Search Results (60)

The fibrillary aggregation of α-synuclein is a hallmark of Parkinson’s disease (PD) and a potential target for diagnostics and therapeutics. Although substantial effort has been devoted to the development of positron emission tomography (PET) probes for detecting α-synuclein aggregates, no clinically suitable tracer has been reported. The design and synthesis of 43 new N-(6-methoxypyridin-3-yl)quinolin-2-amine derivatives and an evaluation of their α-synuclein binding affinity is reported here. Compounds 7f, 7j, and 8i exhibited high affinity for α-synuclein and were selected for ¹¹C, ¹⁸F, ¹²⁵I, or ³H radiolabeling. A photoaffinity variant, TZ-CLX, structurally related to 7j and 8i, demonstrated preferential binding to the C-terminal region of α-synuclein fibrils. PET brain imaging studies using [¹¹C]7f, [¹⁸F]7j, and [¹¹C]8i in non-human primates indicated that these three α-synuclein PET tracers penetrated the blood–brain barrier. Both [¹¹C]7f and [¹⁸F]7j showed more favorable brain washout pharmacokinetics than [¹¹C]8i. In vitro binding assays showed that [¹²⁵I]8i is a very potent α-synuclein radioligand, with K_d values of 5 nM for both PD brain tissues and LBD-amplified fibrils; it is also selective for PD tissues versus AD or control tissues. These results strongly suggest that the PET probes based on the N-(6-methoxypyridin-3-yl)quinoline-2-amine scaffold have potential utility in detecting α-synuclein aggregates in vivo. Full article

This research addresses critical challenges in clinical gait analysis by developing an automated video quality assessment framework to support Edinburgh Visual Gait Score (EVGS) scoring. The proposed methodology uses the MoveNet Lightning pose estimation model to extract body keypoints from video frames, enabling detection of multiple persons, tracking the person of interest, assessment of plane orientation, identification of overlapping individuals, detection of zoom artifacts, and evaluation of video resolution. These components are integrated into a unified quality classification system using a random forest classifier. The framework achieved high performance across key metrics, with 96% accuracy in detecting multiple persons, 95% in assessing overlaps, and 92% in identifying zoom events, culminating in an overall video quality categorization accuracy of 95%. This performance not only facilitates the automated selection of videos suitable for analysis but also provides specific video improvement suggestions when quality standards are not met. Consequently, the proposed system has the potential to streamline gait analysis workflows, reduce reliance on manual quality checks in clinical practice, and enable automated EVGS scoring by ensuring appropriate video quality as input to the gait scoring system. Full article

The Edinburgh Visual Gait Score (EVGS) is a commonly used clinical scale for assessing gait abnormalities, providing insight into diagnosis and treatment planning. However, its manual implementation is resource-intensive and requires time, expertise, and a controlled environment for video recording and analysis. To address these issues, an automated approach for scoring the EVGS was developed. Unlike past methods dependent on controlled environments or simulated videos, the proposed approach integrates pose estimation with new algorithms to handle operational challenges present in the dataset, such as minor camera movement during sagittal recordings, slight zoom variations in coronal views, and partial visibility (e.g., missing head) in some videos. The system uses OpenPose for pose estimation and new algorithms for automatic gait event detection, stride segmentation, and computation of the 17 EVGS parameters across the sagittal and coronal planes. Evaluation of gait videos of patients with cerebral palsy showed high accuracy for parameters such as hip and knee flexion but a need for improvement in pelvic rotation and hindfoot alignment scoring. This automated EVGS approach can minimize the workload for clinicians through the introduction of automated, rapid gait analysis and enable mobile-based applications for clinical decision-making. Full article

