Search Results (927)

Background/Objectives: This study aimed to evaluate the volumes of the maxillary sinus, nasal cavity, and nasolacrimal duct in individuals with unilateral and bilateral cleft lip and palate (CLP) using an artificial intelligence-assisted segmentation method and to compare the findings with those of healthy controls. Methods: This retrospective study included 25 unilateral CLP patients, 20 bilateral CLP patients, and 25 healthy controls. Maxillary sinus, nasal cavity, and nasolacrimal duct volumes were measured on cone-beam computed tomography (CBCT) images using an artificial intelligence-assisted segmentation method. Total volume differences among groups were analyzed using analysis of covariance (ANCOVA) adjusted for age and sex. Side-based comparisons were performed using linear mixed-effects models. Benjamini–Hochberg correction was applied for multiple comparisons. Results: The control group exhibited greater maxillary sinus, nasal cavity, and nasolacrimal duct volumes than the CLP groups. ANCOVA demonstrated nominally significant group differences for the maxillary sinus (p = 0.008), nasal cavity (p = 0.034), and nasolacrimal duct (p = 0.023); however, these differences were no longer significant after Benjamini–Hochberg correction (q > 0.05). Pairwise comparisons showed greater maxillary sinus volumes in controls than in the unilateral (p = 0.037) and bilateral CLP groups (p = 0.007), and greater nasal cavity volumes than in the unilateral (p = 0.049) and bilateral CLP groups (p = 0.045). Nasolacrimal duct volume differed only between the bilateral CLP and control groups (p = 0.021). No significant volumetric differences were found between unilateral and bilateral CLP groups. Conclusions: Although individuals with CLP showed a trend toward reduced maxillary sinus, nasal cavity, and nasolacrimal duct volumes, the total-volume differences did not remain significant after correction for multiple comparisons; reductions relative to the control sides persisted after correction only for the maxillary sinus and the nasolacrimal duct in the side-based analysis. No significant differences were observed between unilateral and bilateral CLP or between the two sides within any group. Full article

Background/Objectives: Non-syndromic orofacial clefts (NSOFCs) are among the most common congenital craniofacial anomalies, with genetic factors playing a major role in their etiology. Transforming growth factor-β-induced (TGFBI) protein is an extracellular matrix protein implicated in cell adhesion and apoptosis. Although experimental studies have implicated TGFBI in palatal fusion, its contribution to human NSOFCs remains unclear. This study investigated the genetic basis of hereditary NSOFCs in a Chinese family. The functional consequences of the identified TGFBI variant were subsequently evaluated. Methods: Whole-exome sequencing was performed in a Chinese NSOFC pedigree, followed by Sanger validation and ophthalmological evaluation. The functional impact of the identified variant was investigated through evolutionary and structural analyses, TGFBI expression analysis during mouse palatal development, and cellular functional assays. Results: A novel heterozygous stop-gain variant in TGFBI (NM_000358.3:c.230C > A; p.Ser77X) was identified in affected family members but not in the unaffected father. No corneal abnormalities were observed in variant carriers. TGFBI was expressed in the midline epithelial seam during palatal fusion. The p.Ser77X variant generated a truncated protein lacking all four FAS1 domains and the C-terminal RGD motif, resulting in abnormal localization, impaired cellular apoptosis and proliferation, and altered p38-MAPK signaling. Conclusions: This study identifies a rare loss-of-function TGFBI variant associated with NSOFCs and provides genetic and functional evidence supporting a role for TGFBI variation in human palatal development. Full article

