Immune checkpoint inhibitors (ICIs) combined with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have transformed the treatment landscape of advanced clear cell renal cell carcinoma (ccRCC). Current guidelines favour ICI plus VEGF-TKI (IO+TKI) combinations for favourable-risk disease (International Metastatic RCC Database Consortium [IMDC] score 0) based on improved objective response rates and progression-free survival. However, no IO+TKI combination has demonstrated a statistically significant overall survival (OS) benefit in this subgroup. A pooled analysis of four pivotal phase III trials (n = 839 favourable-risk patients) revealed no OS advantage for IO+TKI versus sunitinib monotherapy (hazard ratio [HR] 1.24; 95% CI 0.86-1.78) despite higher toxicity rates (71-82% Grade ≥ 3 adverse events vs. 63-72% with sunitinib) and substantially greater cost. The IMDC favourable-risk category represents approximately 20% of metastatic ccRCC cases and is often characterised by indolent disease biology. Emerging molecular classifications reveal distinct transcriptomic subgroups, including an angiogenic subtype (ccA/CC-e.2/clusters 1-2) enriched in favourable-risk patients, characterised by high hypoxia-inducible factor (HIF) pathway gene expression, frequent PBRM1 mutations, robust VEGF-TKI responsiveness, and comparatively lower benefit from immunotherapy. Current clinical risk stratification fails to capture this molecular heterogeneity, limiting optimal treatment selection. VEGF-TKI monotherapy (median OS 47.6-79.4 months) and active surveillance remain valid, evidence-based alternatives in carefully selected favourable-risk patients, particularly those with asymptomatic, metachronous, or otherwise indolent disease. Uncritical universal use of IO+TKI in this population may therefore represent overtreatment. The development and validation of predictive biomarkers, refinement of molecular risk stratification, and exploration of novel agents with more favourable toxicity profiles (e.g., HIF-2α inhibitors) are urgently required to personalise therapy and identify candidates for rational treatment de-escalation.
With the rising prevalence of metabolic diseases, their comorbidity is increasingly common. Glucolipid metabolic disorders (GLMD) constitute a major health challenge associated with increased cardiovascular risk and mortality. Despite many advances in disease mechanisms and therapeutic strategies, the metabolic disease burden remains substantial. Routine clinical practice still lacks straightforward approaches for identifying individuals at elevated risk, and the challenge of effectively preventing and controlling GLMD has become an urgent clinical problem. Significant gaps remain in our understanding of metabolic disease. Advances in high-throughput sequencing and omics technologies have expanded the research perspective, shifting attention from organ-centered pathology toward microecological and metabolic networks, elucidating the interactions between the oral microbiota and host metabolism. As the second largest microbial community after the gut microbiota, the oral microbiome provides an integrative lens for examining GLMD-related microbial signatures, plausible mechanistic pathways, and translational opportunities, including inflammation, taste signaling, nitric oxide metabolism, and microbial translocation. This review aims to clarify the relationship between the oral microbiome and GLMD, outline characteristic microbial alterations in metabolic diseases, and summarize the plausible mechanisms linking oral microorganisms with metabolic homeostasis. Current evidence indicates partially recurrent microbial patterns across GLMD-related conditions, but no universal oral microbial signature has been established. Building on recent findings, we conclude by outlining the methodological requirements for evaluating the clinical utility of oral microbiome-based markers and interventions, and further discuss the value of oral microbiota in disease prediction, risk assessment, and individualized intervention. We also summarize the key limitations and challenges in the field and outline directions for future prevention and control of GLMD based on oral microecology.
