bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rare case of myopathy with fatigability due to PYROXD1 variation
Authors: Baskar Dipti , Thomas Aneesha , Boddu Vijay Kumar , Santhoshkumar Rashmi , Anjanappa Ram Murthy , Nashi Saraswati , Srivastava Kosha , Polavarapu Kiran , Arunachal Gautham , Kotambail Ananthapadmanabha , Rao Bhoomika , Mahadevan Anita , Nalini Atchayaram , Vengalil Seena 
Published: December 2024

Introduction: Congenital myopathies are a group of heterogenous inherited muscle diseases. With advances in genetics, newer genes with novel features are being described. Pyridine nucleotide-disulfide oxidoreductase domain 1 ( PYROXD1) related myopathy is an ultrarare congenital myopathy. Only few cases have been reported worldwide till now. We report the first interesting case of PYROXD1 related myopathy from India. Methods: This is a retrospective study done from a quaternary neurology referral centre from southern India. All clinical, laboratory and electrophysiological data were collected from the medical records. Institutional ethics approval and informed consent from patient were obtained. Results: A 9 year-old-boy of non-consanguineous parentage presented with progressive fatigable proximo-distal weakness of upper and lower limbs with facial weakness from the age of 4 years. This was followed by chewing and swallowing difficulty. However speech was normal. There was profound proximal and distal joint hyperextensibility along with hip and ankle contractures. There was facial dysmorphism with high arched palate and retrognathism. Investigations showed normal serum creatine kinase levels. Nerve conduction studies showed axonal sensorimotor neuropathy. There was significant decremental response in tibialis anterior. Muscle biopsy showed both myopathic and neurogenic changes with novel findings of mitochondrial aggregates in subsarcolemmal and perinuclear regions. Next generation sequencing revealed a missense variant NM_024854.5:c.394C > T (NP_079130.2:p.Arg132Cys) of uncertain significance in exon 4 of PYROXD1 gene. Conclusion: This is the first report of PYROXD1 related myopathy from India. There were novel features of muscle fatigability, contractures, novel muscle biopsy features and a variant of uncertain significance expanding the phenotypic and genotypic spectrum of this rare myopathy.
Retinal vascular changes are associated with PET-based biomarkers of Alzheimer's disease: A pilot study
Authors: Leung Kristie Hing Chi , Chan Victor T.T. , Lam Bonnie Yin Ka , Mok Vincent CT , Cheung Carol Y 
Published: December 2024

Background Retina is a non-invasive channel for assessing changes in brain microvasculature, which has been implicated in the pathophysiology of Alzheimer's disease (AD). Previous studies revealed significant relationship between clinically diagnosed AD and retinal vasculature. However, clinical diagnosis has limited sensitivity and specificity, and those investigations were conducted from traditional retinal fundus photographs which only captured a narrow section of the fundus. Objective Determining changes in retinal vasculature from larger area of retina between subjects with positron emission tomography (PET) biomarker-confirmed AD compared to controls. Methods Participants were recruited from the community and cognitive disorder clinics. Diagnosis of AD was confirmed by significant amyloid-β (Aβ) and tau uptake on PET scan. Retinal vasculature was imaged with ultra-widefield (UWF) scanning laser ophthalmoscopy and a series of vessel parameters were quantified using the semi-automated Singapore I Vessel Assessment (SIVA) software. Statistical analyses were adjusted for age, gender and systolic blood pressure. In addition, arteriole parameters were adjusted against the same measurements in venules, and vice versa. Results Out of the 39 patients, 18 had radiologically confirmed AD. These individuals with AD showed significantly smaller arteriolar fractal dimension ( p = 0.032) in UWF images and greater venular tortuosity ( p = 0.011) in standard fundus images compared with controls. Presence of significant Aβ and tau burden was associated with lower arteriolar caliber (OR 3.857; 95% CI 1.014–14.67; p = 0.048). Conclusions Reduction of fractal dimension in retinal arterioles observed in UWF imaging is associated with cerebral Aβ and tau burden in people with biomarker-confirmed AD. Wide field retinal imaging provides an alternative perspective in demonstrating microvascular alterations related to AD in this pilot study.
Development and microstructural characterization of ultra-lightweight aggregate concrete incorporating different sizes of polypropylene fibers
Authors: Chung Sang-Yeop , Oh Seo-Eun , Sikora Pawel , Stephan Dietmar , Abd Elrahman Mohamed , Al-kroom Hussein 
Published: December 2024

