Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated resting blood pressure augments autonomic imbalance in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is characterized by increased sympathetic nervous system (SNS) activity, blunted parasympathetic nervous system (PNS) activity, and impaired baroreflex sensitivity (BRS), which contribute to accelerated cardiovascular disease. Patients with PTSD also have chronic stress-related elevations in resting blood pressure (BP), often in the prehypertensive range; yet, it is unclear if elevated resting blood pressure (ERBP) augments these autonomic derangements in PTSD. We hypothesized that compared with normotensive PTSD (N-PTSD), those with ERBP (E-PTSD) have further increased SNS, decreased PNS activity, and impaired BRS at rest and exaggerated SNS reactivity, PNS withdrawal, and pressor responses during stress. In 16 E-PTSD and 17 matched N-PTSD, we measured continuous BP, ECG, muscle sympathetic nerve activity (MSNA), and heart rate variability (HRV) markers reflecting cardiac PNS activity [standard deviation of R-R intervals (SDNN), root mean square of differences in successive R-R intervals (RMSSD), and high frequency power (HF)] during 5 min of rest and 3 min of mental arithmetic. Resting MSNA ( P = 0.943), sympathetic BRS ( P = 0.189), and cardiovagal BRS ( P = 0.332) were similar between groups. However, baseline SDNN (56 ± 6 vs. 78 ± 8 ms, P = 0.019), RMSSD (39 ± 6 vs. 63 ± 9 ms, P = 0.018), and HF (378 ± 103 vs. 693 ± 92 ms2, P = 0.015) were lower in E-PTSD versus N-PTSD. During mental stress, the systolic blood pressure response ( P = 0.011) was augmented in E-PTSD. Although MSNA reactivity was not different ( P > 0.05), the E-PTSD group had an exaggerated reduction in HRV during mental stress ( P < 0.05). PTSD with ERBP have attenuated resting cardiac PNS activity, coupled with exaggerated BP reactivity and PNS withdrawal during stress.
Caloric restriction rescues yeast cells from alpha-synuclein toxicity through autophagic control of proteostasis

α-Synuclein (SNCA) is a presynaptic protein that is associated with the pathophysiology of synucleinopathies, including Parkinson’s disease. SNCA is a naturally aggregation-prone protein, which may be degraded by the ubiquitin-proteasome system (UPS) and by lysosomal degradation pathways. Besides being a target of the proteolytic systems, SNCA can also alter the function of these pathways further, contributing to the progression of neurodegeneration. Deterioration of UPS and autophagy activities with aging further aggravates this toxic cycle. Caloric restriction (CR) is still the most effective non-genetic intervention promoting lifespan extension. It is known that CR-mediated lifespan extension is linked to the regulation of proteolytic systems, but the mechanisms underlying CR rescue of SNCA toxicity remain poorly understood. This study shows that CR balances UPS and autophagy activities during aging. CR enhances UPS activity, reversing the decline of the UPS activity promoted by SNCA, and keeps autophagy at homeostatic levels. Maintenance of autophagy at homeostatic levels appears to be relevant for UPS activity and for the mechanism underlying rescue of cells from SNCA-mediated toxicity by CR.
IGF2BP2 Overexpression Indicates Poor Survival in Patients with Acute Myelocytic Leukemia