Human Papillomavirus (HPV) infection is the leading cause of cervical cancer, presenting a significant global health challenge. While natural infection is widespread, the resulting immune response is often characterized by weak, delayed, and type-specific antibody production, offering unreliable protection against reinfection. This review provides a comparative analysis of natural versus vaccine-induced immunity, focusing on antibody kinetics, duration of protection, and cancer prevention efficacy. A comprehensive search of the literature from the last decade was conducted using PubMed, ScienceDirect, and Web of Science. The findings demonstrate that, unlike natural immunity, which is dominated by cellular responses with often incomplete seroconversion, prophylactic vaccination induces high titers of neutralizing IgG antibodies against the L1 capsid protein. These responses are durable, with protection persisting for over a decade, and recent data support the high efficacy of single-dose regimens. Furthermore, vaccination has shown utility in reducing infection persistence in HPV-positive individuals and provides critical protection in immunocompromised groups. Consequently, vaccine-induced immunity is consistently superior to naturally acquired immunity, supporting World Health Organization recommendations for universal vaccination as the primary intervention for reducing the global burden of HPV-related malignancies.
Patient portals are essential tools for patient engagement, transparency, and communication in US health care. Federal health information technology (IT) policies, such as Meaningful Use, Promoting Interoperability, and the 21st Century Cures Act, have played a pivotal role in driving the adoption of these tools. Despite prior work on portal availability and use, longitudinal, hospital-level analyses aligned with major policy milestones remain limited. This study examines national trends in hospital adoption of patient portal functionalities from 2012 to 2024 and assesses alignment with federal health IT policy initiatives. We analyzed 2012-2024 data from the American Hospital Association Annual Survey Information Technology Supplement. Three functional domains were evaluated: (1) patient access to information (view, download, and amend); (2) online administrative tools (bill payment, appointment scheduling, and prescription refill); and (3) patient-provider communication (secure messaging, patient-generated data submission, and external record import). Annual adoption rates were calculated, and monotonic trends were assessed using the Mann-Kendall test. By 2024, 92% of hospitals had adopted both viewing and downloading functionalities (τ = 0.94 and τ = 0.97; P < .001). Bill payment increased from 45.9% (2012) to 87.0% (2020). By 2020, prescription refill (74.6%) exceeded appointment scheduling (66.5%). Secure messaging increased from 28.2% (2012) to 88.7% (2024), and patient-generated data submission from 8.4% to 67.7%. In contrast, amending information and importing external records showed greater volatility, with no significant monotonic trends over their measurement windows. US hospitals have made substantial progress in adopting patient portal functionalities over the past decade, broadly paralleling federal policy developments. Core access tools (view/download) are now nearly universal, whereas administrative and communication features continue to expand. Uneven uptake of advanced capabilities highlights variability in implementation and underscores the need for sustained policy support, technical assistance, and equity-focused strategies to ensure that all hospitals-and patients-realize the full benefits of digital engagement.
Nigeria's path to Universal Health Coverage is constrained by high out-of-pocket spending and low health-insurance enrolment. Although the National Health Insurance Authority Act of 2022 strengthened the legal basis for coverage, financing and service-delivery gaps remain. With more than 220 million mobile subscriptions, the telecommunications sector offers a practical route for linking digital payments with health-insurance financing. This review examines how telecommunications can support health-insurance financing in Nigeria through a techno-economic lens, highlighting opportunities, barriers, and policy requirements. A narrative literature review was conducted between March and August 2025 using PubMed, Scopus, and Web of Science. English-language publications from 2010 to 2025 focusing on digital health, telecommunications, health financing, and health insurance in Nigeria and comparable low- and middle-income countries were included. Additional evidence from policy documents, regulatory frameworks, institutional reports, and grey literature was integrated. Data were thematically synthesised across five domains: health financing, telecom and fintech infrastructure, techno-economic frameworks, operational models, and governance. The review found that telecom-supported initiatives, including MTN Y'ello Health, Airtel-AXA Mansard, and WellaHealth, show potential to improve enrolment, affordability, premium collection, and claims processing through mobile payment systems. These models may strengthen financial inclusion and administrative efficiency, particularly for informal-sector and underserved populations. However, persistent challenges include poor broadband access, high data costs, regulatory overlap, low public awareness, limited benefit coverage, and uncertain long-term sustainability. Technoeconomic evaluation highlights the need for interoperability, scalability, equity, and sustainable financing. Telecom-driven health insurance can contribute to more equitable coverage in Nigeria if embedded within the national healthfinancing architecture and supported by interoperable data systems, strong consumer protection, affordable benefit design, and inclusive implementation. Adaptive techno-economic evaluation should guide pricing, subsidies, regulation, and scale-up.
