Miracle-dz/UniFAR-FTUs huggingface dataset:
A Stage-Based Approach to Therapy in Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD.
Prevalence of acute kidney injury in a population of hospitalized horses

Abstract Background Hospital‐acquired acute kidney injury (AKI) in humans and dogs increases morbidity and nonsurvival. Azotemia at presentation has been associated with a poor outcome in horses; however, prevalence and consequences of hospital‐acquired AKI are unreported. Hypothesis/Objectives To evaluate the prevalence of AKI in hospitalized horses, risk factors associated with AKI, and the effect of AKI on short‐term survival. We hypothesized that the prevalence of AKI in horses is similar to that reported in other domestic mammalian species and would be associated with nonsurvival. Animals Adult horses hospitalized for >2 days from which a minimum of 2 measurements of serum creatinine concentration were available. Methods Retrospective cohort study. Clinical records were reviewed and horses grouped according to their baseline serum creatinine concentration and change in serum creatinine concentration from baseline. The associations between signalment, diagnosis, and treatment variables, and the presence of azotemia or AKI were assessed using multinomial logistic regression. The relationship between these conditions and survival to discharge was evaluated. Results Three hundred twenty‐five horses were included; 4.3% (14/325) had azotemia at baseline and 14.8% (48/325) developed AKI. There were no significant associations between investigated risk factors and development of AKI. The presence of azotemia and AKI did not significantly affect survival to discharge (P = .08 and .81, respectively). Conclusions and Clinical Importance The prevalence of AKI in this population of hospitalized horses is similar to that reported in dogs and humans; however, in this study population, there was less impact on morbidity and short‐term survival.
BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation

There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistry, using a ligustrazine–betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional Prunella vulgaris plaster, BA-12 was synthesized according to our previous study, as it exhibited better antitumor activities than other derivatives on human bladder carcinoma cells (T24); it was then uploaded for target prediction. Secondly, the efficacy and biotoxicity of BA-12 on angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs), a quail chick chorioallantoic membrane, and Caenorhabditis elegans. According to the prediction results, the main mechanisms of BA-12 were metabolic pathways. Thus, multiple metabolomics approaches were applied to reveal the mechanisms of BA-12. Finally, the predictive mechanisms of BA-12 on glutathione metabolism and glycerophospholipid metabolism activation were validated using targeted metabolomics and pharmacological assays. This strategy may provide a reference for highly efficient drug discovery, with the aim of sharing TCM wisdom for unmet clinical needs.
Phosphorylation of importin-α1 by CDK1–cyclin B1 controls mitotic spindle assembly

ABSTRACT Importin-α serves as an adaptor linking importin-β to proteins carrying a nuclear localization sequence (NLS). During interphase, this interaction enables nuclear protein import, while in mitosis it regulates spindle assembly factors (SAFs) and controls microtubule nucleation, stabilization and spindle function. Here, we show that human importin-α1 is regulated during the cell cycle and is phosphorylated at two sites (threonine 9 and serine 62) during mitosis by the major mitotic protein kinase CDK1–cyclin B. Mutational analysis indicates that the mitotic phosphorylation of importin-α1 inhibits its binding to importin-β and promotes the release of TPX2 and KIFC1, which are then targeted like importin-β to the spindle. Loss of importin-α1 or expression of a non-phosphorylated mutant of importin-α1 results in the formation of shortened spindles with reduced microtubule density and induces a prolonged metaphase, whereas phosphorylation-mimicking mutants are functional in mitosis. We propose that phosphorylation of importin-α1 is a general mechanism for the spatial and temporal control of mitotic spindle assembly by CDK1–cyclin B1 that acts through the release of SAFs such as TPX2 and KIFC1 from inhibitory complexes that restrict spindle assembly. Summary: Phosphorylation of importin-α1 by cyclin-dependent kinase 1 provides spatial and temporal control of mitotic spindle assembly through the release of spindle-assembly factors from inhibitory complexes during mitosis.
Physical activity, dietary calcium to magnesium intake and mortality in the National Health and Examination Survey 1999–2006 cohort

