Miracle-dz/UniFAR-FTUs huggingface dataset:
Common and Contrasting Characteristics of the Chronic Soft-Tissue Pain Conditions Fibromyalgia and Lipedema

Objective To examine the common and specific characteristics of fibromyalgia and lipedema, two chronic soft-tissue pain syndromes without curative therapy options. Methods Diseases’ characteristics were compared using the findings of extensive literature and the empiric data from two cohorts, both fulfilling standardized diagnostic criteria. Outcome was measured by various socio-demographics, the generic Short Form 36 (SF-36), the Fibromyalgia Severity Questionnaire (FSQ), and the 6-minute walk distance (6MWD). Empiric SF-36 data were compared to specific population-based norms and between the diagnostic groups, using standardized mean differences (SMD). Results Female participants with fibromyalgia (n = 77) and lipedema (n = 112) showed comparable education levels and living situations. Lipedema cases were, on average, 3.9 years younger and BMI 6.3kg/m2 more obese. Women with fibromyalgia smoked more, did less sport, had more comorbidities, and worked less. Compared to the norms, health in fibromyalgia was worse than expected by SMD = –1.60 to –2.35 and in lipedema by –0.44 to –0.82 on the SF-36. The score differences between the two conditions ranged from SMD = –0.96 to –1.34 (all p < 0.001) on the SF-36 and the FSQ. For the inpatients (n = 77 fibromyalgia, n = 38 lipedema), the 6MWD was comparable (SMD = –0.09, p = 0.640). These findings were consistent with detailed data from the literature reviewed. Discussion Fibromyalgia and lipedema share characteristics of clinical phenomenology and comorbid conditions. Disease perception is more pronounced in fibromyalgia than in lipedema, especially in social and role dysfunction, whereas the walking distance was similar for both syndromes. This difference may be explicable by limited coping skills in fibromyalgia.
Auditory speed processing in sighted and blind individuals

Multisensory experience is crucial for developing a coherent perception of the world. In this context, vision and audition are essential tools to scaffold spatial and temporal representations, respectively. Since speed encompasses both space and time, investigating this dimension in blindness allows deepening the relationship between sensory modalities and the two representation domains. In the present study, we hypothesized that visual deprivation influences the use of spatial and temporal cues underlying acoustic speed perception. To this end, ten early blind and ten blindfolded sighted participants performed a speed discrimination task in which spatial, temporal, or both cues were available to infer moving sounds’ velocity. The results indicated that both sighted and early blind participants preferentially relied on temporal cues to determine stimuli speed, by following an assumption that identified as faster those sounds with a shorter duration. However, in some cases, this temporal assumption produces a misperception of the stimulus speed that negatively affected participants’ performance. Interestingly, early blind participants were more influenced by this misleading temporal assumption than sighted controls, resulting in a stronger impairment in the speed discrimination performance. These findings demonstrate that the absence of visual experience in early life increases the auditory system’s preference for the time domain and, consequentially, affects the perception of speed through audition.
Improving the Lung Cancer Clinical Trial Development by Incorporating Competing Risk Factors

Introduction Distinct from other diseases, as cancer progresses, both the symptoms and treatments evolve, resulting in a complex, time-dependent relationship. Many competing risk factors influence the outcome of cancer. An improved method was used to evaluate the data from 6 non-small-cell lung cancer (NSCLC) clinical trials combined in our center since 2016 to deal with the bias caused by competing risk factors. Material and Methods. Data of 118 lung cancer patients were collected from 2016 to 2020. Fine and Gray's model for competing risk was used to evaluate survival of different treatment group compares with the classic survival analysis model. Results Immunotherapy had better progression-free survival than chemotherapy. (HR: 0.62, 95% CI: 0.41-0.95, p = 0.0260). However, there were no significant differences in patients who withdrew due to treatment-related adverse events from different groups. (Z = 0.0508, p = 0.8217). The PD-1/PD-L1 inhibitors in our study did not significantly improve overall survival compared with chemotherapy (HR:0.77, 95% CI:0.48-1.24, p = 0.2812), estimated 1-year overall survival rates were 55% and 46%, and 3-year overall survival rates were 17% and 10%, respectively. Conclusion When the outcome caused by competing risk exists, the corresponding competing risk model method should be adopted to eliminate the bias caused by the classic survival analysis.
Extraction Optimization of Polysaccharides From Corn Silk and Their Antioxidant Activities in vitro and in vivo

