The answer to the question, "Is Roger Bacon's scientific practice scientific?" concerns an assessment of whether Bacon's scientific practice exhibits traits of modern science. This paper uses the theoretical framework proposed by Hon and Goldstein (2023) for defining modern science, which identifies three salient, constitutive features: commitment, methodology and technique. These features function together as a skeleton of the argumentative structure which combines presuppositions and rules of inference to reach a conclusion. The fundamental assumption is that scientific knowledge is argumentative. Against this background we examine three scientific results that Bacon included in his Opus majus. Although Bacon's methodology involves the use of geometrical proofs and his technique employs diagrams and geometrical analysis of the relations embedded in them-both features seemingly indicative of modern scientific practice-a characteristic alien to modern practice surfaces in the feature Hon and Goldstein refer to as "commitment." Specifically, Bacon's commitment is rooted in theology and its dependence on sacred scripture. It is this characteristic that sets Bacon's scientific practice apart from modern science. In a nutshell, Bacon's commitment implies that final causes are not directly and fully known from the natural world but are revealed through scripture. Consequently, since understanding the nature of a thing requires knowing all four Aristotelian causes, those ignorant of sacred scripture cannot grasp the final cause and thus miss the true nature of the thing. It thus follows that Bacon's approach is not what we associate with modern science.
This project elucidates the pivotal scientific discoveries that culminated in the isolation of luteinizing hormone-releasing hormone (LH-RH). It details the contributions of scientists Andrew Schally and Roger Guillemin, whose competitive biochemical research led to the Nobel Prize in 1977. This project entails a comprehensive review of the pivotal scientific developments that culminated in the discovery of LHRH, examined through the historical lens. The sources included peer-reviewed articles, Nobel lectures, and oral history transcripts. G.W. Harris first showed the anterior pituitary's regulation by the hypothalamus in 1937, establishing the principles for Schally and Guillemin. Schally and Guillemin independently isolated TRF in 1969, requiring 160,000 porcine hypothalami for purification. Both then pursued LHRH, isolating it independently in 1971 using 240,000 porcine brains and developing advanced biochemical techniques. These methods have enabled LHRH analog synthesis for prostate cancer research. In 1971, Schally demonstrated that LHRH could suppress gonadotropin secretion. Synthetic LHRH infusion in monkeys showed LHRH's ability to desensitize pituitary GnRH receptors. This discovery enabled the use of LHRH analog treatments for hormone-sensitive conditions. Schally conducted the first clinical trials in Mexico in 1972 and organized the first LHRH agonist study for prostate cancer, which was published in 1982. The discovery of LHRH represents a landmark convergence of evolving physiological concepts, rigorous biochemical innovation, and impactful clinical translation, leading to the Nobel Prize. The rivalry between Schally and Guillemin led to foundational discoveries that transformed the management of androgen-dependent malignancies.
Reports an error in "Rapid cognitive screening of patients with substance use disorders" by Marc L. Copersino, William Fals-Stewart, Garrett Fitzmaurice, David J. Schretlen, Jody Sokoloff and Roger D. Weiss (Experimental and Clinical Psychopharmacology, 2009[Oct], Vol 17[5], 337-344; see record 2009-17802-007). In the article, scoring instructions in the MoCA Assessment subsection of the Method section included an erroneous parenthetical statement: "(31 if the patient is age 12 or younger)." This statement should have read "(with one point added if the patient has 12 years or fewer of formal education)." This error does not reflect how assessment data were collected in the study and does not affect the results or the conclusions drawn from the data. (The following abstract of the original article appeared in record 2009-17802-007). To date, there has not been a time-efficient and resource-conscious way to identify cognitive impairment in patients with substance use disorders (SUDs). In this study, we assessed the validity, accuracy, and clinical utility of a brief (10-min) screening instrument, the Montreal Cognitive Assessment (MoCA), in identifying cognitive impairment among patients with SUDs. The Neuropsychological Assessment Battery-Screening Module, a 45-min battery with known sensitivity to the mild to moderate deficits observed in patients with SUDs, was used as the reference