bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant Human Bone Morphogenetic Proteins-4 Enhanced the Tendon-to-bone Attachment Healing in a Murine Model of Rotator Cuff Tear: A Randomized Controlled Trial
Authors: Chen Huabin , Wang Zhanwen , Zhou Li , Wu Bing , Lu Hongbin , Zhang Ciliu , Zhang Tao 
Published: September 2020

Abstract
Background: Injuries on tendon-to-bone attachment (TBA) are common clinical dilemmas. Bone Morphogenetic Proteins-4 (BMP-4) has been found the potency in chondrogenesis. But there is rare studies focusing the influence of BMP-4 on the TBA healing. Thus, the objective of this study was to explore the effect of BMP-4 on the healing of TBA in murine model of rotator cuff tear.Methods: 120 mature C57BL/6 mice (12 weeks old) were randomly divided into BMP-4 group, noggin (an inhibitor of all BMP activities) group and control group after being established an injury model of supraspinatus tendon insertion. At week 2 and 4 after surgery, the supraspinatus tendon- humerus complex (SSTHC) were harvested for microradiographic, histologic, immunofluorescent and biomechanical evaluations.Results: Radiographic data showed that BMP-4 was able to improve the quality of subchondral bone, manifested as higher BV/TV, Tb.N, TB.Th, and lower Tb.Sp. Histologically, the BMP-4 group at week-2 and -4 showed better BTA healing interface, characterized by better organizational integration and remodeling, thicker fibrocartilage layer and more fibrocartilage cells. Immunoflorescence evaluation demonstrated the number of SOX 9 positive cells in the BMP-4 group was significantly more than that in the control or noggin group at postoperative weeks 2 and 4 (p<0.05 for all). Mechanical testing results demonstrated the failure load and stiffness in the BMP-4 group were significantly higher (p<0.05 for both), while in the noggin group were lower (p<0.05 for both), compared to the control group at postoperative weeks 4.Conclusion: BMP-4 might enhance the TBA healing by promoting the regeneration of fibrocartilaginous enthesis and mineralization, while noggin inhibited this process.Clinical Relevance: BMP-4 may be a potential therapy to augment TBA healing, and finally lead to more rapid rehabilitation and reduce risk of recurrent repair.
Targeting BACH2-FOS signaling overcomes chemoresistance via stromal microenvironment alterations in pediatric acute lymphoblastic leukemia
Authors: Zhang Han , Zhang Ruidong , Zheng Xueling , Sun Ming , Fan Jia , Fang Chunlian , Tian Xin , Zheng Huyong 
Published: September 2020

Abstract
Background

Acute lymphoblastic leukemia (ALL) is an aggressive hematological cancer that mainly affects children. Relapse and chemoresistance result in treatment failure, underlining the need for improved therapies. BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription repressor recognized as a tumor suppressor in lymphomas, but little is known about the function and regulatory network of BACH2 in pediatric ALL (p-ALL).
Methods

We analyzed the clinical relevance of BACH2 in nearly 450 published p-ALL microarray data. The mRNA and protein levels of BACH2 were validated in an independent cohort of p-ALL samples. The roles of BACH2 in leukemogenesis were examined using cell growth and proliferation assays, cell cycle and BrdU assays, cell apoptosis and cell adhesion assays as well as in vivo mouse models. Multiplexed flow cytometric assay was utilized to detect the bone marrow environmental alterations. Luciferase activity assay and CUT&Tag sequencing were applied to determine the downstream target of BACH2. The therapeutic effects of chemicals were evaluated in precursor B (pre-B) ALL cells, primary p-ALL cells and in vivo pre-B ALL-driven leukemia xenografts.
Results

We found aberrant BACH2 expression at newly diagnosis not only facilitated risk stratification of p-ALL but also served as a sensitive predictor for early treatment response and clinical outcome. Silencing BACH2 in pre-B ALL cells increased cell proliferation and accelerated cell cycle progression. BACH2 blockade also promoted cell adhesion to bone marrow stromal cells and conferred chemo-resistant properties to leukemia cells by altering stromal microenvironment. Strikingly, we identified FOS, a transcriptional activator competing with BACH2, as a novel downstream target repressed by BACH2. Blocking FOS by chemical compounds enhanced the effect of cytarabine treatment in both primary p-ALL cells and pre-B ALL-driven leukemia xenografts and prolonged survival of tumor-bearing mice.
Conclusions

