Search Results (193)

Background: Malnutrition is frequently under-investigated during remission in patients with Inflammatory Bowel Disease (IBD), despite its significant impact on clinical outcomes and quality of life. This study aimed to evaluate the increase in diagnostic performance of five nutritional screening tools (NSTs) when serially administered to IBD outpatients in sustained clinical remission. Methods: In this prospective, single-center cohort study, NSTs were administered, and body composition analysis was performed in IBD patients at baseline and after six months. At both time points, the sensitivity, specificity, predictive values, and accuracy of NSTs in detecting malnutrition and persistent malnutrition per ESPEN and GLIM criteria were evaluated, comparing repeated to single-point assessments. A sensitivity analysis using low FFMI as a reference was also performed. Results: Sixty-six IBD patients (32 Crohn’s disease; 34 ulcerative colitis) were enrolled. At baseline, 25.7% and 9% of patients were malnourished according to ESPEN and GLIM criteria, respectively, with 7.5% exhibiting low FFMI. Malnutrition prevalence increased over time to 53%, 16.6%, and 16.6%, respectively. Among NSTs, MUST and SaskIBD-NR consistently exhibited the highest specificity for malnutrition detection at baseline, at 6 months, and for persistent malnutrition for ESPEN, GLIM and low FFMI. Serial (repeated) NST administration markedly improved the specificity of all tools, compared to single-point assessments. Conclusions: Serial nutritional screening with MUST or SaskIBD-NR significantly enhances the specificity of malnutrition risk detection in IBD patients in remission, supporting the incorporation of repeated nutritional assessments into clinical practice to offer a practical strategy to enhance screening effectiveness in IBD outpatient care. Full article

Accurate detection of premature atrial contractions (PACs) and premature ventricular contractions (PVCs) in single-lead electrocardiograms (ECGs) is crucial for early identification of patients at risk for atrial fibrillation, cardiomyopathy, and other adverse outcomes. In this work, we present a fully convolutional one-dimensional U-Net that reframes beat classification as a segmentation task and directly detects normal beats, PACs, and PVCs from raw ECG signals. The architecture employs a ConvNeXt V2 encoder with simple decoder blocks and does not rely on explicit R-peak detection, handcrafted features, or fixed-length input windows. The model is trained on the Icentia11k database and an in-house single-lead ECG dataset that emphasizes challenging, noisy recordings, and is validated on the CPSC2020 database. Generalization is assessed across several benchmark and clinical datasets, including MIT-BIH Arrhythmia (ADB), MIT 11, AHA, NST, SVDB, CST STRIPS, and CPSC2020. The proposed method achieves near-perfect QRS detection (sensitivity and precision up to 0.999) and competitive PVC performance, with sensitivity ranging from 0.820 (AHA) to 0.986 (MIT 11) and precision up to 0.993 (MIT 11). PAC detection is more variable, with sensitivities between 0.539 and 0.797 and precisions between 0.751 and 0.910, yet the resulting F1-score of 0.72 on SVDB exceeds that of previously published approaches. Model interpretability is addressed using Layer-wise Gradient-weighted Class Activation Mapping (LayerGradCAM), which confirms physiologically plausible attention to QRS complexes for PVCs and to P-waves for PACs. Overall, the proposed framework provides a robust, interpretable, and hardware-efficient solution for joint PAC and PVC detection in noisy, single-lead ECG recordings, suitable for integration into Holter and wearable monitoring systems. Full article

