bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor networks in B-cell differentiation link development to acute lymphoid leukemia
Authors: Somasundaram Rajesh , Prasad Mahadesh A. J. , Ungerbäck Jonas , Sigvardsson Mikael 
Published: May 2015

Abstract
B-lymphocyte development in the bone marrow is controlled by the coordinated action of transcription factors creating regulatory networks ensuring activation of the B-lymphoid program and silencing of alternative cell fates. This process is tightly connected to malignant transformation because B-lineage acute lymphoblastic leukemia cells display a pronounced block in differentiation resulting in the expansion of immature progenitor cells. Over the last few years, high-resolution analysis of genetic changes in leukemia has revealed that several key regulators of normal B-cell development, including IKZF1, TCF3, EBF1, and PAX5, are genetically altered in a large portion of the human B-lineage acute leukemias. This opens the possibility of directly linking the disrupted development as well as aberrant gene expression patterns in leukemic cells to molecular functions of defined transcription factors in normal cell differentiation. This review article focuses on the roles of transcription factors in early B-cell development and their involvement in the formation of human leukemia.
A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis
Authors: Palladini Giovanni , Sachchithanantham Sajitha , Milani Paolo , Gillmore Julian , Foli Andrea , Lachmann Helen , Basset Marco , Hawkins Philip , Merlini Giampaolo , Wechalekar Ashutosh D. 
Published: May 2015

Key Points
CyBorD achieves excellent outcome in noncardiac patients with AL amyloidosis and can rescue subjects with reversible heart damage. The outcome of high-risk patients remains poor, but response to CyBorD can also improve survival in this group.
Upregulation of T-Type Ca2+ Channels in Long-Term Diabetes Determines Increased Excitability of a Specific Type of Capsaicin-Insensitive DRG Neurons
Authors: Duzhyy Dmytro E , Viatchenko-Karpinski Viacheslav Y , Khomula Eugen V , Voitenko Nana V , Belan Pavel V 
Published: May 2015

Background Previous studies have shown that increased excitability of capsaicin-sensitive DRG neurons and thermal hyperalgesia in rats with short-term (2–4 weeks) streptozotocin-induced diabetes is mediated by upregulation of T-type Ca2+ current. In longer–term diabetes (after the 8th week) thermal hyperalgesia is changed to hypoalgesia that is accompanied by downregulation of T-type current in capsaicin-sensitive small-sized nociceptors. At the same time pain symptoms of diabetic neuropathy other than thermal persist in STZ-diabetic animals and patients during progression of diabetes into later stages suggesting that other types of DRG neurons may be sensitized and contribute to pain. In this study, we examined functional expression of T-type Ca2+ channels in capsaicin-insensitive DRG neurons and excitability of these neurons in longer-term diabetic rats and in thermally hypoalgesic diabetic rats. Results Here we have demonstrated that in STZ-diabetes T-type current was upregulated in capsaicin-insensitive low-pH-sensitive small-sized nociceptive DRG neurons of longer-term diabetic rats and thermally hypoalgesic diabetic rats. This upregulation was not accompanied by significant changes in biophysical properties of T-type channels suggesting that a density of functionally active channels was increased. Sensitivity of T-type current to amiloride (1 mM) and low concentration of Ni2+ (50 μM) implicates prevalence of Cav3.2 subtype of T-type channels in the capsaicin-insensitive low-pH-sensitive neurons of both naïve and diabetic rats. The upregulation of T-type channels resulted in the increased neuronal excitability of these nociceptive neurons revealed by a lower threshold for action potential initiation, prominent afterdepolarizing potentials and burst firing. Sodium current was not significantly changed in these neurons during long-term diabetes and could not contribute to the diabetes-induced increase of neuronal excitability. Conclusions Capsaicin-insensitive low-pH-sensitive type of DRG neurons shows diabetes-induced upregulation of Cav3.2 subtype of T-type channels. This upregulation results in the increased excitability of these neurons and may contribute to nonthermal nociception at a later-stage diabetes.
Nurses’ worry or concern and early recognition of deteriorating patients on general wards in acute care hospitals: a systematic review
Authors: Douw Gooske , Schoonhoven Lisette , Holwerda Tineke , Huisman-de Waal Getty , van Zanten Arthur R H , van Achterberg Theo , van der Hoeven Johannes G 
Published: May 2015

Abstract
Introduction
Nurses often recognize deterioration in patients through intuition rather than through routine measurement of vital signs. Adding the ‘worry or concern’ sign to the Rapid Response System provides opportunities for nurses to act upon their intuitive feelings. Identifying what triggers nurses to be worried or concerned might help to put intuition into words, and potentially empower nurses to act upon their intuitive feelings and obtain medical assistance in an early stage of deterioration. The aim of this systematic review is to identify the signs and symptoms that trigger nurses’ worry or concern about a patient’s condition.

