Miracle-dz/UniFAR-FTUs huggingface dataset:
Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer*

Background: LIN28A may function as a critical oncogene in human cancer. Results: LIN28A controls expression of numerous cell cycle regulatory genes, including CDK2, CCND1, and CDC25A, in cancer. Conclusion: LIN28A promotes cell cycle progression in cancer mediated by both let-7-dependent and -independent mechanisms. Significance: Our data shed new light on how LIN28A regulates cell cycle in cancer. The RNA-binding protein LIN28A regulates the translation and stability of a large number of mRNAs as well as the biogenesis of certain miRNAs in embryonic stem cells and developing tissues. Increasing evidence indicates that LIN28A functions as an oncogene promoting cancer cell growth. However, little is known about its molecular mechanism of cell cycle regulation in cancer. Using tissue microarrays, we found that strong LIN28A expression was reactivated in about 10% (7.1–17.1%) of epithelial tumors (six tumor types, n = 369). Both in vitro and in vivo experiments demonstrate that LIN28A promotes cell cycle progression in cancer cells. Genome-wide RNA-IP-chip experiments indicate that LIN28A binds to thousands of mRNAs, including a large group of cell cycle regulatory mRNAs in cancer and embryonic stem cells. Furthermore, the ability of LIN28A to stimulate translation of LIN28A-binding mRNAs, such as CDK2, was validated in vitro and in vivo. Finally, using a combined gene expression microarray and bioinformatics approach, we found that LIN28A also regulates CCND1 and CDC25A expression and that this is mediated by inhibiting the biogenesis of let-7 miRNA. Taken together, these results demonstrate that LIN28A is reactivated in about 10% of epithelial tumors and promotes cell cycle progression by regulation of both mRNA translation (let-7-independent) and miRNA biogenesis (let-7-dependent).
Perioperative diabetes care: development and validation of quality indicators throughout the entire hospital care pathway

Background In this study, we aim to develop a set of quality indicators for optimal perioperative diabetes care throughout the hospital care pathway and to gain insight into the feasibility of the indicator set in daily clinical practice by assessing the clinimetric properties of the indicators in a practice test. Methods A literature-based modified Delphi method was used to develop a set of quality indicators. To assess clinimetric properties of each indicator (measurability, applicability, reliability, improvement potential and case-mix stability), a practice test was performed in six Dutch hospitals using a sample of 389 major surgery patients with diabetes who underwent abdominal, cardiac or large joint orthopaedic surgery. Results We developed a set of 36 quality indicators for perioperative diabetes care. The practice test showed that one indicator was inapplicable, and nine indicators were unmeasurable. Interobserver reliability was good (0.61≤k≤0.8) for all indicators except for one with moderate (0.41≤k≤0.6) interobserver reliability. Improvement potential was low (<10%) for five indicators. Twenty-one indicators, including three outcome indicators, nine process indicators and nine structure indicators, could be used to assess the quality of care delivered in our six study hospitals. Conclusion We developed a face and content valid set of quality indicators for optimal perioperative diabetes care throughout the hospital care pathway, using a rigorous and systematic approach. The results from our practice test show that it is essential to subject indicators to a practice test before applying them for quality improvement purposes. Trial registration number ClinicalTrials.gov: NCT01610674.
Enalapril Prevents Perpetuation of Atrial Fibrillation by Suppressing Atrial Fibrosis and Over-Expression of Connexin43 in a Canine Model of Atrial Pacing-Induced Left Ventricular Dysfunction