AbstractIn this study, ultra-lightweight concrete with an oven-dry density of 800 kg/m3 was produced using expanded glass as the lightweight aggregate. Polypropylene fibers of different sizes were incorporated into the specimens to examine their effects on the material properties, such as drying shrinkage and flexural strength. The target dry density was achieved by applying the packing density concept to optimize the mix grading and calculate the content of each concrete component. Specimens with different ratios of short and long fibers were produced. Their fresh state, mechanical performance, and physical properties were extensively analyzed using various methods, including X-ray micro-computed tomography to examine the microstructure. The experimental results indicated a significant reduction in drying shrinkage for the fiber incorporated specimens, dependent on the fiber length and content. The compressive strength of the specimens exceeded 12 MPa. Moreover, the inclusion of polypropylene fibers notably enhanced the flexural strength by approximately 60%, while the lower density contributed to substantially reduced thermal conductivity by up to 26%, which is beneficial for thermal insulation. These results confirm that polypropylene fibers can be used to produce ultra-lightweight concrete with self-leveling properties, without compromising mechanical and physical performance.
Quercetin mitigates iron-induced cell death in chicken granulosa cell
Authors: Wei Shuo , Amevor Felix Kwame , Du Xiaxia , Li Linxiang , Yi Zhixin , Shu Gang , Wang Yan , Zhao Xiaoling 
Published: December 2024

Abstract
Background
Granulosa cell (GC) apoptosis, ferroptosis, and other programmed cell death processes are markers of follicular aging. Quercetin has been shown to reduce ferroptosis, however, its effects on ferroptosis in poultry remains unexplored. Our preliminary study identified ferroptosis in aging ovaries. Therefore, in the present study, 540-day-old Mountain Plum-blossom chickens were fed with quercetin supplementation at varying doses (0.2, 0.4, and 0.6 g/kg), and examined its molecular effects on GC ferroptosis using an in vitro Erastin-induced model.

Results
The results showed that quercetin supplementation significantly increased egg production, which confirmed its potential to alleviate ferroptosis in chicken ovarian tissue. The in vitro experiment revealed that quercetin and Fer-1 (positive control) mitigated Erastin-induced ferroptosis in GCs. Further, transcriptome analysis revealed that quercetin modulated key genes such as acyl-CoA synthetase long-chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor (TFRC), involved in ferroptosis regulation. The results further showed that quercetin also reduced Erastin-induced apoptosis and inflammation by modulating the expression of genes and proteins related to apoptosis and inflammatory factors (NF-κB, TNF-α, IL-6, and IL-10).

Conclusion
Taken together, the results showed that quercetin improves egg production performance in chickens and mitigates ovarian ferroptosis in aging hens, and inhibits Erastin-induced ferroptosis, inflammation, and apoptosis in GCs. These findings revealed the protective role of quercetin in poultry ovarian tissue and its cellular mechanisms against detrimental factors in poultry production.

Graphical Abstract
Waning success: a 2013–2022 spatial and temporal trend analysis of malaria in Ethiopia
Authors: Jalilian Abdollah , Ayana Galana Mamo , Ashine Temesgen , Hailemeskel Elifaged , Ebstie Yehenew Asmamaw , Molla Eshetu , Esayas Endashaw , Negash Nigatu , Kochora Abena , Assefa Muluken , Teferi Natnael , Teshome Daniel , Reynolds Alison M. , Weetman David , Wilson Anne L. , Kenate Birhanu , Donnelly Martin J. , Sedda Luigi , Gadisa Endalamaw 
Published: December 2024

Abstract
Background
Despite consecutive decades of success in reducing malaria transmission, Ethiopia went off track towards its goal of malaria elimination by 2030, as outlined in the NMCP malaria strategy. Recent malaria outbreaks in Ethiopia are attributed to the emergence and spread of diagnostic and drug-resistant Plasmodium falciparum, increased insecticide resistance in major vectors and the spread of invasive Anopheles stephensi. The effects of the COVID-19 pandemic, environmental anomalies and internal conflicts have also potentially played a role in increasing malaria transmission. This study aimed to evaluate the contribution of environmental factors and An. stephensi to the spatiotemporal trends of recent malaria cases in Ethiopia.

