Search Results (5,830)

Drug-resistant tuberculosis (DR-TB) represents a major public health threat, particularly in the prisons of Latin America and the Caribbean, where rates are up to 40 times higher than those observed in the general population. These facilities act as community amplifiers due to overcrowding, poor ventilation, diagnostic delays, and treatment discontinuity. This study offers a critical reflection on the magnitude, determinants, and implications of DR-TB in regional penitentiary contexts. A reflective analytical review was conducted in PubMed, Scopus, Web of Science, SciELO, and LILACS, complemented by WHO and PAHO reports, prioritising studies from 2019 to 2024. The findings reveal MDR-TB and pre-extensively drug-resistant (pre-XDR) outbreaks in Peru, Paraguay, and the Dominican Republic, as well as community transmission linked to prisons in Brazil and Colombia. Persistent gaps remain in systematic screening, drug susceptibility testing coverage, and post-release follow-up. Scientific production continues to be uneven and predominantly biomedical, with limited consideration of social and human rights determinants. DR-TB in prisons reflects the structural deficiencies of health and justice systems; its control requires intersectoral policies, genomic surveillance, and strategies that ensure early diagnosis, treatment continuity, and dignified detention conditions. Full article

Diabetic retinopathy (DR) is the largest cause of permanent vision loss in the working-age population, making automated grading critical for timely therapeutic intervention. While recent deep learning algorithms have improved feature discrimination, modern state-of-the-art systems have two fundamental drawbacks. First, most models rely on standard Convolutional Neural Networks, which struggle to capture long-range relationships and lack semantic reasoning, resulting in visual findings that do not correlate with clinical knowledge. Second, present approaches often consider grading as a nominal classification or a pure ordinal regression task, failing to strike a compromise between high classification accuracy and severity-consistent predictions (Quadratic Weighted Kappa). To address these challenges, we propose Dual-SwinOrd, a novel framework that integrates a hierarchical Vision Transformer with a semantically guided dual-head mechanism. Specifically, we use a Swin Transformer backbone to extract hierarchical features, effectively capturing global retinal structures. To handle diverse lesion scales, we incorporate a Progressive Lesion-aware Kernel Attention (PLKA) module and a Semantic Prior Modulation (SPM) module guided by PubMedCLIP, bridging the gap between visual features and medical linguistic priors. In addition, we propose a Dual-Head learning strategy that decouples the optimization objective into two parallel streams: a Classification Head to maximize diagnostic accuracy and an Ordinal Regression Head (DPE) to enforce rank-consistency. This design effectively mitigates the trade-off between precision and ordinality. Extensive experiments on the APTOS 2019 and DDR datasets demonstrate that Dual-SwinOrd achieves state-of-the-art performance, yielding an Accuracy of 87.98% and a Quadratic Weighted Kappa (QWK) of 0.9370 on the APTOS 2019 dataset, as well as an Accuracy of 86.54% and a QWK of 0.9040 on the DDR dataset. Full article

Diabetic retinopathy (DR) is more than a capillary disorder. Diabetes affects neurons, glial cells, vascular cells, and immune signals within the retinal neurovascular unit (NVU). Retinal neurovascular coupling (NVC) is a useful functional marker of NVU integrity because it reflects the rise in local blood flow that follows neural activity. Many human flicker-light studies report smaller vessel dilation or weaker flow responses in diabetes. This finding can appear even in patients without clear fundus lesions. When NVC is reduced, retinal tissue may receive less oxygen. Lower oxygen delivery can raise oxidative stress and promote inflammation. These changes can then worsen vascular injury. This review describes key NVC pathways and diabetes-related NVU changes in Müller glia, astrocytes, microglia, pericytes, and endothelial cells. The review highlights sympathetic activation as a common stress signal. Pain, anxiety, perioperative stress, and sleep loss can increase sympathetic activity and circulating catecholamines. In the diabetic retina, vascular reserve is often limited. Under these conditions, catecholamines can increase mural cell constriction, reduce nitric oxide (NO)-dependent relaxation, and increase endothelial activation and barrier strain. These effects can shift the baseline state of glial and immune cells and further weaken NVC. The review also summarizes translational tools that can test these links. These tools include heart rate variability, standardized NVC protocols with diameter and flow measures, and retinal organoid and organ-on-a-chip platforms with controlled adrenergic exposure. The review discusses perioperative care packages that reduce stress responses, protect sleep, and manage glucose as practical ways to support retinal microcirculation. More longitudinal human studies are still needed. Retina-specific perioperative endpoints are also needed to clarify causality and to guide intervention trials. Full article

