Search Results (4,709)

Background/Objectives: Antimicrobial peptides (AMPs) are promising therapeutic agents due to their broad-spectrum activity against bacteria, viruses, and fungi. Unlike traditional antibiotics, AMPs target microbial membranes directly and are less likely to induce resistance. They also possess immunomodulatory and wound-healing properties. However, clinical application remains limited by factors such as salt sensitivity, low bioavailability, and poor stability. To address these challenges, researchers have turned to structural optimization strategies. Recently, artificial intelligence (AI) has facilitated peptide drug design by rapidly screening large peptide libraries. Still, AI struggles to predict how subtle sequence changes affect peptide structure and function. Traditional sequence permutation offers a complementary approach by analyzing structural and functional effects without altering amino acid composition. Methods: In this study, we applied a clockwise sequence permutation strategy to the AMP W5K/A9W, generating derivative peptides with identical molecular weight, net charge, and hydrophobicity. We aimed to investigate how lysine and tryptophan distribution affects antimicrobial activity, membrane permeability, and selectivity. We assessed the secondary structures using circular dichroism (CD) spectroscopy and evaluated in vitro antimicrobial activity, salt resistance, membrane-permeabilizing ability, hemolysis, and wound healing effects. Results: The results revealed that the sequence arrangement of key residues significantly impacts peptide bioactivity and therapeutic index. Conclusions: This study highlights the importance of sequence order in determining AMP function. It also supports integrating permutation strategies with AI-based design to enhance AMP discovery. Together, these approaches offer new opportunities to combat drug-resistant pathogens and advance next-generation anti-infective therapies. Full article

This paper proposes a metal defect detection method based on laser-induced audible sound testing (LAST). Defective and defect-free martensitic stainless-steel cubes were used as study samples, and the spectral characteristics of the acoustic signals generated under laser irradiation were comparatively analyzed. Based on F-ratio analysis, weighting curves characterizing the discrimination capability of each frequency band were calculated. Subsequently, nonlinear filter banks were designed according to the spectrum discrimination weights, tailored to the degree of spectrum discrimination. Finally, a globally weighted cepstral coefficient (GWCC) extraction algorithm for laser-induced acoustic signals was developed to determine whether defects are present in metals. Experimental results show that the recognition rate of defective samples based on GWCC features reached 94%, higher than that of traditional acoustic features, effectively enhancing feature discriminability. The results of this study demonstrate that applying LAST to metal defect detection is feasible. This method leverages laser-generated acoustic signals from a more comprehensive and economical perspective, pioneering a new solution for non-destructive testing of metal defects. Full article

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is an extremely rare neurological condition caused by a disruption in the NR2F-1 gene. The most common clinical features are optic atrophy and intellectual and developmental delay. This case report aims to describe the cognitive and language profile of a six-year-old girl diagnosed with BBSOAS, with a focus on the syndrome’s impact on her developmental outcomes. A detailed assessment of her cognitive and speech–language abilities is provided. Given the limited number of published case studies on BBSOAS, this report integrates relevant findings from the literature, including information on epidemiology, diagnostics, clinical manifestations, and developmental outcomes. It contributes to the expansion of the known mutational spectrum of BBSOAS, in addition to documenting its phenotypic presentation of cognitive and speech–language development. The case is analyzed within the context of current evidence, emphasizing the importance of early assessment, individualized intervention, ongoing developmental monitoring, and the potential for tailored support to promote optimal developmental outcomes. Full article

Background/Objectives: Cannabis sativa (CS) exerts its effects through the endocannabinoid system. Although studies have shown limited evidence regarding the plant’s therapeutic efficacy, little is known about the standardization of doses and their corresponding effects. This study aims to analyze changes in muscle electrical activity and cardiovascular hemodynamics before, during, and after administering doses of full-spectrum cannabis and tetrahydrocannabinol (THC) oils. Methods: Participants will be assigned to a single group that will undergo five different interventions: CBD + THC at 12.50 mg, CBD + THC at 18.75 mg, THC intervention at 12.50 mg, THC at 18.75 mg, and placebo intervention (PI). The study will enroll healthy, self-reported men and women aged 18 to 50, with no mental health disorders and no exposure to CS in the past six months. Interventions will occur on five randomized days, following three phases: (1) pre-intervention (PRE-IN); (2) intervention (IN)—1 h after oral oil ingestion; and (3) post-intervention (POST-IN)—2 h 30 min after ingestion. At each stage, 2 min of quiet breathing (QB); 2 min with an inspiratory resistance valve (30% of maximal inspiratory pressure—PImax) and expiratory valve (10% of maximal expiratory pressure—PEmax) (VAL); and 4 min of recovery without the valve (REC) were evaluated. Register: RBR-3jsvtbr. Conclusions: This study will enhance the understanding of the dose–response effects of full-spectrum cannabis and THC oils and may serve as a model for future research in this field. Full article

