Evaluation of Three Atlas Lateral Mass Screw Trajectories: A Computed Tomography-Based Analysis of Anatomical Parameters.

The anchor at C2 often serves as a key stabilizer in cervical spine fusion surgery. Although the pedicle screw is considered the standard fixation method at C2, the laminar screw is also a widely used alternative due to its biomechanical stability, comparable to that of C2 PS. However, malpositioning of C2 LS carries a risk of neural injury and compromised fixation stability, and the use of surgical assistance has been reported to improve placement accuracy. The robotic system is a relatively new technology for PS placement, and its application has recently expanded to the cervical spine. The present study aimed to investigate the accuracy of C2 laminar screw placement with robot assistance. This prospective study evaluated 11 C2 laminar screws in 11 patients who underwent cervical fusion surgery with the robot assistance between March 2024 and June 2025. All 11 C2 laminar screws were successfully placed with no cortical breaches and no screw-related complications. The mean deviations at both the entry point and at a depth of 20 mm were less than 1.0 mm in both the axial and sagittal planes. The results of this study suggest that the robotic system is a potential tool to facilitate accurate C2 laminar screw placement in clinical settings.

Methylotrophic yeasts are promising hosts for bioproduction from methanol, but their growth is significantly reduced in the presence of methanol. In this study, we investigated metabolic bottlenecks in Komagataella phaffii, Ogataea polymorpha, and Candida boidinii during methanol assimilation through comparative metabolome analysis. We found a common decrease in α-ketoglutarate-derived amino acids and tricarboxylic acid (TCA) cycle intermediates in all three species during methanol assimilation, suggesting a metabolic bottleneck around the TCA cycle entry. Additionally, K. phaffii and O. polymorpha accumulate trehalose in the presence of methanol. ΔΔG analysis suggested reduced activity of pyruvate kinase and TCA cycle entry enzymes as potential rate-limiting steps. Biosynthesis of TCA cycle-derived amino acids, including Glu, Arg, and Pro, is a limiting factor because supplementation with these amino acids significantly enhanced growth rates and final cell density for all three species. Furthermore, disruption of the trehalose biosynthesis gene (TPS2) in K. phaffii further improved growth, indicating that trehalose accumulation negatively affects methanol-based growth. Amino acid supplementation with TPS2 disruption in K. phaffii resulted in a 1.2-fold increase in the specific growth rate and a 2.73-fold increase in final cell density. These findings provide insights into the metabolic limitations of methylotrophic yeast growth in the presence of methanol and offer strategies for improving bioproduction efficiency.

Neuritin protects spiral ganglion neurons via NKA-Ca²⁺ homeostasis and CaMKII/MAPK suppression.

Cities worldwide are rethinking the use of curbside space to balance accessibility, sustainability, and urban liveability. Yet, increasingly complex curbside regulations face low enforcement capacities and high misuse. This undermines policy objectives for efficient goods movement, sustainable urban mobility, and equitable access to the curbside. In response, municipalities explore static Internet of Things (IoT) technologies to digitalize curbside management. However, past implementations of static IoT technologies, such as in-ground sensors and cameras, have often failed to achieve long-term operation. This study investigates how static IoT technologies can support digital curbside management while recognizing local contexts. We examine this question through the lens of innovating mindfully, which conceptualizes innovating as a context-sensitive process that balances outside experience with decision-making grounded in local facts and specifics. Combining this lens with expert interviews and Design Science Research, we derive 16 principles and testable propositions for innovation adoption in the three phases that entertain outside experience: comprehension, adoption, and implementation. Our results show that IoT technologies are initially most suitable for enforcement challenges in no-parking, time-limited, and permitted parking. These lay the foundation for future user-oriented services. We thus propose an iterative process for innovating mindfully with IoT technologies. It allows cities to assess feasibility and avoid premature commitment, while iteratively building internal sensitivity and external legitimacy. The study advances transport policy research by offering a transferable framework for evidence-based policy designs and actionable guidance to enhance parking compliance, operational efficiency, and the integration of IoT technologies into urban mobility strategies. • Innovating mindfully as lens for IoT innovations in curbside management • 16 principles and propositions guide mindful IoT sensor adoption • Enforcement use cases as entry point for digital curbside management • User services follow as technical and institutional maturity grows

Development of a river habitat quality index (RHQI) framework for dry-hot valleys: Unraveling driving mechanisms and management implications.

