bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to maintain and transport equine adipose tissue for isolating mesenchymal stem cells?
Authors: Rezaei Faezeh , Khasaf Samira , Ghasemi Samaneh , Parham Abbas , Mirshokraei Pezhman 
Published: July 2022

Abstract
Background
Adipose tissue (AT) is one of the most important mesenchymal stem cell (MSC) sources because of its high quantities, availability and ease of collection. After being collected samples, they should be transported to a laboratory for stem cell (SC) isolation, culture and expansion for future clinical application. Usually, laboratories are distant from animal husbandry centers; therefore, it is necessary to provide suitable conditions for adipose tissue transportation, such that adipose-derived MSCs are minimally affected. In the current study, the impact of tissue maintenance under different conditions on MSCs derived from these tissues was evaluated. We aimed at finding suitable and practical transportation methods in which ASCs go through the slightest changes.

Results
In the current study, after being collected, equine AT was randomized into eight groups: four samples were maintained in stem cell culture media at 25 οC and 4 οC for 6 and 12 hrs. as transportation via SC media groups. Three samples were frozen at three different temperatures (− 20, − 75 and − 196 οC) as cryopreserved groups; these samples were defrosted 1 week after cryopreservation. Fresh and unfrozen AT was evaluated as a control group. The tissue samples were then initiated into enzymatic digestion, isolation and the culturing of SCs. Cells at passage three were used to evaluate the ability to form colonies, proliferation rate, plotting of the cell growth curve, and viability rate. All experiments were performed in triplicate. Stem cell isolation was successful in all groups, although purification of SCs from the first series of cryopreservation at − 196 οC and two series of − 20 οC was unsuccessful. There was no significant difference between the surface area of colonies in all groups except for − 20 οC. The growth rate of transportation via stem cell media at 25 οC for 6 hrs. was similar to that of the control group. MTT analysis revealed a significant difference between 25 οC 12 hrs. Group and other experimental groups except for control, 4 οC 12 hrs. and − 196 οC group.

Conclusion
Data have shown freezing at − 75 οC, transportation via stem cell media at 4 οC for 12 hrs. and 25 οC for 6 hrs. are acceptable tissue preservation and transportation methods due to minor effects on MSCs features.
Proteomic analysis of cardiometabolic biomarkers and predictive modeling of severe outcomes in patients hospitalized with COVID-19
Authors: Schroeder Philip H. , Brenner Laura N. , Kaur Varinderpal , Cromer Sara J. , Armstrong Katrina , LaRocque Regina C. , Ryan Edward T. , Meigs James B. , Florez Jose C. , Charles Richelle C. , Mercader Josep M. , Leong Aaron 
Published: July 2022

AbstractBackgroundThe high heterogeneity in the symptoms and severity of COVID-19 makes it challenging to identify high-risk patients early in the disease. Cardiometabolic comorbidities have shown strong associations with COVID-19 severity in epidemiologic studies. Cardiometabolic protein biomarkers, therefore, may provide predictive insight regarding which patients are most susceptible to severe illness from COVID-19.MethodsIn plasma samples collected from 343 patients hospitalized with COVID-19 during the first wave of the pandemic, we measured 92 circulating protein biomarkers previously implicated in cardiometabolic disease. We performed proteomic analysis and developed predictive models for severe outcomes. We then used these models to predict the outcomes of out-of-sample patients hospitalized with COVID-19 later in the surge (N = 194).ResultsWe identified a set of seven protein biomarkers predictive of admission to the intensive care unit and/or death (ICU/death) within 28 days of presentation to care. Two of the biomarkers, ADAMTS13 and VEGFD, were associated with a lower risk of ICU/death. The remaining biomarkers, ACE2, IL-1RA, IL6, KIM1, and CTSL1, were associated with higher risk. When used to predict the outcomes of the future, out-of-sample patients, the predictive models built with these protein biomarkers outperformed all models built from standard clinical data, including known COVID-19 risk factors.ConclusionsThese findings suggest that proteomic profiling can inform the early clinical impression of a patient’s likelihood of developing severe COVID-19 outcomes and, ultimately, accelerate the recognition and treatment of high-risk patients.
The autophagy inducer trehalose stimulates macropinocytosis in NF1-deficient glioblastoma cells
Authors: Del Bello Barbara , Gamberucci Alessandra , Marcolongo Paola , Maellaro Emilia 
Published: July 2022

Abstract
Background
Glioblastoma is a highly aggressive brain tumor. A big effort is required to find novel molecules which can cross the blood–brain barrier and efficiently kill these tumor cells. In this perspective, trehalose (α-glucopyranosyl‐[1→1]‐α‐d‐glucopyranoside), found in various dietary sources and used as a safe nutrient supplement, attracted our attention for its pleiotropic effects against tumor cells.

Methods
Human glioblastoma cell lines U373-MG and T98G were exposed to trehalose and analyzed at different time points. Cell proliferation was evaluated at medium term, and clonogenic capacity and cell morphology were evaluated at long term. Western blot was used to evaluate biochemical markers of autophagy (also measured in cells co-treated with EIPA or chloroquine), and mTOR, AMPK and ERK 1/2 signalling. Macropinocytosis was evaluated morphologically by bright-field microscopy; in cells loaded with the fluorescein-conjugated fluid-phase tracer dextran, macropinocytic vacuoles were also visualized by fluorescence microscopy, and the extent of macropinocytosis was quantified by flow cytometry.

Results
The long-term effect of trehalose on U373-MG and T98G cell lines was impressive, as indicated by a dramatic reduction in clonogenic efficiency. Mechanistically, trehalose proved to be an efficient autophagy inducer in macropinocytosis-deficient T98G cells and an efficient inducer of macropinocytosis and eventual cell death by methuosis in U373-MG glioblastoma cells, proved to be poorly responsive to induction of autophagy. These two processes appeared to act in a mutually exclusive manner; indeed, co-treatment of U373-MG cells with the macropinocytosis inhibitor, EIPA, significantly increased the autophagic response. mTOR activation and AMPK inhibition occurred in a similar way in the two trehalose-treated cell lines. Interestingly, ERK 1/2 was activated only in macropinocytosis-proficient U373-MG cells harbouring loss-of-function mutations in the negative RAS regulator, NF1, suggesting a key role of RAS signalling.

Conclusions
Our results indicate that trehalose is worthy of further study as a candidate molecule for glioblastoma therapy, due to its capacity to induce a sustained autophagic response, ultimately leading to loss of clonogenic potential, and more interestingly, to force macropinocytosis, eventually leading to cell death by methuosis, particularly in tumor cells with RAS hyperactivity. As a further anticancer strategy, stimulation of macropinocytosis may be exploited to increase intracellular delivery of anticancer drugs.
Functional interplay between long non-coding RNAs and Breast CSCs
Authors: Hussen Bashdar Mahmud , Kheder Ramiar Kamal , Abdullah Sara Tharwat , Hidayat Hazha Jamal , Rahman Heshu Sulaiman , Salihi Abbas , Taheri Mohammad , Ghafouri-Fard Soudeh 
Published: July 2022

AbstractBreast cancer (BC) represents aggressive cancer affecting most women’s lives globally. Metastasis and recurrence are the two most common factors in a breast cancer patient's poor prognosis. Cancer stem cells (CSCs) are tumor cells that are able to self-renew and differentiate, which is a significant factor in metastasis and recurrence of cancer. Long non-coding RNAs (lncRNAs) describe a group of RNAs that are longer than 200 nucleotides and do not have the ability to code for proteins. Some of these lncRNAs can be mainly produced in various tissues and tumor forms. In the development and spread of malignancies, lncRNAs have a significant role in influencing multiple signaling pathways positively or negatively, making them promise useful diagnostic and prognostic markers in treating the disease and guiding clinical therapy. However, it is not well known how the interaction of lncRNAs with CSCs will affect cancer development and progression.Here, in this review, we attempt to summarize recent findings that focus on lncRNAs affect cancer stem cell self-renewal and differentiation in breast cancer development and progression, as well as the strategies and challenges for overcoming lncRNA's therapeutic resistance.
Modified thromboelastometric tests provide improved sensitivity and specificity to direct oral anticoagulants compared to standard thromboelastometric tests in-vitro
Authors: Groene Philipp , Butte Jennifer , Thaler Sarah , Görlinger Klaus , Schäfer Simon T. 
Published: July 2022

Abstract
Background
The detection of direct oral anticoagulants (DOACs) is still challenging but important in emergency patients. We recently demonstrated that modified thromboelastometry can detect rivaroxaban and dabigatran. Data on the detection rates of modified compared to standard thromboelastometric tests of apixaban and edoxaban, are missing. The aim of this in-vitro dose-effect-study was to add data on these DOACs and to evaluate thromboelastometric tests in-vitro using data of both studies.

Methods
The study was approved by the Ludwig-Maximilians-University ethics committee (No 17-525-2). Written informed consent was obtained from all individuals. Blood samples of healthy volunteers and samples of 10 volunteers for each DOAC were used. Blood samples were spiked with six different concentrations of edoxaban and apixaban (0ng/ml; 31.25ng/ml; 62.5ng/ml; 125ng/ml; 250 ng/ml; 500ng/ml). Modified tests (low-tissue-factor test TFTEM and ecarin-based test ECATEM) as well as standard tests (e.g. FIBTEM) analyzing extrinsic pathway of coagulation were used. Receiver operating characteristics analyzes were performed as well as regression analyzes.

Results
TFTEM CT correlated well with anti-Xa levels of apixaban and edoxaban (apixaban: r2 = 0.8064 p < 0.0001; edoxaban: r2 = 0.8603; p < 0.0001). The detection of direct FXa inhibitors (> 30 ng/mL) was successful with FIBTEM CT with a sensitivity and specificity of 81% and 90%, respectively. As expected, ECATEM CT was not prolonged by direct FXa-inhibitors due to its specificity for direct thrombin inhibitors. Again, TFTEM CT provided the highest sensitivity and specificity for the detection of direct FXa inhibitors with 96% and 95%, respectively. ECATEM test showed 100% sensitivity and 100% specificity for the detection of dabigatran.

Conclusions
Our study presents modified thromboelastometric tests with improved detection of even low DOAC concentrations > 30 ng/mL, including apixaban in-vitro. The study thus complements the previously published data on dabigatran and rivaroxaban. Validation studies must confirm the results due to the explanatory design of this study.
Transplanted allogeneic cardiac progenitor cells secrete GDF-15 and stimulate an active immune remodeling process in the ischemic myocardium
Authors: Mishra Rachana , Saha Progyaparamita , Datla Srinivasa Raju , Mellacheruvu Pranav , Gunasekaran Muthukumar , Guru Sameer Ahmad , Fu Xuebin , Chen Ling , Bolli Roberto , Sharma Sudhish , Kaushal Sunjay 
Published: July 2022

Abstract
Background
Despite promising results in clinical studies, the mechanism for the beneficial effects of allogenic cell-based therapies remains unclear. Macrophages are not only critical mediators of inflammation but also critical players in cardiac remodeling. We hypothesized that transplanted allogenic rat cardiac progenitor cells (rCPCs) augment T-regulatory cells which ultimately promote proliferation of M2 like macrophages by an as-yet undefined mechanism.

Methods and results
To test this hypothesis, we used crossover rat strains for exploring the mechanism of myocardial repair by allogenic CPCs. Human CPCs (hCPCs) were isolated from adult patients undergoing coronary artery bypass grafting, and rat CPCs (rCPCs) were isolated from male Wistar-Kyoto (WKY) rat hearts. Allogenic rCPCs suppressed the proliferation of T-cells observed in mixed lymphocyte reactions in vitro. Transplanted syngeneic or allogeneic rCPCs significantly increased cardiac function in a rat myocardial infarct (MI) model, whereas xenogeneic CPCs did not. Allogeneic rCPCs stimulated immunomodulatory responses by specifically increasing T-regulatory cells and M2 polarization, while maintaining their cardiac recovery potential and safety profile.
Mechanistically, we confirmed the inactivation of NF-kB in Treg cells and increased M2 macrophages in the myocardium after MI by transplanted CPCs derived GDF15 and it’s uptake by CD48 receptor on immune cells.

Conclusion
Collectively, these findings strongly support the active immunomodulatory properties and robust therapeutic potential of allogenic CPCs in post-MI cardiac dysfunction.
Immunotherapy landscape analyses of necroptosis characteristics for breast cancer patients
Authors: Yu Honghao , Lv Wenchang , Tan Yufang , He Xiao , Wu Yiping , Wu Min , Zhang Qi 
Published: July 2022

AbstractNecroptosis plays a major role in breast cancer (BC) progression and metastasis. Besides, necroptosis also regulates inflammatory response and tumor microenvironment. Here, we aim to explore the predictive signature based on necroptosis-related genes (NRGs) for predicting the prognosis and response to therapies. Using Lasso multivariate cox analysis, we firstly established the NRG signature based on TCGA database. A total of 6 NRGs (FASLG, IPMK, FLT3, SLC39A7, HSP90AA1, and LEF1), which were associated with the prognosis of BC patients, were selected to establish our signature. Next, CIBERSORT algorithm was utilized to evaluate immune cell infiltration levels. We compare the response to immunotherapy using IMvigor 210 database, and also compared immune indicators in two risk groups via multiple methods. The biological function of IPMK was explored via in vitro verification. Finally, our results indicated that the signature was an independent prognostic indicator for BC patients with better efficiency than other reported signatures. The immune cell infiltration levels were higher, and the response to immunotherapy and chemotherapy was better in the low-risk groups. Besides, other immunotherapy-related factors, including TMB, TIDE, and expression of immune checkpoints were also increased in the low-risk group. Clinical sample validation showed that CD206 and IPMK in clinical samples were both up-regulated in the high-risk group. In vitro assay showed that IPMK promoted BC cell proliferation and migration, and also enhanced macrophage infiltration and M2 polarization. In summary, we successfully established the NRG signature, which could be used to evaluate BC prognosis and identify patients who will benefit from immunotherapy.
Kagami–Ogata syndrome: a case report
Authors: Suriapperuma Tharindi , Randeny Shobhavi , Mettananda Sachith 
Published: July 2022

Abstract
Background
Kagami–Ogata syndrome is a rare genetic imprinting disorder involving the 14q32.2 genomic location of chromosome 14. The estimated incidence is less than 1 per 1 million. Here we report a male neonate with Kagami–Ogata syndrome presenting with severe respiratory distress requiring mechanical ventilation since birth.

Case presentation
A Sri Lankan male neonate born at term via caesarean section to a mother with type 1 diabetes mellitus and hypothyroidism developed respiratory distress immediately after birth. On examination, the baby had facial dysmorphism with a hirsute forehead, full cheeks, flat nasal bridge, elongated protruding philtrum, and micrognathia. His chest was small and bell shaped, and he had severe intercostal and subcostal recessions. His abdominal wall was lax and thin, with evidence of divarication of the recti. Bowel peristalsis was easily visible through the abdominal wall. The chest x-ray showed narrowing of the rib cage with crowding of the ribs in a “coat-hanger” appearance. The coat-hanger angle was 32°, and the mid-to-widest thoracic diameter was 68%. On the basis of facial dysmorphism, chest and anterior abdominal wall abnormalities, coat-hanger appearance of the rib cage, increased coat-hanger angle, and reduced mid-to-widest thoracic diameter, a clinical diagnosis of Kagami–Ogata syndrome was made. Owing to severe respiratory distress, the baby required intubation and ventilation immediately after birth. He was ventilator-dependent for 3 weeks; however, he was successfully weaned off the ventilator on day 22 after several failed extubation attempts. At 3-month follow-up, he had generalized hypotonia and mild global developmental delay. His developmental age corresponded to 2 months.

Conclusions
We report a patient with Kagami–Ogata syndrome presenting with respiratory distress immediately after birth. This case report highlights the importance of being aware of this rare condition, which could present as severe respiratory distress in term and preterm newborns. A positive diagnosis could avoid unnecessary treatment and aid in accurate prognostication.
The university students’ self-regulated effort, flexibility and satisfaction in distance education
Authors: Turan Zeynep , Kucuk Sevda , Cilligol Karabey Sinem 
Published: July 2022

AbstractDistance education offers flexible learning opportunities in terms of time, place and learning speed to teachers and students through internet technologies. However, the learning opportunities provided in distance education environments require students to act more autonomously and take more responsibility for regulating their learning processes to achieve their learning goals. For this reason, it is crucial to reveal the relationships between flexibility, self-regulated effort and satisfaction factors to provide efficient and effective learning environments in distance education. Accordingly, within the scope of this study, it is aimed to investigate university students’ perceptions of flexibility, self-regulated effort and satisfaction with the distance education process, and their views on distance education. Survey research was used as the research method in the study. The study sample consisted of 1760 university students studying at 28 different universities. Data were analysed using t-test, ANOVA, and regression methods. As a result of the study, male students were more satisfied with distance education than female students, and education faculty students had the highest level of satisfaction. In addition, self-regulated effort and flexibility variables were significant factors affecting students’ satisfaction towards distance education. Furthermore, the advantages and problems of distance education and suggestions for future distance learning environments were presented in the light of students views. Finally, the study’s implications and various recommendations for practitioners and researchers were discussed in detail.
Polymorphism of the IL-10 gene in Azeri population of Iran
Authors: Asgharzadeh Mohammad , Taghinejad Zahra , Asgharzadeh Vahid , Mehramouz Bahareh , Rashedi Jalil , Mahdavipoor Behroz , Pourostadi Mahya , Vegari Ali , Vishkaei Ali Safarzad , Taghizadeh Sepehr , Kafil Hossein Samadi 
Published: July 2022

Abstract
Background
Interleukin (IL)-10 is one of the key interleukins in the immune system. It plays an anti-inflammatory role in body by inhibition of the synthesis of pro-inflammatory cytokines and reducing the expression of major histocompatibility complex II molecules. The single-nucleotide polymorphism in the gene of this interleukin affects its expression level. Thus, this study was conducted to investigate the IL-10 gene polymorphism at position -1082A/G in Azeri population of Iran.

Methods
Blood samples were taken from 254 healthy and non-relevant Iranian Azeri individuals. After DNA extraction, the frequency of IL-10 genotypes and alleles at -1082A/G position was determined by allele specific-PCR method. Then, q-square test was used to compare allele frequencies and IL-10 genotypes with other populations, and p value of < 0.05 was considered significant.

Results
In Iranian Azeri population, the frequency percentage of AA, AG and GG genotypes in IL-10 gene at the -1082A/G location was 37.4, 43.3 and 19.3%, respectively. The frequency percentage of A and G alleles also were 59.1 and 40.9%, respectively. Based on statistical analysis, frequency of IL-10 genotypes in the current study was very similar to the population of Saudi Arabia, but it had a significant difference with East Asia and Ireland populations.

Conclusion
Results of the present study indicate similar polymorphism of IL-10 genotype with neighbor ethnicities in Middle East country. Based on patients backgrounds mentioned in their questioners, this polymorphism was associated with the susceptibility to asthma and Alzheimer in this population which are common in the region.
The therapeutic role of repetitive transcranial magnetic stimulation in children with attention deficit/hyperactivity disorder in Egypt a randomized sham controlled clinical trial
Authors: Nagy Nahla Al Sayed , Amin Ghada Refaat , Khalil Sherine Ahmed , Mahmoud Dalia Abdel Moneim , Elkholy Hussien , Shohdy Mostafa 
Published: July 2022

Abstract
Background
Repetitive transcranial magnetic stimulation showed some evidence for improving symptoms of ADHD along with its relative safety, thus could serve as a treatment strategy or an alternative to stimulant medication. Accordingly, 60 children with ADHD were assessed, and 30 participants were allocated to the rTMS group and received 15 sessions of rTMS over the right dorsolateral prefrontal cortex combined with Atomoxetine 1.2 mg/kg/day. The other 30 participants were allocated to the Sham group and received 15 sessions of sham rTMS and atomoxetine 1.2 mg/kg/day. Clinical assessments of ADHD symptoms and severity were done and compared at 3 points, before treatment, after receiving 15 sessions of rTMS and follow-up 1 month after the last rTMS session, using Conner’s Parent Rating Scale-Revised-Long form, Children’s Global Assessment Scale, and Clinical Global Impression.

Results
The two groups show significant improvement in the T scores of all CPRS subscales, CGI and CGAS. However, the rTMS group had a significantly more improvement than the sham group in inattention, total ADHD severity, CGI, and CGAS after rTMS and continued to the follow-up after 1 month.

Conclusions
rTMS is an efficacious intervention for treating ADHD, and combined rTMS and atomoxetine is superior to atomoxetine alone in improving attention deficit symptoms and total ADHD symptoms severity.

Trial registration
PACTR, PACTR202110558451583. Registered 25 June 2021. Approved 29 October 2021- Retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=15968.