Methods
We searched the databases PubMed, CINAHL, Psychinfo and Cochrane Library (Clinical Trials) using synonyms related to the three concepts: ‘nurses’, ‘worry/concern’ and ‘deterioration’. We included studies concerning adult patients on general wards in acute care hospitals. The search was performed from the start of the databases until 14 February 2014.

Results
The search resulted in 4,006 records, and 18 studies (five quantitative, nine qualitative and four mixed-methods designs) were included in the review. A total of 37 signs and symptoms reflecting the nature of the criterion worry or concern emerged from the data and were summarized in 10 general indicators. The results showed that worry or concern can be present with or without change in vital signs.

Conclusions
The signs and symptoms we found in the literature reflect the nature of nurses’ worry or concern, and nurses may incorporate these signs in their assessment of the patient and their decision to call for assistance. The fact that it is present before changes in vital signs suggests potential for improving care in an early stage of deterioration.
Neuroprotective properties of dehydroepiandrosterone-sulfate and its relationship to interleukin 6 after aneurysmal subarachnoid hemorrhage: a prospective cohort study
Authors: Höllig Anke , Thiel Miriam , Stoffel-Wagner Birgit , Coburn Mark , Clusmann Hans 
Published: May 2015

Abstract
Introduction
The established neuroprotective property of the sex steroid precursor dehydroepiandrosterone-sulfate (DHEAS) has not yet been investigated in the context of aneurysmal subarachnoid hemorrhage (aSAH). The influence of DHEAS on inflammatory response resulting in modulation of interleukin 6 (IL-6) synthesis has been shown. Here, we evaluate DHEAS serum levels after aSAH (day 0–14) and levels of IL-6 related to functional outcome at discharge and at six months.

Methods
A complete data set (DHEAS and IL-6 serum levels for days 0, 1, 4, 7, 10 and 14 after aSAH) and outcome assessment at discharge according to modified Rankin Scale score (mRS) was available for 53 patients of the initially screened cohort (n = 109). Outcome assessment six months after aSAH was obtained from 41 patients. Logarithmized levels of DHEAS and IL-6 were related to dichotomized functional outcome either assessed at discharge or at six months. A mixed between-within subjects ANOVA was applied for statistical analysis (SPSS 21.0).

Results
DHEAS and IL-6 levels across time were related to functional outcome. Regarding outcome assessment at discharge and at six months after aSAH, DHEAS levels (transformed to square root for statistical purposes) were considerably higher in patients with favorable outcome (mRS 0–2) (p = .001; p = .020). Inversely, in patients with favorable outcome either at discharge or six months after aSAH, lower IL-6 levels (logarithmized for statistical purposes) were observed across time (both p < .001).

Conclusion
We provide new evidence that DHEAS is associated with protective properties resulting in improvement of functional outcome after aSAH, possibly by influencing the inflammatory response after aSAH shown in the decreasing IL-6 serum levels. But the results for outcome six months after SAH are limited due to a high drop-out rate.
Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced pulmonary fibrosis
Authors: Lan Ying-Wei , Choo Kong-Bung , Chen Chuan-Mu , Hung Tsai-Hsien , Chen Young-Bin , Hsieh Chung-Hsing , Kuo Han-Pin , Chong Kowit-Yu 
Published: May 2015

Abstract
Introduction
Idiopathic pulmonary fibrosis is a progressive diffuse parenchymal lung disorder of unknown etiology. Mesenchymal stem cell (MSC)-based therapy is a novel approach with great therapeutic potential for the treatment of lung diseases. Despite demonstration of MSC grafting, the populations of engrafted MSCs have been shown to decrease dramatically 24 hours post-transplantation due to exposure to harsh microenvironments. Hypoxia is known to induce expression of cytoprotective genes and also secretion of anti-inflammatory, anti-apoptotic and anti-fibrotic factors. Hypoxic preconditioning is thought to enhance the therapeutic potency and duration of survival of engrafted MSCs. In this work, we aimed to prolong the duration of survival of engrafted MSCs and to enhance the effectiveness of idiopathic pulmonary fibrosis transplantation therapy by the use of hypoxia-preconditioned MSCs.

