Search Results (1,909)

Hereditary ataxias are a highly heterogenous group of diseases characterized by loss of coordination. In this study, we investigated a family of random-bred dogs, in which two siblings were affected by a slowly progressive ataxia. They presented with clinical signs of progressive cerebellar ataxia, hypermetria, and absent menace response. The MRI revealed generalized brain atrophy, reduced cortical demarcation, hypoplastic corpus callosum, and cerebellar folia thinning, highly suggestive of a neurodegenerative disorder. We sequenced the genomes of the two affected dogs and their unaffected parents. Filtering for protein-changing variants that had homozygous alternate genotypes in the affected dogs, heterozygous genotypes in the parents, and homozygous reference genotypes in 1576 control genomes yielded a single missense variant in the RAB24 gene, XM_038534663.1:c.239G>T or XP_038390591.1:p.(Gly80Val). Genotypes at this variant showed the expected co-segregation with the ataxia phenotype in the investigated family. The predicted amino acid affects the conserved RabF4 motif. Glycine-80 resides at the protein surface and the introduction of a hydrophobic isopropyl side chain of the mutant valine might impede solvent accessibility. Another missense variant in RAB24, p.Glu38Pro, was previously reported to cause a clinically similar form of cerebellar ataxia in Gordon Setters and Old English Sheepdogs. Taken together, the available data suggest that RAB24:p.Gly80Val represents the causal variant in the studied dogs. To the best of our knowledge, this is only the second report of a potentially pathogenic RAB24 variant in any species and further supports that RAB24 should be considered a candidate gene in human ataxia patients with unclear molecular etiology. Full article

We consider the problem of privately updating a message out of K messages from N replicated and non-colluding databases where a user has an outdated version of the message ${\hat{W}}_{\theta }$ of length L bits that differ from the current version $W_{\theta }$ in at most f bits. The user also has a cache containing coded combinations of the K messages (with a pre-specified structure), which are unknown to the N databases (unknown prefetching). The cache Z contains ℓ linear combinations from all K messages in the databases with $r=\frac{\mathcal{l}}{L}$ being the caching ratio. The user needs to retrieve $W_{\theta }$ correctly using a private information retrieval (PIR) scheme without leaking information about the message index $\theta$ to any individual database. Our objective is to jointly design the prefetching (i.e., the structure of said linear combinations) and the PIR strategies to achieve the least download cost. We propose a novel achievable scheme based on syndrome decoding where the cached linear combinations in Z are designed to be bits pertaining to the syndrome of $W_{\theta }$ according to a specific linear block code. We derive a general lower bound on the optimal download cost for $0\le r\le 1$, in addition to achievable upper bounds. The upper and lower bounds match for the cases when r is exceptionally low or high, or when $K=3$ messages for arbitrary r. Such bounds are derived by developing novel cache-aided arbitrary message length PIR schemes. Our results show a significant reduction in the download cost if $f<{\displaystyle \frac{L}{2}}$ when compared with downloading $W_{\theta }$ directly using typical cached-aided PIR approaches. Full article

Climate extremes threaten the resilience of Eucalyptus plantations, yet hybridization with drought-tolerant species may enhance stress tolerance. This study analyzed xylem anatomical and functional drought responses in commercial Eucalyptus grandis (GG) clones and hybrids: E. grandis × camaldulensis (GC), E. grandis × tereticornis (GT), and E. grandis × urophylla (GU1, GU2). We evaluated vessel traits (water transport), fibers (mechanical support), and wood density (D) in stems and branches. Theoretical stem hydraulic conductivity (k_Stheo), vessel lumen fraction (F), vessel composition (S), and associations with previous hydraulic and growth data were assessed. While general drought responses occurred, GC had the most distinct xylem profile. This may explain it having the highest performance in different irrigation conditions. Red gum hybrids (GC, GT) maintained k_Stheo under drought, with stable F and a narrower vessel size, especially in branches. Conversely, GG and GU2 reduced F and S; and stem k_Stheo declined for a similar F in these clones, indicating vascular reconfiguration aligning the stem with the branch xylem. Almost all clones increased D under drought in any organ, with the highest increase in red gum hybrids. These results reveal diverse anatomical adjustments to drought among clones, partially explaining their growth responses. Full article

