Search Results (106)

Background: Non-syndromic orofacial clefts (NSOFCs) are one of the common congenital malformations in Vietnam, with 1.4 per 1000 live births, with notable sex differences in occurrence. This case–control study aims to investigate potential sex-specific interactions of WNT3 and NOG polymorphisms across NSOFC subtypes in a Vietnamese population. Methods: A total of 720 participants were separated into 4 groups with a male/female ratio of 1:1 (160 individuals with cleft lip and palate (NSCLP), 160 with cleft lip only (NSCLO), 160 with cleft palate only (NSCPO), 240 healthy controls). Two single-nucleotide polymorphisms (SNPs), rs3809857 and rs227731, were genotyped by using the StepOnePlus Real-Time PCR System. Results: The most significant findings were found in the male NSCLO group under a recessive model of WNT3 rs3809857 after applying Bonferroni correction, as a five-fold protective factor with OR = 0.18 (95% confidence interval: 0.05–0.64, p = 0.0033). Additionally, the weak or moderate protective association between rs3809857 and male NSCLP was found with p < 0.05 under the dominant model. However, there were no significant findings in the female NSOFC subtypes associated with WNT3. Conversely, NOG rs227731 results showed a weak increased risk in female NSCLO and NSCPO with p < 0.05. Conclusion: this study identified the critical role of WNT3 rs3809857 in reducing NSCLO risk in males. These findings support the potential influence of sex as a modifying factor in the genetic susceptibility to non-syndromic orofacial clefts. Full article

Background/Objectives: The Motor Speech Hierarchy (MSH) Probe Words (PWs) have yet to be validated as effective in discriminating between children with impaired and children with typically developing speech motor control. This preliminary study first examined the effectiveness of the mandibular control subtest of the MSH-PWs in distinguishing between typically developing (TD) and speech sound-disordered (SSD) children aged between 3 years 0 months and 3 years 6 months. Secondly, we compared automatically derived kinematic measures of jaw range and control with MSH-PW consensus scoring to assist in identifying deficits in mandibular control. Methods: Forty-one children with TD speech and 13 with SSD produced the 10 words of the mandibular stage of the MSH-PWs. A consensus team of speech pathologists observed video recordings of the words to score motor speech control and phonetic accuracy, as detailed in the MSH-PW scoring criteria. Specific measures of jaw and lip movements during speech were also extracted to derive the objective measurements, with agreement between the perceptual and objective measures of jaw range and jaw control evaluated. Results: A significant difference between TD and SSD groups was found for jaw range (p = 0.006), voicing transitions (p = 0.004) and total mandibular scores (p = 0.015). SSD and TD group discrimination was significant (at alpha = 0.01) with a balanced classification accuracy of 0.79. Initial analysis indicates objective kinematic measures using facial tracking show good agreement with perceptual judgements of jaw range and jaw control. Conclusions: The preliminary data indicate the MSH-PWs can discriminate TD speech from SSD at the level of mandibular control and can be used by clinicians to assess motor speech control. Further investigation of objective measures to support perceptual scoring is indicated. Full article

The optimization of bioactive compound mixtures is critical for enhancing pharmacological efficacy. This study investigates, for the first time, the combined effects of eugenol, camphor, and terpineol, focusing on their half-maximal inhibitory concentrations (IC₅₀) across multiple biological responses related to diabetes management. Using a mixture design approach, the objective was to determine the optimal formulation that maximizes bioactivity and validate the findings experimentally. A simplex-centroid design was applied to evaluate the combined effects of eugenol, camphor, and terpineol on AAI _IC50, AGI _IC50, LIP _IC50, and ALR _IC50 responses. The desirability function was used to determine the ideal composition. The optimized formulation was experimentally validated using in vitro assays, and IC50 values were measured for each response using standard protocols. Results: The optimal formulation identified was 44% eugenol, 0.19% camphor, and 37% terpineol, yielding IC₅₀ values of 10.38 µg/mL (AAI), 62.22 µg/mL (AGI), 3.42 µg/mL (LIP), and 49.58 µg/mL (ALR). The desirability score (0.99) confirmed the effectiveness of the optimized blend. Experimental validation of the optimal mixture resulted in IC₅₀ values of 11.02 µg/mL (AAI), 60.85 µg/mL (AGI), 3.75 µg/mL (LIP), and 50.12 µg/mL (ALR), showing less than 10% deviation from predicted values, indicating high model accuracy. This study confirms the combined potential of eugenol, camphor, and terpineol, with eugenol and terpineol significantly enhancing bioactivity. The validated formulation demonstrates potential for pharmaceutical and cosmeceutical applications. Future research should explore mechanistic interactions, bioavailability, and in vivo efficacy to support the development of optimized natural compound-based therapies. Full article

Continental rifting is the process by which land masses separate and create new ocean basins. The emplacement of large igneous provinces (LIPs) is thought to have played a key role in (super) continental rifting; however, this relationship remains controversial due to the lack of a clearly established mechanism linking LIP emplacement to continental fragmentation. Here, we show that plume flow links LIP magmatism to continental rifting quantitatively. Our findings are further supported by the sedimentary record, as well as by the mineralogy and petrology of the rocks. This study analyzes the early Cretaceous separation of West Gondwana into South America and Africa. Prior to rifting, Jurassic hiatuses in the stratigraphic record of continental sediments from both continents indicate plume ascent and the resulting dynamic topography. Cretaceous mafic dyke swarms and sill intrusions are products of major magmatic events that coincided with continental rifting, leading to the formation of large igneous provinces in South America and Africa, including the Central Atlantic Magmatic Province, Equatorial Magmatic Province, Paraná–Etendeka, and Karoo. It has been suggested that dyke intrusions may weaken the lithosphere by reducing its mechanical strength, creating structural weaknesses that localize extensional deformation and facilitate rift initiation. The sedimentary analysis and petrological evidence from flood basalt magmas indicate that plumes may have migrated from the depths toward the surface during the Jurassic and erupted during the Cretaceous. It is thought that the resulting fast plume flow, induced by one or more mantle plumes, generated a dynamic force that, in combination with lithospheric weakening from dyke intrusion, eventually rifted the lithosphere of West Gondwana. Full article

Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential of a new liposomal vaccine formulation, Tuft-lip-WCAgs, comprising Tuftsin and C. albicans whole cell antigens, in providing immune protection against systemic candidiasis. Methods: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-γ and IL-4) from splenocytes. Results: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 ± 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 ± 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-γ (634 ± 128 pg/mL) and IL-4 (582 ± 82 pg/mL), indicating a balanced Th1/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 ± 197 CFUs/g). Conclusions: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis. Full article

Background/Objectives: Oral health is an important element of overall health and quality of life. However, few studies have evaluated the association between quality of life (QOL) and oral function, including tongue and lip movements. This study aimed to investigate the relationship between oral-related QOL and oral function, including tongue and lip movements, in independent elderly people. Methods: The participants were 143 community-dwelling elderly people in Taiwan (40 men, 103 women; 76.4 ± 6.4 years). We used the General Oral Health Assessment Index (GOHAI) to evaluate oral-related QOL. The items used to evaluate oral function were as follows: the speed of tongue movement from side to side, maximum tongue pressure, maximum lip pressure, the repeated saliva swallowing test, oral diadochokinesis (speed and dexterity when pronouncing /pa/, /ta/, and /ka/), and masticatory performance. In addition, we surveyed the number of remaining teeth, denture use, and awareness of problems at mealtimes. For the analysis, we compared the GOHAI score for each group, divided by cutoff values. Results: The univariate analysis revealed significant differences in the GOHAI score according to denture use, the number of remaining teeth, the state of occlusal support areas, the speed of tongue movement from side to side, oral diadochokinesis /ta/ and /ka/, and masticatory performance. The logistic regression analysis revealed that oral diadochokinesis /ka/ was a significant explanatory variable for low GOHAI scores (odds ratio = 13.145). Conclusions: Our results imply that lower oral-related QOL was associated with slow motor function at the rear area of the tongue. Full article

To investigate the physical phenomena interactions between airstream and liquid injection or droplets within a complex multi-stage swirl flow field, this study investigated the flow field and spray characteristics in a central stage direct injection combustor with a variety of optical diagnostic techniques, including using time-resolved particle image velocimetry (PIV) to measure the swirl flow field, using time-resolved planar Mie scattering (PMie) to measure the spray pattern, and using a laser particle size analyzer (LPSA) to measure the spray droplet size and its distribution. The results indicate that the lip recirculation zone (LRZ) and the swirl jet zone (SJZ) significantly influence droplet spatial and size distribution characteristics, such as spray penetration, cone angle, and droplet size. Due to the unique characteristics of the dual-stage swirl atomizer, the spray cone angle and penetration do not increase monotonically with the gas Weber number (${We}_g$). For the pilot stage, at a constant ${We}_g$, both the spray cone angle and penetration increase with higher fuel injection velocity. At different fuel injection velocities, the spray penetration increases with rising ${We}_g$. When the fuel injection velocity is low, the cone angle initially increases and then decreases as ${We}_g$ grows. The results about the effect of ${We}_g$ on droplet size distribution further support this conclusion. The Sauter mean diameter (SMD) of the main and pilot stage decreases with increasing relative pressure drop of air until reaching a stable state. The aerodynamic shear of the swirling airstream is sufficient to promote thorough fuel atomization, ensuring that the SMD remains low at the whole operating condition. Therefore, for the dual-stage swirl atomizer investigated in this study, good atomization can be achieved under low operating conditions, which provides a theoretical foundation and data support for the improvement and design of a low-emission, high-performance atomizer. Full article