Methods
Hypoxic preconditioning was achieved in MSCs under an optimal hypoxic environment. The expression levels of cytoprotective factors and their biological effects on damaged alveolar epithelial cells or transforming growth factor-beta 1-treated fibroblast cells were studied in co-culture experiments in vitro. Furthermore, hypoxia-preconditioned MSCs (HP-MSCs) were intratracheally instilled into bleomycin-induced pulmonary fibrosis mice at day 3, and lung functions, cellular, molecular and pathological changes were assessed at 7 and 21 days after bleomycin administration.

Results
The expression of genes for pro-survival, anti-apoptotic, anti-oxidant and growth factors was upregulated in MSCs under hypoxic conditions. In transforming growth factor-beta 1-treated MRC-5 fibroblast cells, hypoxia-preconditioned MSCs attenuated extracellular matrix production through paracrine effects. The pulmonary respiratory functions significantly improved for up to 18 days of hypoxia-preconditioned MSC treatment. Expression of inflammatory factors and fibrotic factor were all downregulated in the lung tissues of the hypoxia-preconditioned MSC-treated mice. Histopathologic examination observed a significant amelioration of the lung fibrosis. Several LacZ-labeled MSCs were observed within the lungs in the hypoxia-preconditioned MSC treatment groups at day 21, but no signals were detected in the normoxic MSC group. Our data further demonstrated that upregulation of hepatocyte growth factor possibly played an important role in mediating the therapeutic effects of transplanted hypoxia-preconditioned MSCs.

Conclusion
Transplantation of hypoxia-preconditioned MSCs exerted better therapeutic effects in bleomycin-induced pulmonary fibrotic mice and enhanced the survival rate of engrafted MSCs, partially due to the upregulation of hepatocyte growth factor.
Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations?
Authors: Bajusz Dávid , Rácz Anita , Héberger Károly 
Published: May 2015

Abstract

Background
Cheminformaticians are equipped with a very rich toolbox when carrying out molecular similarity calculations. A large number of molecular representations exist, and there are several methods (similarity and distance metrics) to quantify the similarity of molecular representations. In this work, eight well-known similarity/distance metrics are compared on a large dataset of molecular fingerprints with sum of ranking differences (SRD) and ANOVA analysis. The effects of molecular size, selection methods and data pretreatment methods on the outcome of the comparison are also assessed.

Results
A supplier database (https://mcule.com/) was used as the source of compounds for the similarity calculations in this study. A large number of datasets, each consisting of one hundred compounds, were compiled, molecular fingerprints were generated and similarity values between a randomly chosen reference compound and the rest were calculated for each dataset. Similarity metrics were compared based on their ranking of the compounds within one experiment (one dataset) using sum of ranking differences (SRD), while the results of the entire set of experiments were summarized on box and whisker plots. Finally, the effects of various factors (data pretreatment, molecule size, selection method) were evaluated with analysis of variance (ANOVA).

Conclusions
This study complements previous efforts to examine and rank various metrics for molecular similarity calculations. Here, however, an entirely general approach was taken to neglect any a priori knowledge on the compounds involved, as well as any bias introduced by examining only one or a few specific scenarios. The Tanimoto index, Dice index, Cosine coefficient and Soergel distance were identified to be the best (and in some sense equivalent) metrics for similarity calculations, i.e. these metrics could produce the rankings closest to the composite (average) ranking of the eight metrics. The similarity metrics derived from Euclidean and Manhattan distances are not recommended on their own, although their variability and diversity from other similarity metrics might be advantageous in certain cases (e.g. for data fusion). Conclusions are also drawn regarding the effects of molecule size, selection method and data pretreatment on the ranking behavior of the studied metrics.
An evaluation of two types of nickel-titanium wires in terms of micromorphology and nickel ions’ release following oral environment exposure
Authors: Ghazal Abdul Razzak A. , Hajeer Mohammad Y. , Al-Sabbagh Rabab , Alghoraibi Ibrahim , Aldiry Ahmad 
Published: May 2015

Abstract

Background
This study aimed to compare superelastic and heat-activated nickel-titanium orthodontic wires’ surface morphology and potential release of nickel ions following exposure to oral environment conditions.

