Search Results (3,352)

Maternal folate receptor alpha autoantibodies (FRAA) have been associated with impaired placental folate transport, fetal cerebral folate deficiency (CFD) and neurodevelopmental risks including autism spectrum disorder (ASD); however, first-trimester-specific reference intervals remain undefined. This prospective single-center study of 534 healthy pregnant women at 10 + 0 to 15 + 6 weeks’ gestation (week 10 n = 26; week 11 n = 155; week 12 n = 203; week 13 n = 105; week 14 n = 39; week 15 n = 6) used a CE-IVDR FRAA ELISA, following CLSI EP28-A3c and IFCC C-RIDL protocols, to establish week-specific percentiles (P5, P50, P95, P99) via non-parametric estimation and log-smoothed regression with a 1-week rolling window. An internal-consistency ROC analysis was performed against the within-dataset ≥P99 designation and is therefore not interpretable as discrimination against an independent clinical outcome. Median FRAA declined from 29 ng/mL (week 10) to 25 ng/mL (week 14), with provisional clinically actionable thresholds of P95 ≈ 120 ng/mL and P99 ≈ 150 ng/mL. These data provide the first first-trimester normative percentile curves for maternal FRAA and may support prioritizing FRAA assessment before 15 weeks (onset of accelerated transplacental IgG transfer). Given the cross-sectional, single-center design, the small samples at weeks 14–15, and the absence of long-term neurodevelopmental outcome data, the proposed thresholds and any downstream clinical implications, including folinic acid intervention and ASD risk mitigation, should be considered hypothesis-generating and require external and longitudinal validation. Full article

Background: Late-onset neonatal sepsis (LONS) remains a major cause of morbidity in preterm neonates admitted to the neonatal intensive care unit (NICU), yet the contribution of vitamin D status to neonatal infectious susceptibility remains uncertain. Objective: To evaluate clinical and demographic variables and serum vitamin D levels assessed at birth in preterm neonates with and without LONS. Methods: A retrospective observational cohort study was conducted in a tertiary NICU in northeastern Mexico between May 2023 and October 2024. Preterm neonates (<37 weeks of gestation) with serum 25(OH)D measured within the first hour of life were included. Vitamin D status was classified as sufficient (≥30 ng/mL), insufficient (20–29 ng/mL), or deficient (<20 ng/mL). LONS was defined as sepsis occurring after 72 h of life. Comparisons between neonates with and without LONS were performed using Fisher’s exact test for categorical variables and Student’s t-test or Mann–Whitney U test for continuous variables, as appropriate. Results: Twenty-nine preterm neonates were included (mean gestational age: 32.0 ± 2.6 weeks; mean birth weight: 1748 ± 545 g). The mean serum 25(OH)D level at birth was 35.5 ± 13.0 ng/mL. LONS occurred in 31% (9/29) of neonates, of which 55% were microbiologically confirmed. No significant differences were observed in vitamin D levels between neonates with and without LONS (35.0 ± 12.0 vs. 35.7 ± 13.7 ng/mL; p = 0.899). Vitamin D deficiency was not associated with LONS (OR 1.13, 95% CI 0.09–14.28). The prevalence of vitamin D deficiency was low (10%) in this cohort. Conclusions: A clear association between serum 25(OH)D levels at birth and the development of LONS could not be demonstrated in this small exploratory cohort. Given the limited sample size and low prevalence of vitamin D deficiency, further multicenter prospective studies are required to better understand the potential relationship between vitamin D status and neonatal infectious outcomes. Full article

