Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin Resistance Exacerbates Alzheimer Disease via Multiple Mechanisms

Alzheimer disease (AD) is a chronic neurodegenerative disease that accounts for 60–70% of dementia and is the sixth leading cause of death in the United States. The pathogenesis of this debilitating disorder is still not completely understood. New insights into the pathogenesis of AD are needed in order to develop novel pharmacologic approaches. In recent years, numerous studies have shown that insulin resistance plays a significant role in the development of AD. Over 80% of patients with AD have type II diabetes (T2DM) or abnormal serum glucose, suggesting that the pathogenic mechanisms of insulin resistance and AD likely overlap. Insulin resistance increases neuroinflammation, which promotes both amyloid β-protein deposition and aberrant tau phosphorylation. By increasing production of reactive oxygen species, insulin resistance triggers amyloid β-protein accumulation. Oxidative stress associated with insulin resistance also dysregulates glycogen synthase kinase 3-β (GSK-3β), which leads to increased tau phosphorylation. Both insulin and amyloid β-protein are metabolized by insulin degrading enzyme (IDE). Defects in this enzyme are the basis for a strong association between T2DM and AD. This review highlights multiple pathogenic mechanisms induced by insulin resistance that are implicated in AD. Several pharmacologic approaches to AD associated with insulin resistance are presented.
Validation of Potential Protein Markers Predicting Chemoradioresistance in Early Cervical Cancer by Immunohistochemistry

Background In a previous study, a proteomic panel consisting of BCL-2, HER2, CD133, CAIX, and ERCC1 significantly predicted survival in patients with locally advanced cervical cancer. However, the prognostic significance of these proteins has not been assessed in early cervical cancer. The present study investigated the clinical significance and chemoradioresistance prediction power of these proteins in patients with early-stage cervical cancer. Materials and Methods BCL-2, HER2, CD133, CAIX, and ERCC1 expression was determined by the immunohistochemical staining of 336 cervical cancer tissue microarrays. The associations of these proteins with clinicopathologic characteristics and disease progression were assessed. Results There was a trend of low CAIX expression (p=0.082) and high ERCC1 expression (p=0.059) in patients with a favorable response to adjuvant radiation. High HER2 expression was significantly associated with shorter disease-free survival (DFS) in the total group (5-year DFS of 80.1% vs. 92.2%, p=0.004). A prognostic significance remained in multivariate analysis (Hazard ratio, HR=2.10, p=0.029). In the adjuvant radiation group, low CAIX and high ERCC1 expression indicated significantly unfavorable DFS (75.0% vs. 89.0%, p=0.026 and 76.8% vs. 88.6%, p=0.022, respectively). Low CAIX expression remained an independent prognostic marker in multivariate analysis (HR=0.45, p=0.037). The combined molecular-clinical model using random survival forest method predicted DFS with improved power compared with that of the clinical variable model (C-index 0.77 vs. 0.71, p=0.006). Conclusion HER2, CAIX, and ERCC1 expression can be predictive protein markers for clinical outcomes in early cervical cancer patients treated primarily with radical surgery with or without adjuvant radiation.
Stage-Dependent Within-Individual Comparison Reveals SIV-Specific Activation/Exhaustion Shift in Rhesus Macaques