Methods
Twenty-four 20-mm-length distal cuts of superelastic (NiTi Force I®) and 24 20-mm-length distal cuts of heat-activated (Therma-Ti Lite®) nickel-titanium wires (American Orthodontics, Sheboygan, WI, USA) were divided into two equal groups: 12 wire segments left unused and 12 segments passively exposed to oral environment for 1 month. Scanning electron microscopy and atomic force microscopy were used to analyze surface morphology of the wires which were then immersed in artificial saliva for 1 month to determine potential nickel ions’ release by means of atomic absorption spectrophotometer.

Results
Heat-activated nickel-titanium (NiTi) wires were rougher than superelastic wires, and both types of wires released almost the same amount of Ni ions. After clinical exposure, more surface roughness was recorded for superelastic NiTi wires and heat-activated NiTi wires. However, retrieved superelastic NiTi wires released less Ni ions in artificial saliva after clinical exposure, and the same result was recorded regarding heat-activated wires.

Conclusions
Both types of NiTi wires were obviously affected by oral environment conditions; their surface roughness significantly increased while the amount of the released Ni ions significantly declined.
Computational fluid dynamics analysis of the upper airway after rapid maxillary expansion: a case report
Authors: Ghoneima Ahmed , AlBarakati Sahar , Jiang Feifei , Kula Katherine , Wasfy Tamer 
Published: May 2015

Abstract

Background
Assessment of the upper airway volume, morphology, and mechanics is of great importance for the orthodontic patient. We hypothesize that upper airway dimensions have significant effects on the dynamics of the airway flow and that both the dimensions and mechanics of the upper airway are greatly affected by orthodontic and orthopedic procedures such as rapid maxillary expansion (RME). The aim of the current study was to assess the effect of RME on the airway flow rate and pattern by comparing the fluid dynamics results of pre- and post-treatment finite element models.

Methods
Customized pre- and post-treatment computational fluid dynamics models of the patient’s upper airway were built for comparison based on three-dimensional computed tomogram. The inhalation process was simulated using a constant volume flow rate for both models, and the wall was set to be rigid and stationary. Laminar and turbulent analyses were applied.

Results
Comparisons between before and after RME airway volume measurements showed that increases were only detected in nasal cavity volume, nasopharynx volume, and the most constricted area of the airway. Pressure, velocity, and turbulent kinetic energy decreased after dental expansion for laminar and turbulent flow. Turbulent flow shows relatively larger velocity and pressure than laminar flow.

Conclusions
RME showed positive effects that may help understand the key reasons behind relieving the symptom of breathing disorders in this patient. Turbulence occurs at both nasal and oropharynx areas, and it showed relatively larger pressure and velocity compared to laminar flow.
Cymothoa frontalis, a cymothoid isopod parasitizing the belonid fish Strongylura strongylura from the Malabar Coast (Kerala, India): redescription, description, prevalence and life cycle
Authors: Thamban Aneesh Panakkool , Kappalli Sudha , Kottarathil Helna Ameri , Gopinathan Anilkumar , Paul Trilles Jean 
Published: May 2015

Abstract

Background

Cymothoa frontalis Milne Edward, 1840 is a very poorly described cymothoid, notwithstanding the previous redescription of the female. Pertinently, to date, the host of C. frontalis has not been identified with adequate precision. Most of the descriptions of cymothoids carried out hitherto were based primarily on females, but practically ignoring other life cycle stages. The present paper redescribes the female and describes other life cycle stages of the species C. frontalis to get better precision in their identification.