Background: Lung resections in children are rare but critical for congenital lung malformations (CLMs) and acquired pathologies; few studies have analyzed the full spectrum of indications. This study evaluated indications, complications, outcomes, and temporal trends in a tertiary pediatric center. Methods: We retrospectively analyzed patients who underwent lung resection (2012–2024), focusing on indications, approaches, complications, and outcomes. Comparisons between pathologies (CLMs vs. acquired pathologies), approaches (thoracoscopy vs. thoracotomy), an temporal trends were evaluated. Results: Among 160 patients (mean age: 7.8 years), acquired lesions (68.6%) were more common than CLMs (31.4%), predominating in children under 8 years. Compared with thoracotomy, thoracoscopy (72.8% of cases, conversion rate: 22.8%) was correlated with shorter operative times (p < 0.001) and hospital stays (p = 0.001). The complication rate was 19.5%, with 71.9% of patients achieving disease-free, asymptomatic status at follow-up. Risk factors for conversion from thoracoscopy to open surgery included intraoperative adhesions (p = 0.003), underlying pathology (p = 0.013), and age < 8 years (p = 0.017). Compared with acquired lesions, CLMs were associated with fewer complications (14.3% vs. 23.1%, p = 0.041) and more favorable outcomes (89.2% vs. 64.7%; p < 0.05). Over time, the use of thoracoscopy increased (p = 0.012), with reduced operative time (p = 0.005); complication and outcome rates remained stable. Conclusions: Pediatric lung resections address diverse pathologies; outcomes are linked to the pathology, and CLMs are associated with lower complication rates in our cohort. Thoracoscopy has progressively become the preferred approach in the last decade, offering advantages particularly in postoperative recovery, though its success depends on careful, pathology-driven patient selection. Full article

Purpose: To describe the indication spectrum for high-dose 8 mg aflibercept for neovascular age-related macular degeneration (nAMD) in a real-world cohort in a tertiary referral center. Methods: The database of the University Eye Hospital Munich, Ludwig Maximilians-University was screened for eyes with nAMD treated with 8 mg aflibercept. Demographic data, multimodal imaging and treatment parameters were recorded. Reasons for treatment with 8 mg aflibercept were analyzed. Results: Thirty-four consecutive eyes of 31 patients (mean age 78.6 ± 8.9 years) were identified. There were 22 women (70.1%) and 9 men (29.9%). In all eyes (100%), 8 mg Aflibercept was applied as switching therapy. Prior to switching, the mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 3.9 ± 2.9 years, pretreatment amounted to a mean of 34.5 ± 26.3 injections, equaling 9.2 ± 2.4 injections/year, and the mean visual acuity (VA) was 0.4 ± 0.4 logMAR. The last treatment before switching was 2 mg aflibercept in 76%, faricimab in 18%, ranibizumab in 3% and bevacizumab in 3% of cases. Reasons for switching included (A) recalcitrant nAMD with persistent fluid despite q4w dosing (17 eyes, 50%), (B) the wish for interval extension (15 eyes, 44%) and (C) macular hemorrhage (2 eyes, 6%). In group B, two-thirds of eyes (10/15, 66.7%) were maintained at ≤q6w prior to switching. Conclusions: In this study, high-dose 8 mg aflibercept was exclusively used as a switch therapy. Most eyes (76%) switched were from pretreatment with 2 mg aflibercept. The main reasons for switching were recalcitrant nAMD with persistent fluid despite q4w dosing (50%) or the wish for treatment extension beyond 6 weeks (32%). In the future, these data will aid in the design of prospective real-world studies comparing the efficacy of high-dose 8 mg aflibercept with older generation treatment options, especially 2 mg aflibercept. Full article

Background: Major clinical trials regarding sodium–glucose cotransporter 2 inhibitors (SGLT2is) have focused on estimated glomerular filtration rate (eGFR) slope and composite kidney outcomes, with limited evaluation of eGFR variability as a kidney outcome or its long-term implications in patients receiving SGLT2i versus placebo. Methods: This retrospective study analyzed 3777 propensity score-matched patients with type 2 diabetes receiving either SGLT2i or dipeptidyl peptidase-4 inhibitor (DPP4i) between June 2016 and December 2021. Each patient had eGFR data at three time points before (−15, −9, and −3 months) and after (3, 9, and 15 months) the drug-index date. eGFR variability was assessed using the coefficient of variation (COV) and standard deviation (SD) of eGFR values. Results: SGLT2i therapy was associated with a significant reduction in eGFR variability by both COV (from 0.072 (0.001) to 0.069 (0.001); p = 0.014) and SD (mL/min/1.73 m²) (from 5.34 (0.07) to 4.82 (0.07); p < 0.001). In contrast, DPP4i therapy resulted in increased COV (from 0.072 (0.001) to 0.080 (0.001); p < 0.001) and no significant improvement in SD (from 5.06 (0.07) to 5.22 (0.07); p = 0.082). Greater reduction in eGFR variability was observed in SGLT2i relative to DPP4i with high pre-treatment eGFR variability, pre-existing chronic kidney disease, or rapid pre-treatment eGFR decline. Greater pre-treatment eGFR variability predicted risk of major adverse kidney events (MAKEs) and abrupt kidney decline in DPP4i-treated patients, but not in those on SGLT2is. SGLT2i consistently reduced the risk of MAKE and abrupt kidney decline across the spectrum of pre-treatment eGFR variability, with a greater risk reduction on the MAKE for SGLT2i versus DPP4i therapy with a higher pre-treatment eGFR variability estimated by SD (p interaction = 0.014). Conclusions: SGLT2i therapy improved eGFR variability and reduced the risk of adverse kidney outcomes compared to DPP4i, particularly in patients with higher pre-treatment eGFR variability. Full article

Exploration for hydrocarbon reservoirs is currently focused on increasingly difficult targets and geological structures, thus stimulating a growing requirement for new measurement methods and techniques that can provide more detailed information about lithology and reservoir parameter distribution in the vicinity of the target zone. This publication presents a method for increasing the resolution of the recorded surface seismic wavefield in the vicinity of example borehole Well-1 (western Poland) for reservoir horizons of the Rotliegend and Zechstein formations. The main stage of the research was the introduction of frequencies from vertical seismic profiling (VSP) into seismic traces. The shape filter deconvolution procedure was applied based on the operator calculated from VSP data, which was applied to seismic profiles extracted from 3D data. The procedure applied allowed for the reconstruction of higher-frequency spectrum necessary for a detailed imaging of the geological framework of the analyzed reservoir formations. In the next stage, seismic inversion calculations were conducted, both on VSP data (corridor stack and VSP-CDP transformation) and on surface seismic time sections. The results obtained as an acoustic impedance distribution enabled a more comprehensive structural interpretation and detailed analysis of the variability of reservoir properties in the analyzed well area. Full article

This scoping review systematically maps the rapidly evolving application of Artificial Intelligence (AI) in Autism Spectrum Disorder (ASD) diagnostics, specifically focusing on computational behavioral phenotyping. Recognizing that observable traits like speech and movement are critical for early, timely intervention, the study synthesizes AI’s use across eight key behavioral modalities. These include voice biomarkers, conversational dynamics, linguistic analysis, movement analysis, activity recognition, facial gestures, visual attention, and multimodal approaches. The review analyzed 158 studies published between 2015 and 2025, revealing that modern Machine Learning and Deep Learning techniques demonstrate highly promising diagnostic performance in controlled environments, with reported accuracies of up to 99%. Despite this significant capability, the review identifies critical challenges that impede clinical implementation and generalizability. These persistent limitations include pervasive issues with dataset heterogeneity, gender bias in samples, and small overall sample sizes. By detailing the current landscape of observable data types, computational methodologies, and available datasets, this work establishes a comprehensive overview of AI’s current strengths and fundamental weaknesses in ASD diagnosis. The article concludes by providing actionable recommendations aimed at guiding future research toward developing diagnostic solutions that are more inclusive, generalizable, and ultimately applicable in clinical settings. Full article

This study introduces a novel approach for analyzing theoretical Raman spectra, designed to facilitate spectral interpretation, particularly for complex systems such as functional mesoporous silica-based thin films. The proposed methodology relies on spectral decomposition supported by theoretical calculations, representing a step toward the development of autonomous research laboratories. The method assigns vibrational shifts to individual atoms within a molecular model and uses this information to generate partial spectra corresponding to specific atomic groupings. Unlike separate calculations for isolated components, this approach preserves the mutual interactions within the entire molecular structure, providing a more accurate representation of the vibrational environment. Decomposing the theoretical spectrum into contributions from atomic groups significantly simplifies the assignment of Raman bands to specific structural units, thereby enhancing the interpretative power of theoretical spectra and their correlation with experimental data. The method was demonstrated using real Raman spectroscopic data obtained from mesoporous SBA-15 silica thin films containing copper phosphonate groups. This work also highlights the critical role of molecular modeling and DFT calculations in Raman spectral analysis and outlines future perspectives for the use of artificial intelligence to automate and optimize the spectral interpretation process. Full article

Background/Objectives: Chemotherapy often leads to persistent physical and cognitive impairments, and while the dual-task paradigm is a sensitive tool for detecting such deficits, its application to functional strength in oncology remains largely unexplored. Methods: This cross-sectional study, while not designed to establish causality, included 44 participants including cancer patients (11 undergoing chemotherapy and 15 post-treatment survivors) and healthy controls. Functional fitness was assessed with the Senior Fitness Test battery under single- and dual-task conditions. The dual-task condition incorporated a cognitive subtraction task, and the dual-task cost was calculated. Group comparisons were analyzed using t-tests and ANOVA with effect sizes reported (p < 0.05). Results: Within-group comparisons showed that the cancer group exhibited reduced performance from the single- to the dual-task condition, with significant declines in strength and mobility (Chair Stand Test, p = 0.011; Timed Up and Go, p < 0.001). Greater dual-task costs were observed in the Arm Curl Test for cognitive (p = 0.005) and success (p = 0.004) outcomes. Conclusions: Dual-task testing revealed greater impairments in cancer patients and survivors, supporting the impact of chemotherapy-related cognitive impairment and highlighting the need for integrated motor–cognitive rehabilitation strategies. Further research is warranted in this field, employing larger sample sizes and stratified analyses by specific cancer types, and including a spectrum of complexity in the cognitive task to characterize the effects of cancer and its treatment on motor–cognitive integration. Full article

The SARS-CoV-2 pandemic presents a broad clinical spectrum from asymptomatic cases to severe respiratory failure with high mortality. Severe COVID-19 is characterized by immune dysregulation, including lymphopenia and alterations in the counts of T, B, and NK cells in peripheral blood. Due to the limited data on long-term outcomes related to immune dysregulation, we aimed to analyze immunologic features at baseline in severe and mild COVID-19 cases and assess follow-up characteristics associated with later mortality and long-COVID signs. We included adult patients consecutively hospitalized with COVID-19 between June and November 2020 at the University Hospital in Kraków, corresponding to the first and second waves of COVID-19 in Poland. We enrolled only those who had been thoroughly assessed in terms of clinic and laboratory data, including immunological workups, and survived the acute phase of the disease. In 2025, between February and April (median time of follow-up: 54 months), we conducted a telephone questionnaire on long-COVID symptoms among survivors who had given their consent. Statistical analyses were performed to compare groups with severe and mild disease in terms of dysregulation in lymphocyte subpopulations and the follow-up outcomes. The study included 103 COVID-19 patients, comprising 53 severe (based on the need for at least high-flow nasal oxygen therapy) and 50 mild cases, with no differences in age, sex, and body mass index. Severe COVID-19 patients compared to mild cases had lower CD3+ T cells (count and percentage), CD4+ T cells (count and percentage), CD8+ T cells (count), and NK cells (count), but higher CD19+ B cells (percentage) at baseline (p < 0.05, all). At the time of follow-up, we evaluated 80 patients (77.7% of the baseline participants), with 23 (22.3%) patients lost to follow-up. Among patients analyzed in the follow-up, 23 (28.8%) had died, and 29 of the 57 survivors (50.9%) reported persistent long-COVID symptoms. Patients who died had significantly lower baseline counts of CD3+ T cells (377 vs. 655 cells/µL), CD4+ T cells (224 vs. 372 cells/µL), CD8+ T cells (113 vs. 188 cells/µL), and NK cells (118 vs. 157 cells/µL) compared to survivors (p < 0.05, all). Notably, the percentage of CD19+ B cells was higher in deceased individuals (19.2% vs. 13.5%; p = 0.049). In contrast, we did not document differences in baseline immunological data among survivors with and without long-COVID signs. Our study suggests that dysregulation in lymphocyte subpopulations during the COVID-19 acute phase may be associated with increased late mortality, but not with the persistence of long-COVID symptoms. Full article