Background/Objectives: Cleft palate is developmentally and clinically distinct from cleft lip with or without cleft palate. Prenatal ultrasound reliably identifies clefts involving the lip but performs poorly for the secondary palate, whereas early feeding difficulty is concentrated in palatal clefts. These two observations have not previously been quantified within a single cohort. We aimed to determine whether prenatal detectability and neonatal feeding support requirements follow opposite gradients across cleft phenotypes. Methods: We conducted an ambispective study of a nationally ascertained referral-centre cohort of 328 consecutive children with an orofacial cleft and no clinically recognised syndrome, managed at the national referral centre for cleft surgery in Croatia. The cohort comprises children reaching surgical care and is not a population-based birth registry. Documented prenatal ultrasound diagnosis and feeding method during the first weeks of life were abstracted from medical records; cleft phenotype was confirmed by clinical examination. Proportions were compared with chi-square tests and exact binomial confidence intervals, and factors independently associated with each outcome were identified by multivariable logistic regression. Results: Overall prenatal detection was 76/316 (24.1%; 95% CI 19.4–29.2). Detection differed markedly by phenotype: 38.2% for cleft lip only, 34.0% for cleft lip and palate and 2.0% for cleft palate only (p < 0.001). Nasogastric tube feeding was required by 46/325 children (14.2%; 95% CI 10.6–18.4) and followed the opposite gradient: 0.0%, 14.2% and 24.8%, respectively (p < 0.001). Isolated cleft palate showed the strongest independent negative association with prenatal detection (adjusted OR 0.037; 95% CI 0.009–0.154) and was independently associated with tube feeding (adjusted OR 3.07; 95% CI 1.37–6.89). Of children requiring tube feeding, 43/46 (93.5%; 95% CI 82.1–98.6) had not been detected prenatally. Observed detection rose with year of birth in unadjusted analysis (OR 1.095 per year; 95% CI 1.012–1.185; p = 0.023) but was attenuated and no longer significant after adjustment (OR 1.071; 95% CI 0.991–1.157; p = 0.082); the temporal trend is therefore reported descriptively. An initial refer result at newborn hearing screening was markedly more frequent in children with palatal involvement than in those with cleft lip only (2.8%, 31.6% and 25.5% for cleft lip only, cleft lip and palate and cleft palate only; p < 0.001), contrasting cleft lip only with clefts involving the palate rather than following a monotonic gradient. Conclusions: Prenatal detectability and neonatal nasogastric tube use follow opposite gradients across cleft phenotypes. Children with cleft palate only are simultaneously the least likely to be identified before birth and the most likely to require assisted feeding, and almost all tube-fed infants arrive without a prenatal diagnosis. These findings support, as a practice consideration, routine structured neonatal feeding assessment for every newborn with a palatal cleft irrespective of prenatal findings. Full article

Background and Objectives: Presurgical infant orthopedics aims to reduce cleft severity and facilitate primary surgical repair during the early neonatal period, when increased tissue plasticity enhances molding. Nasoalveolar molding is widely used but requires intraoral appliances, laboratory support, specialized training, and frequent follow-up visits, which may limit accessibility and adherence. This case series reports the clinical application of presurgical lip–alveolus–nose approximation (PLANA), an extraoral technique for early presurgical cleft management, and describes the clinical changes observed during treatment in four infants. Materials and Methods: A prospective case series conducted in neonates with non-syndromic unilateral or bilateral cleft lip and/or palate referred within the first 10 days of life to the Alabama Cleft Center. Treatment consisted of a prefabricated silicone nasal aligner combined with hydrocolloid lip adhesive taping. No intraoral plates or dental impressions were used. Devices were worn 20 to 22 h daily. Follow up occurred every 2 to 4 weeks, with remote monitoring used when appropriate. Qualitative clinical observations focused on apparent changes in nasal symmetry, columellar length, septal alignment, nasal tip projection, premaxillary position, nostril dimensions, alar base width, cleft width, and lip approximation, as well as feeding tolerance, skin tolerance, and treatment adherence. These observations were assessed qualitatively through serial clinical examinations and clinical photographs; no standardized quantitative morphometric measurements were performed. Results: Four infants with complete unilateral or bilateral cleft lip and palate received PLANA treatment. Serial clinical examinations and photographs documented qualitative changes in nasolabial morphology over the course of treatment in all four patients. Qualitative clinical assessment of serial photographs and examinations suggested greater apparent nasal symmetry, apparent columellar elongation, more central-appearing nasal alignment, increased apparent nasal tip projection, apparent cleft-width reduction, and progressive lip approximation. In unilateral clefts, changes were observed in both the cleft and non-cleft nasal sides, while bilateral clefts demonstrated changes in nasal morphology bilaterally. No device-related complications or clinically significant skin intolerance were documented during the reported treatment periods. Parent-reported device wear was approximately 20–22 h per day. Conclusions: In this four-patient prospective descriptive case series, PLANA was applied clinically, with no clinically significant treatment-related complications documented during the reported treatment periods. Serial clinical observations suggested changes in nasolabial morphology during treatment. Given the small sample size, absence of a contemporaneous control group, and qualitative nature of the assessments, these findings should be interpreted as preliminary and hypothesis-generating rather than as evidence of treatment efficacy or comparative effectiveness. Larger prospective, multicenter comparative studies incorporating standardized quantitative measurements, objective adherence assessment, and long-term surgical and aesthetic outcomes are needed to evaluate the effectiveness, reproducibility, and clinical applicability of the PLANA approach. Full article

