LOF) in ISCs led to high proliferation and cell growth, a phenotype influenced by dietary nutrients. NF-Y LOF also increased nutrient metabolism, as shown by more mitochondria and larger lipid droplets in progenitors. Mechanistically, NF-Y restrains mTOR complex 1 (mTORC1) activity in ISC by controlling transcription of mTORC1 signaling components such as Pras40 and Sestrin. Overall, our results demonstrate that NF-Y limits excessive nutrient-adaptive intestinal epithelial growth.

Glucose is traditionally viewed as a substrate for ATP production and glycogen storage in skeletal muscle. Here, we review evidence that glucose also serves as a building block for biomass synthesis in proliferating muscle satellite (stem) cells and hypertrophying skeletal muscle fibers, drawing parallels to anabolic metabolic reprogramming in cancer cells. In cancer and other growing cells, increased glucose uptake, aerobic glycolysis (Warburg effect), and the TCA cycle provide substrates for anabolic pathways that generate macromolecules required for growth and proliferation. Radiotracer studies in mammalian cancer and muscle cells demonstrate that approximately 8-15% of the cell dry mass originates from glucose. Mechanistic insights, obtained predominantly from cell culture models, indicate that glucose-derived glycolytic and TCA cycle intermediates provide substrates for serine synthesis and the pentose phosphate pathway, glycine and one-carbon metabolism, non-essential amino acid synthesis, nucleotide and lipid synthesis as well as for epigenetic methylation and acetylation. We further review evidence that human resistance training, hypertrophy through muscle-specific expression of Akt1 in mice, loss or inhibition of myostatin/activin signaling, and other hypertrophy-inducing interventions improve glucose homeostasis under conditions of obesity, insulin resistance, and type 2 diabetes. We discuss the possibility that glucose incorporation into biomass contributes to this effect.

Plumage colour in domestic geese is an important economic trait and a selection target since the early days of domestication. In European domestic geese of greylag goose (Anser anser) origin, white plumage is known to be determined by two independent loci, one causing white spotting and another sex-linked dilution, together producing white plumage. Strong candidate genetic variants have been identified upstream of the EDNRB2, that is, LOC106047519 gene (endothelin receptor B-like) and within the sex-linked MLANA gene (melan-A). To confirm these candidate variants, we genotyped differently coloured European domestic goose breeds, wild greylag geese, Chinese domestic geese (derived from swan goose A. cygnoid) and European and Chinese domestic geese crossbreeds. One base pair deletion in the MLANA gene (NW_013185876.1: g.950868 C>-) was confirmed to cause sex-linked dilution, and thus autosexing (almost white gander and diluted grey goose). However, a genetic variant upstream of EDNRB2 (NW_013185915.1: g.775151&#x2009;G>T) was not causative of saddleback pattern but strongly linked to it in European domestic geese. We sequenced the EDNRB2 gene and coding sequence of a neighbouring VAMP7 gene (vesicle-associated membrane protein 7) but found no genetic variation linked to colour. Additionally, we sequenced the coding sequence of TYRP1 (tyrosinase related protein 1), a candidate gene for buff colouration, but no variation linked to colour was found. Further, we genotyped a 14-bp insertion in exon 3 of the EDNRB2 gene, known to be causative of the white phenotype in the Chinese domestic goose, and identified it in one European domestic goose.

When training new skills, it is beneficial if they generalize to new items beyond those explicitly trained. In this study, we investigated whether game-based training of second-language speech sounds and words affects the processing of untrained sounds, specifically focusing on the pitch of nonspeech sounds. Thirty-seven school-aged children participated in a longitudinal study with two or three measurement points, during which mismatch negativity (MMN) responses were recorded using electroencephalography. The treatment group received 4-5&#x2009;weeks of game-based training between the first and second measurement sessions. The delayed-treatment group waited for 4-5&#x2009;weeks between the first and second sessions and then received the game-based training, the effects of which were assessed in a third session. Results showed that MMN peak amplitude increased across measurement sessions. However, MMN latency decreased in the treatment group following the gaming period, whereas it increased in the delayed-treatment group. After receiving the game-based training, MMN latency decreased also in the delayed-treatment group. This pattern of results suggests that the effects of second-language speech training may generalize to the processing of untrained, nonspeech sounds. The observed improvement in pitch processing may be due to the link between pitch perception and phonological skills targeted by the game-based training. Additionally, the gaming approach itself may contribute to the reduction in MMN latency. Taken together, the findings indicate that second-language speech training can enhance neural processing of untrained auditory stimuli, thereby demonstrating cross-domain auditory plasticity.

