Miracle-dz/UniFAR-FTUs huggingface dataset:
Multidimensional Extension of Multiple Indicators Multiple Causes Models to Detect DIF

A number of studies have found multiple indicators multiple causes (MIMIC) models to be an effective tool in detecting uniform differential item functioning (DIF) for individual items and item bundles. A recently developed MIMIC-interaction model is capable of detecting both uniform and nonuniform DIF in the unidimensional item response theory (IRT) framework. The goal of the current study is to extend the MIMIC-interaction model for detecting DIF in the context of multidimensional IRT modelling and examine the performance of the multidimensional MIMIC-interaction model under various simulation conditions with respect to Type I error and power rates. Simulation conditions include DIF pattern and magnitude, test length, correlation between latent traits, sample size, and latent mean differences between focal and reference groups. The results of this study indicate that power rates of the multidimensional MIMIC-interaction model under uniform DIF conditions were higher than those of nonuniform DIF conditions. When anchor item length and sample size increased, power for detecting DIF increased. Also, the equal latent mean condition tended to produce higher power rates than the different mean condition. Although the multidimensional MIMIC-interaction model was found to be a reasonably useful tool for identifying uniform DIF, the performance of the model in detecting nonuniform DIF appeared to be questionable.
Amyotrophic Lateral Sclerosis and Oxidative Stress: A Double-Blind Therapeutic Trial After Curcumin Supplementation.

OBJECTIVE To investigate the efficacy of curcumin oral supplementation (600 mg/day, Brainoil), a natural antioxidant compound, in Amyotrophic Lateral Sclerosis (ALS). METHODS Patients were randomized into two groups: Group A received placebo for 3 months, then Brainoil for the following 3 months, Group B took Brainoil for 6 months. The evaluations were conducted at basal (T0), after 3 months of double blinded Brainoil or placebo treatment (T1), and after the 3 month open-label phase (T2). Clinical evaluations and oxidative stress biomarkers, including oxidative protein products (AOPPs), ferric reducing ability (FRAP), total thiols (T-SH) and lactate, were evaluated, compared to a control group, during an incremental forearm exercise test. RESULTS Over the entire study Group B showed a stable score of the ALS-FRS-r which decreased in Group A (p<0.01), in parallel with a reduction of AOPPs (p<0.01) which was not detected into Group A. Also FRAP exercise values remained stable in Group B, while in Group A they were reduced without treatment at T1 (0.05T0 exercise lactate was lower compared to Group A (p<0.01). Compared to controls, the whole ALS population showed a greater oxidative stress (p<0.001), those treated with curcumin (Group B) exhibiting decreased exercise AOPPs at T2 with values approaching those of controls. CONCLUSION Although further studies are needed to confirm these data, treatment with curcumin shows encouraging results indicating a slight slowdown in disease progression, improving aerobic metabolism and oxidative damage, this also contributing to deepen knowledge into the pathogenic mechanisms of ALS.
Metformin and FTY720 Synergistically Induce Apoptosis in Multiple Myeloma Cells

Background/Aims: Patients with multiple myeloma (MM) invariably relapse with chemotherapy-resistant disease, underscoring the need for new therapeutic options that bypass these resistance mechanisms. Metformin is a widely prescribed antidiabetic drug with direct antitumor activity against various tumor cell lines. FTY720, also known as fingolimod, is an immune-modulating agent approved by the FDA as oral medication to treat the relapsing form of multiple sclerosis (MS). In recent years, FTY720 has attracted attention due to its anti-tumor activity. To explore an optimized combinational therapy, interactions between metformin and FTY720 were examined in MM cells. Methods: MTT assays were employed to assess the viability of MM cells. An apoptotic nucleosome assay was employed to measure apoptosis. Loss of mitochondrial membrane potential (MMP, ΔΨm) and cellular levels of ROS were measured by flow cytometry. qRT-PCR was used to analyze the expression of mRNAs. Western blotting assays were applied to measure the levels of proteins involved in different signaling pathways. Results: Coadministration of metformin and FTY720 synergistically inhibited the proliferation of MM cells. Increased levels of apoptosis, activation of caspase-3 and cleavage of PARP were detected after cotreatment with metformin and FTY720. These events were associated with modulation of Bcl-2 proteins, loss of MMP, ER stress induction, and inhibition of the PI3K/AKT/mTOR signaling pathway. The metformin/FTY720 regimen markedly induced ROS generation; moreover, apoptosis, ER stress and inhibition of PI3K/AKT/ mTOR were attenuated by the ROS scavenger NAC. Conclusions: Exposure to metformin in combination with FTY720 potently induces apoptosis in MM cells in a ROS-dependent manner, suggesting that a strategy combining these agents warrants further investigation in MM.
Source and amount of carbohydrate in the diet and inflammation in women with polycystic ovary syndrome