Background and Purpose: Stratification based on specific image biomarkers applicable in clinical settings could help optimize treatment outcomes for recurrent non-small cell lung cancer patients. For this purpose, we aimed to determine the clinical impact of positive delta changes (any difference above zero > 0) between baseline [¹⁸F]FDG PET/CT metrics before the first treatment course and reirradiation. Material/Methods: Forty-seven patients who underwent thoracic reirradiation with curative intent at our institute between 2013 and 2021 met the inclusion criteria. All patients had histologically verified NSCLC, ECOG (Eastern Cooperative Oncology Group) ≤ 2, and underwent [¹⁸F]FDG PET/CT for initial staging and re-staging before primary radiotherapy and reirradiation, respectively. The time interval between radiation treatments was at least nine months. Quantitative metabolic volume and intensity parameters were measured before first irradiation and before reirradiation, and the difference above zero (>0; delta change) between them was statistically correlated to locoregional control (LRC), progression-free survival (PFS), and overall survival (OS). Results: Patients were followed for a median time of 33 months after reirradiation. The median OS was 21.8 months (95%-CI: 16.3–27.3), the median PFS was 12 months (95%-CI: 6.7–17.3), and the median LRC was 13 months (95%-CI: 9.0–17.0). Multivariate analysis revealed that the delta changes in SULpeak, SUVmax, and SULmax of the lymph nodes significantly impacted OS (SULpeak p = 0.017; SUVmax p = 0.006; SULmax p = 0.006), PFS (SULpeak p = 0.010; SUVmax p = 0.009; SULmax p = 0.009), and LRC (SULpeak p < 0.001; SUVmax p = 0.003; SULmax p = 0.003). Conclusions: Delta changes in SULpeak, SUVmax, and SULmax of the metastatic lymph nodes significantly impacted all clinical endpoints (OS, PFS and LRC) in recurrent NSCLC patients treated with reirradiation. Hence, these imaging biomarkers could be helpful with regard to patient selection in this challenging clinical situation. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

The Xiong’an New Area, a newly established national-level zone in China, faces the threat of land subsidence and ground fissure due to groundwater overexploitation and geothermal extraction, threatening urban safety. This study integrates time-series InSAR and GNSS monitoring to analyze spatiotemporal deformation patterns from 2017/05 to 2025/03. The key results show: (1) Three subsidence hotspots, namely northern Xiongxian (max. cumulative subsidence: 591 mm; 70 mm/yr), Luzhuang, and Liulizhuang, strongly correlate with geothermal wells and F4/F5 fault zones; (2) GNSS baseline analysis (e.g., XA01-XA02) reveals fissure-induced differential deformation (max. horizontal/vertical rates: 40.04 mm/yr and 19.8 mm/yr); and (3) InSAR–GNSS cross-validation confirms the high consistency of the results (Pearson’s correlation coefficient = 0.86). Subsidence in Xiongxian is driven by geothermal/industrial groundwater use, without any seasonal variations, while Anxin exhibits agricultural pumping-linked seasonal fluctuations. The use of rooftop GNSS stations reduces multipath effects and improves urban monitoring accuracy. The spatiotemporal heterogeneity stems from coupled resource exploitation and tectonic activity. We propose prioritizing rooftop GNSS deployments to enhance east–west deformation monitoring. This framework balances regional and local-scale precision, offering a replicable solution for geological risk assessments in emerging cities. Full article

