Search Results (2,854)

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality despite major advances in diagnostics and therapies. The prognosis remains poor, mostly due to late-stage presentation and molecular heterogeneity. Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. The development of EGFR tyrosine kinase inhibitors (TKIs) has significantly improved outcomes in patients with EGFR mutations. Variant allele frequency (VAF) is a quantitative genomic measure representing the proportion of sequencing reads harboring a given mutation. In NSCLC tissue, the EGFR mutation VAF reflects tumor clonality and intratumoral heterogeneity, and accumulating evidence suggests an association between EGFR VAF and response to EGFR-targeted TKIs. Methods: To address the limited synthesis of data on the relevance of EGFR mutation VAF in NSCLC, we conducted a narrative review of the literature using PubMed/MEDLINE and Embase databases and current clinical guidelines, synthesizing available evidence on EGFR VAF, including its biological, molecular, and therapeutic implications in EGFR-mutated disease. The review was structured in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) checklist. Results: EGFR VAF and on-treatment VAF dynamics are consistently associated with treatment response, progression-free survival, and overall survival in osimertinib-treated NSCLC. Baseline VAF enables risk stratification, early clearance kinetics predict durable benefit, and longitudinal VAF monitoring facilitates early detection of resistance. Importantly, the prognostic implications of VAF differ fundamentally between tissue-based and plasma-based measurements: high tissue VAF reflects clonal homogeneity and predicts favorable TKI response, whereas high plasma VAF indicates elevated tumor burden and is associated with inferior outcomes. In the second-line setting, the T790M/activating mutation ratio serves as a surrogate for resistance clonality and independently predicts osimertinib efficacy. Conclusions: EGFR VAF represents a promising dynamic molecular biomarker for treatment monitoring and precision decision-making in EGFR-mutated NSCLC. Full article

Background: Supplementation with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may mitigate exercise-induced muscle damage (EIMD) and enhance post-exercise recovery. However, the systematic reviews/meta-analyses evaluating these effects across populations and exercise models are limited and do not provide dosing recommendations. Objective: This systematic review and meta-analysis aimed to evaluate the effects of LC n-3 PUFA supplementation on key post-exercise recovery outcomes, including muscle soreness, muscle function, and muscle damage biomarkers in healthy adults. Methods: Following the PRISMA guidelines, a comprehensive search of PubMed, Scopus, and clinical trial registry databases was conducted (to January 2025). All studies that met the inclusion criteria underwent appropriate methodological quality assessments using established tools. The data were extracted for inputting into random-effects models, with effect sizes reported as Hedges’ g and 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. Results: Among the 2539 records, 43 studies met the inclusion criteria for the systematic review, and nine met the inclusion criteria for the meta-analysis. The effect of LC n-3 PUFA supplementation on recovery outcomes was equivocal, with significant methodological limitations noted across the literature. However, the meta-analysis of nine placebo-controlled, eccentric exercise trials demonstrated that LC n-3 PUFA supplementation significantly reduced delayed onset muscle soreness (DOMS) (Hedges’ g = −0.75; 95% CI: −1.14 to −0.36), creatine kinase (CK) (Hedges’ g = −0.40; 95% CI: −0.70 to −0.10), and muscle swelling (Hedges’ g = −0.45; 95% CI: −0.83 to −0.07), and significantly improved muscle strength (Hedges’ g = 0.45; 95% CI: 0.07 to 0.83) and range of motion (ROM) (Hedges’ g = 0.93; 95% CI: 0.33 to 1.53) at peak impairment compared with placebo. Conclusions: LC n-3 PUFA supplementation may support recovery from EIMD. However, due to the methodological limitations across the literature base it was not possible to assess effective dosing strategies. Future studies should address dose–response and duration requirements and incorporate objective assessments of omega-3 status (e.g., the Omega-3 Index [O3I] or comparable biomarkers) alongside standardized compliance measures. These approaches are necessary to determine effective dosing strategies and to test the relationship between omega-3 status and recovery outcomes. Full article

Glioblastoma (GB) remains the most aggressive primary brain malignancy, with the Stupp regimen persisting as the standard of care for nearly two decades despite poor survival outcomes. This review was synthesized by extensively reviewing and analyzing the literature from PubMed, Scopus, and Web of Science to evaluate the emerging promising therapeutic and diagnostic strategies for combating GB. Results indicate significant progress in molecularly targeted therapies, biomimetic nanocarriers, and advanced radiotherapy. While immunotherapeutic approaches, such as checkpoint inhibitors and vaccines, show variable clinical success, the integration of bioinformatics and machine learning has significantly enhanced treatment response prediction. Furthermore, advances in radiomics and molecular imaging have improved the differentiation between true tumor progression and pseudoprogression, potentially reducing invasive diagnostic requirements. Additionally, other emerging and investigational adjuvant therapeutic approaches have shown promise. We conclude that, while multimodal strategies integrating molecular and computational approaches offer a path toward personalized GB management, significant barriers—namely tumor heterogeneity and the blood–brain barrier—persist. Future research must prioritize precision-based combinatorial models to successfully translate these preclinical advancements into improved clinical outcomes for patients. Full article

