bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of potential blood biomarkers for early diagnosis of Alzheimer’s disease through RNA sequencing analysis
Authors: Shigemizu Daichi , Mori Taiki , Akiyama Shintaro , Higaki Sayuri , Watanabe Hiroshi , Sakurai Takashi , Niida Shumpei , Ozaki Kouichi 
Published: July 2020

Abstract
Background
With demographic shifts toward older populations, the number of people with dementia is steadily increasing. Alzheimer’s disease (AD) is the most common cause of dementia, and no curative treatment is available. The current best strategy is to delay disease progression and to practice early intervention to reduce the number of patients that ultimately develop AD. Therefore, promising novel biomarkers for early diagnosis are urgently required.

Methods
To identify blood-based biomarkers for early diagnosis of AD, we performed RNA sequencing (RNA-seq) analysis of 610 blood samples, representing 271 patients with AD, 91 cognitively normal (CN) adults, and 248 subjects with mild cognitive impairment (MCI). We first estimated cell-type proportions among AD, MCI, and CN samples from the bulk RNA-seq data using CIBERSORT and then examined the differentially expressed genes (DEGs) between AD and CN samples. To gain further insight into the biological functions of the DEGs, we performed gene set enrichment analysis (GSEA) and network-based meta-analysis.

Results
In the cell-type distribution analysis, we found a significant association between the proportion of neutrophils and AD prognosis at a false discovery rate (FDR) < 0.05. Furthermore, a similar trend emerged in the results of routine blood tests from a large number of samples (n = 3,099: AD, 1,605; MCI, 994; CN, 500). In addition, GSEA and network-based meta-analysis based on DEGs between AD and CN samples revealed functional modules and important hub genes associated with the pathogenesis of AD. The risk prediction model constructed by using the proportion of neutrophils and the most important hub genes (EEF2 and RPL7) achieved a high AUC of 0.878 in a validation cohort; when further applied to a prospective cohort, the model achieved a high accuracy of 0.727.

Conclusions
Our model was demonstrated to be effective in prospective AD risk prediction. These findings indicate the discovery of potential biomarkers for early diagnosis of AD, and their further improvement may lead to future practical clinical use.
Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration
Authors: Asgari Negin , Bagheri Fatemeh , Eslaminejad Mohamadreza Baghaban , Ghanian Mohammad Hossein , Sayahpour Forogh Azam , Ghafari Amir Mohammad 
Published: July 2020

Abstract
Background
Regeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregates have been developed. Multicellular aggregates of mesenchymal stem cells (MSCs) can be used as microscale building blocks of cartilage due to their potential for cell-cell contact, cell proliferation, and differentiation.

Methods
Chondrogenic microtissues were developed through incorporation of kartogenin-releasing poly (lactic-co-glycolic acid) (PLGA) microparticles (KGN-MP) within the MSC aggregates. The chondrogenic potential of KGN-MP treated MSC aggregates was proven in vitro by studying the chondrogenic markers at the RNA level and histological analysis. In order to address the inflammatory responses at the defect site, the microtissues were delivered in vivo via an injectable, anti-inflammatory hydrogel that contained gelatin methacryloyl (GelMA) loaded with curcumin (Cur).

Results
The KGN-MPs were fabricated to support MSCs during cartilage differentiation. According to real-time RT-PCR analysis, the presence of KGN in the aggregates led to the expression of cartilage markers by the MSCs. Both toluidine blue (TB) and safranin O (SO) staining demonstrated homogeneous glycosaminoglycan production throughout the KGN-MP incorporated MSC aggregates. The curcumin treatment efficiently reduced the expressions of hypertrophy markers by MSCs in vitro. The in vivo results showed that implantation of chondrogenic microtissues (KGN-MP incorporated MSC aggregates) using the curcumin loaded GelMA hydrogel resulted in cartilage tissue regeneration that had characteristic features close to the natural hyaline cartilage according to observational and histological results.

Conclusions
The use of this novel construct that contained chondrogenic cell blocks and curcumin is highly desired for cartilage regeneration.