Background/Objectives: The diagnosis and prognosis of arrested foveal development or foveal hypoplasia (FH) can be made using the Leicester grading system for FH and optical coherence tomography (OCT). In clinical practice, ophthalmologists and ophthalmic health professionals with varying experience consult patients with FH; however, to date, the FH grading system has only been validated amongst experts. We compare the inter-grader and intra-grade agreement of healthcare professionals against expert consensus across all grades of FH. Methods: Handheld and table-mounted OCT images (n = 341) were graded independently at a single centre by experts (n = 3) with over six years of experience and “novice” medical and allied health professionals (n = 5) with less than three years of experience. Sensitivity, specificity, and Cohen’s kappa scores were calculated for each grader, and expert vs. novice performance was compared. Results: All graders showed high sensitivity (median 97% (IQR: 94–99)) and specificity (median 94% (IQR: 90–95)) in identifying the presence or absence of FH. No significant difference was seen in specificity between expert and novice graders, but experts had significantly greater diagnostic sensitivity (median difference = 5.3%, H = 5.00, p = 0.025). Expert graders had the highest agreement with the ground truth and novice graders showed great variability in grading uncommon grades, such as atypical FH. The proposed causes of misclassification included macular decentring in handheld OCT scans in children. Conclusions: Ophthalmologists of varying experience and allied health professionals can accurately identify FH using handheld and table-mounted OCT images. FH identification and paediatric OCT interpretation can be improved in wider ophthalmic clinical settings through the education of ophthalmic staff. Full article

The Modified Mallet Score (MMS) is widely used to assess upper limb function but requires evaluation by experienced clinicians. This study automated MMS assessments using smartphone videos, artificial intelligence (AI), and new algorithms. A total of 125 videos covering all MMS grades were recorded from four neurotypical participants. For all recordings, an expert physician provided manual scores as the ground truth. The OpenPose BODY25 model extracted body keypoint data, which were used to calculate joint angles for an automated scoring algorithm. The algorithm’s scores were compared to the ground truth and expert manual scoring. High accuracy was achieved for the global abduction, hand-to-neck, hand-on-spine, and hand-to-mouth movements, with Pearson correlation coefficients (PCCs) > 0.9 and a low root mean square error (RMSE). Although slightly less accurate for global external rotation, the algorithm still showed strong agreement. This study demonstrates the potential of using AI and smartphone videos for reliable, remote upper limb assessments. Full article

Salmonella enterica infections can significantly impact the health and productivity of dairy cattle. Asymptomatic carriage of Salmonella can make it difficult to identify and monitor this pathogen across a herd. Therefore, a more focused Salmonella census on dairy farms is needed to better understand the dynamics of asymptomatic carriage. Here, we monitored the prevalence of Salmonella enterica on a dairy operation in Wisconsin, USA. Fecal samples were collected over 12 months from cattle and the farm environment, subjected to Salmonella isolation, serogrouped, and tested for antibiotic resistance. Salmonella was highly prevalent on this farm, with an average of 90% of the cattle being carriers. Total recovery of Salmonella from environmental samples ranged from 40 to 90%. Four serogroups were identified on the farm, with K being most common in cattle and C being most common in the environment. Antibiotic resistance was tested against eight antibiotics and was found to be highest for neomycin (44.5%) and sulfadimethoxine (86.3%). Our data show that serogroups associated with asymptomatic carriages are persistent and highly prevalent, with niche specificity to different locations. These results provide useful information for studying within-herd transmission of Salmonella and contributes to our understanding of transmission risks within the farm ecosystem. Full article

Background: The early exposure of nutrients during pubertal mammary gland development may reduce the risk of developing breast cancer later in life. Anticancer n-3 polyunsaturated fatty acids (n-3 PUFA) are shown to modulate pubertal mammary gland development; however, the mechanisms of action remain unclear. Prior work focused on effects at the whole tissue level, and little is known at the cellular level, such as at the level of mammary epithelial cells (MECs), which are implicated in cancer development. Methods: This pilot study examined the effects of lifelong n-3 PUFA exposure on the transcriptome by RNA-Seq in the isolated MECs of pubertal (6–8-week-old) female fat-1 transgenic mice capable of de novo n-3 PUFA synthesis. edgeR and DESeq2 were used separately for the differential expression analysis of RNA sequencing data followed by the Benjamani–Hochberg procedure for multiple testing correction. Results: Nine genes were found concordant and significantly different (p ≤ 0.05) by both the DESeq2 and edgeR methods. These genes were associated with multiple pathways, suggesting that n-3 PUFA stimulates estrogen-related signaling (Mlltl0, Galr3, and Nrip1) and a glycolytic profile (Soga1, Pdpr, and Uso1) while offering protective effects for immune and DNA damage responses (Glpd1, Garre1, and Rpa1) in MECs during puberty. Conclusions: This pilot study highlights the utility of RNA-Seq to better understanding the mechanistic effects of specific nutrients such as n-3 PUFA in a cell-specific manner. Thus, further studies are warranted to investigate the cell-specific mechanisms by which n-3 PUFA influences pubertal mammary gland development and breast cancer risk later in life. Full article