The long-term accumulation of polyethylene terephthalate (PET) in marine environments may drive the evolution of microbial degradation capabilities, positioning the ocean as a valuable reservoir for discovering novel PET-degrading microorganisms. In this study, we isolated 305 marine-derived microorganisms with potential PET-degrading capability from samples collected from mangrove areas of Zhanjiang and the intertidal zones of Daya Bay, Shenzhen, China, using PET powder as a major carbon source. Subsequent evaluation of degradation performance via scanning electron microscopy and Fourier-transform infrared spectroscopy analysis identified 14 isolates capable of degrading PET film. These 14 strains belonged to 14 distinct species, none of which, to the best of our knowledge, has been previously documented as PET degraders. Among them, Microbacterium aurum SCSIO 85700 exhibited the most potent PET-degrading activity, achieving a weight loss of 2.1 mg (2.1%) and a 6.5% increase in relative crystallinity over 30 days. Genome analysis revealed the genetic basis underlying PET degradation and associated metabolic pathways in strain SCSIO 85700. Notably, genome mining and structural modeling identified two candidate polyester hydrolases, MA2267 and MA2443, possessing conserved His–Asp–Ser catalytic triads and exposed substrate-binding clefts resembling those of characterized PET-degrading enzymes, suggesting their potential involvement in PET depolymerization. Collectively, this study expands the recognized diversity of marine PET-degrading microorganisms and provides microbial resources for sustainable PET bioremediation. Full article

Objective: The aim of this study is to assess caries-related indicators (DMFT and ICDAS indices), plaque index, salivary pH and buffering capacity, and dietary and oral hygiene habits in patients with cleft lip and/or palate undergoing orthodontic treatment, compared with a control group of healthy patients. Methods: This pilot case–control study included 26 patients undergoing orthodontic treatment, 13 patients with cleft lip and/or palate and 13 healthy individuals. The following variables were assessed: diet and oral hygiene through a questionnaire; salivary pH and buffering capacity; caries risk, using the DMFT and ICDAS indices; and plaque index, using the ImageJ Software. Results: No statistically significant differences were detected in the DMFT index, salivary pH, and plaque index; nor in the diet, oral hygiene and salivary buffering capacity. A slightly higher plaque index was observed in patients with cleft lip and/or palate compared to healthy patients. There was a statistically significant difference in the location of plaque, with a higher incidence in the upper central incisors in the study group. Conclusion: This pilot study suggests no statistically significant differences in the DMFT index, plaque index, salivary pH, and buffering capacity between patients with cleft lip and/or palate and healthy controls undergoing orthodontic treatment. However, a higher incidence of bacterial plaque on the upper central incisors was observed in patients with cleft lip and/or palate. Full article

