Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran

ABSTRACT: Neurodegeneration with brain iron accumulation (NBIA) is a term used for a group of hereditary neurological disorders with abnormal accumulation of iron in basal ganglia. It is clinically and genetically heterogeneous with symptoms such as dystonia, dysarthria, Parkinsonism, intellectual disability, and spasticity. The age at onset and rate of progression are variable among individuals. Current therapies are exclusively symptomatic and unable to hinder the disease progression. Approximately 16 genes have been identified and affiliated to such condition with different functions such as iron metabolism (only two genes: Ferritin Light Chain (FTL) Ceruloplasmin (CP)), lipid metabolism, lysosomal functions, and autophagy process, but some functions have remained unknown so far. Subgroups of NBIA are categorized based on the mutant genes. Although in the last 10 years, the development of whole-exome sequencing (WES) technology has promoted the identification of disease-causing genes, there seem to be some unknown genes and our knowledge about the molecular aspects and pathogenesis of NBIA is not complete yet. There is currently no comprehensive study about the NBIA in Iran; however, one of the latest discovered NBIA genes, GTP-binding protein 2 (GTPBP2), has been identified in an Iranian family, and there are some patients who have genetically remained unknown.
Efficacy of cogmed working memory training program in improving working memory in school-age children with and without neurological insults or disorders: A meta-analysis

Abstract This meta-analysis assessed the efficacy of the Cogmed Working Memory Training program in improving near-transfer measures (verbal and visuospatial working memory) and far-transfer measures (attention, executive function, and academic achievement) in school-age children with and without neurological insults or disorders. Relevant studies were searched in databases and clinical trial registries using the keyword Cogmed. Ten published studies and unpublished data from one study met the inclusion criteria. Hedges g was calculated for each outcome measure obtained at pre-intervention, post-intervention, and 3–6 month time points. Analysis compared outcome measures in the control versus experimental groups and examined the role of moderators on treatment effects (control group intervention, intervention environment). Data revealed significant medium-size effects of the Cogmed program in improving verbal and visuospatial working memory post-intervention and for verbal working memory only at the 3–6 month time point. However, the training did not generalize to the far-transfer measures. Analyses indicated that only the type of intervention provided for the control group moderated treatment effects on verbal and visual working memory. Meta-analytic findings suggest that the Cogmed program leads to short-term improvements and in some cases, long-term improvements in working memory in school-age children; however, these effects may not generalize to far-transfer measures.
Unveiling the Virulent Genotype and Unusual Biochemical Behavior of Escherichia coli ST59

The use of selective and differential media is a rule that guides presumptive bacterial identification based on specific metabolic traits that are specific to each bacterial species. When a bacterial specimen displays an unusual phenotype in these media, this characteristic may lead to bacterial misidentification or a significant delay in its identification, putting a patient at risk depending on the infection type. ABSTRACT Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of human and animal infections worldwide. The utilization of selective and differential media to facilitate the isolation and identification of E. coli from complex samples, such as water, food, sediment, and gut tissue, is common in epidemiological studies. During a surveillance study, we identified an E. coli strain isolated from human blood culture that displayed atypical light cream-colored colonies in chromogenic agar and was unable to produce β-glucuronidase and β-galactosidase in biochemical tests. Genomic analysis showed that the strain belongs to sequence type 59 (ST59) and phylogroup F. The evaluation in silico of 104 available sequenced lineages of ST59 complex showed that most of them belong to serotype O1:K1:H7, are β-glucuronidase negative, and harbor a virulent genotype associated with the presence of important virulence markers such as pap, kpsE, chuA, fyuA, and yfcV. Most of them were isolated from extraintestinal human infections in diverse countries worldwide and could be clustered/subgrouped based on papAF allele analysis. Considering that all analyzed strains harbor a virulent genotype and most do not exhibit biochemical behavior typical of E. coli, we report that they could be misclassified or underestimated, especially in epidemiological studies where the screening criteria rely only on typical biochemical phenotypes, as happens when chromogenic media are used. IMPORTANCE The use of selective and differential media guides presumptive bacterial identification based on specific metabolic traits that are specific to each bacterial species. When a bacterial specimen displays an unusual phenotype in these media, this characteristic may lead to bacterial misidentification or a significant delay in its identification, putting a patient at risk depending on the infection type. In the present work, we describe a virulent E. coli sequence type (ST59) that does not produce beta-glucuronidase (GUS negative), production of which is the metabolic trait widely used for E. coli presumptive identification in diverse differential media. The recognition of this unusual metabolic trait may help in the proper identification of ST59 isolates, the identification of their reservoir, and the evaluation of the frequency of these pathogens in places where automatic identification methods are not available.
Polyvinylpyrrolidone in hemodialysis membranes: Impact on platelet loss during hemodialysis