Abstract High carbohydrate intake and low-grade inflammation cooperate with insulin resistance and hyperandrogenism to constitute an interactive continuum acting on the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age characterised by oligo-anovulatory infertility and cardiometabolic disorders. The role of insulin in PCOS is pivotal both in regulating the activity of ovarian and liver enzymes, respectively involved in androgen production and in triggering low-grade inflammation usually reported to be associated with an insulin resistance, dyslipidaemia and cardiometabolic diseases. Although an acute hyperglycaemia induced by oral glucose loading may increase inflammation and oxidative stress by generating reactive oxygen species through different mechanisms, the postprandial glucose increment, commonly associated with the Western diet, represents the major contributor of chronic sustained hyperglycaemia and pro-inflammatory state. Together with hyperinsulinaemia, hyperandrogenism and low-grade inflammation, unhealthy diet should be viewed as a key component of the ‘deadly quartet’ of metabolic risk factors associated with PCOS pathophysiology. The identification of a tight diet–inflammation–health association makes the adoption of healthy nutritional approaches a primary preventive and therapeutic tool in women with PCOS, weakening insulin resistance and eventually promoting improvements of reproductive life and endocrine outcomes. The intriguing nutritional–endocrine connections operating in PCOS underline the role of expert nutritionists in the management of this syndrome. The aim of the present review is to provide an at-a-glance overview of the possible bi-directional mechanisms linking inflammation, androgen excess and carbohydrate intake in women with PCOS.
Age- and Gender-Specific Normative Values for the Self-Reported Foot and Ankle Score (SEFAS)

Background: The Self-Reported Foot and Ankle Score (SEFAS) is a foot- and ankle-specific patient-reported outcome measurement (PROM) score that has been validated with good results for a variety of foot and ankle disorders. SEFAS is sensitive detecting improvement or deterioration after surgery. However, normative values, required to put a specific patient’s summary score into perspective, are lacking. Methods: In this report, we included 396 population-based men and 383 women (43% of the invited individuals), age 20-89 years, who had completed the SEFAS questionnaire and questions regarding anthropometrics and health. We used Mann-Whitney U test to test gender differences and Spearman correlation coefficients to determine any association between SEFAS score and age. We present gender-specific median SEFAS scores with range and 5th to 95th percentiles and mean with standard deviation. Results: The SEFAS normative values were median 48 in men (range 11-48), 5th to 95th percentiles 31 to 48 and mean 45 ± 6, and in women, median 47 (range 6-48), 5th to 95th percentiles 23 to 48 and mean 43 ± 8 (gender comparison P < .001). SEFAS normative values correlated inversely with age (r = −0.12, P < .001). Conclusion: In the general population, older age was associated with lower SEFAS value, and men had higher values than women. The population-based normative SEFAS values provided in this study can facilitate quantification of disability related to foot and ankle with and without surgery in the foot and ankle. Level of Evidence: Level II, prospective comparative study.
Endovascular treatment of small cerebral arteriovenous malformations as a primary therapy