Response surface technique was employed for improving the extraction of corn silk polysaccharides (CSP). Temperature, liquid-to-solid ratio, and per extraction time were all examined as separate factors. The optimal extraction parameters were determined by fitting experimental data to a second-order polynomial; a liquid-to-solid ratio of 21.5 ml/g, temperature equivalent to 88°C, and extraction time of 1.87 h. The experimental yield of the extracted polysaccharides following the application of these conditions was 4.33 ± 0.08% (dry weight), which fit quite well with the predicted value. CSP’s strong scavenging capabilities against hydroxyls, 1,1-diphenyl-2-picrylhydrazyl radicals, and superoxide anions along with its excellent reducing potential, were demonstrated in an in vitro antioxidant experiment. Meanwhile, in vivo testing revealed that CSP substantially enhanced glutathione peroxidase and superoxide dismutase activities. The Malondialdehyde levels in the liver and serum of aged mice also underwent a decrease. This study found that CSP has a substantial antioxidant potential in vitro and in vivo, suggesting that it might be used as an antioxidant in food and medicine.
The Positive Role and Mechanism of Herbal Medicine in Parkinson's Disease

Parkinson's disease (PD) is a complex neurodegenerative disease, manifested by the progressive functional impairment of the midbrain nigral dopaminergic neurons. Due to the unclear underlying pathogenesis, disease-modifying drugs for PD remain elusive. In Asia, such as in China and India, herbal medicines have been used in the treatment of neurodegenerative disease for thousands of years, which recently attracted considerable attention because of the development of curative drugs for PD. In this review, we first summarized the pathogenic factors of PD including protein aggregation, mitochondrial dysfunction, ion accumulation, neuroinflammation, and oxidative stress, and the related recent advances. Secondly, we summarized 32 Chinese herbal medicines (belonging to 24 genera, such as Acanthopanax, Alpinia, and Astragalus), 22 Chinese traditional herbal formulations, and 3 Indian herbal medicines, of which the ethanol/water extraction or main bioactive compounds have been extensively investigated on PD models both in vitro and in vivo. We elaborately provided pictures of the representative herbs and the structural formula of the bioactive components (such as leutheroside B and astragaloside IV) of the herbal medicines. Also, we specified the potential targets of the bioactive compounds or extractions of herbs in view of the signaling pathways such as PI3K, NF-κB, and AMPK which are implicated in oxidative and inflammatory stress in neurons. We consider that this knowledge of herbal medicines or their bioactive components can be favorable for the development of disease-modifying drugs for PD.
Olaparib: A Clinically Applied PARP Inhibitor Protects from Experimental Crohn's Disease and Maintains Barrier Integrity by Improving Bioenergetics through Rescuing Glycolysis in Colonic Epithelial Cells

Crohn's disease (CD) is an inflammatory disorder of the intestines characterized by epithelial barrier dysfunction and mucosal damage. The activity of poly(ADP-ribose) polymerase-1 (PARP-1) is deeply involved in the pathomechanism of inflammation since it leads to energy depletion and mitochondrial failure in cells. Focusing on the epithelial barrier integrity and bioenergetics of epithelial cells, we investigated whether the clinically applied PARP inhibitor olaparib might improve experimental CD. We used the oral PARP inhibitor olaparib in the 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced mouse colitis model. Inflammatory scoring, cytokine levels, colon histology, hematological analysis, and intestinal permeability were studied. Caco-2 monolayer culture was utilized as an epithelial barrier model, on which we used qPCR and light microscopy imaging, and measured impedance-based barrier integrity, FITC-dextran permeability, apoptosis, mitochondrial oxygen consumption rate, and extracellular acidification rate. Olaparib reduced the inflammation score, the concentration of IL-1β and IL-6, enhanced the level of IL-10, and decreased the intestinal permeability in TNBS-colitis. Blood cell ratios, such as lymphocyte to monocyte ratio, platelet to lymphocyte ratio, and neutrophil to lymphocyte ratio were improved. In H2O2-treated Caco-2 monolayer, olaparib decreased morphological changes, barrier permeability, and preserved barrier integrity. In oxidative stress, olaparib enhanced glycolysis (extracellular acidification rate), and it improved mitochondrial function (mitochondrial coupling efficiency, maximal respiration, and spare respiratory capacity) in epithelial cells. Olaparib, a PARP inhibitor used in human cancer therapy, improved experimental CD and protected intestinal barrier integrity by preventing its energetic collapse; therefore, it could be repurposed for the therapy of Crohn's disease.
Weak spatial-genetic structure in a native invasive, the southern pine beetle (Dendroctonus frontalis), across the eastern United States