Since its inclusion in the Sustainable Development Goals in 2015, the global health target of achieving Universal Health Coverage (UHC) has largely stalled. This article contends that one of the reasons for this lacking progress refers to the fact that the current definition of UHC does not sufficiently account for the transnational realities of global health. This article seeks to develop a more conceptually robust understanding of what UHC is, and what is normatively required to achieve it. In this context, the article proposes a novel definition of UHC that is adapted to the transnational realities of global health and advances an understanding of UHC as a global distributive justice norm. This normative theorising draws on literature in global distributive justice, which has largely been neglected in research and policy-led efforts to understand UHC. In this reconceptualisation, the article accentuates three required discursive shifts: from 'good health' to 'fair health'; from 'assistance' to 'duty'; and from 'cost' to 'investment'. To illustrate the conceptual and empirical validity of this reconceptualisation of UHC, it is then empirically applied to the activities of the Drugs for Neglected Diseases initiative (DNDi) in its health system strengthening efforts on Chagas disease in Latin America.
KIF1A-associated neurological disorder (KAND) encompasses a broad neurodevelopmental and neurodegenerative spectrum in which motor and movement disorders are common but incompletely defined. To systematically characterize motor and movement disorder phenotypes in KAND. In this cross-sectional study, 51 individuals with likely-pathogenic or pathogenic KIF1A variants underwent standardized neurological assessment using the Spastic Paraplegia Rating Scale (SPRS), SPATAX disability scale, Gross Motor Function Classification System (GMFCS), and Modified Ashworth Scale. A history of global developmental delay was present in 96.1% and neonatal or infantile hypotonia in 62.7%. Progressive spasticity occurred in 72.5%, predominantly affecting the lower extremities and correlated with age (β = 0.45, odds ratio [OR] = 1.56, 95% confidence intervals [95% CI] 1.09-2.25, P = 0.016). Lower extremity weakness was nearly universal (88.2%) and inversely related with age (β = -0.08, OR = 0.93, 95% CI 0.86-0.99, P = 0.032). Independent walking was achieved by 62.7% at a median age of 24 months, but only 31.4% retained independent ambulation at last evaluation. Movement disorders included motor stereotypies (43.1%), ataxia (19.6%), action tremor (15.6%), and dystonia (3.9%). Cerebellar signs were present in 37.2%. The p.Glu253Lys variant was associated with the most severe phenotype. KAND encompasses a continuous spectrum of motor and movement disorders that integrates developmental and neurodegenerative features. These findings inform clinical management, genetic counseling, and the design of future clinical trials. © 2026 International Parkinson and Movement Disorder Society.
Phenotypic plasticity is a universal property of living organisms, denoting the ability of a single genotype to produce different phenotypes in response to environmental variation (Bradshaw, 1965). This fundamental property is particularly relevant for plants which, due to their sessile nature, must rapidly respond to accommodate effects of global change on their development, growth, and reproduction (Schneider et al., 2026). Therefore, there has been a recent growing interest to uncover the genetic and molecular mechanisms underpinning phenotypic plasticity, with particular focus on agronomically relevant focal traits in different crops (Li et al., 2021; Liu et al., 2021).