Hydrophilic modification with polyvinylpyrrolidone (PVP) increases the biocompatibility profile of synthetic dialysis membranes. However, PVP may be eluted into the patient's blood, which has been discussed as a possible cause for adverse reactions rarely occurring with synthetic membranes. We investigated the content of PVP and its elution from the blood‐side surface from commercially available dialyzers, including the novel FX CorAL, with PVP‐enriched and α‐tocopherol‐stabilized membrane, and link the results to the level of platelet loss during dialysis as a maker of biocompatibility.
Inflammation-Induced Histamine Impairs the Capacity of Escitalopram to Increase Hippocampal Extracellular Serotonin

Commonly prescribed selective serotonin reuptake inhibitors (SSRIs) inhibit the serotonin transporter to correct a presumed deficit in extracellular serotonin signaling during depression. These agents bring clinical relief to many who take them; however, a significant and growing number of individuals are resistant to SSRIs. There is emerging evidence that inflammation plays a significant role in the clinical variability of SSRIs, though how SSRIs and inflammation intersect with synaptic serotonin modulation remains unknown. In this work, we use fast in vivo serotonin measurement tools to investigate the nexus between serotonin, inflammation, and SSRIs. Upon acute systemic lipopolysaccharide (LPS) administration in male and female mice, we find robust decreases in extracellular serotonin in the mouse hippocampus. We show that these decreased serotonin levels are supported by increased histamine activity (because of inflammation), acting on inhibitory histamine H3 heteroreceptors on serotonin terminals. Importantly, under LPS-induced histamine increase, the ability of escitalopram to augment extracellular serotonin is impaired because of an off-target action of escitalopram to inhibit histamine reuptake. Finally, we show that a functional decrease in histamine synthesis boosts the ability of escitalopram to increase extracellular serotonin levels following LPS. This work reveals a profound effect of inflammation on brain chemistry, specifically the rapidity of inflammation-induced decreased extracellular serotonin, and points the spotlight at a potentially critical player in the pathology of depression, histamine. The serotonin/histamine homeostasis thus, may be a crucial new avenue in improving serotonin-based treatments for depression. SIGNIFICANCE STATEMENT Acute LPS-induced inflammation (1) increases CNS histamine, (2) decreases CNS serotonin (via inhibitory histamine receptors), and (3) prevents a selective serotonin reuptake inhibitor (SSRI) from effectively increasing extracellular serotonin. A targeted depletion of histamine recovers SSRI-induced increases in extracellular hippocampal serotonin.
DOES GENDER AFFECT THE OUTCOMES OF PATIENTS IN PROGRAM OF MANAGED CARE FOR ACUTE MYOCARDIAL INFARCTION