Effects of enalapril on a canine model of atrial pacing-induced atrial fibrillation (AF) with rapid ventricular responses were determined. Methods: Four weeks of atrial rapid pacing was performed on twenty-four beagles pretreated with placebo (Group I, n = 14) or enalapril 1 mg/kg (Group II, n = 10). Atrial effective refractory period (ERP), P-wave width, duration of AF, and left ventricular ejection fraction (LVEF) were evaluated every week. AF cycle length was determined by spectral analyses of fibrillation waves. Quantitative analysis of histology was added. Results: After 4 weeks of pacing, P-wave width was longer in Group I than in Group II, and the duration of induced AF was significantly longer in Group I (59.6 ± 66.3 seconds) than in Group II (3.6 ± 3.4 seconds, P < 0.05). AF cycle length was longer in Group I than in Group II despite similar shortening of atrial ERP. Mean ventricular rate during rapid atrial pacing was not different between the two groups. LVEF similarly decreased in both groups. Interstitial fibrosis and expression of connexin43 was greater in Group I than in Group II (interstitial fibrosis, 9.2 ± 8.4 versus 1.9 ± 2.1%, P < 0.05; connexin43, 5.3 ± 2.2 versus 1.1 ± 1.1%, P < 0.05). Conclusions: Enalapril suppressed atrial pacing-induced AF with tachycardia-mediated cardiomyopathy by suppressing interstitial fibrosis, connexin43 over-expression and conduction delay.
Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells

Neural computation is performed by transforming input signals into sequences of action potentials (APs), which is metabolically expensive and limited by the energy available to the brain. The metabolic efficiency of single AP has important consequences for the computational power of the cell, which is determined by its biophysical properties and morphologies. Here we adopt biophysically-based two-compartment models to investigate how dendrites affect energy efficiency of APs in cortical pyramidal neurons. We measure the Na+ entry during the spike and examine how it is efficiently used for generating AP depolarization. We show that increasing the proportion of dendritic area or coupling conductance between two chambers decreases Na+ entry efficiency of somatic AP. Activating inward Ca2+ current in dendrites results in dendritic spike, which increases AP efficiency. Activating Ca2+-activated outward K+ current in dendrites, however, decreases Na+ entry efficiency. We demonstrate that the active and passive dendrites take effects by altering the overlap between Na+ influx and internal current flowing from soma to dendrite. We explain a fundamental link between dendritic properties and AP efficiency, which is essential to interpret how neural computation consumes metabolic energy and how biophysics and morphologies contribute to such consumption.
Expression of leukaemia inhibitory factor and interleukin 15 in endometrium of women with recurrent implantation failure after IVF; correlation with the number of endometrial natural killer cells.

BACKGROUND Several studies have suggested that endometrial interleukin 15 (IL-15) and the leukaemia inhibitory factor (LIF) may be important in embryo implantation. IL-15 is postulated to play a role in the control of uterine natural killer (uNK) cell proliferation and function, and uNK cells are also known to play a role in implantation. The aims of this study was to (1) compare endometrial levels of IL-15 and the LIF in women with recurrent implantation failure (RIF) after IVF with those in fertile women (controls) and (2) examine the relation of IL-15 and LIF levels to the uNK cell number. METHODS We investigated IL-15 and LIF in precisely timed endometrial biopsies (days LH + 7-LH + 9, where the day of the LH surge is LH + 0) obtained from control women (n = 15) and women with RIF (n = 45) by immunohistochemistry. A semi-quantitative analysis was performed by the H-score analysis of staining intensity in the stroma, glandular epithelium and luminal epithelium, separately. We also correlated expression of LIF and IL15 with uNK cell numbers (obtained in an earlier study of the same samples). RESULTS The quantity of the LIF protein in endometrial glandular epithelium in women with RIF [median and range; 179 (70-365)] was lower (P = 0.01) than in control women [median and range; 247 (120-287)]. In contrast, the level of the IL-15 protein in the stroma in women with RIF [median and range; 90 (0-175)] was higher (P = 0.009) than in control women [median and range; 60 (15-150)]. There was a significant correlation between the uNK cell number and stromal expression of IL-15 (r = 0.427, P = 0.001). No correlation between the LIF expression in any compartment and the uNK cell number was seen. CONCLUSIONS The results show an altered expression of LIF and IL-15 in the endometrium of women with RIF. Despite the limitation of not identifying uNK cells by phenotypic markers, the correlation between the uNK cell number and the stromal cell IL-15 suggests that IL-15 may play a role in the control of endometrial uNK cell function or proliferation.
Trends and black/white differences in treatment for nonmetastatic prostate cancer.