The 2025-2030 Dietary Guidelines for Americans (DGA) introduced substantial controversy by diverging from long-standing practices and many scientific recommendations of the 2025 Dietary Guidelines Advisory Committee (DGAC). The final guidelines promote dietary protein intakes of 1.2-1.6 grams per kilogram of body weight per day (g/kg/d). These recommendations rely on a rapid systematic review of randomized controlled trials focused on weight-management outcomes and, to a lesser extent, a narrative review on nutrient adequacy. Recognizing protein as a component of a healthy diet is consistent with recent editions and a strength of the 2025-2030 DGA. However, the 2025-2030 DGA emphasize a single dimension of the evidence base and give limited attention to the relationship between protein intake and risk for, or management of, diet-related chronic disease, including cardiovascular disease, type 2 diabetes, chronic kidney disease, cancer, and bone disease. The scientific basis underlying the new protein guidance was, in our assessment, insufficiently comprehensive, while also departing from the DGA process to be food based and not nutrient based in the context of protein. These recommendations also lack sufficient clarity to distinguish between varying dietary macronutrient strategies for managing body weight in individuals with overweight or obesity and the specific protein requirements linked to the physiological roles of individual amino acids. The Scientific Foundation for the 2025-2030 DGA states that the recommendations were developed independent of equity and inclusion, raising practical concerns with how new higher protein targets will be interpreted and applied across diverse populations and federal nutrition programs. In this Perspective, we summarize the new protein recommendations, compare them with past DGA editions, the Scientific Report of the 2025 DGAC, and current population-level protein intake patterns, as well as highlight strengths and areas needing additional clarity or research. Central to our perspective is the view that evidence derived from weight loss studies does not provide a sufficient scope of evidence to support a universal dietary protein recommendation for all Americans across the lifespan.
The 16p11.2 deletion is one of the most frequent recurrent copy number variations associated with a broad neurodevelopmental and phenotypic spectrum. Despite its relatively well-characterized genomic region, clinical expressivity remains highly variable, posing challenges for diagnosis and management. We conducted a retrospective single-centre study of 25 individuals with molecularly confirmed 16p11.2 deletions, including 13 males (52%), 12 females (48%), and 7 familial (28%). Both de novo and inherited cases were included. The main testing method was chromosomal microarray, although karyotyping and additional tests such as sequencing and trinucleotide repeat testing were also utilized. Comprehensive clinical data were collected from medical records, including neurodevelopmental, neuropsychiatric, metabolic, skeletal, and systemic features. The majority of the cases had the typical ~600 kilobase deletion while two had distal ~220kb deletion. One patient was found to have a double genetic diagnosis. Developmental delay was almost universal in the probands, with expressive language significantly more impaired than receptive language abilities. Intellectual disability / learning difficulties and language problems were observed in 18/25 (72%) cases. Around half of the probands showed obesity and related hyperphagia. Autism spectrum disorder, attention deficit hyperactivity disorder, stereotypic movements, and aggressive behaviour were frequently reported. Epilepsy was present in thirteen patients (52%), with electroencephalographic abnormalities supporting generalized or focal epileptiform activity. Dysmorphic facial features and skeletal anomalies such as pes equinovarus, syndactyly, and scoliosis were variably present. Brain magnetic resonance imaging revealed abnormalities in several patients, including hypoplasia of the corpus callosum and intracranial hypertension. Additional systemic findings included hepatic steatosis, constipation, and ophthalmologic anomalies. Parental testing revealed asymptomatic or mildly affected carriers in multiple cases. Our findings emphasize the broad and heterogeneous clinical spectrum of 16p11.2 deletions in a Turkish cohort. Early recognition, multidisciplinary evaluation, and family-based genetic counselling are essential for timely diagnosis and optimal care of affected individuals.