Obesity has reached epidemic proportions, driven by energy imbalance and limited capacity for adaptive thermogenesis. Brown (BAT) and beige adipose tissues dissipate energy through non-shivering thermogenesis (NST), primarily via uncoupling protein-1 (UCP1), making them attractive targets for increasing energy expenditure (EE). The canonical β-adrenergic pathway robustly activates NST in rodents through β3 adrenoceptors; however, translational success in humans has been limited by low β3 expression, off-target cardiovascular effects, and the emerging dominance of β2-mediated signaling in human BAT. Consequently, attention has shifted to non-adrenergic and UCP1-independent mechanisms that offer greater tissue distribution and improved safety profiles. This review examines a broad spectrum of alternative receptors and pathways—including GPRs, TRP channels, TGR5, GLP-1R, thyroid hormone receptors, estrogen receptors, growth hormone, BMPs, sirtuins, PPARs, and interleukin signaling—as well as futile substrate cycles (Ca²⁺, creatine, and glycerol-3-phosphate) that sustain thermogenesis in beige adipocytes and skeletal muscle. Pharmacological agents (natural compounds, peptides, and small molecules) and non-pharmacological interventions (cold exposure, exercise, diet, and time shift) targeting these pathways are critically evaluated. We highlight the translational gaps between rodent and human studies, the promise of multimodal therapies combining low-dose adrenergic agents with non-adrenergic activators, and emerging strategies such as sarco/endoplasmic reticulum calcium ATPase protein (SERCA) modulators and tissue-specific delivery. Ultimately, integrating adrenergic and non-adrenergic approaches holds the greatest potential for safe, effective, and sustainable obesity management. Full article

Although occult breast carcinomas and lesions with uncertain malignant potential are rare, their incidental discovery during symmetrizing mammoplasty can significantly alter the treatment approaches and cancer staging. In the context of oncoplastic surgery, the systematic evaluation of the contralateral breast is a clinical priority that has been underexplored in Eastern Europe. Background/Objectives: This study aimed to assess the incidence and histological characteristics of incidental carcinomas and B 3 lesions detected during contralateral symmetry mammoplasty in patients with breast cancer. Methods: This retrospective study was conducted at the Plastic and Reconstructive Surgery Clinic of the “Pius Brînzeu” County Emergency Clinical Hospital in Timisoara, Romania, over six years (2018–2024), and included 180 of 256 patients who underwent contralateral breast symmetrization. Results: Among the 180 patients, 21 (11.66%) had incidental findings: eight (4.44%) had contralateral carcinomas, and 13 (7.22%) had B3 lesions. The histopathological types identified were invasive ductal carcinoma NST (one case), ductal carcinoma in situ (one case), invasive lobular carcinoma (five cases), and mucinous/papillary carcinoma (one case). Compared to the reported international range of 2–10%, our observed incidence of 11.66% reflects the unique aspects of our patient cohort and the thoroughness of our histological analyses. Conclusions: Detection of contralateral carcinomas and B3 lesions during symmetry mammoplasties underscores the importance of a multidisciplinary approach, comprehensive bilateral screening, and detailed histopathological examination of specimens. Full article

Background/Objectives: The antenatal management of Down syndrome (DS) is difficult as it is associated with a high risk for in utero fetal demise (IUFD) with a paucity of literature to guide antenatal surveillance. Avoidance of preterm delivery in the DS fetus, so commonly affected by anomalies, compounds the dichotomy of achieving term delivery while balancing against the risk for IUFD as gestational age advances. Higher-performing tests are needed to predict, and, thus, hopefully prevent, both preterm delivery and fetal mortality. Our study was undertaken to evaluate the performance metrics of current antenatal surveillance parameters that might suggest an increased risk for IUFD. Methods: We studied a retrospective cohort of all continuing pregnancies with a cytogenetically confirmed DS fetus between 2009 and 2019 at a single institution. Cases were investigated for abnormalities in fetal growth, anatomy, UA Doppler, and amniotic fluid volume to analyze their interrelationships and their association with the primary outcome, IUFD. Nonstress testing (NST) and biophysical profile data as available were also reviewed for analysis on each case. Maternal demographic data were also collected. Results: A total of 41 DS pregnancies at >20 weeks gestation were included. Eight (19.5%) resulted in IUFD, while thirty-three (80.5%) resulted in live birth. Between these groups, there was no significant difference in the incidence of fetal structural anomalies. FGR was present in 8/41 fetuses or 19.5% of all cases. FGR was present in 1 of 8 (12.5%) IUFD cases and 7 of 33 (21.2%) live births (p = 0.50). Thus, notably, 87.5% (7/8) of the IUFDs occurred in the absence of FGR. Furthermore, 1/8 (12.5%) FGR cases resulted in IUFD vs. 7/33 (21.2%) of non-FGR cases (p = 0.50). In DS fetuses after 24 weeks gestation, UA Doppler abnormalities developed in 75% of FGR cases (6/8) and in 64.5% of normally grown cases (20/31) (p = 0.33). Abnormal UA Dopplers were noted in 83.3% of IUFD and in 84.8% of liveborn cases (p = 0.34). Eleven of thirty-three live births, however, underwent iatrogenic delivery secondary to worsening fetal surveillance, including ten with worsening UA Doppler indices. There was an increased frequency of abnormal NST in the IUFD group (66.7% vs. 23.8%), although this difference did not reach statistical significance. Polyhydramnios was more frequent in the IUFD group (62.5% vs. 16.1%, p = 0.04). Conclusions: Aside from polyhydramnios, no fetal surveillance parameter demonstrated an association with IUFD that reached statistical significance. A majority of fetuses with DS are normally grown and demonstrate abnormal UA Doppler indices in the absence of FGR. Within our cohort, a substantial number of liveborn deliveries were prompted following worsening UA Dopplers. Both polyhydramnios and UA Doppler indices are worthy of further investigation to inform clinically useful fetal surveillance strategies in DS. Full article