criterion for determining agreement, rates of correct and incorrect decision classifications, and criterion-related validity for the MoCA. Classification accuracy of the MoCA, based on receiver operating characteristic (ROC) analysis, was strong, with an area under the ROC curve of 0.86, 95% confidence interval [0.75, 0.97]. The MoCA also showed acceptable sensitivity (83.3%) and specificity (72.9%) for the identification of cognitive impairment. Using a cutoff of 25 on the MoCA, the overall agreement was 75.0%; chance-corrected agreement (kappa) was 41.9%. These findings indicate that the MoCA provides a time-efficient and resource-conscious way to identify patients with SUDs and neuropsychological impairment, thus addressing a critical need in the addiction treatment research community. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Evidence for After Action Reviews (AAR), a non-hierarchical debriefing approach, is limited. We explored AAR implementation and measured safety culture and second victim experience and support, before and after introduction of AAR at an Irish hospital. A mixed-methods study which coincided with the COVID-19 pandemic and a health system cyber-attack was conducted. Hospital selected staff were trained as AAR facilitators using a simulation-based programme (July-Sept 2021). The intervention was the hospital introduction of AAR over 12-months (Sept 2021-Aug 2022). Before training, the Hospital Survey on Patient Safety 2.0 (HSOPS 2.0) and Second Victim Experience and Support Tool (SVEST) were distributed to all staff (N = 586), and repeated at 12-months with additional questions on AAR awareness, frequency and duration. At 6-months, focus groups with trained facilitators explored implementation enablers and barriers. Costs were estimated. Quantitative analysis used chi-squared, Fisher's exact and t-tests to compare pre-/post- responses. Qualitative data was analysed using the Capability, Opportunity, Motivation - Behaviour (COM-B) model. Findings were integrated via triangulation, and the level of implementation was categorised using Roger's theory of the diffusion of innovations. Nine per cent (n = 50) of staff were trained as AAR facilitators. Survey response rates were 33% pre- and 16% post- AAR implementation. After 12-months, 37% of staff were aware of AAR and 10% had participated in one, at €48 average cost. Approximately, 39 AARs were conducted. The ratio of informal to formal AARs was 2.6:1. No change in overall safety culture occurred despite a pandemic and cyber-attack. Response to error improved. Triangulation of results confirmed improvement in response to error was associated with staff awareness and participation in AAR. Second victim experience and support showed no change in psychological and physical distress, yet professional self-efficacy, perceived organisational support and turnover intentions worsened, with no observed association with AAR. Simulation-based training and national-level policy supported early adoption of AAR. Implementation of AAR was associated with improved response to error at the hospital, but not second victim experiences.
Patients' preferences are crucial to formulating personalised treatment plans. We developed a self-reported questionnaire, therapy preference scale (TPS), to examine treatment preferences of patients with cancer. TPS has 30 questions: 19 on patients' preferences on safety, quality of life and treatment effectiveness, 8 questions on the importance of various treatment characteristics and 3 on patients' preferred intent of therapy, expenses and life expectancy gain. We recruited 300 adults >18 years with a cancer diagnosis and categorised them into 4 age-by-sex groups (younger men <60 years, older men ≥60 years, younger women< 60 years, older women ≥60 years). Kruskal-Wallis non-parametric ANOVA method was used to compare responses among four groups. Older women, compared to other groups, were more likely to value maintenance of cognitive function and ability to perform daily activities. Older women were more likely to risk having a shorter life expectancy rather than facing the risk of long-term cognitive impairments. Younger men and women were more likely to accept more effective treatment, even if it caused significant pain. A higher percentage of younger men, compared to other groups, valued maintaining sex life. Older men and women were more likely to prefer oral pills over intravenous therapy. Patient preferences may vary based on age and sex, with older women prioritising cognitive and physical function independence more frequently, whereas younger men and women are willing to pursue more effective treatment options even with a greater risk of significant pain. TPS can elicit detailed preferences of an individual patient to facilitate shared decision-making with their oncologists.
Precise and spatially controlled modulation of peripheral arterial tone is important for treating microvascular disorders. Current pharmacological vasodilators are typically systemic and lack local specificity. Light-induced photorelaxation has been proposed as an alternative method for vascular modulation. However, its structural and hemodynamic effects in vivo have not been fully characterized. In this study, real-time functional optical coherence tomography (OCT) was used to visualize and quantify blue-light-induced peripheral arterial photorelaxation in living mice. Arteries in the femoral, tail, and auricular regions were exposed to 473-nm blue-light stimulation and imaged using OCT angiography and Doppler OCT to monitor changes in vessel diameter and blood flow. Blue-light stimulation induced rapid, reversible, and artery-selective vasodilation with minimal effects on adjacent veins. Flow velocity decreased during stimulation, whereas the increase in vessel cross-sectional area resulted in higher volumetric blood flow. The vasodilatory response was retained in single opsin-deficient mouse models (Opn3-/-, Opn4-/-, and Opn5-/-) but was absent in Opn4/Opn5 double-knockout mice, indicating a cooperative role of non-visual opsins. These findings demonstrate increased local perfusion during optical stimulation and highlight the potential of photorelaxation as a spatially targeted approach to vascular modulation.
Metabolic dysfunction-associated steatotic liver disease (MASLD) progresses along a continuum from simple steatosis to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. However, current clinical and research frameworks rely primarily on static, histology-defined stages that fail to capture the continuous nature of disease progression. Here, we present a data-driven framework that reconstructs MASLD progression as a continuous molecular trajectory from cross-sectional liver transcriptomic profiles. By positioning patients along this trajectory, we move beyond conventional stage-based classifications and resolve the ordered activation of regulatory programmes, signalling pathways and cellular remodelling processes underlying disease progression. To enable non-invasive patient stratification, we integrate the inferred molecular trajectory with paired liver-plasma proteomics data and identify a 57-gene plasma-accessible biomarker panel that accurately predicts advanced fibrosis and continuously positions patients along the disease trajectory across independent cohorts, outperforming established non-invasive clinical scores. Together, this work establishes a generalizable trajectory-based framework for understanding MASLD pathophysiology and provides a foundation for mechanistically informed biomarker discovery, precision staging and stage-aware therapeutic prioritization.
To examine the association between body mass index (BMI), Body Roundness Index (BRI), and A Body Shape Index (ABSI), with handgrip strength (HGS) and dynapenia in postmenopausal women. This is a cross-sectional study involving 259 postmenopausal women. Age, age at menopause, alcohol consumption, height, weight, waist circumference, and smoking status were recorded. BMI, BRI, and ABSI were separately calculated. Serum creatinine, glucose, glycated hemoglobin, and uric acid were evaluated. HGS was measured using a digital dynamometer, and physical activity was assessed by the International Physical Activity Questionnaire. Student t test, χ2 test, Pearson correlation coefficient, and multivariable linear and logistic regression models were performed for data analysis. HGS was not correlated with BMI (r=-0.004, P=0.930), BRI (r=-0.080, P=0.190), and ABSI (r=-0.019, P=0.750). The multivariable linear regression models showed that HGS was not significantly associated with BMI (β= 0.01; 95% CI, -0.11 to 0.12), BRI (β= -0.04; 95% CI, -0.34 to 0.25), and ABSI (β= 43; 95% CI, -38 to 124). The multivariable logistic regression models displayed no significant association between dynapenia with BMI (OR= 1.00; 95% CI, 0.92-1.09), BRI (OR= 1.06; 95% CI, 0.84-1.34), and ABSI (OR= 0.80; 95% CI, 0.55-1.14). There were no associations between BMI, BRI, and ABSI with HGS. Furthermore, in postmenopausal women, dynapenia was also not associated with these anthropometric indices of obesity.
The emergence of antigenically distinct SARS-CoV-2 variants increases the risk of immune escape and requires continually updated vaccines. In addition, short-lived specific immunity is a limitation faced by current COVID-19 mRNA vaccines against Sarbecoviruses. This underscores the need for new vaccine approaches providing lasting immunity against SARS-CoV-2. Here, we demonstrate the capacity of two non-adjuvanted subunit vaccines to induce long-lasting and protective immunity against SARS-CoV-2 variants in macaques. We designed antibody-mediated vaccines (AMV) leveraging an anti-CD40 monoclonal antibody to enhance immune responses by targeting selected antigens to antigen-presenting cells through the CD40 receptor. The CD40.RBDv vaccine targets sequences from the original Wuhan RBD and a mutated RBD, while CD40.Pan.CoV incorporates a conserved nucleocapsid sequence and a mutated RBD region. We show that both adjuvant-free vaccines induce robust and durable systemic and mucosal anti-RBD antibody responses that neutralise multiple SARS-CoV-2 variants in naive and SARS-CoV-2 convalescent animals, including recent variants such as XFG. In convalescents, mathematical modelling predicted persistence of vaccine-induced antibody for decades. Additionally, the vaccines boost immune responses in mRNA-vaccinated animals, demonstrating the efficiency of CD40-based vaccines as boosters. Both vaccines protect animals against B.1.617.2 Delta and BA.1 Omicron challenges. Viral control correlates with vaccine-induced systemic and mucosal antibody levels and T-cell responses. These findings support the ability of AMV targeting CD40 to induce strong, long-lasting responses against adapted antigens and broad protection against evolving SARS-CoV-2 variants without requiring adjuvant. These two vaccine candidates are currently under clinical testing. The Investissements d'Avenir program (ANR-10-LABX-77-01 and ANR-11-INBS-0008), the PSPC COVID-19 - Project EVIDENCE.
To ensure patient safety, nursing students must acquire sufficient bioscience knowledge. Previous research has emphasized the importance of high-quality learning environments and opportunities for students to act upon their learning needs. However, to our knowledge, no studies have examined nursing students' construction of learning spaces in bioscience from an ecological perspective. This study explores how undergraduate nursing students use elements in their learning environment and construct their learning space within a bioscience course. A qualitative descriptive design was employed. Three focus group interviews were conducted in April 2024, facilitated by an interview guide, to collect qualitative data from 17 first-year nursing students. The data were analyzed using systematic text condensation, followed by interpretive analyses. Three categories emerged from the data analysis: 1) high expectations and a belief in succeeding, 2) standing together, even when alone, and 3) freedom within established frameworks. The findings underscore the importance of a supportive and flexible learning environment that acknowledges students' agency and social dynamics. Drawing on ecological theory, we posit that learning spaces are co-constructed through interactions among students, resources, and institutional structures. Elements in the learning environment should therefore balance structure with flexibility, foster competence through optimal challenge, and promote inclusive relatedness to sustain motivation and meaningful engagement.
Pure laparoscopic donor right hepatectomy (PLDRH) is a safe technique, but its learning curve is often oversimplified. This study evaluates variables contributing to evolutional patterns for mastering PLDRH. Consecutive donors undergoing PLDRH at a single center (2014-2021) were collected. A cumulative sum (CUSUM) method assessed a composite score derived from graft weight (GW), bile duct (BD) anatomy, operative time (OT), and warm ischemia time (WIT). Segmented regression identified the statistical breakpoint in the composite learning curve. Among 215 donors, no conversion occurred. Major post-operative complications (Clavien-Dindo ≥ 3) were reported in 2 (0.9%) cases with no mortality. CUSUM analysis identified a significant technical breakpoint at case 180 (p < 0.001). While OT and WIT improved after 60 cases (p < 0.001), surgical complexity, specifically GW and multiple BD, simultaneously increased between 60 and 180 cases. This demonstrates a multiphasic learning process where technical maturity was achieved by case 180, maintaining high safety standards despite progressive inclusion of larger grafts and more complex anatomy. The PLDRH learning curve is multifactorial and non-linear. While approximately 60 cases suffice for technical standardization, achieving full mastery over complex donors requires further caution. This multifactorial "evolutional" approach provides a comprehensive understanding for targeted improvement and surgical coaching.
Site rate and profile mixture models capture the heterogeneity of the amino acid substitution process across sites. However, these models typically use a single matrix of amino acid exchangeabilities and ignore potential heterogeneities of these exchangeabilities across sites. Simply combining multiple exchangeability matrices with rate and profile mixtures leads to a combinatorial explosion of mixture components and a prohibitive increase in free parameters. Here, we introduce GTRspmix, a novel framework that incorporates multiple exchangeability matrices into profile and site rate mixture models while effectively managing model complexity. GTRspmix employs a clustering-based strategy that groups profiles and assigns a distinct exchangeability matrix to each profile cluster. Evaluations using both empirical and simulated datasets demonstrate that GTRspmix fits empirical data significantly better than conventional models, and that overparameterization does not present a problem for sufficiently large alignments. Based on these results, we estimated general-purpose empirical models (SXXpfamCYY series available in IQ-TREE3) from the Pfam database. These general-purpose models not only fit data much better, but they also influence branch length and tree topology estimates, effectively mitigating long-branch attraction artifacts. Because the total number of rate matrices remains manageable, the computational efficiency of the inference is identical to that of conventional profile mixture models (e.g., LG+C60+G4). GTRspmix provides a more realistic and flexible model of protein evolution, offering a robust foundation for the inference of reliable phylogenetic trees.
Contact zones, where genetic lineages meet, provide a unique opportunity to study speciation and reveal how reproductive barriers emerge.1,2,3 However, species ranges are dynamic, contact zones may be ephemeral,4,5 and reinforcement-selection against hybrids-is an elusive phenomenon.6,7,8 We use an integrative approach-genomic, chemical, and morphological data coupled with ecological and demographic modeling-to evaluate lineage limits, reconstruct contact history, and infer reproductive isolation strength and mechanisms in the protected Clouded Apollo butterfly (Parnassius mnemosyne) in Europe.9 The status of this taxon is highly debated: a potential cryptic species (Parnassius turatii) edging P. mnemosyne sensu stricto in the Eastern Alps has been proposed, yet evidence remains inconsistent in the absence of genomic data.10,11,12,13,14,15,16,17,18 We reveal two genetic lineages that diverged about 0.8 million years ago and experienced two successive episodes of secondary contact. During the last glaciation, the lineages met in western Europe, which resulted in admixture and the formation of hybrid Pyrenean populations before reproductive isolation had evolved. In contrast, genomic data show no detectable gene flow at their present-day contact zone in the Eastern Alps, despite morphological and ecological similarity. Evidence of mutual chemical character displacement in males at this contact suggests bidirectional reinforcement in action. These findings portray a system in which lineages that once exchanged genes now re-encounter each other and reproductive isolation is generated-a second chance for speciation to succeed-and demonstrate that the Clouded Apollo comprises two cryptic species, with implications for EU legislation implementation and IUCN assessments.9,19,20.
[This corrects the article DOI: 10.1016/j.ekir.2026.106364.].
Background: Cage subsidence after minimally invasive transforaminal lumbar interbody fusion raises revision risk and costs. Intraoperative computed tomography (CT) provides high-resolution, three-dimensional visualization of the endplate-cage interface and serves as a practical-though itself imperfect-reference standard for early subsidence, but it is not available at all institutions. Plain X-ray is widely available and inexpensive, but lower in resolution. The clinically relevant question is therefore not whether CT and X-ray are equivalent, but rather which X-ray protrusion depth measurement most reliably identifies CT-confirmed subsidence, and whether a positive intraoperative CT meaningfully predicts later radiographic subsidence. Objective: Using intraoperative CT as reference, we aimed to (1) determine the optimal X-ray protrusion depth threshold for CT-confirmed early subsidence; (2) test whether intraoperative CT predicts late radiographic subsidence; and (3) examine how early X-ray depth relates to intervertebral disc height (IVDH) and segmental lordosis (SL) loss. Methods: In a retrospective single-surgeon cohort (March 2015-July 2023), subsidence was defined as ≥2.0 mm endplate penetration on CT and measured on X-ray by parallax technique. Sensitivity, specificity, accuracy, and Cohen's κ were calculated. Receiver operating characteristic (ROC) analysis evaluated X-ray depth as a continuous predictor and identified the Youden-optimal cutoff. Intraoperative CT was tested against late radiographic subsidence; no-intercept linear models estimated per-millimeter IVDH and SL loss. Results: Of 100 patients, 93 had paired imaging (mean age 66.7 years; body mass index 26.8 kg/m2). Subsidence appeared on CT in 16.1% and on X-ray in 15.1%. X-ray showed 80.0% sensitivity, 97.4% specificity, 94.6% accuracy, and κ = 0.80; ROC analysis demonstrated strong discrimination (area under the curve 0.91; 95% confidence interval 0.81-1.00), Youden-optimal cutoff 1.90 mm. Intraoperative CT predicted late subsidence (n = 76) with only 45.8% sensitivity and 96.2% specificity; missed cases had penetration depths indistinguishable from non-subsiders. Each 1 mm of early X-ray depth corresponded to 0.45 mm IVDH and 0.37° SL loss. Conclusions: An X-ray protrusion depth of 2.0 mm reliably identifies CT-confirmed early subsidence, providing a preliminary diagnostic cutoff for use when CT is unavailable. Intraoperative CT is highly specific but insensitive for late subsidence; meaningful risk stratification will require additional inputs. These hypothesis-generating findings warrant prospective validation.