Branched-chain keto acid dehydrogenase kinase (BCKDK) is a mitochondrial kinase that suppresses branched-chain amino acid (BCAA) oxidative catabolism by phosphorylating and inhibiting the branched-chain α-keto acid dehydrogenase complex. Beyond this canonical metabolic function, accumulating evidence indicates that aberrant BCKDK activation contributes to tumor metabolic rewiring, signaling adaptation, malignant progression and therapy resistance. This review summarizes the regulatory position of BCKDK in BCAA catabolism, its context-dependent functions across tumor types, and recent progress in BCKDK inhibitor development. Although selected non-oncological studies are discussed to inform inhibitor mechanism, pharmacology and safety, this review focuses on the oncology relevance of BCKDK. Particular attention is given to the transition from early proof-of-concept inhibitors to BT2-derived allosteric compounds, Pfizer-developed clinical candidates, and emerging non-BT2 scaffolds or alternative binding regions. A PubMed search was conducted to identify relevant studies on BCKDK, BCAA metabolism, cancer progression and BCKDK-targeted inhibitors. BCKDK is unlikely to function as a universal pan-cancer target. Its therapeutic value will depend on identifying tumor contexts with true BCKDK dependency, especially those relying on BCKDK-driven metabolic adaptation or downstream signaling. For BCKDK inhibitors, future development should integrate biochemical potency with mechanism-aligned conformational effects, long-term pharmacological consequences and biomarker-supported patient stratification.
BackgroundCervical cancer is the leading cause of cancer-related mortality among women in Uganda, with national screening coverage critically low at 20.6%. The disease is largely preventable through early detection, yet client-level and health-system failures conspire to suppress uptake.ObjectivesTo integrate client and provider perspectives to construct a comprehensive explanatory model of barriers to cervical cancer screening uptake in Hoima district, rural Uganda.DesignA convergent mixed-methods design, with quantitative and qualitative data collected concurrently across 20 health facilities and integrated through systematic triangulation.MethodsThe quantitative component recruited 400 women aged 20-60 years through systematic random sampling, analysed using binary logistic regression. The qualitative component recruited 30 health workers for key informant interviews, analysed using Braun and Clarke's thematic analysis framework. Reporting conforms to STROBE and COREQ guidelines.ResultsOnly 3.0% of women (n = 12/400) reported ever undergoing screening. Three significant determinants of uptake were identified: awareness of screening importance (AOR = 7.34, 95% CI: 2.41-22.37, p = 0.021); unmarried marital status (AOR = 8.69, 95% CI: 1.85-40.82, p = 0.006); and student occupation (AOR = 6.92, 95% CI: 1.51-31.81, p < 0.05). Wide confidence intervals reflect the small number of screened women. Qualitative analysis identified five supply-side themes: extreme centralisation of services; near-universal lack of trained personnel (96.7% untrained); absence of essential equipment; variable health worker knowledge; and workload-related resistance to expansion. Triangulation revealed strong convergence: the supply-side training deficit directly explains the demand-side knowledge gap. Apparent dissonance around cost was resolved by recognising that indirect access costs represent the true financial barrier for rural women.ConclusionLow screening uptake reflects a self-reinforcing cycle of structural weakness and uninformed community demand. Effective intervention requires simultaneously strengthening health system capacity and stimulating demand through targeted health education via preferred channels, notably radio and churches. BackgroundCervical cancer is the leading cause of cancer-related mortality among women in Uganda, with national screening coverage critically low at 20.6%. The disease is largely preventable through early detection, yet client-level and health-system failures conspire to suppress uptake.ObjectivesTo integrate client and provider perspectives to construct a comprehensive explanatory model of barriers to cervical cancer screening uptake in Hoima district, rural Uganda.DesignA convergent mixed-methods design, with quantitative and qualitative data collected concurrently across 20 health facilities and integrated through systematic triangulation.MethodsThe quantitative component recruited 400 women aged 20-60 years through systematic random sampling, analysed using binary logistic regression. The qualitative component recruited 30 health workers for key informant interviews, analysed using Braun and Clarke's thematic analysis framework. Reporting conforms to STROBE and COREQ guidelines.ResultsOnly 3.0% of women (n = 12/400) reported ever undergoing screening. Three significant determinants of uptake were identified: awareness of screening importance (AOR = 7.34, 95% CI: 2.41-22.37, p = 0.021); unmarried marital status (AOR = 8.69, 95% CI: 1.85-40.82, p = 0.006); and student occupation (AOR = 6.92, 95% CI: 1.51-31.81, p < 0.05). Wide confidence intervals reflect the small number of screened women. Qualitative analysis identified five supply-side themes: extreme centralisation of services; near-universal lack of trained personnel (96.7% untrained); absence of essential equipment; variable health worker knowledge; and workload-related resistance to expansion. Triangulation revealed strong convergence: the supply-side training deficit directly explains the demand-side knowledge gap. Apparent dissonance around cost was resolved by recognising that indirect access costs represent the true financial barrier for rural women.