Background: The emergence of extended-spectrum β-lactamase (ESBL) producing and colistin-resistant Escherichia coli in retail meat poses a significant public health risk. Method: A total of 180 retail meat samples (chicken parts, internals, processed products; lamb; beef; fish) were purchased from markets and butcher shops across Turkiye. Presumptive ESBL-producing isolates were screened on chromogenic agar and phenotypically confirmed. Species identity was verified by uspA PCR, and resistance genes (blaCTX-M, blaTEM, blaOXA, blaSHV, mcr-1, mcr-2, mcr-3) were analyzed. Colistin MICs were determined by broth microdilution, while antimicrobial susceptibility of ESBL-positive isolates was assessed by disk diffusion. Results: Overall, ESBL-producing E. coli were detected in 21.7% (n = 39) of the 180 meat samples analyzed, with the highest prevalence observed in chicken parts (26/40, 65.0%) and giblets (6/10, 60%). All ESBL-E. coli isolates harbored blaCTX-M, with blaCTX-M-1 identified as the sole variant. The blaTEM gene was detected in 61.5% (24/39) of ESBL-positive E. coli isolates. Colistin resistance was identified in six isolates (15.4%), all of which carried the mcr-1 gene. Additionally, one lamb minced meat isolate harbored the mcr-2 gene. Co-occurrence analysis revealed that the most frequent resistance gene combination among ESBL-producing isolates was blaCTX-M1 + blaTEM, detected predominantly in chicken meat samples, while mcr-1 was observed only in isolates harboring single or limited resistance genes, suggesting a distinct acquisition pattern. Conclusions: A high prevalence of blaCTX-M-1 and the co-occurrence of mcr genes were detected in E. coli isolates from retail meat, particularly poultry. The detection of mcr-1/mcr-2 co-carriage in lamb meat, though rare, highlights the need for broader surveillance. These findings underscore the need for integrated monitoring and prudent antimicrobial use in food animals. The use of antibiotics as growth promoters is prohibited in Türkiye, and therapeutic applications require a veterinary prescription; however, stronger enforcement remains essential to limit the dissemination of multidrug-resistant bacteria in the food chain. Full article

(1) Background: Individuals affected by schizophrenia spectrum disorders (SSDs) have an increased risk for cardiometabolic diseases. Improved cardiorespiratory fitness (CRF) is associated with lower cardiometabolic risk. The aim of the study was to analyze the effect of a six-month-long physical exercise intervention on CRF and cardiometabolic risk factors as well as whether the effect differed between sexes and different baseline CRF in SSD patients. (2) Methods: 122 patients at psychiatric open care units agreed to participate, 55 did not provide blood samples, and 14 dropped out, leaving 53 patients with complete pre–post data. BMI, waist–hip ratio, blood pressure, HbA1c, blood lipids, and CRF from ergometer bicycle tests were measured before and after the intervention. CRF was stratified into three groups. (3) Results: Cardiometabolic disturbances were common at baseline. After the intervention, all females and the group with the lowest CRF at baseline improved in triglyceride levels. The latter group also improved in CRF. (4) Conclusions: Females and those with the lowest baseline CRF had improved post-intervention, but causality cannot be inferred because our study was a non-randomized study without a control group. Full article

This long-term observational study aimed to define the spectrum of genetic variation in a congenital hypothyroidism (CH) cohort and investigate the correlations between specific genotypes and clinical phenotypes, including treatment requirements and outcomes. We analyzed the maintenance dose of L-thyroxine (L-T4) at 6, 12, 18, and 24 months, alongside clinical outcomes after 3 years. Data were collected from the Neonatal Disease Screening Center at our hospital between January 2011 and March 2024. Of 247 patients with confirmed CH, 119 had available genetic testing and complete clinical information. The genetic positivity rate was 56.3% (67/119). DUOX2 was the most frequently mutated gene (28.57%), followed by TPO, TG, and TSHR. Phenotypic correlation analysis revealed that patients with DUOX2 variants had significantly lower initial screening TSH levels and required lower L-T4 maintenance doses at 12 months compared to those with TPO or TSHR variants. Patients with TPO and TSHR variants exhibited more severe clinical phenotypes and a higher prevalence of thyroid enlargement on ultrasound. Notably, no significant differences in biochemical data, L-T4 doses, or clinical outcomes were observed between patients with monoallelic and biallelic DUOX2 variations, or among the negative, monogenic, and oligogenic variation groups. This study establishes a high genetic diagnostic yield for CH in the studied cohort, with DUOX2 as the predominant genetic etiology. The findings demonstrate significant genotype–phenotype correlations, where variations in different genes are associated with distinct biochemical severities and treatment demands. Crucially, the lack of correlation between the number of affected DUOX2 alleles and disease severity highlights the complex genetic and phenotypic heterogeneity of CH. These results provide valuable insights for the precise management and prognostic counseling of patients with CH. Full article