Background: Vitamin D deficiency is a common global health problem and remains highly prevalent in Türkiye, where limited food fortification and heterogeneous clinical practices contribute to variability in testing and supplementation strategies. Aims: To provide Türkiye-specific best practice recommendations for defining clinically relevant serum 25-hydroxyvitamin D [25(OH)D] thresholds, identifying adult risk groups for targeted testing, and recommending evidence-based prevention, treatment, and monitoring approaches while minimizing under-treatment and inappropriate high-dose use. Methods: This national expert consensus document was developed by endocrinologists from across Türkiye using a structured, modified Delphi methodology. Draft statements informed by systematic literature reviews were rated via online surveys using a 9-point Likert scale, followed by two Delphi rounds and a face-to-face consensus meeting in İstanbul in October 2025. Results: Recommendations addressed sun exposure, laboratory assessment, screening, supplementation, treatment, and follow-up. Serum 25(OH)D <20 ng/mL was defined as deficiency and <12 ng/mL as severe deficiency, with a target range of 20–50 ng/mL. Routine population-wide screening was not recommended; instead, targeted testing in high-risk adults and symptom-driven biochemical evaluation were endorsed. Empiric supplementation was recommended for selected high-risk groups, with cholecalciferol as the preferred agent. Higher individualized doses were suggested in obesity or malabsorption, while loading regimens were reserved for specific clinical indications, such as severe deficiency or certain medical conditions that impair vitamin D metabolism. Reassessment of 25(OH)D at 8–12 weeks was recommended. Conclusion: These consensus-based recommendations provide a practical, context-specific framework for assessing, preventing, treating, and monitoring vitamin D deficiency in adults in Türkiye. Full article

SIRT2 (Sirtuin 2) is an NAD+-dependent deacetylase that exerts crucial regulatory effects on immune homeostasis and macrophage activation. While chronic cold exposure is a known predisposing factor for pulmonary dysfunction, the precise mechanisms by which SIRT2 potentially modulates lung macrophage polarization under cold stress remains poorly understood. In this study, we evaluated the protective capacity of SIRT2 using both wild-type (WT) and Sirt2-knockout (Sirt2−/−) murine models subjected to chronic cold exposure (4 °C for 3 h daily over 21 days). Our results demonstrated that Sirt2 deficiency significantly exacerbated cold-induced pulmonary histopathological damage and increased the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) (p < 0.05). Furthermore, chronic cold stress triggered a macrophage-centered inflammatory response, a process wherein SIRT2 was found to curtail M1 pro-inflammatory polarization. To further investigate these mechanisms, in vitro experiments were conducted using the mouse alveolar macrophage cell line MH-S. While LPS was utilized as a canonical inflammatory stimulus to mimic the injury environment, SIRT2 overexpression was found to reverse the LPS-induced increase in M1 markers and attenuate inflammatory cytokine secretion. These findings suggest that SIRT2 maintains intracellular homeostasis by modulating macrophage plasticity and plays a protective role in the development of chronic cold stimulus-induced lung injury. Consequently, SIRT2 activation may represent a potential therapeutic pathway for the treatment of environment-related respiratory diseases. Full article

Background/Objectives: Iron deficiency early in life can impair infant growth and cognitive development. Here, we follow infants’ plasma ferritin levels—an indicator of iron stores—over the first year of life and relate these to birth characteristics, maternal characteristics, and infant feeding. Methods: Children and their mothers enrolled in the Swedish birth cohort NICE (ClinicalTrials.gov identifier: NCT05809479) were followed from pregnancy to twelve months postpartum. Plasma ferritin was quantified in umbilical cord blood at birth (n = 345), in venous plasma at four months after birth (mother–infant dyads, n = 133), and at twelve months of age (n = 158), using sandwich ELISA. Perinatal and postnatal growth, together with infant and maternal characteristics, were extracted from medical birth records. Breastfeeding and formula feeding were assessed using repeated monthly questionnaires during the first year. Longitudinal changes were analyzed using linear mixed-effects models, and factors associated with ferritin concentrations were examined using Spearman correlations, linear regression models, and segmented generalized additive models. Results: The ferritin concentration declined over time (birth: 267 ng/mL; four months: 146 ng/mL; twelve months: 30 ng/mL). Boys had lower ferritin levels than girls at all timepoints. Ferritin status at four and twelve months was positively associated with ferritin concentrations in cord blood and with gestational age. Breastfeeding and formula feeding were not associated with ferritin concentrations. Conclusions: Infant sex, cord ferritin concentrations, and maternal ferritin concentrations were independently associated with infant ferritin concentrations across the first year of life, whereas neither breastfeeding nor formula feeding was associated with ferritin concentrations in the present analyses. Infant sex, cord ferritin, and maternal ferritin measured four months postpartum may help identify children at risk of low iron stores, with maternal ferritin potentially offering a less intrusive alternative to repeated infant sampling. However, the clinical relevance and potential use of maternal ferritin as a proxy for infant ferritin concentrations require further investigation. Full article