Distal biceps tendon ruptures result in significant functional deficits, including 40% to 50% loss of supination strength if left untreated. Current hardware-based fixation methods achieve excellent outcomes but are associated with higher costs, 20% to 25% complication rates, and technical complexity. The bone tunnel technique represents a cost-effective alternative that eliminates hardware-related complications while maintaining anatomic restoration. This technique utilizes a single 5 cm anterior incision with protection of the lateral antebrachial cutaneous nerve. A bone tunnel is created at the anatomic footprint using a spade-tip drill, followed by 7 mm reaming, sized 1 mm smaller than the tendon diameter. The tendon is secured with #2 FiberLoop (Arthrex, Naples, FL) whip-stitch sutures, seated into the tunnel, and fixed by passing sutures around the radial aspect of the radius shaft and through the tendon with square knots. Key advantages include elimination of expensive implants, no intraoperative imaging requirements, preservation of natural tendon-bone healing, and universal accessibility. This technique provides reliable fixation through biological integration with reduced complexity and cost compared with hardware-based methods.
Coastal heritage sites face significant global challenges such as flooding and coastal erosion, exacerbated by climate-induced sea-level rise and coastal development. The ability to accurately simulate and assess potential exposure of heritage sites to these hazards has been hampered by a lack of digital high resolution spatial data accurately recording the topographic boundaries of heritage sites. The Glo-CoH dataset contains digitized boundary extents of all the heritage sites inscribed by the United Nations Educational, Scientific and Cultural Organization (UNESCO) as World Heritage properties of Outstanding Universal Value that are situated along the global coastline under 20 m Above Mean Sea Level (AMSL). It comprises a total of 1,250 individual serial sites covering the breadth of designated cultural, natural and mixed heritage sites and encompasses an area covering over 235 million hectares. A programme of site digitisation utilised extant site plans and Google Earth worldwide satellite imagery to locate and digitise heritage site boundaries. The quality of the resulting dataset was assessed by applying a mixed qualitative/quantitative validation procedure to a stratified sub-sample, encompassing the quality of source material, site identification, visibility and digitising accuracy. The validation procedure suggests 92% of digitized sites obtain validation scores indicative of optimal digitisation accuracy. The Glo-CoH dataset is made available for geo-spatial analysis and intended for use by researchers and practitioners looking to assess or plan environmental, climatic, economic, infrastructural and societal dimensions relating to coastal heritage at site, city, and regions up to global scales.
Empty sella (ES) is characterized by the replacement of pituitary tissue with cerebrospinal fluid (CSF) in the sella turcica. Despite its frequency in clinical settings, ES is often underrecognized and incompletely evaluated. The aim of this study was to examine patterns of care and potential disparities across different ES etiologies. This retrospective cross-sectional study aimed to evaluate differences in hormonal assessment and referral patterns among patients with various etiologies of empty sella. All patients aged ≥14 years diagnosed with ES between February 2021 and December 2022 at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, were included. Relevant data were extracted from electronic medical records, and comparisons of hormonal assessment were made based on etiology and reason for endocrine referral. Among 287 patients (75.3% female, mean age 49.7 years), 84.6% had primary ES. Only 29.9% were referred to endocrinology (52.4% for ES-specific evaluation). Secondary ES patients received more comprehensive hormonal assessments than primary ES (P<0.001). Primary ES referrals for ES-specific evaluation correlated with thorough testing (P<0.001). Significant disparities exist in ES management, driven by etiology and referral intent. Standardized referral pathway and universal screening are essential to improve care.
