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32 pages, 2452 KB  
Review
Clinical Presentation, Genetics, and Laboratory Testing with Integrated Genetic Analysis of Molecular Mechanisms in Prader–Willi and Angelman Syndromes: A Review
by Merlin G. Butler
Int. J. Mol. Sci. 2026, 27(3), 1270; https://doi.org/10.3390/ijms27031270 - 27 Jan 2026
Abstract
Prader–Willi (PWS) and Angelman (AS) syndromes were the first examples in humans with errors in genomic imprinting, usually from de novo 15q11-q13 deletions of different parent origin (paternal in PWS and maternal in AS). Dozens of genes and transcripts are found in the [...] Read more.
Prader–Willi (PWS) and Angelman (AS) syndromes were the first examples in humans with errors in genomic imprinting, usually from de novo 15q11-q13 deletions of different parent origin (paternal in PWS and maternal in AS). Dozens of genes and transcripts are found in the 15q11-q13 region, and may play a role in PWS, specifically paternally expressed SNURF-SNRPN and MAGEL2 genes, while AS is due to the maternally expressed UBE3A gene. These three causative genes, including their encoding proteins, were targeted. This review article summarizes and illustrates the current understanding and cause of both PWS and AS using strategies to include the literature sources of key words and searchable web-based programs with databases for integrated gene and protein interactions, biological processes, and molecular mechanisms available for the two imprinting disorders. The SNURF-SNRPN gene is key in developing complex spliceosomal snRNP assemblies required for mRNA processing, cellular events, splicing, and binding required for detailed protein production and variation, neurodevelopment, immunodeficiency, and cell migration. The MAGEL2 gene is involved with the regulation of retrograde transport and promotion of endosomal assembly, oxytocin and reproduction, as well as circadian rhythm, transcriptional activity control, and appetite. The UBE3A gene encodes a key enzyme for the ubiquitin protein degradation system, apoptosis, tumor suppression, cell adhesion, and targeting proteins for degradation, autophagy, signaling pathways, and circadian rhythm. PWS is characterized early with infantile hypotonia, a poor suck, and failure to thrive with hypogenitalism/hypogonadism. Later, growth and other hormone deficiencies, developmental delays, and behavioral problems are noted with hyperphagia and morbid obesity, if not externally controlled. AS is characterized by seizures, lack of speech, severe learning disabilities, inappropriate laughter, and ataxia. This review captures the clinical presentation, natural history, causes with genetics, mechanisms, and description of established laboratory testing for genetic confirmation of each disorder. Three separate searchable web-based programs and databases that included information from the updated literature and other sources were used to identify and examine integrated genetic findings with predicted gene and protein interactions, molecular mechanisms and functions, biological processes, pathways, and gene-disease associations for candidate or causative genes per disorder. The natural history, review of pathophysiology, clinical presentation, genetics, and genetic-phenotypic findings were described along with computational biology, molecular mechanisms, genetic testing approaches, and status for each disorder, management and treatment options, clinical trial experiences, and future strategies. Conclusions and limitations were discussed to improve understanding, clinical care, genetics, diagnostic protocols, therapeutic agents, and genetic counseling for those with these genomic imprinting disorders. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
13 pages, 486 KB  
Article
A National Forecast and Clinical Analysis of Pediatric Acute Mastoiditis in Kazakhstan
by Nazik Sabitova, Timur Shamshudinov, Assiya Kussainova, Dinara Toguzbayeva, Bolat Sadykov, Yevgeniya Rahanskaya and Laura Kassym
Children 2026, 13(2), 170; https://doi.org/10.3390/children13020170 - 26 Jan 2026
Abstract
Background: Ongoing healthcare and medical education reforms in Kazakhstan have been accompanied by persistent workforce shortages and reduced inpatient capacity in pediatric care. Therefore, this study aimed to assess and forecast selected healthcare system indicators using acute mastoiditis (AM) as a sentinel condition [...] Read more.