Background: Guidelines recommend neoadjuvant systemic therapy (NST) as the preferred treatment approach for stage II–III triple-negative breast cancer (TNBC), an aggressive form of breast cancer (BC) that lacks specific therapeutic targets. This study primarily aimed to assess the NST adoption among stage II–III TNBC patients in Greece under real-world conditions during the pre-immunotherapy era. Methods: This multicenter, observational, retrospective chart review included 230 female patients (≥18 years) with early-stage or locally advanced TNBC across 10 public and private BC reference centers over 6.5 years. Data included demographics and clinical characteristics at diagnosis, treatment details, clinical outcomes, and survival status. Descriptive statistics followed by uni/multivariate analyses were performed. Survival outcomes were assessed using survival analysis methods. Results: Women with stage II (67.4%) or stage III (32.6%) TNBC were included, with a median age of 53.1 years (range 23.9–84.1). Patients received NST [113 (49.1%)] and non-NST [117 (50.9%)]. NST utilization was significantly associated with larger tumor size and BRCA1/2 testing and status. Overall, 43.9% underwent BRCA1/2 testing, and 32.7% of those were positive for a BRCA1/2 mutation. More than half of the patients (n = 61) achieved pathological complete response (pCR) following NST. Event rates were lower with NST (16.8%) versus without (24.8%). Utilization increased over time, peaking at 63.5% in 2020–2022. Conclusions: NST use showed moderate uptake with notable practice variations, emphasizing the need for multidisciplinary strategies to improve guideline adherence. Over half achieved pCR post-NST, setting a benchmark for TNBC care. Ongoing real-world monitoring is vital to guide long-term outcomes. Full article

Fertilization plays a vital role in replenishing soil nutrients, shaping microbial community composition, and enhancing agricultural productivity. Castor bean cake (CBC) is a nitrogen- and carbon-rich by-product increasingly used as an organic amendment, yet its effects on soil microbiomes remain unclear. Here, we compared CBC with a compound chemical fertilizer (CF) and a manure-based organic fertilizer (OF) across dose gradients using 16S rRNA sequencing and multi-level ecology analyses (α/β diversity, co-occurrence networks, and community assembly models). The results revealed that CBC increased bacterial richness and phylogenetic breadth relative to the unfertilized cultivated control, whereas OF showed dose-dependent declines in richness and CF maintained relatively stable richness with slight reductions in evenness at higher doses. Phylum-level composition shifted strongly with fertilizer identity: Bacillota decreased, whereas Pseudomonadota and Acidobacteriota increased under fertilization, with the largest compositional changes under CBC. CBC strengthened nutrient–enzyme–microbe coupling and generated increasingly complex, highly connected, and robust co-occurrence networks along the dose gradient, outperforming high-dose OF in network complexity and robustness, while OF maintained higher modularity. Null-model partitions (βNTI/RC_bray, NST, NCM, iCAMP) indicated that stochastic processes dominated community assembly across treatments; along the CBC gradient, dispersal limitation decreased from CBC1 to CBC2 and drift remained dominant, indicating increasing stochastic stabilization at moderate–high doses. Together, CBC promoted microbiome recovery and ecological resilience and represents a promising amendment for soil health. Full article