Our results highlight an interconnected network of BACH2-FOS, disruption of which could render current ALL chemotherapies more effective and offer a promising therapeutic strategy to overcome chemoresistance in p-ALL.
Effects of Field-Grown Transgenic Cry1Ah1 Poplar on the Rhizosphere Microbiome
Authors: Wei Hui , Movahedi Ali , Peijun Zhou , Xu Chen , Sun Weibo , Li Dawei , Zhuge Qiang 
Published: September 2020

Abstract
Background: Poplar (Populus) is a genus of globally important plantation trees used widely in industrial and agricultural production. However, poplar is easily damaged by Micromelalopha troglodyta and Hyphantria cunea, resulting in a decline in poplar quality. Due to their strong insect resistance, Bt toxin-encoded Cry genes have been widely adopted in poplar breeding; however, potential adverse effects of Cry1Ah1-modified poplars on the ecological environment have raised concerns. Results: In this study, we comprehensively analyzed the structural and functional composition of the rhizosphere microbiome in field-grown transgenic Bt poplar. Conclusions: Our analysis of soil chemistry patterns revealed that soil alkaline nitrogen, soil available phosphorus, and microbial biomass nitrogen and phosphorus levels were improved, whereas microbial biomass carbon declined in Cry1Ah1-modified poplar rhizosphere samples. We applied metagenomic sequencing of Non-Transgenic (NT) and Cry1Ah1-modified poplar rhizosphere samples collected from a natural field; the predominant taxa included Proteobacteria, Acidobacteria, and Actinobacteria. We also identified microbial functional traits involved in membrane transport, amino acid metabolism, carbohydrate metabolism, and replication and repair in NT and Cry1Ah1-modified poplars. Together, these results demonstrate that the NT and Cry1Ah1-modified poplar rhizosphere microbiomes had similar diversity and structure. These differences in relative abundance were observed in a few genera but did not affect the primary genera or soil.
The Significance Of Hormone Receptors In Male Breast Cancer
Authors: Hotko Yevhen 
Published: September 2020

Abstract
Background Male mammary glands are usually considered a rudimentary organ. However, they may be exposed to similar pathological influences as female breasts. These pathological influences may cause the development of malignant breast tumors. Breast cancer in males is a rare disease, nevertheless, it is a serious problem. According to numerous national cancer registries from around the world, this disease takes 1% on average in the structure of morbidity of malignant neoplasms of this organ in both sexes. Methods In our study (168 patients) estrogen receptors were positive in the tumors of 75% of patients. The positive rate of progesterone receptors was observed in 44% of patients. The detection rate of steroid hormone receptors in malignant tumors of the male breast ranges from 65 to 100%, depending on the criteria for identifying their positivity level. The hormone therapy in the early and late stages of cancer include antiestrogens, steroid and non-steroid aromatase inhibitors, both as monotherapy and in combination with LHRH-agonists, fulvestrant and other hormonal agents. Results There was no dependence found between the receptor status of the tumors and the age of patients with breast cancer. Breast cancer in men has a more aggressive course than the same disease in women. This means lower survival rate of male patients, greater number of locally advanced and metastatic cases, with delayed primary treatment, and resistance to treatment compared to female breast cancer patients. The incidence of receptor positive tumors in men does not increase with age, as observed in women with breast cancer. Despite numerous reports on the effectiveness of hormone therapy in men with breast cancer, many aspects of this type of therapy remain largely unexplained. Conclusions Hormone therapy appears the most effective in patients with the so-called feminization syndrome, which includes signs of hyperestrogenemia, as well as in patients with multiple unfavorable prognostic signs (stage III of cancer, low differentiation of tumor cells, status of regional lymph nodes N2-3, medium, severe and morbid obesity). Orchiectomy does not increase the survival rate, therefore, its application is impractical.
Bacterial and Fungal Gut Community Dynamics Over the First Five Years of Life in Predominantly Rural Communities in Ghana
Authors: Amenyogbe Nelly Aku , Adu-Gyasi Dennis , Enuameh Yeetey , Asante Kwaku Poku , Konadu Dennis Gyasi , Seyram Kaali , Dosoo David , Panigrahi Pinaki , Kollmann Tobias , Mohn William , Owusu-Agyei Seth 
Published: September 2020

