Virtual reality-based robotic surgery training has received significant attention in recent years due to its numerous advantages, notably improved safety, an enhanced learning experience, and reduced cost. The visual realism and user immersiveness of such platforms are enhanced through the integration of appropriate soft tissue deformation models. This study presents a modified mass-spring-damper framework designed to provide stable, realistic soft tissue deformation while maintaining real-time performance, even for high-density mesh models. The proposed framework extends the conventional mass-spring model by introducing two kinds of spring-damper elements: deformation and restoring components. Optimization of the model parameters is performed through a combination of analytical derivation and empirical tuning. Various numerical simulation studies are performed to assess model restoring capability, numerical stability, and real-time performance. The results show that the model produces physiologically realistic deformation responses, regains its initial shape characteristics when the external force is removed, and provides a stable response in real-time simulation. A high performance rate of 171.11 frames per second is achieved on high-density mesh models consisting of approximately 29,754 vertices. Moreover, the deformation solver consistently maintains an average update frequency of 2828.14 Hz, with a mean step time of 0.354 ms, demonstrating its real-time capability. Additional experiments involving synthetic tissue and a surgical end-effector validate the tissue response to external forces. The ability of the proposed framework to deliver real-time performance on high-density mesh models highlights its suitability for haptic-enabled robotic surgical training environments that demand both computational efficiency and visual realism.
Divergent synthetic transformations that convert a single precursor into a range of structurally distinct products are powerful tools for rapidly exploring chemical space. Although numerous strategies exist for converting versatile functional handles such as halides and boronic acids into a multitude of reactive intermediates, there remains a pressing need for methodologies that exploit alternative linchpin fragments to open complementary avenues to molecular complexity. Herein, we report a divergent, anomeric amide-enabled, aldehyde functionalization strategy, allowing access to unsymmetrical ureas, carbamates, thiocarbamates, thioesters, amines, or amides, all in a one-pot procedure. Unique to this transformation is the formation of N-Boc-hydroxamate intermediates, which serve as privileged platforms for orthogonal activation via Lossen-type rearrangements, single-electron transfer, or nucleophilic substitution, generating a diverse selection of reactive intermediates. Overall, this work establishes N-halo-O-activated hydroxycarbamate-type anomeric amides as valuable reagents for aldehyde diversification, offering a complementary approach to molecular complexity generation from feedstock compounds.
Reconciling therapeutic efficacy with a low risk of systemic toxicity persists as a critical hurdle in developing topical AR antagonists for AGA. Our first-generation soft drug AR antagonist 14-P1 showed pyrilutamide-comparable efficacy with enhanced pharmacokinetics and safety, yet required high dosing due to suboptimal AR antagonism. Here, structural optimization of 14-P1 focused on enhancing intrinsic AR antagonism through thiohydantoin scaffold refinement. Additionally, the implementation of a dual soft drug design strategy yielded the best-performing candidate 39, demonstrating potent AR antagonism (IC50 = 20.6 ± 2.3 nM) and favorable PK profiles. In a hair-growth mouse model, 0.5% 39 achieved comparable efficacy to 0.5% pyrilutamide with accelerated response kinetics (14-day vs 21-day onset) and preserved safety. This dual metabolic inactivation strategy successfully reconciles therapeutic potency with a low risk of systemic toxicity, providing a paradigm for next-generation topical AR antagonist development.