Background: Neoadjuvant systemic therapy (NST), whose primary purposes include response assessment and treatment individualization, is a key strategy in the treatment of HER2-positive breast cancer. This study investigated the predictive value of the magnetic resonance imaging (MRI)-derived tumor volume reduction rate (δV1) for the early identification of pathological complete response (pCR) during NST and established clinically applicable δV1 thresholds for patient stratification. Methods: HER2-positive breast cancer patients who received THP (taxane, trastuzumab, pertuzumab) followed by epirubicin/cyclophosphamide (EC) were enrolled. MRI was performed at baseline, after THP, and after EC. Tumor volumes were manually segmented using 3D Slicer, and δV1/δV2 were calculated via Python (version3.13). Longest diameter reduction rates (δL1/δL2) were recorded. pCR (ypT0/is ypN0) was the primary endpoint. Receiver operating characteristic (ROC) analysis determined predictive accuracy, and logistic regression identified independent predictors. Thresholds for δV1 were explored, and subgroup analyses were conducted by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Results: Overall, 59.3% of patients achieved pCR. δV1 demonstrated superior predictive accuracy compared with longest diameter reduction (δL1), with an AUC of 0.745 (95% CI: 0.642–0.847) vs. 0.634 (95% CI: 0.512–0.757). A δV1 cutoff of 0.85 discriminated responders (68.4% vs. 41.4%, p = 0.016), while one of 0.91 represented the optimal predictive threshold. In multivariate analysis, δV1 was independently associated with pCR (OR = 1227.1, 95% CI: 6.86–219,562; p = 0.007), along with HER2 3+ expression (OR = 4.24, 95% CI: 1.26–14.31; p = 0.020). Among HR-positive patients, δV1 < 0.93 identified a subgroup with significantly lower pCR rates (19.0% vs. 81.0%, p < 0.001). Conclusions: δV1 is a reliable and early MRI-based imaging biomarker for predicting pCR in HER2-positive breast cancer. Defining thresholds such as 0.85 and 0.91 supports early therapeutic stratification and may help identify patients who could benefit from anthracycline-containing regimens. Full article

Introduction: Breast cancer is a heterogeneous malignancy influenced by diverse molecular profiles. The L-type amino acid transporter 1 (LAT1), encoded by the SLC7A5 gene, plays a key role in tumor metabolism, growth, and angiogenesis. Through its role in amino acid transport and activation of the mTORC1 signaling pathway, LAT1 has emerged as a potential therapeutic target. Objective: To evaluate SLC7A5/LAT1 expression and its association with clinicopathological parameters and molecular subtypes of invasive carcinoma of no special type (NST) in a Pakistani cohort. Methods: Eighty-three patients who underwent mastectomy or modified radical mastectomy for histologically confirmed primary invasive carcinoma of no special type were included. Immunohistochemistry was used to assess SLC7A5/LAT1 expression. Associations with clinicopathological features and molecular groups were analyzed using the Chi-square test. Results: The mean age of SLC7A5-positive patients were 48.4 ± 10.8 years. Overall, 24.1% of patients demonstrated SLC7A5 positivity. Although SLC7A5 expression was more frequent in cases categorized as having moderate or poor prognosis based on the Nottingham Prognostic Index (NPI), this trend was not statistically significant. Similarly, no significant associations were observed between SLC7A5 expression and other clinicopathological or molecular variables. Conclusions:SLC7A5/LAT1 expression was identified in approximately one-quarter of invasive breast carcinoma cases. Its expression appeared more common in tumors with poorer NPI categories, but without statistically verified associations. These findings suggest that SLC7A5 may act independently of conventional clinicopathological parameters. Larger, longitudinal studies with survival follow-up are required to clarify its prognostic and therapeutic significance. Full article

Eragrostis nindensis is a resurrection grass capable of surviving near-complete desiccation. We compared non-senescent leaf tissue (NST) and senescent leaf tissue (ST) to investigate the cellular and molecular basis of desiccation tolerance and senescence. NST recovered fully after drying, while ST failed to regain viability. Integrated transcriptomic (using RNA-Seq), lipidomic (using LC-MS), and ultrastructural (Transmission Electron Microscopical) analyses revealed that NST maintain RNA processing, protein folding, and translational activity during desiccation. Lipidomic data and ultrastructure showed preferential accumulation of polyunsaturated triacylglycerols (TAGs) and lipid droplets in NST, supporting membrane protection and energy buffering. In contrast, ST showed cellular collapse, reduced oleosin protein accumulation, and signatures of senescence. These findings highlight the importance of post-transcriptional and post-translational regulation, as well as lipid metabolism, in preserving cellular integrity during desiccation in this species. Full article