Graphical abstract
Pluripotent stem cell differentiation as an emerging model to study human prostate development
Authors: Yu Yangyang , Jiang Wei 
Published: July 2020

AbstractProstate development is a complex process, and knowledge about this process is increasingly required for both basic developmental biology studies and clinical prostate cancer research, as prostate tumorigenesis can be regarded as the restoration of development in the adult prostate. Using rodent animal models, scientists have revealed that the development of the prostate is mainly mediated by androgen receptor (AR) signaling and that some other signaling pathways also play indispensable roles. However, there are still many unknowns in human prostate biology, mainly due to the limited availability of proper fetal materials. Here, we first briefly review prostate development with a focus on the AR, WNT, and BMP signaling pathways is necessary for prostate budding/BMP signaling pathways. Based on the current progress in in vitro prostatic differentiation and organoid techniques, we propose human pluripotent stem cells as an emerging model to study human prostate development.
A synergistic role of convalescent plasma and mesenchymal stem cells in the treatment of severely ill COVID-19 patients: a clinical case report
Authors: Peng Hongbing , Gong Tiefeng , Huang Xiaoying , Sun Xun , Luo Hong , Wang Weizhong , Luo Junbiao , Luo Baowei , Chen Yanhui , Wang Xingxing , Long Haifeng , Mei Hua , Li Chuang , Dai Yanni , Li Honghui 
Published: July 2020

AbstractAcute respiratory distress syndrome virus-2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) infection, which causes global public health emergencies, has sped widely for more than 5 months and has the risk of long-term transmission. No effective treatment has been discovered to date. In the cases we report, the patient continued to deteriorate even after administration of antiviral drugs such as lopinavir/ritonavir, interferon-α, and ribavirin, as well as intravenous injection of meropenem, methylprednisolone, and immunoglobulin. So, we infused the patient with convalescent plasma (CP), and the absolute lymphocyte count increased the next day and returned to normal on the fourth day. Followed by intravenous infusion of mesenchymal stem cells (MSCs), bilateral infiltrates were absorbed and the pulmonary function was significantly improved. We note that the intravenous infusion of CP and MSCs for the treatment of severe COVID-19 patients may have synergistic characteristics in inhibiting cytokine storm, promoting the repair of lung injury, and recovering pulmonary function. We hope to provide a reference for the research direction of COVID-19 clinical strategies.
Human amnion mesenchymal stem cells restore spermatogenesis in mice with busulfan-induced testis toxicity by inhibiting apoptosis and oxidative stress
Authors: Qian Chunfeng , Meng Qingxia , Lu Jiafeng , Zhang Liya , Li Hong , Huang Boxian 
Published: July 2020

Abstract
Background
Before starting gonadotoxic therapies, cryopreservation of mature sperm has been proposed worldwide as a method for male fertility preservation and for enabling the conception of a healthy baby with assisted reproductive technology (ART); however, these technologies are not feasible for prepubertal boys and men with spermatogenic failure. Transplantation of mesenchymal stem cells has exhibited successful therapeutic benefits in restoring spermatogenesis via gonadal graft angiogenesis, transplanted cell clonogenesis, and disordered somatic compartment recovery. This study aimed to elucidate the fertility protective effects and the underlying mechanisms of human amnion mesenchymal stem cells (hAMSCs) against busulfan-induced testis toxicity.

Methods
An in vivo busulfan-induced testis toxicity mouse model and an in vitro busulfan-administered mouse Sertoli cell line were employed to evaluate the efficacy and mechanisms of hAMSC transplantation on male fertility preservation. The process of spermatogenesis was evaluated histologically, and the percentage of seminiferous tubules with vacuoles was evaluated by HE staining. Semen parameters were calculated by computer-assisted semen analysis. ELISA was employed to test the testosterone concentration and the levels of oxidative- and antioxidative-associated substances LDH, MDA, GR, SOD, GPx, and CAT. The rates of proliferation (Ki67), apoptosis (Annexin V), and ROS were measured by FACS. The fluorescence intensity of a marker of apoptosis (TUNEL) and a meiosis gene in spermatogenesis (SCP3) were detected by immunofluorescence assay. The expression of mRNA in germ cell-specific (GCS) genes (Dazl, Ddx4, and Miwi) and meiosis genes (Scp3, Cyclin A1, and Stra8) was tested by qPCR. The expression of antiapoptotic proteins (SURVIVIN and BCL2), apoptotic proteins (CASPASE3 and CASPASE9), GCS proteins (Dazl, Ddx4, and Miwi), and meiosis proteins (Scp3, Cyclin A1, and Stra8) was tested by western blotting.

Results
hAMSC transplantation following disruption by busulfan-induced testis toxicity restored spermatogenesis, elevating testosterone levels and enhancing testicular weight, size, and semen parameters in vivo. In addition, hAMSCs clearly ameliorated cell apoptosis, enhanced cell proliferation, repressed oxidative damage, and augmented oxidative defense in vivo and in vitro. Moreover, hAMSCs distinctly increased the expression of the GCS genes Dazl, Ddx4, and Miwi and the meiosis genes Scp3, Cyclin A1, and Stra8 in vivo.