This paper focuses on the acceptance of ADASs in the traffic safety and human factor domain. More specifically, it examines the predictive validity of the Unified Model of Driver Acceptance (UMDA) for an ADAS bundle that includes forward collision warning, headway monitoring and warning, and lane-keeping assistance in Belgium and Vietnam, two substantially different geographical, socio-cultural, and macroeconomic settings. All systems in the studied ADAS bundle are located at the Society of Automotive Engineer (SAE)-level 0 of automation. We found moderate acceptance towards such an ADAS bundle in both countries, and respondents held rather positive opinions about system-specific characteristics. In terms of predictive validity, the UMDA scored quite well in both countries, though better in Belgium than in Vietnam. Macroeconomic factors and socio-cultural characteristics could explain these differences between the two countries. Policymakers are encouraged to prioritise initiatives that stimulate the purchase and use of the ADAS, rather than on measures meant to influence the underlying decisional balance. Full article

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. Full article

Dog and cat preference has been associated with a few factors, like owner personality traits, but data regarding other aspects of preference ontogeny and the impact of preferences on pet wellbeing have yet to be examined. In this exploratory study, several of these characteristics, such as exposure to pets when young and as adults and current pet interactions and diet were analyzed from internet survey data. We found that more people identified as dog people (63.3%) versus cat people (36.7%) and preference for dogs remained consistent from childhood to adulthood compared with cats. In individuals who changed species preference, a lack of childhood exposure to cats (47.2%) was significantly associated with the group that changed preferences from dogs to cats from childhood to adulthood, compared with dog ownership as a child in the group that changed preferences from cats to dogs (24.4%). The number of cats and dogs in the home directly correlated with species preference (p < 0.001). Dwelling location was also significantly associated with species preference, with cat people being more likely to live in an urban area and dog people in a rural area (p = 0.002). More time was spent in both active and passive interactions with pets of the preferred species. Cats owned by cat people were more likely to be fed prescription diets compared with cats owned by dog people (p < 0.001). Interestingly, dog people were more likely to feed both their cats (p = 0.012) and dogs (p < 0.001) a raw diet compared with cat people. Additional research is needed to understand the development and impact of owner species preferences on pets to identify risks of suboptimal wellbeing. Full article

Background: Although heartburn and reflux are frequently reported in ulcerative colitis [UC], the correlation between UC and gastroesophageal reflux disease [GERD], and its complications, esophageal stricture and Barrett’s esophagus [BE], is not well understood. This study aims to examine the prevalence and associated risk of GERD and its complications within the UC population. Methods: We analyzed the National Inpatient Sample (NIS) dataset, consisting of 7,159,694 patients, comparing GERD patients with and without UC to those without GERD. We assessed the degree of colonic involvement in UC and the occurrence of esophageal complications. Bivariate analyses were conducted using the chi-squared test or Fisher exact test (two-tailed). Results: A higher prevalence of GERD (23.0% vs. 16.5%) and GERD phenotypes, such as non-erosive reflux disease (NERD) (22.3% vs. 16%) and erosive esophagitis (EE) (1.2% vs. 0.6%), was found in UC patients (p < 0.01), including pancolitis, proctitis, proctosigmoiditis, left-sided colitis, and indetermined UC (with undefined colonic involvement). UC patients were more likely to develop GERD (1.421), NERD (1.407), and EE (1.681) (p < 0.01). A higher prevalence of esophageal stricture (16.9 vs. 11.4 per 10,000 patients) and BE without dysplasia (94.5 vs. 39.3 per 10,000 patients) was found in UC (p < 0.05). The odds of developing BE without dysplasia were higher (1.892) in patients with UC (p < 0.01), including ulcerative pancolitis, proctitis, and indeterminate UC (OR of 1.657, 3.328, and 1.996, respectively) (p < 0.05). Conclusions: Our study demonstrates an increased risk of developing GERD and its complications in UC. This highlights the importance of vigilant monitoring and early intervention to minimize associated GERD-related risks in patients with UC. Full article

