Miracle-dz/UniFAR-FTUs huggingface dataset:
RUNX3 inhibits laryngeal squamous cell carcinoma malignancy under the regulation of miR‐148a‐3p/DNMT1 axis

Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer and accounts for 1% to 2% of all malignancies diagnosed worldwide. Runt‐related transcription factor 3 (RUNX3), an important tumor suppressor, is known to related to lymph node metastasis and the development of LSCC. However, the biological roles and potential mechanisms RUNX3 expression was not well understood. In this study, we reported that the RUNX3 was significantly downregulated and highly methylated in LSCC compared with their matched normal. The enforced expression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. We identified that RUNX3 was regulated by miR‐148a‐3p and found that the expression level of miR‐148‐3p was significantly decreased and positively related with the expression of RUNX3 in LSCC. We also identified that DNA methyltransferase enzyme DNA (cytosine‐5‐)‐methyltransferase 1 (DNMT1) was targeted by miR‐148a‐3p in LSCC. The knockdown of DNMT1 promoted the expression of RUNX3 and inhibited migration, invasion, and proliferation in LSCC cells. In summary, our study demonstrated that miR‐148a‐3p may regulate RUNX3 expression through the modulation of DNMT1‐dependent DNA methylation in LSCC, providing a novel target and a potential therapeutic pathway against LSCC. LSCC is a highly aggressive malignant cancer and accounts for 1% to 2% of all malignancies diagnosed worldwide. In this study, we reported that RUNX3, an important tumor suppressor, was significantly downregulated and highly methylated in LSCC compared with their matched normal. The overexpression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. Moreover, RUNX3 was regulated by miR‐148a‐3p, which targeted DNA methyltransferase enzyme DNMT1 in LSCC cells. Therefore, miR‐148a‐3p may regulate RUNX3 expression through the modulation of DNMT1‐dependent DNA methylation in LSCC, providing a novel target and a potential therapeutic pathway against LSCC.
Lack of Interaction of Erythromycin with Temazepam

Erythromycin is a strong inhibitor of cytochrome P450 [CYP3A4] and has a potentially dangerous interaction with midazolam and triazolam. The possible interaction between erythromycin and a short-acting benzodiazepine, temazepam, was investigated in a double-blind, randomized crossover study. Ten healthy volunteers received 500 mg erythromycin or placebo orally three times a day for 6 days followed by a challenge dose of 20 mg temazepam. Plasma samples were collected for the determination of temazepam, oxazepam, and erythromycin, and psychomotor effects were measured during the 24 h after intake of temazepam. Erythromycin did not change the pharmacokinetics or pharmacodynamics of temazepam to a statistically significant degree. The metabolic fate of temazepam and its almost complete bioavailability explain the lack of interaction. Temazepam, unlike midazolam or triazolam, can thus be prescribed in the usual doses for patients receiving erythromycin.
Minicell-forming mutants of Escherichia coli: production of minicells and anucleate rods

The Escherichia coli minB mutant originally isolated is known to septate at cell poles to form spherical anucleate minicells. Three new minicell-producing mutants were isolated during a screening by autoradiography for chromosome partition mutants giving rise spontaneously to normal-sized anucleate cells. These min mutants were affected close to or in the minB locus. Autoradiography analysis as well as fluorescent staining of DNA showed that in addition to minicells, these strains and the original minB mutant also spontaneously produced anucleate rods of normal size and had an abnormal DNA distribution in filaments. These aberrations were not associated with spontaneous induction of the SOS response. Inhibition of DNA synthesis in these mutants gave rise to anucleate cells whose size was longer than unit cell length, suggesting that the min defect allows septation to take place at normally forbidden sites not only at cell poles but also far from poles. Abnormal DNA distribution and production of anucleate rods suggest that the Min product(s) could be involved in DNA distribution.
Complexity based ranking of biomedical ontologies

A large number of ontologies representing domains of knowledge are accessible on the internet and there is an increasing need for evaluating and assessing their features. Ontology complexity is considered as one of the features to monitor and improve the structure of a given ontology. Despite the fact that many complexity metrics have been proposed, to our best knowledge no study has focused on ranking ontologies based on their level of complexity. This study ranks a set of 25 biomedical ontologies based on their level of complexity. The complexity level of an ontology is determined through the computation of 8 complexity metrics and the metrics values are used as input of Multi-Attributes Decision Making (MADM) methods to get a score representing the level of complexity.
Abnormal telomere shortening in leucocytes of children with Shwachman–Diamond syndrome

Summary. Haemopoietic dysfunction, ranging from single‐lineage cytopenia to severe aplasia and/or myelodysplasia (MDS), is prominent in Shwachman–Diamond syndrome (SDS). To assess haemopoietic stem cell proliferation in SDS, we compared leucocyte telomere length in 12 patients with SDS to that of 41 controls, using an in‐gel hybridization technique. SDS patients had an age‐adjusted mean telomere length 1·4 kilobase pairs (kbp) shorter than controls (P < 0·0001). Patients with'non‐severe′ SDS (one‐ or two‐lineage cytopenias; no MDS) had shortened telomeres (−1·4 kbp; P = 0·0004), as did those with ‘severe’ SDS. We conclude that stem cell hyperproliferation is a feature of SDS from its outset.
Model Based Systems Engineering with Department of Defense Architectural Framework

This paper presents a methodology for Model Based Systems Engineering (MBSE) utilizing the guidelines provided by the Department of Defense Architectural Framework (DoDAF). MBSE focuses the system engineering process on system modeling. Thus, requirements derivation, system design, integration, verification, and validation activities all center around the model of the system. System models can be built in many ways. This paper presents an approach using DoDAF. Visual accessibility of the DoDAF views facilitates full participation by all system stakeholders, including the customers, developers, and implementers, and enables the necessary dialogue. The approach promotes communications among the members of the development team and speeds up the iterations of the systems engineering process. The paper illustrates the utility of the DoDAF artifacts by means of a simplified but comprehensive, easy to follow, illustrative example. © 2011 Wiley Periodicals, Inc. Syst Eng
Mobile and Interactive Media Use by Young Children: The Good, the Bad, and the Unknown

The use of interactive screen media such as smartphones and tablets by young children is increasing rapidly. However, research regarding the impact of this portable and instantly accessible source of screen time on learning, behavior, and family dynamics has lagged considerably behind its rate of adoption. Pediatric guidelines specifically regarding mobile device use by young children have not yet been formulated, other than recent suggestions that a limited amount of educational interactive media use may be acceptable for children aged <2 years.1 New guidance is needed because mobile media differs from television in its multiple modalities (eg, videos, games, educational apps), interactive capabilities, and near ubiquity in children’s lives. Recommendations for use by infants, toddlers, and preschool-aged children are especially crucial, because effects of screen time are potentially more pronounced in this group. The aim of this commentary is to review the existing literature, discuss future research directions, and suggest preliminary guidance for families. ### Educational Value Although well-researched television programs such as Sesame Street or Blue’s Clues can promote early academic skills in preschool-aged children, children <30 months cannot learn from television and videos as they do from real-life interactions.2 Interactive media, on the other hand, allow for contingent responses to children’s actions and thus may facilitate more retention of taught material. For example, socially contingent media (ie, with appropriate content, timing, and intensity) such as videophone apps are just as effective as real-life encounters in teaching language to 24 month olds,3 but otherwise, published research on whether infants and toddlers can learn from interactive screens is scant. Promising research suggests that interactive media such as learn-to-read apps and electronic books (e-books) may increase early literacy … Address correspondence to Jenny S. Radesky, Boston Medical Center, Vose 4, 88 E Newton St, Boston, MA 02118. E-mail: jenny.radesky{at}bmc.org
Erythropoietin improves brain mitochondrial function in rats after traumatic brain injury

Abstract Mitochondria play a central role in cellular energetics, calcium homeostasis and apoptosis. Our previous study demonstrates traumatic brain injury induces brain mitochondrial dysfunction after injury. Preservation and/or restoration of mitochondrial function may be one of the strategies for neuroprotection. Erythropoietin, a hormone for erythropoiesis, also provides tissue protection against traumatic brain injury and stroke. The present study was undertaken to evaluate the effect of erythropoietin on traumatic brain injury-induced brain mitochondrial dysfunction. Traumatic brain injury decreased rates of respiration at the active state (state 3), increased that at the resting state (state 4) and consequently decreased respiratory control index (state 3/state 4 ratio) and the efficiency of ATP synthesis (the amount of ADP phosphorylated by inorganic phosphate divided by the amount of oxygen consumed during state 3 respiration). Erythropoietin administered intraperitoneally 30 minutes post-injury at 1000 U/kg partially improved mitochondrial function at day 1 post-injury. However, erythropoietin-induced improvement was not sustained at day 7 post-injury. Erythropoietin at 2000 or 5000 U/kg restored states 3 and 4 examined at day 1 post-injury to the sham levels. Consequently, the energy coupling capacities, such as respiratory control index and/or the efficiency of ATP synthesis, were also improved. The beneficial effect of erythropoietin at these doses persisted for at least 7 days post-injury. The beneficial effect of erythropoietin on brain mitochondrial function was observed with a wide therapeutic window from 5 minutes to 6 hours post-injury. Our data, for the first time, demonstrate that erythropoietin treatment restores brain mitochondrial function after traumatic brain injury, which will enhance cellular energy generation and reduce oxidative stress, strongly supporting erythropoietin as a promising agent for the therapeutic treatment of traumatic brain injury.
Increased incidence of differentiated thyroid carcinoma and detection of subclinical disease

Background: Recent reports from North America and Europe have documented an annual increase in the incidence of differentiated thyroid carcinoma. We sought to investigate the relation between rates of detection, tumour size, age and sex. Methods: Using the Ontario Cancer Registry, we identified 7422 cases of differentiated thyroid carcinoma diagnosed from Jan. 1, 1990, to Dec. 31, 2001. We obtained pathology reports for a random 10% of the 7422 patients for each year of the study period. The sample represented all Cancer Care Ontario regions. We compared the size of the patients' tumours by year, sex and age. Results: As expected, the incidence of differentiated thyroid carcinoma increased over the 12-year period. A significantly higher number of small (≤ 2 cm), nonpalpable tumours were resected in 2001 than in 1990 (p = 0.001). The incidence of tumours 2–4 cm in diameter remained stable. When we examined differences in tumour detection rates by age and sex, we observed a disproportionate increase in the number of small tumours detected among women and among patients older than 45 years. Interpretation: Our findings suggest that more frequent use of medical imaging has led to an increased detection rate of small, subclinical tumours, which in turn accounts for the higher incidence of differentiated thyroid carcinoma. This suggests that we need to re-evaluate our understanding of the trends in thyroid cancer incidence.
A Spatially Periodic Solute Boundary for MT3DMS and PHT3D

The assumption of spatial repetition is commonly made when producing bedform scale models of the hyporheic zone. Two popular solute transport codes, MT3DMS and PHT3D, do not currently provide the necessary boundary condition required to simulate spatial periodicity in hyporheic zone transport problems. In this study, we develop a spatially periodic boundary (SPB) for solutes that is compatible with a SPB that was previously developed for MODFLOW to simulate the flow component of spatially periodic problems. The approach is ideal for simulating groundwater flow and transport patterns under repeating surface features, such as ripples or dunes on the bottom of a lake or stream. The appropriate block‐centered finite‐difference approach to implement the boundary is presented and the necessary source code modifications are discussed. The performance of the solute SPB, operating in conjunction with the groundwater flow SPB, is explored through comparison of a multi‐bedform hyporheic‐zone model with a single bedform variant. The new boundary conditions perform well in situations where both dispersive effects and lateral seepage flux in the underflow regime beneath the hyporheic zone are minimal.
Catalan and Hungarian Validation of the Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ)

