Nevin Manimala

Pediatr Pulmonol. 2025 Dec;60(12):e71419. doi: 10.1002/ppul.71419.

ABSTRACT

BACKGROUND: In cystic fibrosis (CF), the defect of the CF transmembrane conductance regulator (CFTR) can also affect sensory nerve cell function, as recently demonstrated in animal models. The aim of this prospective cohort study was to investigate whether taste and smell disorders in CF correlate with persistent CFTR dysfunction detectable by iontophoresis or rather with inflammation or lung function. Participants with primary ciliary dyskinesia (PCD) and controls without pulmonary disease served as comparators.

METHODS: In 65 participants (age median 19 years IQR [12-26]; CF n = 23, PCD n = 22, controls n = 20) at the University Children´s Hospital Bochum, we measured taste (salty, sweet, sour, bitter) at four concentrations (“Taste-Strips,” score 0-16, hypogeusia age-adjusted < 8/< 9/< 9.9/< 10 points) and smell (“U-Sniff”-test, score 0-12, reduced odor identification performance < 8 points), pilocarpine iontophoresis, spirometry, inflammatory markers (e.g., CRP) and subjective chemosensory impairment.

STATISTICS: Chi²/Fisher’s-exact, Mann-Whitney-U, Kruskal-Wallis, linear regression; p < 0.05.

RESULTS: Hypogeusia occurred only in CF (17.4%). Particularly misidentification of the taste “salty” occurred significantly more frequently in CF (34.8% vs. PCD 19.3% and controls 17.5%), especially in the CF subgroup with elevated sweat chloride ≥ 60 mmol/l. Reduced odor identification performance was significantly more common in PCD (30% vs. CF 4%). Chemosensory disorders were not related to current lung function or inflammation.

CONCLUSION: Taste disorders in CF are mostly attributed to difficulties tasting salty and are associated with elevated sweat chloride, probably caused by increased salivary salt following CFTR dysfunction in salivary glands rather than in the nerve cells. Smell disorders, however, remain a significant issue, particularly in PCD.

PMID:41347296 | DOI:10.1002/ppul.71419

JB JS Open Access. 2025 Dec 8;10(4):e25.00179. doi: 10.2106/JBJS.OA.25.00179. eCollection 2025 Oct-Dec.

ABSTRACT

BACKGROUND: Geographic access to orthopaedic surgery remains limited in nonmetropolitan regions, where over half of US counties lack an orthopaedic surgeon. Osteopathic physicians (DOs) are nearly twice as likely as allopathic physicians (MDs) to practice in these areas, making them a key component of the rural surgical workforce. However, their representation in orthopaedic training has declined since the ACGME-AOA merger.

METHODS: This cross-sectional national study used 2022 Area Health Resource Files, National Residency Matching Program Match data (2020-2024), and USDA Rural-Urban Continuum Codes (RUCC) to evaluate workforce distribution and match outcomes. Statistical analysis included chi-square testing and odds ratios to assess nonmetropolitan representation by degree and state.

RESULTS: Of 30,243 orthopaedic surgeons, 92.9% practiced in metropolitan counties and 7.1% in nonmetropolitan areas. Among DOs, 12.5% practiced in nonmetropolitan regions compared with 6.9% of MDs (OR = 1.92; 95% CI: 1.67-2.19). Eleven states showed significantly higher odds of DOs practicing in nonmetropolitan counties, 9 of these states with longstanding in-state osteopathic schools. From 2010 to 2022, DO presence in nonmetropolitan areas increased by 59%, nearly double the rate of MDs. Despite these contributions, DO match rates in orthopaedic surgery declined from 63.3% to 45.7% between 2020 and 2024, widening the DO-MD gap.

CONCLUSIONS: DOs play an important role in orthopaedic coverage, as a percentage of their total, in nonmetropolitan communities. Declining match rates raise concerns about the sustainability of this workforce, particularly in states where DOs help maintain surgical access. Structural reforms in training pathways and residency selection may help preserve geographic workforce diversity.