The southern pine beetle, Dendroctonus frontalis, is a native pest of pine trees that has recently expanded its range into the northeastern United States. Understanding its colonization, dispersal, and connectivity will be critical for mitigating negative economic and ecological impacts in the newly invaded areas. Characterization of spatial-genetic structure can contribute to this; however, previous studies have reached different conclusions about regional population genetic structure, with one study reporting a weak east-west pattern, and the most recent reporting an absence of structure. Here we systematically assessed several explanations for the absence of spatial-genetic structure. To do this, we developed nine new microsatellite markers and combined them with an existing 24-locus data matrix for the same individuals. We then reanalyzed this full dataset alongside datasets in which certain loci were omitted with the goal of creating more favorable signal to noise ratios. We also partitioned the data based on the sex of D. frontalis individuals, and then employed a broad suite of genotypic clustering and isolation-by-distance (IBD) analyses. We found that neither inadequate information content in the molecular marker set, nor unfavorable signal-to-noise ratio, nor insensitivity of the analytical approaches could explain the absence of structure. Regardless of dataset composition, there was little evidence for clusters (i.e., distinct geo-genetic groups) or clines (i.e., gradients of increasing allele frequency differences over larger geographic distances), with one exception: significant IBD was repeatedly detected using an individual-based measure of relatedness whenever datasets included males (but not for female-only datasets). This is strongly indicative of broad-scale female-biased dispersal, which has not previously been reported for D. frontalis, in part owing to logistical limitations of direct approaches (e.g., capture-mark-recapture). Weak spatial-genetic structure suggests long-distance connectivity and that gene flow is high, but additional research is needed to understand range expansion and outbreak dynamics in this species using alternate approaches.
Carbon-Ion Beam Irradiation and the miR-200c Mimic Effectively Eradicate Pancreatic Cancer Stem Cells Under in vitro and in vivo Conditions

Purpose The study investigated the molecular mechanisms that killed pancreatic cancer cells, including cancer stem cells (CSCs), by carbon ion beam irradiation alone or in combination with miRNA-200c under in vitro and in vivo conditions. Methods Human pancreatic cancer (PC) cells, PANC1 and PK45, were treated with carbon-ion beam irradiation alone or in combination with microRNA-200c (miR-200c) mimic. Cell viability assay, colony and spheroid formation assay, quantitative real-time PCR analysis of apoptosis-, autophagy-, and angiogenesis-related gene expression, xenograft tumor control and histopathological analyses were performed. Results The cell viability assay showed that transfection of the miRNA-200c (10 nM) mimic into pancreatic CSC (CD44+/ESA+) and non-CSC (CD44-/ESA-) significantly suppressed proliferation of both types of cell populations described above. Combining carbon-ion beam irradiation with the miRNA-200c mimic significantly reduced the colony as well as spheroid formation abilities compared to that observed with the treatment of carbon-ion beam alone or X-ray irradiation combined with the miRNA-200c mimic. Moreover, the combination of carbon ion beam irradiation and miRNA-200c mimic increased the expression of apoptosis-related gene BAX, autophagy-related genes Beclin-1 and p62, addition of gemcitabine (GEM) further enhanced the expression of these genes. In vivo data showed that carbon-ion beam irradiation in combination with the miRNA-200c mimic effectively suppressed xenograft tumor growth and significantly induced tumor necrosis and cavitation. Conclusion The combination of miRNA-200c mimic and carbon ion beam irradiation may be powerful radiotherapy that significantly kills pancreatic cancer cells containing CSCs and enhances the effect of carbon-ion beam irradiation compared to carbon-ion beam irradiation alone.
Epidemiology of Isolated Impaired Glucose Tolerance Among Adults Aged Above 50 Years in Rural China

Introduction Isolated impaired glucose tolerance (i–IGT) is a subtype of prediabetes in which an individual demonstrates elevated 2-h post-glucose load glucose levels but normal fasting plasma glucose levels. However, few studies have explored the prevalence and risk factors of i–IGT among adults in rural China. Thus, we aimed to explore the prevalence and risk factors of i–IGT among adults ≥50 years old in a low-income, rural population in China. Materials and Methods Individuals aged ≥50 years with normal fasting plasma glucose levels were included in the final analysis. Fasting and 2-h venous blood samples were collected to assess the selected parameter measurements. Results A total of 2175 individuals were included in this study. The i–IGT prevalence was 22.9% and significantly higher among females than among males (P<0.05). Older age [odds ratio (OR), 1.606; 95% confidence interval (CI), 1.101–2.342; P=0.014), hypertension (OR, 1.554; 95% CI, 1.152–2.019; P=0.004), and central obesity (OR, 1.395; 95% CI, 1.099–1.771; P=0.006) were associated with i–IGT. Moreover, white blood cell (OR, 1.089; 95% CI, 1.009–1.175; P=0.029), high-sensitivity C-reactive protein (OR, 1.049; 95% CI, 1.020–1.078; P=0.001), serum uric acid (OR, 1.0003; 95% CI, 1.001–1.004; P=0.001), triglyceride (OR, 1.540; 95% CI, 1.105–2.147; P=0.011), and alanine aminotransferase (OR, 1.012; 95% CI, 1.004–1.021; P=0.004) levels were also linked to i–IGT in the analyzed population. Conclusion Health promotion education and a standardized approach to managing body weight, BP, and lipid and uric acid levels would benefit this low-income population in rural China for reducing the risk of cardiovascular disease.
The biomechanical characteristics of the strongman atlas stone lift

