Miracle-dz/UniFAR-FTUs huggingface dataset:
Clonality of neutrophilia associated with plasma cell neoplasms: report of a SETBP1 mutation and analysis of a single institution series

Abstract A rare but well-known association between plasma cell neoplasms and neutrophilia is known to exist. Whether the neutrophilia is secondary to the plasma cell neoplasm or this convergence represents two independent clonal disorders is unclear. We reviewed five consecutive cases from a single institution over a 3-year period, applying molecular, cytogenetic and cytokine-profiling approaches to determine whether neutrophilia associated with plasma cell neoplasms represents a reactive or clonal process. We report, for the first time, the occurrence of a SETBP1 mutation in two cases, as well as changes in G-CSF and IL-6 in SETBP1 wild type vs. mutated patients that are supportive of a hypothesis that neutrophilia associated with plasma cell neoplasms may sometimes be reactive and may sometimes represent a second clonal entity. Finally, using an ex vivo drug screening platform we report the potential efficacy of the multi-kinase inhibitor dasatinib in select patients.
BMI-for-age in South Asian children of 0–20 years in the Netherlands: secular changes and misclassification by WHO growth references

Abstract Background: South Asians are prone to cardiometabolic disease at lower BMI levels than most other ethnic groups, starting in childhood. The magnitude of BMI misclassifications is unknown. Aim: To compare the BMI distribution of contemporary South Asian 0–20 year olds in the Netherlands with: (1) The South Asian norm reference (secular trends); and (2) The WHO child growth standard and reference. Subjects and methods: The BMI-for-age distribution of 6677 routine measurements of 3322 South Asian children, aged 0–20 years, was described with the LMS method and BMI z-scores. Results: The BMI distribution in South Asian 0–4 year olds was almost similar to the norm reference (mean BMI z-score = 0.11, skewness = 0.31, SD = 1.0), whereas in 5–19 year olds the distribution had shifted upwards (mean = 0.53) and widened (skewness = −0.12, SD = 1.08). Overweight (incl. obesity) and obesity peaked at 8–10 years, at 45–48% and 35–37%, respectively. Relative to the WHO references, the BMI distribution was left-shifted at ages 0–4 years (mean BMI z-score = −0.46, skewness = 0.23, SD = 0.98) and widened at ages 5–20 years (mean = 0.05; skewness = −0.02, SD = 1.40). At most ages, thinness rates were significantly higher and obesity rates lower than based on South Asian norms. Conclusions: A secular change of BMI-for-age in South Asian children mostly affected children >4 years. WHO references likely under-estimate overweight and obesity rates in South Asian children.
Mitochondrially targeted fluorescent redox sensors

The balance of oxidants and antioxidants within the cell is crucial for maintaining health, and regulating physiological processes such as signalling. Consequently, imbalances between oxidants and antioxidants are now understood to lead to oxidative stress, a physiological feature that underlies many diseases. These processes have spurred the field of chemical biology to develop a plethora of sensors, both small-molecule and fluorescent protein-based, for the detection of specific oxidizing species and general redox balances within cells. The mitochondrion, in particular, is the site of many vital redox reactions. There is therefore a need to target redox sensors to this particular organelle. It has been well established that targeting mitochondria can be achieved by the use of a lipophilic cation-targeting group, or by utilizing natural peptidic mitochondrial localization sequences. Here, we review how these two approaches have been used by a number of researchers to develop mitochondrially localized fluorescent redox sensors that are already proving useful in providing insights into the roles of reactive oxygen species in the mitochondria.
Mindfulness-Based Stress Release Program for University Employees: A Pilot, Waitlist-Controlled Trial and Implementation Replication