Conclusions
hAMSCs might represent a promising tool for the use in regenerative medicine, as these cells can restore spermatogenesis in a busulfan-induced testis toxicity mouse model and facilitate activity in a busulfan-administered mouse Sertoli cell line by resisting apoptosis and oxidative stress.
Garcinone-E exhibits anticancer effects in HeLa human cervical carcinoma cells mediated via programmed cell death, cell cycle arrest and suppression of cell migration and invasion
Authors: Yang Linli , Xu Zhen , Wang Wuliang 
Published: July 2020

AbstractXanthones are an important class of natural compounds bearing huge bioactivity profiles. Garcinone-E is one among most active xanthones showing potential anticancer activity against various human cancer cell lines. Therefore, the current study was performed to explore the anticancer potency of naturally occurring garcinone-E xanthone against human HeLa cervical cancer cells. The underlying mechanism of action was also tried to be explored via testifying its induction of programmed cell death, arrest of cell cycle, suppression of cell migration, cell invasion and cell adhesion. MTT assay was implemented to estimate the viability of HeLa cells after garcinone-E exposure and clonogenic assay was used to analyze the effect on clonogenic potential. Acridine orange/ethidium bromine (AO/EB) staining assay was performed for monitoring of programmed cell death along with western blotting. Flow cytometric studies were carried out to analyze cell cycle check points. Transwell chambers assays were carried out for studying the impact of garcinone-E on migration and invasion potency of HeLa cells. Western blotting was used to study the expressions of apoptosis linked proteins in HeLa cells. Results indicated that garcinone-E remarkably decreased the viability to minimum in HeLa cells in both dose and time-reliant manner. The clonogenic capacity of HeLa cells was efficiently reduced by garcinone exposure. AO/EB staining showed that the anti-viability action of garcinone-E was apoptosis allied which was supported by western blotting as well. The cell cycle check points study indicated cell cycle arrest at G2/M-phase. HeLa cell migration and invasion were reduced efficiently after being subjected to garcinone-E treatment in a dose reliant fashion. In conclusion, garcinone-E has a remarkable potential to act as anti-cervical cancer chemopreventive provided further in vivo studies are required.
Recent eruption history inferred from eruption ages of the two latest lava flows using multi-dating at Yokodake Volcano, Japan
Authors: Nitta Hiroya , Saito Takeshi , Shitaoka Yorinao 
Published: July 2020

AbstractReconstruction of the eruption history of an active volcano is necessary to elucidate its volcanic activity and to assess the probability of its volcanic eruption. Yokodake volcano in central Japan is the only active volcano among the Yatsugatake volcano group. It has effused nine lava flows, most of which have not been dated. For this study, we ascertained the eruption ages of the latest lava (Y9) and second most recent lava (Y8) using radiocarbon (14C), thermoluminescence (TL), and paleomagnetic dating methods. Results revealed the eruption ages of the two lava flows and the recent eruption history of Yokodake volcano. Yokodake volcano effused its Y8 lava flow at ca. 3.4 ka, ejected NYk-2 tephra with explosive eruption at ca. 2.4–2.2 ka, and effused the Y9 lava flow associated with Y9-T tephra at ca. 0.6 ka. Magma eruption rates of Yokodake at 34 ky and 3.4 ky were estimated as about 9 × 10−3 km3/ky and 1 × 10−2 km3/ky, indicating a stable eruption rate maintained during the past 34 ky. This result suggests that Yokodake volcano retains some potential for eruption, although the volcanic activity of the Yatsugatake volcanoes (10−1–10−2 km3/ky) has weakened over time.
Influence of adult diet on biological parameters of the housefly, Musca domestica L. (Diptera: Muscidae)
Authors: Ganda Haffizou , Abihona Hermann A. , Zannou-Boukari Elisabeth T. , Kenis Marc , Chrysostome Christophe A. A. M. , Mensah Guy A. 
Published: July 2020

Abstract
Background
Housefly (Musca domestica L. 1758) larvae are used in various parts of the world for animal feeding either by exposing substrates for natural oviposition or in industrial systems involving an adult rearing unit to produce eggs that are then placed in a substrate suitable for larval development. In order to develop M. domestica rearing system in Benin, effects of five types of food (pineapple, papaya, banana, honey, and a mixture of milk + sugar) on some biological parameters (female fecundity, adult mortality, egg hatching, pupation, and emergence time and rates) have been evaluated.

Results
Flies fed with pineapple and milk + sugar showed the highest fecundity (respectively 321 and 325 eggs per female within 10 days). Adult mortality rates decreased significantly with flies fed with honey (27% in 10 days) and milk + sugar (37%) compared to flies fed on local fruits (57 to 62%). Only minor differences were observed between the five foods in egg hatching, pupation and emergence rates.