CLINICAL RELEVANCE: Targeted strategies, such as rural training programs, holistic applicant evaluation, and state-specific recruitment efforts, may strengthen access to musculoskeletal care in underserved regions and support a more equitable orthopaedic workforce.

PMID:41347250 | PMC:PMC12674144 | DOI:10.2106/JBJS.OA.25.00179

NAR Genom Bioinform. 2025 Dec 3;7(4):lqaf169. doi: 10.1093/nargab/lqaf169. eCollection 2025 Dec.

ABSTRACT

Current strategies for optimizing gene therapeutics and recombinant protein production typically rely on universal host codon usage indices. However, there is a growing shift toward incorporating gene-specific traits to enhance therapeutic characteristics. In this study, we investigate position-specific variations in codon and adjacent codon-pair usage biases (CPUBs), offering potential for more tailored gene engineering approaches. We focus our analysis on the coding sequences of four coagulation factors: ADAMTS13, von Willebrand factor, factor VIII, and factor IX, which have been used in therapeutic applications. By aligning transcript homologs with human sequences for each gene using Discontiguous Megablast and MACSE, we assess “sequence-position-specific” codon and CPUBs; 157 homologous sequences for ADAMTS13, 148 for F8, 96 for F9, and 202 for VWF. Species with homologs ranged from Primates and Artiodactyla (Even-toed Ungulates) to Testudines. Statistically significant, position-specific positive CPUBs were observed that contrasted with conventional, alignment-specific negative CPUBs. Moreover, we observed that codon and codon-pair usages are highly associated at sequence positions despite little or no association in conventional-position-agnostic analyses. The distinct biases observed at different positions/functionally critical domains in coding sequences highlight the importance of considering position-specific effects in codon optimization strategies.

PMID:41347229 | PMC:PMC12673856 | DOI:10.1093/nargab/lqaf169

Neuroophthalmology. 2025 Jul 14;49(6):456-463. doi: 10.1080/01658107.2025.2521785. eCollection 2025.

ABSTRACT

This study was designed to compare optical coherence tomography angiography (OCTA) microvasculature characteristics of the optic disc and peripapillary retina in ischemic and non-ischemic optic disc edema and to compare them to normals. We hypothesized that ischemic edema would show significantly decreased vascular density when compared with non-ischemic edema and normals. Swept source OCTA imaging (Zeiss PLEX 9000) centered on the optic disc (6 X 6 mm) was performed in 17 eyes with acute ischemic optic disc edema, 22 eyes with acute optic disc edema from other causes, and 26 eyes with normal optic disc and retina. Vessel density (VD) within the superficial (SVC) and deep (DVC) vascular retinal complexes were computed. The mean superficial VD for the optic nerve in ischemic edema cases was 31.86%, compared to 36.10% in non-ischemic edema cases (p = .002) and 35.64% in normals (p = .0019); for the peripapillary retina, the means were 34.50% compared to 37.02% (p = .0006) and 34.70% (p = .8177). The mean deep VD for the optic nerve in ischemic edema cases was 30.41%, compared to 33.29% for non-ischemic cases (p = .0234) and 36.01% in normals (p = .0001); for the peripapillary retina, the means were 31.28% compared to 33.62% (p = .0217) and 35.31% (p = .0001). The optic disc and peripapillary VD were statistically significantly decreased in ischemic vs non-ischemic optic disc edema at both SVC and DVC. The findings highlight a possible role of the central retinal artery-derived circulation in ischemic optic nerve edema.

PMID:41347214 | PMC:PMC12674231 | DOI:10.1080/01658107.2025.2521785

J Clin Pract Res. 2025 Oct 23;47(5):512-518. doi: 10.14744/cpr.2025.78636. eCollection 2025 Oct.