Olive mill wastewaters (OMWWs) are an environmental problem in the Mediterranean region, and it is crucial to explore strategies for their treatment and repurposing. The chemical precipitation technique (CPT) has been presented as a cost-effective wastewater treatment solution that might be applied to OMWW. The CPT-resulting precipitant subproducts (sludge) may be reprocessed (e.g., agricultural fertilizer and/or soil amendment), while the treated wastewater may be repurposed or reused (e.g., irrigation, aquaponic, or industrial processes). This study aimed to evaluate the efficacy of CPT in treating wastewater from the olive oil industry from an ecotoxicological perspective. Additionally, to assess the safe use of the obtained sludge in CPT treatment, its effects on soil biota were assessed. For this, a set of ecotoxicological assays using freshwater (Raphidocelis subcapitata, Daphnia magna and Danio rerio), terrestrial invertebrates (Folsomia candida and Enchytraeus crypticus), and plants (Brassica oleracea and Lolium perenne) were used as model organisms. Results demonstrated that CPT reduced OMWW toxicity to freshwater organisms, offering a favorable outlook on CPT’s potential as a wastewater treatment method. Increasing application rates of sludge in soil reduced the shoot biomass and the hydric content of both plants compared to the control. Survival of F. candida and E. crypticus was not affected by sludge in soil at any tested application rate, yet sludge application negatively affected the reproduction of both species, even at relevant sludge application rates (2%) of sludge in soils. Overall, the applicability of this sludge obtained by the CPT treatment in soils should be carefully evaluated due to the observed adverse effects on soil biota. Although the results of CPT were promising in reducing the toxicity of OMWW for these aquatic species, some adjustments/improvements should be performed to improve this technique and use all the obtained resources (treated water and sludge) in a fully circular perspective. Full article

Timely and accurate diagnosis of gastrointestinal diseases (GIDs) remains a critical bottleneck in clinical endoscopy, particularly due to the limited contrast and sensitivity of conventional white light imaging (WLI) in detecting early-stage mucosal abnormalities. To overcome this, this research presents Spectrum Aided Vision Enhancer (SAVE), an innovative, software-driven framework that transforms standard WLI into high-fidelity hyperspectral imaging (HSI) and simulated narrow-band imaging (NBI) without any hardware modification. SAVE leverages advanced spectral reconstruction techniques, including Macbeth Color Checker-based calibration, principal component analysis (PCA), and multivariate polynomial regression, achieving a root mean square error (RMSE) of 0.056 and structural similarity index (SSIM) exceeding 90%. Trained and validated on the Kvasir v2 dataset (n = 6490) using deep learning models like ResNet-50, ResNet-101, EfficientNet-B2, both EfficientNet-B5 and EfficientNetV2-B0 were used to assess diagnostic performance across six key GI conditions. Results demonstrated that SAVE enhanced imagery and consistently outperformed raw WLI across precision, recall, and F1-score metrics, with EfficientNet-B2 and EfficientNetV2-B0 achieving the highest classification accuracy. Notably, this performance gain was achieved without the need for specialized imaging hardware. These findings highlight SAVE as a transformative solution for augmenting GI diagnostics, with the potential to significantly improve early detection, streamline clinical workflows, and broaden access to advanced imaging especially in resource constrained settings. Full article

We describe an attempt to derive the binarity rate of samples of 166 A-, F-, G-, and K-type stars from LAMOST DR5 and 1000 randomly selected presumably single stars from Gaia DR3 catalogs. To this end, we compared continua of the observed spectra with the continua of synthetic spectra from within 3700 $<\lambda <9097$ Å. The latter spectra were reduced to the LAMOST set of wavelengths, while the former ones were smoothed. Next, we searched for every observed star of the nearest synthetic spectrum using a four-parameter representation—$T_{\mathrm{eff}}$, $logg$, $\left[\mathrm{Fe}/\mathrm{H}\right]$, and a range of interstellar absorption values. However, rms deviations of observed spectra from synthetic ones appeared to be not sufficient to claim that any of the stars is a binary. We conclude that comparison of the intensity of pairs of spectral lines remains the best way to detect binarity. Full article