It is challenging to trace the complicated individual-based variations of HIV-specific immunocompetence shift during the successful antiretroviral therapy (ART) era. Using eight rhesus monkeys simulating a longitudinal stage-dependent cohort (baseline-SIV acute infection-SIV suppression by ART-ART withdrawal), baseline immunocompetence monitoring for 28 days (SIV-negative stage, SN) was compared with host immunocompetence undergoing 90-day ART treatment (SIV-suppressed stage, SS) to reveal the SIV-specific immunity shift aroused by undetectable individual viral replication. During acute SIV infection for 98 days (SIV-emerged stage, SE), immune activation was compared with re-immune activation post ART for 49-day follow-up (SIV-rebounded stage, SR) to reveal the SIV-specific immune activation variation aroused by detectable individual viral replication. Individual immunocompetence was measured by co-expression of CD4, CD8, CD38, HLA-DR, CCR7, CD45RA, and PD-1 on T cells and a cytokine panel. Compared with SN, mild immune activation/exhaustion was characterized by increased CD38+ HLA-DR– CD4+/CD8+ T-cell subsets and PD-1+ memory CD4+/CD8+ T-cell subsets with three elevated cytokines (MIP-1β, IL-8, and IL-10) significantly emerged in SS. Compared with SE, SR produced more exhaustion characterized by increased PD-1+ CD4+ TCM cells and decreased PD-1+ CD4+ TEM cells with four elevated pro-inflammatory cytokines (IFN-γ, IL-1β, IL-6, and TNF-α). By such individualized stage-dependent comparison, the sustainable immune activation was found from activation/exhaustion shifted into exhaustion during the longitudinal viral persistence. Further, validated SIV accelerates host immunosenescence continuously independent of viral replication.
Aesthetic Experience of Representational Art: Liking Is Affected by Audio-Information Naming and Explaining Inaccuracies of Historical Paintings

Paintings in museums are often accompanied by additional information, such as titles or audio-texts. Previous research has reported mostly positive effects of additional information on the liking and subjective understanding of a painting. However, some studies have also reported negative effects when additional information introduces inconsistencies between the painting’s content and the represented reality. Therefore, the present study examined the negative effects of naming a painting’s historical inaccuracies, which are inconsistencies between the content of the painting and the real historic event, and whether these negative effects can be compensated by an explanation for the inaccuracies. The results revealed that liking was lower with inaccuracies named and that this effect was compensated by an explanation for the inaccuracies. No significant effects were observed for subjective understanding and aesthetic emotions. The results corroborate parts of the Vienna integrated model of art perception and have practical implications for the design of audio-texts in museums.
Comparison of the Safety and Efficacy of Interferon Alpha-2a and Cyclosporine-A When Combined With Glucocorticoid in the Treatment of Refractory Behçet’s Uveitis: A Randomized Controlled Prospective Study

Purpose: To evaluate and compare the efficacy and safety of interferon alpha-2a (IFN-α2a) and cyclosporine-A (CsA) in patients with refractory Behçet’s uveitis (BU). Methods: In this 12-month randomized, controlled, prospective trial, 26 participants (44 eyes) completed the study. Patients were randomly allocated to the IFN-α2a or CsA groups. All patients in both groups received a standardized prednisone burst and tapering schedule as per protocol. The primary outcome measures were response rate, complete remission rate, and tolerance rate. The secondary outcome measures included time to achieve complete remission, the logarithm of the minimum angle of resolution (logMAR) of best-corrected visual acuity (BCVA), and Behçet’s disease ocular attack score 24 (BOS24). T-tests and non-parametric tests were used to compare quantitative variables, and chi-square tests were performed to compare qualitative variables. Results: The response and complete remission rates were 85.7% (12/14 patients) and 50.0% (7/14 patients) in the IFN-α2a group, compared with 66.7% (8/12 patients) and 25.0% (3/12 patients) in the CsA group, respectively (p > 0.05). Complete remission was achieved at 3.3 and 7.0 months after initiation of IFN-α2a and CsA (p = 0.023). LogMAR BCVA significantly improved 1 month after IFN-α2a initiation (23 eyes) (p = 0.002), and this beneficial effect remained statistically significant during the entire follow-up period (p < 0.05); however, this improvement was not observed in the CsA group (21 eyes). At the endpoint, LogMAR BCVA in the IFN-α2a group was significantly better (0.22 vs. 0.31, p = 0.031) with a higher improvement rate (60.9 vs. 47.6%, p > 0.05). Moreover, compared to the CsA group, more eyes in the IFN-α2a group had a lower BOS24 score (87.0 vs. 57.1%, p = 0.042). None of the patients had any side effects that influenced the medication adherence. Conclusion: Compared to CsA plus corticosteroid, IFN-α2a plus corticosteroid appears to induce a better treatment response, a significantly greater improvement in visual acuity, and more stable remission of intraocular inflammation in a 12-month study period.
The Influencing Mechanism of Interaction Quality of UGC on Consumers’ Purchase Intention – An Empirical Analysis