ABSTRACT

OBJECTIVE: The primary aim of this research was to assess whether individuals with obesity or opioid use disorder (OUD) exhibit altered levels of specific adipokines compared with healthy subjects.

MATERIALS AND METHODS: A total of 90 participants were included (obesity group: 30, OUD group: 30, control group: 30).

RESULTS: Participants in both the obesity and OUD groups exhibited significantly increased concentrations of resistin, chemerin, and omentin-1 (p<0.05). Conversely, apelin levels were substantially reduced in both groups compared to healthy controls (p=0.001). Notably, nesfatin-1 levels were significantly lower only in the OUD group relative to controls (p=0.005). No statistically significant difference in body mass index (BMI) was found between individuals with OUD and healthy subjects (p=0.619).

CONCLUSION: These findings suggest that obesity may share pathophysiological similarities with addiction. Therefore, obesity management should include psychological support. Additionally, considering the physiological roles of adipokine-related hormones, patients should be closely monitored for blood glucose levels, insulin resistance, diabetes mellitus, lipolysis, inflammation, and clinical complications such as atherosclerosis.

PMID:41347199 | PMC:PMC12673317 | DOI:10.14744/cpr.2025.78636

J Clin Pract Res. 2025 Oct 23;47(5):550-559. doi: 10.14744/cpr.2025.78739. eCollection 2025 Oct.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the immunoreactivity of sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) in colorectal cancer tissues using immunohistochemistry and to investigate their potential roles in the diagnosis and prognosis of colorectal cancer.

MATERIALS AND METHODS: Colon specimens from 104 patients diagnosed with colorectal adenocarcinoma at SBÜ Kartal Dr. Lütfi Kırdar City Hospital between 2016 and 2021 were analyzed. Immunohistochemical staining was performed to assess the immunoreactivity of SIRT1 and SIRT2. Associations between the clinicopathological parameters of colorectal cancer patients and the expression levels of SIRT1 and SIRT2 (categorized as low or high) were examined.

RESULTS: SIRT1 expression was significantly associated with K-RAS mutations (p=0.021) but showed no significant association with N-RAS (p=0.114) or B-RAF (p=0.624) mutations. SIRT2 expression levels were significantly associated with TNM stage (p=0.043), presence of metastasis (p=0.004), K-RAS mutations (p=0.047), and N-RAS mutations (p=0.020). Co-expression of SIRT1 and SIRT2 was significantly correlated with TNM stage (p=0.041), presence of metastasis (p=0.012), and mutations in K-RAS (p=0.028) and N-RAS (p=0.022).

CONCLUSION: SIRT2 expression levels were significantly correlated with TNM classification, as well as the presence of metastasis. In contrast, SIRT1 expression was not significantly associated with these parameters. Both SIRT1 and SIRT2 showed a statistically significant relationship with K-RAS mutations, highlighting their potential roles in the molecular pathology of colorectal cancer.

PMID:41347196 | PMC:PMC12673322 | DOI:10.14744/cpr.2025.78739

J Clin Pract Res. 2025 Oct 23;47(5):503-511. doi: 10.14744/cpr.2025.58891. eCollection 2025 Oct.

ABSTRACT

OBJECTIVE: Endometrial cancer (EC) is the most frequent gynecological malignancy in women worldwide. This study aims to develop a predictive model integrating machine learning (ML) approaches with explainable artificial intelligence (XAI) using metabolomics panel data for significant biomarker discovery in EC.

MATERIALS AND METHODS: This study applied metabolomics and XAI to uncover diagnostic biomarkers for EC, the most common gynecologic malignancy. A total of 191 EC cases and 204 controls were analyzed using mass spectrometry. ML and XAI techniques were incorporated, including SHapley Additive exPlanation, Random Forest, BaggedCART, LightGBM, Adaptive Boosting, and Extreme Gradient Boosting.

RESULTS: Statistically significant differences (adjusted p<0.05) were found in 25 metabolites. Effect sizes (ES) of m/z=219.125 (ES=1.516), m/z=672.6961 (ES=0.913), and m/z=203.1564 (ES=0.839) were notably large, suggesting strong discriminatory ability. These metabolites are involved in lipid dysregulation, steroid hormone pathways, and oxidative stress, reflecting cancer-specific metabolic reprogramming. The ML models, particularly LightGBM, demonstrated high accuracy and good calibration. After training with the final feature dataset, SHapley Additive exPlanations (SHAP) analysis identified m/z=219.125, m/z=672.6961, and m/z=127.0769 as the top contributing features, aligning with their biological impact on EC pathogenesis.

CONCLUSION: This study suggests non-invasive biomarkers for early detection of EC screening, highlighting the heterogeneity of metabolic adaptation in EC and the need for multi-omics approaches to understand disease mechanisms. Limitations include diverse cohorts and reliance on tandem mass spectrometry. Nonetheless, these findings represent a step forward in precision oncology.

PMID:41347192 | PMC:PMC12673311 | DOI:10.14744/cpr.2025.58891

J Clin Pract Res. 2025 Oct 23;47(5):480-485. doi: 10.14744/cpr.2025.87060. eCollection 2025 Oct.

ABSTRACT

OBJECTIVE: The objective of this study is to investigate the frequency and clinical spectrum of subclinical spondyloarthritis (SpA) manifestations among patients with hidradenitis suppurativa (HS) and to evaluate their association with cutaneous disease severity and clinical characteristics.

MATERIALS AND METHODS: In this prospective, cross-sectional real-world study, 120 adults with a confirmed diagnosis of HS were systematically assessed for musculoskeletal involvement. The evaluation included clinical examination for inflammatory back pain, peripheral arthritis, enthesitis, and targeted magnetic resonance imaging (MRI) for sacroiliitis when indicated. Laboratory analyses included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and human leukocyte antigen B27 (HLA-B27) status. Spearman’s rank correlation was used to analyze relationships between SpA-related features and HS clinical parameters, including the International Hidradenitis Suppurativa Severity Score System (IHS4) score, Hurley stage, and smoking.

RESULTS: Among the cohort, MRI-confirmed sacroiliitis was detected in 13.3%, enthesitis in 18.3%, HLA-B27 positivity in 12.5%, and peripheral arthritis in 10.0% of patients. A total of 12.5% fulfilled the modified New York criteria for ankylosing spondylitis. No statistically significant correlations were observed between SpA findings and HS severity indices. Weak associations were noted between smoking and both HLA-B27 positivity (ρ=0.27) and peripheral arthritis (ρ=0.21).

CONCLUSION: Subclinical axial and peripheral SpA features are frequently encountered in patients with HS, often in the absence of musculoskeletal complaints. The lack of correlation with skin disease activity highlights the need for routine rheumatologic evaluation in this population to enable early recognition and tailored treatment of inflammatory joint disease.

PMID:41347191 | PMC:PMC12673314 | DOI:10.14744/cpr.2025.87060

Biodivers Data J. 2025 Nov 25;13:e175486. doi: 10.3897/BDJ.13.e175486. eCollection 2025.

ABSTRACT

BACKGROUND: A continental-scale, georeferenced checklist of slime moulds (Eumycetozoa) for Central and Eastern Europe, supplemented with standardised environmental covariates and with a particular emphasis on forest ecosystems, has not previously been available. The absence of a harmonised corpus has constrained statistically supported tests of habitat- and substrate-related patterns and limited objective gap-mapping, particularly within forest ecosystems, where microclimatic buffering, dead-wood continuity and stand history are expected to be decisive; it has also hindered rigorous evaluation of slime moulds’ role as bioindicators of forest habitat types, substrate associations and gradients in anthropogenic pressure (naturalness).