Background: Maxillary sinus lift is among the most common preprosthetic procedures in the posterior maxilla due to alveolar ridge resorption and the maxillary sinus pneumatization. It often extends treatment duration, significantly increases costs, and is not without complications. Objective: To explore the prevalence and morphology of the palatal bone reservoir as a viable site for dental implant insertion, offering a conservative alternative to avoid maxillary sinus lift. Methods: DICOM data sets from helical CT of maxillofacial trauma patients aged 50 years and older were used to perform virtual dental implant positioning in the edentulous second premolar, first molar, or second molar areas using ImplaStation software (version 5.3.2; ProDigiDent, Inc., Scottsdale, AZ, USA). A 3D Slicer software (version 5.3.2; ProDigiDent, Inc., Scottsdale, AZ, USA) was used to calculate the volume of the palatal bone reservoir and identify its mean density. The density of the residual alveolar process was also identified and compared with that of the previous one. Results: A total of 1822 maxillofacial trauma cases with helical CT between 2015 and 2025 were retrieved. After exclusion, 305 cases were analyzed. A total of 65 implants were virtually positioned in 50 patients. The mean volume of the palatal bone reservoir was 229 ± 139.2 mm³ with a mean radiodensity of 546.7 ± 159.6 HU. The mean radiodensity of the residual alveolar process was 286.3 ± 118.0 HU. The palatal bone reservoir was significantly denser than the residual alveolar process (95% CI [184.2, 336.6]; p < 0.01). Conclusions: The presence of a palatal bone reservoir is not uncommon and can offer a more conservative alternative for implant placement, potentially increasing primary stability and facilitating immediate loading. Full article

This article outlines the life of James Clerk Maxwell (1831–1879) and presents some aspects of his philosophy of science. It describes the influence of the philosopher Sir William Hamilton on Maxwell’s general thinking. It considers Maxwell’s view that the boundary conditions of science (the ultimate origin of matter, the ultimate origin of the logic of the universe, and the initial characteristics of fundamental entities) appear to point to a Creator. It sets these issues within their historical context. Full article

Dietary polyunsaturated fatty acids (PUFAs) are vital for brain health and cognitive function. The dorsal raphe nucleus (DRN) regulates mood via serotonin, while the hypothalamus (HYP) controls energy homeostasis. Flaxseed oil (FLAX) is rich in omega-3 PUFAs like α-linolenic acid (ALA), and has been reported to influence serotonergic signaling in mammals, but data in poultry are scarce. This study investigated the effects of FLAX on metabolites crossing the blood-brain barrier (BBB) to serotonergic brain regions and on growth performance in broiler chickens. Day-old chicks (n = 160) were assigned to two diets (5 replicates/treatment): control (CON; poultry fat-based diet) or FLAX (3% inclusion level). Growth performance was recorded, and DRN, HYP, and plasma were analyzed using HPLC-MS metabolomics. Serotonin and its metabolite 5-HIAA were quantified using LC-MS/MS. FLAX-fed birds had higher body weight gain (p < 0.0055) and better feed conversion ratio (p < 0.0049) than CON. Metabolomics identified 2271 features, of which 650 were annotated as metabolites. Of 35 differentially abundant plasma metabolites, eight were also differentially abundant in brain tissues. In the DRN, tryptophan (serotonin precursor) and corydaline (neuroprotective) were upregulated. Serotonin levels were significantly higher in both the DRN and HYP of FLAX-fed birds compared to CON. This suggest that dietary flaxseed oil may modulate stress responses, behavior, and welfare in broilers. In the HYP, dethiobiotin (energy), galanthamine (neuroprotective), and gambogic acid (antioxidative) were upregulated, while xanthoxyletin (anti-inflammatory) was downregulated. In conclusion, flaxseed oil improved growth and elevated serotonin in the DRN and HYP via enhanced tryptophan availability, suggesting potential benefits for stress resilience and welfare. Full article

Post-processing remains a major bottleneck in the fabrication of microfluidic devices using Digital Light Processing Stereolithography (DLP-SLA) 3D printing, where unpolymerized resin trapped within internal structures must be removed without damaging delicate features such as thin membranes, valves, and pumps. Manual flushing is slow, inconsistent, and prone to structural failure, especially as device complexity and port counts increase. Here, we present the first fully automated flushing system for DLP-SLA microfluidic devices, enabled by a standardized chip-to-chip (C2C) interconnect architecture and an electronically controlled pneumatic routing platform. A reusable 32-port flushing interface chip provides alignment, sealing, and modular coupling to arbitrary device chips through integrated microgaskets, while a network of electronic pressure controllers, differential pressure sensors, and multi-port rotary valves enable precise, programmable application of pressure, vacuum, and solvent conditions. We introduce a fluidic-circuit model of the system that relates applied pressure to the pressure drop across device structures and experimentally validate this model using channels with varying fluidic resistances. Using this platform, we demonstrate robust flushing of both passive (straight and serpentine channels) and active (valves, pumps) microfluidic elements, as well as application-specific devices including mixers and concentration-gradient generators. Our system eliminates manual handling, improves valve membrane survival, and provides repeatable flushing across a broad range of device geometries. This work establishes a scalable foundation for automated post-processing in 3D-printed microfluidics and significantly advances the practicality of DLP-SLA fabrication for complex, multi-layered microfluidic devices. Full article

Background: Acute type A aortic dissection (ATAAD) is a life-threatening condition that may be complicated by malperfusion, particularly in patients with prior aortic interventions such as Thoracic Endovascular Aortic Repair (TEVAR). Management becomes increasingly complex when the dissection involves supra-aortic branches and compromises previously placed stents. Methods: We report the case of a 58-year-old male presenting with ATAAD and left lower limb paralysis, with a history of prior TEVAR. Imaging demonstrated an entry tear in the ascending aorta with extension into the distal left main and supra-aortic branches, resulting in a dissection flap obstructing the proximal end of the TEVAR stent. The patient underwent emergency surgical intervention including a Bentall procedure, coronary artery bypass grafting (CABG), and deployment of a small Ascyrus Medical Dissection Stent (AMDS) distally within the TEVAR stent. Pre-operatively, the patient had severe lower limb ischemia due to near-complete obstruction of distal flow. Results: Following surgical intervention, there was restoration of true lumen perfusion with resolution of malperfusion. The patient was successfully weaned from cardiopulmonary bypass, extubated on post-operative day 4, and discharged on day 7 with stable hemodynamics and intact bilateral lower limb perfusion. Post-operative computed tomography (CT) demonstrated a well-seated AMDS with no evidence of ongoing false lumen perfusion. At 30-day follow-up, there was no clinical or biochemical evidence of organ malperfusion. Conclusions: The use of an AMDS deployed within a pre-existing TEVAR stent may represent an effective strategy for managing complex ATAAD with malperfusion, particularly in cases requiring combined surgical interventions. Full article

Despite the availability of clinical guidelines aimed at managing pregnancy complications, maternal deaths related to obstetric emergencies remain unacceptably high in South Africa, especially in rural provinces like Limpopo. These preventable deaths are often linked to delayed response to complications, poor adherence to protocols, and lack of essential resources. The study aimed to explore the experiences of health professionals regarding the implementation of maternal guidelines used to manage obstetric emergencies. The study adopted a qualitative, descriptive, and explorative design. Data were analysed thematically, and trustworthiness was maintained throughout the research process. Sixteen participants from four selected hospitals in a rural area of South Africa (Vhembe District, Limpopo Province) were purposively sampled and interviewed using semi-structured interviews; data were analysed thematically. The findings highlighted multiple critical barriers to guideline implementation, including shortages of printed clinical protocols, inconsistent patient follow-up, poor referral systems, infrastructure deficits, medication stock-outs, and negative staff attitudes. Most doctors and midwives working in maternity units lacked training on the Essential Steps in the Management of Obstetric Emergencies (ESMOE), resulting in insufficient knowledge and skills to manage obstetric emergencies. Therefore, there is an urgent need for comprehensive ESMOE training for all doctors and midwives in maternity units. Full article

The prevalence of chronic conditions such as hypertension, diabetes, and Human Immunodeficiency Virus (HIV) is rising globally, yet access to continuous care remains limited, particularly in rural low- and middle-income countries. This study evaluated the acceptability and psychosocial predictors of retention in a linkage-to-care (LTC) intervention for patients with chronic conditions in rural South Africa. We conducted a cross-sectional analytical study with a retrospective cohort component among 1673 patients diagnosed with hypertension, diabetes, and/or HIV in Limpopo Province, South Africa. Acceptability and psychosocial factors were assessed cross-sectionally using a theory-informed, interviewer-administered questionnaire between January and June 2024. Retention in care over the preceding six months (July–December 2023) was extracted from routine clinic records and classified as consistent (no gaps > 6 months between visits) or inconsistent (≥1 gap > 6 months. Logistic regression examined associations between psychosocial factors and retention outcomes, adjusting for age, gender, marital status, and diagnostic category. Overall, 25.1% of participants maintained consistent retention over six months, while 74.9% were retained inconsistently. Acceptability of the LTC intervention varied significantly by diagnosis (p < 0.001): 79.5% of participants with multimorbidity rated the intervention as acceptable compared to 54.9% with hypertension, 64.5% with diabetes, and 46.8% with HIV. However, only 12.8% of multimorbid participants agreed that intervention activities fit well with their daily lives. In adjusted analyses, participants who were not happy to participate had 85% lower odds of consistent retention (adjusted odds ratio [AOR] = 0.15, 95% CI: 0.09–0.22) and 7.2 times higher odds of inconsistent retention (AOR = 7.2, 95% CI: 4.8–10.9). Most participants supported de-identified data sharing, though privacy concerns were elevated among those with multimorbidity. Acceptability of LTC interventions differs by diagnosis, with multimorbid patients reporting poorer alignment with daily routines. Retention is strongly associated with emotional engagement and self-efficacy, suggesting that LTC interventions should integrate psychosocial support and be contextually adapted for multimorbid patients in rural settings. Full article

Human Papillomavirus (HPV) is one of the most prevalent infections worldwide and a leading cause of cervical cancer, as well as anal, oropharyngeal, penile, vulval, and vaginal cancers. Despite the availability of safe and effective vaccines, coverage beyond female adolescent programmes remains often insufficient, leaving many adolescents and adults unprotected. The World Federation of Public Health Associations (WFPHA) convened a year-long global expert engagement forum to develop evidence-informed policy recommendations to advance HPV elimination. Building on this work, the resulting Call-to-Action urges countries to expand access to boys and adults. Adopting a life-course approach, integrated with screening, equitable access policies, and sustainable financing, can significantly increase coverage and reduce the burden of HPV-related cancers. This article outlines the main outcomes of the Call-to-Action and highlights key priorities for policy and decision makers committed to accelerating HPV elimination. Full article

Background: Translocation morphology renal cell carcinoma (tRCC) accounts for nearly half of all pediatric RCC cases. Biological study AREN14B4-Q aimed to characterize the molecular landscape of tRCC using samples acquired from patients enrolled in the Children’s Oncology Group Risk Classification and Biobanking study AREN03B2. Methods: From 2006 to 2014, patients <30 yr old with renal tumors were prospectively enrolled in AREN03B2, a Central IRB-approved biobanking study. All pediatric RCC cases underwent a detailed central pathology review and molecular diagnostics to accurately classify RCC subtypes. Samples with confirmed tRCC and appropriate informed consent were identified with adequate tissue for RNA and DNA extraction, along with germline DNA, for whole-genome sequencing (WGS), RNA sequencing, and DNA methylation analyses. Results: From 41 patients, high-quality samples allowed for 18 tumors and non-tumor DNA to be analyzed via WGS, 19 via DNA methylation, and 36 RNA samples via transcriptome sequencing. Consistent with and extending clinical cytogenetic findings, WGS and fusion transcript analyses confirmed very few additional mutations beyond the tRCC translocation. No recurrent genomic copy number gains/losses were found. RNA and WGS analyses enabled sub-classification of tRCC, closely aligning with the different TFE3 fusion partners. DNA methylation analyses demonstrated less tRCC sub-stratification compared with RNA analyses. Pathways activated in tRCC were involved in epithelial differentiation, extracellular matrix organization, apoptosis, immune regulation, signal transduction, and angiogenesis. Conclusions: Arrested epithelial differentiation is the overarching driver in tRCC and is strongly correlated with the specific subclasses of fusion transcript generated by the genetic translocation TFE fusion partner. Negative regulation of apoptosis, increased M2 macrophage expression, and enhanced angiogenesis also appear to be functional features of tRCCs, as are increased expression of matrix metalloproteinases, PI3K-AKT/mTOR/MAPK signaling, and mitochondrial metabolism, highlighting potential therapeutic options beyond direct targeting of the oncogenic driver fusions. Full article

Background: The dorsal raphe nucleus (DRN) produces and distributes serotonin, while the hypothalamus (HYP) uses serotonergic signals to regulate physiological processes in chickens. Coconut oil (COCO), rich in medium-chain fatty acids, is rapidly absorbed without re-esterification. Methods: Day-old broilers (Ross 708 male, n = 160) were distributed into two dietary treatments with five replicates of 16 birds each. The birds were fed a corn–soybean meal (SBM) basal diet supplemented with 3% of poultry fat (CON) or coconut oil (COCO). The body-weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were recorded over a 3-week period, and the data were subjected to a t-test. Untargeted metabolomic analysis by high-performance liquid chromatography (HPLC-MS) was used to evaluate the influence of the type of dietary fat on metabolite profiles in the DRN, HYP, and plasma of broiler chickens. Principal component analysis (PCA) was used to identify unique metabolites, and ANOVA was used to identify the metabolites that were significantly abundant (p < 0.05). The metabolites were then annotated using the KEGG and HMDB databases. Results: Birds in the COCO treatment gained more weight on average (0.8446 kg/bird) than birds in the CON group (0.8132 kg/bird; p = 0.0496). Five metabolites associated with multiple significant cellular processes, such as brain function, energy metabolism, and neurotransmission, showed similar differential expression patterns, while two metabolic pathways (butanoate metabolism and alanine, aspartate and glutamate metabolism) were identified. Conclusions: The dietary inclusion of COCO improves BWG in poultry and enhances their overall well-being by modulating metabolite profiles, supporting neurotransmission, and enriching the metabolic pathways essential for growth and brain function. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder marked by progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of Lewy bodies, intracellular inclusions enriched in α-synuclein. Synphilin-1 interacts with α-synuclein, localizes to Lewy bodies, and has been implicated in inclusion formation and neuroprotection in cellular and animal models; however, its physiological function in vivo remains poorly defined. Here, we generated and characterized a synphilin-1 knockout (Sph-1 KO) mouse by targeted genetic deletion of the Sph-1 locus and performed a comprehensive phenotyping battery including behavioral testing as well as biochemical, histological, structural, and ultrastructural analyses. Sph-1 KO mice survived to nearly two years of age and showed normal body weight, lifespan, motor performance, learning and memory, anxiety-like behavior, attention, and gross brain morphology. Western blot analyses indicated that levels of α-synuclein and synaptic proteins were largely unchanged. While outer mitochondrial membrane proteins were unaffected, the mitochondrial matrix protein HSP60 was reduced, consistent with altered mitochondrial proteostasis in the absence of synphilin-1. Strikingly, histochemical analyses, magnetic resonance imaging, and electron microscopy revealed early-onset hydrocephalus in Sph-1 KO mice associated with severe loss and disorganization of motile ependymal cilia in the ventricular lining, a cell type that normally expresses high levels of synphilin-1. Ultrastructural and immunohistochemical analyses revealed disrupted ependymal architecture, mislocalization of acetylated α-tubulin to the cytoplasm, cellular swelling, and enlarged, aberrant mitochondria, whereas cortical neurons appeared largely structurally unaffected. Together, these findings identify synphilin-1 as a key regulator of microtubule organization and cytoskeletal/organelle homeostasis in ependymal cells, required to maintain motile ciliogenesis, cerebrospinal fluid flow, and ventricular integrity. This unexpected role for synphilin-1 in ciliated brain epithelia, along with a reduction in the critical mitochondrial chaperone HSP60, broadens our understanding of synphilin-1 biology and provides a new framework for its potential relevance to PD-associated pathology. Full article

The question of which Scottish surnames constitute a Clan and which do not is hotly contested. It is wrongly felt, especially in the Scots-abroad communities, that Clan is somehow of higher status than “Family” or “House” and/or applies to everyone of Scottish heritage. Opinions and assertions are on a spectrum between two absolutes: (a) “everyone in Scotland is in a Clan, and everyone should wear kilts and tartans”; to (b) “Clans disappeared in the 18th century and there is no point clinging to a Romantic notion with no modern relevance”. Historically, the Clan is a phenomenon of the Gaelic-speaking Highlands and Islands and was not found as a social structure in the Lowlands; the Southern Uplands (Scottish Borders) are a special case. The “everyone” persuasion leads to cultural nonsenses such as Lowland-ancestry Scots abroad forming “Clan” Societies and adopting Highland dress. Scots overseas are looking for an authoritative statement as to whether their surname constitutes a Clan, a family, or some other nomenclature. Yet, there is no official or agreed historically based list of who are Clans and who are not. There is no such list—or a formula by which an answer can be derived. This essay is intended as a step towards that. Also, the non-historical concept of “Septs” is dismissed. Full article