Background: Ongoing healthcare and medical education reforms in Kazakhstan have been accompanied by persistent workforce shortages and reduced inpatient capacity in pediatric care. Therefore, this study aimed to assess and forecast selected healthcare system indicators using acute mastoiditis (AM) as a sentinel condition while also describing its clinical and epidemiological characteristics. Materials and Methods: This study combined an analysis of national healthcare and demographic statistics in Kazakhstan from 1998 to 2024 with a retrospective review of pediatric AM patients treated at a tertiary referral center. Long-term trends in healthcare resources were assessed, and future needs were projected via average annual percentage change (AAPC) and time series forecasting methods. Clinical, laboratory, and radiological data were extracted from medical records. Statistical analyses were performed via SPSS version 24.0 (IBM Corp., Armonk, NY, USA). Results: From 1998 to 2024, the number of pediatricians and ENT hospital beds declined, whereas the density of ENT physicians remained relatively stable, and the proportion of ENT surgical procedures increased. Projections to 2030 suggest continued constraints in pediatric and ENT workforce capacity and further reductions in inpatient beds despite sustained growth in surgical demand. Among 95 pediatric AM cases, complications, most commonly subperiosteal abscess and zygomatic abscess, were identified in 40% of patients. Conclusions: AM may be considered a contextual indicator of pressures within specialized pediatric ENT services rather than a direct measure of healthcare system performance. These findings highlight the need for further studies to validate these observations and better inform healthcare planning. Full article
(This article belongs to the Special Issue Diagnosis and Management of Pediatric Ear and Vestibular Disorders)
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29 pages, 11156 KB  
Article
Mesoscopic Heterogeneous Modeling Method for Polyurethane-Solidified Ballast Bed Based on Virtual Ray Casting Algorithm
by Yang Xu, Zhaochuan Sheng, Jingyu Zhang, Hongyang Han, Xing Ling, Xu Zhang and Luchao Qie
Materials 2026, 19(3), 474; https://doi.org/10.3390/ma19030474 - 24 Jan 2026
Viewed by 208
Abstract
This study introduces a mesoscale modeling methodology for polyurethane-solidified ballast beds (PSBBs) that eliminates reliance on X-ray computed tomography (XCT) and addresses constraints in specimen size, capital cost, and post-processing complexity. The approach couples the Discrete Element Method (DEM) with the Finite Element [...] Read more.
This study introduces a mesoscale modeling methodology for polyurethane-solidified ballast beds (PSBBs) that eliminates reliance on X-ray computed tomography (XCT) and addresses constraints in specimen size, capital cost, and post-processing complexity. The approach couples the Discrete Element Method (DEM) with the Finite Element Method (FEM). A high-fidelity discrete-element geometry is reconstructed from three-dimensional laser scans of ballast particles. The virtual-ray casting algorithm is then employed to identify the spatial distribution of ballast and polyurethane and map this information onto the finite-element mesh, enabling heterogeneous material reconstruction at the mesoscale. The accuracy of the model and mesh convergence are validated through comparisons with laboratory uniaxial compression tests, determining the optimal mesh size to be 0.4 times the minimum particle size (0.4 Dmin). Based on this, a parametric study on the effect of sleeper width on ballast bed mechanical responses is conducted, revealing that when the sleeper width is no less than 0.73 times the ballast bed width (0.73 Wb) an optimal balance between stress diffusion and displacement control is achieved. This method demonstrates excellent cross-material applicability and can be extended to mesoscale modeling and performance evaluation of other multiphase particle–binder composite systems. Full article
(This article belongs to the Section Materials Simulation and Design)
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14 pages, 682 KB  
Article
Efficacy and Safety of SA001 in Patients with Primary Sjögren’s Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
by Jaewon Park, Kyoung Yul Seo, Hyunmin Ahn, Yearim Shin, Ikhyun Jun, Tae-im Kim, Bum Kyu Shin, Da-Young Yoon and Soo-Min Lee
Pharmaceuticals 2026, 19(1), 189; https://doi.org/10.3390/ph19010189 - 22 Jan 2026
Viewed by 79
Abstract
Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to [...] Read more.
Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article
(This article belongs to the Section Pharmacology)
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16 pages, 9958 KB  
Review
The Role of Imaging Techniques in the Evaluation of Extraglandular Manifestations in Patients with Sjögren’s Syndrome
by Marcela Iojiban, Bogdan-Ioan Stanciu, Laura Damian, Lavinia Manuela Lenghel, Carolina Solomon and Monica Lupșor-Platon
Diagnostics 2026, 16(2), 358; https://doi.org/10.3390/diagnostics16020358 - 22 Jan 2026
Viewed by 62
Abstract
Sjögren’s syndrome is a chronic autoimmune disease marked by lymphocytic infiltration of the exocrine glands and the development of sicca symptoms, yet some patients also develop extraglandular involvement. Imaging has become relevant for describing these systemic features and supporting clinical assessment. This review [...] Read more.