Carbon dioxide (CO₂) is one of the infamous greenhouse gases, resulting in increased global temperature and climate change. The steady rise in atmospheric CO₂ levels, primarily driven by anthropogenic activities, poses serious environmental and socio-economic challenges. Understanding and forecasting CO₂ emission trends are essential for guiding global mitigation efforts and assessing progress toward climate commitments. In this study, we aim to investigate the monthly CO₂ emission trend from direct measurement data collected by the National Oceanic and Atmospheric Administration and build predictive models from three different modeling approaches: statistical: autoregressive integrated moving average, seasonal autoregressive integrated moving average; machine learning: Random Forest, adaptive boosting; and deep learning models: long short-term memory, gated recurrent unit. We constructed and trained multiple model configurations through a data-driven approach, then evaluated and selected a top-performing model from each category, enabling a robust performance comparison. Based on the experimental results on test data, the Random Forest model with 250 decision trees outperformed all other models with the best scores: root mean square error 0.2401, mean absolute percentage error 0.0005, and directional accuracy 0.9544. Forecasting was performed for the next 3 years from the top-performing models in each category. Experimenting from statistical to state-of-the-art deep learning models, this study serves as a baseline case study for developing advanced computational frameworks on emission data forecasting for the future. Overall, this research provides valuable tools and perspectives for climate scientists, stakeholders, and policymakers aiming to combat climate change through informed, predictive strategies.
Clear cell renal cell carcinoma (ccRCC) is largely driven by the transcription factor hypoxia-inducible factor 2α (HIF-2α)1. Here we show that monotherapy with casdatifan-an orally bioavailable, potent and selective HIF-2α inhibitor2-produces meaningful, durable antitumour activity with manageable safety in individuals with refractory metastatic ccRCC. Dose-expansion data from the ARC-20 study ( NCT05536141 ) are presented, including for the 100 mg once daily (QD) cohort (n = 32) and the total cohort (n = 127). Treatment discontinuation from casdatifan-related adverse events was infrequent (3%), and class-effect toxicities included anaemia and hypoxia. The confirmed objective response rates (ORRs) were 35% (95% confidence intervals (CI) = 19-55%; 100 mg QD) and 31% (95% CI = 23-40%; total); median progression-free survival (PFS) was not estimable (95% CI = 5.7-not estimable; 100 mg QD) and 12.2 months (9.4-20.6; total). Greater maximal reductions in serum erythropoietin were associated with improved clinical outcomes, including a higher ORR (P = 0.001), lower rates of progressive disease (P = 0.003) and longer PFS (P = 0.006). Erythropoietin expression was restricted to cancer cells and was significantly higher at the mRNA level in patients with clinical benefit. Concordantly, HIF-2α protein expression and HIF-2α expression signature were associated with prolonged PFS. Overall, our findings show that casdatifan achieves meaningful, durable responses with manageable safety. These data establish a link between on-target HIF-2α pathway modulation, tumour biology and clinical efficacy.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a central regulator of lipid metabolism and a well-established determinant of cardiovascular risk. In addition to its hepatic role in cholesterol homeostasis, PCSK9 is increasingly linked to immunometabolic processes that overlap with biological alterations commonly observed in psychiatric disorders, including dyslipidemia, insulin resistance, and low-grade systemic and neuroinflammation. This narrative review synthesizes experimental, genetic, and clinical evidence on lipid metabolism and PCSK9-related pathways in psychiatric disorders. Disorder-specific patterns of peripheral lipid abnormalities are reviewed alongside evidence for altered central lipid composition and cholesterol turnover in major psychiatric and neuropsychiatric conditions. Available data on PCSK9 expression and regulation within the central nervous system (CNS) are summarized, together with studies examining circulating PCSK9 levels in relation to metabolic burden, inflammation, and psychiatric symptomatology. Overall, the literature positions PCSK9 within interconnected metabolic and inflammatory pathways associated with psychiatric vulnerability, primarily as a peripheral marker. Although PCSK9 is implicated in neuroinflammation and may intersect with pathways relevant to brain insulin resistance, its role within the CNS remains incompletely characterized in relation to psychiatric disorders, highlighting an important area for future mechanistic and translational research.