Background/Aims: IGF2BP2 has been reported to serve as an oncogene in various solid cancers. However, the role of IGF2BP2 in acute myelocytic leukemia (AML) is still unknown. Methods: Public databases Gene Omnibus was used to evaluate the expression of IGF2BP2 in AML patients and healthy controls. In addition, primary cells from these two populations were prepared by Ficoll density centrifugation. Rt-qPCR and western blot were used to detect IGF2BP2 expression in the primary cells from these two populations. Meta-analysis was performed to evaluate the association of IGF2BP2 and prognosis. Lentivirus-based shRNAs were used to knock down IGF2BP2 in AML cell lines KG-1a and Kasumi. Results: We searched the public database Gene Omnibus and analyzed IGF2BP2 expression in both AML and healthy populations. The results showed that IGF2BP2 was overexpressed in AML patients. To verify this phenomenon in fresh human samples, we compared the expression of IGF2BP2 in primary cells from 10 AML patients and 10 healthy controls and found that the expression of IGF2BP2 was upregulated in AML primary cells. More importantly, we observed that IGF2BP2 expression was negatively correlated with the CEBPA mutation status, which is an indicator of good prognosis (RR=0.648, p=0.0001). In addition, IGF2BP2 expression was positively associated with poor prognostic factors, such as the FLT3-ITD mutation (RR=1.198, p=0.0009) and IDH1 mutation (RR=1.354, p=0.0003), as well as intermediate and poor cytogenetic risk (RR=1.214, p=0.0026). To evaluate the prognostic value of IGF2BP2 in AML, we further performed a meta-analysis of 8 studies consisting of 1731 patients and found that IGF2BP2 overexpression was correlated with worse overall survival in AML patients [HR=1.31(1.16-1.49); p = 0.00]. Furthermore, we performed Gene Omnibus and Gene Set Enrichment analyses and found that the genes regulated by IGF2BP2 were mainly enriched in cell proliferation. IGF2BP2 knockdown by 4 different shRNA vectors significantly inhibited the growth of two AML cell lines, KG-1a and Kasumi. Conclusion: Thus, IGF2BP2 may serve as a biomarker to predict the prognosis of AML and as a potential target in AML.
A Novel WDR45 Mutation in a 9-Month-Old Male Infant with Epileptic Spasms

To the Editor: Neurodegeneration with brain iron accumulation (NBIA) comprises a group of disorders that manifest as early‐ or late‐onset parkinsonism, dystonia, spasticity, and cognitive impairment. [1] One subtype of NBIA, β‐propeller protein‐associated neurodegeneration (BPAN), is caused by mutation of the WDR45 gene. To date, 59 novel WDR45 mutations have been reported. The literature indicates that it is difficult to detect the disorder in early childhood because no specific clinical or imaging features exist. In this report, we describe the case of a 9‐month‐old male Chinese infant with a novel mutation (c.977‐1 C>T) in the WDR45 gene.
Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved

It has become clear from multiple studies that WWOX (WW domain-containing oxidoreductase) operates as a “non-classical” tumor suppressor of significant relevance in cancer progression. Additionally, WWOX has been recognized for its role in a much wider array of human pathologies including metabolic conditions and central nervous system related syndromes. A myriad of putative functional roles has been attributed to WWOX mostly through the identification of various binding proteins. However, the reality is that much remains to be learned on the key relevant functions of WWOX in the normal cell. Here we employed a Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach in order to better define direct WWOX protein interactors and by extension interaction with multiprotein complexes under physiological conditions on a proteomic scale. This work led to the identification of both well-known, but more importantly novel high confidence WWOX interactors, suggesting the involvement of WWOX in specific biological and molecular processes while delineating a comprehensive portrait of WWOX protein interactome. Of particular relevance is WWOX interaction with key proteins from the endoplasmic reticulum (ER), Golgi, late endosomes, protein transport, and lysosomes networks such as SEC23IP, SCAMP3, and VOPP1. These binding partners harbor specific PPXY motifs which directly interact with the amino-terminal WW1 domain of WWOX. Pathway analysis of WWOX interactors identified a significant enrichment of metabolic pathways associated with proteins, carbohydrates, and lipids breakdown. Thus, suggesting that WWOX likely plays relevant roles in glycolysis, fatty acid degradation and other pathways that converge primarily in Acetyl-CoA generation, a fundamental molecule not only as the entry point to the tricarboxylic acid (TCA) cycle for energy production, but also as the key building block for de novo synthesis of lipids and amino acids. Our results provide a significant lead on subsets of protein partners and enzymatic complexes with which full-length WWOX protein interacts with in order to carry out its metabolic and other biological functions while also becoming a valuable resource for further mechanistic studies.
Sexuality and intimacy in ALS: systematic literature review and future perspectives