Background: We previously reported that knocking down the ubiquitin E3 ligase LNX2 in bone marrow monocytes by shRNAs attenuated osteoclastogenesis in vitro. However, the role of LNX2 in the regulation of osteoclasts and bone homeostasis in vivo remains unknown. Methods: In this study, we generated myeloid Lnx2 conditional knockout mice by crossing Lnx2-flox mice with LysM-Cre mice. The role of LNX2 was verified through in vitro osteoclast induction experiments using mononuclear macrophages and experiments on estrogen-deficient osteoporosis models. Results: Micro-CT and histological analysis unveiled that loss of Lnx2 in osteoclast precursor cells decreased osteoclast numbers and increased trabecular bone mass in mice. Moreover, Lnx2 deficiency prevented bone loss in an ovariectomized mouse model of postmenopausal osteoporosis. In vitro mechanistic studies identified that the loss of Lnx2 had little effect on cell proliferation but significantly inhibited the formation of osteoclasts and bone resorption. Furthermore, the deletion of Lnx2 decreased the expression of NOTCH2 and its downstream HES1 via enhancing the level of the NOTCH2 inhibitor, NUMB. Conclusions: Our findings elucidate an important role of Lnx2 in the regulation of osteoclasts and bone metabolism and indicate that Lnx2 is a potential therapeutic target for the treatment of osteoporosis. Full article

A total of 192 weaned piglets (Topigs TN70), 26 days of age, with an initial body weight of 7.2 ± 0.5 kg, were used to determine the standardized ileal digestible (SID) histidine (His) to lysine (Lys) ratio required to maximize growth performance. Six dietary treatments with graded SID His to Lys ratios ranging from 0.2 to 0.38 were generated with the supplementation of L-His to a grain-based basal diet deficient in His. At the end of the trial (day 41 post weaning), 72 male piglets were euthanized for the analysis of histidine-containing dipeptides, particularly carnosine, in the M. longissimus dorsi. In addition, blood samples were collected from 72 piglets to determine plasma urea-nitrogen and hematological parameters. Piglets fed low dietary His (SID His to Lys < 0.27) exhibited hemoglobin concentrations below the reference value, indicating anemia. Muscle carnosine content increased linearly with increasing dietary His and did not reach a plateau within the tested range. Based on growth performance responses, the SID His to Lys ratio required to achieve maximum growth performance in fast-growing piglets is 0.34. These findings emphasize the importance of supervising the SID His to Lys ratio, particularly in practical piglet feed formulations. Full article

Rice depends on its root system to perceive drought, a major environmental constraint that leads to severe yield losses worldwide. To dissect the underlying molecular basis, we conducted a comparative analysis of drought-sensitive (WAB) and drought-tolerant (IR65) rice genotypes that exhibited divergent drought tolerance at the seedling stage. After exposure to 15% PEG6000 (−0.4 MPa) for two days, the shoot and root architectural traits of IR65 were better than those of WAB seedlings. Measurements of physio-biochemical parameters (SOD, CAT, POD, APX, H₂O₂, and proline) suggest that IR65 seedling roots exhibit greater ROS scavenging and osmotic adjustment capacity than WAB, aligning with tolerance to PEG-induced water deficiency. Transcriptomic assessments of roots identified 802 commonly differentially expressed genes (DEGs) during the drought time course (12, 24, and 48 h) in WAB and IR65. They were clustered into eight groups based on their expression profiles and mainly enriched in phytohormone signaling, protein phosphorylation, and transcription factors. Using weighted gene co-expression network analysis (WGCNA), nine significant modules were identified based on n = 382 of the DEGs. A total of 12 DEGs up-regulated in IR65 were distributed in five modules, and five of them were selected for rapid functional validation through in vivo yeast expression. The results showed that transgenic yeasts were tolerant to simulated drought conditions (135 mM PEG3350), indicating that these genes would be potential targets for rice improvement in drought tolerance in the future. Full article