This paper proposes a safety-constrained Transformer–PPO framework for low-carbon economic dispatch with settable incentive-based demand response (DR) in wind–PV integrated electro–thermal–hydrogen industrial-park energy systems. Hydrogen is modeled as exogenous hydrogen-domain demand and is satisfied through electrolyzer production and hydrogen inventory dynamics. A causal Transformer captures long-horizon multi-energy coupling and intertemporal constraints and is trained with PPO under uncertainty. A dual-layer safety mechanism combines dual-variable (Lagrange multiplier) updates for statistical constraints with an execution-layer quadratic-programming action projection to enforce hard physical constraints, including operating limits, ramping, battery SOC, hydrogen inventory bounds, and energy balance. Baseline–verification–settlement rules and budget-ledger states are embedded to ensure verifiable response quantities and settlement outcomes that are traceable and independently recompilable. Case studies on a real industrial-park scenario in Inner Mongolia show reduced peak-hour maximum grid purchase demand and constraint violations, together with lower total cost, carbon cost, and curtailment penalties versus MILP, PPO-MLP, and Transformer–PPO without safety mechanisms. Full article

Background/Objectives: This observational study investigated associations between human leukocyte antigen (HLA) polymorphisms and imaging-defined hepatic steatosis (non-alcoholic fatty liver disease—NAFLD) and liver fibrosis in patients with rheumatoid arthritis (RA). Methods: Steatosis was assessed by transient elastography (FibroScan) and defined as controlled attenuation parameter (CAP) ≥ 275 dB/m; fibrosis was defined as liver stiffness measurement ≥ 8 kPa. We tested 11 frequent HLA alleles (HLA-A*02, HLA-B*07, HLA-B*08, HLA-B*27, HLA-B*35, HLA-B*44, HLA-B*51, HLA-DRB1*11, HLA-DRB1*14, HLA-DRB1*15, and HLA-DRB1*16). Associations were evaluated using multivariable logistic regression (individual and omnibus models) adjusted for age, body mass index (BMI), triglycerides, and glucose. Results: A total of 176 patients with rheumatoid arthritis were enrolled. NAFLD/steatosis was present in 35.2% of patients (n = 62), and fibrosis in 10.8% (n = 19). No HLA allele was significantly associated with steatosis or fibrosis after correction for multiple testing. BMI and triglycerides were independently associated with steatosis (BMI OR 1.22, 95% CI 1.12–1.34; triglycerides OR 1.48, 95% CI 1.04–2.18). For fibrosis, HLA-DRB1*15 showed the strongest trend-level association (OR ~2.6–2.9) but did not remain significant after correcting for multiple testing. Conclusions: In this RA cohort, metabolic factors (particularly BMI and triglycerides) were the dominant predictors of CAP-defined steatosis. No robust association between the tested HLA markers and steatosis or fibrosis was identified. Trend-level signals—most notably HLA-DRB1*15 for fibrosis—should be considered hypothesis-generating and warrant replication in larger, adequately powered cohorts. Full article

The introduction of significantly shorter, all-oral regimens has significantly shifted the management of drug-resistant tuberculosis (DR-TB) towards a more tolerable and patient-centred therapeutic approach that aims to enhance treatment adherence, clinical outcomes, and quality of life among patients. Nigeria has gradually adopted this all-oral, shorter regimen, but the impact of this regimen in programmatic settings has not yet been studied. In 2022, a longitudinal, two-armed cohort study was conducted to explore the effectiveness, safety, and feasibility of the all-oral shorter regimen in the programmatic management of RR/MDR-TB in Nigeria. Consenting and eligible RR/MDR-TB patients receiving the all-oral regimen (intervention group) in four states were consecutively enrolled and compared to those receiving the standard of care (SOC). Treatment effectiveness, proportion, and 95% confidence intervals of favourable and unfavourable outcomes were measured at the end of treatment and during follow-up (six and 12 months post-treatment). In total 383 Participants were followed monthly throughout the 9–12-month treatment phase and then reassessed at 6 and 12 months after treatment completion, giving a total possible observation period of up to 24 months (185 received the intervention and 198 the standard of care). At the end of follow-up, there was a higher but non-significant proportion of favourable outcomes among the intervention vs. SOC group (80% vs. 69.7%); a higher proportion of favourable outcomes was also noted at the end of treatment among intervention participants (81.1 vs. 76.8%). Around one third of patients reported at least one serious adverse event (SAE), with no significant differences between arms, and none were deemed related to the use of medication. Intervention participants reported greater improvements in health-related quality of life between baseline and four months compared to those receiving the SOC. These findings support the programmatic use of all-oral shorter treatment for RR/MDR-TB as a regimen that is effective, tolerable, safe, and associated with enhanced health-related quality of life for patients in Nigeria. Full article

In this study, the in situ solvothermal synthesis of a copper-based metal–organic framework (Cu-BTC MOF) into two porous ceramic substrates with a 10 cm diameter and 2 cm thickness was reported. X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, diffuse reflectance spectroscopy (DRS), Tauc plot analysis, optical microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were the techniques that were utilized to verify the formation and incorporation of the MOF into ceramics (two samples, with different SiO₂ particles; 500 µm (Ceramic 1), and 150 µm (Ceramic 2)). The synthesized Cu-MOF exhibited a crystalline structure. Both the composites and the Cu-MOF exhibited visible-light absorption, with optical band gaps of 2.5 eV and 2.4 eV, respectively, as determined by DRS. TEM images demonstrated that crystalline MOF domains were successfully included inside the ceramics. Methyl orange (MO), Congo red (CR), and methylene blue (MB) were used to assess the composites’ ability to remove dyes. Catalytic hydrogenation, powered by in situ hydrogen production from NaBH₄ hydrolysis, demonstrated high removal efficiencies of 91–97% after 60 min. Adsorption, on the other hand, was ineffective. Despite undergoing four consecutive cycles without performance degradation, the materials demonstrated remarkable recyclability. Cu-MOF@ceramic composites are effective, durable, and practically applicable for improved wastewater treatment. Full article

Background/Objectives: Optical coherence tomography angiography (OCTA) enables noninvasive quantitative assessment of the retinal microvasculature and is widely used in diabetic retinopathy (DR). However, OCTA-derived metrics are highly dependent on post-processing techniques, particularly vessel binarization. This study aimed to compare local and global binarization methods applied after Frangi filtering for vessel enhancement in parafoveal vessel density analysis. Methods: This cross-sectional study included 69 participants: 17 healthy controls and 52 diabetic patients, classified as the following: no DR (n = 14), non-proliferative DR (NPDR, n = 18), or proliferative DR (PDR, n = 20). All subjects underwent comprehensive ophthalmological examination and OCTA imaging of the superficial capillary plexus using a Topcon OCTA system. Images were processed using a custom MATLAB protocol. Following Frangi filtering, five binarization methods were applied: three local (Phansalkar, local Otsu, adaptive mean) and two global (global mean and global Otsu). Parafoveal vessel density was quantified within the four inner quadrants of the ETDRS grid. Results: Statistically significant differences in vessel density were consistently observed between PDR group and both the control and no DR groups across all local binarization methods. Among global methods, only global Otsu thresholding detected a significant difference between PDR and control. The most robust differences were predominantly identified in the nasal and inferior quadrants. Conclusions: Local adaptive binarization methods demonstrated superior sensitivity and structural preservation for parafoveal vessel density analysis in DR. Global methods showed limited discriminative capability. These findings support the preferential use of local adaptive techniques for reliable OCTA-based vascular assessment in diabetic retinopathy. Full article

Recent evidence suggests that type I interferon (IFN) activity has prognostic relevance in systemic lupus erythematosus (SLE). This study investigated whether combining IFN activity with elevated peripheral blood plasmablast (PB) levels—another key feature of lupus pathophysiology—improves risk stratification for poor clinical outcomes. Clinical data were prospectively collected at a single lupus center. Flow cytometry was performed on freshly isolated peripheral blood mononuclear cells to investigate Sialic acid-binding Immunoglobulin-like Lectin 1 (SIGLEC-1) as a surrogate marker of IFN activity, alongside CD19⁺CD20⁻CD27^highHLA-DR⁺ PB frequencies. A total of 1276 samples from 121 patients were analyzed. At baseline, 48.8% of patients exhibited high IFN activity, including 27.3% with concurrent elevation in IFN and PB activity and 21.5% with isolated IFN activity. Patients with simultaneous IFN and PB activity showed higher anti-dsDNA antibody levels, were less frequently in DORIS remission (24.2% vs. 50.0%) and required higher daily prednisolone dosages (6.3 vs. 2.0 mg) than those with isolated IFN activity. During a median follow-up of 4.5 years (range 0.8–6.6), these patients experienced more flares (132 vs. 54, OR 1.42), required longer to achieve remission (median 399 vs. 140 days), and had a higher median time-adjusted prednisolone dose (5.6 vs. 3.0 mg). Concurrent elevation in IFN and PB activity identifies SLE patients with a poorer prognosis compared to isolated IFN activity. These findings suggest that combined IFN and PB assessment may improve prognostic stratification and support personalized treatment strategies in SLE. Full article

The escalating threat of antimicrobial resistance (AMR) and the environmental impact of industrial pollutants, particularly synthetic dyes, emphasize the pressing requirement for novel solutions. This study investigates the green synthesis of ZnO/Fe₂O₃ nanocomposites using Urtica dioica extract with the aim of achieving dual functionality as both antimicrobial agents and photocatalysts for pollutant degradation. The nanocomposites were synthesized with varying loads of Fe₂O₃ (5–50%) and characterized using X-ray diffraction (XRD) and diffuse reflectance spectroscopy (DRS). XRD analysis confirmed the presence of both the hexagonal wurtzite ZnO phase and the α-Fe₂O₃ hematite phase in all the composites, while DRS analysis revealed that the bandgap energy decreased progressively (from 1.89 to 1.72 eV) as the Fe₂O₃ content increased. The photocatalytic efficiency of the composites was evaluated by degrading methylene blue (MB), Congo Red (CR) and safranin O (SO) dyes under visible light. This demonstrated that the degradation performance depends on the composition, with the best activity being observed at 5% Fe₂O₃. Antioxidant activity was assessed using a DPPH• free radical scavenging assay. This showed that Urtica dioica extract exhibits superior radical scavenging capacity (maximum inhibition of 38%) compared to ZnO/Fe₂O₃ nanoparticles (maximum inhibition of 18%). The antibacterial efficacy against Pseudomonas aeruginosa was evaluated using direct confrontation and disk diffusion methods. This revealed that the activity was dose- and light-dependent, with enhanced performance under light exposure (10 mm inhibition zone) compared to dark conditions (1 mm). This study demonstrates the successful green synthesis of biphasic ZnO/Fe₂O₃ nanocomposites with promising photocatalytic and antimicrobial properties. While the results suggest possible synergistic interactions between the oxides, the underlying mechanisms, including potential charge transfer effects, require further investigation using advanced characterization techniques. Using Urtica dioica extract as a biogenic source provides a promising eco-friendly approach to synthesizing nanomaterials, with potential applications in wastewater treatment and the biomedical field. Full article

Background: Focal segmental glomerulosclerosis (FSGS) is a leading cause of renal disease presenting with steroid-resistant nephrotic syndrome (SNRS) and variable stages of chronic kidney disease (CKD). Monogenic etiologies for FSGS are increasingly recognized, particularly in pediatric and familial cases. Missense variants in the MAF BZIP Transcription Factor B (MAFB) gene cause a dominantly inherited condition with variable phenotype, ranging from isolated ocular or renal manifestations to syndromic FSGS. Methods: Detailed clinical and genetic investigations were conducted in an extended family presenting with a spectrum of renal and extra-renal manifestations. Results: Using Exome Sequencing (ES), a heterozygous variant, c.797T>C; p.(Leu266Pro) in the MAFB gene was identified in multiple affected family members. Variant segregation confirmed its presence in additional family members. The proband exhibited CKD accompanied by congenital auricular anomalies, hearing loss, and neurodevelopmental delay. An affected sibling presented with nephrotic-range proteinuria, Duane retraction syndrome (DRS) and neurodevelopmental involvement, while another family member had an isolated renal phenotype. Several of these features have not been previously associated with MAFB. Tools for structural modeling and stability predictions supported the functional impact of this variant. Conclusions: Our findings expand the phenotypic spectrum of MAFB-associated disease and further emphasize its variability. Full article

Benzothiophene polymers, as a class of novel organic semiconductor materials, exhibit significant potential in the field of photocatalysis due to their broad light-responsive range and tunable energy level structures. In this study, a benzothiophene-based polymer organic semiconductor (denoted as P42) was integrated with titanium dioxide (TiO₂) via a simple sol–gel method, yielding an organic–inorganic hybrid material. This composite facilitates the modulation of energy level potentials and promotes the effective separation of photogenerated charges, thereby demonstrating remarkable synergistic catalytic performance in the photocatalytic oxidative coupling of benzylamines. By optimizing the ratio of organic to inorganic components and various photocatalytic reaction conditions, the hybrid material 1.7%P42-TiO₂, containing 1.7 wt% of the dithiophene polymer without any metal cocatalysts, exhibited outstanding performance under an air atmosphere and visible light irradiation after 12 h. It achieved a yield of over 88.7% and a selectivity exceeding 89.8% in the synthesis of N-benzoylaniline, significantly surpassing the performance of pure TiO₂ (52.9% yield, 54.9% selectivity) and P42 (54.4% yield, 54.9% selectivity). Structural and photophysical characterizations, including UV–Vis DRS, XRD, SEM, TEM, and EPR, reveal that the enhanced photocatalytic activity originates from broad visible-light absorption, improved charge separation, and well-matched energy levels. Mechanistic investigations suggest a synergistic pathway involving photoinduced hole oxidation and radical-mediated coupling. This work provides valuable insights and a reference for the solar-driven photocatalytic synthesis of nitrogen-containing platform molecules under mild conditions. Full article

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and can lead to severe visual impairment. Based on disease severity, DR is classified into no clinically apparent diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Although nearly all retinal cell types are involved in DR progression, the dominant cell populations and their pathophysiological changes at each stage remain unclear. By integrating bulk and single-cell transcriptomic data from human and mouse retinas, this study revealed the following: (1) In the NDR stage, photoreceptors exhibit significant changes in ribosomal pathways. (2) In the NPDR stage, endothelial cells and pericytes show marked transcriptional alterations, accompanied by enhanced LAMININ signaling in cell-cell communication. (3) At the PDR stage, neural and glial cells are extensively involved in disease progression, with notable changes in ANGPTL signaling. Additionally, this study observed DR-specific subtypes of endothelial cells and pericytes and potentially identifies gene signatures in macroglia cells that correlate with disease duration. The altered expression of several key genes in early diabetic retina was confirmed by qPCR. These findings may offer a comprehensive view of the cellular and molecular landscape underlying DR and may suggest potential targets. Full article