Integrins are heterodimeric transmembrane receptors that mediate bidirectional signaling and regulate cell–cell and cell–extracellular matrix interactions. Integrin αvβ6 is an epithelial-associated integrin that has emerged as a promising molecular target for PET/CT imaging using integrin αvβ6-directed radiotracers such as ⁶⁸Ga-Trivehexin, and, most recently, for antibody–drug conjugate therapy in epithelial malignancies. Unexpected physiological and incidental uptake within the pituitary gland has been reported in integrin αvβ6-targeted PET studies, including uptake in morphologically normal pituitary glands and pituitary neuroendocrine tumors (PitNETs). However, the histological basis of integrin αvβ6 expression in the human pituitary gland remains poorly understood. The aim of this study is to characterize the immunohistochemical expression of integrin αvβ6 in normal human pituitary tissue and PitNETs and to evaluate its potential implications for integrin αvβ6-targeted imaging and theranostic applications. Five complete adult pituitary glands obtained at autopsy and 28 PitNETs were examined by immunohistochemistry for integrin αvβ6. Staining distribution, intensity, and cellular localization were assessed in the adenohypophysis, neurohypophysis, and Rathke’s cleft remnants. PitNETs were classified according to transcription factor expression (PIT1, TPIT, and SF1). Among the 28 PitNETs, 17 were SF1-lineage (60.7%), three were PIT1-lineage (10.7), two were TPIT-lineage (7.1%), three lacked a dominant transcription factor (10.7%), and three showed plurilineage expression (10.7%). Integrin αvβ6 expression was evaluated semiquantitatively according to staining intensity and the percentage of positive tumor cells. In normal pituitary glands, integrin αvβ6 immunoreactivity was predominantly membranous and localized to larger adenohypophyseal cells irrespective of transcription factor lineage or hormone phenotype. Strong expression was also observed in the epithelial lining cells of Rathke’s cleft remnants, whereas the neurohypophysis lacked detectable integrin αvβ6 expression. Among the 28 PitNETs, integrin αvβ6 expression was detected in 20 cases (71.4%). Positive tumors demonstrated variable staining intensity and extent, ranging from 20% to 100% positive tumor cells. By lineage, integrin αvβ6 expression was detected in 13 of 17 SF1-lineage tumors (76.5%), one of three PIT1-lineage tumors (33.3%), and zero of two TPIT-lineage tumors (0%). Additionally, all three tumors lacking a dominant transcription factor (100%) and all three plurilineage tumors (100%) demonstrated integrin αvβ6 expression. Eleven integrin αvβ6-positive tumors showed expression in ≥50% of tumor cells, and six exhibited strong or diffuse immunoreactivity. Integrin αvβ6 expression in adenohypophyseal cells and Rathke’s cleft remnants provides a histological explanation for physiological pituitary uptake observed on αvβ6-targeted PET/CT imaging. The high prevalence of integrin αvβ6 expression in PitNETs, particularly in a subset demonstrating strong and diffuse immunoreactivity, suggests potential applicability of integrin αvβ6-targeted molecular imaging and theranostic approaches, including both radioligand- and antibody-based strategies. However, these applications remain investigational and require further validation in preclinical and clinical studies. At the same time, physiological integrin αvβ6 expression in normal anterior pituitary tissue may limit imaging specificity and should be considered when developing integrin αvβ6-targeted radioligand therapies. Further clinicopathological and imaging correlation studies are warranted to define the diagnostic and therapeutic role of integrin αvβ6-targeted approaches in PitNETs. Full article

Background/Objectives: Branchio-oto syndrome (BOS) is an autosomal dominant disorder primarily associated with pathogenic variants in EYA1, mainly characterized by branchial anomalies, auricular abnormalities, and hearing loss. However, the co-occurrence of inner ear malformations in BOS remains understudied, especially severe malformations. This study aimed to investigate the clinical and genetic characteristics of patients with EYA1-associated BOS, with emphasis on cochlear nerve deficiency (CND). Methods: From January 2020 to April 2026, patients diagnosed with EYA1-associated BOS at an otology outpatient clinic in a tertiary hospital were included. Clinical manifestations, audiological assessments, imaging and genetic findings were analyzed. Results: Thirteen patients (six females and seven males) from eight unrelated families aged 0.3–58.3 years were enrolled. Branchial cleft fistulas and preauricular pits were each observed in 76.9% (10/13) of patients. The mean pure-tone average was 74.3 ± 20.7 dB HL. Eight EYA1 variants (four truncating, two large deletions, and two splicing) were identified. Among these, five were novel (c.320_329del, c.518del, c.1307dupT, c.1475+1G>A, and exon 12–18 deletion). CND was detected in 38.5% (5/13) of patients and 26.9% (7/26) of ears. Patients with CND carried either truncating variants (n = 3) or large deletions (n = 2) of EYA1. No CND was observed in patients with splicing variants. Conclusions: This study identifies five novel EYA1 pathogenic variants and suggests that CND may be a relatively common radiologic feature in EYA1-associated BOS, particularly among patients with truncating variants or large deletions, although larger studies are needed to confirm this association. Full article