85 Background: Colorectal cancer continues to be one of the leading cancers, ranking third in occurrence and second in cancer-associated fatalities worldwide. Additionally, its therapy is limited by drug solubility, systemic toxicity and resistance. The high rates of incidence, death and treatment challenges emphasize the critical need, for improved therapeutic approaches. Sorafenib (SOR), a multi-targeted kinase inhibitor inducing apoptosis and ferroptosis, and paclitaxel (PTX), a microtubule-stabilizing agent, are mechanistically complementary but limited by poor bioavailability. Sigma-1 receptor (σ1R), overexpressed on CRC cells, offers a targetable entry point via anisamide (AA), a benzamide ligand. This study developed AA-conjugated PLGA nanoparticles co-loaded with SOR and PTX as targeted CRC nanotherapy. Methods: AA was conjugated to Pluronic F-127 via DCC condensation, confirmed by FTIR and ¹H NMR. SOR+PTX AA-PLGA NPs were fabricated by nanoprecipitation and optimized using Box-Behnken Design. The formulation was optimized and assessed for characteristics in-vitro uptake, cytotoxic effects, and apoptosis in HCT116, HT29, and CT26 cells. In vivo antitumor efficacy, pharmacokinetics, hemocompatibility, and organ toxicity were assessed. Results: After optimization, the SOR+PTX-AA-PLGA nanoparticles displayed a size of 192.21±7.55 nm, a PDI of 0.252±0.065, and drug loading (%) of 8.87±1.03 (SOR) and 8.43±1.44 (PTX). The drugs were released slowly in two phases and followed Korsmeyer-Peppas law of drug release. Targeted nanoparticles exhibited 2.0-2.7 fold higher cytotoxic activity compared to free drug combinations. Significant decreases in IC 50 value were evidenced in all the three colorectal cancer cell lines with HT29 at 1.81 µg/mL, HCT116 at 1.41 µg/mL, and CT26 at 1.62 µg/mL. The apoptotic index radically increased up to 1.44 (HT29), 1.28 (HCT116), and 1.38 (CT26), the maximum values, in all the groups. In vivo SOR+PTX AA, PLGA nanoparticles resulted in a tumor size of 6.51 fold smaller than the control and was even more effective than free SOR (1.22 fold) and PTX (1.50 fold). Pharmacokinetic analysis demonstrated that the AUC was increased by 2.31 times, and the half life was extended by 4.5 times compared to free drugs, pointing to greater drug persistence in the body. At the same time, no alterations were detected in the liver/kidney function markers (ALT, AST, BUN, creatinine; P>0.05) of the treated groups, and only trace levels of hemolysis were observed, which are indications of safety. Conclusions: Anisamide targeted PLGA nanoparticles markedly enhanced co, delivery, cellular uptake, cytotoxicity, and apoptosis, which were reflected in better tumor suppression and longer systemic exposure. This delivery system has great potential for targeted colorectal cancer therapy.

Cichlid fish as a model for understanding social dysfunction.

Dengue continues to be a global public health challenge despite sustained control efforts. Dengue control strategies rely primarily on effective Aedes mosquito control. Sustaining community participation in mosquito control requires innovative efforts, especially in achieving consistent behavioural change. Schools offer a strategic entry point, with children being both learners and influencers. This leads to a ripple effect of intervention impacting beyond the classroom. While behaviour change strategies for dengue prevention exist, there is sparsity of studies addressing the implementation aspects including contextual factors and sustainable mechanisms. We propose a hybrid type 3 effectiveness-implementation study to design, implement and evaluate a school-based dengue control initiative in Puducherry. The study will be conducted in three phases: (1) formative research and co-development of the intervention package and implementation strategies, (2) implementation and (3) evaluation. The intervention will be co-developed using the principles of Communication for Behavioural Impact, with school teachers serving as key change agents to deliver knowledge and promote dengue prevention practices among students. The Consolidated Framework for Implementation Research 2.0 will guide the implementation process across all phases. Evaluation will be carried out using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, adopting a mixed-methods approach to assess intervention effectiveness, implementation outcomes and cost implications. The study protocol was approved by ICMR- NIVCR Institutional Human Ethics Committee (IHEC 0123/N/D). All standard ethical practices will be adhered to. Written informed consent (or age-appropriate assent) will be obtained from all participants. Findings will be shared via policy briefs/reports to stakeholders followed by publication in reputed journals. CTRI/2026/02/104985.