Objective: This study aims to critically review and synthesize the existing literature on the use of voice analysis in assessing nasal obstruction, with a particular focus on acoustic parameters. Data sources: PubMed, Scopus, Web of Science, Ovid Medline, and Science Direct. Review methods: A comprehensive literature search was conducted without any restrictions on publication year, employing Boolean search techniques. The selection and review process of the studies followed PRISMA guidelines. The inclusion criteria comprised studies with participants aged 18 years and older who had nasal obstruction evaluated using acoustic voice analysis parameters, along with objective and/or subjective methods for assessing nasal obstruction. Results: Of the 174 abstracts identified, 118 were screened after the removal of duplicates. The full texts of 37 articles were reviewed. Only 10 studies met inclusion criteria. The majority of these studies found no significant correlations between voice parameters and nasal obstruction. Among the various acoustic parameters examined, shimmer was the most consistently affected, with statistically significant changes identified in three independent studies. A smaller number of studies reported notable findings for fundamental frequency (F0) and noise-related measures such as NHR/HNR. Conclusion: This systematic review critically evaluates existing studies on the use of voice analysis for assessing and monitoring nasal obstruction and hyponasality. The current evidence remains limited, as most investigations predominantly focus on glottic sound and dysphonia, with insufficient attention to the influence of the vocal tract, particularly the nasal cavities, on voice production. A notable gap exists in the integration of advanced analytical approaches, such as machine learning, in this field. Future research should focus on the use of advanced analytical approaches to specifically extrapolate the contribution of nasal resonance to voice thus defining the specific parameters in the voice spectrogram that can give precise information on nasal obstruction. Full article

As the resolution and conversion speed of time-to-digital conversion (TDC) chips continue to improve, the bit error rate also increases, leading to a decrease in the linearity of TDC and seriously affecting measurement accuracy. This paper presents a high-linearity, low-power-consumption, and wide dynamic range TDC that was achieved based on the SMIC 180 nm BCD process. Compared with previous research methods, the proposed phase arbiter structure can eliminate sampling errors and improve the linearity of TDC. The preprocessing circuit can eliminate fixed errors caused by START and STOP signal transmission delays. Post-simulation results show that the TDC has high linearity, with ranges of DNL and INL being −0.98 LSB < DNL < 0.93 LSB and −0.88 LSB < INL < 0.95 LSB, respectively. The highest resolution is 156 ps, the maximum measurement time range is 1.2 μs, and the power consumption is 1.625 mW. The overall system architecture of TDC is very simple, and it can be applied to dToF LIDAR to measure photon flight time, capable of measuring a range of up to hundreds of meters, with an accuracy of 2.25 cm, high linearity, and without any post-processing or time calibration. Full article

Background: Chryseobacterium indologenes, an environmental bacterium, is increasingly recognized as an emerging nosocomial pathogen, particularly in Asia, and is often characterized by multidrug resistance. Objectives: This study aimed to investigate the genomic features of clinical C. indologenes isolates from Maharaj Nakorn Chiang Mai Hospital, Thailand, to understand their mechanisms of multidrug resistance, virulence factors, and mobile genetic elements (MGEs). Methods: Twelve C. indologenes isolates were identified, and their antibiotic susceptibility profiles were determined. Whole genome sequencing (WGS) was performed using a hybrid approach combining Illumina short-reads and Oxford Nanopore long-reads to generate complete bacterial genomes. The hybrid assembled genomes were subsequently analyzed to detect antimicrobial resistance (AMR) genes, virulence factors, and MGEs. Results: C. indologenes isolates were primarily recovered from urine samples of hospitalized elderly male patients with underlying conditions. These isolates generally exhibited extensive drug resistance, which was subsequently explored and correlated with genomic determinants. With one exception, CMCI13 showed a lower resistance profile (Multidrug resistance, MDR). Genomic analysis revealed isolates with genome sizes of 4.83–5.00 Mb and GC content of 37.15–37.35%. Genomic characterization identified conserved resistance genes (bla_IND-2, bla_CIA-4, adeF, vanT, and qacG) and various virulence factors. Phylogenetic and pangenome analysis showed 11 isolates clustering closely with Chinese strain 3125, while one isolate (CMCI13) formed a distinct branch. Importantly, each isolate, except CMCI13, harbored a large genomic island (approximately 94–100 kb) carrying significant resistance genes (bla_OXA-347, tetX, aadS, and ermF). The absence of this genomic island in CMCI13 correlated with its less resistant phenotype. No plasmids, integrons, or CRISPR-Cas systems were detected in any isolate. Conclusions: This study highlights the alarming emergence of multidrug-resistant C. indologenes in a hospital setting in Thailand. The genomic insights into specific resistance mechanisms, virulence factors, and potential horizontal gene transfer (HGT) events, particularly the association of a large genomic island with the XDR phenotype, underscore the critical need for continuous genomic surveillance to monitor transmission patterns and develop effective treatment strategies for this emerging pathogen. Full article