Parkinson’s disease (PD) is characterised by the pathological aggregation of α-synuclein (α-syn) into Lewy body inclusions, yet no disease-modifying therapy exists. To address this, we developed an integrated computational pipeline combining quantitative structure–activity relationship (QSAR) modelling, structure-based virtual screening, molecular dynamics (MD) simulation, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) binding free energy calculations to repurpose FDA-approved drugs as α-syn fibril inhibitors. Two complementary QSAR model families were trained on 501 α-syn binding affinity records from BindingDB: Morgan extended-connectivity fingerprint (ECFP4) classifiers and a frozen ChemBERTa-77M-MLM transformer encoder, each using Random Forest and Logistic Regression. The applicability domain (AD) was assessed using Morgan–Tanimoto similarity (Tc ≥ 0.40) and calibrated ChemBERTa cosine distance (θ ≤ 0.367). A three-stage funnel applying central nervous system (CNS) permeability filters, a consensus QSAR probability threshold (≥0.80), and AD gating reduced 2241 FDA-approved drugs to 205 candidates for AutoDock Vina 1.2.6 docking against two sites on the cryo-electron microscopy (cryo-EM) α-syn fibril structure, PDB 6SSX: the inter-protofilament cleft (Site 1) and the non-amyloid-beta component (NAC) groove (Site 2). The Morgan fingerprint models achieved an area under the receiver operating characteristic curve (AUROC) of up to 0.940 and a balanced accuracy of 0.810; the ChemBERTa models achieved an AUROC of 0.785 and a balanced accuracy of 0.728. Notably, ChemBERTa AD covered 76.8% of the FDA drugs versus only 5.5% for Morgan–Tanimoto, enabling broad-spectrum screening. The top docking candidates were Olaparib (−7.91 kcal/mol), Paliperidone (−7.75 kcal/mol), Niraparib (−7.18 kcal/mol), Dordaviprone (−7.06 kcal/mol), and Parecoxib (−6.89 kcal/mol). The MD simulations over 200 ns across three independent replicates confirmed stable NAC groove binding, and replicate-averaged MM-PBSA calculations yielded ΔG = −20.6 ± 1.9 kcal/mol for Olaparib at Site 2, −17.1 ± 0.9 kcal/mol for Risperidone, and −16.9 ± 0.8 kcal/mol for Paliperidone, reported as the mean ± standard error of the mean (SEM) across replicates. Olaparib additionally formed five hydrogen bonds in the representative pose, while MD trajectories maintained approximately 2–5 hydrogen bonds, together with a halogen bond within the NAC groove, the largest contact count of any screened compound. These findings identify Olaparib as a novel high-affinity repurposing lead, while Paliperidone and Risperidone are reported as chemically informative secondary NAC–groove binders rather than proposed antiparkinsonian therapeutics, given that their dopamine D2-antagonist pharmacology is clinically associated with drug-induced parkinsonism. All of the candidates warrant experimental validation via thioflavin-T fluorescence or nuclear magnetic resonance (NMR) spectroscopy. Full article

Acute myeloid leukemia (AML) remains a therapeutic challenge due to complex oncogenic networks, including the often-undruggable MYC pathway. Here, we present an integrated in silico framework combining transcriptomic analysis, machine learning, and molecular dynamics (MD) simulations to explore potential therapeutic approaches targeting vault RNA1-1 (VTRNA1-1) in AML. RNA-seq profiling revealed that VTRNA1-1 depletion is associated with a profound disruption of the MYC and FOXM1 regulatory axes. To highlight compounds capable of recapitulating this transcriptomic signature, we developed a machine learning pipeline utilizing a Random Forest classifier trained on a fully compiled L1000FWD database subset. Virtual screening of approved drugs predicted the anthelmintic niclosamide as a top candidate (98.17% mimic probability). Explainable AI further rationalized this prediction by highlighting specific fragments within niclosamide’s salicylanilide core. Furthermore, a 200 ns MD simulation indicated favorable computational stability of niclosamide bound to the p62 (SQSTM1) ZZ domain. The complex showed rapid structural convergence (ligand RMSD plateauing at 1.65 nm) without dissociation, while maintaining strict receptor compactness (steady Radius of Gyration and solvent-accessible surface area) and a persistent interaction network of ~73 close atomic contacts. These findings suggest that niclosamide may function as a stable physical “lid” over the p62 ZZ domain, occluding its N-degron-binding cleft. Taken together, our computational framework highlights niclosamide as a promising candidate for AML drug repurposing, providing a hypothesis-generating foundation that warrants rigorous experimental validation. Full article