OBJECTIVES Controversy and uncertainty surround use of radical prostatectomy, radiation therapy, and conservative symptomatic management in treating elderly men with nonmetastatic prostate cancer. Prior studies have demonstrated variations in use of these therapies by patient age, race, and geographic region. This study examined trends in treatment for nonmetastatic prostate cancer in black and white men aged 65 and older during the period 1986 to 1993. The study also explored factors related to use of initial therapies in these men. METHODS A cohort of 52,915 men (48,410 white; 4,505 black) obtained from the linked SEER-Medicare dataset was used in an observational design. Various sociodemographic and clinical measures were incorporated in the analysis. RESULTS For both races, use of aggressive therapy had increased with time, although this trend appears to be slowing. Black men were less likely to undergo radical prostatectomy than were white men, but use of radiation therapy did not differ markedly by race. High socioeconomic status and a lack of comorbid conditions were among the factors predictive of aggressive therapy receipt. The relation between race and receipt of aggressive therapy was dependent on whether prostate cancer was detected by transurethral resection of the prostate. Sociodemographic and clinical characteristics explained approximately half the difference between black men and white men in radical prostatectomy use. CONCLUSIONS This study documents racial differences and changing practice patterns in the treatment of nonmetastatic prostate cancer in elderly men. Further research is required to more fully understand reasons for racial differences, as well as to promote rational use of health care resources.
Green chemistry approach for the synthesis and stabilization of biocompatible gold nanoparticles and their potential applications in cancer therapy

The biological approach to synthesis of AuNPs is eco-friendly and an ideal method to develop environmentally sustainable nanoparticles alternative to existing methods. We have developed a simple, fast, clean, efficient, low-cost and eco-friendly single-step green chemistry approach for the synthesis of biocompatible gold nanoparticles (AuNPs) from chloroauric acid (HAuCl4) using a water extract of Eclipta Alba leaves at room temperature. The AuNPs using Eclipta extract have been formed in very short time, even in less than 10 min. The as-synthesized AuNPs were thoroughly characterized by several physico-chemical techniques. The in vitro stability of as-synthesized AuNPs was studied in different buffer solutions. A plausible mechanism for the synthesis of AuNPs by Eclipta extract has been discussed. The biocompatibility of AuNPs was observed by in vitro cell culture assays. Finally, we have designed and developed a AuNPs-based drug delivery system (DDS) (Au-DOX) containing doxorubicin (DOX), a FDA approved anticancer drug. Administration of this DDS to breast cancer cells (MCF-7 and MDA-MB-231) shows significant inhibition of breast cancer cell proliferation compared to pristine doxorubicin. Therefore we strongly believe that the use of Eclipta Alba offers large-scale production of biocompatible AuNPs that can be used as a delivery vehicle for the treatment of cancer diseases.
Spatial aspects of an intrametropolitan central place hierarchy

raising some previously neglected issues. By considering the application of central place theory to the intraurban distribution of commercial centres it is hoped in this paper to respond constructively to these ideas. It will be argued that developments of the theory and of empirical tests have been most concerned with the structures of hierarchies, and that less attention has been given to the locating principles and spatial predictions of different
Primary vs. secondary recurrent pregnancy loss – epidemiological characteristics, etiology, and next pregnancy outcome

Abstract Objective: To compare epidemiological and obstetric characteristics, etiology and next pregnancy outcomes of women with primary vs. secondary recurrent pregnancy loss (RPL). Study design: A retrospective cohort study, including 420 patients with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy, of whom 162 were primary RPL women and 258 were secondary RPL women. All patients were evaluated and treated in the RPL clinic at the Soroka University Medical Center. Results: Live birth rate in the index pregnancy was not statistically different between primary and secondary RPL women (75.9 and 70.9%, respectively). The only significant difference in the etiology evaluation was in abnormal prolactin levels (14.1% of the primary and 1.4% of the secondary RPL group). Women with primary RPL had, at the index pregnancy, significantly higher rates of preterm delivery, fetal growth restriction, and gestational diabetes mellitus. In a multivariable logistic regression analysis, primary RPL adjusted for maternal age and gravidity, was an independent risk factor for preterm delivery compared with secondary RPL [adjusted OR 2.62, CI (95%) 1.30–5.26]. Conclusions: The prognosis of the two groups was similar regarding live birth rate at the index pregnancy; however, women with primary RPL were more prone to adverse obstetric and neonatal outcomes.
The capacity to refuse psychiatric treatment: A guide to the law for clinicians and tribunal members