Calcium and magnesium affect muscle mass and function. Magnesium and calcium are also important for optimal vitamin D status. Vitamin D status modifies the associations between physical activity and risk of incident cardiovascular disease (CVD) and CVD mortality. However, no study examined whether levels of magnesium and calcium and the ratio of dietary calcium to magnesium (Ca:Mg) intake modify the relationship between physical activity and mortality. We included 20,295 National Health and Nutrition Examination Survey participants (1999–2006) aged >20 years with complete dietary, physical activity and mortality data (2,663 deaths). We assessed physical activity based on public health guidelines and sex‐specific tertiles of MET‐minutes/week. We used Cox proportional hazards models adjusted for potential confounding factors and stratified by the intakes of magnesium, calcium, Ca:Mg ratio. We found higher physical activity was significantly associated with reduced risk of total mortality and cause‐specific mortality, regardless of Ca:Mg ratio, magnesium or calcium intake. In contrast, both moderate and high physical activity were significantly associated with substantially reduced risks of mortality due to cancer when magnesium intake was above the RDA level. We also found higher physical activity was significantly associated with a reduced risk of mortality due to cancer only when Ca:Mg ratios were between 1.7 and 2.6, although the interaction was not significant. Overall, dietary magnesium and, potentially, the Ca:Mg ratio modify the relationship between physical activity and cause‐specific mortality. Further study is important to understand the modifying effects of the balance between calcium and magnesium intake on physical activity for chronic disease prevention.
Target Doppler Rate Estimation Based on the Complex Phase of STFT in Passive Forward Scattering Radar

This article presents a novel approach to the estimation of motion parameters of objects in passive forward scattering radars (PFSR). In such systems, most frequency modulated signals which are used have parameters that depend on the geometry of a radar scene and an object’s motion. Worth noting is that in bistatic (or multistatic) radars forward scattering geometry is present thus in this case only Doppler measurements are available while the range measurement is unambiguous. In this article the modulation factor, also called the Doppler rate, was determined based on the chirp rate (equivalent Doppler rate) estimation concept in the time-frequency (TF) domain. This approach utilizes the idea of the complex phase of the short-time Fourier transform (STFT) and its modification known from the literature. Mathematical dependencies were implemented and verified and the simulation results were described. The accuracy of the considered estimators were also verified using the Cramer-Rao lower bound (CRLB) to which simulated data for the considered estimators was compared. The proposed method was validated using a real-life signal collected from a radar operating in PFSR geometry. The Doppler rate provided by a car crossing the baseline between the receiver and the GSM transmitter was estimated. Finally, the concept of using CR estimation, which in the case of PFSR can be understood as Doppler rate, was confirmed on the basis of both simulated and real-life data.
Ataxia–telangiectasia mutated coordinates the ovarian DNA repair and atresia-initiating response to phosphoramide mustard†

Abstract Ataxia–telangiectasia-mutated (ATM) protein recognizes and repairs DNA double strand breaks through activation of cell cycle checkpoints and DNA repair proteins. Atm gene mutations increase female reproductive cancer risk. Phosphoramide mustard (PM) induces ovarian DNA damage and destroys primordial follicles, and pharmacological ATM inhibition prevents PM-induced follicular depletion. Wild-type (WT) C57BL/6 or Atm+/– mice were dosed once intraperitoneally with sesame oil (95%) or PM (25 mg/kg) in the proestrus phase of the estrous cycle and ovaries harvested 3 days thereafter. Atm+/– mice spent ∼25% more time in diestrus phase than WT. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) on ovarian protein was performed and bioinformatically analyzed. Relative to WT, Atm+/– mice had 64 and 243 proteins increased or decreased in abundance, respectively. In WT mice, PM increased 162 and decreased 20 proteins. In Atm+/– mice, 173 and 37 proteins were increased and decreased, respectively, by PM. Exportin-2 (XPO2) was localized to granulosa cells of all follicle stages and was 7.2-fold greater in Atm+/– than WT mice. Cytoplasmic FMR1-interacting protein 1 was 6.8-fold lower in Atm+/– mice and was located in the surface epithelium with apparent translocation to the ovarian medulla post-PM exposure. PM induced γ H2AX, but fewer γ H2AX-positive foci were identified in Atm+/– ovaries. Similarly, cleaved caspase-3 was lower in the Atm+/– PM-treated, relative to WT mice. These findings support ATM involvement in ovarian DNA repair and suggest that ATM functions to regulate ovarian atresia. Summary sentence The TGF beta superfamily are expressed in the placenta, and regulate the process of placentation through the activation of several signaling pathways.
Entropy Analysis of High-Definition Transcranial Electric Stimulation Effects on EEG Dynamics

A foundation of medical research is time series analysis—the behavior of variables of interest with respect to time. Time series data are often analyzed using the mean, with statistical tests applied to mean differences, and has the assumption that data are stationary. Although widely practiced, this method has limitations. Here we present an alternative statistical approach with sample analysis that provides a summary statistic accounting for the non-stationary nature of time series data. This work discusses the use of entropy as a measurement of the complexity of time series, in the context of Neuroscience, due to the non-stationary characteristic of the data. To elucidate our argument, we conducted entropy analysis on a sample of electroencephalographic (EEG) data from an interventional study using non-invasive electrical brain stimulation. We demonstrated that entropy analysis could identify intervention-related change in EEG data, supporting that entropy can be a useful “summary” statistic in non-linear dynamical systems.
Investigation of Anthocyanins Stability from Pomegranate Juice (Punica Granatum L. Cv Ermioni) under a Simulated Digestion Process