Family environments play a critical role in shaping children's lifestyle behaviours that influence obesity risk. However, culturally validated instruments to assess these behaviours are lacking in Portuguese primary care. This study aims to translate and culturally adapt the Family Nutrition and Physical Activity (FNPA) screening tool for use in Portugal (FNPA-PT) and to evaluate its face and content validity through cognitive interviews with parents attending well-child visits. An exploratory, descriptive study followed internationally endorsed guidelines (Beaton; MAPI) for translation and cross-cultural adaptation. The process comprised seven stages: forward translations, synthesis, back translations, comparisons of back translations, expert committee review, cognitive debriefing and final proofreading. Ten parents of five-year-old children attending a public primary care centre in Lisbon completed the FNPA-PT while participating in individual cognitive interviews. Data were analysed using Content Analysis, guided by Tourangeau's four-stage response model. Semantic equivalence between forward and back translations was high (85% of items with satisfactory or perfect equivalence). Minor linguistic and cultural adaptations were introduced to improve clarity and contextual relevance. Cognitive interviews indicated that the FNPA-PT was well understood, acceptable to parents, and feasible to complete during well-child visits. Parents valued the questionnaire's comprehensiveness and its potential to enhance awareness and stimulate discussion about family health behaviours. Minor revisions addressed comprehension issues in three items related to milk consumption, screen time and sleep. The FNPA-PT demonstrated strong face and content validity and high acceptability among Portuguese parents. It provides a culturally appropriate, family-centred tool for health professionals to support early identification of obesogenic environments and to guide preventive counselling in primary care. The study also offers a transparent methodological pathway for translating and adapting behavioural measures across languages and settings.

Peri-implant diseases are characterized by complex host-microbe interactions. This study aimed to investigate the levels of pro-apoptotic Bcl-2 family proteins and their relationship with Porphyromonas gingivalis-gingipain and Treponema denticola-dentilisin in peri-implant tissues. Tissue samples were collected from 72 participants: healthy controls (n&#x2009;=&#x2009;24), peri-implant mucositis (n&#x2009;=&#x2009;23), and peri-implantitis (n&#x2009;=&#x2009;25). Levels of pro-apoptotic proteins (Bax, Bad, Bim, Smac, and Lamin B) quantified via multiplex immunoassays, and proteases were analyzed using western blotting and normalized to total protein content. Regression models adjusted for age and clinical parameters assessed associations between microbial protease levels and apoptotic proteins. Pro-apoptotic protein levels were significantly lower in diseased sites compared to healthy controls (p&#x2009;<&#x2009;0.001). While absolute protease levels did not differ significantly between groups (p&#x2009;>&#x2009;0.05), multivariate regression models, adjusted for clinical parameters, revealed significant associations between gingipain/dentilisin and Bax/Bad levels (p&#x2009;<&#x2009;0.05). The downregulation of pro-apoptotic proteins suggests a suppressed apoptotic response in peri-implant lesions, potentially contributing to disease persistence. The preliminary associations between bacterial proteases and apoptotic markers, independent of clinical severity, highlights these virulence factors as potential modulators of tissue homeostasis and candidates for future diagnostic and therapeutic targets. Bacterial proteases show modest associations with host apoptotic pathways in peri-implant diseases. A better understanding of these relationships may potentially help develop new preventive and therapeutic strategies in the future.

To achieve a more comprehensive understanding of cancer, novel computational methods are required for the integrative analysis of data from different molecular layers, such as genomics, transcriptomics, and epigenomics. Here, we present an innovative multi-omics integrative method that performs unsupervised representation learning, referred to as OMIDIENT: multiOMics Integration for cancer by DIrichlet auto-ENcoder neTworks. OMIDIENT provides a natural framework for modeling sparse and compositional latent representations by employing a deep generative model, where the latent space is distributed as the product of Dirichlet distributions. Applied to five different cancers, we demonstrate that OMIDIENT outperforms the top state-of-the-art unsupervised multi-omics integrative analysis approaches in clustering, classification, and reconstruction of missing data using mRNA expression data, DNA methylation data, and microRNA expression data. Furthermore, we provide interpretability analyses for OMIDIENT that not only support its improved performance, but also offer valuable insights into the underlying structure captured by the learned representations.