Despite major advances in care for patients admitted to the intensive care unit (ICU), mortality remains high and functional outcomes for ICU survivors are often poor. The persistent burden underscores the need for innovative, mechanism-based approaches. Precision medicine has emerged as a promising paradigm in critical illness, and regulated cell death (RCD) may offer a novel entry point for targeted interventions. Among the various RCD pathways, ferroptosis, an iron-dependent form of RCD driven by excessive lipid peroxidation within cellular membranes, has gained increasing attention. Its mechanistic distinctiveness from other RCDs and potential reversibility make it particularly relevant in acute, dynamic disease states. In this narrative review, we explore the role of ferroptosis in critical care, focusing on high-impact conditions such as sepsis, COVID-19, ischaemia-reperfusion injury, and neurological emergencies. We outline the molecular mechanisms of ferroptosis and discuss how it may contribute to organ dysfunction across systems. While most insights to date stem from preclinical models, emerging clinical data suggest translational potential. We highlight key studies, discuss current limitations in detection and therapeutic targeting, and consider how the evaluation of ferroptosis could help shape the future of precision medicine in the ICU.

The health care system is a critical entry point for sexual violence response including care and linkages to auxiliary services. However, detailed data on quality and readiness of facility-based sexual violence care in African settings is sparse, hindering measurement and improvements. We report results from the first wave of longitudinal mixed-methods study conducted between July and September 2022 to assess readiness and quality of sexual violence services in 4 counties in Kenya supported by the Accelerate program. Health facility assessments were conducted within all (N=123) program-supported facilities in the 4 counties, including provider interviews; visual inspection and audit of essential infrastructure and commodities; and chart abstraction. We computed descriptive data summaries, and in-depth interviews from 40 purposively selected providers were analyzed thematically. Of 123 study facilities, 54% had a provider who received GBV in-service training in the past 12 months. Most facilities (85%) routinely offered GBV care. Of facilities offering GBV care, most stocked antibiotic for sexually transmitted infections (STIs) (71%), any emergency contraception pill (ECP) option (88%), and tetanus vaccine (93%), and most provided GBV counseling (90%). However, availability of hepatitis B vaccine was low across facility tiers (14%-25%). Dispensaries/clinics documented low availability of HIV post-exposure prophylaxis (PEP) for children and adults (20% and 47%, respectively), SGBV register (20%), and post-rape care forms (27%). Of 285 abstracted charts, most were in hospitals (62%) and for survivors under 18 years (69%). Just 59% of survivors presented promptly, within 3 days, for health care services. Of survivors who were eligible for care, a considerable proportion missed psychosocial assessment (32%), PEP for HIV (22%), ECP (17%), and treatment for bacterial STIs (15%). Qualitative data revealed service delivery gaps driven by disruptions in supplies and provider capacity gaps. Many providers indicated concerns in the chain of evidence due to gaps in documentation and logistical support for health care providers when providing legal testimony in courts. Readiness to provide a minimum care package for sexual violence was low, with steep gradients across facility tiers. Delivery of timely and quality-assured sexual violence care requires addressing structural gaps driven by stock-out of supplies and inadequate providers' support including training. These corrective actions should be augmented by community-based interventions that link survivors to health care.