Background There is increasing evidence that cardiac rehabilitation and regular follow-ups are associated with reduced mortality and morbidity. A programme of Managed Care for Patients with Acute Myocardial Infarction was developed in Poland (MC-AMI; in Polish, KOS-zawał), based on current scientific evidence. However, there is a lack of data on possible improvement in long-term prognosis among women after acute myocardial infarction. Aims To compare the male and female population who participated in MC-AMI, regarding major cardiovascular events, defined as a composite of death, recurrent myocardial infarction, and hospitalization for heart failure, in a 1-year follow-up. Methods A prospective research study from a single cardiology care centre. The study compared 2 groups: women and men who agreed to participate in the MC-AMI programme. Results A total of 529 patients were included in the study (167 women and 362 men). In the 12-month follow-up, the difference in major cardiovascular events events was not statistically significant for women and men, respectively (11.38% women vs 11.33% men; p = 0.98). Cox multivariate regression analysis of the surveyed population showed that coronary heart disease, diabetes mellitus type II, and previous percutaneous coronary intervention were significantly correlated with the primary endpoint. Conclusion Women participating in the MC-AMI programme did not have a worse prognosis regarding major cardiovascular events, compared with men in a 12-month follow-up. Given the benefits of the MCAMI programme, the proportion of women participating in the programme should be increased. LAY ABSTRACT Despite the development of new treatment techniques, myocardial infarction remains one of the leading causes of death in Europe. Women account for 48% of patients with myocardial infarction. Due to clinical, economic, demographic and sociological conditions, the long-term prognosis for women after myocardial infarction is worse than for men. A national programme of managed care after myocardial infarction has been introduced in 2019 year in Poland (MC-AMI; in Polish, KOS-zawał). The programme comprises 4 stages: hospitalization and treatment of the acute phase of myocardial infarction; early cardiological rehabilitation; regular follow-up at in-patient clinic; and evaluation of indications for advanced methods of treatment of post-infarction complications. Implementation of this programme in Poland has resulted in a comparable long-term prognosis being achieved for the male and female population. Widespread use of the MC-AMI programme is a promising option to equalize the prognosis for both sexes after a heart attack.
DNA-methylation-based telomere length estimator: comparisons with measurements from flow FISH and qPCR

Telomere length (TL) is a marker of biological aging associated with several health outcomes. High throughput reproducible TL measurements are needed for large epidemiological studies. We compared the novel DNA methylation-based estimator (DNAmTL) with the high-throughput quantitative PCR (qPCR) and the highly accurate flow cytometry with fluorescent in situ hybridization (flow FISH) methods using blood samples from healthy adults. We used Pearson’s correlation coefficient, Bland Altman plots and linear regression models for statistical analysis. Shorter DNAmTL was associated with older age, male sex, white race, and cytomegalovirus seropositivity (p<0.01 for all). DNAmTL was moderately correlated with qPCR TL (N=635, r=0.41, p < 0.0001) and flow FISH total lymphocyte TL (N=144, r=0.56, p < 0.0001). The agreements between flow FISH TL and DNAmTL or qPCR were acceptable but with wide limits of agreement. DNAmTL correctly classified >70% of TL categorized above or below the median, but the accuracy dropped with increasing TL categories. The ability of DNAmTL to detect associations with age and other TL-related factors in the absence of strong correlation with measured TL may indicate its capture of aspects of telomere maintenance mechanisms and not necessarily TL. The inaccuracy of DNAmTL prediction should be considered during data interpretation and across-study comparisons.
Effects of Eccentric Single-Leg Decline Squat Training Performed With Different Execution Times on Maximal Strength and Muscle Contraction Properties of the Knee Extensor Muscles

Abstract Abián-Vicén, J, Martínez, F, Jiménez, F, and Abián, P. Effects of eccentric single-leg decline squat training performed with different execution times on maximal strength and muscle contraction properties of the knee extensor muscles. J Strength Cond Res 36(11): 3040–3047, 2022—The eccentric phase of the single-leg decline squat (SLDSe) has been described as a method to maximally load the knee extensor and has been used as an easy and effective rehabilitation exercise for patellar tendinopathy. The purpose of this study was to examine the impact of 6-week SLDSe training with 2 technical execution times on changes related to strength and muscle contractile properties. Thirty-six healthy volunteers were randomly divided into 3 groups: a control group (CG, n = 13, no training), a slow training group (n = 11, SLDSe in 6 seconds), and a fast training group (n = 12, SLDSe in 3 seconds). Subjects completed a 6-week SLDSe training program (80% of eccentric one repetation maximum [1RM]) 3 days a week. Pre, post, and 6-week follow-up of maximal dynamic and isometric strength and muscle contractile properties were assessed. After 6 weeks, training maximal loads showed a significant increase (p < 0.05) in 1RM of the SLDSe (∼92–95%), the concentric peak torque at 180°·s−1 (∼38%) and 60°·s−1 (∼25%), and the extension isometric peak torque (∼12%), with no differences between both experimental groups. Moreover, a decrease (p < 0.05) was found in the contraction time of the vastus medialis (VM) and the response time of the 3 analyzed quadriceps muscles. After the 6-week detraining period, there was a decrease in strength in all tests and in both experimental groups (1RM = 28–37%, isometric and isokinetic tests = 7–17%) and all contractile properties returned to baseline, except for the response time of the vastus lateralis in the fast training group and the contraction time of the VM in the STG. In conclusion, the SLDSe training protocol produced significant increases in muscle strength, showing important neuromuscular changes regardless of the technical execution time. It was also found that the training reduced the response and contraction time of the knee extensor musculature.
Maybe favors: How to get more good deeds done.