Background: Pomegranate gained a widespread popularity as a functional food due to the high content of bioactive components of the whole fruit, as well as its juice and extracts. There is a large amount of research that assigns them very important functions for the human organism. Methods: The anthocyanins (ACNs) of pomegranate juice (PJ) from the Ermioni variety are quantitatively identified and their stability under a simulated digestion process (SDP) is investigated. ACNs, as well as phenolic compounds, were isolated through solid phase extraction and determined using high-performance liquid chromatography in every stage of the SDP. Total phenolics, total monomeric ACNs, polymeric color and antioxidant activity were also determined in pomegranate juice and during the digestion process. Results: The predominant anthocyanin was Cy-3-glucoside followed by the corresponding 3,5-diglucoside, which accounted for 40.8% and 27.4% of the total ACN content, respectively. About 65% of the total monomeric ACN content remained intact by the end of the simulated digestion process. Conclusions: The PJ of the Ermioni variety seems to retain a large amount of the bioactive compounds after the SDP. The antioxidant activity and total phenolic content (TPC) remain almost stable during the SDP, suggesting that the products formed during ACN degradation maintain the antioxidant activity of the parent molecule.
Water Immersion During the Labour and Effects on Oxidative Stress

Abstract Objective: The study aims to investigate maternal serum thiol/disulfide homeostasis and ischemia-modified albumin (IMA) levels of women who were submerged during labor. Material and methods: Sixty-four pregnant women were enrolled in this study. Thirty-four women were submerged during the first stage of labor and 30 women were not. Native thiol, total thiol, disulfide, albumin, IMA, disulfide/native thiol, disulfide/total thiol and native thiol/total thiol concentrations were measured and demographic data were obtained. Results: Cord blood pH, serum disulfide levels and (disulfide/total thiol) × 100 levels were significantly lower in the water immersion group (P < 0.01, P = 0.01 and P < 0.01, respectively). Native thiol, total thiol, albumin and IMA levels were higher in the water immersion group P < 0.01, P < 0.01, P = 0.001 and P < 0.01, respectively). Conclusion: Water immersion during the first stage of labor was found to be associated with deterioration of thiol-disulfide homeostasis with respect to antioxidant status while IMA levels were higher, suggesting an ischemic condition.
Nonintrusive Appliance Load Monitoring: An Overview, Laboratory Test Results and Research Directions

Nonintrusive appliance load monitoring (NIALM) allows disaggregation of total electricity consumption into particular appliances in domestic or industrial environments. NIALM systems operation is based on processing of electrical signals acquired at one point of a monitored area. The main objective of this paper was to present the state-of-the-art in NIALM technologies for the smart home. This paper focuses on sensors and measurement methods. Different intelligent algorithms for processing signals have been presented. Identification accuracy for an actual set of appliances has been compared. This article depicts the architecture of a unique NIALM laboratory, presented in detail. Results of developed NIALM methods exploiting different measurement data are discussed and compared to known methods. New directions of NIALM research are proposed.
Blockchain: an overview

During the late 1990s, investors were eager to invest in any company with an Internet-related name or a “. com” suffix. Today, the word “blockchain” has a similar effect. Like the Internet, blockchains are an open source technology that becomes increasingly valuable as more people use it due to what economists call “the network effect”. Blockchains allow digital information to be transferred from one individual to another without an intermediary. Bitcoin was the first use of the blockchain technology. However, the volatility, transaction fees, and uncertain legal framework have stalled bitcoin’s widespread adoption.
Computational architecture of a visual model for biological motions segregation

ABSTRACT This paper outlines a neural model inspired by the dorsal stream of the visual system for motion recognition. Two areas are considered: the primary visual area (V1) and the middle temporal area (MT). In model area, V1 neurons are organized to detect eight local motion directions. MT is modelled using classical receptive field (CRF), where the cells respond to wide-field motion. The biological motion can be identified through spatial motion dynamics for the limbs and body. In this article, we propose spatio-temporal sampling detectors, where a set of circular masks over motion scenario are utilized to detect the motion dynamics. Two alternative mechanisms, Max-pooling and Sum-pooling, are used to extracting spatio-temporal descriptors from motion energy occupied by the circular masks. To improve the classification results, centroid kinematics is added to the feature vectors, where this feature contributes substantially to characterizing the motion pattern of an action. We evaluate our model by using two challenging datasets: the Weizmann biological action dataset and the KTH biological motion dataset. Our results reflect the potential of spatio-temporal sampling detectors in describing the biological motion of body and limbs using only short video frames (snippets). In addition, the centroid kinematic feature improves the recognition rate and refines the action classification.
Effect of Stacked Sodium Bicarbonate Loading on Repeated All-out Exercise