Carbon layer-coated μm-sized carbon fiber has the potential to be developed as an electrode, as it can be directly used as an electrode without any preparation process in the absence of an insulating binder. In our work, a carbon layer-coated carbon fiber (C@CF) coaxial structure is constructed by in situ conversion of the epoxy resin around the carbon fiber into a carbon layer, in which a sandwich scaffold of cover/CFRP/screen is designed and adopted. The activated SC@CF, i.e., A-SC@CF, can be directly served as the electrode, and has excellent supercapacitor performance: a high specific capacity of 227.1 F g⁻¹ at 0.5 A g⁻¹, with a capacitance retention of 98.9% after 20,000 cycles for the electrode, and an energy density of 16.68 Wh kg⁻¹ at the power density of 1400 W kg⁻¹ for its symmetrical supercapacitor (SSC). Full article

An expanded Pacific Earthquake Engineering Research (PEER) Center Next Generation Attenuation Phase 2 (NGA-West2) ground motion database, compiled using shallow crustal earthquakes in active crustal regions (ACRs), was used to develop the closed-form GS24b backbone ground motion model (GMM) for the RotD50 horizontal components of peak ground acceleration (PGA), peak ground velocity (PGV), and 5% damped elastic pseudo-absolute response spectral accelerations (SA). The GS24b model is applicable to earthquakes with moment magnitudes of 4.0 ≤ M ≤ 8.5, at rupture distances of 0 ≤ $R_{rup}$ ≤ 400 km, with time-averaged S-wave velocity in the upper 30 m of the profile at 150 ≤ $V_{S30}$ ≤ 1500 m/s, and for periods of 0.01 ≤ T ≤ 10 s. The new backbone model includes $V_{S30}$ site correction developed based on multiple representative S-wave velocity profiles. For crustal wave attenuation, we used the apparent anelastic attenuation of SA—Q_SA (f, M). In contrast to the GK17, the GS24b backbone is a generic ACR model designed specifically to be adjusted to any ACRs. The GS24bc is an example of a partially non-ergodic model created by adjusting the backbone GS24b model for magnitude M, S-wave velocity $V_{S30}$, and fault rupture distance residuals. Full article

Federated learning (FL) struggles under non-IID client data when local models drift toward conflicting optima, impairing global convergence and performance. We introduce entropy-regularized federated optimization (ERFO), a lightweight client-side modification that augments each local objective with a Shannon entropy penalty on the per-parameter update distribution. ERFO requires no additional communication, adds a single-scalar hyperparameter $\lambda$, and integrates seamlessly into any FedAvg-style training loop. We derive a closed-form gradient for the entropy regularizer and provide convergence guarantees: under $\mu$-strong convexity and L-smoothness, ERFO achieves the same $O(1/T)$ (or linear) rates as FedAvg (with only $O\left(\lambda \right)$ bias for fixed $\lambda$ and exact convergence when ${\lambda }_t\to 0$); in the non-convex case, we prove stationary-point convergence at $O(1/T)$. Empirically, on five-client non-IID splits of the UNSW-NB15 intrusion-detection dataset, ERFO yields a +1.6 pp gain in accuracy and +0.008 in macro-F1 over FedAvg with markedly smoother dynamics. On a three-of-five split of PneumoniaMNIST, a fixed $\lambda$ matches or exceeds FedAvg, FedProx, and SCAFFOLD—achieving 90.3% accuracy and 0.878 macro-F1—while preserving rapid, stable learning. ERFO’s gradient-only design is model-agnostic, making it broadly applicable across tasks. Full article