Abstract
BackgroundBacterial and fungal microbiotas are increasingly recognized as important in health and disease starting early in life. However, microbiota composition has not yet been investigated in most rural, low-resource settings, and in such settings, bacterial and fungal microbiotas have not been compared. Thus, we applied 16S and ITS2 amplicon sequencing, respectively, to investigate bacterial and fungal fecal microbiotas in rural Ghanaian children from birth to 5 years of age. Corresponding maternal fecal and breastmilk microbiotas were additionally investigated. ResultsWhile bacterial communities differed systematically across the age spectrum in composition and diversity, the same was not observed for the fungal microbiota. We also identified a novel and dramatic change in the maternal postpartum microbiota. This change included much higher abundance of E. coli and much lower abundance of Prevotella in the first versus fourth week postpartum. While infants shared more bacterial taxa with their mother’s stool and breastmilk than with those of unrelated mothers, there were far fewer shared fungal taxa. ConclusionGiven the known ability of commensal fungi to influence host health, the distinct pattern of their acquisition likely has important health consequences. Similarly, the dynamics of mothers’ bacterial microbiotas around the time of birth may have important consequences for their children’s health. Both topics require further study.
Implementation Research Training for Learners in Low- and Middle-income Countries: Evaluating Behavior Change After Participating in a Massive Online Open Course
Authors: Launois Pascal , Maher Dermot , Certain Edith , Ross Bella , Penkunas Michael J. 
Published: September 2020

Abstract
Background: Implementation research (IR) can play a critical role in the delivery of disease control interventions, particularly in low- and middle-income countries (LMICs). The growing demand for IR training has led to the development of a range of training programs and university courses, the majority of which can not be accessed by learners in LMICs. This article reports on the evaluation of a massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases hosted by the World Health Organization on the topic of IR with a focus on infectious diseases of poverty. This study followed Kirkpatrick’s Model to evaluate training programs with a specific focus on post-training changes in behavior.Methods: MOOC participants were invited to take part in an anonymous online survey examining their IR knowledge and how they applied it in their professional practice approximately 1-1.5 years after completing the MOOC. The survey contained 43 open-ended, multiple choice and Likert-type questions. Descriptive statistics were calculated for the quantitative data and responses to the open-ended questions were thematically coded.Results: A total of 748 MOOC participants responded to the survey. The demographic profile of the survey respondents aligned with that of the MOOC participants, with nearly 70% of respondents originating from Africa. Responses to the quantitative and open-ended survey questions revealed that respondents’ IR knowledge had improved to a large extent as a result of the MOOC, and that they used the knowledge and skills gained in their professional lives frequently. Respondents most often cited changes in their conceptual understanding of IR and understanding of the research process as substantial areas of change influenced by participating in the MOOC.Conclusions: These findings indicate that the MOOC was successful in targeting learners from LMICs, in strengthening their IR knowledge and in contributing to their ability to apply it in their professional practice. The utility of MOOCs for providing IR training to learners in LMICs, where implementation challenges are encountered often, makes this platform an ideal standalone learning tool or one that could be combined with other training formats.
A Long Way Home. Biventricular Impella®, VA-ECMO and Extracorporeal LVAD as Bridge to a Permanent LVAD in Severe Ischemic Cardiogenic Shock: A Case Report
Authors: Sadlonova Monika , Gerecke Birgit , El-Essawi Aschraf , Harnisch Lars-Olav , Moerer Onnen , Meissner Konrad , Jacobshagen Claudius , Baraki Hassina , Kutschka Ingo 
Published: September 2020

Abstract
Background: A severe cardiogenic shock can present with clinical complications such as arrhythmias, ischemia and organ failure and even today is associated with a high mortality. Extracorporeal life support (ECLS) by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), Impella® and other mechanical circulatory support systems can reduce the acute circulatory failure. Case presentation: We present the case of a 38-year-old woman with an acute heart failure due to a coronary artery disease who underwent emergency coronary artery bypass grafting and intraoperative implantation of a VA-ECMO. Over the next 4 months, a multidisciplinary team-approach bridged the patient using first a left ventricular (LV) support system (Impella), then additionally a right ventricular (RV) Impella and finally a temporary paracorporeal continuous flow left ventricular support (Rotaflow). Following a promising neurological recovery, a long-term left ventricular assist device (LVAD) was implanted in a bride to transplant (BTT) concept. Conclusions: The addition of LV Impella and RV support by Impella (BiPELLA) on top of VA-ECMO may support survival of patients with refractory cardiogenic shock. In complex biventricular heart failure, an expert center must be able to provide an early multi-modular intervention with elaborated mechanical circulatory support due to a multidisciplinary expertise.
Meningioma Induced by Radiotherapy and a Silicone Foreign Body – Case Report and Literature Review
Authors: Siedlecki Zygmunt , Grzanka Dariusz , Nowak Karol , Grzyb Sebastian , Śniegocki Maciej 
Published: September 2020