This study begins by examining phenotypic variations in field growth among four parental Vietnamese rice lines, consisting of two Indica (PD211/GL37) and two Japonica (J23/SRA2-1) cultivars, which differ in life-cycle durations. Their phenotypic observations revealed both similarities and differences in growth patterns and field responses, setting the stage for further genomic investigation. We then focused on the sequencing and de novo genome assembly of these lines using high-coverage Illumina sequencing and achieving pseudochromosome assemblies ranging between 379 Mbp and 384 Mbp. The assemblies were further enhanced by annotation processes, designating between 44,427 and 48,704 gene models/genome. A comparative genomic analysis revealed that the Japonica varieties (J23/SRA2-1) exhibited more genetic similarity than the Indica varieties (PD211/GL37). From this, a phylogenetic analysis on the phytochrome C (phyC) gene distinctly positions the Indica and Japonica lines within their respective clades, affirming their genetic diversity and lineage accuracy. These genomic resources will pave the way for identifying quantitative trait loci (QTLs) critical for developing rice cultivars with shorter life cycles, thus enhancing resilience to adverse climatic impacts in Vietnam. This study provides a foundational step towards leveraging genomic data for rice breeding programs aimed at ensuring food security in the face of climate change. Full article

François’ langur is an Endangered colobine inhabiting limestone habitats in southern China and northern Vietnam. Its global population has been estimated to be just more than 2000 mature individuals. Populations in Vietnam are highly fragmented with reportedly fewer than 200 adults in total and 50 in a single location. Although the François’ langur in Vietnam is highly imperiled as remnant populations persist in only three to four sites, little research has been carried out to provide a reliable estimate of its remaining population. In this study, we conducted field surveys in Lam Binh District, Tuyen Quang Province, northeastern Vietnam. In total, we recorded at least 16 groups of François’ langurs, with 156 individuals, raising the total number of individuals by approximately 10% compared to a previous study. The group structure, group size, activity budget, and density of the Lam Binh population resemble those reported in François’ langurs in China and other limestone langur species. The results show that the behavior ecology of limestone langurs significantly differs from that of forest langurs probably because they occupy separate habitats with distinctly different environmental variables. During our surveys, we detected a number of direct threats to this population, namely illegal logging, hunting, firewood collecting, hydropower development, grazing, and mining. It is recommended that the protection forest be elevated to the nature reserve status to better protect the most important population of the François’ langur in Vietnam. Full article

This study investigates the relationship between market power and bank profitability, and the impacts of CEOs’ personality traits, in Vietnam from 2007 to 2020. The analysis of CEOs’ signatures is used to determine their characteristics. The findings support the quiet-life hypothesis, which suggests that the negative relationship between market power and bank profitability may depend on CEOs’ characteristics. More specifically, the results show that conscientious CEOs with market power tend to reduce bank profitability, and this effect is more pronounced for foreign-owned banks. Therefore, our findings have critical implications for bank management. Full article

The Sample Analysis at Mars-Evolved Gas Analyzer (SAM-EGA) on the Curiosity rover detected hydrogen chloride (HCl) and sulfur dioxide (SO₂) gas evolutions above 600 °C and 700 °C, respectively, from several drilled rock and soil samples collected in Gale crater, which have been attributed to NaCl and Mg sulfates. Although NaCl and Mg sulfates do not evolve HCl or SO₂ within the SAM temperature range (<~870 °C) when analyzed individually, they may evolve these gases at <870 °C and become detectable by SAM-EGA when mixed. This work aims to determine how Mg sulfate and NaCl interact during heating and how that affects evolved HCl and SO₂ detection temperatures in SAM-EGA. Solid mixtures of NaCl and kieserite were analyzed using a thermogravimeter/differential scanning calorimeter furnace connected to a quadrupole mass spectrometer, configured to operate under similar conditions as SAM, and using X-ray diffraction of heated powders. NaCl analyzed individually did not evolve HCl; however, NaCl/kieserite mixtures evolved HCl releases with peaks above 600 °C. The results suggested that kieserite influenced HCl production from NaCl via two mechanisms: (1) kieserite depressed the melting point of NaCl, making it more reactive with evolved water; and (2) SO₂ from kieserite decomposition reacted with NaCl and water (i.e., Hargreaves reaction). Additionally, NaCl catalyzed the thermal decomposition of kieserite, such that the evolved SO₂ was within the SAM-EGA temperature range. The results demonstrated that SAM-EGA can detect chlorides and Mg sulfates when mixed due to interactions during heating. These phases can provide information on past climate and mineral formation conditions. Full article