User-generated content (UGC) refers to online information created and shared by consumers that can influence other users’ purchase decisions. Due to the rapid development of new technologies in business, marketers’ dependency on UGC is rising. This study aims to explain how the interaction quality of UGC affects its credibility as a source and the usefulness of its information, as well as how it influences consumers’ online purchase intention. In addition, we examine the moderating effect of product involvement. We collected data from 272 users of social media in China to conduct empirical research. The SPSS and Amos were used to analyze the data and test the hypotheses. The results reveal that UGC interaction quality is positively related to purchase intention, and this relationship is mediated by perceived usefulness and trust. Further, consumers’ product involvement negatively moderates the effect of perceived usefulness and trust on purchase intention. Findings from this study are expected to extend the literature on UGC and give benefits to marketers and online business operators.
Corneal Cross-Linking: The Evolution of Treatment for Corneal Diseases

Corneal cross-linking (CXL) using riboflavin and ultraviolet A (UVA) light has become a useful treatment option for not only corneal ectasias, such as keratoconus, but also a number of other corneal diseases. Riboflavin is a photoactivated chromophore that plays an integral role in facilitating collagen crosslinking. Modifications to its formulation and administration have been proposed to overcome shortcomings of the original epithelium-off Dresden CXL protocol and increase its applicability across various clinical scenarios. Hypoosmolar riboflavin formulations have been used to artificially thicken thin corneas prior to cross-linking to mitigate safety concerns regarding the corneal endothelium, whereas hyperosmolar formulations have been used to reduce corneal oedema when treating bullous keratopathy. Transepithelial protocols incorporate supplementary topical medications such as tetracaine, benzalkonium chloride, ethylenediaminetetraacetic acid and trometamol to disrupt the corneal epithelium and improve corneal penetration of riboflavin. Further assistive techniques include use of iontophoresis and other wearable adjuncts to facilitate epithelium-on riboflavin administration. Recent advances include, Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) for treatment of infectious keratitis, customised protocols (CurV) utilising riboflavin coupled with customised UVA shapes to induce targeted stiffening have further induced interest in the field. This review aims to examine the latest advances in riboflavin and UVA administration, and their efficacy and safety in treating a range of corneal diseases. With such diverse riboflavin delivery options, CXL is well primed to complement the armamentarium of therapeutic options available for the treatment of a variety of corneal diseases.
Microbiome Fingerprint as Biomarker for Geographical Origin and Heredity in Crocus sativus: A Feasibility Study

Host–microbiome interactions are specific and not random, making them defining entities for the host. The hypothesis proposed by various researchers earlier, that both plants and animals harbor specific inheritable core microbiome, is being augmented in the present study. Additionally, a case for using microbial fingerprint as a biomarker, not only for plant identification but also as a geographical indicator, has been investigated, taking Crocus sativus, saffron, as a study material. Crocus sativus, a monogenetic herb, on account of its male sterility and vegetative propagation, is reported to lack genome based molecular markers. Cormosphere microbiome (microbiome associated with corm) has been compared across three geographical locations, in two continents, to identify the core and unique microbiome, during the vegetative phase of its growth. Microbiome analysis done at phylum and genus level, using next generation sequencing technology, revealed that cormosphere at three locations harbored common phyla. At genus level, 24 genera were found common to all three geographical locations, indicating them to be part of the core microbiome of saffron. However, there were some bacterial genera unique to Kashmir, Kishtwar, and Morocco that can be used to develop microbial markers/geographical indicators for saffron grown in these regions. This is a preliminary study, indicating that the location specific bacterial community can be used to develop microbial barcodes but needs further augmentation with high coverage data from other saffron growing geographical regions.
Thermal Regime and Variations in the Island Permafrost Near the Northern Permafrost Boundary in Xidatan, Qinghai–Tibet Plateau