Objective: The aim of this study was to evaluate the effectiveness of a 6-week mindfulness-based stress release program (SRP) on stress and work engagement in fulltime university employees. Methods: Perceived stress, workplace wellbeing, and engagement were measured at baseline and within 1 week of the SRP completion, and contemporaneously 6 weeks apart for a waitlist control group. A second program was implemented to examine reproducibility of results. Results: Fifty participants undertook the SRPs, and 29 participants were waitlisted. A significant improvement in distress, workplace wellbeing, and vigor was observed within the first SRP group, when compared with the control group. The improvement in distress and wellbeing was reproduced in the second SRP group. Conclusions: This study adds to the growing body of research that mindfulness may be an effective method for reducing workplace stress, improving employee wellbeing, and enhancing work engagement.
Random-walk domination in large graphs

We introduce and formulate two types of random-walk domination problems in graphs motivated by a number of applications in practice (e.g., item-placement problem in online social networks, Ads-placement problem in advertisement networks, and resource-placement problem in P2P networks). Specifically, given a graph G, the goal of the first type of random-walk domination problem is to target k nodes such that the total hitting time of an L-length random walk starting from the remaining nodes to the targeted nodes is minimized. The second type of random-walk domination problem is to find k nodes to maximize the expected number of nodes that hit any one targeted node through an L-length random walk. We prove that these problems are two special instances of the submodular set function maximization with cardinality constraint problem. To solve them effectively, we propose a dynamic-programming (DP) based greedy algorithm which is with near-optimal performance guarantee. The DP-based greedy algorithm, however, is not very efficient due to the expensive marginal gain evaluation. To further speed up the algorithm, we propose an approximate greedy algorithm with linear time complexity w.r. t. the graph size and also with near-optimal performance guarantee. The approximate greedy algorithm is based on carefully designed random walk sampling and sample-materialization techniques. Extensive experiments demonstrate the effectiveness, efficiency and scalability of the proposed algorithms.
BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice

Significance The bromodomain and extraterminal domain (BET) proteins regulate transcription of subset-specifying genes during lineage-specific T-helper-cell differentiation in adaptor immunity and are also implicated in inflammatory disorders. The available pan-BET bromodomain inhibitors such as JQ1 indiscriminately block the tandem bromodomains (BD1 and BD2) of the BET proteins, broadly render differentiation of different Th subsets, and have limited therapeutic potential. Here we report a small molecule, MS402, that can selectively inhibit BD1 over BD2 of the BET proteins and block Th17 maturation from mouse naive CD4+ T cells, with limited or no effects on Th1, Th2, or Treg cells. MS402 effectively prevents and ameliorates T-cell transfer-induced colitis in mice by disrupting Th17 cell development, thus representing a therapeutic approach for inflammatory bowel diseases. T-helper 17 (Th17) cells have important functions in adaptor immunity and have also been implicated in inflammatory disorders. The bromodomain and extraterminal domain (BET) family proteins regulate gene transcription during lineage-specific differentiation of naïve CD4+ T cells to produce mature T-helper cells. Inhibition of acetyl-lysine binding of the BET proteins by pan-BET bromodomain (BrD) inhibitors, such as JQ1, broadly affects differentiation of Th17, Th1, and Th2 cells that have distinct immune functions, thus limiting their therapeutic potential. Whether these BET proteins represent viable new epigenetic drug targets for inflammatory disorders has remained an unanswered question. In this study, we report that selective inhibition of the first bromodomain of BET proteins with our newly designed small molecule MS402 inhibits primarily Th17 cell differentiation with a little or almost no effect on Th1 or Th2 and Treg cells. MS402 preferentially renders Brd4 binding to Th17 signature gene loci over those of housekeeping genes and reduces Brd4 recruitment of p-TEFb to phosphorylate and activate RNA polymerase II for transcription elongation. We further show that MS402 prevents and ameliorates T-cell transfer-induced colitis in mice by blocking Th17 cell overdevelopment. Thus, selective pharmacological modulation of individual bromodomains likely represents a strategy for treatment of inflammatory bowel diseases.
Self-Sterilizing Sputtered Films for Applications in Hospital Facilities