Purpose The patient population that would benefit most from endovascular curative treatment of intracranial arteriovenous malformations is not clearly established. The aim of the study was to determine the effect of curative embolization of cerebral arteriovenous malformations with special regard to radiographic and clinical outcomes and procedure-related complications. Material and methods Between January 2009 and December 2014, 18 patients with intracranial arteriovenous malformations were embolized with Onyx with intent to cure. There were 4 women and 14 men with a mean age of 40 years (range 10-62 years). Inclusion criteria were: maximal diameter of the lesions ≤ 3 cm and arterial supply consisting of no more than 2 major arteries. There were 5 (27.8 %) patients with ruptured and 13 (72.2%) with unruptured lesions. Mean arteriovenous malformations size was 2.3 cm (range 1.5-2.9 cm). Results Thirty-three procedures were performed in 18 patients. Total obliteration was achieved in 5 patients (27.8%). The most common reason for initial incomplete angiographic occlusion were unfavorable angioarchitectural features of arteriovenous malformations with the rate of 44.4%. The mean follow-up of patients with complete occlusion was 35.2 months (range 18-60 months). Complication rate was 12.1%. One patient had permanent neurological deficit with resulting morbidity of 5.6%. There were no deaths. Conclusions Embolization of intracranial arteriovenous malformations plays a limited role as a sole therapeutic modality even in terms of small lesions with two or less arterial feeders, although larger prospective series are necessary to confirm your findings. Associated complications are not trivial and should be considered when choosing this form of treatment.
The impact of exercise training on the lipid peroxidation metabolomic profile and respiratory infection risk in older adults

Abstract Aging is associated with oxidative stress that may increase susceptibility to respiratory infections (RIs). We aimed to assess the impact of exercise training on the risk of RIs in older adults and on a targeted metabolomic profile of stress oxidative lipid peroxidation-related metabolites. Methods: In an 8-month clinical trial, 38 participants over 60 years of age were allocated to an exercise group (EG), in which participants underwent 90-min training sessions three times/week(n = 20), or a control group (CG), in which participants maintained daily physical activities(n = 18). Daily respiratory symptoms and RIs number and severity were collected. Serum by-products were assessed by comprehensive two-dimensional gas chromatography coupled to mass spectrometry with time of flight analyzer. Serum metabolomic profiling comprised 76 metabolites (alcohols, aldehydes, alkanes, and ketones). Principal components analysis and ANOVA-simultaneous component analysis were used to evaluate the metabolomic profile change. Results: The odds ratio of RIs for the EG was 2.0 CI 95% [0.2;25]. The incidence of RIs was 47% [23;70] in the EG vs. 44%[12;77] in the CG. The metabolomic profiling showed that alkanes and aldehydes classes differed between the EG and the CG before and after intervention. A calibration model showed a relation between the metabolites from four main classes (ketones, alcohols, alkanes and aldehydes) and the prediction of the number of RIs. Conclusion: Moderate exercise training, in older adults, compared with no exercise in controls, did not show a difference in the risk of RIs. A pattern of lipid peroxidation was associated with the number of RIs.
A full-scale clinical prototype for proton range verification using prompt gamma-ray spectroscopy

We present a full-scale clinical prototype system for in vivo range verification of proton pencil-beams using the prompt gamma-ray spectroscopy method. The detection system consists of eight LaBr3 scintillators and a tungsten collimator, mounted on a rotating frame. Custom electronics and calibration algorithms have been developed for the measurement of energy- and time-resolved gamma-ray spectra during proton irradiation at a clinical dose rate. Using experimentally determined nuclear reaction cross sections and a GPU-accelerated Monte Carlo simulation, a detailed model of the expected gamma-ray emissions is created for each individual pencil-beam. The absolute range of the proton pencil-beams is determined by minimizing the discrepancy between the measurement and this model, leaving the absolute range of the beam and the elemental concentrations of the irradiated matter as free parameters. The system was characterized in a clinical-like situation by irradiating different phantoms with a scanning pencil-beam. A dose of 0.9 Gy was delivered to a cm3 target with a beam current of 2 nA incident on the phantom. Different range shifters and materials were used to test the robustness of the verification method and to calculate the accuracy of the detected range. The absolute proton range was determined for each spot of the distal energy layer with a mean statistical precision of 1.1 mm at a 95% confidence level and a mean systematic deviation of 0.5 mm, when aggregating pencil-beam spots within a cylindrical region of 10 mm radius and 10 mm depth. Small range errors that we introduced were successfully detected and even large differences in the elemental composition do not affect the range verification accuracy. These results show that our system is suitable for range verification during patient treatments in our upcoming clinical study.
Epidermal growth factor induces STAT1 expression to exacerbate the IFNr‐mediated PD‐L1 axis in epidermal growth factor receptor‐positive cancers