Objectives: Nasal mucosa wound healing faces challenges such as acidic microenvironments and bacterial proliferation. Persistent mucosal defects predispose to complications such as nasal septal perforation. Conventional drug delivery systems suffer from nonspecific release and short-term efficacy. This study aimed to develop a pH-responsive liposome-hydrogel composite (HYD-Lip/DXMS@HG) to integrate pH-triggered dexamethasone (DXMS) delivery, antifouling properties, and mechanical support for refractory injuries. Methods: The composite combined acylhydrazone-modified liposomes with a hydrogel synthesized from hydroxyethylacrylamide (HEAA) and diethylacrylamide (DEAA). In vitro assays evaluated DXMS release kinetics, RPMI 2650 cell migration/proliferation, and antibacterial properties. In vivo rabbit nasal mucosal injury models assessed healing efficacy via histology analyses. RNA sequencing was performed to identify key signaling pathways. Results: HYD-Lip/DXMS@HG exhibited sustained DXMS release in acidic conditions, accelerating cell migration/proliferation in vitro. In rabbits, the composite reduced TNF-α expression and CD45+ leukocyte infiltration, while enhancing collagen alignment and epithelial thickness. RNA sequencing identified upregulated ECM receptor interaction, Hippo, TGF-β, and PI3K-Akt pathways, linked to collagen remodeling, anti-apoptosis, and angiogenesis. Conclusions: This multifunctional platform synergizes pH-triggered drug delivery, mechanical support, and antibacterial activity, offering a promising therapeutic strategy for refractory nasal mucosal injuries and postoperative recovery. Full article

Wood waste, primarily composed of lignin, cellulose, and hemicellulose, which is typically disposed of through burning and crushing, poses environmental challenges. However, conventional wood waste disposal methods present critical limitations, such as environmental pollution and resource waste. To develop sustainable processing strategies to dispose wood waste, we identified two fungal isolates, SMF410-5-1 and ME1-1, from decayed wood trunks, demonstrating high lignocellulose-degrading enzyme activities, including laccase (Lac, 125.7 U/mL), manganese peroxidase (MnP, 89.3 U/mL), and lignin peroxidase (LiP, 67.9 U/mL). Isolates of ME1-1 and SMF410-5-1 both exhibited superior poplar lignin degradation, while SMF410-5-1 excelled in coniferous wood weight losses, which reached 19.7% for pine after 180 days post inoculation. Moreover, biochemical analyses revealed that isolates of ME1-1 and SMF410-5-1 accelerated the degradation by producing various lignocellulose-degrading enzymes to hydrolyze wood waste. In addition, through multi-locus phylogenetic analysis using sequences of the internal transcribed spacer (ITS), large subunit ribosomal RNA (LSU), and RNA polymerase II second largest subunit (RPB2), SMF410-5-1 and ME1-1 were identified as Phlebia formosana and Auricularia cornea, respectively. This study provides novel insights into fungal-driven biodegradation, offering eco-friendly solutions for forest waste recycling and supporting circular bioeconomy strategies. Full article