This review addresses the preparation of antibacterial 2D textile and thin polymer films and 3D surfaces like catheters for applications in hospital and health care facilities. The sputtering of films applying different levels of energy led to the deposition of metal/oxide/composite/films showing differentiated antibacterial kinetics and surface microstructure. The optimization of the film composition in regards to the antibacterial active component was carried out in each case to attain the fastest antibacterial kinetics, since this is essential when designing films avoiding biofilm formation (under light and in the dark). The antimicrobial performance of these sputtered films on Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) were tested. A protecting effect of TiO2 was found for the release of Cu by the TiO2-Cu films compared to films sputtered by Cu only. The Cu-released during bacterial inactivation by TiO2-Cu was observed to be much lower compared to the films sputtered only by Cu. The FeOx-TiO2-PE films induced E. coli inactivation under solar or under visible light with a similar inactivation kinetics, confirming the predominant role of FeOx in these composite films. By up-to-date surface science techniques were used to characterize the surface properties of the sputtered films. A mechanism of bacteria inactivation is suggested for each particular film consistent with the experimental results found and compared with the literature.
MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1

Congenital heart defects are the most common birth defects in humans, and those that affect the proper alignment of the outflow tracts and septation of the ventricles are a highly significant cause of morbidity and mortality in infants. A late differentiating population of cardiac progenitors, referred to as the anterior second heart field (AHF), gives rise to the outflow tract and the majority of the right ventricle and provides an embryological context for understanding cardiac outflow tract alignment and membranous ventricular septal defects. However, the transcriptional pathways controlling AHF development and their roles in congenital heart defects remain incompletely elucidated. Here, we inactivated the gene encoding the transcription factor MEF2C in the AHF in mice. Loss of Mef2c function in the AHF results in a spectrum of outflow tract alignment defects ranging from overriding aorta to double-outlet right ventricle and dextro-transposition of the great arteries. We identify Tdgf1, which encodes a Nodal co-receptor (also known as Cripto), as a direct transcriptional target of MEF2C in the outflow tract via an AHF-restricted Tdgf1 enhancer. Importantly, both the MEF2C and TDGF1 genes are associated with congenital heart defects in humans. Thus, these studies establish a direct transcriptional pathway between the core cardiac transcription factor MEF2C and the human congenital heart disease gene TDGF1. Moreover, we found a range of outflow tract alignment defects resulting from a single genetic lesion, supporting the idea that AHF-derived outflow tract alignment defects may constitute an embryological spectrum rather than distinct anomalies. Summary: In the developing mouse anterior second heart field, the transcription factor MEF2C directly controls expression of the Nodal co-receptor Cripto to regulate outflow tract alignment.
Numerical Analyze of Corona Discharge on HVDC Transmission Lines

This study and the field test comparisons were carried out on the Algerian Derguna – Setif transmission systems. The transmission line of normal voltage 225 kV is 65 km long, transported and uses twin bundle conductors protected with two shield wires of transposed galvanized steel. An iterative finite-element method is used to solve Poisons equation. Two algorithms are proposed for satisfying the current continuity condition and updating the space-charge density. A new approach to the problem of corona discharge in transmission system has been described in this paper. The effect of varying the configurations and wires number is also investigated. The analysis of this steady is important in the design of HVDC transmission lines. The potential and electric field have been calculating in locations singular points of the system. Keywords—Corona discharge, Electric field, Finite element method, HVDC.
Impact of National Comprehensive Cancer Network Guidelines on Case Selection and Outcomes for Sentinel Lymph Node Biopsy in Thin Melanoma

