bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salidroside prevents cognitive impairment induced by chronic cerebral hypoperfusion in rats
Authors: Yan Zhi-Qiang , Chen Jun , Xing Guo-Xiang , Huang Jian-Guo , Hou Xiang-Hong , Zhang Yong 
Published: April 2015

Objective To investigate the effects of salidroside on cognitive dysfunction induced by chronic cerebral hypoperfusion in rats. Methods Male Sprague–Dawley rats ( n = 36) were divided into three groups ( n = 12 per group): sham operation; bilateral permanent occlusion of the common carotid arteries (2-VO); 2-VO + salidroside. Rats received 20 mg/kg per day salidroside or vehicle intraperitoneal injection beginning the day before surgery and continuing until 34 days postoperatively. Cognitive function was evaluated by Morris water maze test and hippocampal long-term potentiation (LTP) measurement. Hippocampal neuronal apoptosis was evaluated via immunofluorescence. Results Chronic cerebral hypoperfusion caused marked cognitive deficit and LTP inhibition. These effects were largely ameliorated by salidroside administration. Salidroside prevented caspase-3 activation, increased the ratio of Bax/Bcl-2, and reversed hippocampal neuronal loss induced by chronic cerebral hypoperfusion. Conclusions Salidroside prevents cognitive deficits caused by chronic cerebral hypoperfusion in rats, and alleviates apoptosis in the hippocampal CA1 area.
Autologous, Noncultured Epidermal Cell Suspension Grafting in the Management of Mechanically and Chemically Induced Leukodermic Scars
Authors: Vyas Nikki S. , Lawrence Kelsey L. , Griffith James L. , Hamzavi Iltefat H. 
Published: April 2015

Background: Melanocyte-keratinocyte transplant procedure (MKTP) successfully repigments postburn leukodermic scars. Objective: To further investigate the efficacy and limitations of MKTP for treatment of mechanically and chemically induced leukodermic scars. Methods: Ten patients with mechanically or chemically induced, depigmented or hypopigmented scars were preoperatively evaluated with Wood’s light examination, treated with MKTP, and followed for at least 6 months, with monitoring of repigmentation and colour matching. Results: Nine patients attended at least 6 months of follow-up. Six patients showed no fluorescence of scars under Wood’s lamp. All patients whose lesions didn’t fluoresce displayed less than 50% repigmentation, with 5 of 6 attaining 0% to 24%. Of the 3 patients displaying bright or some fluorescence, more than 95% repigmentation was achieved in 2 patients (skin phototypes V and VI), while less than 24% was attained for the third (skin phototype II). Conclusions: In this small case series, lack of fluorescence in leukodermic scars may be a useful negative prognostic indicator for MKTP, but additional trials are needed to verify that this is not due to melanocompetency.
Testing the waters: Ethical considerations for including PrEP in a phase IIb HIV vaccine efficacy trial
Authors: Dawson Liza , Garner Sam , Anude Chuka , Ndebele Paul , Karuna Shelly , Holt Renee , Broder Gail , Handibode Jessica , Hammer Scott M , Sobieszczyk Magdalena E ,   for the NIAID HIV Vaccine Trials Network
Published: April 2015

Background: The field of HIV prevention research has recently experienced some mixed results in efficacy trials of pre-exposure prophylaxis, vaginal microbicides, and HIV vaccines. While there have been positive trial results in some studies, in the near term, no single method will be sufficient to quell the epidemic. Improved HIV prevention methods, choices among methods, and coverage for all at-risk populations will be needed. The emergence of partially effective prevention methods that are not uniformly available raises complex ethical and scientific questions regarding the design of ongoing prevention trials. Methods: We present here an ethical analysis regarding inclusion of pre-exposure prophylaxis in an ongoing phase IIb vaccine efficacy trial, HVTN 505. This is the first large vaccine efficacy trial to address the issue of pre-exposure prophylaxis, and the decisions made by the protocol team were informed by extensive stakeholder consultations. The key ethical concerns are analyzed here, and the process of stakeholder engagement and decision-making described. Discussion: This discussion and analysis will be useful as current and future research teams grapple with ethical and scientific study design questions emerging with the rapidly expanding evidence base for HIV prevention.
Digital collaboration inside and outside educational systems
Authors: Birkeland Nils Rune , Drange Eli-Marie Danbolt , Tønnessen Elise Seip 
Published: April 2015