The epidermal growth factor (EGF) receptor (EGFR) overexpressed in many cancers, including lung and head and neck cancers, and is involved in cancer cell progression and survival. PD‐L1, increases in tumor cells to evade and inhibit CD8+ T cells, is a clinical immunotherapeutic target. This study investigated the molecular mechanism of EGF on regulating PD‐L1 in EGFR‐positive cancers and determined potential agents to reduce PD‐L1 expression. RNA sequencing (RNAseq) and bioinformatics analysis were performed to determine potential driver genes that regulate PD‐L1 in tumor cells‐derived tumorspheres which mimicking cancer stem cells. Then, the specific inhibitors targeting EGFR were applied to reduce the expression of PD‐L1 in vitro and in vivo. We validated that EGF could induce PD‐L1 expression in the selected EGFR‐positive cancers. RNAseq results revealed that STAT1 increased as a driver gene in KOSC‐3‐derived tumorspheres; these data were analyzed using PANTHER followed by NetworkAnalyst. The blockade of EGFR by afatinib resulted in decreased STAT1 and IRF‐1 levels, both are transcriptional factors of PD‐L1, and disabled the IFNr‐STAT1‐mediated PD‐L1 axis in vitro and in vivo. Moreover, STAT1 knockdown significantly reduced EGF‐mediated PD‐L1 expression, and ruxolitinib, a JAK1/JAK2 inhibitor, significantly inhibited STAT1 phosphorylation to reduce the IFNr‐mediated PD‐L1 axis. These results indicate that EGF exacerbates PD‐L1 by increasing the protein levels of STAT1 to enforce the IFNr‐JAK1/2‐mediated signaling axis in selected EGFR‐positive cancers. The inhibition of EGFR by afatinib significantly reduced PD‐L1 and may be a potential strategy for enhancing immunotherapeutic efficacy.
From microbial eukaryotes to metazoan vertebrates: Wide spectrum paleo‐diversity in sedimentary ancient DNA over the last ~14,500 years

Most studies that utilize ancient DNA have focused on specific groups of organisms or even single species. Instead, the whole biodiversity of eukaryotes can be described using universal phylogenetic marker genes found within well‐preserved sediment cores that cover the post‐glacial period. Sedimentary ancient DNA samples from Lake Lielais Svētiņu, eastern Latvia, at a core depth of 1,050 cm in ~150 year intervals were used to determine phylotaxonomy in domain Eukaryota. Phylotaxonomic affiliation of >1,200 eukaryotic phylotypes revealed high richness in all major eukaryotic groups—Alveolata, Stramenopiles, Cercozoa, Chlorophyta, Charophyta, Nucletmycea, and Holozoa. The share of organisms that originate from terrestrial ecosystems was about one third, of which the most abundant molecular operational taxonomic units were Fungi and tracheal/vascular plants, which demonstrates the usefulness of using lake sediments to reconstruct the terrestrial paleoecosystems that surround them. Phylotypes that originate from the lake ecosystem belonged to various planktonic organisms; phyto‐, proto,‐ and macrozooplankton, and vascular aquatic plants. We observed greater richness of several planktonic organisms that can be associated with higher trophic status during the warm climate period between 4,000 and 8,000 years ago and an increase in eukaryotic richness possibly associated with moderate human impact over the last 2,000 years.
Severe and Enduring Anorexia Nervosa? Illness Severity and Duration Are Unrelated to Outcomes From Cognitive Behaviour Therapy

Objective: The present study aimed to examine whether Anorexia Nervosa (AN) illness severity or duration is associated with retention or treatment response in outpatient, enhanced cognitive–behavioral therapy (CBT-E). Method: Patients with a confirmed AN diagnosis (N = 134) completed measures of eating disorder symptoms and quality of life, and had their BMI objectively measured before, during, and after treatment. We evaluated whether illness severity or duration predicted treatment outcomes, using longitudinal regression models. Results: Greater levels of illness severity and duration were not associated with poorer treatment outcomes. Conclusions: Patients with more severe or long-standing AN illness did just as well in CBT-E as any other patient starting treatment. Therefore, classifying individuals as “severe and enduring” appears to lack clinical utility in CBT-E. Clinicians should continue to administer evidence-supported treatments such as CBT-E for patients with AN, regardless of duration or severity of AN illness.
Topical efinaconazole: A promising therapeutic medication for tinea unguium