Although the thermal regime and degradation of permafrost on the Qinghai-Tibet Plateau (QTP) have been widely documented, little information exists regarding the island permafrost in the area. Ground temperatures were therefore measured for 8 years (2013–2020) at a permafrost island and at two contrasting sites in the Xidatan region to elucidate the permafrost in this area. Results indicate that the ground temperatures in the island permafrost were markedly higher than those at the same depth in the nearby marginal permafrost and the interior continuous permafrost. In addition, a distinct increasing trend was observed in the ground temperature of the island permafrost over the past 8 years, and warming was signficanty faster in the deep soil than in the topsoil, indicating a bottom–up degradation pattern in the island permafrost. Moreover, due to the persistent increase in the thickness of the active-layer and the decrease in the depth of permafrost table, the permafrost island abruptly disappeared in 2018, which may be attributed to the anomalously high air temperatures that occurred in 2016 and 2017. The results of this study may provide references for understanding of the thermal regime and degradation process of island permafrost on the QTP.
Automatic Intra-/Extra-Dimensional Attentional Set-Shifting Task in Adolescent Mice

Adolescence is a developmental period crucial for the maturation of higher-order cognitive functions. Indeed, adolescence deficits in executive functions are strong predictors of increased vulnerability to several mental disabilities later in life. Here, we tested adolescent mice in a fully-automated attentional set-shifting task equivalent to the humans’ Wisconsin Card Sorting Test (WCST) and the Cambridge Neuropsychological Test Automated Battery Intra-/Extra-Dimensional set-shift task (ID/ED). Compared to an adult, adolescent mice required more time to complete the task (≈16 days), and a higher percentage failed to finish the entire task. Nevertheless, adolescent mice completing this demanding task showed an increased effort in solving the extradimensional shift stage (EDS) compared to previous stages. Moreover, we found that this paradigm can be used to detect early cognitive dysfunctions in adolescent genetically modified mice. Thus, this automatic paradigm provides a further tool to assess attentional control in adolescent mice, and the development of dysfunctional executive functions from adolescence to adulthood.
Evaluation of micronutrient potentials of seven commonly consumed indigenous spices from Nigeria

Micronutrient deficiencies remain a public health challenge globally, especially among developing countries of the world. Spices constitute an important part of daily diets of many populations but their nutritional roles are yet to be fully investigated. Micronutrient potentials of seven indigenous spices in Nigeria (Allium Ascalonicum, Piper guneensis, Aframomum melegueta, Zingiber officinale, Ocimum basilicum, Allium sativum, and Eugenia caryophyllata) were evaluated using standard methods of AOAC and atomic absorption spectrophotometry. The results revealed that 100g edible portion of the spices contained between 15.5 – 91.1g moisture, 0.29 – 1.77g ash, 7.00 – 750.00mg calcium, 74.00 – 261.00mg phosphorus, 98.1 – 356. 5µg β-carotene and 7.30 – 38.30mg ascorbic acid. O basilicum, P. guineensis and A. ascalonicum were very high in calcium content while Z. officinale, O. basilicum and A. melegueta were high in phosphorus and can be good sources of these minerals. All the spices were poor in iron and zinc, and might not make significant contribution to intake of these minerals. The spices can be good sources of βcarotene and ascorbic acids which are antioxidants. 100g edible portion of the spices can contribute between 0.7 – 75% calcium, 9.8 –35.7% β-carotene, and 12.1 – 63.8% ascorbic acid to % RDAs of consumers, hence their consumption should be encouraged.
Rapid Identification of QTL for Mesocotyl Length in Rice Through Combining QTL-seq and Genome-Wide Association Analysis

