bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human bone marrow-derived stromal cell behavior when injected directly into the bone marrow of NOD-scid-gamma mice pre-conditioned with sub-lethal irradiation
Authors: Nowlan Bianca , Futrega Kathryn , Williams Elizabeth Deborah , Doran Michael Robert 
Published: April 2021

AbstractBackgroundDirect bone marrow injection of cells into murine marrow cavities is used in a range of cell characterization assays and to develop disease models. While human bone marrow-derived stromal cells (hBMSC, also known as mesenchymal stem cells (MSC)) are frequently described in therapeutic applications, or disease modeling, their behavior following direct injection into murine bone marrow is poorly characterized. Herein, we characterized hBMSC engraftment and persistence within the bone marrow of NOD-scidinterleukin (IL)-2γ−/−(NSG) mice with or without prior 2 Gy total-body γ-irradiation of recipient mice.MethodsOne day after conditioning NSG mice with sublethal irradiation, 5 × 105luciferase (Luc) and green fluorescent protein (GFP)-expressing hBMSC (hBMSC-Luc/GFP) were injected into the right femurs of animals. hBMSC-Luc/GFP were tracked in live animals using IVIS imaging, and histology was used to further characterize hBMSC location and behavior in tissues.ResultshBMSC-Luc/GFP number within injected marrow cavities declined rapidly over 4 weeks, but prior irradiation of animals delayed this decline. At 4 weeks, hBMSC-Luc/GFP colonized injected marrow cavities and distal marrow cavities at rates of 2.5 ± 2.2% and 1.7 ± 1.9% of total marrow nucleated cells, respectively in both irradiated and non-irradiated mice. In distal marrow cavities, hBMSC were not uniformly distributed and appeared to be co-localized in clusters, with the majority found in the endosteal region.ConclusionsWhile significant numbers of hBMSC-Luc/GFP could be deposited into the mouse bone marrow via direct bone marrow injection, IVIS imaging indicated that the number of hBMSC-Luc/GFP in that bone marrow cavity declined with time. Irradiation of mice prior to transplant only delayed the rate of hBMSC-Luc/GFP population decline in injected femurs. Clusters of hBMSC-Luc/GFP were observed in the histology of distal marrow cavities, suggesting that some transplanted cells actively homed to distal marrow cavities. Individual cell clusters may have arisen from discrete clones that homed to the marrow, and then underwent modest proliferation. The transient high-density population of hBMSC within the injected femur, or the longer-term low-density population of hBMSC in distal marrow cavities, offers useful models for studying disease or regenerative processes. Experimental designs should consider how relative hBMSC distribution and local hBMSC densities evolve over time.
Farnesoid X receptor via Notch1 directs asymmetric cell division of Sox9+ cells to prevent the development of liver cancer in a mouse model
Authors: Chen Mi , Lu Chenxia , Lu Hanwen , Zhang Junyi , Qin Dan , Liu Shenghui , Li Xiaodong , Zhang Lisheng 
Published: April 2021

Abstract
Background
Asymmetrical cell division (ACD) maintains the proper number of stem cells to ensure self-renewal. The rate of symmetric division increases as more cancer stem cells (CSCs) become malignant; however, the signaling pathway network involved in CSC division remains elusive. FXR (Farnesoid X receptor), a ligand-activated transcription factor, has several anti-tumor effects and has been shown to target CSCs. Here, we aimed at evaluating the role of FXR in the regulation of the cell division of CSCs.

Methods
The FXR target gene and downstream molecular mechanisms were confirmed by qRT-PCR, Western blot, luciferase reporter assay, EMAS, Chip, and IF analyses. Pulse-chase BrdU labeling and paired-cell experiments were used to detect the cell division of liver CSCs. Gain- and loss-of-function experiments in Huh7 cells and mouse models were performed to support findings and elucidate the function and underlying mechanisms of FXR-Notch1 in liver CSC division.

Results
We demonstrated that activation of Notch1 was significantly elevated in the livers of hepatocellular carcinoma (HCC) in Farnesoid X receptor-knockout (FXR-KO) mice and that FXR expression negatively correlated with Notch1 level during chronic liver injury. Activation of FXR induced the asymmetric divisions of Sox9+ liver CSCs and ameliorated liver injury. Mechanistically, FXR directs Sox9+ liver CSCs from symmetry to asymmetry via inhibition of Notch1 expression and activity. Deletion of FXR signaling or over-expression of Notch1 greatly increased Notch1 expression and activity along with ACD reduction. FXR inhibited Notch1 expression by directly binding to its promoter FXRE. FXR also positively regulated Numb expression, contributing to a feedback circuit, which decreased Notch1 activity and directed ACD.

Conclusion
Our findings suggest that FXR represses Notch1 expression and directs ACD of Sox9+ cells to prevent the development of liver cancer.
Angiogenesis imaging study using interim [18F] RGD-K5 PET/CT in patients with lymphoma undergoing chemotherapy: preliminary evidence
Authors: Tonnelet David , Bohn M. D. Pierre , Becker Stephanie , Decazes Pierre , Camus Vincent , Thureau Sebastien , Tilly Hervé , Jardin Fabrice , Vera Pierre 
Published: April 2021

Abstract
Background
Our aim was to measure the impact of two cycles of standard chemotherapy on tumoural neoangiogenesis by [18F] fluorine arginine-glycine-aspartic (RGD-K5) positron emission tomography–computed tomography (PET) on patients presenting with lymphoma. Nineteen patients at Rouen’s Henri Becquerel Cancer Centre were prospectively included. Fluorodeoxyglucose (FDG) and RGD-K5 PET were performed before (C0) and after (C2) two cycles of chemotherapy. End-of-treatment FDG PET was performed for final evaluation. Maximum standardised uptake value (SUVmax), SUVmean, Metabolic Tumour Volume (MTV) and Angiogenic Tumour Volume (ATV) were measured for all lesions. RGD SUVmax and SUVmean were also analysed in 13 normal organs at C0 and C2. The patient’s treatment response was considered using the Deauville score (DS) at the end of FDG PET treatment (DS 1–3 were considered responders, and 4 and 5 non-responders).

Results
Eighteen patients had both C0 FDG and RGD PET. Twelve patients had both C2 FDG and RGD, completed the treatment protocol and were included in end-of-treatment analysis. No statistical difference was found in RGD uptake of normal organs before and after chemotherapy for SUVmax and SUVmean. On C0 RGD, apart from classical Hodgkin lymphoma (cHL; n = 5) and grey zone lymphoma (GZL; n = 1), other lymphoma sub-types (n = 12) had low RGD uptake (p < 0.001). Regarding FDG, there was no significant difference for SUVmax, SUVmean and MTV at C0 and C2 between patients with cHL and non-Hodgkin lymphoma (NHL). At C2 RGD, non-responders had higher SUVmax and SUVmean compared to responders (p < 0.001). There was no significant difference in RGD ATV between responders and non-responders.

Conclusions
Our study showed significant higher initial RGD uptake in patients presenting with cHL and GZL compared to NHL. Non-responder also had higher post-chemotherapy RGD uptake compared to responders. Issues raised by RGD uptake, particularly in cHL, are yet to be explored and need to be confirmed in a larger population.
Effectiveness of community-based interventions for patients with schizophrenia spectrum disorders: a study protocol for a systematic review
Authors: Kim Soo-Yeon , Kim Ah. Rim 
Published: April 2021

Abstract
Background
Schizophrenia requires a community-based intervention approach combined with standard treatment to prevent relapses. A literature review is required to understand the effectiveness of community-based interventions and to enhance quality in countries where they have not been fully established. This is a protocol for a systematic review of the effectiveness of community-based interventions for patients with schizophrenia spectrum disorders.

Methods
We will search (from inception to January 2021) PubMed/MEDLINE, EMBASE, PsycINFO, CENTRAL, CINAHL, and Research Information Sharing Service/Korean databases. Randomized controlled trials on community-based interventions for patients with schizophrenia spectrum disorders will be eligible. The comparison groups will include patients with schizophrenia spectrum disorders who are only receiving the usual care and those who also receive community-based interventions. The schizophrenia spectrum disorders referred to in this study are defined according to the DSM-5: delusional disorders, schizophrenic disorders, and schizoaffective disorder will be included. Relapse/re-hospitalization rates (primary outcome) and quality of life (secondary outcome) will be identified for each group. Two reviewers will independently screen study titles, abstract data, and full-text articles and perform the data extraction process. Potential conflicts will be resolved through discussion. The study risk of bias will be appraised using the Cochrane Risk of Bias 2.0 tool. Results will be descriptively synthesized and will be structured according to patients’ characteristics, intervention type and exposure, and outcome type. If feasible and appropriate, outcome data will be used to perform random effects meta-analyses. Discrete variables will be calculated via odds ratio, and continuous variables will be calculated via standardized mean difference using RevMan 5.3 software.

Discussion
We will provide a summary of the available evidence on the effectiveness of community-based interventions and specific guidelines to improve their outcomes.

Systematic review registration
PROSPERO (CRD42019145660).
Targeted exome sequencing identifies mutational landscape in a cohort of 1500 Chinese patients with non-small cell lung carcinoma (NSCLC)
Authors: Zhou Ya-jun , Zheng Wei , Zeng Qing-hua , Ye Yang , Wang Ce , Fang Cheng , Liu Chao-jun , Niu Li , Wu Li-ming 
Published: April 2021

Abstract
Background
Non-small cell lung carcinoma (NSCLC) is one of the most common human cancers, comprising approximately 80–85% of all lung carcinomas. An estimated incidence of NSCLC is approximately 2 million new cases per year worldwide.

Results
In recent decade, the treatment of NSCLC has made breakthrough progress owing to a large number of targeted therapies which were approved for clinical use. Epidemiology, genetic susceptibility, and molecular profiles in patients are likely to play an important factor in response rates and survival benefits to these targeted treatments and thus warrant further investigation on ethnic differences in NSCLC. In this study, a total number of 1500 Chinese patient samples,1000 formalin fixed paraffin-embedded (FFPE) and 500 blood samples, from patients with NSCLC were analyzed by targeted sequencing to explore mutational landscape in ethnic groups associated with China.

Conclusions
Overall, the data presented here provide a comprehensive analysis of NSCLC mutational landscape in Chinese patients and findings are discussed in the context of similar studies on different ethnic groups.
Learner-content interaction in e-learning- the moderating role of perceived harm of COVID-19 in assessing the satisfaction of learners
Authors: Kumar Pardeep , Saxena Charu , Baber Hasnan 
Published: April 2021

AbstractEnvisioning learning sans interaction is absurd. Interaction plays a pivotal role in the efficacy and effectiveness of the present-day blended learning systems. Learner-content interaction contributes predominately towards the successful realization of the expected learning outcomes. In order to satisfy the learners and to impart them quality knowledge and education, e-learning content comprising of excellent learning and website content is of paramount importance. In the present COVID-19 outbreak challenging times the significance of e-learning system development and its application is much more pronounced. To gauge this, the study aims to examine the relationship between learner-content and the e-learning quality to determine the impact of e-learning quality on learners’ satisfaction under the moderating effect of perceived harm due to COVID-19. A structured questionnaire was used to gather data from 435 graduate and undergraduate management students (International and national) in Indian Universities. Findings indicate statistically significant relationships between the e-learning content and e-learning quality and; e-learning quality and the students’ satisfaction. The perceived harm has an insignificant moderating effect on students’ satisfaction. The results of the study further depict that the quality of e-learning has a significant positive relationship with the students’ satisfaction, and this relationship is not affected by the threat of being infected on the campus during the pandemic of COVID-19. To achieve the learners’ satisfaction, the institutions should strive for rendering the e-learning content of supreme quality. The mediating role of e-learning quality between content and students’ satisfaction is also established to be a significant one.
Carbohydrate-binding modules targeting branched polysaccharides: overcoming side-chain recalcitrance in a non-catalytic approach
Authors: Liu Jiawen , Sun Di , Zhu Jingrong , Liu Cong , Liu Weijie 
Published: April 2021

AbstractExtensive decoration of backbones is a major factor resulting in resistance of enzymatic conversion in hemicellulose and other branched polysaccharides. Employing debranching enzymes is the main strategy to overcome this kind of recalcitrance at present. A carbohydrate-binding module (CBM) is a contiguous amino acid sequence that can promote the binding of enzymes to various carbohydrates, thereby facilitating enzymatic hydrolysis. According to previous studies, CBMs can be classified into four types based on their preference in ligand type, where Type III and IV CBMs prefer to branched polysaccharides than the linear and thus are able to specifically enhance the hydrolysis of substrates containing side chains. With a role in dominating the hydrolysis of branched substrates, Type III and IV CBMs could represent a non-catalytic approach in overcoming side-chain recalcitrance.
Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy
Authors:   Chinese People’s Liberation Army Professional Committee of Critical Care Medicine and Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association, Song Jing-Chun , Yang Li-Kun , Zhao Wei , Zhu Feng , Wang Gang , Chen Yao-Peng , Li Wei-Qin 
Published: April 2021

AbstractTrauma-induced coagulopathy (TIC) is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage. Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC, while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2–85.1% of trauma patients, in whom it can increase the risk of thrombotic events and mortality by 2- to 4-fold. Therefore, the Chinese People’s Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.
A case of pericarditis caused by Mycoplasma hyorhinis in a weaned piglet
Authors: Ustulin Martina , Rossi Erica , Vio Denis 
Published: April 2021

Abstract
Background
Mycoplasma hyorhinis (M. hyorhinis) is a bacterium commonly found in the upper respiratory tract of healthy pigs and an agent of polyserositis and polyarthritis. Moreover, it can carry antibiotic resistance genes (Wu et al, Vet. Microbiol. 76: 25–30, 2000). Economic losses caused by M. hyorhinis can be reduced by antibiotic therapy, however, isolation and antimicrobic susceptibility profile are rarely performed.

Case presentation
The present report describes a case of pericarditis caused by M. hyorhinis in a weaned piglet with respiratory symptoms and reduced growth performance.
At post mortem examination, the main macroscopic finding was a severe fibrinous pericarditis and M. hyorhins was the only agent isolated from the pericardial fluid.
In this strain, Minimum Inhibitory Concentration (MIC) determination revealed resistance to various antimicrobial molecules such as erythromycin, tylosin and tilmicosin.

Conclusion
This paper highlights the importance of including M. hyorhins in the differential diagnosis of polyserositis in swine. Moreover, due the possible presence of multidrug resistance, the determination of antimicrobial susceptibility pattern should be performed on a regular basis.
In-vitro cytotoxic and anti-Vibrio cholerae activities of alcoholic extracts of Desmodium triflorum (L.) whole plant and Terminalia citrina (Roxb.) fruits
Authors: Karim Rubaba , Begum Mst Marium , Jui Yeasmin , Islam Tanjina , Billah Masum , Arafat Yeasir , Karim Mehnaz , Khan Ashfia Fatima , Rahman Md. Sohanur 
Published: April 2021

AbstractBackgroundThe majority of epidemicVibrio choleraestrains have become resistant to multiple antimicrobial agents for many reasons, including mutations, horizontal gene transfers, etc. Therefore, secondary means of treatment are needed to overcome this impediment in combating cholera.Desmodium triflorum (L.)andTerminalia citrina (Roxb.)are extensively used in traditional medicine. Therefore, the present study aims to evaluate the antibacterial activity of methanolic and ethanolic extracts ofDesmodium triflorum (L.)whole plant andTerminalia citrina (Roxb.)fruits againstV. choleraeisolates.MethodsInitially, different extracts of both plant materials were subjected to qualitative phytochemical screening. Anti-V. choleraeactivities were assessed by performing MIC (minimum inhibitory concentration) test using disc diffusion method with different concentrations (1.25, 2.50, 8.00, 10.00, 12.50, 15.00 mg/ml) where standard discs of gentamycin and meropenem (10 μg/disc) were used. Further, Brine shrimp lethality bioassay was done to evaluate the extracts’ cytotoxic activities using different concentrations (800, 400, 200, 100, 50, 25, 12.5, 6.25 μg/ml) against vincristine sulphate.ResultsThe preliminary screening confirms the presence of convenient phytochemical constituents like flavonoids, alkaloids, glycosides, tannins, etc., and are liable for the emergence of the antibacterial activities in different strains. The minimum inhibitory concentrations of both methanolic and ethanolic extracts ofTerminalia citrina(fruits) andDesmodium triflorum (L.)(whole plant) were found to be 2.50 mg/ml and 5 mg/ml, respectively. Moreover, 100% mortality was observed only in ethanolic extract ofTerminalia citrinafruits at the highest concentration (800 μg/ml). In comparison, the rest of the test extracts showed less than 90% mortality at the highest concentration (800 μg/ml).ConclusionsBoth plants possess significant phytoconstituents and showed appreciable anti-V. choleraeactivities with mild toxicity. Hence,Desmodium triflorum (L.)whole plant andTerminalia citrina (Roxb.)fruits may be recommended as potential phytotherapy against cholera disease.
Phytotherapeutic potential of bi-herbal extract of cinnamon and turmeric: in vivo antidiabetic studies
Authors: Sivaranjani R. , Zachariah T. John , Leela N. K. 
Published: April 2021

Abstract
Background
The spices, cinnamon and turmeric have both culinary and pharmaceutical applications. Earlier studies proved their effect on reducing the symptoms associated with type 2 diabetes, a major lifestyle disease affecting millions world over. In our work, we prepared a bi-herbal extract of cinnamon and turmeric and studied its effect to alleviate the symptoms of type 2 diabetes in rat model.

Method
The phenolic rich bi-herbal extract was given to diabetes induced male wistar rats for 28 days at two different concentrations (50 and 150 mg/Kg bwt.). The changes in blood glucose level were monitored at weekly interval. At the end of the experiment, blood serum was collected and used for the estimation of lipid profile, Glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Total Protein (TP), Albumin, Urea and Creatinine levels.

Result
The serum analysis revealed that administration of the bi-herbal extract at 150 mg/Kg bwt. significantly reduced the blood glucose level (152.60 ± 40.2 mg/dL; p < 0.05) of diabetic animals as compared to diabetic control (335.40 ± 67.3 mg/dL; p < 0.05) at the end of 4 weeks. The treatment also resulted in the reduction of total cholesterol and LDL-cholestrol levels as compared to diabetic control animals. The histopathological examination of tissues showed the improvement in pancreatic architecture and restoration of tissue integrity in liver and kidney.

Conclusion
The study concludes that methanol extract of combination of cinnamon and turmeric has good hypoglycemic, hypolipidemic and organ protective potential in diabetic rats which could be developed into functional food supplementation for the prevention of type 2 diabetes.
Effects of BNO 1016 on ciliary transport velocity and cell culture surface liquid height of sinonasal epithelial cultures
Authors: Workman Alan D. , Maina Ivy W. , Triantafillou Vasiliki , Patel Neil N. , Tong Charles C. L. , Kuan Edward C. , Kennedy David W. , Palmer James N. , Adappa Nithin D. , Cohen Noam A. 
Published: April 2021

Abstract
Background
BNO 1016 is an ethanolic extract of a mixture of five herbs that has been sold in different formulations for decades in the European market and more recently, in the United States market as an over-the-counter treatment for rhinosinusitis. Previous studies indicated activation of chloride secretion and increase in ciliary beat frequency by BNO 1016 but the functional consequences on mucociliary transport velocity and airway surface liquid homeostasis are unknown. This study intends to examine the effects of BNO 1016 on these properties in vitro.

Results
Human sinonasal epithelial cells were grown at an air-liquid interface, with addition of BNO 1016 basolaterally in each experiment. Polystyrene fluorescent microspheres were added to the apical surface of the culture, and distance traveled across the surface of the culture over a fixed time period was measured using live imaging. BNO 1016 concentrations of 50 μg/ml and 500 μg/ml were tested. Basolateral application of compound resulted in a non-dose-dependent increase in culture surface liquid height compared to controls at 30 min, and this effect persisted through the one-hour duration of the experiment (p < 0.01). Basolateral application of BNO 1016 also resulted in a non-dose-dependent increase in microsphere transport velocity at 45 and 60 min following compound application (p < 0.01).

Conclusions
Basolateral application of BNO 1016 at a concentration mimicking post-ingestion serum levels appears to elicit increases in cell culture surface liquid height and mucociliary clearance, as assessed by microsphere transport velocity. These properties can potentially be leveraged for therapeutic efficacy in diseases affecting mucus production and mucociliary transport.