This article takes its outset in findings from an ongoing research project investigating the use of digital and multimodal resources in teacher education (TE) in Norway. The material studied is mandatory assignments in different courses in TE, asking how teacher students collaborate through digital media in their production of texts for learning, and how the design of these literacy practices can be influenced through the teachers’ design of the assignments. In focus group interviews the researchers found that the students preferred organizing collaborative processes through Facebook groups rather than through the university’s learning management system. This created a space between formal and informal learning, often mediated by “power users” performing a curatorial function on behalf of the group. Furthermore, the quality of the processes seemed to depend on how the assignments were designed for different modes and for individual or group work. The tasks that inspired genuine collaborative learning were characterized by a certain complexity in terms of multimodality and technology, or professional knowledge combining academic and practical experience. In other cases tasks to be performed in groups were split between the students, and probably did not add the same value to individual learning. This is discussed as an encounter between the teachers’ design of the assignments and the students’ design of their learning processes. When teacher students tell us how they work with assignments, they at the same time explain how their knowledge is designed through social and textual practices. Reflections on these practices are relevant to developing their awareness of didactic design in their future profession as teachers.
Simultaneous combined balloon‐occluded retrograde transvenous obliteration and partial splenic embolization for gastric fundal varices
Authors: Waguri Nobuo , Osaki Akihiko , Ikarashi Shunzo , Ogawa Masahiro , Kuraoka Naosuke , Ogawa Kohei , Sato Munehiro , Aiba Tsuneo , Yoneyama Osamu , Furukawa Koichi , Sugimura Kazuhito , Igarashi Kentarou 
Published: April 2015

BackgroundWe previously reported the techniques and usefulness of simultaneous combined balloon‐occluded retrograde transvenous obliteration (B‐RTO) and partial splenic embolization (PSE), based on the hypothesis that concomitant PSE can diminish the increase in portal venous pressure after B‐RTO.ObjectiveAfter experiencing more cases and performing longer‐term follow‐up, we re‐evaluated the efficacy of simultaneous combined B‐RTO and PSE for gastric fundal varices (GVs).MethodsWe performed B‐RTO in 36 consecutive patients treated for GVs from 2005 to 2013. Twenty‐three patients underwent simultaneous combined B‐RTO and PSE (Group 1) and 13 underwent B‐RTO monotherapy (Group 2). The outcomes were retrospectively evaluated.ResultsThere were no significant differences in baseline characteristics between the two groups except that the splenic volumes were larger in Group 1 than 2. B‐RTO was technically successful in 21 of 23 patients (91.3%) in Group 1 and in 12 of 13 patients (92.3%) in Group 2. In all patients with ruptured GVs (six in Group 1 and five in Group 2), complete hemostasis was obtained by B‐RTO. Exacerbation of esophageal varices was significantly less frequent in Group 1 than 2 (p  = 0.0017).ConclusionConcomitant PSE with B‐RTO may contribute to prevention of the exacerbation of esophageal varices after B‐RTO.
Long non-coding RNA expression profiles predict metastasis in lymph node-negative breast cancer independently of traditional prognostic markers
Authors: Sørensen Kristina P , Thomassen Mads , Tan Qihua , Bak Martin , Cold Søren , Burton Mark , Larsen Martin J , Kruse Torben A 
Published: April 2015

Abstract
Introduction
Patients with clinically and pathologically similar breast tumors often have very different outcomes and treatment responses. Current prognostic markers allocate the majority of breast cancer patients to the high-risk group, yielding high sensitivities in expense of specificities below 20%, leading to considerable overtreatment, especially in lymph node-negative patients. Seventy percent would be cured by surgery and radiotherapy alone in this group. Thus, precise and early indicators of metastasis are highly desirable to reduce overtreatment. Previous prognostic RNA-profiling studies have only focused on the protein-coding part of the genome, however the human genome contains thousands of long non-coding RNAs (lncRNAs) and this unexplored field possesses large potential for identification of novel prognostic markers.