Methods
Clinical malaria case data reported weekly between January 2013 and January 2023 were obtained from the Ethiopian Public Health Institute (EPHI), Addis Ababa. A negative binomial regression model was used to explain the variability and potential overdispersion in the weekly number of malaria cases reported across Ethiopian administrative zones. This model incorporated fixed effects for selected environmental factors and random effects to capture temporal trends, zone specific seasonal patterns, spatial trends at the zone level, and the presence of An. stephensi and its impact.

Results
Our negative binomial regression model highlighted 56% variability in the data and slightly more than half (55%) was due to environmental factors, while the remainder was captured by random effects. A significant nationwide decline in malaria risk was observed between 2013 and 2018, followed by a sharp increase in early 2022. Malaria risk was higher in western and northwestern zones of Ethiopia compared to other zones. Zone-specific seasonal patterns, not explained by environmental factors, were grouped into four clusters of seasonal behaviours. The presence of An. stephensi was not shown to have any significant impact on malaria risk.

Conclusions
Understanding the spatial and temporal drivers of malaria transmission and therefore identifying more appropriate malaria control strategies are key to the success of any malaria elimination and eradication programmes in Ethiopia. Our study found that approximately 50% of malaria risk variability could be explained by environmental, temporal, and spatial factors included in the analysis, while the remaining variation was unexplained and may stem from other factors not considered in this study. This highlights the need for a better understanding of underlying factors driving local malaria transmission and outbreaks, to better tailor regional programmatic responses.

Graphical Abstract
Exploring the efficacy of Transcutaneous Auricular Vagus nerve stimulation (taVNS) in modulating local and systemic inflammation in experimental models of colitis
Authors: Hesampour Fatemeh , Tshikudi Diane M , Bernstein Charles N , Ghia Jean-Eric 
Published: December 2024

Abstract
Background
Current inflammatory bowel disease (IBD) treatments often fail to achieve lasting remission and have adverse effects. Vagus nerve stimulation (VNS) offers a promising therapy due to its anti-inflammatory effects. Its invasive nature, however, has led to the development of non-invasive methods like transcutaneous auricular VNS (taVNS). This study assesses taVNS’s impact on acute colitis progression, inflammatory, anti-inflammatory, and apoptosis-related markers.

Methods
Male C57BL/6 mice (11–12 weeks) were used for dextran sulfate sodium (DSS)- and dinitrobenzene sulfonic acid (DNBS)-induced colitis studies. The administration of taVNS or no stimulation (anesthesia without stimulation) for 10 min per mouse began one day before colitis induction and continued daily until sacrifice. Ulcerative colitis (UC)-like colitis was induced by administering 5% DSS in drinking water for 5 days, after which the mice were sacrificed. Crohn’s disease (CD)-like colitis was induced through a single intrarectal injection of DNBS/ethanol, with the mice sacrificed after 3 days. Disease activity index (DAI), macroscopic evaluations, and histological damage were assessed. Colon, spleen, and blood samples were analyzed via qRT-PCR and ELISA. One-way or two-way ANOVA with Bonferroni and Šídák tests were applied.

Results
taVNS improved DAI, macroscopic, and histological scores in DSS colitis mice, but only partially mitigated weight loss and DAI in DNBS colitis mice. In DSS colitis, taVNS locally decreased colonic inflammation by downregulating pro-inflammatory markers (IL-1β, TNF-α, Mip1β, MMP 9, MMP 2, and Nos2) at the mRNA level and upregulating anti-inflammatory TGF-β in non-colitic conditions at both mRNA and protein levels and IL-10 mRNA levels in both non-colitic and colitic conditions. Systemically, taVNS decreased splenic TNF-α in non-colitic mice and increased serum levels of TGF-β in colitic mice and splenic levels in non-colitic and colitic mice. Effects were absent in DNBS-induced colitis. Additionally, taVNS decreased pro-apoptotic markers (Bax, Bak1, and caspase 8) in non-colitic and colitic conditions and increased the pro-survival molecule Bad in non-colitic mice.