Objective: In some Australian states clinicians and mental health tribunal members are already required to assess a person’s decision-making capacity before involuntary treatment can be applied. Professionals in other jurisdictions will likely soon be required to do the same as mental health law reform in most Australian jurisdictions makes the assessment of decision-making capacity a central component of the process of providing unconsented psychiatric treatment. We provide a guide to the legal issues around the capacity to refuse psychiatric treatment to assist with this task. Method: We review the legislation in the four Australian states most advanced in the mental health law reform process and use examples from clinical practice and the common law to describe how decision-making capacity should be assessed by these statutory standards. Results: Clinicians and tribunal members will primarily be required to judge whether a person with mental illness can understand the information relevant to the treatment decision and whether he or she can use or weigh that information to come to a decision. A person with a mental illness is presumed to have capacity, but that presumption can be rebutted. Capacity is specific to the decision at hand and cannot be determined by the nature of the decision made. Conclusions: The information provided should assist clinicians and tribunal members to make determinations of decision-making capacity around treatment refusal in the context of mental illness.
Infrastructure-dependent wireless multicast - improving the code rate

This paper shows how a novel infrastructure which makes use of the multiple antennas available on IEEE 802.11n Access Points can be combined with block erasure coding to multicast video with no packet loss. This paper also shows that this can be obtained while maintaining an efficient code rate, which is better than 1) packet repetition on the new infrastructure, 2) Block erasure coding on the legacy infrastructure and 3) Leader-Based Protocols used on the legacy infrastructure. This study employs physical layer data rates of 52Mbps, 58.5Mbps and 65Mbps. Hence the infrastructure proposed solves also the “Performance Anomaly Problem” which results with legacy multicast that transmits the data using the most robust modulation and coding scheme.
Enduring war: Heroes’ Acre, ‘the empty throne’, and the politics of disappearance

ABSTRACT War memorials are a common and often controversial part of the commemoration of past wars. In order to better grasp their importance for the way war endures below the surface of peace, this article stages an ethnographic encounter with a Namibian monument: Heroes’ Acre. The memorial embodies the official Namibian narrative on past wars by emphasizing a nationalist and quasi-religious symbolism, a framing that has been challenged by a number of writers pointing to the need for going beyond the state discourse. This article complements and complicates the way Heroes’ Acre appears in discourse by focusing on the interstices and absences at the site. By drawing upon my own visit to the monument as well as theoretical engagements, most notably Georgio Agamben’s discussion of ‘the empty throne’, I read Heroes’ Acre as a place where political power functions through emptiness, as it allows the future of war to endure in the present. Engaging particularly with the empty graveyard at the site, I argue that its emptiness needs to be understood as a guarantee for war – not in case it occurs – but as a ready-made symbol of glory, always virtually there, waiting to be fulfilled.
Lack of spontaneous venous pulsation: possible risk indicator in normal tension glaucoma?

Purpose: Recently, the absence of spontaneous venous pulsation (SVP) has been suggested as a vascular risk factor for primary open‐angle glaucoma (POAG). As the mechanism behind this phenomenon is still unknown, the authors have studied this vascular component using colour Doppler imaging (CDI).
The Ellagic Acid Derivative 4,4′-Di-O-Methylellagic Acid Efficiently Inhibits Colon Cancer Cell Growth through a Mechanism Involving WNT16