Abstract The purpose of this study was to evaluate whether NaHCO3, administered via a 9-h stacked loading protocol (i.e. repeated supplementation with small doses in order to obtain a gradual increase in blood [HCO3 -]), has an ergogenic effect on repeated all-out exercise. Twelve physically active males were randomly assigned to receive either NaHCO3 (BIC) or placebo (PL) in a double-blind cross-over design. NaHCO3 supplementation was divided in three identical 3-h cycles: a 6.3 g bolus at the start, followed by 2.1 g doses at +1-h and +2-h, yielding a total NaHCO3 intake of 0.4 g·kg−1 BM over 9-h. At the end of each cycle, participants performed 2-min all-out cycling. Capillary blood samples were analyzed for [HCO3 -], pH and [La-]. Pre-exercise blood [HCO3 -] in PL decreased from 25.6±0.2 mmol·L−1 in bout 1 to 23.6±0.2 mmol·L−1 in bout 4, while increasing from 25.5±0.2 to 31.2±0.4 mmol·L−1 in BIC (P<0.05). Concomitantly, pre-exercise pH values gradually decreased in PL (from 7.41±0.00 to 7.39±0.01) and increased in BIC (from 7.41±0.01 to 7.47±0.01; P<0.05). Mean power output of the four bouts was higher in BIC (428±20 W) than in PL (420±20 W; P<0.05). The ergogenic effect on repeated all-out exercise occurred in the absence of gastrointestinal distress.
Lessons From an Analysis of Newborn Hearing Screening Data for Children With Cochlear Implants.

OBJECTIVES The aims of the study are to identify the limitations of the current newborn hearing screening (NHS) programs and provide recommendations for better protocols. STUDY DESIGN Retrospective analysis. SETTING Tertiary referral center. PATIENTS The study participants were 185 children who received cochlear implants (CIs) at ≤5 years of age. INTERVENTIONS Therapeutic and rehabilitative. MAIN OUTCOME MEASURES The results of NHS, screening tools used, age, and hearing thresholds at which hearing loss was confirmed, causes of the hearing loss, age of CI insertion, aided pure-tone audiogram findings, and language development level were analyzed. RESULTS NHS data was available for 109 children, and 24 patients (22.0%) had passed NHS for both ears. Hearing loss was confirmed considerably later in children who had passed NHS than in children who were referred for further evaluation (p < 0.01). The most common cause for hearing loss in the NHS-pass group was SLC26A4 mutations (41.7%). Patients in the NHS-pass group received CIs considerably later than those in the NHS-referred group (p < 0.01). Among patients with SLC26A4 mutations, the language development level was significantly lower in the NHS-pass group than in the NHS-referred group (p < 0.01). CONCLUSIONS Careful counseling regarding NHS results is necessary for parents to understand that the absence of hearing loss at birth does not mean that the child will not develop hearing loss later in life. Genetic testing for SLC26A4 mutations may be necessary in regions with a high incidence of these mutations, such as East Asia.
Cross-talk between TGF-β and PDGFRα signaling pathways regulates the fate of stromal fibro–adipogenic progenitors

ABSTRACT Fibro–adipogenic progenitors (FAPs) are tissue-resident mesenchymal stromal cells (MSCs) required for proper skeletal muscle development, regeneration and maintenance. However, FAPs are also responsible for fibro-fatty scar deposition following chronic damage. We aimed to investigate the role of functional cross-talk between TGF-β and PDGFRα signaling pathways in the fate of FAPs. Here, we show that the number of FAPs correlates with TGF-β levels and with extracellular matrix deposition during regeneration and repair. Interestingly, the expression of PDGFRα changed dynamically in the fibroblast lineage after injury. Furthermore, PDGFRα-dependent immediate early gene expression changed during regeneration and repair. We also found that TGF-β signaling reduces PDGFRα expression in FAPs, mouse dermal fibroblasts and in two related mesenchymal cell lines. Moreover, TGF-β promotes myofibroblast differentiation of FAPs but inhibits their adipogenicity. Accordingly, TGF-β impairs the expression of PDGFRα-dependent immediate early genes in a TGFBR1-dependent manner. Finally, pharmacological inhibition of PDGFRα activity with AG1296 impaired TGF-β-induced extracellular matrix remodeling, Smad2 signaling, myofibroblast differentiation and migration of MSCs. Thus, our work establishes a functional cross-talk between TGF-β and PDGFRα signaling pathways that is involved in regulating the biology of FAPs and/or MSCs. This article has an associated First Person interview with the first author of the paper. Summary: TGF-β signaling in skeletal muscle mesenchymal stromal cells suppresses PDGFRα expression and compromises PDGFRα-dependent signaling, resulting in impaired TGF-β-mediated responses.