Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanistic pain profiling in young adolescents with patellofemoral pain before and following treatment: a prospective cohort study.

Patellofemoral pain (PFP) is a common complaint among young sports active adolescents. This study evaluated the longitudinal changes in pro-nociceptive and anti-nociceptive mechanisms in young adolescents with PFP, their impact on prognosis and responsiveness to treatment. Adolescents (N=151, aged 10-14 years) diagnosed with PFP were compared to age-matched controls (N=50) and subsequently tracked while participating in an intervention focussed on activity modification. They underwent quantitative sensory testing at baseline (pre-intervention), four weeks (during initial treatment), and twelve weeks (following treatment). Pressure pain thresholds (PPTs) were recorded on the knee, shin and elbow. Temporal summation of pain (TSP) was assessed by the increase in pain intensity during ten repeated cuff pressure pain stimulations on the leg. Conditioned pain modulation (CPM) was defined as change in cuff pain thresholds on one leg, during painful cuff conditioning on the contralateral leg. At baseline, adolescents with PFP had decreased PPTs at the knee, shin and elbow (P<0.001) as well as more facilitated TSP (P<0.05) compared with controls. For CPM at baseline, controls displayed an increase in cuff pain thresholds during conditioning (P<0.05), while those with PFP did not. More facilitated baseline TSP was associated with less improvements in pain intensity during the intervention (P<0.01). PPTs increased at both follow-ups (P<0.001), and the PPT-increase were associated with decreases in pain intensity (r=0.316; P<0.001). Overall, TSP remained facilitated at follow-ups, and there was no change in CPM. This is the first study to demonstrate a pro-nociceptive mechanism as a prognostic factor in young adolescents with PFP.
Thermodynamic and Kinetic Study of Diels–Alder Reaction between Furfuryl Alcohol and N-Hydroxymaleimides—An Assessment for Materials Application

The study of Diels–Alder reactions in materials science is of increasing interest. The main reason for that is the potential thermoreversibility of the reaction. Aiming to predict the behavior of a material modified with maleimido and furyl moieties, 1H NMR and UV-Vis solution studies of the Diels–Alder reaction between furfuryl alcohol and two N-hydroxymaleimides are explored in the present study. Rate constants, activation energy, entropy, and enthalpy of formation were determined from each technique for both reacting systems. Endo and exo isomers were distinguished in 1H NMR, and the transition from a kinetic, controlled Diels–Alder reaction to a thermodynamic one could be observed in the temperature range studied. A discussion on the effect of that on the application in a material was performed. The approach selected considers a simplified equilibrium of the Diels–Alder reaction as the kinetic model, allowing materials scientists to evaluate the suitability of using the reacting molecules for the creation of thermoresponsive materials. The proposed approach determines the kinetic constants without the direct influence of the equilibrium constant value, thereby allowing a more objective data analysis. The effects of the selection of kinetic model, analytical method, and data treatment are discussed.
A Quantitative Centrosomal Amplification Score Predicts Local Recurrence of Ductal Carcinoma In Situ

Purpose: The purpose of this study is to predict risk of local recurrence (LR) in ductal carcinoma in situ (DCIS) with a new visualization and quantification approach using centrosome amplification (CA), a cancer cell–specific trait widely associated with aggressiveness. Experimental Design: This first-of-its-kind methodology evaluates the severity and frequency of numerical and structural CA present within DCIS and assigns a quantitative centrosomal amplification score (CAS) to each sample. Analyses were performed in a discovery cohort (DC, n = 133) and a validation cohort (VC, n = 119). Results: DCIS cases with LR exhibited significantly higher CAS than recurrence-free cases. Higher CAS was associated with a greater risk of developing LR (HR, 6.3 and 4.8 for DC and VC, respectively; P < 0.001). CAS remained an independent predictor of relapse-free survival (HR, 7.4 and 4.5 for DC and VC, respectively; P < 0.001) even after accounting for potentially confounding factors [grade, age, comedo necrosis, and radiotherapy (RT)]. Patient stratification using CAS (P < 0.0001) was superior to that by Van Nuys Prognostic Index (VNPI; HR for CAS = 6.2 vs. HR for VNPI = 1.1). Among patients treated with breast-conserving surgery alone, CAS identified patients likely to benefit from adjuvant RT. Conclusions: CAS predicted 10-year LR risk for patients who underwent surgical management alone and identified patients who may be at low risk of recurrence, and for whom adjuvant RT may not be required. CAS demonstrated the highest concordance among the known prognostic models such as VNPI and clinicopathologic variables such as grade, age, and comedo necrosis.
Decoding the Role of Satellite DNA in Genome Architecture and Plasticity—An Evolutionary and Clinical Affair

Repetitive DNA is a major organizational component of eukaryotic genomes, being intrinsically related with their architecture and evolution. Tandemly repeated satellite DNAs (satDNAs) can be found clustered in specific heterochromatin-rich chromosomal regions, building vital structures like functional centromeres and also dispersed within euchromatin. Interestingly, despite their association to critical chromosomal structures, satDNAs are widely variable among species due to their high turnover rates. This dynamic behavior has been associated with genome plasticity and chromosome rearrangements, leading to the reshaping of genomes. Here we present the current knowledge regarding satDNAs in the light of new genomic technologies, and the challenges in the study of these sequences. Furthermore, we discuss how these sequences, together with other repeats, influence genome architecture, impacting its evolution and association with disease.
Comparison of the recruitment of transverse abdominis through drawing-in and bracing in different core stability training positions

There are many proposed core stability exercises in a variety of positions; however, it is not clear that in which position, activation of transverse abdominis muscle is utmost. We aimed to compare the activation of transverse abdominis muscle in different core stability exercise positions through ultrasound imaging. in a 20 subjects’ study we compared the effectiveness of drawing-in and bracing maneuvers on transverse abdominis in different core stability exercise positions (supine, hook lying, supine with 90° flexed knee and hip, supine with stretched knees and 90° flexed hips, bridge, bridge with one stretched knee and Bird dog). We used activation ratio and preferential activation ratio as measurements of transverse abdominis activation. Abdominal Bracing in the bridge position showed the highest activation of transverse abdominis (P<0.05). The results showed significantly higher activation of transverse abdominis, measured by preferential activation ratio, in bridge position during abdominal bracing.
Advances on Studies of Anti-osteoporosis Applications and Mechanisms by Herba Epimedii and Fructus Ligustri Lucidi

To study the anti-osteoporosis applications and mechanisms of Herba Epimedii and Fructus Ligustri Lucidi with the collation and analysis of litertures.Herba Epimedii,Fructus Ligustri Lucidi and anti-osteoporosis as the subject headings are used to screen litertures in the last five years by CNKI and Pubmed,and then make an overview of anti-osteoporosis effects of Herba Epimedii and Fructus Ligustri Lucidi.This anticle summarizes the clinical application reports of anti-osteoporosis by Herba Epimedii and Fructus Ligustri Lucidi,and analyzes the progress in the study of the mechanisms of anti-osteoporosis effect of the two herbs.Herba Epimedii and Fructus Ligustri Lucidi has made a significant effect in the prevention and treatment of osteoporosis,but the development of research is in its infancy,long-term efficacy of the compound preparation is inaccurate,and do not find the reports of the two herbs compatibility of anti-osteoporosis.So research on compatibility of the two herbs in the anti-osteoporosis has broad prospects.
Insights into Activation Mechanisms of Store-Operated TRPC1 Channels in Vascular Smooth Muscle

In vascular smooth muscle cells (VMSCs), the stimulation of store-operated channels (SOCs) mediate Ca2+ influx pathways which regulate important cellular functions including contraction, proliferation, migration, and growth that are associated with the development of vascular diseases. It is therefore important that we understand the biophysical, molecular composition, activation pathways, and physiological significance of SOCs in VSMCs as these maybe future therapeutic targets for conditions such as hypertension and atherosclerosis. Archetypal SOCs called calcium release-activated channels (CRACs) are composed of Orai1 proteins and are stimulated by the endo/sarcoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1) following store depletion. In contrast, this review focuses on proposals that canonical transient receptor potential (TRPC) channels composed of a heteromeric TRPC1/C5 molecular template, with TRPC1 conferring activation by store depletion, mediate SOCs in native contractile VSMCs. In particular, it summarizes our recent findings which describe a novel activation pathway of these TRPC1-based SOCs, in which protein kinase C (PKC)-dependent TRPC1 phosphorylation and phosphatidylinositol 4,5-bisphosphate (PIP2) are obligatory for channel opening. This PKC- and PIP2-mediated gating mechanism is regulated by the PIP2-binding protein myristoylated alanine-rich C kinase (MARCKS) and is coupled to store depletion by TRPC1-STIM1 interactions which induce Gq/PLCβ1 activity. Interestingly, the biophysical properties and activation mechanisms of TRPC1-based SOCs in native contractile VSMCs are unlikely to involve Orai1.
Impulsivity, Emotional Intelligence, and Alcohol Consumption in Young People: A Mediation Analysis

Alcohol consumption in young people is a public health problem. Due to the harmful consequences and the large population using alcoholic substances, it would be important to determine the biological, psychological, and social factors associated with alcohol use and abuse. The main object of this study is to explore which components of impulsivity, according to the main theoretical models, have predictive power regarding alcohol consumption in young people. A secondary objective is to determine if emotional intelligence has a mediating role between the components of impulsivity and alcohol consumption, and thus specifically contribute to the knowledge about the mediation processes between those variables that are involved in the initiation and maintenance of alcohol consumption. For this purpose, 384 participants were recruited (83.1% females, n = 319), with mean age of 20.46 years (SD = 1.90; range 18–25). All participants were alcohol consumers at the beginning of the study. Data collection was conducted via online survey; impulsivity was evaluated by several questionnaires (Sensation Seeking Scale Form V, Barratt Impulsivity Scales 11, and Sensitivity to Punishment and Sensitivity to Reward), and emotional intelligence was evaluated by the Trait Meta-Mood Scale. The results reveal that the dimension of disinhibition (a dimension of the sensation search scale) significantly has the highest predictive value on alcohol consumption. Moreover, our data show that the total effect and direct effect of disinhibition on frequency of alcohol consumption were both significant. The mediating role of emotional intelligence in this process was also significant. These findings show which variables should be considered to prevent alcohol consumption in young people.
Getting Well Is More Than Gaining Weight – Patients’ Experiences of a Treatment Program for Anorexia Nervosa Including Ear Acupuncture

Abstract This study illuminates how 25 in-patients who were treated for anorexia nervosa in a highly specialized clinic for eating disturbances in Sweden experienced the treatment program. The program included structured eating, medication, restrictions in physical activity and supportive dialogues. Patients were also offered semi-standardized NADA ear acupuncture as a complement to relieve stress, anxiety and tension. In total, 46 interviews were analysed qualitatively using latent content analysis. The results showed how participants strived with their slow transition towards recovery. The novelty of integrating acupuncture in psychiatric treatment makes this study interesting. Acupuncture was experienced to relieve anxiety and somatic symptoms through the whole process. Further research is needed to evaluate the effect of acupuncture on the patient’s subjective sense of well-being when used as an adjunct to usual care.
Influence of Composition and Spray-Drying Process Parameters on Carrier-Free DPI Properties and Behaviors in the Lung: A review

Although dry powder inhalers (DPIs) have attracted great interest compared to nebulizers and metered-dose inhalers (MDIs), drug deposition in the deep lung is still insufficient to enhance therapeutic activity. Indeed, it is estimated that only 10–15% of the drug reaches the deep lung while 20% of the drug is lost in the oropharyngeal sphere and 65% is not released from the carrier. The potentiality of the powders to disperse in the air during the patient’s inhalation, the aerosolization, should be optimized. To do so, new strategies, in addition to classical lactose-carrier, have emerged. The lung deposition of carrier-free particles, mainly produced by spray drying, is higher due to non-interparticulate forces between the carrier and drug, as well as better powder uniformity and aerosolization. Moreover, the association of two or three active ingredients within the same powder seems easier. This review is focused on a new type of carrier-free particles which are characterized by a sugar-based core encompassed by a corrugated shell layer produced by spray drying. All excipients used to produce such particles are dissected and their physico-chemical properties (Péclet number, glass transition temperature) are put in relation with the lung deposition ability of powders. The importance of spray-drying parameters on powders’ properties and behaviors is also evaluated. Special attention is given to the relation between the morphology (characterized by a corrugated surface) and lung deposition performance. The understanding of the closed relation between particle material composition and spray-drying process parameters, impacting the final powder properties, could help in the development of promising DPI systems suitable for local or systemic drug delivery.
The Impact of Leadership Involvement on College Students' Experience and Wellbeing

The purpose of this qualitative study was to explore how involvement in leadership positions in clubs and organizations impact students’ college experience and wellbeing. The questions that guided the research were (a) how does a student’s involvement in leadership positions in clubs and organizations impact how he or she views the college experience, and (b) how is a student’s sense of wellbeing affected by his or her participation in leadership positions? Through semi-structured interviews, six major themes emerged: mentorship, past experiences, increase in leadership skills, being in relationships with others, leadership identity development, and difficult transitions. The essence of this study is that a student’s involvement in leadership positions in clubs and organizations has a positive and formative impact on a student’s overall college experience and wellbeing. A discussion of the connections between involvement, leadership, and wellbeing is provided, in addition to research limitations, implications for future research, and implications for practice.
Nutritional Feeding Strategies in Pediatric Intestinal Failure

Intestinal failure is defined as a critical reduction of the gut mass or function, below the minimum needed to absorb nutrients and fluids. The ultimate goal in intestinal failure is to promote bowel adaptation and reach enteral autonomy while a healthy growth and development is maintained. The condition is heterogeneous and complex. Therefore, recommendations for the type and duration of parenteral, enteral, and oral nutrition are variable, with the child’s age as an additional key factor. The aim of this review is to provide an overview of nutritional feeding strategies in this heterogeneous population. Different perspectives on nutritional management, nutrition and adaptation, and microbiome and nutrition will be discussed.
Effects of growth hormone in the central nervous system

ABSTRACT Growth hormone (GH) is best known for its effect stimulating tissue and somatic growth through the regulation of cell division, regeneration and proliferation. However, GH-responsive neurons are spread over the entire central nervous system, suggesting that they have important roles in the brain. The objective of the present review is to summarize and discuss the potential physiological importance of GH action in the central nervous system. We provide evidence that GH signaling in the brain regulates the physiology of numerous functions such as cognition, behavior, neuroendocrine changes and metabolism. Data obtained from experimental animal models have shown that disruptions in GH signaling in specific neuronal populations can affect the reproductive axis and impair food intake during glucoprivic conditions, neuroendocrine adaptions during food restriction, and counter-regulatory responses to hypoglycemia, and they can modify gestational metabolic adaptions. Therefore, the brain is an important target tissue of GH, and changes in GH action in the central nervous system can explain some dysfunctions presented by individuals with excessive or deficient GH secretion. Furthermore, GH acts in specific neuronal populations during situations of metabolic stress to promote appropriate physiological adjustments that restore homeostasis. Arch Endocrinol Metab. 2019;63(6):549-56
CRISPR-cas3 of Salmonella Upregulates Bacterial Biofilm Formation and Virulence to Host Cells by Targeting Quorum-Sensing Systems

Salmonella is recognized as one of the most common microbial pathogens worldwide. The bacterium contains the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems, providing adaptive immunity against invading foreign nucleic acids. Previous studies suggested that certain bacteria employ the Cas proteins of CRISPR-Cas systems to target their own genes, which also alters the virulence during invasion of mammals. However, whether CRISPR-Cas systems in Salmonella have similar functions during bacterial invasion of host cells remains unknown. Here, we systematically analyzed the genes that are regulated by Cas3 in a type I-E CRISPR-Cas system and the virulence changes due to the deletion of cas3 in Salmonella enterica serovar Enteritidis. Compared to the cas3 gene wild-type (cas3 WT) Salmonella strain, cas3 deletion upregulated the lsrFGBE genes in lsr (luxS regulated) operon related to quorum sensing (QS) and downregulated biofilm-forming-related genes and Salmonella pathogenicity island 1 (SPI-1) genes related to the type three secretion system (T3SS). Consistently, the biofilm formation ability was downregulated in the cas3 deletion mutant (Δcas3). The bacterial invasive and intracellular capacity of Δcas3 to host cells was also reduced, thereby increasing the survival of infected host cells and live chickens. By the transcriptome-wide screen (RNA-Seq), we found that the cas3 gene impacts a series of genes related to QS, the flagellum, and SPI-1-T3SS system, thereby altering the virulence phenotypes. As QS SPI-1-T3SS and CRISPR-Cas systems are widely distributed in the bacteria kingdom, our findings extend our understanding of virulence regulation and pathogenicity in mammalian hosts for Salmonella and potentially other bacteria.
Identification and Biological Evaluation of CK2 Allosteric Fragments through Structure-Based Virtual Screening

Casein kinase II (CK2) is considered as an attractive cancer therapeutic target, and recent efforts have been made to develop its ATP-competitive inhibitors. However, achieving selectivity with respect to related kinases remains challenging due to the highly conserved ATP-binding pocket of kinases. Allosteric inhibitors, by targeting the much more diversified allosteric site relative to the highly conserved ATP-binding pocket, might be a promising strategy with the enhanced selectivity and reduced toxicity than ATP-competitive inhibitors. The previous studies have highlighted the traditional serendipitousity of discovering allosteric inhibitors owing to the complicate allosteric modulation. In this current study, we identified the novel allosteric inhibitors of CK2α by combing structure-based virtual screening and biological evaluation methods. The structure-based pharmacophore model was built based on the crystal structure of CK2α-compound 15 complex. The ChemBridge fragment library was searched by evaluating the fit values of these molecules with the optimized pharmacophore model, as well as the binding affinity of the CK2α-ligand complexes predicted by Alloscore web server. Six hits forming the holistic interaction mechanism with the αD pocket were retained after pharmacophore- and Alloscore-based screening for biological test. Compound 3 was found to be the most potent non-ATP competitive CK2α inhibitor (IC50 = 13.0 μM) with the anti-proliferative activity on A549 cancer cells (IC50 = 23.1 μM). Our results provide new clues for further development of CK2 allosteric inhibitors as anti-cancer hits.
Selenium incorporation to amino acids in Chlorella cultures grown in phototrophic and heterotrophic regime.

Microalgae accumulate bioavailable selenium containing amino acids (Se-AAs) and these are useful as a food supplement. While this accumulation has been studied in phototrophic algal cultures, little data exists for heterotrophic cultures. We have determined Se-AAs content, selenium/sulphur (Se/S) substitution rates and overall Se accumulation balance in photo- and heterotrophic Chlorella cultures. Laboratory trials revealed that heterotrophic cultures tolerate Se doses ~8-fold higher compared to phototrophic cultures, resulting in a ~2-3-fold higher Se-AAs content. In large-scale experiments both cultivation regimes provided comparable Se-AAs content. Outdoor phototrophic cultures accumulated up to 400 μg g-1 of total Se-AAs and exhibited a high level of Se/S substitution (5-10%) with 30-60% organic/total Se embedded in the biomass. A slightly higher content of Se-AAs and ratio of Se/S substitution was obtained for a heterotrophic culture in pilot-scale fermentors. The data presented here shows that heterotrophic Chlorella cultures provide an alternative for Se-enriched biomass production and provides information on Se-AAs content and speciation in different cultivation regimes.