Background/Objectives: Breast cancer is a leading cause of cancer-related mortality among women worldwide. Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs with potential as novel biomarkers applicable to improve diagnostic and prognostic applications. Methods: We performed a comprehensive evaluation of the snoRNA-related gene expression by qPCR using benign and tumor tissue samples associated with invasive breast carcinomas of no special type (NST). Selected candidate snoRNAs, i.e., SCARNA2, SCARNA3, SNORD15B, SNORD94, SNORA68, and SNHG1, along with RNU2-1 snRNA, were further validated and their associations with clinicopathological parameters were examined. External datasets and plasma samples were used for additional validation. Results: SCARNA2 was identified as the most promising snoRNA biomarker candidate, showing a positive association with better progression-free survival (PFS) in our data (13.3-month survival difference between low- and high-expression groups) and with both PFS and overall survival in external RNA-seq datasets. SNORD94, SNORD15B, SCARNA3, and RNU2-1 snRNA were also indicated as putative tumor suppressors. SNORD94 was associated with better progression-free survival (PFS) in our data as well (12.4-month survival difference between low- and high expression groups). Greater downregulation in the low-expression tumor subgroup compared to benign samples further supports the prognostic potential of SCARNA2 and SNORD94. Evidence for SNHG1 and SNORA68 as putative oncogenes was less conclusive. Conclusions: Several small nucleolar RNAs were found to be dysregulated in breast cancer specimens, supporting their further evaluation as potential biomarkers. In particular, SCARNA2, SNORD94, SNORD15B, SCARNA3, and RNU2-1 snRNA merit further investigation to determine their clinical relevance and biological roles in breast cancer. Full article

Background/Objectives: Breast cancer incidence is increasing in younger Ghanaian women. However, few epidemiological studies have evaluated the modifiable risk factors in this population. Additionally, these studies have classified breast cancer in Ghanaian women based on the global menopausal case classification. This study reclassified premenopausal and postmenopausal breast cancer in a Ghanaian cohort, assessing the risk factors using the observed menopausal age in Ghanaian women of 48 years, rather than the global standard of 50 years. Methods: Women diagnosed with breast cancer and scheduled for surgery from December 2018 to March 2023 were recruited across four hospitals in Ghana for the Ghana Breast Cancer Omics Project (BCOPGh), and data were collected using a questionnaire. Cross-tabulation and linear regression were used to evaluate the relationships between categorical variables and age at diagnosis. Results: Out of a total of 262 women recruited, 34.4% were classified as having premenopausal breast cancer, while early-onset breast cancer (EOBC) accounted for 14.9% of all cases. The molecular subtypes were predominantly hormone receptor (HR)-positive (61%) while triple-negative breast cancer (TNBC) accounted for 16%. The tumours were predominantly at stage II (62%) and grade 2 (51%), with invasive carcinoma NST (56%) being the most common subtype. Within this cohort, nulliparity increased the odds of EOBC by 13.5-fold, while having a first birth after the age of 23 doubled the odds of premenopausal breast cancer. Reproductive factors (menarche and menopause) and lifestyle (alcohol intake, smoking, contraceptive use, and breastfeeding duration) were not associated with premenopausal breast cancer in this cohort. About 13% of participants reported a family history of breast cancer, and 79% had prior knowledge of the disease. Conclusion: This study supports previous reports of the relatively higher incidence of aggressive disease in young Ghanaian women and the protective effect of early age at first birth. It further underscores the need to investigate its genetic underpinnings, whilst highlighting the importance of public education on self-examination techniques to reduce advanced disease presentation in Ghanaian women. Full article

