Search Results (88)

Background: Following a significant decline during the 2020–2021 SARS-CoV-2 pandemic, Mycoplasma pneumoniae (MP) experienced a resurgence across Europe in 2023–2024. Although macrolide-resistant MP has increased globally, severe disease can occur even in the absence of resistance, which highlights the importance of rapid molecular characterization for clinical purposes. In this context, clinical severity is often improperly used as a surrogate marker of macrolide resistance, potentially driving unnecessary antibiotic escalation. Methods: We report a severe MP pneumonia occurring during the 2023–2024 resurgence and evaluate macrolide resistance through a rapid two-step workflow (Real Time-PCR screening for A2063G/A2064G followed by confirmatory 23S rRNA sequencing), to assess whether severity predicts resistance and to support antibiotic stewardship. Results: The patient developed acute hypoxic respiratory failure (PaO₂ 54.9 mmHg; P/F ratio 110), extensive centrilobular micronodules on chest CT imaging, significant systemic inflammation and elevated liver enzymes. Respiratory support was escalated from a Venturi mask to a high-flow nasal cannula and BiPAP. MP infection was confirmed by multiplex Real Time-PCR (RT-PCR) and supported by positive IgM/IgG serology. RT-PCR targeting A2063G/A2064G mutations revealed no resistance-associated variants, and Sanger sequencing of an 807 bp 23S rRNA fragment confirmed a wild-type genotype. Despite severe hypoxemic respiratory failure, no resistance-associated variants were detected, documenting a clear severity–genotype mismatch. Clinical and radiological improvement followed second-line antibiotic therapy. Conclusions: Severe MP pneumonia can occur despite the absence of macrolide resistance. During MP re-emergence, clinical severity should not be used to infer macrolide resistance. Integrating nucleic acid amplification test (NAAT) diagnosis with rapid genotyping/confirmatory 23S rRNA sequencing can prevent misclassification, reduce unwarranted broad-spectrum escalation, and strengthen antimicrobial stewardship decisions. Full article

Goal orientation is a key motivational factor in individuals’ career development, yet its links with emotional and personality-related career decision-making difficulties (EPCD) have received limited attention. According to the Career Construction Model of Adaptation (CCMA), this study examined how goal orientation relates to EPCD and whether four dimensions of career adaptability (CA)—career concern, career curiosity, career control, and career confidence—mediate these relationships. In total, 450 Chinese university students completed an online questionnaire measuring learning goal orientation (LGO), performance-approach (PAPG) and performance-avoidance goal orientations (PAVG), CA, and EPCD. The results showed that PAPG and PAVG were positively associated with EPCD, whereas LGO was not directly associated with EPCD. Mediation analyses indicated that concern, curiosity, and confidence mediated the relationships between LGO, PAPG, and EPCD; confidence mediated the relationship between PAVG and EPCD. The findings extend the application of CCMA and offer implications for career counseling and intervention for university students. Full article

The Papanicolaou (Pap) smear, a cornerstone of cervical cancer prevention, has emerged as a compelling, though unconventional, biospecimen for the detection of ovarian cancer (OC). This structured narrative review synthesizes the evolving evidence on the utility of cervicovaginal cytology and molecular analysis of Pap test material for OC detection. While conventional cytology provides a proof of concept, its sensitivity is low, ranging from incidental detection of OC in 0.004% of routine screens to 19.3% in patients with known OC. Specific cytologic findings, however, carry significant predictive value: atypical glandular cells (AGC) confer a two-fold increased OC risk, and psammoma bodies (PB) are strongly associated with serous malignancies. Driven by the sensitivity limitations of morphology, the field has undergone a paradigm shift towards molecular detection. Foundational studies confirmed tumor-derived DNA, including hallmark TP53 mutations, is detectable in Pap samples years before diagnosis, though sensitivity is constrained by low DNA abundance and confounded by background clonal mutations. To overcome this, strategies have expanded to target broader genomic signatures, such as somatic copy number alterations (EVA test: 75% sensitivity, 96% specificity), and multi-gene mutation panels (PapSEEK: 33–45% sensitivity). The most promising advances lie in multi-omic approaches, particularly DNA methylation biomarkers, which have demonstrated sensitivities up to 81% with high specificity. Collectively, this evidence argues against repurposing the Pap test as a standalone OC screen but supports its strategic integration into a risk-stratified clinical algorithm. We propose a “reflex-to-molecular” model where high-risk cytology (e.g., AGC, PB) automatically triggers advanced molecular testing on the same sample. This model efficiently leverages existing infrastructure to triage high-risk women for definitive diagnostics. Prospective validation of this integrated approach is the essential next step toward transforming this test into a sentinel for malignancies of the upper female reproductive tract. Full article

Although urban streetscape visual esthetic quality (VAQ) assessment has progressed markedly, its findings are rarely operationalized in urban planning policy-making. The resulting discontinuity in the assessment–policy linkage is a critical impediment to streetscape VAQ enhancement. We propose an eye-tracking-enabled, end-to-end decision support framework that links evidence acquisition, intervention prioritization, design strategy formulation, and outcome feedback. Eye tracking is integrated to establish a three-dimensional assessment system spanning spatial, psychological, and physiological dimensions. Within this integrated system, we construct a three-level eye-tracking-based visual characteristics (ET-VC) framework across streetscape elements, formal characteristics, and public esthetic perception (PAP). Together, the three-dimensional system provides a theoretical basis for acquiring the multi-modal data required for VAQ enhancement. Building on this integrated assessment, we embed scenario planning theory to construct a planning facing decision model with PAP as the core outcome. The model combines importance-performance analysis (IPA) with the coupling coordination degree model (CCDM) to guide resource allocation decisions and intervention prioritization, and further uses eye-tracking evidence to support the development of refined, actionable enhancement strategies. A case study in Wudadao validates the framework’s robustness and feasibility. The ET-VC results provide additional evidence for interpreting esthetic perception: (1) ET-VC indicators differ significantly across streetscape elements, and “being viewed more” does not necessarily correspond to higher esthetic ratings; (2) four groups of key formal characteristic indicators—color configuration, naturalness, historicity and planning/regulatory control, and visual scale—systematically reshape fixation onset and maintenance patterns; and (3) PAP appears to involve partially nonlinear relationships between material landscape features and additional top-down influences (e.g., historical narratives and individual experience), rather than being fully explained by linear associations alone. Overall, this study provides both a theoretical basis and an applied demonstration for evidence-based streetscape VAQ enhancement. Full article

This study assessed the effects of eco-efficient aquafeed formulations on the growth, body composition, nutrient retention, and flesh quality of rainbow trout (Oncorhynchus mykiss). Four extruded diets were tested: a conventional control (Ctrl) and three eco-efficient formulations (No-PAP, PAP, and Mix) combining single-cell ingredients, insect meal, selected plant proteins, and aquaculture by-products, with long-chain omega-3 fatty acids (DHA and EPA) supplied primarily from microalgae. Rather than isolating single-ingredient replacements, the objective was to evaluate the efficacy of complex, industry-feasible formulations designed for practical application. These experimental feeds were administered to 800 trout (initial body weight 63 g), distributed across four replicates per diet. After a 97-day trial, results showed no significant differences in growth performance (final weight, weight gain, and relative growth rate) between diets. Feed conversion ratios (~0.78) were within expected ranges for rainbow trout under these conditions. Fillet texture and composition were similar across all groups; however, trout fed the No-PAP diet developed a significantly more yellow tint in fillet color, likely attributed to xanthophyll pigments from plant- and algae-based ingredients. The environmental impact of the diets was driven by specific ingredient choices, as evidenced by a carbon footprint analysis ranging from 1.39 kg CO₂ eq. (PAP diet) to 2.36 kg CO₂ eq. (Ctrl diet). These findings demonstrate that the three alternative formulations matched the efficacy of conventional feed, offering a sustainable option for trout aquafeed production. Full article

Automated analysis of liquid-based cervical cytology is increasingly supported by digital microscopy and deep learning. However, model generalization remains challenging due to scanner- and laboratory-induced domain shifts affecting color, texture, and morphology. In this study, we present a robust cell-level classification framework for liquid-based Pap smear cytology based on deep transfer learning, designed to operate under heterogeneous acquisition conditions. We construct a multi-source dataset by integrating three widely used public reference repositories (SIPaKMeD, Herlev, CRIC Cervix) with a proprietary cohort comprising 416 Whole Slide Images (WSIs) collected from two medical centers and digitized using different scanning systems. All labels are harmonized into four Bethesda categories (NILM, ASC-US, LSIL, HSIL), and cell-centered 224 × 224 patches are used as standardized inputs for model development and benchmarking. We evaluate state-of-the-art CNN backbones (ResNet50, EfficientNetB0, VGG16) and perform systematic ablation across data-source combinations to quantify robustness under acquisition variability. Among the evaluated models, ResNet50 yields the best overall performance on the independent test set (accuracy = 0.91; macro-F1 = 0.91), consistently outperforming EfficientNetB0 and VGG16. Importantly, incorporating proprietary multi-center WSI-derived data improves robustness to scanner-induced variation compared to training on public data alone. These findings demonstrate that combining diverse data sources can mitigate domain shift in cell-level cervical cytology classification. While clinically actionable screening requires slide-level aggregation (e.g., MIL-based WSI inference), the proposed classifier provides a robust component that can be integrated into end-to-end WSI screening pipelines in future work. Full article

Breast cancer is the most frequently diagnosed malignancy among women worldwide, with the luminal A subtype being the most prevalent. Several studies have reported a complex interplay between breast cancer cells and the local microbiome; however, the mechanisms by which tumor cell-secreted factors influence bacterial biological properties remain insufficiently explored. In this study, we established an in vitro model that partially recapitulates the luminal A breast cancer microenvironment by exposing three breast-associated bacterial species, Pseudomonas aeruginosa, Enterococcus faecalis, and Escherichia coli, to conditioned media (CM) derived from MCF-7 (tumor) or MCF-10A (non-tumor control) cell lines. A combination of complementary approaches, including ultrastructural morphological assessment, biofilm formation assays, antimicrobial susceptibility testing, and virulence gene abundance profiling by genomic qPCR, was employed to reveal distinct tumor-microbiota interactions. Exposure to MCF-7 CM induced dose-dependent structural alterations in P. aeruginosa and E. faecalis, with pronounced membrane blebbing and structural disruption in E. faecalis. Biofilm formation was differentially modulated in a species- and concentration-dependent manner, with a persistent increase observed in E. coli. Antibiotic susceptibility profiles were selectively altered in E. faecalis, which displayed increased sensitivity to vancomycin, penicillin, and imipenem, along with decreased sensitivity to chloramphenicol. P. aeruginosa exhibited increased sensitivity to imipenem along with reduced sensitivity to meropenem and gentamicin, whereas no significant changes were observed in E. coli. qPCR analyses demonstrated that MCF-7 CM was associated with enrichment of multiple virulence-associated genes (e.g., lasB, exoS, pilB, plcH, fsrC, esp, fimH, and papG), reflecting enhanced pathogenic and adhesive potential. Collectively, these findings suggest that luminal A breast cancer-derived factors can reprogram microbial phenotypes in a species-specific manner, providing mechanistic insight into breast tumor-microbiome crosstalk and a platform to explore microbiome-targeted interventions. Full article

Texture image retrieval based on subjective visual descriptions remains a significant challenge due to the “semantic gap”, where conventional Content-Based Image Retrieval (CBIR) methods rely on low-level features or reference images that often diverge from human perception. To bridge this gap, this paper proposes a reference-free, perception-driven retrieval framework that enables users to query textures directly via abstract perceptual attributes. First, we constructed a human-centric perceptual feature space through controlled psychophysical experiments, quantifying 12 explicit texture attributes (e.g., granularity, directionality) using a 9-point Likert scale. Second, addressing the variability in visual sensitivity across user demographics, we developed a user-adaptive mechanism incorporating dual perceptual libraries tailored for art-major and non-art-major groups. Retrieval is formulated as a perception-aligned similarity optimization problem within this normalized space. Experimental evaluations on the Describable Textures Dataset (DTD) demonstrate that our method achieves superior perceptual consistency compared to both handcrafted descriptors (GLCM, LBP, HOG) and deep learning baselines (VGG16, ResNet50). Notably, the framework attained high PAP@3 performance across both user groups, validating its effectiveness in decoding fuzzy human intent without the need for query images. This work provides a robust solution for semantic-based texture retrieval in human–computer interaction scenarios. Full article

Background and Clinical Significance: Scurvy, caused by chronic vitamin C deficiency, is re-emerging in Western countries, particularly among pediatric patients with highly selective diets. While its musculoskeletal and mucocutaneous manifestations are well-known, its association with pulmonary arterial hypertension (PAH) is rare and poorly understood. Ascorbic acid and iron are essential cofactors for prolyl hydroxylases (PHD), which regulate Hypoxia-Inducible Factors. Their combined deficiency may trigger a “pseudohypoxic” state, leading to pulmonary vascular remodeling and vasoconstriction. Case Presentation: A 30-month-old female presented with a one-month history of limping, lower limb pain, and gingival hypertrophy. Dietary history revealed an almost exclusive cow’s milk-based intake. Physical examination showed diffuse petechiae, pallor, and right knee edema. Laboratory findings confirmed scurvy (undetectable vitamin C), severe iron-deficiency anemia (Hb: 72 g/L; ferritin: 22 mcg/L; RDW: 30%), folate deficiency, and hyperhomocysteinemia. Notably, elevated copper and vitamin B12 levels suggested a state of metabolic dysregulation. Echocardiography revealed moderate PAH phenotype (estimated sPAP: 47–50 mmHg) and a hyperdynamic contractility. A “perfect storm” mechanism was hypothesized, involving iron–ascorbate-dependent PHD impairment, high-output state, and oxidative-stress-induced hepcidin dysregulation (suggested by elevated copper). Following intravenous vitamin C and multivitamin supplementation, pulmonary pressures normalized within one week. Conclusions: PAH phenotype in scurvy represents a reversible metabolic disruption of pulmonary vascular tone rather than a structural disease. This case underscores the synergistic role of vitamin C, iron, and folate in vascular homeostasis. Clinicians should maintain high suspicion for scurvy in children with selective diets and unexplained PAH, as nutritional restoration is curative. Full article

Chronic thromboembolic pulmonary disease (CTEPD) is a severe long-term complication of acute pulmonary thromboembolism (PTE). Its pathogenesis is multifactorial, involving incomplete thrombus resolution, hemodynamic burden, comorbidities, and genetic factors. However, the contribution of inherited thrombophilic mutations to CTEPD development remains controversial. This retrospective cohort study included 204 patients diagnosed with acute PTE at a tertiary referral center between December 2023 and December 2024. Baseline demographic, clinical, laboratory, and echocardiographic data were collected. Genetic analysis assessed Factor II, Factor V Leiden, MTHFR C677T, MTHFR A1298C, Factor XIII V34L, and PAI-1 4G/5G polymorphisms. Patients were followed for at least 12 months for the development of CTEPD, defined according to guideline-based hemodynamic and imaging criteria. During follow-up, 17 patients (8.3%) developed CTEPD. Patients with CTEPD were significantly older and had higher baseline and follow-up systolic pulmonary artery pressure (sPAP) (p < 0.001), elevated NT-proBNP and troponin levels (both p < 0.001), and more frequent comorbidities, including cardiac and renal disease. Multivariate logistic regression identified comorbid diseases (HR: 0.17, 95% CI: 0.039–0.80, p = 0.025) and genetic thrombophilic factors (HR: 0.30, 95% CI: 0.10–0.91, p = 0.034) as independent predictors. Among genetic variants, only the PAI-1 4G/5G polymorphism was significantly associated with CTEPD (p = 0.001). Our study demonstrates that advanced age, comorbid diseases, elevated cardiac biomarkers, and genetic predisposition are associated with the development of CTEPD after acute PTE, while the PAI-1 4G/5G polymorphism may contribute to CTEPD susceptibility within a multifactorial context. Full article

Crack segmentation in cluttered scenes with slender and irregular patterns remains difficult, and practical systems must balance accuracy and efficiency. We present CONTI-CrackNet, which is a lightweight visual state-space network that integrates a Multi-Directional Selective Scanning Strategy (MD3S). MD3S performs bidirectional scanning along the horizontal, vertical, and diagonal directions, and it fuses the complementary paths with a Bidirectional Gated Fusion (BiGF) module to strengthen global continuity. To preserve fine details while completing global texture, we propose a Dual-Branch Pixel-Level Global–Local Fusion (DBPGL) module that incorporates a Pixel-Adaptive Pooling (PAP) mechanism to dynamically weight max-pooled responses and average-pooled responses. Evaluated on two public benchmarks, the proposed method achieves an F1 score (F1) of 0.8332 and a mean Intersection over Union (mIoU) of 0.8436 on the TUT dataset, and it achieves an mIoU of 0.7760 on the CRACK500 dataset, surpassing competitive Convolutional Neural Network (CNN), Transformer, and Mamba baselines. With 512 × 512 input, the model requires 24.22 G floating point operations (GFLOPs), 6.01 M parameters (Params), and operates at 42 frames per second (FPS) on an RTX 3090 GPU, delivering a favorable accuracy–efficiency balance. These results show that CONTI-CrackNet improves continuity and edge recovery for thin cracks while keeping computational cost low, and it is lightweight in terms of parameter count and computational cost. Full article

Background: Extra digits on the hands and/or feet are a frequent condition known as polydactyly. Twelve nonsyndromic polydactyly genes have been identified, including KIAA0825. Methods: Four consanguineous Pakistani families that segregate nonsyndromic postaxial polydactyly (PAP) with an autosomal recessive mode of inheritance were clinically and genetically evaluated. Exome sequencing or genotyping of polymorphic microsatellite markers followed by Sanger sequencing were used to identify the variants underlying the PAP etiology. Results: Three novel KIAA0825 variants were identified that segregate with PAP: a nonsense variant c.2319G>A; p.(Trp773*) in two families; a missense variant c.970G>T; p.(Val324Phe) in one family; and a four amino acids in-frame deletion c.2743_2754del; p.(Gln915_Val918del) in one family. The nonsense variant segregated in families with PAP type B (PAPB), while the missense and the in-frame deletion variants segregated with PAP type A and B. Conclusions: The findings of this study expanded the clinical and genetic spectrum of PAP due to KIAA0825 variants including the first KIAA0825 variant specific to PAPB. Full article

Background and Objectives: Congenital thrombophilias are biologically plausible contributors to chronic thromboembolic pulmonary hypertension (CTEPH), yet their frequency and clinical impact remain uncertain. We undertook a systematic review to (i) estimate the pooled prevalence of specific hereditary defects among adults with CTEPH, (ii) characterise associated demographic and haemodynamic phenotypes, and (iii) summarise peri-operative and survival outcomes after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in genetically defined subgroups. Methods: A protocol compliant with PRISMA-2020 was registered prospectively on the Open Science Framework (OSF). PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 1 June 2025 using validated, PRESS-reviewed strings combining CTEPH and thrombophilia terms. Observational cohorts, case–control studies and trials reporting laboratory-confirmed congenital thrombophilias in adults with right-heart-catheter-defined CTEPH were eligible. Results: Eight studies encompassing 677 unique CTEPH patients met the inclusion criteria. Among the 400 individuals screened for deficiencies of the natural anticoagulant pathways, 56 possessed a defect: protein S deficiency 5.3% (21/400; 95% CI 3.3–8.0), protein C deficiency 4.3% (17/400; 2.5–6.8), and antithrombin deficiency 1.5% (6/400; 0.6–3.3). In 520 genotyped patients, factor V Leiden and prothrombin G20210A were infrequent (1.3% and 1.0%, respectively) and confined to European/North American cohorts. Baseline haemodynamics were uniformly severe (mean mPAP 46.7 mm Hg; pulmonary vascular resistance ≈ 9 WU). Definitive reperfusion therapy was common (PEA 63%; BPA 18%), reducing mPAP to 20.5 mm Hg and yielding a weighted one-year survival of 96.2%. No study demonstrated a thrombophilia-specific effect on surgical candidacy or early survival. Conclusions: Approximately one in seven patients with CTEPH harbours a congenital thrombophilia, most often protein S or protein C deficiency, whereas classic venous-thrombo-embolism mutations are rare and ethnically restricted. Current evidence indicates that genetic status does not materially influence haemodynamic severity, uptake of PEA/BPA, or short-term survival, supporting guideline recommendations for universal referral to specialist reperfusion centres. Future multicentre registries integrating systematic genotyping and long-term outcome capture are needed to clarify genotype-specific prognostic and therapeutic implications. Full article

Objective: The aim of the present study was to investigate the association of polymorphic variants in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-3 (MMP-3) genes and the occurrence of persistent apical periodontitis (PAP). Methods: DNA samples from 180 individuals were recruited and divided into two groups: Case group, 79 subjects with a history of PAP; control group, 101 healthy subjects. Five single nucleotide polymorphisms (SNPs) were selected for genotyping: rs243865, rs2285053, and rs2287074 in the MMP-2 gene, and rs679620 and rs522616 in the MMP-3 gene. The chi-square test or Exact Fisher (p < 0.05) and Odds Ratio (CI = 95%) were used to compare the frequencies of genotypes and alleles between the two groups. Results: A positive association was found for the MMP-3 rs522616 AG genotype (p = 0.025), the AG + GG genotypes (p = 0.015), and the G allele (p = 0.016) with PAP. Conclusions: The MMP-3 variant rs522616 was associated with PAP. Similar studies are needed analyzing other genes involved in extracellular matrix dynamics under inflammatory conditions to clarify the role of the genetic factors of PAP. Full article

Background: The Profunda Artery Perforator (PAP) flap is a viable alternative to the Deep Inferior Epigastric Perforator (DIEP) flap, particularly for patients with low BMI and therefore insufficient abdominal tissue. To reduce the high complication rate, especially in our low BMI patient population, we have adapted the use of the vertical skin island design. This study compares complication rates and long-term outcomes of vertical versus horizontal skin island designs in PAP flap breast reconstruction. Methods: This prospective, single-center study included 20 patients who underwent PAP flap breast reconstruction. Quality of life and scar quality were assessed using the BREAST-Q and POSAS questionnaires. Additionally, the cosmetic outcomes were analyzed by four plastic surgeons. Results: Mean BMI in the vertical group was 23.9 kg/m² and 22.7 kg/m² in the horizontal group. Mean flap weight was 326 g for the vertical group and 355 g for the horizontal group. Fewer complications were observed at the donor site in the vertical group (Clavien–Dindo Classification 3b at donor site: p = 0.25). The BREAST-Q evaluation revealed significantly better results regarding the psycho-social well-being (p = 0.04) in patients with the horizontalskin island design. Scar evaluation using the POSAS revealed that the scar was perceived as thinner (p = 0.02), less pigmented (p = 0.03), and showed less relief (p = 0.02) in the vertical group. No significant difference was observed in the overall scar assessment by observers (p = 0.46). The aesthetic analysis by plastic surgeons showed significantly better results in the horizontal group. Conclusions: The vertical skin island design in PAP flap breast reconstruction was associated with lower complication rates and better scar quality compared to the horizontal design. Surgeons, however, rated the overall aesthetic outcome of the vertical design less favorably. These findings highlight the importance of balancing donor site morbidity with overall aesthetic results. Full article