Abstract
Background: Meningiomas are the most common radiotherapy related brain tumors, their development can also be induced by intracranial foreign bodies like intraventricular drains in mechanism of chronic intracranial inflammation. The authors present casuistic case of intracranial meningioma developed in contact with a silicone intraventricular in patient who had also brain radiotherapy in childhood. In references, there are only two descriptions about meningiomas induced by both radiotherapy and a silicone foreign body.Case presentation: 30-year-old patient with intracranial meningioma was admitted to neurosurgical department with hemiparesis and severe headaches. Shunt was placed 15 years earlier due to hydrocephalus and the patient had also brain radiation therapy at that time. The neurosurgical tumor removal (Simpson I) was achieved by authors. Shunt was removed during tumor resection but it had to be placed again after few days due to hydrocephalus. During ten years follow-up no tumor recurrence was observed and it can be assessed that the prognosis is favorable.Conclusions: Combination of these two factors is extremely rare however such case can be significant advice for oncological patients with shunts systems who had undergone brain radiotherapy.
Effect of Initial Infusion Doses of Fluid Resuscitation on Prognosis in Patients with Septic Shock: A Prospective Multicentre Observational Study
Authors: Chen Qi-hong , Liu Wei-li , Wu Fei , Chen Han-bing , Shao Jun , Zheng Rui-qiang , Wang Hua-ling 
Published: September 2020

Abstract
OBJECTIVESThe 2018 Surviving Sepsis Campaign (SSC) recommends rapid administration of 30 ml/kg crystalloid for hypotension or lactate ≥4 mmol/L in patients with septic shock; however, there is no credible evidence to support this recommendation. The purpose of this study was to examine the relationship between initial fluid resuscitation doses and prognosis in patients with septic shock.METHODSThis was a multicentre prospective observational study of adult patients with septic shock admitted to four intensive care units (ICUs) in a total of three Jiangsu province teaching hospitals over a 1-year span from May 8, 2018, to June 31, 2020. All enrolled patients with septic shock were categorized as below 20 ml/kg fluid, 20-30 ml/kg fluid and above 30 ml/kg fluid groups according to initial infusion doses of fluid resuscitation. Various demographic and other variables were collected from medical records. Logistic regression analysis and curve fitting were used to determine the relationship between initial fluid resuscitation and patient outcome.MEASUREMENTS AND MAIN RESULTSA total of 153 patients who presented to the ICU were diagnosed with septic shock. The 28-day mortality was highest in the fluid above 30 ml/kg group (47.8%) and lowest in the fluid 20-30 ml/kg group (26.5%, P<0.05). Patients who completed 30 ml/kg initial fluid resuscitation between the first 1-2 h had the lowest 28-day mortality rate (25.9%, P<0.05). Logistic regression showed that an initial liquid dose of 20-30 ml/kg was an independent protective factor, with a significant Odds Ratio(OR) or decreased mortality (OR, 0.393; 95% CI, 0.178-0.866; P<0.05). According to the curve fit, the sequential organ failure assessment change value (∆SOFA) was highest for initial fluid resuscitation with 25.7 ml/kg within 1 h, reaching 5.807; the ∆SOFA score reached the maximum value (5.56) when the initial fluid resuscitation of 30 ml/kg was completed in 2.18 hours.CONCLUSIONIn septic shock patients, an initial fluid resuscitation rate of 20-30 ml/kg within the first 1 h or completion of the initial 30 ml/kg fluid resuscitation between the first 1-2 h may be associated with faster organ function recovery and lower 28-day mortality.Trial registration: Chinese Clinical Trial Registry, ChiCTR-OOC-17013223. Registered 2 November 2017, http://www.chictr.org.cn/showproj.aspx?proj=22674
Identification and Validation of Aurora Kinase A (AURKA) Involved in the Progression and Imatinib Resistance of Advanced Gastrointestinal Stromal Tumors
Authors: Cheng Xiaobin , Wang Jinhai , Lu Sen , Fan Weina , Wang Weilin 
Published: September 2020