Background/Objectives: Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that regulates multiple oncogenic and tumor-suppressive pathways and has emerged as a promising target for anticancer drug discovery. However, most reported USP7 inhibitors belong to a limited number of structural classes, and no USP7-targeted therapy has yet reached clinical application. This study aimed to identify structurally diverse candidate USP7-inhibitory scaffolds with antiproliferative activity using an integrated computational and experimental screening strategy. Methods: A drug discovery workflow combining pharmacophore modelling, structure-based virtual screening, molecular docking, and in silico pharmacokinetic assessment was employed to identify candidate USP7 inhibitors. Selected compounds were evaluated for inhibition of recombinant USP7 and for antiproliferative activity in a panel of human cancer cell lines. Molecular docking analyses were performed to investigate predicted binding modes. Results: The primary screening campaign identified four active compounds (>50% inhibition at 10 µM) and twenty-one weakly active compounds (10–49% inhibition at 10 µM), including structurally distinct approved drugs and compounds from an in-house chemical library. The four active compounds were subsequently validated by dose–response assays against recombinant USP7 and exhibited micromolar inhibitory activity. These candidate USP7-inhibitory scaffolds also exhibited antiproliferative activity across cancer cell lines with different molecular backgrounds. Docking studies predicted binding within a pharmacologically relevant region of the USP7 catalytic cleft and revealed putative interactions with key residues involved in ligand recognition. Among the compounds evaluated, rafoxanide demonstrated the most favorable combination of predicted USP7 binding and antiproliferative activity. Conclusions: This integrated virtual screening and experimental validation approach enabled the identification of candidate USP7-inhibitory scaffolds with preliminary antiproliferative activity. The identified hits include approved drugs with previously unreported USP7 inhibitory activity, as well as underexplored scaffolds that expand the chemical space of candidate USP7-targeting molecules. These candidate scaffolds warrant further medicinal chemistry optimization, orthogonal validation, and mechanistic characterization to establish their potential as USP7-targeted anticancer agents. Full article

Objectives: The aims of this study were to explore the genetic variants identified by Next-Generation Sequencing (NGS) in patients presenting syndromic/non-syndromic cleft palate (CP) associated with tooth agenesis (TA) and to describe the observed phenotype–genotype correlations. Methods: A systematic review exploring PubMed, Scopus and Web of Science was conducted. Data extraction and bias assessment were performed. Results: From 227 screened articles, 8 studies were included. Second premolars were the most frequently missing teeth, followed by central incisors in non-syndromic CP cases. Genetic variants were most commonly reported in IRF6, FGFR1, NOTCH2, CTNND1, ZFHX4 and AXIN2. Several mutations in these genes were associated with syndromic forms such as Pierre Robin Sequence, Kallmann syndrome, and Van der Woude syndrome. Conclusions: This study suggests a potential shared genetic pathway between CP and TA and supports further exploration of TA as a possible clinical indicator of syndromic cases. NGS emerges as a valuable exploratory tool for identifying such associations, though validation in larger patient cohorts remains necessary. Full article