Plants restrict microbial entry into their leaves by closing their stomata upon recognition of conserved microbe-associated molecular patterns (MAMPs). The hydathode pore is a stomata-like opening on leaf margins which are thought to lack MAMP recognition and to be an entry point for microbial pathogens. Here, we observe marginal hydathode pore closure in response to abscisic acid, and the MAMPs chitin and flg22 in Arabidopsis thaliana leaves. Hydathode pore closure occurs within 3-9 hours of chitin exposure and pores reopen after 12 hours. Under conditions when hydathode pores are open, external fluids enter approximately 80% of the marginal hydathodes within a leaf. After hydathode pores close in response to ABA, chitin or flg22, external fluids accumulate in under 20% of hydathodes with in a leaf. MAMP-induced hydathode restriction was similar for dye or fluorescent Pseudomonas syringae pv. tomato bacteria and was dependent on pattern recognition receptors including CERK1 for chitin and FLS2 for flg22. Chitin-induced hydathode limitation was also dependent on the NADPH oxidase RBOHF and was partially hampered in rbohD, lyk4 lyk5, bak1-5 bkk1, slac1-3 slah3-1 knockout mutants. Together, this work indicates that MAMP recognition regulates entry into the hydathode and induces transient closure of the hydathode pores.

ABSTRACTBackgroundSeveral techniques have been developed to facilitate safe and accurate thoracic pedicle screw placement. However, their impact on screw anchorage has not been systematically evaluated. This study compared thoracic pedicle screw anchorage following placement using the Modified Slide, Slide, Funnel, and Conventional techniques under cyclic loading.Study DesignCadaveric biomechanical study.MethodsForty‐five fresh‐frozen human thoracic vertebrae (T4–T11) were allocated to three experimental groups (n = 15 each). For standardized paired comparisons, one randomly selected pedicle of each vertebra was instrumented using the Modified Slide technique, developed by the authors as a refinement of the original Slide technique, and the contralateral pedicle with one of three established techniques. Screws were subjected to cyclic craniocaudal loading until loosening or a maximum load level of 750 N.ResultsScrews placed using the Modified Slide technique withstood 1.9‐fold and 1.5‐fold more load cycles until loosening than those placed with the Slide and Funnel techniques, respectively (both p < 0.001), but only 0.9‐fold that of screws inserted with the Conventional technique (p = 0.008).ConclusionsThe Modified Slide technique preserves the advantage of the Funnel and original Slide techniques by allowing direct visualization of the pedicle entry point for accurate screw placement, yet substantially enhances thoracic pedicle screw anchorage compared with those techniques. Although anchorage was lower than that of the Conventional technique, screws placed using the Modified Slide technique still withstood loads substantially exceeding those reported to occur during daily activities.

Background & ObjectivesCholangiocarcinoma (CCA) is a rare and aggressive malignancy of the bile ducts characterized by complex imaging patterns, high inter-reader variability, and limited subspecialty expertise. Despite the critical importance of early detection for improving patient outcomes, most artificial intelligence (AI) tools developed for radiology have focused on other organ systems, leaving CCA largely underserved. Furthermore, clinicians with relevant domain expertise frequently lack the programming background required to participate meaningfully in AI development. This work aimed to create an accessible, educational AI framework “AI Starter” designed to empower radiologists and clinicians to initiate medical image analysis projects for CCA without requiring extensive coding knowledge.MethodsA structured, end-to-end AI pipeline was introduced covering the key stages of image acquisition, preprocessing, segmentation, feature extraction, and predictive modeling. Open-source frameworks, specifically MONAI and PyTorch, were employed to ensure reproducibility and accessibility. Transfer learning strategies were incorporated to address the challenge of limited CCA-specific training datasets. The pipeline was designed with modular components to reduce technical barriers and accommodate users across varying levels of computational experience.ResultsRadiologists and clinicians were able to successfully engage with and deploy AI tools for CCA imaging analysis using this framework. Transfer learning demonstrably improved model performance under data-limited conditions, and the open-source implementation supported reproducible research workflows. Key challenges identified included scanner variability, segmentation instability, feature instability, and model overfitting, all of which were transparently mapped within the pipeline.ConclusionThe AI Starter framework offers a practical and educational entry point for the CCA community including basic scientists and clinicians to meaningfully engage with and understand AI-driven imaging analysis.