Conclusions
This study demonstrates that taVNS has model-dependent local and systemic effects, reducing inflammation and apoptosis in UC-like colitis while offering protective benefits in non-colitic conditions. These findings encourage further research into underlying mechanisms and developing adjunct therapies for UC.
Toward generalizable phenotype prediction from single-cell morphology representations
Authors: Tomkinson Jenna , Kern Roshan , Mattson Cameron , Way Gregory P. 
Published: December 2024

Abstract
Background
Functional cell processes (e.g., molecular signaling, response to stimuli, mitosis, etc.) impact cell phenotypes, which scientists can measure with cell morphology. However, linking these measurements with phenotypes remains challenging because it requires manually annotated labels. We propose that nuclear morphology can be a predictive marker for cell phenotypes that are generalizable across contexts.

Methods
We reanalyzed a pre-labeled, publicly-available nucleus microscopy dataset from the MitoCheck consortium. We extracted single-cell morphology features using CellProfiler and DeepProfiler, which provide robust processing pipelines. We trained multinomial, multi-class elastic-net logistic regression models to classify nuclei into one of 15 phenotypes such as ‘Anaphase,’ ‘Apoptosis’, and ‘Binuclear’. We rigorously assessed performance using F1 scores, precision-recall curves, and a leave-one-image-out (LOIO) cross-validation analysis. In LOIO, we retrained models using cells from every image except one and predicted phenotype in the held-out image, repeating this procedure for all images. We evaluated each morphology feature space, a concatenated feature space, and several feature space subsets (e.g., nuclei AreaShape features only). We applied models to the Joint Undertaking in Morphological Profiling (JUMP) data to assess performance using a different dataset.

Results
In a held-out test set, we observed an overall F1 score of 0.84. Individual phenotype scores ranged from 0.64 (moderate performance) to 0.99 (high performance). Phenotypes such as ‘Elongated’, ‘Metaphase’, and ‘Apoptosis’ showed high performance. While CellProfiler and DeepProfiler features were generally equally effective, concatenation yielded the best results for 9/15 phenotypes. LOIO showed a performance decline, indicating our model could not reliably predict phenotypes in new images. Poor performance was unrelated to illumination correction or model selection. Applied to the JUMP data, models trained using nuclear AreaShape features only increased alignment with the annotated MitoCheck data (based on UMAP space). This approach implicated many chemical and genetic perturbations known to be associated with specific phenotypes.

Discussion
Poor LOIO performance demonstrates challenges of single-cell phenotype prediction in new datasets. We propose several strategies that could pave the way for more generalizable methods in single-cell phenotype prediction, which is a step toward morphology representation ontologies that would aid in cross-dataset interpretability.
Metastatic Pheochromocytoma/Paraganglioma Overproducing Multiple Catecholamines
Authors: Yoshioka Keiko , Nakano Yujiro , Horichi Moeka , Aono Daisuke , Takeshita Yumie , Takamura Toshinari 
Published: December 2024

Abstract
Pheochromocytoma and paraganglioma (PPGL) are rare chromaffin-cell tumors producing adrenaline and/or noradrenaline, or solely dopamine. A 52-year-old man presenting with hypertension (141/79 mm Hg) and weight loss (10 kg in 6 months) was admitted to our hospital. Computed tomography revealed a massive right adrenal mass (150 mm) with partial necrosis, accompanied by multiple liver nodules. These nodules showed a high signal intensity on T2-weighted magnetic resonance imaging. Subsequently, a diagnosis of PPGL was made based on elevated urinary excretion of adrenaline (355 µg/day [1937 nmol/day]; normal range: 3.4-26.9 µg/day; 18-146 nmol/day), noradrenaline (1690 µg/day [9989 nmol/day]; normal range: 48.6-168.4 µg/day; 287-995 nmol/day), and dopamine (53 000 µg/day [258 322 nmol/day]; normal range: 365-961.5 µg/day; 1779-4686 nmol/day). The 123I-metaiodobenzylguanidine scintigraphy and fluorodeoxyglucose positron emission tomography scan showed heterogenous uptake among the adrenal and the liver foci, respectively. Clustering analysis of previous PPGL cases highlighted the unique catecholamine profile of this case. These findings suggest a possibility that internodular heterogeneity between primary and metastatic foci on nuclear imaging may indicate varying differentiation grades and resultant catecholamine secretion. Further studies will be needed to verify these results and confirm this hypothesis.
Genetically Supported Causality between Brain Structural Connectome and Sleep Duration in Children: A Two-Sample Mendelian Randomization Study
Authors: Zhang Ruijie , Luo Liyan , Zhang Lu , Lin Xinao , Wu Chuyan , Jiang Feng , Wang Jimei 
Published: December 2024