Ellagic acid (EA) and some derivatives have been reported to inhibit cancer cell proliferation, induce cell cycle arrest, and modulate some important cellular processes related to cancer. This study aimed to identify possible structure-activity relationships of EA and some in vivo derivatives in their antiproliferative effect on both human colon cancer and normal cells, and to compare this activity with that of other polyphenols. Our results showed that 4,4′-di-O-methylellagic acid (4,4′-DiOMEA) was the most effective compound in the inhibition of colon cancer cell proliferation. 4,4′-DiOMEA was 13-fold more effective than other compounds of the same family. In addition, 4,4′-DiOMEA was very active against colon cancer cells resistant to the chemotherapeutic agent 5-fluoracil, whereas no effect was observed in nonmalignant colon cells. Moreover, no correlation between antiproliferative and antioxidant activities was found, further supporting that structure differences might result in dissimilar molecular targets involved in their differential effects. Finally, microarray analysis revealed that 4,4′-DiOMEA modulated Wnt signaling, which might be involved in the potential antitumor action of this compound. Our results suggest that structural-activity differences between EA and 4,4′-DiOMEA might constitute the basis for a new strategy in anticancer drug discovery based on these chemical modifications.
U7 small nuclear ribonucleoprotein represses histone gene transcription in cell cycle-arrested cells

Histone gene expression is tightly coordinated with DNA replication, as it is activated at the onset of S phase and suppressed at the end of S phase. Replication-dependent histone gene expression is precisely controlled at both transcriptional and posttranscriptional levels. U7 small nuclear ribonucleoprotein (U7 snRNP) is involved in the 3′-end processing of nonpolyadenylated histone mRNAs, which is required for S phase-specific gene expression. The present study reports a unique function of U7 snRNP in the repression of histone gene transcription under cell cycle-arrested conditions. Elimination of U7 snRNA with an antisense oligonucleotide in HeLa cells as well as in nontransformed human lung fibroblasts resulted in elevated levels of replication-dependent H1, H2A, H2B, H3, and H4 histone mRNAs but not of replication-independent H3F3B histone mRNA. An analogous effect was observed upon depletion of Lsm10, a component of the U7 snRNP-specific Sm ring, with siRNA. Pulse–chase experiments revealed that U7 snRNP acts to repress transcription without remarkably altering mRNA stability. Mass spectrometric analysis of the captured U7 snRNP from HeLa cell extracts identified heterogeneous nuclear (hn)RNP UL1 as a U7 snRNP interaction partner. Further knockdown and overexpression experiments revealed that hnRNP UL1 is responsible for U7 snRNP-dependent transcriptional repression of replication-dependent histone genes. Chromatin immunoprecipitation confirmed that hnRNP UL1 is recruited to the histone gene locus only when U7 snRNP is present. These findings support a unique mechanism of snRNP-mediated transcriptional control that restricts histone synthesis to S phase, thereby preventing the potentially toxic effects of histone synthesis at other times in the cell cycle.
A New Electromyographic Definition of Laryngeal Synkinesis

Laryngeal synkinesis involves the misdirected reinnervation of an injured recurrent laryngeal nerve to vocal fold abductor and adductor musculature. The resultant laryngeal dyscoordination can cause vocal fold immobility and airway compromise. Although this entity is sometimes considered in the differential diagnosis, it is only demonstrable with laryngeal electromyography (EMG). We propose a new EMG definition of synkinesis to assist in its identification during workup of vocal fold immobility. A retrospective chart review from 1992 to 1997 in the Voice Disorders Clinic identified 10 patients with laryngeal synkinesis. Five patients had bilateral immobility, and 5 had unilateral immobility. Monopolar EMG was performed on all patients. Fine-wire EMG was performed when monopolar EMG did not elucidate the cause of the immobility. The EMG studies revealed synkinetic reinnervation in all subjects. On the basis of the EMG results, 7 of the 10 patients were treated with botulinum toxin to weaken the undesired reinnervation. Three of the 7 patients had benefit from this therapy. Laryngeal synkinesis should be considered as part of the differential diagnosis of vocal fold immobility. Awake laryngeal EMG is the only method to demonstrate synkinesis of the larynx. The diagnosis of synkinesis is clinically significant in cases of immobility to identify patients who might benefit from botulinum toxin therapy. Additionally, the presence of synkinesis in cases of unilateral immobility may be a contraindication to laryngeal reinnervation procedures. The benefit of botulinum toxin therapy is likely greater in the treatment of bilateral as opposed to unilateral immobility.