Ascorbic acid (AA) or vitamin C is an important biomolecule that plays a crucial role in biological and physiological systems. Deficiency and/or excess of AA in the body can lead to severe diseases such as scurvy and gastrointestinal complications. Therefore, it is crucial to monitor the levels of AA in the body and supplements. Polyvinylpyrrolidone nickel oxide nanoparticles (PVP-NiONPs) are prepared and evaluated for their potential as nanozymes with peroxidase-like activity. o-Phenylenediamine (OPD) was used as a chromogen in the presence of hydrogen peroxide. The oxidized OPD was produced by ROS from PVP-NiONPs and H₂O₂. This was monitored using UV-vis spectra and by colour changes using the naked eye. AA reduced the oxidized OPD during its sensing. The UV-vis signal was linear for AA concentrations ranging from 40 µM to 400 μM. The limit of detection (LOD) for AA was calculated to be 0.11 μM using 3σ and the limit of quantification (LOQ) was 0.36 μM using 10σ indicating a very high sensitivity. The colorimetric sensor showed good reproducibility and a recovery rate between 92.3% and 102.6%, indicating high accuracy and reliability. The findings of this work confirmed that PVP-NiONPs possess enzyme-like activity and are a promising alternative for the quantitative, on-site detection of ascorbic acid. Full article

Background: Primary hyperparathyroidism (PHPT) has undergone notable clinical changes over recent decades, with asymptomatic cases now prevailing in Western countries. In contrast, a broad spectrum of clinical manifestations remains common in Romania, an Eastern European country. This study aims to provide a representative descriptive analysis of clinical presentations and related complications observed in this setting. Methods: We performed a cross-sectional, single-center study of 413 consecutive PHPT cases diagnosed between 2000 and 2020 at a tertiary endocrinology center in Romania. Data included demographics, clinical features, biochemistry, bone turnover markers, 25OHD, BMD by DXA, TBS, fractures, renal involvement, and etiology. Results: Patients were predominantly female (88.6%), with a mean age of 60 ± 11.7 years and a mean BMI of 27.3 ± 5.7 kg/m². Familial forms were identified in 4.4%. Mean serum calcium was 11.28 ± 1.09 mg/dL, mean PTH 248.31 ± 361.94 pg/mL, and mean 25OHD 17.95 ± 9.6 ng/mL. Symptomatic hypercalcemia was present in 23.2% and severe vitamin D deficiency in 21%. Fractures were present in 25.2% and osteitis fibrosa cystica in 1.7%. Mean T-scores (SD): LS –2.23, FN –1.85, 1/3 distal radius –1.96. Osteoporosis prevalence: LS 47%, FN 24.1%, 1/3 distal radius 38%. Mean TBS was 1.258 ± 0.115. Renal involvement included calcifications (56.7%), nephrolithiasis (53%), nephrocalcinosis (3.6%), hypercalciuria (31.7%), and reduced renal function (9.93%). Non-classical manifestations were mainly cardiovascular (58%) and osteoarticular (24.5%). Parathyroidectomy was performed in 217 patients (53%); histopathology showed adenoma (88.8%), carcinoma (5.2%), and hyperplasia (6%), with a mean adenoma weight of 2.86 ± 5.92 g. Conclusions: PHPT in Romania shows a heterogeneous phenotypic spectrum, reflecting variability in clinical presentation and suggesting an evolving epidemiological profile. Full article