Certain structural brain connections have been confirmed to influence sleep duration in children. However, the causal relationships between all brain regions and children's sleep duration remain unclear. A two-sample Mendelian randomization analysis was conducted using data from genome-wide association studies (GWAS) to examine the relationships between 206 structural connections and sleep duration in children. Sensitivity analyses were employed to validate the findings and assess the robustness of the causal inferences. Stronger connectivity from the left hemisphere (LH) control network to the accumbens (
β
= −0.15; 95% CI = [−0.30, −2.88 × 10
−3
];
p
= 0.05) and from the LH somatomotor network to the LH default network (
β
= −0.18; 95% CI = [−0.34, −0.03];
p
= 0.02) in white-matter structural connectivity (SC) were associated with shorter sleep durations. Conversely, increased white-matter SC from the LH dorsal attention network to the thalamus (
β
= 0.14; 95% CI = [8.45 × 10
−4
, 0.27];
p
= 0.05), from the right hemisphere (RH) control network to the thalamus (
β
= 0.10; 95% CI = [0.01, 0.19];
p
= 0.03), from the RH default network to the thalamus (
β
= 0.08; 95% CI = [4.53 × 10
−3
, 0.16];
p
= 0.04), from the RH limbic network to the thalamus (
β
= 0.15; 95% CI = [0.05, 0.26];
p
= 3.77 × 10
−3
), and from the RH somatomotor network to the thalamus (
β
= 0.20; 95% CI = [0.07, 0.32];
p
= 1.63 × 10
−3
) correlated with longer sleep durations in children. Two-sample Mendelian randomization provides novel insights into the relationships between brain regions and sleep duration in children. Our findings demonstrate a causal relationship between specific brain areas and sleep duration.
Color Assessment of Screw-Retained Implant Prostheses Access Hole Fillings: An In-Vitro Study
Authors: Sarrafzadeh Arash , Nakhostin Afrooz , Jadidi Soheila , Safari Malihe 
Published: December 2024

Objectives: This study aimed to investigate the aesthetic aspect of screw-retained restorations by examining three different types of filling materials used for the access cavity, highlighting the significance of aesthetics in implant restorations.
Materials and Methods: In this laboratory investigation, simulation samples of screw-retained restorations were filled with flowable composite resin (group F), opaque and flowable composite resin (group O) and porcelain plug (group P) at baseline (T0). The samples were subjected to thermocycling twice (T1 and T3), undergoing 1000 cycles in coffee, orange juice, and distilled water, followed by washing performed after each thermocycling (T2 and T4). Colorimetric analysis and surface roughness measurements were conducted, and the data were statistically analyzed using. two-way analysis of variance (ANOVA), ,Tukey post hoc, two-way analysis of covariance (ANCOVA), and paired-t test. P<0.05 was considered significant.
Results: The type of filling material had a significant effect on the color difference observed between the restoration and filling materials (P<0.05). Notably, samples from group P exhibited a more pronounced color difference at T4, despite showing a lower color difference at T0, when compared to group O.
Conclusion: The use of porcelain plugs did not provide a notable advantage over the combination of flowable and opaque composite resins, particularly given the difficulties in fabricating and positioning porcelain plugs within the access cavity. Therefore, it is recommended to utilize flowable composite resins in conjunction with an opaque composite resin layer beneath, to effectively conceal any dark shades from the underlying metal.