Suicidal ambivalence, the co-occurring desire to live and die is widely discussed in clinical practice yet remains understudied in empirical research. This qualitative study explored how young adult suicide attempt survivors understand and experience suicidal ambivalence. Using a phenomenological approach, in-depth semi-structured interviews were conducted with 19 young adult suicide attempt survivors between the ages of 18 and 29. Data were analyzed using thematic analysis. Five themes emerged across two areas. First, participants described suicidal ambivalence as a (1) internal conflict (2) a dynamic process, and (3) a source of comfort. Second, their experiences were characterized by (4) conflicting desires between life and death and (5) feelings of numbness. Suicidal ambivalence was seen as a dynamic psychological process that holds the tension between life and death. Future research should investigate how suicidal ambivalence can serve as a protective factor to serve as a potential entry point for crisis intervention.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally and can progress to metabolic dysfunction-associated steatohepatitis, a more severe and fibrotic form. Although the recent FDA approval of Resmetirom and Semaglutide, represents a major therapeutic milestone, its efficacy is limited to a subset of patients. Thus, identifying additional molecular targets is essential. This study aimed to investigate the role of lymphocyte antigen 6 complex locus D (LY6D) in hepatic lipid accumulation and MASLD pathogenesis. LY6D expression was assessed in liver tissue samples from patients with MASLD and validated in leptin or leptin receptor knockout mice (ob/ob and db/db) and high-fat diet-fed mouse models. Transcriptomic profiling was performed using RNA sequencing to identify LY6D-associated metabolic pathways. Functional analyses were conducted using LY6D-overexpressing mice to evaluate hepatic lipid content, gene expression, and protein signaling. Protein-protein interactions were assessed via co-immunoprecipitation, and downstream effects on AMP-activated protein kinase (AMPK) phosphorylation and sterol regulatory element-binding protein 1(SREBP1) activation were evaluated by Western blotting. LY6D expression was significantly elevated in liver samples from patients with MASLD and in mouse models of hepatic steatosis. Transcriptomic analysis revealed enrichment of fatty acid synthesis pathways in LY6D-high livers. In LY6D-overexpressing mice, de novo lipogenesis was increased, with upregulation of lipogenic genes including Srebf1, Fasn, Acaca, and Scd1. Mechanistically, LY6D associated with growth factor receptor-bound protein 2 (GRB2) and was accompanied by reduced AMPK phosphorylation at Thr172. Modulation of AMPK activity altered LY6D-dependent SREBP1c abundance and nuclear accumulation, supporting an LY6D-associated GRB2-AMPK-SREBP1c regulatory node that promotes lipogenic transcription. LY6D is an upstream regulator of hepatic de novo lipogenesis in MASLD. Our data support a model in which LY6D promotes lipogenic signaling via an LY6D-associated GRB2-AMPK-SREBP1c pathway, and suggest that LY6D may represent a therapeutic entry point to complement current MASLD/MASH treatments. LY6D was found to bind GRB2, leading to suppression of AMPK phosphorylation at Thr172. This inhibition promoted transcription and nuclear translocation of SREBP1, thereby enhancing transcription of key lipogenic genes (Acaca, Fasn, and Scd1) and consequently increasing hepatic de novo lipogenesis.

This study aims to synthesize global research trends and theoretical developments regarding the integration of APOS (Action, Process, Object, Schema) Theory and Computational Thinking (CT) in mathematics education over the past decade. The method used is a Systematic Literature Review (SLR) of 18 reputable journal articles with a time span of 2016–2026. The results of the review indicate that the integration of CT and APOS is not merely a pedagogical choice, but an epistemological necessity that forms a complementary symbiosis. On the one hand, APOS provides a structured cognitive map that reveals the urgency of providing scaffolding at the Action and Process stages to prevent missing stages in students who are still stuck at the basic computational level. On the other hand, empirical findings support the implementation of the M-APOS model which is proven to significantly improve CT abilities with Cohen's d of 1.57 raises a critical reciprocal hypothesis: that the CT pillars are suspected to act as facilitators that activate the effectiveness of the transition between APOS stages. This study concludes that designing learning tools such as diagnostic instruments, modules, and digital worksheets that position CT as a cognitive entry point in the APOS traversal is an urgent priority. This adaptive instructional design is projected to transform students from mere mechanical calculators into autonomous, reflective problem solvers with systemic thinking capabilities.