Mesocotyl is a crucial organ for pushing buds out of soil, which plays a vital role in seedling emergence and establishment in direct-seeded rice. Thus, the identification of quantitative trait loci (QTL) associated with mesocotyl length (ML) could accelerate genetic improvement of rice for direct seeding cultivation. In this study, QTL sequencing (QTL-seq) applied to 12 F2 populations identified 14 QTL for ML, which were distributed on chromosomes 1, 3, 4, 5, 6, 7, and 9 based on the Δ(SNP-index) or G-value statistics. Besides, a genome-wide association study (GWAS) using two diverse panels identified five unique QTL on chromosomes 1, 8, 9, and 12 (2), respectively, explaining 5.3–14.6% of the phenotypic variations. Among these QTL, seven were in the regions harboring known genes or QTLs, whereas the other 10 were potentially novel. Six of the QTL were stable across two or more populations. Eight high-confidence candidate genes related to ML were identified for the stable loci based on annotation and expression analyses. Association analysis revealed that two PCR gel-based markers for the loci co-located by QTL-seq and GWAS, Indel-Chr1:18932318 and Indel-Chr7:15404166 for loci qML1.3 and qML7.2 respectively, were significantly associated with ML in a collection of 140 accessions and could be used as breeder-friendly markers in further breeding.
Shifts in Estimated Preferred Directions During Simulated BMI Experiments With No Adaptation

Experiments with brain-machine interfaces (BMIs) reveal that the estimated preferred direction (EPD) of cortical motor units may shift following the transition to brain control. However, the cause of those shifts, and in particular, whether they imply neural adaptation, is an open issue. Here we address this question in simulations and theoretical analysis. Simulations are based on the assumption that the brain implements optimal state estimation and feedback control and that cortical motor neurons encode the estimated state and control vector. Our simulations successfully reproduce apparent shifts in EPDs observed in BMI experiments with different BMI filters, including linear, Kalman and re-calibrated Kalman filters, even with no neural adaptation. Theoretical analysis identifies the conditions for reducing those shifts. We demonstrate that simulations that better satisfy those conditions result in smaller shifts in EPDs. We conclude that the observed shifts in EPDs may result from experimental conditions, and in particular correlated velocities or tuning weights, even with no adaptation. Under the above assumptions, we show that if neurons are tuned differently to the estimated velocity, estimated position and control signal, the EPD with respect to actual velocity may not capture the real PD in which the neuron encodes the estimated velocity. Our investigation provides theoretical and simulation tools for better understanding shifts in EPD and BMI experiments.
Aging Affects Lower Limb Joint Moments and Muscle Responses to a Split-Belt Treadmill Perturbation

Age-related changes cause more fall-related injuries and impede the recoveries by older adults compared to younger adults. This study assessed the lower limb joint moments and muscle responses to split-belt treadmill perturbations in two groups (14 healthy young group [23.36 ± 2.90 years] and 14 healthy older group [70.93 ± 4.36 years]) who performed two trials of unexpected split-belt treadmill perturbations while walking on a programmable split-belt treadmill. A motion capture system quantified the lower limb joint moments, and a wireless electromyography system recorded the lower limb muscle responses. The compensatory limb's (i.e., the tripped limb's contralateral side) joint moments and muscle responses were computed during the pre-perturbation period (the five gait cycles before the onset of a split-belt treadmill perturbation) and the recovery period (from the split-belt treadmill perturbation to the baseline gait relying on the ground reaction forces' profile). Joint moments were assessed by maximum joint moments, and muscle responses were quantified by the normalization (%) and co-contraction index (CCI). Joint moments and muscle responses of the compensatory limb during the recovery period were significantly higher for the YG than the OG, and joint moments (e.g., knee flexion and extension and hip flexion moments) and muscle responses during the recovery period were higher compared to the pre-perturbation period for both groups. For CCI, the older group showed significantly higher co-contraction for biceps femoris/rectus femoris muscles than the young group during the recovery period. For both groups, co-contraction for biceps femoris/rectus femoris muscles was higher during the pre-perturbation period than the recovery period. The study confirmed that older adults compensated for muscle weakness by using lower joint moments and muscle activations and increasing muscle co-contractions to recover balance after split-belt treadmill perturbations. A better understanding of the recovery mechanisms of older adults who train on fall-inducing systems could improve therapeutic regimens.