Results
The female phase of C. frontalis is redescribed according to type specimens extant in the NMNH, Paris, and also by the data obtained from live specimens collected during the present study. The general morphology and appendages of various life cycle stages of the species are described. Among 80 fish species from 35 families examined, C. frontalis was recovered only from Strongylura strongylura signifying its oligoxenous host specificity, the prevalence and intensity being 68.65% and 1.9, respectively. Each host fish in more than 85% of the population was infested with a pair of C. frontalis, in three combinations, predominantly with male-female pair (70.9%). C. frontalis exhibited strict site specificity attaching to the buccal cavity of the host fish. The study has also identified three major phases (marsupial, free living and infective) in the life cycle of C. frontalis. The zygotic-staged marsupiumites were developed through five sequential ontogenetic stages. The manca released from the marsupium become infective after a brief period of free swimming life. During the infective phase, C. frontalis completes remaining life cycle stages with successive moulting. Further, six successive stages of the ovigerous females have also been identified.

Conclusions
The present redescription of the female and the description of transitional, male, juvenile and larvae of C. frontalis facilitate precise identification of the species at any stage of the life cycle. Further, the strict host and site specificities of the parasite, as borne out from the present study, and its high degree of prevalence in the host make C. frontalis as an ideal model organism to study the strategies to be adopted for the management of parasites infesting edible fishes.
Differentiation of visual spectra and nuptial colorations of two Paratanakia himantegus subspecies (Cyprinoidea: Acheilognathidae) in response to the distinct photic conditions of their habitats
Authors: Chang Chia-Hao , Shao Yi Ta , Fu Wen-Chung , Anraku Kazuhiko , Lin Yeong-Shin , Yan Hong Young 
Published: May 2015

Abstract

Background
Vision, an important sensory modality of many animals, exhibits plasticity in that it adapts to environmental conditions to maintain its sensory efficiency. Nuptial coloration is used to attract mates and hence should be tightly coupled to vision. In Taiwan, two closely related bitterlings (Paratanakia himantegus himantegus and Paratanakia himantegus chii) with different male nuptial colorations reside in different habitats. We compared the visual spectral sensitivities of these subspecies with the ambient light spectra of their habitats to determine whether their visual abilities correspond with photic parameters and correlate with nuptial colorations.

Results
The electroretinogram (ERG) results revealed that the relative spectral sensitivity of P. h. himantegus was higher at 670 nm, but lower at 370 nm, than the sensitivity of P. h. chii. Both bitterlings could perceive and reflect UV light, but the UV reflection patterns differed between genders. Furthermore, the relative irradiance intensity of the light spectra in the habitat of P. h. himantegus was higher at long wavelengths (480–700 nm), but lower at short wavelengths (350–450 nm), than the light spectra in the habitats of P. h. chii.

Conclusions
Two phylogenetically closely related bitterlings, P. h. himantegus and P. h. chii, dwell in different waters and exhibit different nuptial colorations and spectral sensitivities, which may be the results of speciation by sensory drive. Sensory ability and signal diversity accommodating photic environment may promote diversity of bitterling fishes. UV light was demonstrated to be a possible component of bitterling visual communication. The UV cue may assist bitterlings in gender identification.
Functionally and morphologically distinct populations of extracellular vesicles produced by human neutrophilic granulocytes
Authors: Lőrincz Ákos M , Schütte Maria , Timár Csaba I , Veres Daniel S , Kittel Ágnes , McLeish Kenneth R , Merchant Michael L , Ligeti Erzsébet 
Published: May 2015

Abstract
EVs in the microvesicle size range released during spontaneous death of human neutrophils were characterized and their properties compared with previously described EVs with antibacterial effect (aEVs, generated on specific activation) or produced spontaneously (sEVs). The 3 vesicle populations overlapped in size and in part of the constituent proteins were stained with annexin V and were impermeable to PI. However, none of them produced superoxide. In contrast, remarkable differences were observed in the morphology, abundance of proteins, and antibacterial function. EVs formed spontaneously in 30 min (sEVs) were more similar to EVs released during spontaneous death in 1–3 d than to EVs formed in 30 min on stimulation of opsonin receptors (aEVs). Spontaneously generated EVs had no antibacterial effect despite their large number and protein content. We hypothesized 2 parallel mechanisms: one that proceeds spontaneously and produces EVs without antibacterial effect and another process that is triggered by opsonin receptors and results in differential sorting of proteins into EVs with antibacterial capacity. Our results call attention to the functional and morphologic heterogeneity within the microvesicle/ectosome fraction of EVs.