Nutrition shapes development, health and risk of disease over the life course and across generations. The predominant approaches to understanding these relationships have either been to consider the effects of single nutrients, one at a time, or to consider associations with food types and dietary patterns. Although, to date, the single-nutrient approach has defined much of the scientific enquiry and public debate on the macronutrients - carbohydrate, fat and protein - there is an emerging appreciation that their proportions and quality matter more than their individual effects. Growing evidence demonstrates that macronutrient interactions operate at multiple biological levels, and research on dietary protein has proven a particularly productive entry point for characterizing these mixture effects. In this narrative Review, we begin by analysing key issues and introducing a framework for navigating the complexity of macronutrient mixtures (nutritional geometry), then consider the role of macronutrient proportions on food intake, systemic physiology, health and the risk of disease across the life course. Finally, we discuss how human nutritional biology has been subverted within the modern, industrialized food environment, contributing to the global burden of obesity and related diseases of unhealthy ageing.

Shelter and settlement are critical determinants of health in humanitarian crises, yet their impacts on health outcomes remain underexplored. This review synthesizes published evidence on how shelter and settlement interventions impact health outcomes in humanitarian crises. A systematic review of peer-reviewed literature was conducted to identify studies examining the association between shelter and settlement interventions and health outcomes in humanitarian crises. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines a protocol was developed and three databases were searched for studies published between 2005 and 2025. Relevant data were extracted and thematically analysed. A total of 138 articles were found. Thematic analysis identified six themes (living conditions, accommodation type, camp and site planning, displacement status, essential household items and cash-based interventions). Three cross cutting themes of gender, climate change and vulnerability were also identified. Two themes (living conditions and accommodation type) are presented here. Poor living conditions including damaged shelters, poor housing design and materials were associated with increased risks of communicable diseases such as malaria, diarrhoea, and soil-transmitted helminth infections while overcrowding heightened injury risk and psychological distress. Accommodation type influenced health outcomes with short-term shelters linked to acute mental health challenges and increased injuries; medium-term shelters with increased risk of non-communicable disease; and long-term housing with deteriorations in chronic disease management. This systematic review synthesises the evidence base showing how shelter and settlement interventions play a role in influencing health outcomes in humanitarian crises. It shows that shelter is a critical yet often under recognised determinant of health in these settings. Health outcomes are influenced by housing quality, accommodation type and duration, camp and settlement planning, displacement dynamics including frequency and length of displacement, and access to essential household items. Poor shelter conditions are likely to increase the risk of communicable diseases and mental health issues and have the potential to worsen chronic disease outcomes and risk. A key contribution of this review is the identification of shelter as a core entry point for public health action, highlighting the need for clearer operational guidance on shelter typologies, minimum standards, and their integration with health, protection and social services.

AI companion platforms like Character.ai and Replika now sustain emotionally deep, continuous relationships with millions of users. As algorithms increasingly mediate human intimacy, we must under-stand how these platforms simultaneously foster genuine connection and extract valuable behavioural data. This is crucial for communication, platform, and digital labour studies. Existing frameworks – parasocial theory, artificial sociality, and social substitution – capture specific dimensions of AI intimacy. However, they fail to explain how the exact same architecture sustaining these relationships also converts them into commercial AI training data. This study asks: (RQ1) What technical architecture converts users’ relational agency into training data? (RQ2) Why doesn’t knowing the AI is artificial stop emotional investment? (RQ3) How does the ACG subculture’s “2.5D cognitive infrastructure” enable and intensify this extraction? Integrating mediatization, media dependency, and platform studies, this critical analysis of interface affordances argues that user agency and data extraction are co-produced. The very mechanisms giving users relational control simultaneously generate high-signal data for commercial model optimization. Three key findings emerge. First, a two-stage architecture – In-Context Learning and batch RLHF – drives this co-production. Second, “Affective Playbor” is introduced to describe extracting data through interactions that users experience as autonomous emotional expression. Third, ACG database-consumption practices structurally pre-adapt users for this extraction; knowing the AI is fake acts as a platform entry point, not a safeguard. Finally, this study reframes social substitution as intensified media dependency. When a medium stops merely providing information and directly replaces the human interlocutor, dependency saturates into total substitution. This provides a testable analytical vocabulary for the mediatization of intimate life, repositioning AI companionship within core communication research.