Background The atlas stone lift is a popular strongman exercise where athletes are required to pick up a large, spherical, concrete stone and pass it over a bar or place it on to a ledge. The aim of this study was to use ecologically realistic training loads and set formats to (1) establish the preliminary biomechanical characteristics of athletes performing the atlas stone lift; (2) identify any biomechanical differences between male and female athletes performing the atlas stone lift; and (3) determine temporal and kinematic differences between repetitions of a set of atlas stones of incremental mass. Methods Kinematic measures of hip, knee and ankle joint angle, and temporal measures of phase and repetition duration were collected whilst 20 experienced strongman athletes (female: n = 8, male: n = 12) performed three sets of four stone lifts of incremental mass (up to 85% one repetition maximum) over a fixed-height bar. Results The atlas stone lift was categorised in to five phases: the recovery, initial grip, first pull, lap and second pull phase. The atlas stone lift could be biomechanically characterised by maximal hip and moderate knee flexion and ankle dorsiflexion at the beginning of the first pull; moderate hip and knee flexion and moderate ankle plantarflexion at the beginning of the lap phase; moderate hip and maximal knee flexion and ankle dorsiflexion at the beginning of the second pull phase; and maximal hip, knee extension and ankle plantarflexion at lift completion. When compared with male athletes, female athletes most notably exhibited: greater hip flexion at the beginning of the first pull, lap and second pull phase and at lift completion; and a shorter second pull phase duration. Independent of sex, first pull and lap phase hip and ankle range of motion (ROM) were generally smaller in repetition one than the final three repetitions, while phase and total repetition duration increased throughout the set. Two-way interactions between sex and repetition were identified. Male athletes displayed smaller hip ROM during the second pull phase of the first three repetitions when compared with the final repetition and smaller hip extension at lift completion during the first two repetitions when compared with the final two repetitions. Female athletes did not display these between-repetition differences. Conclusions Some of the between-sex biomechanical differences observed were suggested to be the result of between-sex anthropometric differences. Between-repetition differences observed may be attributed to the increase in stone mass and acute fatigue. The biomechanical characteristics of the atlas stone lift shared similarities with the previously researched Romanian deadlift and front squat. Strongman athletes, coaches and strength and conditioning coaches are recommended to take advantage of these similarities to achieve greater training adaptations and thus performance in the atlas stone lift and its similar movements.
C-DeepTrust: A Context-Aware Deep Trust Prediction Model in Online Social Networks

Trust prediction provides valuable support for decision making, information dissemination, and product promotion in online social networks. As a complex concept in the social network community, trust relationships among people can be established virtually based on: 1) their interaction behaviors, e.g., the ratings and comments that they provided; 2) the contextual information associated with their interactions, e.g., location and culture; and 3) the relative temporal features of interactions and the time periods when the trust relationships hold. Most of the existing works only focus on some aspects of trust, and there is not a comprehensive study of user trust development that considers and incorporates 1)–3) in trust prediction. In this article, we propose a context-aware deep trust prediction model C-DeepTrust to fill this gap. First, we conduct user feature modeling to obtain the user’s static and dynamic preference features in each context. Static user preference features are obtained from all the ratings and reviews that a user provided, while dynamic user preference features are obtained from the items rated/reviewed by the user in time series. The obtained context-aware user features are then combined and fed into the multilayer projection structure to further mine the context-aware latent features. Finally, the context-aware trust relationships between users are calculated by their context-aware feature vector cosine similarities according to the social homophily theory, which shows a pervasive property of social networks that trust relationships are more likely to be developed among similar people. Extensive experiments conducted on two real-world datasets show the superior performance of our approach compared with the representative baseline methods.
Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase

Abstract Background At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported. Methods We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021. Results The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. Conclusions The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)