Objectives: To examine the association of contextual school performance, individual educational delay, and socioeconomic conditions with untreated dental caries and tooth loss in Brazilian adolescents. Methods: Data from two nationally representative surveys (SB Brasil, 2010, n = 11,895; 2023, n = 9181 after exclusions). Outcomes were untreated caries and any tooth loss from the DMFT index. Contextual exposure was a Public School Performance Score (PSPS) derived by principal component analysis of school dropout, grade retention, and the Basic Education Development Index. Multilevel logistic models estimated odds ratios (ORs) per 1-unit SD increase in the PSPS for each survey year, adjusting for sex, age, equivalised income, educational delay, municipal income tertiles, and water fluoridation. Results: The PSPS distribution shifted rightwards between surveys (median rose from 0.99 to 2.43), reflecting improvements in IDEB and reductions in dropout and grade retention. In 2010, a 1-SD higher PSPS was associated with significantly lower odds of untreated caries (OR = 0.92, 95%CI 0.84, 0.99) and tooth loss (OR = 0.88, 95%CI 0.81, 0.97). By 2023, the associations had weakened and were no longer statistically significant: caries OR = 0.97 (95%CI 0.86, 1.10); tooth loss OR = 0.95 (95%CI 0.83, 1.08). The year-by-score and cross-level interactions were not statistically significant. Conclusion: The contextual gradient in oral health associated with school performance observed in 2010 was not detectable in 2023, despite overall improvements in educational indicators. Clinical Significance: Even when average school performance rises, additional school-based oral health strategies may be needed to maintain the health gradient, as universal improvements do not automatically translate into reduced inequalities.
Sustainable head and neck cancer (HNC) surgery is challenged by environmental impact, workforce shortages, inequitable access to advanced techniques, and policy constraints. Addressing these areas is critical for equitable, high-quality care. This structured narrative review synthesizes evidence on environmental sustainability, workforce development, technological innovation, health policy, and socioeconomic determinants in HNC surgery, without aiming to provide a systematic or exhaustive evidence synthesis. Sources included peer-reviewed literature, global workforce surveys, and international policy reports, with a focus on disparities between high-income countries (HICs) and low- and middle-income countries (LMICs). Operating rooms produce up to 70% of hospital solid waste and consume 3-6 times more energy than other units; reusable instruments and improved waste segregation can reduce carbon footprints by over 50%. Workforce shortages are severe in LMICs, where subspecialty training is scarce; global partnerships, bidirectional education, and simulation-based learning can expand local capacity. Telemedicine, artificial intelligence, and three-dimensional printing enhance surgical planning, training, and access but may widen disparities without equitable deployment. Policy tools-including diagnosis-related groups, bundled payments, and universal coverage-affect access and innovation uptake. Pandemic preparedness underscores the value of resilient systems with flexible staffing and telehealth integration. HNC surgery requires coordinated action across environmental, workforce, technological, socioeconomic, and policy domains; however, future systematic reviews are needed to comprehensively map the evidence base and assess its methodological quality. Embedding sustainability in clinical practice, ensuring equitable innovation access, and aligning reimbursement with high-value care can strengthen system resilience, improve outcomes, and support long-term surgical service viability.