Background/Objectives: High-dose-rate (HDR) interventional radiotherapy (IRT) represents a valuable treatment alternative for basal cell carcinoma (BCC) of the midface, especially in the presence of esthetic or functional issues related to surgery. This retrospective study examines the clinical outcomes of patients who underwent HDR-IRT at our institution. Methods: Patients (pts) with histologically confirmed midface BCC were treated with HDR-IRT using superficial, interstitial, or endocavitary implants depending on tumor characteristics. Fractionation regimens were tailored to tumor location: 45 Gy in 9 fractions twice a day (the cheeks/lips) and 44 Gy in 14 fractions (the nose, with the first and last fractions delivering 4 Gy each, administered once daily, and the remaining 12 fractions delivering 3 Gy each, administered twice daily (BID) with an inter-fraction interval of at least 6 h). Treatment efficacy was assessed based on local control rates, toxicity (CTCAE criteria), and cosmetic outcomes. Results: Eight patients were considered. The most common tumor site was the nose (seven patients, 87.5%), followed by the upper lip. Tumors were either primary (three patients, 37.5%) or residual/recurrent after previous surgery with involved margins (five patients, 62.5%). The median follow-up was 6 months (range: 1–19 months). Clinical local control was achieved in all cases, with persistent alteration at dermoscopy in one patient six months after the completion of treatment. Acute toxicities were minimal, with two patients developing grade 3 skin toxicity, which resolved within 1–3 months with topical management. Cosmetic outcomes were favorable across all patients. Conclusions: HDR-IRT is a well-tolerated, effective, and cosmetically favorable treatment for midface BCC. Our institutional experience supports its use as an alternative to surgery in cosmetically sensitive areas and in selected patients/lesions unfit for surgery. Endocavitary implants appear to be an effective option to cover the full thickness nasal wall without resorting to interstitial implants. Full article

This paper extends our previous work on cleft lip and/or palate (CL/P) classification, which employed vision transformers (ViTs) and Siamese neural networks. We now integrate SigLIP 2, a state-of-the-art multilingual vision–language model, for feature extraction, replacing the previously utilized BiomedCLIP. SigLIP 2 offers enhanced semantic understanding, improved localization capabilities, and multilingual support, potentially leading to more robust feature representations for CL/P classification. We hypothesize that SigLIP 2’s superior feature extraction will improve the classification accuracy of CL/P types (bilateral, unilateral, and palate-only) from the UltraSuite CLEFT dataset, a collection of ultrasound video sequences capturing tongue movements during speech with synchronized audio recordings. A comparative analysis is conducted, evaluating the performance of our original ViT-Siamese network model (using BiomedCLIP) against a new model leveraging SigLIP 2 for feature extraction. Performance is assessed using accuracy, precision, recall, and F1 score, demonstrating the impact of SigLIP 2 on CL/P classification. The new model achieves statistically significant improvements in overall accuracy (86.6% vs. 82.76%) and F1 scores for all cleft types. We discuss the computational efficiency and practical implications of employing SigLIP 2 in a clinical setting, highlighting its potential for earlier and more accurate diagnosis, personalized treatment planning, and broader applicability across diverse populations. The results demonstrate the significant potential of advanced vision–language models, such as SigLIP 2, to enhance AI-powered medical diagnostics. Full article

Objectives: Monitoring pregnancies is essential for community well-being. However, not all pregnancies progress normally, and some require termination. The objective was to emphasize the importance of trust in the doctor–patient relationship during this challenging time for expectant parents. Case report: During fetal morphology examination, parents were warned of a poor fetal prognosis, prompting a request for pregnancy termination. They consulted another specialist, who reassured them that the fetus appeared normal, though slightly hypotrophic. The child was born at 35 weeks gestational age and admitted to the neonatal ICU level III in an impaired general condition and polymalformative syndrome (triangular facies, epicanthic eyes, hypertelorism, retrognathia, low base of the nose, triangular mouth, lips angled downward, and small, dysplastic, and low-set earlobes). The child had syndactyly of fingers and toes. Cytogenetic analysis revealed a karyotype of 69, XX, +mar. The indirect DNA analysis revealed that the third gonosome is a Y chromosome. Death occurred 30 days post delivery, following severe dyspnea and bronchial obstruction, with desaturation and bradycardia. Conclusions: Triploid pregnancies are usually lost in the first trimester; however, very rarely, live births can occur. Hope for a positive outcome encouraged parents to continue the pregnancy, leading to a profoundly sorrowful experience and added strain on the healthcare system. Complex decisions put pressure on the patient–doctor relationship, as misplaced hope can impact both parties. Expectant parents facing difficult diagnoses require attentive support during this challenging time, grounded on a foundation of trust between doctor and patient. Full article

Background/Objectives: [6]-Gingerol ([6]-G), a bioactive compound derived from Zingiber officinale (ginger), exhibits strong anticancer potential but is hindered by poor aqueous solubility and low bioavailability. This study aimed to develop and evaluate PEGylated liposomal [6]-G (6-G-Lip) to enhance its stability, bioavailability, and chemopreventive efficacy in benzo[a]pyrene (BaP)-induced lung carcinogenesis. Methods: 6-G-Lip was synthesized using a modified thin-film hydration technique and characterized for size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE%), and release kinetics. The chemopreventive effects were assessed in BaP-induced lung cancer in Swiss albino mice, with prophylactic 6-G-Lip administration from two weeks before BaP exposure through 21 weeks. Cancer biomarkers, antioxidant enzyme activity, reactive oxygen species (ROS) generation, induction of apoptosis, and histopathological alterations were analyzed. Results: 6-G-Lip exhibited a particle size of 129.7 nm, a polydispersity index (PDI) of 0.16, a zeta potential of −18.2 mV, and an encapsulation efficiency (EE%) of 91%, ensuring stability and effective drug loading. The formulation exhibited a controlled release profile, with 26.5% and 47.5% of [6]-G released in PBS and serum, respectively, at 72 h. 6-G-Lip significantly lowered cancer biomarkers, restored antioxidant defenses (SOD: 5.60 U/min/mg protein; CAT: 166.66 μm H₂O₂/min/mg protein), reduced lipid peroxidation (MDA: 3.3 nm/min/mg protein), and induced apoptosis (42.2%), highlighting its chemopreventive efficacy. Conclusions: This study is the first to prepare, characterize, and evaluate PEGylated [6]-G-Lip for the chemoprevention of lung cancer. It modulates oxidative stress, restores biochemical homeostasis, and selectively induces apoptosis. These findings support 6-G-Lip as a promising nanotherapeutic strategy for cancer prevention. Full article

Background and Clinical Significance: The current study aims to show the diagnostic challenge of mandibular exposed necrotic bone in a patient with locally aggressive cutaneous squamous cell carcinoma of the lower lip and carrying risk factors for osteoradionecrosis and medication-related osteonecrosis of the jaws. Case Presentation: In March 2023, an 80-year-old ex-farmer male patient complaining of feeding difficulty showed a 3 cm area of exposed bone in the left region of the mandible. In July 2020, the patient underwent an incisional biopsy of a lower labial cutaneous keratinizing squamous cell carcinoma, which developed within actinic cheilitis. The cancer was unresectable due to the extent of the local invasion; thus, the patient underwent radiotherapy. In February 2022, the cancer reached the left mandibular canal by completely infiltrating the homolateral canal of the mental nerve. Therefore, the oncologist prescribed cemiplimab and denosumab as palliative immunotherapy. The differential diagnosis included osteoradionecrosis, stage-III medication-related osteonecrosis of the jaws, and intraoral localization of the cutaneous squamous cell carcinoma. The oral surgeon performed a sequestrectomy under local anesthesia and antibiotic prophylaxis; a histological examination confirmed the hypothesis of medication-related osteonecrosis. The patient currently undergoes follow-up visits monthly; the combination of photobiomodulation therapy and cycles of antibiotics keeps the necrotic lesion steady, and the oncological therapy prevents the growth of the cutaneous squamous cell cancer. Conclusions: The current case supports the need for histological examination to resolve the diagnostic challenge of mandibular exposed necrotic bone and to differentiate among osteoradionecrosis, stage-III medication-related osteonecrosis of the jaws, and intraoral localization of cutaneous squamous cell carcinoma. Full article

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is strongly associated with both environmental and genetic risk factors, but its genetic underpinnings remain partially known. While variants in interferon regulatory factor 6 (IRF6) are linked to NSCL ± P risk in populations from Asia and Europe, studies on the highly admixed Brazilian population are scarce and have produced ambiguous results. This study aimed to investigate the contribution of IRF6 variants to the risk of NSCL ± P. Five tag-single nucleotide polymorphisms (rs599021, rs2073485, rs2235375, rs7552506, and rs642961) were analyzed in a large multicenter cohort composed of 1006 patients with NSCL ± P and 942 healthy controls. Statistical analyses involved multiple logistic regression tests consideration the tri-hybrid genetic origin of the Brazilian population, under a Bonferroni p value correcting for multiple comparisons. The A allele (OR: 1.43, 95% CI: 1.22–1.67, p < 0.0001) and AA genotype (OR: 2.04, 95% CI: 1.46–2.86, p < 0.0001) frequencies of rs642961 were significantly associated with NSCL ± P risk. Stratified analyses indicated that the variant is associated with susceptibility to both nonsyndromic cleft lip only (NSCLO) and nonsyndromic cleft lip and palate (NSCLP). However, the association with NSCLO was primarily observed in patients with high African ancestry, whereas the association with NSCLP was predominantly seen in patients with high European ancestry. No significant associations were found for the other investigated variants. Our results support the notion that the IRF6 rs642961 variant represents a marker of susceptibility to NSCL ± P in the Brazilian population, and that genetic ancestry composition plays a central role in the association with the cleft type. Full article