While previous research has revealed several reasons why humans generally do good deeds, we explore a simple nudge that might get more of them done: the "maybe favor. " We first show conceptually that, compared to a conventional favor, humans are more willing to grant a favor to a stranger on which they might eventually not have to make good. Furthermore, we conducted a series of fully incentivized experiments (total N = 3,475) where participants could make actual donations to charity. Introducing a "maybe" into our donation proposals by randomly revoking some donations not only led to significant increases in donation rates but also increased the total amount of donations. That is, due to biased perceptions of costs and benefits combined with nonlinear probability weighting, the donations we revoked due to the "maybe" were overcompensated by an increased overall willingness-to-donate. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Untersuchungen zum Einfluss der DNA-Superhelizität auf die Struktur und Stabilität von Nukleosomen und die interne DNA-Dynamik

Die DNA im Chromatin einer Zelle steht standig unter Torsionsspannung, da ein groser Teil dieser DNA in negativ superhelikalen Windungen um Histonoktamere herum vorliegt. Positive wie auch negative Torsionsspannung wird auch z.B. wahrend der Elongationsphase der Transkription aufgebaut. Sie steuert die Zuganglichkeit nukleosomaler DNA, andert die Struktur genregulatorischer Elemente und fuhrt zu Anderungen der Segmentbeweglichkeit ("interne Dynamik") der DNA. In dieser Dissertation wurde der Einfluss der Torsionsspannung der DNA auf die Struktur und Stabilitat von Nukleosomen untersucht. Plasmide mit biochemisch eingestellter Torsionsspannung und auf ihnen rekonstituierte Nukleosomen, wurden hierfur als experimentelles Modellsystem verwendet. Damit kann einerseits die Struktur der Plasmide und Nukleosomen durch Bindung an eine Oberflache und Bildgebung mittels Rasterkraftmikroskopie (SFM) untersucht werden. Andererseits lasst sich ihr Verhalten in Losung mittels Fluoreszenz-Korrelationsspektroskopie (FCS) beobachten. Fur die FCS-Messungen wurden einzelne Histonproteine fluoreszent markiert. Dies erlaubte es, mit Hilfe von salzinduzierter Destabilisierung, die Stabilitat von Nukleosomen in Abhangigkeit der Torsionsspannung auf dem Plasmid zu untersuchen. Hierbei zeigte sich, dass ein Ubergang von negativer zu positiver Torsionsspannung die Nukleosomenintegritat schwacht. Mittels SFM-Bildgebung konnte weiterhin gezeigt werden, dass sich die Nukleosomenstruktur mit abnehmender negativer Torsionsspannung und dem Auftreten von positiver Torsionsspannung offnet. In weiteren Experimenten wurden spezifische Stellen auf den Plasmiden mit Fluoreszenzfarbstoffen markiert. Hierdurch war es moglich die globale und interne Dynamik der Plasmide auf unterschiedlichen Zeitskalen zu beobachten. In dieser Arbeit wurde mit der beschriebenen Methode der Einfluss der Superhelizitat selbst auf die interne und globale Dynamik, sowie der Einfluss der Ionenstarke der Losung auf selbige untersucht. Die Ergebnisse erweitern altere Messungen mit dynamischer Lichtstreuung (DLS) und bestatigen einige Simulationsergebnisse experimentell. Es werden auserdem zwei weitere biologisch relevante Effekte auf die interne DNA-Dynamik untersucht: das Verhalten der DNA in unterschiedlich viskosen Medien und bei der Verpackung in Nukleosomen. Die erhohte Viskositat fuhrte durch unterschiedliche Verlangsamung der internen DNA-Segmentbewegung und der Gesamtbewegung des Plasmids zu einer Trennung beider Bewegungsmodi mit steigender Viskositat. Mit ansteigender Zahl an Nukleosomen auf dem Plasmid wurde einerseits, durch die Kompaktierung der DNA, die translationale Diffusion beschleunigt. Andererseits kam es hier auf sehr kurzen Zeitskalen zu einer Beschleunigung der internen DNA-Segment-Bewegungen.
Abcc1 and Ggt5 support lymphocyte guidance through export and catabolism of S-geranylgeranyl-l-glutathione