Sjögren’s syndrome is a chronic autoimmune disease marked by lymphocytic infiltration of the exocrine glands and the development of sicca symptoms, yet some patients also develop extraglandular involvement. Imaging has become relevant for describing these systemic features and supporting clinical assessment. This review discusses the roles of ultrasonography, elastography, computed tomography, and magnetic resonance imaging in evaluating multisystem disease associated with Sjögren’s syndrome. Ultrasonography and elastography help assess muscular involvement by showing changes in echogenicity and stiffness that reflect inflammation and later tissue remodeling. In joints, ultrasound can detect synovitis, tenosynovitis, and early erosive changes, including abnormalities not yet evident on examination. Pulmonary disease, most often with interstitial lung involvement, is best evaluated with high-resolution computed tomography, which remains the most reliable imaging modality for distinguishing interstitial patterns. Magnetic resonance imaging is valuable in assessing neurological complications. It can reveal ischemic and demyelinating lesions, neuromyelitis optica spectrum features, or pseudotumoral appearances. Imaging is also essential for detecting lymphoproliferative complications, for which ultrasound and magnetic resonance imaging can reveal characteristic structural and diffusion-weighted imaging findings. When combined with clinical and laboratory information, these imaging methods improve early recognition of systemic involvement and support accurate monitoring of disease progression in Sjögren’s syndrome. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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12 pages, 651 KB  
Article
Real-World Effectiveness of Seasonal Influenza Vaccines During the 2024–2025 Season: Subgroup Analyses by Virus Subtype, Time Since Vaccination, and Diagnostic Method
by Yu Jung Choi, Jungmin Lee, Joon Young Song, Seong-Heon Wie, Jacob Lee, Jin-Soo Lee, Hye Won Jeong, Joong Sik Eom, Jang Wook Sohn, Young Kyung Yoon, Won Suk Choi, Eliel Nham, Jin Gu Yoon, Ji Yun Noh, Man-Seong Park and Hee Jin Cheong
Vaccines 2026, 14(1), 102; https://doi.org/10.3390/vaccines14010102 - 21 Jan 2026
Viewed by 111
Abstract
Background/Objectives: Despite high vaccination coverage, influenza remains a public health concern in South Korea, particularly in older adults. Continuous evaluation of vaccine effectiveness (VE) is essential to optimize immunization strategies. Methods: This study evaluated seasonal influenza VE for preventing laboratory-confirmed influenza [...] Read more.
Background/Objectives: Despite high vaccination coverage, influenza remains a public health concern in South Korea, particularly in older adults. Continuous evaluation of vaccine effectiveness (VE) is essential to optimize immunization strategies. Methods: This study evaluated seasonal influenza VE for preventing laboratory-confirmed influenza using a test-negative design through a hospital-based influenza surveillance system in South Korea from 1 November 2024, to 30 April 2025. Demographic and clinical information was collected through questionnaire surveys and electronic medical records. Influenza was diagnosed using rapid antigen tests (RATs) and reverse transcription polymerase chain reaction (RT-qPCR), and vaccine effectiveness was analyzed using multivariable logistic regression. Results: In total, 3954 participants were included, with 1977 influenza-positive cases and 1977 test-negative controls. Influenza A and B accounted for 93.1% and 7.0% of cases, respectively. The adjusted overall VE was 20.4% (95% confidence interval [CI], 8.2–30.9; p = 0.002). VE was higher in adults aged 50–64 years (46.8%) than in those aged ≥65 years (18.8%). VE was 19.9% against influenza A and 45.7% against A/H3N2. VE was higher among individuals tested using RT-qPCR than among those tested using RATs (21.5% vs. 15.7%), and was also greater during the early period than during the late period (20.5% vs. 11.4%). Vaccination did not reduce influenza-associated hospitalization risk (VE, 17.3%; 95% CI, −9.3 to 37.4). A significant reduction in hospitalization risk was observed in adults aged 50–64 years (VE, 46.8%), with no significant benefit in those aged ≥65 years. Conclusions: The 2024–2025 seasonal influenza vaccine provided moderate protection against laboratory-confirmed influenza in adults, with higher effectiveness in those aged 50–64 years. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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24 pages, 57665 KB  
Article
Geochemical Framework of Ataúro Island (Timor-Leste) in an Arc–Continent Collision Setting
by Job Brites dos Santos, Marina Cabral Pinto, Victor A. S. Vicente, André Ram Soares and João A. M. S. Pratas
Minerals 2026, 16(1), 89; https://doi.org/10.3390/min16010089 - 17 Jan 2026
Viewed by 173
Abstract
Ataúro Island, located in the inner Banda Arc, provides a natural laboratory to investigate the interplay between magmatic evolution, hydrothermal circulation, and near-surface weathering in an active arc–continent collision setting. This study presents the first systematic island-wide geochemical baseline for Ataúro Island, based [...] Read more.