Abstract
Background: Gastrointestinal stromal tumor (GIST) is a common tumor originating from mesenchyme in the alimentary system. GISTs exhibit unique malignant behavior compared to typical carcinomas. Here, we explored genes that drive the progression and imatinib resistance of GISTs by bioinformatic tools and experiments. Methods: We analyzed gene expression profiles of GISTs and identified a key gene, AURKA, which regulated the progression of GISTs. We further determined the clinical significance of AURKA by immunohistochemical (IHC) staining assays and survival analysis. A series of in vitro experiments were performed to investigate in detail the effect of AURKA on the aggressiveness and imatinib resistance of GIST cells.Results: Our results showed that AURKA was higher in advanced GIST tissues than in non-advanced GIST tissues. AURKA mainly involved in cell cycle related biological processes as revealed by GSEA. AURKA was positively related with GIST progression and could be an independent prognostic marker of GISTs. It was also found to exhibit consistent expression patterns in several human malignancies. Additionally, AURKA influenced gene mutations associated with imatinib resistance. Overexpression of AURKA in GIST cells promoted cell proliferation and apoptosis, even after administration of imatinib. But imatinib significantly inhibited the effects of AURKA overexpression on the migration of GIST cells. Conclusions: Bioinformatics analyses and subsequent experiments identified AURKA as a key gene in GIST progression. AURKA showed a contribution to imatinib resistance and could be a candidate therapeutic target for GISTs.
Tidal Disruption of Magnetars as the Sources of Fast Radio Burst
Authors: Pothula Kushaal Kumar 
Published: September 2020

Abstract
Fast Radio Bursts (FRBs) are mysterious millisecond duration radio transients, and some FRBs repeat. FRBs are highly polarized, indicating that the source is within a strong magnetic field. I hypothesize their origin as Tidal Disruption Events (TDEs) of magnetars by black holes. The TDE releases energy stored in the magnetic field of the magnetar, producing an FRB. Occasionally the magnetar is disrupted into multiple debris chunks, and as individual chunks get consumed, multiple FRBs are produced, forming a repeating FRB. Another process of formation of repeating FRBs is starquakes on magnetars because of tidal forces from black holes. Due to the strong magnetic field of the accretion disk, the FRB is produced in jets. Sometimes the magnetar debris surrounding the magnetic field gets accelerated, producing Ultra-high energy cosmic rays, whose source remains unknown. The FRB signal produced gets polarized by the magnetosphere of the accretion disk and intergalactic magnetic fields.
Dynamic Alterations of Histone H3 Phospho-acetylation Correlate With Radio Sensitivity of Mitotic Cells During DNA&nbsp;Damage
Authors: Sharda Asmita , Verma Tripti , Gadewal Nikhil , Gupta Sanjay 
Published: September 2020

Abstract
Background - Histone Post Translational Modifications (PTMs) change in a cell cycle dependent manner and also orchestrate the DNA repair process for radiation induced DNA damage. Mitosis is the most radiosensitive phase of the cell cycle but the epigenetic events that regulate its radiosensitivity remain elusive.Results - This study explored the dynamics between histone marks H3S10/S28ph, H3K9ac and γH2AX during mitotic DNA damage response. The presence of a mononucleosome level association between γH2AX and H3S10ph was observed only during mitosis. This association was abrogated upon cell cycle progression and chromatin de-condensation, concomitant with chromatin recruitment of DNA repair proteins Ku70 and Rad51. Moreover, the levels of H3S10/28ph remained unchanged upon DNA damage during mitosis, but decreased in a cell cycle dependent manner upon mitotic exit. However, the population that arose after mitotic progression of damaged cells comprised of binucleated tetraploid cells. This population was epigenetically distinct from interphase cells, characterized by reduced H3S10/S28ph, increased H3K9ac and more open chromatin configuration. These epigenetic features correlated with decreased survival potential of this population. The low levels of H3S10/28ph were attributed to decreased protein translation and chromatin recruitment of histone kinase Mitogen and Stress-activated Kinase 1 (MSK1) along with persistent levels of Protein phosphatase1 catalytic subunit α (PP1α). Conclusions – This study suggests that a unique epigenetic landscape attained during and after mitotic DNA damage collectively contributed to mitotic radiosensitivity. The findings of this study have potential clinical significance in terms of tackling resistance against anti-mitotic chemotherapeutic agents.