Crossovers (COs) ensure proper chromosome segregation during meiosis and generate genetic diversity. COs are non-uniformly distributed along chromosomes and almost universally suppressed in centromere-proximal regions, notably creating an important bottleneck for plant breeding. The mechanism of this CO suppression is still not fully understood, but the chromatin state is a contributing factor. Here we identify three factors that actively limit proximal CO in Arabidopsis thaliana: the cohesion establishment factor CTF18, the centromeric cohesin protector SGO2 and the deSUMOylase SPF2. The mutation of these factors allows both the formation of COs in the centromere-proximal region where they were completely absent in the wild type and the enhancement of their frequency where they were rare. COs can be further increased by combining these mutations together or with mutation in the DNA methylase CMT3, suggesting that multiple mechanisms prevent proximal COs in parallel. The identification of the very conserved CTF18, SGO2 and SPF2 as suppressors of centromere-proximal COs highlights the importance of cohesin turnover in this process and opens up new possibilities for plant breeding.
Fibroblast activation protein (FAP) is expressed by activated fibroblasts and selected vascular-associated stromal cells in tumors and non-malignant repair processes. Radiolabeled FAP inhibitors (FAPIs) allow PET mapping of FAP-accessible activated stroma, complementing tumor-cell metabolic imaging with FDG. This narrative review summarizes the biological basis of FAP targeting, radiopharmaceutical design, clinical imaging applications, benign fibro-inflammatory pitfalls, and early therapeutic development. FAPI PET can provide high lesion-to-background contrast in desmoplastic and low-FDG-avid tumors and in regions where physiologic FDG uptake complicates interpretation. The strongest current clinical scenarios include problem-solving in gastrointestinal cancers, peritoneal disease, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and biliary tract cancers, as well as whole-body assessment of target expression before therapy trials. However, FAPI uptake is not tumor specific; wound healing, post-treatment remodeling, fibrosis, arthritis, pancreatitis, liver disease, atherosclerosis, and other fibro-inflammatory or repair states require careful correlation with CT, MRI, FDG PET, clinical history, and follow-up. For therapy, high early PET contrast alone is insufficient. First-generation monomeric tracers may wash out rapidly, FAP expression is heterogeneous, and absorbed dose depends on ligand residence time, lesion architecture, perfusion, radionuclide range, normal-organ uptake, marrow reserve, and the fraction of disease that is FAP avid. Longer-retention ligands, dimeric or multimeric constructs, albumin-binding approaches, and beta- or alpha-emitter strategies are expanding clinical development, but prospective dosimetry and outcome data remain limited. Overall, current evidence supports FAPI PET as a complementary imaging method and selection tool for protocolized FAP-targeted radionuclide therapy rather than as a universal replacement for established imaging or a routine therapy platform. Future translation should emphasize standardized acquisition and reporting, disease-specific indications, benign uptake checkpoints, lesion-level dosimetry, physiologically relevant preclinical models, and prospective trials measuring management impact, toxicity, quality of life, and patient-relevant outcomes.
To explore how nurses in Thailand's Nursing Community Clinics (NCCs) enhance client care within the Universal Coverage Scheme (UCS). A qualitative study was employed. Participants were purposively recruited from 254 NCCs across Thailand. Of the 28 NCCs that met the inclusion criteria, 12 participants were recruited, achieving data saturation. Data were collected from January to February 2024 through individual semi-structured interviews. Thematic analysis, guided by the scope of services and relevant literature, identified key themes. Trustworthiness was ensured using Guba and Lincoln's criteria. Three themes emerged. First, nurses enhanced access to care by strategically locating clinics and providing free services, reducing financial and transportation barriers for vulnerable populations. Second, personalised education and self-management support improved patient outcomes and quality of life. Third, effective interdisciplinary collaboration ensured seamless care coordination. This study highlights the critical role of nurses in improving healthcare access and health equity within the Universal Coverage Scheme. The findings have direct implications for public health nursing, as community-based nurses serve as essential first-contact providers for underserved populations. Nursing councils should develop specialised courses and expand the scope of practice for public health nurses to strengthen primary healthcare delivery.