NEW INFORMATION: Literature discovery spanned multidisciplinary and domain-specific platforms; inclusion required a determinable taxon, a locality at least to country level and a year. Records were de-duplicated conservatively; names were harmonised to a single authority (Eumycetozoa.com) with GBIF Species backbone as a fallback and higher taxonomy was filled consistently. The resource comprises presence-only occurrences, a taxonomically standardised checklist and a reference set; the curated bibliography comprises 528 bibliographic entries. Coverage spans Austria, Belarus, Czechia, Estonia, Germany, Hungary, Latvia, Liechtenstein, Lithuania, Moldova, Poland, Russia (European part), Slovakia, Slovenia, Switzerland and Ukraine. Event dates range from 1857 to 2025-08-01 and support ranges and mixed precision. Environmental content includes elevation, consolidated forest class, substrate category, habitat pressure, microhabitat, pH, air temperature, annual precipitation and stand age; controlled vocabularies comprise eight consolidated forest classes, ten substrate categories and seven habitat-pressure classes. The dataset is released under CC-BY-4.0 (Creative Commons Attribution 4.0 International), employs reproducible DwC mapping and stable identifier versioning and is suited to ecological and biogeographic analyses, including forest-focused modelling and gap analyses.

PMID:41347183 | PMC:PMC12673333 | DOI:10.3897/BDJ.13.e175486

Front Pharmacol. 2025 Nov 19;16:1619920. doi: 10.3389/fphar.2025.1619920. eCollection 2025.

ABSTRACT

BACKGROUND: Sufentanil-induced cough (SIC) is prevalent in anesthesia practice. A variety of interventions have been employed to prevent SIC. However, the optimal intervention remains elusive.

METHODS: A comprehensive search of the literature was conducted on the PubMed, Embase, Web of Science, Cochrane Library (CENTRAL) and China National Knowledge Infrastructure (CNKI) databases. The search was limited to publications prior to July 5, 2025. A network meta-analysis (NMA) was conducted using the R software. A Bayesian framework was employed for this NMA. Comparisons of competing models based on the deviance information criterion (DIC) were used to select the optimal model for NMA. The primary outcome is the overall incidence of SIC. The secondary outcomes included the incidence of mild SIC and moderate to severe SIC.

RESULTS: The NMA included 37 randomized controlled trials (RCTs) with 5,105 patients and 18 interventions. Pairwise meta-analysis results indicate that the intervention group significantly decreases the overall incidence of SIC (7.6% vs. 34.8%; OR 0.13; 95% CI 0.09 to 0.18; P < 0.0001; I² = 53.0%), the incidence of mild SIC (4.0% vs. 13.0%; OR 0.28; 95% CI 0.22 to 0.35; P = 0.369; I² = 5.7%), and the incidence of moderate to severe SIC (3.4% vs. 21.7%; OR 0.13; 95% CI 0.10 to 0.16; P = 0.040; I² = 30.6%). NMA results suggested that nalbuphine, dezocine, and butorphanol significantly reduced the overall incidence of SIC, as well as the incidence of mild and moderate-to-severe SIC. Additionally, remifentanil and esketamine were effective in reducing both the overall incidence of SIC and the incidence of moderate to severe SIC. The use of a mechanical dropper was also effective in reducing the incidence of moderate to severe SIC.

CONCLUSION: Three pharmacological interventions-nalbuphine, dezocine, and butorphanol significantly reduced the overall incidence of SIC, as well as the incidence of mild and moderate-to-severe SIC. Additionally, remifentanil and esketamine were effective in reducing the overall incidence of SIC and the incidence of moderate to severe SIC. The application of a mechanical dropper was also effective in reducing the incidence of moderate to severe SIC. The remaining interventions indicated a trend toward reducing SIC incidence; however, this was not statistically significant.

SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024581866 , PROSPERO (CRD42024581866).

PMID:41347178 | PMC:PMC12673273 | DOI:10.3389/fphar.2025.1619920