BACKGROUND In 2010, the National Comprehensive Cancer Network (NCCN) recommended sentinel lymph node biopsy (SLNB) for thin melanomas ⩽1 mm with mitotic rate (MR) ≥1. In 2016, the criteria were changed to Breslow depth >0.75 mm and MR ≥1. OBJECTIVE To compare the impact of 2010 and 2016 NCCN guidelines on SLNB case selection and thin melanoma outcomes. MATERIALS AND METHODS Ten-year retrospective cohort of primary thin melanomas at an academic hospital was retroactively stratified for SLNB eligibility using the 2010 and 2016 NCCN guidelines. Nodal recurrence-free survival (NRFS) and disease-free survival (DFS) were compared. RESULTS Eight hundred two patients with 859 tumors and median follow-up of 79 months were included. Eleven percent fewer tumors qualified for SLNB under 2016 versus 2010 NCCN guidelines (19% vs 8%, p < .001). The 2016-qualifying cases also had lower 10-year NRFS (70.7% vs 95.2%, p < .001) and DFS (64.7% vs 91.4%, p < .001). Among 2016-qualifying cases, those that received SLNB had improved NRFS (85.6% vs 35.3%, p = .001) and DFS (80.2% vs 30.5%, p < .001) as compared to those that did not receive SLNB. CONCLUSION The 2016 NCCN guidelines reduced the number of thin melanomas qualifying for SLNB and more accurately selected cases with higher risks of nodal recurrence and death.
Biomarkers in Lung Diseases : from Pathogenesis to Prediction to New Therapies Cord blood-derived endothelial colony-forming cell function is disrupted in congenital diaphragmatic hernia

Hideshi Fujinaga, Hiroko Fujinaga, Nobuyuki Watanabe, Tomoko Kato, Moe Tamano, Miho Terao, Shuji Takada, Yushi Ito, Akihiro Umezawa, and Masahiko Kuroda Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan; Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo, Japan; Division of Neonatology, Center for Maternal-Fetal and Neonatal Medicine, National Center for Child Health and Development, Tokyo, Japan; Department of Human Genetics, National Institute for Child Health and Development, Tokyo, Japan; and Department of Systems BioMedicine, National Institute for Child Health and Development, Tokyo, Japan
Anesthetic Neuroprotection in Experimental Stroke in Rodents: A Systematic Review and Meta-analysis

Background: Patients undergoing endovascular therapy for acute ischemic stroke may require general anesthesia to undergo the procedure. At present, there is little clinical evidence to guide the choice of anesthetic in this acute setting. The clinical implications of experimental studies demonstrating anesthetic neuroprotection are poorly understood. Here, the authors evaluated the impact of anesthetic treatment on neurologic outcome in experimental stroke. Methods: Controlled studies of anesthetics in stroke using the filament occlusion model were identified in electronic databases up to December 15, 2015. The primary outcome measures, infarct volume, and neurologic deficit score were used to calculate the normalized mean difference for each comparison. Meta-analysis of normalized mean difference values provided estimates of neuroprotection and contributions of predefined factors: study quality, the timing of treatment, and the duration of ischemia. Results: In 80 retrieved publications anesthetic treatment reduced neurologic injury by 28% (95% CI, 24 to 32%; P < 0.0001). Internal validity was high: publication bias enhanced the effect size by 4% or less, effect size increased with study quality (P = 0.0004), and approximately 70% of studies were adequately powered. Apart from study quality, no predefined factor influenced neuroprotection. Neuroprotection failed in animals with comorbidities. Neuroprotection by anesthetics was associated with prosurvival mechanisms. Conclusions: Anesthetic neuroprotection is a robust finding in studies using the filament occlusion model of ischemic stroke and should be assumed to influence outcomes in studies using this model. Neuroprotection failed in female animals and animals with comorbidities, suggesting that the results in young male animals may not reflect human stroke.
Global trends and patterns of commercial milk-based formula sales: is an unprecedented infant and young child feeding transition underway?