Ataúro Island, located in the inner Banda Arc, provides a natural laboratory to investigate the interplay between magmatic evolution, hydrothermal circulation, and near-surface weathering in an active arc–continent collision setting. This study presents the first systematic island-wide geochemical baseline for Ataúro Island, based on multi-element analyses of stream sediments integrated with updated geological, structural, and hydromorphological information. Compositional Data Analysis (CoDA–CLR–PCA), combined with anomaly mapping and spatial overlays, defines a coherent three-tier geochemical framework comprising: (i) a lithogenic component dominated by Fe–Ti–Mg–Ni–Co–Cr, reflecting the geochemical signature of basaltic to andesitic volcanic rocks; (ii) a hydrothermal component characterized by Ag–As–Sb–S–Au associations spatially linked to structurally controlled zones; and (iii) an oxidative–supergene component marked by Fe–V–Zn redistribution along drainage convergence areas. These domains are defined strictly on geochemical criteria and represent geochemical process domains rather than proven metallogenic provinces. Rare earth element (REE) systematics further constrain the geotectonic setting and indicate that the primary geochemical patterns are largely controlled by lithological and magmatic differentiation processes. Spatial integration of geochemical patterns with fault architecture highlights the importance of NW–SE and NE–SW structural corridors in focusing hydrothermal fluid circulation and associated metal dispersion. The identified Ag–As–Sb–Au associations are interpreted as epithermal-style hydrothermal geochemical enrichment and exploration-relevant geochemical footprints, rather than as evidence of confirmed or economic mineralization. Overall, Ataúro Island emerges as a compact natural analogue of post-arc geochemical system evolution in the eastern Banda Arc, where lithogenic background, hydrothermal fluid–rock interaction, and early supergene processes are superimposed. The integrated geochemical framework presented here provides a robust baseline for future targeted investigations aimed at distinguishing lithogenic from hydrothermal contributions and evaluating the potential significance of the identified geochemical enrichments. Full article
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16 pages, 2979 KB  
Article
Non-Invasive Assessment of Water-Based Gel Cleaning on a Capogrossi Oil Painting Using NMR-MOUSE
by Noemi Proietti, Patrizia Moretti, Eleonora Maniccia, Paola Carnazza, Daphne De Luca, Costanza Miliani and Valeria Di Tullio
Heritage 2026, 9(1), 30; https://doi.org/10.3390/heritage9010030 - 15 Jan 2026
Viewed by 154
Abstract
This study investigates water-based gel and gel-like cleaning treatments on Superficie 553, an oil painting on canvas by Giuseppe Capogrossi, using portable NMR to assess their impact. The objective was to evaluate the effects of four cleaning systems composed of a buffer [...] Read more.
This study investigates water-based gel and gel-like cleaning treatments on Superficie 553, an oil painting on canvas by Giuseppe Capogrossi, using portable NMR to assess their impact. The objective was to evaluate the effects of four cleaning systems composed of a buffer solution released in free form and combined with xanthan gum, a cross-linked silicone polymer gel, and an agar gel matrix. Two distinct NMR experiments were conducted. The first involved the acquisition of 1H depth profiles to detect the distribution of the cleaning solution within the painted layer and the thickness variations resulting from cleaning procedures. The second employed the acquisition of relaxation times, facilitating the investigation of molecular mobility within the organic components of the paint layer. NMR results indicated that the agar gel system caused negligible structural changes, whereas the silicone gel induced rigidification, and the other systems permanently increased molecular mobility. These measurements provided insights into alterations in the dynamic behavior of the polymerized oil. A key strength of this investigation lies in the direct application of diagnostic methods on Superficie 553, made possible by the non-invasive nature and portability of the NMR-MOUSE system. Additionally, portable FTIR was used to detect residues and obtain chemical information, confirming that the silicone gel left detectable residues and identifying the agar gel as the most conservative cleaning method. This enabled in situ analysis of the original artwork without sampling or relocation—a crucial advantage given the difficulty of replicating the complex physicochemical conditions of historical paint surfaces under laboratory constraints. Such real-time, on-site monitoring ensured an authentic evaluation of the treatment effects, preserving the integrity of the artwork throughout the conservation process. Full article
(This article belongs to the Special Issue Innovative Materials and Tools for the Cleaning of Cultural Heritage)
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22 pages, 1186 KB  
Article
Diagnostic and Prognostic Utility of DNI and CRP in Patients with Dilated Cardiomyopathy
by Nihat Söylemez, Özkan Karaca, Burak Toprak, Samet Yılmaz and Ahmet Turhan Kılıç
Int. J. Mol. Sci. 2026, 27(2), 871; https://doi.org/10.3390/ijms27020871 - 15 Jan 2026
Viewed by 134
Abstract
Dilated cardiomyopathy is characterized by progressive left ventricular dilation and impaired systolic function, with inflammation recognized as a key contributor to disease onset and adverse outcomes. C-reactive protein reflects systemic biochemical inflammation, whereas Delta Neutrophil Index represents the circulating immature neutrophil fraction and [...] Read more.
Dilated cardiomyopathy is characterized by progressive left ventricular dilation and impaired systolic function, with inflammation recognized as a key contributor to disease onset and adverse outcomes. C-reactive protein reflects systemic biochemical inflammation, whereas Delta Neutrophil Index represents the circulating immature neutrophil fraction and provides a cellular dimension of inflammatory burden. The combined diagnostic and prognostic value of these two biomarkers in dilated cardiomyopathy has not been adequately explored. This retrospective study included one hundred and fifty patients with dilated cardiomyopathy and one hundred and fifty age-, diabetes-, and hypertension-matched controls. Demographic, laboratory, and echocardiographic measurements were analyzed. The diagnostic and prognostic performances of C-reactive protein, Delta Neutrophil Index, and their combined model were assessed using logistic regression, receiver operating characteristic curve analysis, reclassification metrics, calibration testing, and decision curve analysis. Additional analyses were performed for patients with left ventricular ejection fraction below twenty percent, and mortality predictors were examined within the dilated cardiomyopathy cohort. Both C-reactive protein and Delta Neutrophil Index levels were significantly higher in patients with dilated cardiomyopathy than in controls and were further elevated in those with severely reduced ejection fraction. Delta Neutrophil Index remained independently associated with severe left ventricular dysfunction (ejection fraction ≤ 20%) in multivariable analysis (odds ratio 2.51). Each biomarker showed an independent association with the presence of dilated cardiomyopathy, and their combined model achieved the highest diagnostic accuracy. In receiver operating characteristic analysis, the area under the curve was 0.895 for Delta Neutrophil Index, 0.691 for C-reactive protein, and increased to 0.920 for the combined model, with a sensitivity of 81.3% and specificity of 92.0%. Delta Neutrophil Index was independently associated with severe left ventricular dysfunction and mortality, while C-reactive protein, age, ejection fraction, urea, and sodium also contributed to mortality risk. Delta Neutrophil Index was independently associated with mortality (odds ratio 2.51), while C-reactive protein, age, ejection fraction, urea, and sodium also contributed to mortality risk. The combined model provided significant improvement in risk reclassification and demonstrated superior calibration and greater net clinical benefit across a wide range of decision thresholds. C-reactive protein and Delta Neutrophil Index offer complementary diagnostic and prognostic information in dilated cardiomyopathy. Their combined use enhances diagnostic discrimination, strengthens risk stratification, and improves identification of patients at high risk for severe ventricular dysfunction and mortality. Incorporation of these accessible biomarkers into clinical evaluation may support earlier recognition and more tailored management of high-risk individuals. Full article
(This article belongs to the Special Issue Cardiomyopathy: From Molecular Pathology to Treatment)
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17 pages, 1975 KB  
Article
Comparative Longitudinal Evaluation of Systemic Inflammatory Markers in Type 2 Diabetes Treated with Four Oral Antidiabetic Drug Classes
by Mehmet Yamak, Serkan Çakır, Sami Uzun, Egemen Cebeci, Özlem Menken and Savas Ozturk
J. Clin. Med. 2026, 15(2), 688; https://doi.org/10.3390/jcm15020688 - 15 Jan 2026
Viewed by 155
Abstract
Background: Systemic inflammation plays a central role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Hematologic inflammatory indices-such as the Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR)-have emerged as accessible markers of chronic [...] Read more.