Reported are the syntheses, characterizations, and reactivities of the dinuclear nickel(II) complexes [Ni2(κ2-OOCR)3PNNPiPr]+ (R = Me or tBu, PNNPiPr = 2,7-bis-(di-iso-propylphosphino-methyl)-1,8-naphthyridine), isolated as the BF4- salts. Notably, the [Ni2(κ2-OOCR)3PNNPiPr]+ cations can be deprotonated reversibly at the methylene carbon of the ligand scaffold to form the neutral dinuclear Ni(II) complexes [Ni2(κ2-OOCR)3(*PNNPiPr)], where the *PNNPiPr anion is the deprotonated and dearomatized PNNPiPr. The latter complexes were also formed by hydrogen atom transfer (HAT) upon reaction of the mixed valent Ni2(I,II) species [Ni2(κ2-OOCR)3PNNPiPr] with hydrogen atom acceptors 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), 2,4,6-triterbutyl phenoxyl radical (tBu3ArO˙) and 2,4-diethoxybenzoquinone (DEBQ) or with air. Based on the reduction potentials obtained via cyclic voltammetry and the pKa values tracked via UV-Vis spectroscopy, the bond dissociation free energies of the methylene C-H bonds were found between 59 and 61 kcal mol-1. The kinetics of the proton/electron abstraction from the mixed valent complexes by various equivalents of TEMPO were monitored by UV-Vis spectroscopy. This process is reversible upon reaction with 5,10-dihydrophenazine, serving as both an electron and proton donor. No reaction intermediates were detected.
The development of low-frequency electromagnetic wave (EMW) absorbers with excellent stability in extreme environments remains a major challenge for radar stealth and anti-electromagnetic interference applications. Herein, a rare-earth-sulfur (RE─S) (RE = La, Ce, Pr, Sm, Gd, Er) surface modification strategy is first proposed to regulate the electromagnetic response of SiC-based ceramics via surface chemical bond evolution from Si─O to RE─O species. This process transforms fast-relaxation dipoles into slow-relaxation dipoles, thereby prolonging the polarization relaxation time and inducing a low-frequency shift in the absorption peak from the Ku band to the C band. The optimized SiC/Ce-S ceramics exhibits a minimum reflection loss (RL) of -60.08 dB at 5.76 GHz, while the strategy demonstrates broad universality across multiple RE elements. The enhanced EMW absorption performance is attributed to the synergistic regulation of surface chemistry, dipole polarization, and dielectric relaxation. Moreover, the RE─S modified ceramics show rapid thermal response, excellent corrosion resistance, and outstanding oxidation stability, retaining an RL of -54.46 dB at 5.44 GHz after annealing at 500°C. This work provides a viable strategy for designing multifunctional SiC-based EMW absorbers for operation in extreme environments.
Two-dimensional (2D) semiconductors have been widely explored for next-generation electronics, with rapid progress in both large-area synthesis and device integration. However, bridging these advances toward practical semiconductor processing requires batch-level uniformity and wafer-to-wafer reproducibility under a low thermal budget compatible with back-end-of-line (BEOL) integration, which remain insufficiently addressed. Here, we demonstrate a BEOL-compatible, batch-type synthesis of layered 2D-SnS2 at 350 °C and its scalable transistor integration. The sulfurization-based low-temperature conversion technique yields 2H-stacked multilayer SnS2 with a bandgap of ∼2.3 eV and a high work function of ∼5.9 eV. Wafer- and batch-level uniformity are systematically evaluated by Raman spectroscopy and atomic force microscopy (AFM), showing tightly distributed A1g peak positions and minimal thickness variation over 4-inch full wafers (400 measurement points) and across multiple wafers processed in the same run. Statistical analysis of 200 transistors fabricated across ten wafers reveals tightly distributed switching characteristics, with a batch-averaged on/off ratio of (2.95 ± 0.94) × 105, a threshold voltage of 5.22 ± 0.64 V, and an extrinsic field-effect mobility of 0.0367 ± 0.0045 cm2 V-1 s-1. This work provides a practical pathway toward BEOL-compatible low-thermal budget batch processing and transistor integration of 2D semiconductors.