Abstract The goal of this study was to examine the cross-cultural validity and reliability of the Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ) – a recently published instrument for assessing the Zuckerman’s Alternative Five Factor Personality Model – in Catalan and Hungarian speaking populations. The samples consisted of 1,564 subjects from Catalonia and 1,647 from Hungary. Results showed a clear five-factor structure and acceptable alpha reliabilities of the ZKA-PQ in both countries. Facets alpha average was 80.35 and 74.10 for Catalans and Hungarians respectively. The factorial congruency coefficients indicated that both structures were equivalent, with a global value of . 97. However, the robust structure obtained with EFA yielded poor fit indices in the subsequent CFA. Altogether, the psychometric findings were similar to those obtained in the original validation study carried out in Spanish and English populations. Main country differences were found only in Neuroticism factor, with Hungarians scoring significantly lower that Catalans. Nevertheless, country, sex and age explained only 18.6 % of Neuroticism variance (adjusted R squared = .186). Country differences had only medium effect size [F(1, 3188) = 292, p < . 001, η2 = . 084 1 ].
Job Sharing in the Endomembrane System: Vacuolar Acidification Requires the Combined Activity of V-ATPase and V-PPase

Mutant analysis not only reveals that the interactions of the two tonoplast proton pumps V-ATPase and V-PPase are complex but also that they are assisted by the TGN/EE-localized V-ATPase. The presence of a large central vacuole is one of the hallmarks of a prototypical plant cell, and the multiple functions of this compartment require massive fluxes of molecules across its limiting membrane, the tonoplast. Transport is assumed to be energized by the membrane potential and the proton gradient established by the combined activity of two proton pumps, the vacuolar H+-pyrophosphatase (V-PPase) and the vacuolar H+-ATPase (V-ATPase). Exactly how labor is divided between these two enzymes has remained elusive. Here, we provide evidence using gain- and loss-of-function approaches that lack of the V-ATPase cannot be compensated for by increased V-PPase activity. Moreover, we show that increased V-ATPase activity during cold acclimation requires the presence of the V-PPase. Most importantly, we demonstrate that a mutant lacking both of these proton pumps is conditionally viable and retains significant vacuolar acidification, pointing to a so far undetected contribution of the trans-Golgi network/early endosome-localized V-ATPase to vacuolar pH.
Infant Neurological Examination from 3 to 12 Months: Predictive Value of the Single Items

The prognostic value of the single items of a standardised neurological examination, the Hammersmith Infant Neurologic Examination (HINE), was explored longitudinally in 658 infants at 3, 6, 9 and 12 months post-term age. ROC curves were built based on the presence/absence of cerebral palsy at 2 years of age. Global HINE scores showed very high prediction (ROC curve areas above 0.9) at all ages. The items with the highest predictive value were always movement quality and quantity. In the first semester, among the most predictive items were those assessing tone, while beyond that time they were reflexes and reactions. Our results show that the high predictive value of the HINE across the first year of life is granted by the successful combination of different groups of items for each age-period. This should be recognised in clinical practice when assessing the significance of individual neurological profiles.
Use of a social and character development program to prevent substance use, violent behaviors, and sexual activity among elementary-school students in Hawaii.

OBJECTIVES We assessed the effectiveness of a 5-year trial of a comprehensive school-based program designed to prevent substance use, violent behaviors, and sexual activity among elementary-school students. METHODS We used a matched-pair, cluster-randomized, controlled design, with 10 intervention schools and 10 control schools. Fifth-graders (N = 1714) self-reported on lifetime substance use, violence, and voluntary sexual activity. Teachers of participant students reported on student (N = 1225) substance use and violence. RESULTS Two-level random-effects count models (with students nested within schools) indicated that student-reported substance use (rate ratio [RR] = 0.41; 90% confidence interval [CI] = 0.25, 0.66) and violence (RR = 0.42; 90% CI = 0.24, 0.73) were significantly lower for students attending intervention schools. A 2-level random-effects binary model indicated that sexual activity was lower (odds ratio = 0.24; 90% CI = 0.08, 0.66) for intervention students. Teacher reports substantiated the effects seen for student-reported data. Dose-response analyses indicated that students exposed to the program for at least 3 years had significantly lower rates of all negative behaviors. CONCLUSIONS Risk-related behaviors were substantially reduced for students who participated in the program, providing evidence that a comprehensive school-based program can have a strong beneficial effect on student behavior.
“Candidatus Hepatoplasma crinochetorum,” a New, Stalk-Forming Lineage of Mollicutes Colonizing the Midgut Glands of a Terrestrial Isopod