Background: Systemic inflammation plays a central role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Hematologic inflammatory indices-such as the Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR)-have emerged as accessible markers of chronic inflammation, yet longitudinal comparisons across oral antidiabetic therapies remain limited. This study uniquely integrates longitudinal correlation and network analyses in a large real-world T2DM cohort, allowing assessment of the temporal stability and class-specific inflammatory patterns across four oral antidiabetic therapies. Methods: This retrospective, longitudinal study analyzed 13,425 patients with T2DM treated with Biguanidines, Dipeptidyl Peptidase-4 (DPP-4) inhibitors, Sodium–Glucose Cotransporter-2 (SGLT-2) inhibitors or Thiazolidinediones (TZDs) between 2020 and 2024. Data were retrieved from the Probel® Hospital Information System and included baseline, early (30–180 days), and late (180–360 days) follow-up laboratory results. Systemic inflammatory indices were computed from hematologic parameters, and correlations among inflammatory and biochemical markers were assessed using Spearman’s coefficients. Results: At baseline, all hematologic indices were strongly intercorrelated (SII–NLR r = 0.83, p < 0.001; SII–PLR r = 0.73, p < 0.001), with moderate associations to C-reactive protein (CRP; r ≈ 0.3–0.4) and weak or no correlations with Ferritin (r ≈ −0.1). These relationships remained stable throughout follow-up, confirming reproducibility of systemic inflammatory coupling. Longitudinally, SII and NLR showed modest early increases followed by significant declines at one year (p < 0.05), while PLR and MLR remained stable. Class-specific differences were observed: SGLT-2 inhibitors and TZDs demonstrated stronger and more integrated anti-inflammatory networks, whereas Biguanidines and DPP-4 inhibitors exhibited moderate coherence. Principal Component Analysis (PCA) explained 62.4% of total variance and revealed distinct clustering for TZD and SGLT-2 groups, reflecting class-specific inflammatory modulation. Conclusions: Systemic inflammatory indices (SII, NLR, PLR) provide reproducible and accessible measures of low-grade inflammation in T2DM. Despite overall inflammation reduction with treatment, drug-specific patterns emerged-SGLT-2 inhibitors and TZDs showed greater anti-inflammatory coherence, while Biguanidines and DPP-4 inhibitors maintained moderate effects. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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16 pages, 2642 KB  
Study Protocol
A Study Protocol for Developing a Pragmatic Aetiology-Based Silicosis Prevention and Elimination Approach in Southern Africa
by Norman Nkuzi Khoza, Thokozani Patrick Mbonane, Phoka C. Rathebe and Masilu Daniel Masekameni
Methods Protoc. 2026, 9(1), 12; https://doi.org/10.3390/mps9010012 - 14 Jan 2026
Viewed by 167
Abstract
Workers’ exposure to silica dust is a global occupational and public health concern and is particularly prevalent in Southern Africa, mainly because of inadequate dust control measures. It is worsened by the high prevalence of HIV/AIDS, which exacerbates tuberculosis and other occupational lung [...] Read more.
Workers’ exposure to silica dust is a global occupational and public health concern and is particularly prevalent in Southern Africa, mainly because of inadequate dust control measures. It is worsened by the high prevalence of HIV/AIDS, which exacerbates tuberculosis and other occupational lung diseases. The prevalence of silicosis in the region ranges from 9 to 51%; however, silica dust exposure levels and controls, especially in the informal mining sector, particularly in artisanal small-scale mines (ASMs), leave much to be desired. This is important because silicosis is incurable and can only be eliminated by preventing worker exposure. Additionally, several studies have indicated inadequate occupational health and safety policies, weak inspection systems, inadequate monitoring and control technologies, and inadequate occupational health and hygiene skills. Furthermore, there is a near-absence of silica dust analysis laboratories in southern Africa, except in South Africa. This protocol aims to systematically evaluate the effectiveness of respirable dust and respirable crystalline silica dust exposure evaluation and control methodology for the mining industry. The study will entail testing the effectiveness of current dust control measures for controlling microscale particles using various exposure dose metrics, such as mass, number, and lung surface area concentrations. This will be achieved using a portable Fourier transform infrared spectroscope (FTIR) (Nanozen Industries Inc., Burnaby, BC, Canada), the Nanozen DustCount, which measures both the mass and particle size distribution. The surface area concentration will be analysed by inputting the particle size distribution (PSD) results into the Multiple-Path Particle Dosimetry Model (MPPD) to estimate the retained and cleared doses. The MPPD will help us understand the sub-micron dust deposition and the reduction rate using the controls. To the best of our knowledge, the proposed approach has never been used elsewhere or in our settings. The proposed approach will reduce dependence on highly skilled individuals, reduce the turnaround sampling and analysis time, and provide a reference for regional harmonised occupational exposure limit (OEL) guidelines as a guiding document on how to meet occupational health, safety and environment (OHSE) requirements in ASM settings. Therefore, the outcome of this study will influence policy reforms and protect hundreds of thousands of employees currently working without any form of exposure prevention or protection. Full article
(This article belongs to the Section Public Health Research)
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12 pages, 237 KB  
Article
The Role of Routine Surveillance Cultures in Optimising Sepsis Management in High-Risk Patient Groups
by Jan Závora, Václava Adámková, Alžběta Studená and Gabriela Kroneislová
Pathogens 2026, 15(1), 82; https://doi.org/10.3390/pathogens15010082 - 12 Jan 2026
Viewed by 157
Abstract
Background: Sepsis remains a leading cause of morbidity and mortality, particularly when caused by multidrug-resistant organisms (MDROs). Early identification of colonising or infecting pathogens may inform initial antimicrobial selection. Surveillance cultures, providing microbiological data prior to infection onset, could guide timely and targeted [...] Read more.