Newborn screening (NBS) quantifying T-cell receptor excision circles with or without kappa-deleting recombination excision circles (TREC, KREC) enables early detection of severe T- and/or B-cell lymphopenia. However, both markers have limited specificity, often resulting in unnecessary referrals. We compared the effects of alternative risk-stratification strategies to reduce referrals while avoiding missed cases and unnecessary delays. We modeled the effects of multiple TREC and KREC-based NBS algorithms using a comprehensive real-life dataset from the first 6 years of the Swiss NBS program. Stratification approaches included adjustment of cut-offs and integration of clinical data such as gestational age (GA), postmenstrual age (PMA), inpatient vs. outpatient status, family history, and maternal immunosuppression. Lowering cut-offs alone reduced abnormal results by 42% for TREC and 64% for KREC. The most efficient TREC algorithm, based on exact TREC levels and post-menstrual age in preterm infants, reduced referrals by 61% (p < .0001) but missed nearly half of non-SCID T-cell lymphopenias and delayed referral in 2/3 of outpatients who eventually required immunological evaluation. Integration of family history and clinical signs mitigated delays in some cases. For KREC, combining information on gestational age, maternal immunosuppression, and inpatient status enabled a >10-fold reduction in referrals (p < .0001) while still identifying all confirmed agammaglobulinemia cases except two with λ5 deficiency. Risk-stratified, multistep NBS algorithms incorporating readily available clinical data can substantially reduce unnecessary referrals while preserving detection of target conditions. For KREC, simple algorithmic adjustments allow marked improvement in specificity with minimal diagnostic loss.
To assess progress, challenges, and enabling factors for building climate-resilient and low-carbon health systems across Latin America and the Caribbean, a region facing accelerating climate-sensitive health burdens amidst persistent health system fragilities. We conducted an explanatory, sequential, mixed-methods study integrating quantitative analysis of the Pan American Health Organisation Climate Change and Health surveys from 2021/2022 (n = 24 countries) and 2023/2024 (n = 27 countries) with semi-structured interviews involving four countries demonstrating progress (Argentina, Chile, Jamaica, Peru). Quantitative data were analysed descriptively across three sub-regions (Caribbean, Central America, South America). Qualitative data underwent two-stage coding (deductive and inductive) with three-researcher consensus to identify barriers, enablers, and lessons learned. By 2023/2024, 93% of countries had designated climate-health focal points (71% in 2021/2022). However, implementation gaps persist: less than 50% of countries had integrated climate change into national health reports; 22%-40% developed national climate-health strategies; and vulnerability assessments rarely informed policy. Access to international climate finance remained inequitable. Whilst 60%-74% developed disaster preparedness plans, only 30%-44% implemented public health communication campaigns. Training focused on environmental health personnel, with doctors, nurses, and planning staff minimally engaged. Qualitative analysis revealed interconnected barriers: climate change perceived as distant rather than urgent, competing priorities overwhelming decision-makers, institutional silos, and misalignment between available training and local needs. Key enablers included linking climate action to established health priorities, institutionalising responsibilities through formal mechanisms, multi-stakeholder engagement, and committed individuals with diplomatic skills navigating cross-sectoral dynamics. Latin America and the Caribbean countries are establishing foundations for climate-resilient and low-carbon health systems, but translating governance progress into sustained implementation requires addressing systemic barriers through institutionalisation beyond political cycles, tailored capacity building, and innovative financing mechanisms. These findings inform guidance for health systems strengthening amidst accelerating climate change.
Although cancer vaccines have been proposed for decades, their clinical outcomes have remained largely unsatisfactory. Over the past decade, progress in deciphering the interaction between the immune system and cancer, along with widespread adoption of high-throughput sequencing technologies and improved MHC-peptide binding affinity prediction, have revitalized interest in cancer vaccine development. Nanomaterials benefit from the integration of tunable composition, modular architecture, and immunologically relevant dimensions, which collectively enable the rational design of immunomodulatory strategies tailored on demand, ensuring the reliable induction of antitumor immune responses. Given the spatiotemporal nature of immune responses, multifunctional nanomaterials can be further engineered to enable multivalent antigen presentation and controlled vaccine trafficking, thereby confining antitumor immune activation to desired contexts and minimizing off-target immune-related toxicities. Beyond conventional discussions of antigen delivery, this review emphasizes how rational nanomaterial design can be leveraged to regulate multiple stages of the cancer-immunity cycle, providing an updated perspective on the development of next-generation cancer vaccines. This Review will systematically summarize recent advances in nanomaterial-based cancer vaccines and discuss the key challenges and future directions in this rapidly evolving field.