We treated tinea unguium (onychomycosis caused by dermatophytes) patients with efinaconazole 10% solution. All patients with tinea unguium who tested positive for fungi in fingernails and toenails, regardless of age or severity, were eligible for the treatment. The number of patients was 106, consisting of 43 men and 63 women with a mean age of 66.7 years. The patients were treated with efinaconazole for a mean treatment duration of 38.1 weeks. Therapeutic efficacy was rated on a 5‐point scale as follows: “cured”, “markedly improved”, “improved”, “slightly improved” or “no change”. A single nail was selected in each patient as the target nail. Selected nails were the big toenails with less than 50% involvement in 25 patients, the big toenails with 50% or more involvement in 52 patients, the fingernails in 10 patients and the second to fifth toenails in 19 patients with a mean treatment duration of 43.9, 38.1, 38.7 and 33.7 weeks, respectively. All groups showed an improvement in the percentage involvement from 30.6% to 9.8%, 77.6% to 35.7%, 82.7% to 17.6% and 80.3% to 15.5%, respectively (P < 0.01). The improvement rate (i.e. percentage of those rated as improved and better) was 76.0%, 65.4%, 80.0% and 89.5%, respectively. Efinaconazole 10% topical solution is beneficial for patients, regardless of age, severity or clinical type.
Amygdala volume is associated with risky probability cognition in gambling disorder

Gambling disorder (GD) is characterized by continual gambling despite negative consequences. Risky decision‐making is a hallmark of the disorder. We applied a tool from behavioral economics for assessing probability cognition in both gain and loss domains to GD. We aimed to examine the alteration of probability cognition and its relationship with brain structure in GD. Forty‐six GD patients and 52 age‐matched healthy controls (HCs) conducted a risky choice task in which subjects should choose between a sure and a risky option in both loss and gain domains. The distortion and elevation parameters of the probability weighting function were estimated. We compared the parameters between GD and HC and examined their relationships with the striatum and amygdala volumes in GD. GD showed greater elevation parameter in the gain domain and smaller regional gray matter volume in the left amygdala than HC. The elevation parameter in the gain domain showed a negative correlation with the left amygdala volume in GD. Altered probability cognition in the gain domain but not in the loss domain might be more relevant to risky decision‐making in GD. Our findings indicate that alteration in the amygdala might play a significant role in risky decision‐making of GD. Longitudinal studies are recommended to examine the causal relationship between brain abnormalities and risky decision‐making in GD.
Anatomy of the forelimb musculature and ligaments of Psittacus erithacus (Aves: Psittaciformes)

Parrots (order Psittaciformes) are a rather homogeneous group of birds that can be easily distinguished by the notably modified morphology of the skull and hindlimb. Detailed description of the forelimb morphology in these birds has never been provided, though parrots are often used as model objects in flight studies. Parrots are also considered the closest living relatives of the perching birds (Passeriformes), and thus knowledge of the wing morphology in Psittaciformes is important for understanding the evolution of the locomotor apparatus on the way to the most speciose group of birds. Here we provide a comprehensive illustrated description of the wing morphology (musculature and ligaments) of the African grey parrot (Psittacus erithacus) and compare it with several closely related taxa of the high clade Eufalconimorphae and more distantly related outgroups (based on personal dissections and literature data). We note a general similarity of the wing musculature between P. erithacus and Falconidae. A number of features common with the outgroup Columbidae supports a generally plesiomorphic structure of the forelimb in parrots as compared with the Passeriformes. Nevertheless, the wing of the Psittaciformes displays a series of structural (likely autapomorphic) modifications, which can be explained in terms of adaptations for flight with vertical body. An analysis of the anatomical data for parrots (ratio of wing elevators and highly unusual development of the M. supracoracoideus), which is based on the current experiment‐based knowledge of the flapping flight in birds, allows us to hypothesize that parrots are able to produce useful aerodynamic force during the upstroke, which is also known for pigeons and hummingbirds. This supposed ability of vertical flight and the zygodactyl foot together link the origin of parrots with the dense (likely tropical) forests.