This work establishes how P2RY8 ligand is exported and degraded to regulate lymphocyte behavior in lymphoid follicles and bone marrow. A bouncer for the bone marrow P2RY8 is a G protein–coupled receptor (GPCR) that is involved in restraining germinal center (GC) B cell migration and growth. It is unclear how the ligand of P2RY8, S-geranylgeranyl-l-glutathione (GGG), is involved in these processes. Using gain-of-function mouse models and genetically modified human T cells, Gallman et al. showed that expression of gamma-glutamyltransferase-5 (Ggt5) on stromal cells and ATP-binding cassette subfamily C member 1 (Abcc1) on hematopoietic cells was involved in catabolizing and transporting GGG, respectively, and restraining P2RY8+ cells within GCs. GGG and P2RY8 interactions also restrained lymphocyte trafficking to the bone marrow. Thus, GGG and P2RY8 processing and interactions are crucial for the confinement of B cells within GCs and for inhibiting migration of lymphocytes into bone marrow. P2RY8 promotes the confinement and growth regulation of germinal center (GC) B cells, and loss of human P2RY8 is associated with B cell lymphomagenesis. The metabolite S-geranylgeranyl-l-glutathione (GGG) is a P2RY8 ligand. The mechanisms controlling GGG distribution are poorly understood. Here, we show that gamma-glutamyltransferase-5 (Ggt5) expression in stromal cells was required for GGG catabolism and confinement of P2RY8-expressing cells to GCs. We identified the ATP-binding cassette subfamily C member 1 (Abcc1) as a GGG transporter and showed that Abcc1 expression by hematopoietic cells was necessary for P2RY8-mediated GC confinement. Furthermore, we discovered that P2RY8 and GGG negatively regulated trafficking of B and T cells to the bone marrow (BM). P2RY8 loss-of-function human T cells increased their BM homing. By defining how GGG distribution was determined and identifying sites of P2RY8 activity, this work helps establish how disruptions in P2RY8 function contribute to lymphomagenesis and other disease states.
Firm-specific orientations and manufacturing capability under institutional voids

ABSTRACT Manufacturing capability (MC) is widely considered to depend on a strategic orientation of firms and institutional support. Remarkably, little is known about the influence of firm-specific orientations on manufacturing capability under institutional voids. This study examines the extent to which learning orientation (LO) and entrepreneurial orientation (EO) influence institutional support to enhance firms’ MC. While EO prompts effective responses to institutional voids, institutional support reduces them and LO allows a firm to continuously learn in response to such voids. Drawing insights from the resource-based view (RBV) and institutional theory, this study tests this argument using partial least squares path modeling on a sample of 105 surveyed export manufacturers from Tanzania and Kenya. Findings indicate that although both LO and EO are the major antecedents of MC, firms must be entrepreneurially oriented in order to significantly influence the institutional support. Even though the literature states that institutional support plays a great role in enhancing MC, research findings suggest otherwise. Thus, focusing on the novel constructs relationship and importance-performance analysis, this study contributes to the RBV and institutional theory by providing theoretical and practical implications of the research findings for the contexts where national institutions facilitating business activities are inefficient.