This paper explores the role of the "Author of nature" in Charles Lyell's uniformitarianism. I start with a brief explanation of the term "uniformitarianism" and the identification of the fundamental hypotheses of Lyell's theory. Moving forward, I explore his idea of the balance of nature and show that Lyell believes that natural equilibrium represents a state of stability in inorganic and organic nature. As I show, the stability of inorganic nature is achieved through the alternate activity of natural - aqueous and igneous - forces, while the balance of organic nature is established via two processes: migrations of species and struggle for survival. However, the inorganic and organic natures are connected by a unilateral causal relation which enables the first to cause changes within the second. That being the case, the activity of inorganic forces can disturb the balance of organic nature and trigger modifications in the structure of organisms, leading to their evolution. Yet equilibrium can be restored through the interventions of the "Author of nature", who, as the instrument of evolution, equips every organism with useful variations necessary for their survival. Since organic nature represents an essential part of the natural system, the "Author of nature", through his actions, creates and preserves the balance of the whole nature. Thus, it appears that Lyell opts for a specific version of preformationism and that his uniformitarianistic worldview presupposes a significant regulative role for the omnipotent, omnipresent, and omniscient intelligent being.
Chiral discrimination of drug enantiomers is essential in neurodegenerative disease therapy. This study presented a chiral sensing platform utilizing L-histidine-functionalized copper nanoparticles (L-His@Cu NPs) with peroxidase-mimicking activity for the colorimetric detection of DOPA enantiomers. L-His@Cu NPs exhibited enhanced affinity and catalytic inhibition toward L-DOPA over its D-counterpart. Under optimized conditions, the sensor demonstrated a wide linear detection range of 0.02-4 mM and detection limits of 0.0107 mM for D-DOPA and 0.0129 mM for L-DOPA. The system also enabled enantiomeric excess analysis with high accuracy. Practical application in real pharmaceutical and water samples showed excellent recovery (92.32-104.18%) and stability over 50 days. This work offered a simple, cost-effective, and reliable strategy for on-site chiral discrimination, holding significant potential for pharmaceutical analysis and quality control.
Many patients with gastric cancer in low-incidence countries are diagnosed at advanced stages, underscoring the need for earlier detection to enable curative treatment. This systematic review aimed to summarize risk factors affecting the patient interval (symptom recognition to first contact with a healthcare professional) and the diagnostic interval (first contact to diagnosis). We reviewed the peer-reviewed literature from 2012 to 2025. The search was conducted across CINAHL, EMBASE, MEDLINE, and PsycINFO, with each title/abstract and full-text article reviewed by two team members. We extracted publication details, study methodology, variables, participant demographics, clinical descriptors, and interval-related information. We followed PRISMA reporting guidelines. Of 2,848 references screened, 8 studies were included: three on patient intervals and five on diagnostic intervals. Patient-interval studies involved 31 to 187 participants, with median lengths ranging from 9 to 210 days; patient-reported intervals were typically longer than those based on health data alone. Risk factors for longer patient intervals included herbal remedy use, symptom alarm and severity, older age, and multimorbidity. Diagnostic-interval studies included 69 to 2,175 participants, with median intervals of 24 to 84 days; factors associated with longer intervals included lower family-physician density, older age, early-stage disease, female sex, and low diagnostic suspicion. Long intervals between symptom onset and diagnosis remain a major challenge for people diagnosed with gastric cancer in countries without screening programs. This review identifies significant methodological gaps restricting comparability. Further research with standardized definitions and equity-focused approaches is needed to inform early detection and patient education initiatives.