Metastatic pancreatic ductal adenocarcinoma (PDAC) is typically treated with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel (GnP), but the choice between regimens remains largely empirical. This narrative review summarizes biomarkers with potential to inform first-line selection in metastatic PDAC, emphasizing genomic and transcriptomic correlates of differential benefit. Recent head-to-head trials, particularly Pancreatic Adenocarcinoma Signature Stratification for Treatment (PASS-01) and GENERATE (Japan Clinical Oncology Group [JCOG] 1611), indicate that modified FOLFIRINOX (mFOLFIRINOX) is not uniformly superior to GnP, strengthening the rationale for biomarker-guided selection. The strongest evidence favoring platinum-based/FOLFIRINOX strategies involves homologous recombination repair deficiency (HRD), especially alterations in germline breast cancer gene 1/2 (BRCA1/2) or partner and localizer of BRCA2 (PALB2), as well as broader genomic scar signatures. Transcriptomic subtype and GATA-binding protein 6 (GATA6) expression are promising but remain unsettled because retrospective data favor classical/GATA6-high disease for FOLFIRINOX, whereas PASS-01 suggested better outcomes with GnP in classical tumors. Candidate biomarkers favoring GnP include high human equilibrative nucleoside transporter 1 (hENT1), low class III β-tubulin (TUBB3) expression, and exploratory phosphatidylinositol 3-kinase (PI3K)/KIT/NOTCH pathway mutation signals. Comprehensive molecular profiling also identifies actionable alterations that may redirect patients to targeted therapy or clinical trials rather than standard chemotherapy alone. Importantly, no biomarker has yet been prospectively validated in a biomarker-stratified randomized trial with regimen selection as the primary endpoint; all biomarker-regimen associations described in this review should therefore be considered hypothesis-generating rather than practice-defining. Nevertheless, the convergence of genomic, transcriptomic, and organoid-based approaches makes biologically informed first-line selection increasingly feasible in metastatic PDAC. Full article

Background: Women with abnormal uterine bleeding (AUB) is reported in 10–30% of women and is a significant cause of iron deficiency anemia (IDA), with long-term effects on women’s quality of life. This retrospective study looked at the underlying causes of AUB and the contributory factors that required blood transfusions. Objectives: This study aimed to identify the treatable causes of AUB in patients who needed blood transfusion and parenteral iron in the reproductive age group and provide appropriate treatment to these underlying pathologies. Methods: A retrospective study was conducted in reproductive age group women with anemia due to AUB over a period of 10 years from January 2013 to December 2022. All women with significant uterine bleeding, who required blood transfusion were included in this study. Women with pregnancy, and hemolytic anemia, were excluded from the study. Results: During the study period 266 women needed blood transfusion for AUB. The mean age was 37.66 ± 11.4 years, mean parity 3, mean body mass index (BMI): 29.4 ± 8.9 kg/m², and most reported regular cycles. The most common etiology of AUB was uterine fibroids in 37.9% followed by ovulatory dysfunction in 15%. The mean hemoglobin was at 5.7 ± 1.14 gm/L, mean ferritin was 11.01 ± 21.88 ng/mL, mean number of blood transfusion was 2.83 ± 1.2 at first presentation and about 24% needed further transfusions. About 70% of them preferred oral hormonal treatment. Surgical management was required in about 35% of patients. Conclusion: The main cause of AUB was leiomyoma and anovulation. The morbidity of blood transfusion was easily avoidable in these women. Full article