Background and Objectives: Although nutritional status is critical to the clinical outcomes of septic patients, studies on this topic are limited. We aim to assess the prognostic value of five nutritional screening tools (NSTs) for septic patients both at the time of admission to the intensive care unit (ICU) and five days later. Materials and Methods: This prospective observational study included adult septic patients in the ICU. Patients were divided into two groups: survivors and non-survivors. Clinical, laboratory characteristics, and NST values [The Controlling Nutritional Status (CONUT), Prognostic Nutritional Index (PNI), Nutritional Risk Screening (NRS-2002), Geriatric Nutritional Risk Index (GNRI), and Nutrition Risk in the Critically Ill (NUTRIC)] were recorded at admission and on Day-5, and intergroup and intragroup comparisons were performed. Results: A total of 126 patients were included in this study: 97 in the survival group and 29 in the non-survival group. The non-survivors had higher CONUT and NUTRIC scores and lower PNI scores. Multivariate analysis found higher Day-5 NUTRIC scores independently associated with mortality. ROC analysis identified NUTRIC > 6 as a mortality predictor. Conclusions: Although several markers differed significantly between survivors and non-survivors, our findings show that a high Day-5 NUTRIC score was the only factor independently associated with mortality among NSTs. Full article

Against the backdrop of global climate change intensifying seasonal freeze–thaw cycles, deteriorating soil conditions in farmland within seasonal frost zones constrain agricultural sustainability. This study employed an in situ field experiment during seasonal freeze–thaw periods in the black soil zone of Northeast China to investigate the joint regulatory effects of seasonal freeze–thaw processes and tillage practices on multidimensional features of soil bacterial communities. Key results demonstrate that soil bacterial communities possess self-reorganization capacity. α-diversity exhibited cyclical fluctuations: an initial decline followed by a rebound, ultimately approaching pre-freeze–thaw levels. Significant compositional shifts occurred throughout this process, with the frozen period (FP) representing the phase of maximal differentiation. Actinomycetota and Acidobacteriota consistently dominated as the predominant phyla, collectively accounting for 33.4–49% of relative abundance. Bacterial co-occurrence networks underwent dynamic topological restructuring in response to freeze–thaw stress. Period-specific response patterns supported sustained soil ecological functionality. Furthermore, NCM and NST analyses revealed that stochastic processes dominated community assembly during freeze–thaw (NCM R² > 0.75). Tillage practices modulated this stochastic–deterministic balance: no-tillage with straw mulching (NTS) shifted toward determinism (NST = 0.608 ± 0.224) during the thawed period (TP). Across the seasonal freeze–thaw process, soil temperature emerged as the primary driver of temporal community variations, while soil water content governed treatment-specific differences. This work provides a theoretical framework for exploring agricultural soil ecological evolution in seasonal frost zones. Full article

Background/Objectives: Sentinel lymph node biopsy (SLNB) is currently the standard approach for axillary staging in breast cancer. Conventional techniques are radioisotope-based (Technetium-99m, Tc99m) and remain widely used, but novel tracers like Indocyanine Green (ICG) fluorescence provide potential advantages regarding feasibility and logistics. Methods: We conducted a prospective, observational study including 476 female patients diagnosed with primary invasive breast cancer who underwent SLNB at the Institute of Oncology “Prof. Dr. I. Chiricuță”, Cluj-Napoca, Romania, between January 2022 and May 2025. Clinical, surgical, and pathological variables were systematically extracted. SLNB was performed using either Tc99m or ICG, according to institutional protocols. Comparative analyses were performed to evaluate sentinel node characteristics, histopathological parameters, and positive surgical margins predictors. Results: The median age was 60 years (IQR: 52–69). Breast-conserving surgery (BCS) was performed in 77.9% of cases, while mastectomy was performed in 22.1%. Sentinel lymph node positivity was reported in 25.6% of cases, with no significant differences in the number of excised or metastatic nodes between Tc99m and ICG (mean nodes: 3.23 vs. 3.20, p = 0.860; mean positive nodes: 0.35 vs. 0.36, p = 0.897). Histologically, invasive carcinoma NST was predominant (90.1%), and surgical margins were negative in 96.8% of patients, with all margin-positive cases occurring following BCS. No pathological markers (grade, Ki67, TILs, DCIS extent) predicted margin status or nodal involvement. Notably, younger age correlated inversely with the extent of ductal carcinoma in situ (r = −0.21, p < 0.00001). Conclusions: Tc99m and ICG provided comparable diagnostic performance in performing SLNB, with equivalent rates of nodal detection and pathological yield. These findings support that ICG is a safe and effective alternative for routine axillary staging in breast cancer. Full article