Oral cavity cancer represents a public health challenge in Latin America and the Caribbean (LAC), where exposure to modifiable risk factors such as tobacco and alcohol remains high and inequalities in access to health services contribute to delayed diagnosis and poor outcomes. This study aimed to develop consensus-based recommendations to strengthen the prevention and early detection of oral cavity cancer and oral potentially malignant disorders in LAC. A multi-phase study using a Delphi approach was conducted. An initial qualitative survey with regional experts identified barriers, facilitators, and priority actions for oral cavity cancer prevention and early detection. Preliminary recommendations were refined through feasibility assessment by international advisors and subsequently evaluated in a quantitative Delphi round using a Likert scale. Twenty-four experts from 12 LAC countries participated in the Delphi process, including research investigators, clinicians, and health service managers. The panel had a mean age of 49.4 (SD 10.3) years and included 41.7 % women. Seven recommendations achieved consensus, addressing key domains of oral cavity cancer control including primary prevention interventions, screening of high-risk individuals, establishment of structured referral pathways, improved surveillance systems, and expansion of access to diagnostic services in underserved populations. High levels of agreement were observed across all recommendations. These consensus-based recommendations provide a regionally informed framework to guide oral cavity cancer prevention and early detection strategies in LAC. Strengthening coordinated actions across the continuum of care, including primary prevention, screening, referral, and diagnostic capacity, may contribute to reducing diagnostic delays and improving outcomes in the region.
Pheochromocytoma is increasingly diagnosed at the extremes of age due to the availability of genetic screening in young patients and incidental detection on imaging in older patients. The aim of this study was to assess the effect of age on presentation and outcomes after adrenalectomy for pheochromocytoma. A retrospective international multicentre cohort study was performed of patients undergoing adrenalectomy for pheochromocytoma between 2012 and 2022 in 49 centers. Patients were divided into ≤40, 41-59, and ≥60-year-old cohorts. Univariate and multivariate analyses were used to compare cohorts and assess the impact of age on postoperative outcomes. Of 2301 included patients, 551 were ≤40 years (23.9%), 969 between 41 and 59 years (42.1%), and 781 were ≥60 years (33.9%). Younger cohorts were more likely to have a genetic syndrome (≤40 years 29.4% vs 41-59 years 11.5% vs ≥60 years 6.2%, p<0.001), and bilateral tumors (10.2% vs 2.3% vs 1.3%, p<0.001). On multivariable analysis, overall complications seemed less frequent in older cohorts (adjusted odds ratio (aOR) 0.64, p=0.012 and 0.66, p=0.054 for 41-59 and ≥60 years versus ≤40 years), whilst there were no clear trend in severe complications (Clavien-Dindo grade 3a-5) (aOR 0.81, p=0.481 and aOR 0.78, p=0.486, respectively) or Comprehensive Complication Index (beta coefficient -1.49, p=0.046 and -1.66, p=0.083, respectively). Age is associated with significant differences in presentation in patients undergoing adrenalectomy for pheochromocytoma, but does not have a clear association with postoperative complications. Pheochromocytoma postoperative morbidity is more likely affected by 'high-risk' disease rather than exclusively by age.