ABSTRACT Uncultivated bacteria that densely colonize the midgut glands (hepatopancreas) of the terrestrial isopod Porcellio scaber (Crustacea: Isopoda) were identified by cloning and sequencing of their 16S rRNA genes. Phylogenetic analysis revealed that these symbionts represent a novel lineage of the Mollicutes and are only distantly related (<82% sequence identity) to members of the Mycoplasmatales and Entomoplasmatales. Fluorescence in situ hybridization with a specific oligonucleotide probe confirmed that the amplified 16S rRNA gene sequences indeed originated from a homogeneous population of symbionts intimately associated with the epithelial surface of the hepatopancreas. The same probe also detected morphotypically identical symbionts in other crinochete isopods. Scanning and transmission electron microscopy revealed uniform spherical bacterial cells without a cell wall, sometimes interacting with the microvilli of the brush border by means of stalk-like cytoplasmic appendages, which also appeared to be involved in cell division through budding. Based on the isolated phylogenetic position and unique cytological properties, the provisional name “Candidatus Hepatoplasma crinochetorum” is proposed for this new taxon of Mollicutes colonizing the hepatopancreas of P. scaber.
Face, brain, and veins: a new perspective for multiple sclerosis onset.

To the Editor: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system of unknown origin, which is widely considered to be autoimmune in nature. Multiple sclerosis and chronic venous disease (CVD) share some key features such as expression of adhesion molecules, matrix metalloproteinases hyperactivation, macrophage and T-lymphocyte infiltration, and increased iron deposition. Both CVD and MS are histologically characterized by the peculiarity of perivenous iron deposition of extracellular hemosiderin and iron-laden macrophages as well as pericapillary fibrin cuff. Iron stores in the white and deep gray matter in the course of MS have never been explained and could be related to altered modality of venous return determined by extracranial multiple venous strictures. The hampered cerebrospinal venous drainage in patients with MS determines a complex hemodynamic picture defined as chronic cerebrospinal venous insufficiency. It is characterized by multiple substitute circles, with a very high incidence of reflux in both intracranial and extracranial venous segments, and loss of the postural regulation of cerebral venous outflow. The mechanism underlying this reflux differs from the reflux caused by incompetence of the jugular valve. The reflux occurred in any body position without the need to elicit it by a forced movement, suggesting that it is not an expression of valvular incompetence but rather of a stenosing lesion that cannot be crossed with postural or respiratory mechanisms, thereby becoming a long-lasting reverse flow. Substitute circles are alternative pathways or vicarious venous shunts that allow for the piping of blood toward available venous segments outside the central nervous system. Both the intracranial and the intrarrhachidian veins can also become substitute circles, and they permit redirection of the deviated flow, preventing intracranial hypertension. However, over time, they become overloaded because they carry 2 different flows: their own draining flow and the shunted flow. Four main patterns of chronic cerebrospinal venous insufficiency have been identified, according to the location, number and association of venous stenosis, and modality of collateral circulation. The location of venous obstruction seems to be a key element influencing the clinical course of the disease. Compelling evidences derived from patients affected by MS and CVD and treated with angioplasty demonstrating a complete recovery of clinical MS signs, suggesting a pathogenetic role of vein drainage stenosis, including neck vessels, in the onset of MS. Neck dissection and jugular tie could have an impact on MS.