Several features of amyotrophic lateral sclerosis (ALS) impact on sexuality and intimate relationship; however, the issue has received poor attention so far. We performed a systematic literature review in order to provide an up-to-date account of sexuality in ALS. References were identified by searches of PubMed, Web of Science, Scopus and PsycINFO (1970–2017, English literature). The following were the key terms: ‘sexual’ OR ‘sexuality’ OR ‘intimacy’ OR ‘marital’ AND ‘ALS’ OR ‘Amyotrophic Lateral Sclerosis’ OR ‘Motor Neuron Disease’ OR ‘MND’. Titles and abstracts were screened for relevance and a full-text analysis was performed on the selected articles. Studies were included if they referred to sexual well-being/activities/functions or intimate relationship between patients and their partners and management of such topic by clinicians. Eligibility assessment was performed independently by two reviewers. A thematic and level of evidence classification of studies was performed. Studies’ design, objectives, measurements and outcomes were summarised. Thirty articles were included and four topics were identified: intimacy in the dyads; sexual activities in patients and with their partners; sexual function disturbances; and sexuality and cognitive-behavioural alterations. The quality of the studies varies, with globally poor level of evidence. Some sexuality issues have been only sparsely addressed, such as gender-related differences, same-sex relationships and sexual activities other than intercourse. Sexuality in ALS is still not adequately considered by clinicians and researchers. We present preliminary recommendations for improving sexuality and intimacy at any ALS multidisciplinary clinics.
THERABAND® CLX gold reduces knee-width index and range of motion during overhead, barbell squatting

ABSTRACT This study examined the influence of the TherabandTM CLX gold band on lower-limb muscle activity and kinematics during an overhead barbell squat. Participants performed two sets (band and no-band) of 12 repetitions of overhead barbell squats at 25% bodyweight. Three-dimensional kinematics were measured using motion capture with rigid bodies placed bilaterally on the foot, shank, thigh and thorax. Electromyography was collected from seven, bilateral muscles of the lower-limb and was unchanged for all muscles between conditions. Medial knee collapse was calculated using a knee-width index (KWI) ratio of the distance between the lateral epicondyles of the femur and the lateral malleoli. Average KWI was smaller during the band condition for the concentric (No band: 0.99 ± 0.05, Band: 0.97 ± 0.06, p < 0.05) and eccentric phases (No band: 1.00 ± 0.06, Band: 0.97 ± 0.05, p < 0.05). KWI was significantly smaller with the use of the TherabandTM CLX. As the gold band is the strongest of the CLX offerings, any benefit of increased proprioception may have been lost due to the high resistance of the band. Further research examining the dose-response of elastic band resistance to knee alignment may be needed to inform proper exercise prescription.
The Relation of Reciprocated and Nonreciprocated Friendship Nominations to Peer Social Competence for Chinese Elementary School Children

Abstract The authors examined associations between different forms of children’s friendship nomination reciprocity (mutual, unilateral given, unilateral received) and other measures of children’s peer social competence (liking, loneliness, overt aggression, perceived popularity) for 501 Chinese third- to sixth-grade students. Using a multigroup path analysis (with gender as group), for both boys and girls, all three forms of friendship nominations were negatively related to self-reported loneliness. Mutual friendship nominations and unilateral received friendship nominations were positively related to peer nominations for liking and to peer nominations of perceived popularity. The path between unilateral received friendship nominations and perceived popularity was higher for boys than for girls. Also, for boys only, mutual friendship nominations and unilateral received friendship nominations were each negatively related to peer nominations of overt aggression. These patterns are somewhat different from research examining the association of forms of friendships to peer social competence for children in Western cultures. Findings are discussed in terms of the importance of the relation of different forms of friendship nominations to children’s peer social competence as well as the broad association of culture for these relations.
A correlational study between serum asymmetric dimethylarginine level and impaired glucose tolerance patients associated with obesity

Asymmetric dimethylarginine (ADMA) plays a vital role in the regulation of insulin sensitivity and has been shown as a potential marker for various disease, including type 2 diabetes mellitus (DM2). However, the correlation between ADMA and impaired glucose tolerance (IGT) and obesity has not been studied. A total of 195 subjects were involved in our study. The characteristics of the subjects in the study cohort were measured and analyzed. We found that the serum ADMA and C‐reactive protein levels were significantly increased in IGT and diabetic patients, whereas the levels of lipoprotein A and adiponectin were decreased, especially in diabetic patients with obesity. The serum ADMA level was positively correlated to a homeostatic model assessment for insulin resistance, and multivariate regression analysis further indicated that ADMA was an independent factor for DM patients with obesity. Our study expands the understanding of the complicated relationship between obesity, insulin resistance, IGT, and ADMA. In addition, we demonstrated that the serum ADMA level could serve as a diagnositic biomarker of the early signs for IGT patients with obesity.
A multicentre study investigating parameters which influence direct bacterial identification from urine

Rapid diagnosis is one of the best ways to improve patient management and prognosis as well as to combat the development of bacterial resistance. The aim of this study was to study parameters that impact the achievement of reliable identification using a combination of flow cytometry and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS). The study was carried out in nine hospitals in Spain and included 1,050 urine samples with bacterial counts of 5x106 bacteria/ml. MALDI-ToF-MS-based identification was performed according to a previously described protocol. Valid identification by direct MALDI-ToF-MS was obtained in 72.8% of samples, in 80.3% of samples found to be positive by culture, 32.2% of contaminated samples, and 19.7% of negative samples. Among the positives samples with a valid identification the concordance at the species level was 97.2%. The parameters related to success of direct identification were: high bacterial count, the presence of Escherichia coli as a pathogen and rod-bacteria morphology provided by flow cytometry. The parameters related to failure were a high epithelial cell (EC) count, a high white blood cell (WBC) count and urine samples obtained from in-patients. In summary, this multicentre study confirms previously published data on the usefulness and accuracy of direct MALDI-ToF-MS-based identification of bacteria from urine samples. It seems important to evaluate not only the bacterial count, but also other parameters, such as EC and WBC counts, bacterial species and morphology, and the health care setting, to decide whether the sample is suitable for direct identification.
Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis

Dimethyl fumarate (DMF) is an important oral treatment option for various autoimmune diseases, such as multiple sclerosis (MS) and psoriasis. DMF and its dynamic metabolite, monomethyl fumarate (MMF) are the major compounds that exert therapeutic effects on several pathologic conditions in part, through downregulation of immune responses. The exact mechanism of DMF is yet to be fully understood even though its beneficial effects on the immune system are extensively studied. It has been shown that DMF/MMF can affect various immune cells, which can get involved in both the naive and adaptive immune systems, such as T cells, B cells, dendritic cells, macrophages, neutrophils, and natural killer cells. It is suggested that DMF/MMF may exert their effect on immune cells through inhibition of nuclear factor‐κB translocation, upregulation of nuclear factor erythroid‐derived 2(E2)‐related factor antioxidant pathway, and activation of hydroxyl carboxylic acid receptor 2. In this review, the mechanisms underlying the modulatory functions of DMF or MMF on the main immune cell populations involved in the immunopathogenesis of MS are discussed.
ANALISIS KEMAMPUAN KONEKSI MATEMATIK SISWA MTS DITINJAU DARI SELF REGULATED LEARNING

This study aims to describe the extent to which the mathematical connection ability of students who viewed from Self Regulated Learning seen from students' mistakes in solving a problem of mathematical connection ability. The subject of this study students Classes VIIIA MTs AL-Hikmah Talegong Garut II as many as 20 students. The method used in this research is a descriptive method with quantitative approach. The research stage consisted of 4 stages, among others: self-regulated learning questionnaires, tests of mathematical connection ability, data analysis and draw conclusions. The results of the research were obtained that 1) Students who have high learning independence make mistakes on inter-topic relationships in mathematics and apply/use mathematics in other fields or in everyday life, 2) Students who have learning independence are making mistakes in understanding relationships between topics in mathematics as well as in identifying processes or procedures in carrying out basic concepts, 3) Students have low self-reliance to make mistakes in understanding the relationship of mathematics in other fields of science or in everyday life. Based on the results of the study can be concluded that the better the students' independence in learning then the smaller make a mistake in solve the problem of mathematical connection capabilities.
Input of a Multi-Disciplinary Meeting in the Treatment of Osteoarticular Infections in French War Casualties.

INTRODUCTION Extremity war-wounds present an elevated risk of infection and compromise reconstructive procedures. In a French military hospital, a multi-disciplinary meeting (MDM) was created to standardize the care given to soldiers with osteoarticular infection. The aim of this study was to evaluate the usefulness of MDM decisions. METHODS An observational case study was performed including the French wounded at war treated for an osteoarticular infection between 2004 and 2016. They were separated into two groups according to their time of management: before (group A) or after (group B) the MDM creation in September 2010. Various operative and bacteriological parameters were analyzed retrospectively. A questionnaire was created to evaluate healthcare professionals' satisfaction toward the usefulness of the MDM on their practice. RESULTS During the study period, 38 patients were included: 19 in group A and 19 in group B. Initial tests found an infection with one pathogen in 15 patients, an infection with 2 pathogens in 11 patients, and an infection with 3 or more pathogens in 12 patients. Enterobacter cloacae was the most common pathogen. Pseudomonas aeruginosa and Escherichia coli were also frequent. The mean number of samples taken to conduct the bacteriological tests per operating session was significantly higher for group B than for group A. Twelve of the 14 questioned healthcare professionals believed the MDM was very useful in their patient management. CONCLUSION The MDM seems to have had a beneficial impact on orthopedic surgeon practices. A significant increase of the number of samples taken was the most obvious sign that the French recommended practices for osteoarticular infections were followed since the creation of MDM.
Open randomised trial of the (Arabin) pessary to prevent preterm birth in twin pregnancy with health economics and acceptability: STOPPIT-2—a study protocol

Introduction The STOPPIT-2 study aims to determine the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix, about which there is current uncertainty. STOPPIT-2 will resolve uncertainty around effectiveness for women with a twin pregnancy and a cervical length of 35 mm or less, define adverse effects, ascertain acceptability and estimate National Health Service costs and savings. Methods STOPPIT-2 is a pragmatic multicentre open-label randomised controlled trial. Consenting women with twin pregnancy will have an transvaginal ultrasound scan of their cervical length performed between 18+0 and 20+6 weeks’ gestation by an accredited practitioner: women with a cervical length of ≤35 mm will be eligible for inclusion in the treatment phase of the study. The intervention by the insertion of the Arabin cervical pessary will be compared with standard treatment (no pessary). The primary outcomes are (obstetric) spontaneous onset of labour for the mother leading to delivery before 34 weeks’ gestation and (neonatal) a composite of specific adverse outcomes or death occurring up to the end of the first 4 weeks after the estimated date of delivery to either or both babies. We plan to recruit 500 women in the treatment phase of the study. Assuming a treatment effect of 0.6, and background rates of 35% and 18%, respectively, for each of the primary outcomes, our study has 85% power to detect a difference between the intervention and the control groups. Analysis Data will be analysed on the intention-to-treat principle. Ethics STOPPIT-2 was approved by the South East Scotland Ethics Committee 02 on 29 August 2014, reference number 14/SS/1031 IRAS ID 159610. Dissemination Peer reviewed journals, presentations at national and international scientific meetings. Trial registration number ISRCTN98835694 and NCT02235181.