Methods
We evaluated lncRNA microarray data from 164 primary breast tumors from adjuvant naïve patients with a mean follow-up of 18 years. Eighty two patients who developed detectable distant metastasis were compared to 82 patients where no metastases were diagnosed. For validation, we determined the prognostic value of the lncRNA profiles by comparing the ability of the profiles to predict metastasis in two additional, previously-published, cohorts.

Results
We showed that lncRNA profiles could distinguish metastatic patients from non-metastatic patients with sensitivities above 90% and specificities of 64-65%. Furthermore; classifications were independent of traditional prognostic markers and time to metastasis.

Conclusions
To our knowledge, this is the first study investigating the prognostic potential of lncRNA profiles. Our study suggest that lncRNA profiles provide additional prognostic information and may contribute to the identification of early breast cancer patients eligible for adjuvant therapy, as well as early breast cancer patients that could avoid unnecessary systemic adjuvant therapy. This study emphasizes the potential role of lncRNAs in breast cancer prognosis.
Stromal-vascular fraction content and adipose stem cell behavior are altered in morbid obese and post bariatric surgery ex-obese women
Authors: Silva Karina R , Liechocki Sally , Carneiro João R , Claudio-da-Silva Cesar , Maya-Monteiro Clarissa M , Borojevic Radovan , Baptista Leandra S 
Published: April 2015

Abstract
Introduction
Subcutaneous adipose tissue is an interesting source of autologous stem cells with a fundamental role in the pathophysiology of obesity, metabolic syndromes and insulin resistance. We hypothesize that obesity could alter the stromal-vascular fraction (SVF) and adipose stem cell (ASCs) functions, which could compromise its regenerative behavior. Furthermore, we aimed to evaluate whether ASCs derived from post bariatric surgery ex-obese women maintain their functions in a similar fashion as do those from individuals who have never been obese.

Methods
The SVF of subcutaneous adipose tissue from control (n = 6, body mass index – BMI - 27.5 ± 0.5 kg/m2), obese (n = 12, BMI 46.2 ± 5.1 kg/m2) and post bariatric surgery ex-obese (n = 7, initial BMI 47.8 ± 1.3 kg/m2; final BMI 28.1 ± 1.1 kg/m2) women were isolated and evaluated by flow cytometry. ASCs were tested for lipid accumulation by perilipin, adipose differentiation-related protein (ADRP) and Oil Red O staining after adipogenic stimulus. The cytokines secreted by the ASCs and after lipid accumulation induction were also evaluated.

Results
The subcutaneous adipose tissue of obese and post bariatric surgery ex-obese women was enriched in pericytes (p = 0.0345). The number of supra-adventitial cells was not altered in the obese patients, but it was highly enriched in the post bariatric surgery ex-obese women (p = 0.0099). The ASCs of the post bariatric surgery ex-obese patients secreted more MCP-1 (monocyte chemoattractant protein-1; p = 0.0078). After lipid accumulation induction, the ASCs of the patients in all groups secreted less IL-6 than the ASCs with no adipogenic stimulus (p < 0.0001). Obese ASCs with lipid accumulation secreted the highest amount of IL-6 (p < 0.001) whereas the ASCs from the controls secreted the highest amount of adiponectin (p < 0.0001). The ASCs from the post bariatric surgery ex-obese patients showed the highest levels of lipid accumulation whereas those from the obese women had the lowest levels (p < 0.0001).

Conclusions
SVF content and ASC behavior are altered in the subcutaneous adipose tissue of morbid obese women; these changes are not completely restored after bariatric surgery-induced weight loss. The cellular alterations described in this study could affect the regenerative effects of adipose stem cells. Further investigations are required to avoid jeopardizing the development of autologous stem cell-based therapies.
Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus granulocyte-colony stimulating factor: results from a Gruppo Italiano Malattie EMatologiche dell’Adulto Multiple Myeloma Working Party study
Authors: Musto Pellegrino , Simeon Vittorio , Grossi Alberto , Gay Francesca , Bringhen Sara , Larocca Alessandra , Guariglia Roberto , Pietrantuono Giuseppe , Villani Oreste , D’Arena Giovanni , Cuomo Carmela , Musto Clelia , Morabito Fortunato , Petrucci Maria Teresa , Offidani Massimo , Zamagni Elena , Tacchetti Paola , Conticello Concetta , Milone Giuseppe , Palumbo Antonio , Cavo Michele , Boccadoro Mario 
Published: April 2015

Abstract
Introduction
A still not well defined proportion of patients with multiple myeloma (MM) and eligible for autologous stem cell transplantation (AuSCT) fails to mobilize CD34+ peripheral blood stem cells (PBSC) at all or to collect an adequate number for a safe procedure or sufficient for multiple transplants. These so-called “poor-mobilizers” are difficult to be predicted, due to marked difference across previous heterogeneous studies.

Methods
We aimed to develop a method based on simple clinical parameters for predicting unsuccessful (<2 × 106/kg) or sub-optimal (<5 × 106/kg) collections of CD34+ PBSC in newly diagnosed MM patients eligible for AuSCT, treated with novel agents and receiving an homogeneous mobilizing therapy with cyclophosphamide and granulocyte-colony stimulating factor (G-CSF). To this purpose, 1,348 patients enrolled in five consecutive Italian clinical trials were retrospectively analysed. Age, baseline low peripheral blood cell counts, use of lenalidomide, and haematological toxicity developed during induction were taken into account as possible factors associated with poor mobilization.

Results
Overall, 280 patients (20.8%) showed either sub-optimal (167 patients, 12.4%) or unsuccessful (113 patients, 8.4%) collections. All analysed parameters negatively influenced the procedure, but only age and haematological toxicity during induction maintained their significance at multivariate analysis. Based on ordinal logistic regression model, we constructed a risk heat-map where the four parameters were pooled and weighted according to their relevance as single or combined variables. This model was predictive for different probabilities of failure, suboptimal or optimal outcomes.

Conclusions
We found that about one fifth of newly diagnosed MM fails to collect an adequate number of PBSC. Our model, based on a large group of patients treated frontline with novel agents and receiving the most popular mobilizing approach currently employed in Europe, is applicable in individual subjects and may contribute to the early identification of “poor mobilizer” phenotypes.
Biphasic monopolar electrical stimulation induces rapid and directed galvanotaxis in adult subependymal neural precursors
Authors: Babona-Pilipos Robart , Pritchard-Oh Alex , Popovic Milos R , Morshead Cindi M 
Published: April 2015

Abstract
Introduction
Following injury such as stroke, adult mammalian subependymal neural precursor cells (NPCs) are induced to proliferate and migrate toward the lesion site where they differentiate into neural cells, albeit with limited efficacy. We are interested in enhancing this migratory ability of NPCs with the long-term goal of promoting neural repair. Herein we build on our previous studies demonstrating that direct current electric fields (DCEFs) promote rapid and cathode-directed migration of undifferentiated adult NPCs (but not differentiated phenotypes) - a phenomenon known as galvanotaxis. While galvanotaxis represents a promising strategy to promote NPC recruitment to lesion sites, stimulation of neural tissue with DCEFs is not a clinically-viable strategy due to the associated accumulation of charge and toxic byproducts. Balanced biphasic waveforms prevent the accumulation of charge and thus are outside of the limitations of DCEFs. In this study, we investigated the effects of balanced biphasic electrical stimulation on the migratory behaviour of undifferentiated subependymal NPCs and their differentiated progeny.

Methods
NPCs were isolated from the subependymal zone of adult mouse brains and cultured in a NPC colony-forming assay to form neurospheres. Neurospheres were plated onto galvanotaxis chambers in conditions that either promoted maintenance in an undifferentiated state or promoted differentiation into mature phenotypes. Chambers containing cells were then time-lapse imaged in the presence of either biphasic monopolar, or biphasic bipolar electrical stimulation, or in the complete absence of electrical stimulation. Single cell migration was subsequently tracked and the cells’ magnitude of velocity, directedness and tortuosity were quantified.

Results
We demonstrate, for the first time, the use of balanced biphasic electric fields to induce galvanotaxis of NPCs. Undifferentiated adult mouse subependymal NPCs exposed to biphasic monopolar stimulation undergo rapid and directed migration toward the cathode. In contrast, both biphasic bipolar stimulation and the lack of electrical stimulation produced non-directed migration of NPCs. Notably, NPCs induced to differentiate into mature phenotypes prior to exposure to electrical stimulation do not migrate in the presence or absence of biphasic stimulation.

Conclusion
We purport that balanced biphasic stimulation represents a clinically-viable technique for mobilizing NPCs that may be integrated into strategies for promoting endogenous neurorepair.
Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses
Authors: Kol Amir , Wood Joshua A , Carrade Holt Danielle D , Gillette Jessica A , Bohannon-Worsley Laurie K , Puchalski Sarah M , Walker Naomi J , Clark Kaitlin C , Watson Johanna L , Borjesson Dori L 
Published: April 2015

Abstract
Introduction
Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses.

Methods
We injected three doses of 25 × 106 allogeneic MSCs from either AT or BM (a total of 75 × 106 MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets.

Results
Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8+ T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls.

Conclusions
These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8+ T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.
Hematopoiesis: from start to immune reconstitution potential
Authors: Liang Haydn C-Y , Zúñiga-Pflücker Juan Carlos 
Published: April 2015

AbstractThe study of hematopoiesis has been a focus for developmental biologists for over 100 years. What started as a series of microscopic observations in different animal model systems has since evolved into studies of gene expression and regulation, and subsequent protein–protein interactions, cell surface protein expression profiling, and functional mapping of cell fates. In this review, we will discuss the milestone discoveries that have been achieved in the field of hematopoietic development, as well as the techniques that have been employed. Finally, we look toward the future and consider unresolved questions. We also reflect on one of the earliest realizations made in this area of study: that hematopoiesis is evolutionarily conserved, and as a consequence we reflect on the impacts of early and current discoveries and their clinical implications. The future direction of the study of hematopoietic stem cells will probably make use of pluripotent stem cells to yield specific immune cell lineages and eventual clinical applications.
Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer
Authors: Tang Rui-jing , Shen Su-nan , Zhao Xiao-yin , Nie Yun-zhong , Xu Yu-jun , Ren Jing , Lv Ming-ming , Hou Ya-yi , Wang Ting-ting 
Published: April 2015

Abstract
Introduction
Previous studies have produced controversial results regarding whether mesenchymal stem cells (MSCs) promote or inhibit tumor development. Given the dual role of MSCs in inflammation and cancer, in this study the colitis-associated colorectal cancer (CAC) model was used to examine whether umbilical cord tissue-derived MSCs could prevent neoplasm by inhibiting chronic inflammation.

Methods
MSCs were obtained and identified using flow cytometry. Colitis-associated colorectal cancer model was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) and MSCs were injected intravenously twice. Levels of immune cells in mesenteric lymph node including regulatory T (Treg) cells were detected using flow cytometry. Naïve T cells and Jurkat cells were co-cultured with MSCs and the effect of MSCs on Treg cells differentiation was evaluated.

Results
After injection through tail vein, MSCs could migrate to colon and suppress colitis-related neoplasm. This tumor suppressive effect was characterized by longer colon length, decreased tumor numbers and decreased expression of Ki-67. Moreover, MSCs alleviated the pathology of inflammation in the colitis stage of CAC model and inhibited inflammation cytokines both in colon and serum. Furthermore, Treg cells were accumulated in mesenteric lymph node of MSCs-treated mice while the percentage of T helper cells 2 (Th2) and Th17 were not changed. Of note, MSCs secreted transforming growth factor-β (TGF-β) enhanced the induction of Treg cells from naïve T cells. The conditioned medium of MSCs also activated Smad2 signaling, which has been reported to regulate Treg cells.

Conclusions
These results proved that MSCs could migrate to colon tissues and induce the differentiation of Treg cells via Smad2 as so to inhibit the colitis and suppress the development of CAC.