The frequent association between renal and ocular anomalies suggests a common pathophysiological axis between the genetic and molecular mechanisms of the kidneys and multiple ocular structures during tissue formation, differentiation, and remodeling. The search was conducted in the PubMed, SciELO, Scopus, and Web of Science databases. This review article focuses on the common molecular and genetic bases of renal and ocular involvement in both systemic diseases and rare syndromes. The interdependence between renal and ocular morphogenesis is mediated by conserved molecular mechanisms, notably the Bone Morphogenetic Protein-7 (BMP-7) pathway, which regulates nephrogenesis and lens development, and the transcription factor Paired Box 2 (PAX2), which is essential for the formation of the genitourinary tract and the optic nerve. Shared expression of molecular components and dependency on their expression for the integrity of both the eye and the kidney lie in the stability of extracellular matrix components, specifically through laminin β2 (LAMB2) and type IV collagen, whose pathogenic variants underlie syndromic phenotypes such as Pierson and Alport syndromes. In addition, ciliopathies, developmental disorders, immune-mediated diseases, and inborn errors of metabolism, including Fabry disease, cystinosis, and primary hyperoxaluria, promote parallel injury to renal and ocular tissues through mechanisms involving abnormal cellular signaling, metabolite accumulation, complement activation and systemic inflammation. These mutual pathways affect diverse ocular structures, including the cornea, lens, retina, optic nerve, and basement membranes. Furthermore, the presence of the kidney-retina axis enables the use of the retina as a sentinel organ, allowing for non-invasive evaluation of glomerular microvasculature by means of high-resolution imaging technologies of retinal vessels. The kidneys and eyes share several genetic, developmental, structural, metabolic, and immunological mechanisms that explain the frequent association of congenital anomalies and acquired lesions in these organs and the associated diagnostic and prognostic implications.
The CVAC 2.0 ureteroscope enables simultaneous lasing and suctioning capabilities under direct visual guidance and received FDA clearance for use in lithotripsy procedures in early 2024. We report real-world clinical efficacy and safety data of this novel device. A retrospective cohort study was conducted at a single center where five urologists offered CVAC 2.0 treatment to their patients. Baseline demographic characteristics, procedure factors, complications, stone factors, and stone-free status based on volumetric and single-dimension analysis were collected through chart review. Stones volumes were calculated using the scalene ellipsoid formula and stone complexity was characterized by the modified S.T.O.N.E. score. A total of 61 cases and 106 stones were identified and eligible for volumetric analysis. Mean age was 60, mean BMI was 32, 28% were anticoagulated, and 73% had an ASA score of 3 or higher. Median total pre-operative linear stone burden was 2.2 cm and median volume was 1,003mm3. Most stones were classified as "complex" with mean S.T.O.N.E. score of 10. Mean stone clearance by volume reached 97%. 52% of patients were stone-free (zero residual fragments) whereas 84% had either zero stone or residual fragments < 4 mm. There were no immediate peri-operative complications, though 11.5% of patients returned to the ED within 30 days for management of stent colic, urinary retention, hematuria, and in one case, urosepsis. In a medically comorbid cohort with large-volume, complex renal and ureteral stones, CVAC 2.0 demonstrated excellent volumetric stone clearance and an acceptable safety profile with stone free rates comparable to or exceeding published ureteroscopy outcomes. Further comparative assessments and cost-effectiveness studies are needed to define the optimal role of CVAC 2.0 in nephrolithiasis management.
N6-methyladenosine profiles of mRNA transcripts regulate their translocation from the nucleus to the cytosol, stability, and translational efficiency; hence, they have been implicated in gene expression and disease progression. The m6A-methylation is widely associated with various cancers and neurological, cardiovascular, and developmental disorders, which demand early diagnosis. A robust m6A-motif prediction is necessary to enable us to identify the regulatory nucleic acid sequences that determine mRNA fate in normal and diseased conditions. We have developed a transcript-aware computational pipeline, termed m6A Functional Index in Transcription (m6A-FINDiT), that can identify potential m6A sites on mRNA transcripts, considering molecular intricacies associated with their secondary structure. This tool can separately identify m6A motifs within the coding sequences as well as in non-translatable regions, i.e., 5'UTR and 3'UTR, of mRNA transcripts. Parallelly, another technique was developed that quantifies specific m6A methylation motifs through a probe-based ELISA process, MAQ-G. This second method successfully validated the N⁶-methyladenosine motifs predicted by the initially developed motif-finder program. This integrated m6A-FINDiT and MAQ-G, coupled with a real-time qPCR assay, could correlate the methylation profiles of N6-methyladenosine motifs with the expression and stability contours of a gene. To establish the physiological implications of these techniques, we chose three tumour-suppressor genes, viz., IRF8, RB1, and TP53 mRNA transcripts, which may undergo m6A methylation at certain DRACH motifs. The m6A-FINDiT pipeline could successfully predict the specific m6A motifs, and the MAQ-G confirmed the methylation profile of the latter. These duo techniques hold potential for use in clinical settings for early cancer detection.
A lipoic acid(LA)-base hydrogel polymerization, viscosity, and relaxivity were explored by varying several different bases, additives, Gd3+ chelates, and with or without a reducing agent (tris(2-carboxyethyl)phosphine, TCEP). The polymerization of LA was greatly improved by using TCEP to convert the more inert disulfides into thiol initiators. The base deprotonation of LA was found to be essential to solubilize LA for polymer propagation. The various bases and TCEP additions had a substantial effect on viscosity, with values ranging from 1 × 108 to 1 × 103 mPa·s. This can enable targeting of many different applications that depend on viscosity, such as topical ointments or injectable hydrogels. The relaxivity effects of the LA-hydrogels were explored by varying the Gd3+ chelates' inner-sphere coordination or by adding one or two sulfur atoms, thereby allowing for a terminal or internal-linking Gd3+ chelate. It was found that the inner sphere and microenvironment dominate the relaxivity of Gd3+ chelates in the LA-hydrogel, with a high relaxivity of r1 = 49.2 ± 1.2 mM-1 s-1 at 1.4 T and 37 °C. Cellular uptake was confirmed by confocal fluorescence microscopy, and contrast was assessed in vivo at 9.4 T.
Hydroxyapatite nanoparticles (HANPs) have emerged as versatile and biocompatible platforms in cancer nanomedicine, offering multifunctional roles in drug delivery, imaging, and combinatorial therapy. Their structural similarity to bone apatite, tunable surface chemistry, and ion substitution capability enable precise functionalization for targeted and sustained drug release. This review provides a comprehensive overview of HA-mediated combinatorial cancer therapies, emphasizing their role as drug carriers, photothermal agents, and immunomodulators. The integration of HANPs with chemotherapeutic drugs, immunotherapy, photothermal and photodynamic therapy, and trace-element doping has shown significant synergistic effects enhancing antitumor efficacy while minimizing systemic toxicity. Furthermore, HANPs have demonstrated promise as theranostic agents by combining therapeutic and diagnostic functions through multimodal imaging techniques, including MRI, fluorescence, and PET/SPECT. Collectively, these advances underscore HANPs as intelligent, biocompatible nanoplatforms capable of simultaneous diagnosis and therapy. Despite remarkable preclinical progress, future studies must address scalability, long-term biosafety, and clinical translation to realize their potential in precision oncology fully.
Marine alveolate parasites, particularly early-branching dinoflagellates of the order Syndiniales, play critical yet often overlooked roles in shaping marine microbial communities. These parasitoids infect diverse hosts, including dinoflagellates, copepods, and fish eggs, and rely on short-lived, free-living dinospores for transmission. Despite their ecological significance, the distributions of Syndiniales dinospores and host-associated life stages across environmental gradients remain poorly understood. We used 18S rRNA gene region DNA metabarcoding combined with size-fractionated water filtration across vertical and horizontal gradients of salinity, oxygen, and nutrients in the Baltic Sea-Skagerrak system to characterize Syndiniales life-stage distributions and identify clades producing dinospores. This approach enables the differentiation of free-living dinospores and host-associated life stages. Most reads were assigned to Syndiniales groups I and II, indicating the presence of both host associations and dinospore presence. Dinospore communities were more diverse than host-associated life stages and showed variation in spatial distribution and community composition. The spatial variation was related to salinity, oxygen, and nitrogen concentrations, emphasizing the role of environmental conditions in shaping niches suitable for host-parasite associations and infection transmission. Our findings highlight the prevalence of Syndiniales communities across an environmental gradient and the influence of environmental conditions on their distribution patterns.
Primary acquired nasolacrimal duct obstruction (PANDO) is a common cause of epiphora. Because surgical outcomes are highly dependent on the obstruction site and anatomic variations, this study presents a deep learning-based framework for the automated morphological and quantitative analysis of the lacrimal system via CT dacryocystography (CT-DCG). A total of 151 patients with unilateral PANDO who underwent CT-DCG were included. An automated pipeline utilizing a deep learning network (Attention U-Net) was developed to segment and reconstruct the lacrimal sac and bony nasolacrimal duct (BNLD). The system performed automated quantification of the long axis, short axis, and cross-sectional area for each slice from the superior to the inferior opening of the BNLD, as well as for the lacrimal sac. Segmentation accuracy was evaluated using the Dice coefficient, and the clinical agreement of lacrimal sac size classification was assessed using Cohen's kappa coefficient compared to expert manual assessment. The deep learning model achieved robust performance in segmenting the lacrimal drainage system, with an average Dice coefficient of 0.79 for the BNLD. The system successfully enabled automatic, slice-by-slice morphological quantification, providing continuous measurement curves for the cross-sectional area and diameters throughout the entire duct. It accurately identified and localized the narrowest cross-sectional plane and the obstruction site within the BNLD. In the classification of lacrimal sac size, the automated morphological analysis demonstrated high consistency with expert assessment, achieving an overall agreement rate of 84.7% and a Cohen's kappa coefficient of 0.76. The proposed deep learning framework demonstrates the technical feasibility of automated segmentation and morphological quantification of the lacrimal sac and BNLD on CT-DCG. Although further prospective validation is required, the objective anatomic metrics provided by this system hold promising potential to assist in preoperative assessment and surgical planning for PANDO treatment. This proof-of-concept study demonstrates that automating the segmentation and quantification of the lacrimal drainage system on CT-DCG can provide an efficient, objective alternative to manual assessment. Whereas its definitive impact on surgical outcomes remains to be established, the system yields standardized morphological metrics that have the potential to support individualized preoperative evaluation and clinical decision making for nasolacrimal duct obstruction.
Long-read sequencing has enabled the generation of high-quality human genome assemblies, but many previous assemblies were based on blood-derived DNA and often relied on limited data types from a single sequencing strategy. This study aimed to generate high-quality phased genome assemblies of a Korean individual using multiple independent long-read datasets produced from a single sequencing platform and to evaluate their utility for chromosome-scale assembly and variant detection. Genomic DNA was extracted from a semen sample of a Korean male. Long-read, ultra-long-read, and chromatin conformation capture sequencing data were generated using Oxford Nanopore Technologies. These datasets were integrated to construct phased genome assemblies, followed by correction of noticeable phasing errors and assessment of assembly continuity, chromosomal representation, telomeric repeat recovery, and variant detection performance. The final phased assemblies spanned approximately 2.9 Gb and represented 23 pairs of chromosomes with an NG50 of 150 Mb. Telomeric repeats were detected at 36 and 37 of the 48 chromosomal ends in the two assemblies, indicating high end-to-end completeness. In addition, we successfully identified structural variants, including small variants. These results demonstrate that combining multiple Oxford Nanopore data types can produce highly continuous and informative phased human genome assemblies. We generated high-quality phased genome assemblies of a Korean individual using Oxford Nanopore long-read sequencing data derived from semen DNA. This publicly available genome resource will support broader applications of long-read sequencing in human genomics and variant analysis.