Abstract Objective The marketing of infant/child milk-based formulas (MF) contributes to suboptimal breast-feeding and adversely affects child and maternal health outcomes globally. However, little is known about recent changes in MF markets. The present study describes contemporary trends and patterns of MF sales at the global, regional and country levels. Design Descriptive statistics of trends and patterns in MF sales volume per infant/child for the years 2008–2013 and projections to 2018, using industry-sourced data. Setting Eighty countries categorized by country income bracket, for developing countries by region, and in countries with the largest infant/child populations. Subjects MF categories included total (for ages 0–36 months), infant (0–6 months), follow-up (7–12 months), toddler (13–36 months) and special (0–6 months). Results In 2008–2013 world total MF sales grew by 40·8 % from 5·5 to 7·8 kg per infant/child/year, a figure predicted to increase to 10·8 kg by 2018. Growth was most rapid in East Asia particularly in China, Indonesia, Thailand and Vietnam and was led by the infant and follow-up formula categories. Sales volume per infant/child was positively associated with country income level although with wide variability between countries. Conclusions A global infant and young child feeding (IYCF) transition towards diets higher in MF is underway and is expected to continue apace. The observed increase in MF sales raises serious concern for global child and maternal health, particularly in East Asia, and calls into question the efficacy of current regulatory regimes designed to protect and promote optimal IYCF. The observed changes have not been captured by existing IYCF monitoring systems.
Videoconferencing for Management of Heart Failure: An Integrative Review.

Heart failure (HF) is a chronic disease associated with poor prognosis, poor quality of life (QOL), and high medical costs among older adults. Monitoring symptoms, interpreting symptoms, and decision making are self-care skills required for effective HF management. Telemonitoring (TM) is increasingly used to reduce incidence of symptom exacerbation leading to rehospitalization. An integrative review was performed to describe the efficacy of TM interventions that include videoconferencing (VC) on the HF outcomes of hospital service s use, self-care, and QOL. A review of 11 studies using VC combined with remote physiological monitoring demonstrated promising results in all areas except self-care. Additional research is needed to better specify the goals of VC interventions, the mechanisms by which VC interventions improve health outcomes, and the effect of VC interventions with adults of diverse race and ethnicity. [Journal of Gerontological Nursing, 44(4), 45-52. ].
Subcellular Localization of Monoglucosyldiacylglycerol Synthase in Synechocystis sp. PCC6803 and Its Unique Regulation by Lipid Environment

Synthesis of monogalactosyldiacylglycerol (GalDAG) and digalactosyldiacylglycerol (GalGalDAG), the major membrane lipids in cyanobacteria, begins with production of the intermediate precursor monoglucosyldiacylglycerol (GlcDAG), by monoglucosyldiacylglycerol synthase (MGS). In Synechocystis sp. PCC6803 (Synechocystis) this activity is catalyzed by an integral membrane protein, Sll1377 or MgdA. In silico sequence analysis revealed that cyanobacterial homologues of MgdA are highly conserved and comprise a distinct group of lipid glycosyltransferases. Global regulation of lipid synthesis in Synechocystis and, more specifically, the influence of the lipid environment on MgdA activity have not yet been fully elucidated. Therefore, we purified membrane subfractions from this organism and assayed MGS activity in vitro, with and without different lipids and other potential effectors. Sulfoquinovosyldiacylglycerol (SQDAG) potently stimulates MgdA activity, in contrast to other enzymes of a similar nature, which are activated by phosphatidylglycerol instead. Moreover, the final products of galactolipid synthesis, GalDAG and GalGalDAG, inhibited this activity. Western blotting revealed the presence of MgdA both in plasma and thylakoid membranes, with a high specific level of the MgdA protein in the plasma membrane but highest MGS activity in the thylakoid membrane. This discrepancy in the subcellular localization of enzyme activity and protein may indicate the presence of either an unknown regulator and/or an as yet unidentified MGS-type enzyme. Furthermore, the stimulation of MgdA activity by SQDAG observed here provides a new insight into regulation of the biogenesis of both sulfolipids and galactolipids in cyanobacteria.
Structural and Functional Rich Club Organization of the Brain in Children and Adults

Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain’s white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain’s major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism.