bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients with pathogenic variants for breast cancer other than BRCA1 and BRCA2: qualitative interviews about health care experiences
Authors: Clift Kristin E. , Macklin Sarah K. , Hines Stephanie L. 
Published: December 2019

Abstract
Background
Genetic testing for hereditary cancer syndromes has been revolutionized by next-generation sequencing, which allows for simultaneous review of numerous genes. Multigene panels are regularly offered to patients because of their scope and decreased cost and turnaround time. However, many genes included on larger panels have not been studied as extensively as BRCA1 and BRCA2 (BRCA1/2), and their clinical effects are often not as well established.

Methods
We identified patients who received positive test results for pathogenic variants of breast cancer genes from January 2012 through May 2018. We mailed a survey and conducted qualitative interviews to explore the personal and health care experiences of patients with pathogenic variants of BRCA1/2 and patients with “other” (ie, non-BRCA1/2 or PALB2; PTEN; ATM; TP53; NBM, RAD51C; MSH6) variants. We compared the experiences of these patients.

Results
Fifty-nine out of 128 individuals responded to the survey (46%). Thirty-two patients had BRCA1/2 variants, and 27 had other variants. (49 women and 10 men; median [range] age, 63 [34–87] years). We interviewed 21 patients (17 women and 4 men; median [range] age, 59.6 [34–82] years). Of the interview participants, ten patients had BRCA1/2 variants, and 11 had non-BRCA1/2 variants. Patients reported receiving poor information about their genetic test results, and they often educated their physicians about their results. Some patients believed that they had been ignored or “brushed off” by health care professionals because non-BRCA1/2 genes are less understood outside the genetics research community. Patients with BRCA1/2 variants had similar problems with health care providers, despite increased awareness and established guidelines about BRCA1/2.

Conclusions
Research is required to understand the clinical significance and proper management of diseases attributable to newly characterized hereditary cancer genes. Additional evaluation of patient and provider education should be at the forefront of efforts to improve patient care.
Functional electrical stimulation-assisted cycle ergometry in the critically ill: protocol for a randomized controlled trial
Authors: Waldauf Petr , Gojda Jan , Urban Tomáš , Hrušková Natália , Blahutová Barbora , Hejnová Marie , Jiroutková Kateřina , Fric Michal , Jánský Pavel , Kukulová Jana , Stephens Francis , Řasová Kamila , Duška František 
Published: December 2019

Abstract
Background
Intensive care unit (ICU)-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 h of ICU admission may improve muscle function and long-term outcome.

Methods
An assessor-blinded, pragmatic, single-centre randomized controlled trial will be performed. Adults (n = 150) mechanically ventilated for < 48 h from four ICUs who are estimated to need > 7 days of critical care will be randomized (1:1) to receive either standard of care or FES-CE-based intensified rehabilitation, which will continue until ICU discharge. Primary outcome: quality of life measured by 36-Item Short Form Health Survey score at 6 months. Secondary outcomes: functional performance at ICU discharge, muscle mass (vastus ultrasound, N-balance) and function (Medical Research Council score, insulin sensitivity). In a subgroup (n = 30) we will assess insulin sensitivity and perform skeletal muscle biopsies to look at mitochondrial function, fibre typing and regulatory protein expression.

Trial registration
ClinicalTrials.gov, NCT02864745. Registered on 12 August 2016.
Breastfeeding success with the use of the inverted syringe technique for management of inverted nipples in lactating women: a study protocol for a randomized controlled trial
Authors: Nabulsi Mona , Ghanem Rayan , Abou-Jaoude Marlie , Khalil Ali 
Published: December 2019

Abstract
Background
Breastfeeding provides ideal infant nutrition, conferring several health benefits to children and their mothers. Women with inverted nipples, however, face difficulties that force them to prematurely terminate breastfeeding. Whereas available conservative measures for the correction of inverted nipples are of limited success, the use of an inverted syringe may be effective in achieving high rates of infant latching and exclusive breastfeeding. This technique, however, has not been investigated in a clinical trial.

Methods/design
This open-label randomized controlled trial aims to investigate whether, in women with inverted nipples, the use of an inverted syringe increases the rate of exclusive breastfeeding at one month compared to standard care. One-hundred healthy women with grade 1 or 2 inverted nipples will be recruited as of 37 weeks of gestation. They will be randomly allocated to standard care (control group) or to an intervention group. The intervention consists of using an inverted syringe to evert the nipple before every breastfeed, starting with the first feed after delivery. The primary outcome measure is the rate of exclusive breastfeeding at 1 month. Secondary outcome measures include exclusive breastfeeding rates at 3 and 6 months, nipple eversion rate, successful latching rate, rates of any breastfeeding at 1, 3, and 6 months, breastfeeding-associated complications, maternal satisfaction with breastfeeding, maternal quality of life, and adverse events. Descriptive and regression analysis will be conducted under the intention to treat basis.

Discussion
The use of the inverted syringe to evert inverted nipples is a simple, inexpensive, and safe technique that can be performed by mothers with inverted nipples. Findings of this trial, if positive, will provide much needed evidence for a safe, affordable, readily available, and simple intervention to treat inverted nipples, and improve breastfeeding practice among affected women.

Trial registration
ClinicalTrials.gov, NCT03529630. Registered May 8, 2018.
Sports participation related to injuries and illnesses among ambulatory youth with chronic diseases: results of the health in adapted youth sports study
Authors:   on behalf of the HAYS study group, Lankhorst Kristel , de Groot Janke , Takken Tim , Backx Frank 
Published: December 2019

Abstract
Background
Although sports participation leads to important health enhancement for youth with chronic diseases or physical disabilities (CDPD), it may pose an increased risk for injury or illness. This study investigated the incidence, type, severity and risks to (sports-related) injuries and illnesses among ambulatory youth with CDPD.

Methods
Over a 12-month period, every 2 weeks, the characteristics of injuries and illnesses were registered by an online questionnaire and phone-based interview. Physical activity level was measured with the Activ8 during 1 week. Complete data was available of 103 youngsters with CDPD (61 boys, 42 girls), with a mean age of 14.4 (SD = 2.7) years. The personal characteristics, the injury and illness rates per 1000 h of PA were investigated per group of organized sports participation per week (0, 1 or ≥ 2 times p/wk).

Results
Almost half of the youngsters sustained one or more injuries (46%) or illnesses (42%) during 1 year. The injury rate per 1000 h of PA between 0, 1 and ≥ 2 times per week of sports participation was 0.84, 1.88, 133 respectively and the illness rate were 1.87, 1.88 and 1.18 respectively. Differences between the rates were not statically significant. Most reported health problems had no subsequent restriction (49%) or other minor consequences (21%) in school, physical education or sports participation. Most reported health problems were contusions (41%) at the lower extremity (74%) and flu plus fever (58%).

Conclusions
Participation in sports ≥2 times per week does not pose a significant increased risk in the incidence of injury or illness per 1000 h of PA in youth with CDPD compared to their peers who participate less frequent (once weekly) and compared to non-sports participants. Athletes who participate in sports at least twice weekly get injured mostly during their sporting activities, while peers who do participate in sports once a week or not at all, get injured during less intense physical activities during physical eduction lessons, ADL or non-organized sports and play in leisure time. The social impact of injuries or illnesses was limited.
Mesenchymal stem cell-derived exosomal microRNA-133b suppresses glioma progression via Wnt/β-catenin signaling pathway by targeting EZH2
Authors: Xu Haiyang , Zhao Guifang , Zhang Yu , Jiang Hong , Wang Weiyao , Zhao Donghai , Hong Jin , Yu Hongquan , Qi Ling 
Published: December 2019

Abstract
Background
Mesenchymal stem cells (MSCs) play a significant role in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the effects of exosomal miR-133b derived from MSCs on glioma cell behaviors.

Methods
Microarray-based analysis identified the differentially expressed genes (DEGs) in glioma. The expression patterns of EZH2 and miR-133b along with interaction between them were clarified in glioma. The expression of miR-133b and EZH2 in glioma cells was altered to examine their functions on cell activities. Furthermore, glioma cells were co-cultured with MSC-derived exosomes treated with miR-133b mimic or inhibitor, and EZH2-over-expressing vectors or shRNA against EZH2 to characterize their effect on proliferation, invasion, and migration of glioma cells in vitro. In vivo assays were also performed to validate the in vitro findings.

Results
miR-133b was downregulated while EZH2 was upregulated in glioma tissues and cells. miR-133b was found to target and negatively regulate EZH2 expression. Moreover, EZH2 silencing resulted in inhibited glioma cell proliferation, invasion, and migration. Additionally, MSC-derived exosomes containing miR-133b repressed glioma cell proliferation, invasion, and migration by inhibiting EZH2 and the Wnt/β-catenin signaling pathway. Furthermore, in vivo experiments confirmed the tumor-suppressive effects of MSC-derived exosomal miR-133b on glioma development.

Conclusion
Collectively, the obtained results suggested that MSC-derived exosomes carrying miR-133b could attenuate glioma development via disrupting the Wnt/β-catenin signaling pathway by inhibiting EZH2, which provides a potential treatment biomarker for glioma.
The combinatory effect of sinusoidal electromagnetic field and VEGF promotes osteogenesis and angiogenesis of mesenchymal stem cell-laden PCL/HA implants in a rat subcritical cranial defect
Authors: Chen Jingyuan , Tu Chang , Tang Xiangyu , Li Hao , Yan Jiyuan , Ma Yongzhuang , Wu Hua , Liu Chaoxu 
Published: December 2019

AbstractBackgroundRestoration of massive bone defects remains a huge challenge for orthopedic surgeons. Insufficient vascularization and slow bone regeneration limited the application of tissue engineering in bone defect. The effect of electromagnetic field (EMF) on bone defect has been reported for many years. However, sinusoidal EMF (SEMF) combined with tissue engineering in bone regeneration remains poorly investigated.MethodsIn the present study, we investigated the effect of SEMF and vascular endothelial growth factor (VEGF) on osteogenic and vasculogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Furthermore, pretreated rBMSC- laden polycaprolactone-hydroxyapatite (PCL/HA) scaffold was constructed and implanted into the subcritical cranial defect of rats. The bone formation and vascularization were evaluated 4 and 12 weeks after implantation.ResultsIt was shown that SEMF and VEGF could enhance the protein and mRNA expression levels of osteoblast- and endothelial cell-related markers, respectively. The combinatory effect of SEMF and VEGF slightly promoted the angiogenic differentiation of rBMSCs. The proteins of Wnt1, low-density lipoprotein receptor-related protein 6 (LRP-6), and β-catenin increased in all inducted groups, especially in SEMF + VEGF group. The results indicated that Wnt/β-catenin pathway might participate in the osteogenic and angiogenic differentiation of rBMSCs. Histological evaluation and reconstructed 3D graphs revealed that tissue-engineered constructs significantly promoted the new bone formation and angiogenesis compared to other groups.ConclusionThe combinatory effect of SEMF and VEGF raised an efficient approach to enhance the osteogenesis and vascularization of tissue-engineered constructs, which provided a useful guide for regeneration of bone defects.
Allogeneic mesenchymal stem cells for treatment of severe burn injury
Authors: Jeschke Marc G. , Rehou Sarah , McCann Matthew R. , Shahrokhi Shahriar 
Published: December 2019

AbstractThe most important determinant of survival post-burn injury is wound healing. For decades, allogeneic mesenchymal stem cells (MSCs) have been suggested as a potential treatment for severe burn injuries. This report describes a patient with a severe burn injury whose wounds did not heal with over 18 months of conventional burn care. When treated with allogeneic MSCs, wound healing accelerated with no adverse treatment complications. Wound sites showed no evidence of keloids or hypertrophic formation during a 6-year follow-up period. This therapeutic use of allogeneic MSCs for large non-healing burn wounds was deemed safe and effective and has great treatment potential.
Relative safety of various spermatogenic stem cell purification methods for application in spermatogenic stem cell transplantation
Authors: Tian Jia , Ma Ke , Pei Cheng-bin , Zhang Shao-hua , Li Xue , Zhou Yue , Yan Bei , Wang Hong-yan , Ma Liang-hong 
Published: December 2019

Abstract
Background
Spermatogonial stem cell (SSC) transplantation technology as a promising option for male fertility preservation has received increasing attention, along with efficient SSC purification technology as a necessary technical support; however, the safety of such application in patients with tumors remains controversial.

Methods
In this study, we used a green fluorescent protein mouse xenograft model of B cell acute lymphocytic leukemia. We isolated and purified SSCs from the testicular tissue of model mice using density gradient centrifugation, immune cell magnetic bead separation, and flow cytometry. The purified SSCs were transplanted into convoluted seminiferous tubules of the nude mice and C57BL/6 male mice subjected to busulfan. The development and proliferation of SSCs in the recipient testis were periodically tested, along with whether B cell acute lymphocytic leukemia was induced following SSC implantation. The genetic characteristics of the offspring obtained from natural mating were also observed.

Results
In testicular leukemia model mice, a large number of BALL cells infiltrated into the seminiferous tubule, spermatogenic cells, and sperm cells in the testis tissue decreased. After spermatogonial stem cell transplantation, the transplanted SSCs purified by immunomagnetic beads and flow cytometry methods colonized and proliferated extensively in the basement of the seminiferous tubules of mice; a large number of spermatogenic cells and sperm were found in recipient testicular tissue after 12 weeks of SSC transplantation. In leukemia detection in nude mice after transplantation in the three SSC purification groups, a large number of BALL cells could be detected in the blood of recipient mice 2–3 weeks after transplantation in the density gradient centrifugation group, but not in the blood of the flow cytometry sorting group and the immunomagnetic bead group after 16 weeks of observation.

Conclusions
In this study, we confirmed that immunomagnetic beads and flow cytometry methods of purifying SSCs from the testicular tissue of the testicular leukemia mouse model could be safely applied to the SSC transplantation technology without concomitant tumor implantation. The results thus provide a theoretical basis for the application of tumor SSC cryopreservation for fertility preservation in patients with tumors.
The superiority of conditioned medium derived from rapidly expanded mesenchymal stem cells for neural repair
Authors: Chen Ya-Tzu , Tsai May-Jywan , Hsieh Nini , Lo Ming-Jei , Lee Meng-Jen , Cheng Henrich , Huang Wen-Cheng 
Published: December 2019

AbstractsBackgroundSpinal cord injury (SCI) is a complex and severe neurological condition. Mesenchymal stem cells (MSCs) and their secreted factors show promising potential for regenerative medicine. Many studies have investigated MSC expansion efficacy of all kinds of culture medium formulations, such as growth factor-supplemented or xeno-free medium. However, very few studies have focused on the potential of human MSC (hMSC) culture medium formulations for injured spinal cord repair. In this study, we investigated the effect of hMSC-conditioned medium supplemented with bFGF, EGF, and patient plasma, namely, neural regeneration laboratory medium (NRLM), on SCI in vitro and in vivo.MethodsCommercial and patient bone marrow hMSCs were obtained for cultivation in standard medium and NRLM separately. Several characteristics, including CD marker expression, differentiation, and growth curves, were compared between MSCs cultured in standard medium and NRLM. Additionally, we investigated the effect of the conditioned medium (referred to as NRLM-CM) on neural repair, including inflammation inhibition, neurite regeneration, and spinal cord injury (SCI), and used a coculture system to detect the neural repair function of NRLM-MSCs.ResultsCompared to standard culture medium, NRLM-CM had superior in inflammation reduction and neurite regeneration effects in vitro and improved functional restoration in SCI rats in vivo. In comparison with standard culture medium MSCs, NRLM-MSCs proliferated faster regardless of the age of the donor. NRLM-MSCs also showed increased adipose differentiative potential and reduced CD90 expression. Both types of hMSC CM effectively enhanced injured neurite outgrowth and protected against H2O2toxicity in spinal cord neuron cultures. Cytokine arrays performed in hMSC-CM further revealed the presence of at least 120 proteins. Among these proteins, 6 demonstrated significantly increased expression in NRLM-CM: adiponectin (Acrp30), angiogenin (ANG), HGF, NAP-2, uPAR, and IGFBP2.ConclusionsThe NRLM culture system provides rapid expansion effects and functional hMSCs. The superiority of the derived conditioned medium on neural repair shows potential for future clinical applications.
Modeling appendicular skeletal cartilage development with modified high-density micromass cultures of adult human bone marrow-derived mesenchymal progenitor cells
Authors: Pirosa Alessandro , Clark Karen L. , Tan Jian , Yu Shuting , Yang Yuanheng , Tuan Rocky S. , Alexander Peter G. 
Published: December 2019

Abstract
Background
Animal cell-based systems have been critical tools in understanding tissue development and physiology, but they are less successful in more practical tasks, such as predicting human toxicity to pharmacological or environmental factors, in which the congruence between in vitro and clinical outcomes lies on average between 50 and 60%. Emblematic of this problem is the high-density micromass culture of embryonic limb bud mesenchymal cells, derived from chick, mouse, or rat. While estimated predictive value of this model system in toxicological studies is relatively high, important failures prevent its use by international regulatory agencies for toxicity testing and policy development. A likely underlying reason for the poor predictive capacity of animal-based culture models is the small but significant physiological differences between species. This deficiency has inspired investigators to develop more organotypic, 3-dimensional culture system using human cells to model normal tissue development and physiology and assess pharmacological and environmental toxicity.

Methods
We have developed a modified, miniaturized micromass culture model using adult human bone marrow-derived mesenchymal progenitor cells (hBM-MPCs) that is amenable to moderate throughput and high content analysis to study chondrogenesis. The number of cells per culture was reduced, and a methacrylated gelatin (gelMA) overlay was incorporated to normalize the morphology of the cultures.

Results
These modified human cell-based micromass cultures demonstrated robust chondrogenesis, indicated by increased Alcian blue staining and immunodetectable production of collagen type II and aggrecan, and stage-specific chondrogenic gene expression. In addition, in cultures of hBM-MPCs transduced with a lentiviral collagen type II promoter-driven GFP reporter construct, levels of GFP reporter activity correlated well with changes in endogenous collagen type II transcript levels, indicating the feasibility of non-invasive monitoring of chondrogenesis.

Conclusions
The modified hBM-MPC micromass culture system described here represents a reproducible and controlled model for analyzing mechanisms of human skeletal development that may later be applied to pharmacological and environmental toxicity studies.
Genetically modified mesenchymal stem cell therapy for acute respiratory distress syndrome
Authors: Han Jibin , Liu Yuxiang , Liu Hong , Li Yuanyuan 
Published: December 2019

AbstractAcute respiratory distress syndrome (ARDS) is a devastating hypoxemic respiratory failure, characterized by disruption of the alveolar-capillary membrane barrier. Current management for ARDS remains supportive, including lung-protective ventilation and a conservative fluid strategy. Mesenchymal stem cells (MSCs) have emerged as a potentially attractive candidate for the management of ARDS through facilitating lung tissue regeneration and repair by releasing paracrine soluble factors. Over the last decade, a variety of strategies have emerged to optimize MSC-based therapy. Among these, the strategy using genetically modified MSCs has received increased attention recently due to its distinct advantage, in conferring incremental migratory capacity and, enhancing the anti-inflammatory, immunomodulatory, angiogenic, and antifibrotic effects of these cells in numerous preclinical ARDS models, which may in turn provide additional benefits in the management of ARDS. Here, we provide an overview of recent studies testing the efficacy of genetically modified MSCs using preclinical models of ARDS.