Xylanases catalyze the hydrolysis of β-1,4-xylosidic linkages in xylan, a major component of plant cell walls, and are widely used in the food, feed, pulp and paper, and biofuel industries. GH11 xylanase from the hemicellulose-degrading bacterium Thermoanaerobacterium saccharolyticum (TsaGH11) exhibits high catalytic activity, making it an attractive enzyme for industrial applications. The flexibility of the thumb domain of TsaGH11 has been investigated under cryogenic and room temperature conditions; however, the substrate recognition mechanism of TsaGH11 at the optimal temperature is unknown. To better understand the molecular mechanism of substrate recognition, the high-resolution crystal structure of TsaGH11 was determined at 1.4 Å resolution. All-atom molecular dynamics simulations at 300, 320, 340, and 360 K revealed that increasing the temperature induced fluctuations in the substrate-recognizing thumb domain. At an optimal temperature of 340 K, the substrate-binding cleft of TsaGH11 predominantly adopted a closed conformation. However, the thumb domain exhibited larger fluctuations at 340 K than at other temperatures, sampling both open and closed conformations, suggesting that substrate recognition in TsaGH11 proceeds through a conformational selection-like mechanism. At 360 K, TsaGH11 unfolded partially at a site opposite the substrate-binding cleft, providing potential targets for protein engineering to improve its thermostability for industrial applications. These findings provide a better understanding of the molecular mechanism of TsaGH11 and offer valuable guidance for the rational engineering of GH11 xylanases for industrial applications. Full article

Background: Pilonidal sinus disease is an inflammatory condition characterised by formations ranging from minor cysts to extensive sinus tracts in the natal cleft in the sacrococcygeal area. Due to its complex and unique symptoms, the condition may not be adequately captured by the generic quality of life (QoL) instruments. In this study, we evaluated a newly developed pilonidal sinus disease-specific quality of life (SQoL) questionnaire, valuating its validity and applicability for measuring postoperative outcomes of pilonidal sinus disease. Materials and Methods: The study involved developing a SQoL. A total of 116 adult patients with chronic and acute symptomatic disease at the Kaunas Hospital of the Lithuanian University of Health Sciences (LUHS) were asked to complete both the SQoL and the SF-36v2 questionnaire. Key evaluation criteria for the SQoL questionnaire included internal consistency, measurement stability, as well as construct and discriminant validity. Results: 2 months after the procedure, 103 patients (response rate 88.79%) completed both questionnaires. Internal consistency was assessed 1 week after surgery, with the overall questionnaire achieving a Cronbach’s α coefficient of 0.919. The Spearman correlation coefficient for the total questionnaire score in the test–retest validation was 0.55 (CI 0.406–0.679), indicating a moderately significant correlation for all questions. Construct validity was evaluated by comparing the SQoL questionnaire with the results from various SF-36v2 domains 1 week after surgery. The highest inverse correlations were found between the corresponding domains of Physical Functioning and Role Physical Functioning (−0.770 and −0.600), with all correlations being statistically significant. Conclusions: A newly developed SQoL questionnaire has shown promise in assessing the impact of the disease and its treatment, particularly by addressing disease-specific symptoms. Standardising outcome measures can improve the reliability of meta-analyses and systematic reviews, which in turn helps to create more personalised care plans. The trial was registered in ClinicalTrials.gov with the identifier of NCT05982028. Full article

Background: Tooth auto-transplantation (TAT) is a surgical procedure in which a person’s own tooth is extracted and repositioned in the recipient site. The aim of the study is to evaluate the clinical outcomes, treatment strategies, and methodological characteristics, and to propose a preliminary management algorithm of TAT in patients with cleft lip and/or palate (CLP). Methods: A search of the literature was conducted in PubMed, Google Scholar, ClinicalKey, Web of Science, and Cochrane Library databases until 21 June 2026. The systematic review was written according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Risk-of -bias was assessed by the Joanna Briggs Institute (JBI) tool. Results: Five case series and three case reports were included, with four “low” and four “moderate” JBI reporting-quality ratings (reflecting reporting completeness, not low risk of bias). They presented data about 23 patients and 27 TAT cases. The majority of patients (n = 16) received secondary alveolar bone graft with iliac bone. The most common donor teeth were mandibular premolars (n = 20). The most frequent recipient sites were the maxillary 2nd premolar (n = 9) and maxillary incisors (n = 15). Twenty-six teeth (96.3%) survived, and one tooth (3.7%) was extracted. Conclusions: TAT appears to be a promising treatment option in carefully selected CLP patients; however, further high-quality studies are needed with the application of our proposed algorithm. Full article