Background: Sepsis remains a leading cause of morbidity and mortality, particularly when caused by multidrug-resistant organisms (MDROs). Early identification of colonising or infecting pathogens may inform initial antimicrobial selection. Surveillance cultures, providing microbiological data prior to infection onset, could guide timely and targeted therapy. This retrospective study analysed routine surveillance culture results from patients with bloodstream infection (BSI) episodes, assessing pathogen prevalence, resistance phenotypes, and concordance with specimen type in haemato-oncology (HO) and acute care (AC) settings. Methods: Data were retrieved from the institutional Laboratory Information System of the Department of Clinical Microbiology and ATB Centre, General University Hospital in Prague, covering 1 January to 31 December 2024. All positive blood cultures containing ESCAPE pathogens (excluding Clostridioides difficile) were reviewed. Corresponding surveillance culture records were analysed to evaluate concordance with subsequent BSI episodes. Results: In 2024, 6046 AC and 7267 HO surveillance cultures were performed; MDRO prevalence was 5% and 6.56%, respectively. ESBL-producing Enterobacterales predominated (AC 86.9%, HO 81.6%). In HO, BSI-causing Gram-negative and Gram-positive pathogens were frequently detected in rectal swabs, whereas in AC, concordance was higher with upper and lower respiratory tract samples. Rectal screening detected 100% of E. coli and K. pneumoniae BSI episodes in HO. Other specimen types showed limited concordance. Conclusions: Surveillance culture utility varies by specimen type and clinical setting. In both HO and AC units, these cultures provided valuable insights into colonisation and resistance patterns, supporting early risk stratification and guiding initial therapy in high-risk patients. Full article
(This article belongs to the Special Issue Current Progress on Bacterial Antimicrobial Resistance)
17 pages, 1047 KB  
Article
Toward Personalized Withdrawal of TNF-α Inhibitors in Non-Systemic Juvenile Idiopathic Arthritis: Predictors of Biologic-Free Remission and Flare
by Ekaterina I. Alexeeva, Irina T. Tsulukiya, Tatyana M. Dvoryakovskaya, Ivan A. Kriulin, Dmitry A. Kudlay, Anna N. Fetisova, Maria S. Botova, Tatyana Y. Kriulina, Elizaveta A. Krekhova, Natalya M. Kondratyeva, Meiri Sh. Shingarova, Maria Y. Kokina, Alyona N. Shilova and Mikhail M. Kostik
Pharmaceuticals 2026, 19(1), 125; https://doi.org/10.3390/ph19010125 - 10 Jan 2026
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Abstract
Background: Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or [...] Read more.
Background: Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or interval extension. Objective: We aim to identify patient-, disease-, and treatment-related predictors of successful TNF-α inhibitor withdrawal in children with non-systemic JIA. Methods: In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for ≥24 months on etanercept or adalimumab were enrolled. At the time of TNF-α inhibitor discontinuation, all patients underwent a comprehensive evaluation, including a clinical examination, laboratory tests (serum calprotectin [S100 proteins] and high-sensitivity C-reactive protein [hsCRP]), and advanced joint imaging (musculoskeletal ultrasound and magnetic resonance imaging [MRI]) to assess subclinical disease activity. Patients were randomized (1:1:1, sealed-envelope allocation) to one of three predefined tapering strategies: (I) abrupt discontinuation; (II) extension of dosing intervals (etanercept 0.8 mg/kg every 2 weeks; adalimumab 24 mg/m2 every 4 weeks); or (III) gradual dose reduction (etanercept 0.4 mg/kg weekly; adalimumab 12 mg/m2 every 2 weeks). Follow-up visits were scheduled at 3, 6, 9, 12, and 18 months to monitor for disease relapse. Results: Higher baseline Childhood Health Assessment Questionnaire (CHAQ) scores (≥2), elevated serum calprotectin [S100 proteins] and hsCRP levels at withdrawal, imaging evidence of subclinical synovitis, and a history of uveitis were all significantly associated with increased risk of flare. No significant associations were found for other clinical or demographic characteristics. Conclusions: Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA. Full article
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12 pages, 251 KB  
Article
Admission eGFR as a Marker of Systemic Vulnerability in Patients with Spontaneous Intracerebral Hemorrhage: Impact of Premorbid Disability and Acute Kidney Injury on Outcomes
by Kamil Ludwiniak, Piotr Olejnik, Oliwia Maciejewska, Andrzej Opuchlik, Jolanta Małyszko and Aleksandra Golenia
J. Clin. Med. 2026, 15(2), 562; https://doi.org/10.3390/jcm15020562 - 10 Jan 2026
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Abstract
Background: Kidney dysfunction is common in intracerebral hemorrhage (ICH), but it is unclear whether reduced estimated glomerular filtration rate (eGFR) on admission is an independent driver of short-term outcomes or a marker of overall vulnerability. Methods: In this single-center retrospective study, [...] Read more.