This study evaluated the agronomic performance of 15 plum cultivars grafted on both P. cerasifera and ‘Wangenheim Prune’ (P. domestica) seedling rootstocks over nine years at the Lithuanian Research Centre for Agriculture and Forestry. Trees on P. cerasifera were planted 4.5 m × 2.5 m apart, while those on ‘Wangenheim Prune’ were 4 m × 1.5 m apart. On average, trees on ‘Wangenheim Prune’ developed 23% smaller trunk diameters and produced 42% less pruning mass than those on P. cerasifera yet demonstrated higher yield efficiency, except for the ‘Valor’ cultivar, which performed better on P. cerasifera. Mean plot yield was about 40% higher on ‘Wangenheim Prune’. Based on productivity, survival, and fruit quality, the most promising cultivars for Nordic climates are ‘Čačanska Najbolja’ and ‘Jubileum’ on ‘Wangenheim Prune’, while ‘Valor’ was productive on both rootstocks. Leaf nutrient analyses revealed rootstock-dependent differences: leaves on P. cerasifera contained more P, K, Ca, and Mn, whereas Mg, Cu, and Zn were higher on ‘Wangenheim Prune’. Regardless of rootstock, trees grown in calcareous, high-pH soils were deficient in Fe and Mn. Full article

Background/Objectives: Sebocytes, the primary cell type in sebaceous glands (SGs), produce a lipid mixture called sebum that is released onto the skin surface and is required for skin homeostasis. The lipid receptor Peroxisome Proliferator-Activated Receptor gamma (PPARγ) regulates sebocyte proliferation and lipid synthesis and is involved in acne development. As inhibition of PPARγ has been shown to reduce insulin-induced lipogenesis and Akt/mTOR signalling in SZ95 sebocytes, we here investigated the effects of PPARγ deletion on lipid homeostasis and autophagic stress responses and how the secretomes affect dermal fibroblasts. Methods: SZ95 sebocytes wildtype (WT) and PPARγ knockout (KO) were shifted to low serum and EGF-deficient conditions permissive for autophagy. Untargeted and targeted HPLC-MS/MS analyses were used to analyze native and oxidized lipids, respectively. Protein levels of LC3I/II and p62 were assessed using immunoblots and immunofluorescence microscopy to investigate the autophagic flux. Dermal fibroblasts were exposed to conditioned media. Results: In low serum culture media, KO SZ95 sebocytes displayed significantly altered levels of 23 lipid classes. We observed a significant increase in ether-linked fatty acids as components of complex lipids and detected elevated levels of phospholipid hydroperoxides and aldehydolipids in the KO sebocytes. KO SZ95 sebocytes failed to show the typical responses to lipoxidative stress, such as elevated p62 crosslinking or inclusion body formation, and had reduced LC3II/I ratios as compared to WT cells. PPARγ KO conditioned media promoted a trend towards an inflammatory fibroblast phenotype. Conclusions: These findings suggest that PPARγ in sebocytes may alter the lipidome, elevate redox stress, and affect the autophagic machinery, which could cause accumulation of oxidized lipids and other potentially harmful compounds in sebocytes. Full article

Urban flood modelling in heavily engineered catchments requires model structures that capture not only surface runoff processes but also hydraulic infrastructure and operational controls. This study applies a TELEMAC-2D rain-on-grid framework to two urban sub-catchments of the Emscher River (North Rhine-Westphalia, Germany) to quantify the relative effects of surface calibration, explicit infrastructure representation, and operational rules on the simulated flood response. A stepwise model development workflow was implemented, including land use-based calibration of Manning’s n and SCS Curve Numbers, explicit integration of culverts and bridges, and rule-based representation of retention basins and pumping stations. Model performance was evaluated using hydrograph shape, peak discharge, peak timing, event volume, and inundation behaviour across different antecedent moisture conditions (AMC). The results show that surface calibration alone was insufficient to consistently reproduce observed hydrographs. In the Rossbach sub-catchment area, integrating retention basins, pumping stations, and operational rules improved model performance from NSE = −0.129 under AMC I to NSE = 0.773 under AMC III. RMSE decreased from 3.380 to 1.515 m³ s⁻¹, peak discharge error from −6.198 to −0.492 m³ s⁻¹, and volume bias from −0.664 to +0.038. A targeted, routing-focused calibration further improved timing behaviour but increased volume bias, indicating residual deficiencies in the representation of rapid urban conveyance pathways. The findings show that reliable urban flood simulation in infrastructure-rich catchments depends not only on calibrating surface parameters but also on explicitly representing hydraulic structures, operational controls, and antecedent wetness conditions. Full article