Background: Kidney dysfunction is common in intracerebral hemorrhage (ICH), but it is unclear whether reduced estimated glomerular filtration rate (eGFR) on admission is an independent driver of short-term outcomes or a marker of overall vulnerability. Methods: In this single-center retrospective study, we analyzed the data of consecutive patients with spontaneous ICH. Results: Among 276 patients, 92 (33.3%) presented with eGFR < 60 mL/min/1.73 m2 on admission. Only 17/92 (18.5%) had documented pre-existing chronic kidney disease (CKD). Acute kidney injury (AKI) occurred more often in patients with eGFR < 60 mL/min/1.73 m2 than in those with eGFR ≥ 60 mL/min/1.73 m2 (25.0% vs. 10.3%). In survival models, eGFR ≥ 60 mL/min/1.73 m2, predicted higher 90-day survival in the baseline model (OR 3.031, p = 0.013) but was attenuated after adjustment for age and premorbid modified Rankin Scale (mRS) and was no longer independent after additional adjustment for laboratory markers. Across all models, the National Institutes of Health Stroke Scale (NIHSS) score, hematoma volume, and history of coronary artery disease remained robust predictors. Higher leukocyte count predicted lower survival, whereas higher hemoglobin predicted higher survival. Among survivors, favorable functional outcome was independently associated with lower NIHSS, younger age, lower premorbid mRS, and absence of documented CKD. Admission eGFR category was not independently associated. Conclusions: Reduced admission eGFR primarily reflects baseline frailty and systemic derangement rather than an independent determinant of short-term survival after full adjustment, whereas documented CKD is more informative for disability among survivors. AKI occurs more frequently in patients presenting with reduced eGFR, supporting close renal monitoring in acute ICH. Full article
(This article belongs to the Section Clinical Neurology)
18 pages, 2633 KB  
Article
Prediction of Ammonia Mitigation Efficiency in Sodium Bisulfate-Treated Broiler Litter Using Artificial Neural Networks
by Busra Yayli and Ilker Kilic
Animals 2026, 16(2), 210; https://doi.org/10.3390/ani16020210 - 10 Jan 2026
Viewed by 154
Abstract
The increasing demand for poultry meat, driven by its favorable nutritional profile, including low cholesterol and high protein content, has resulted in intensified production volumes and, consequently, elevated ammonia (NH3) emissions. Artificial intelligence-based predictive approaches offer an effective alternative to conventional [...] Read more.
The increasing demand for poultry meat, driven by its favorable nutritional profile, including low cholesterol and high protein content, has resulted in intensified production volumes and, consequently, elevated ammonia (NH3) emissions. Artificial intelligence-based predictive approaches offer an effective alternative to conventional treatment-oriented methods by enabling faster and more accurate estimation of NH3 removal performance. This study aimed to predict the ammonia removal efficiency of broiler litter generated during a production cycle under controlled laboratory-scale conditions using artificial neural networks (ANNs) trained with different learning algorithms. Four ANN models were developed based on the Levenberg–Marquardt (LM), Fletcher–Reeves (FR), Scaled Conjugate Gradient (SCG), and Bayesian Regularization (BR) algorithms. The results showed that the LM-based model with 12 hidden neurons achieved the highest predictive performance (R2 = 0.9777; MSE = 0.0033; RMSE = 0.0574; MAPE = 0.0833), while the BR-based model with 10 neurons showed comparable accuracy. In comparison with the FR and SCG models, the LM algorithm demonstrated superior predictive accuracy and generalization capability. Overall, the findings suggest that ANN-based modeling is a reliable, data-informed approach for estimating NH3 removal efficiency, providing a potential decision-support framework for ammonia mitigation strategies in poultry production systems. Full article
(This article belongs to the Section Poultry)
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