Conclusion
This study showed that pineapple can be used to feed M. domestica instead of the conventional and more expensive milk + sugar mixture without major impact on the efficiency of M. domestica rearing.
Toxic effects of an organophosphate pesticide, envoy 50 SC on the histopathological, hematological, and brain acetylcholinesterase activities in stinging catfish (Heteropneustes fossilis)
Authors: Akter Rabeya , Pervin Mst Arzu , Jahan Halima , Rakhi Sharmin Ferdewsi , Reza A. H. M. Mohsinul , Hossain Zakir 
Published: July 2020

Abstract
Background
Freshwater fish in Bangladesh are adversely affected by the washed off pesticides, used in agriculture. The aim of this study was to evaluate the impacts of a commonly used organophosphate pesticide on freshwater stinging catfish, Heteropneustes fossilis, which envisioned that the possible threats might occur by this organophosphate group to other species in the wild.

Methodology
To study the potential hazards of Envoy 50 SC on H. fossilis, fry of the fish were exposed to the acute toxicity tests. Changes in the hematological parameters, organ-specific histomorphologies, and brain acetylcholinesterase (AChE) activities were determined by treating the fish with agricultural recommended dose and below that dose of 0.015 and 0.0075 ppm, respectively.

Results
LC50 of Envoy 50 SC for the fish was determined as 0.151 (0.014–0.198) ppm. Pesticide abruptly altered the normal tissue structures of the gill, liver, and kidney. The major alterations included were the gill lamellae missing, gill clubbing, hyperplasia, nuclear hypertrophy, vacuolation, glomerular expansion, increasing diameter of the renal tubules, hemorrhage, necrosis, and pyknosis. In blood cells, changes observed in the peripheral nuclear erythrocyte were large lymphocyte, dead cell, fusion of the cells, binucleated cells, tear-shaped cells, ghost cells, senile cells, and abnormal structures of the cells. Significantly lower (P < 0.05) red blood cell (RBC) count and AChE activities in fish brain due to the pesticide exposure suggested the reasons of abrupt behavior, increased oxygen consumption, and fish mortality at higher concentration of this organophosphate pesticide.

Conclusion
The presence of pesticides, even at low concentrations, caused deleterious effects on the earlier life stages of a comparatively harder and robust fish, suggesting a wider range effect on the more sensitive wild life, in particular decrease in survival in their native environment. Therefore, measures should be taken to minimize the risk of contamination of the aquatic environment by such toxic chemicals.
The searching algorithm for detecting a Markovian target based on maximizing the discounted effort reward search
Authors: Abd Allah El-Hadidy Mohamed 
Published: July 2020

AbstractThis paper presents the searching algorithm to detect a Markovian target which moves randomly in M-cells. Our algorithm is based on maximizing the discounted effort reward search. At each fixed number of time intervals, the search effort is a random variable with a normal distribution. More than minimizing the non-detection probability of the targets at time interval i, we seek for the optimal distribution of the search effort by maximizing the discounted effort reward search. We present some special cases of one Markovian and hidden target. Experimental results for a Markovian, hidden target are obtained and compared with the cases of applying and without applying the discounted effort reward search.
Qualitative Study of Pediatric Early Warning Systems’ Impact on Interdisciplinary Communication in Two Pediatric Oncology Hospitals With Varying Resources
Authors: Graetz Dylan , Kaye Erica C. , Garza Marcela , Ferrara Gia , Rodriguez Mario , Soberanis Vásquez Dora Judith , Méndez Aceituno Alejandra , Antillon-Klussmann Federico , Gattuso Jami S. , Mandrell Belinda N. , Baker Justin N. , Rodriguez-Galindo Carlos , Mack Jennifer W. , Agulnik Asya 
Published: July 2020

PURPOSE Hospitalized pediatric oncology patients are at high risk of deterioration and require frequent interdisciplinary communication to deliver high-quality care. Pediatric early warning systems (PEWS) are used by hospitals to reduce deterioration, but it is unknown how these systems affect communication about patient care in high- and limited-resource pediatric oncology settings. METHODS This qualitative study included semistructured interviews describing PEWS and subsequent team communication at 2 pediatric cancer centers, 1 in the United States and 1 in Guatemala. Participants included nurses, and frontline and intensive care providers who experienced recent deterioration events. Transcripts were coded and analyzed inductively using MAXQDA software. RESULTS The study included 41 providers in Guatemala and 42 providers in the United States (33 nurses, 30 ward providers, and 20 pediatric intensive care providers). Major themes identified include “hierarchy,” “empowerment,” “quality and method of communication,” and “trigger.” All providers described underlying medical hierarchies affecting the quality of communication regarding patient deterioration events and identified PEWS as empowering. Participants from the United States described the algorithmic approach to care and technology associated with PEWS contributing to impaired clinical judgement and a lack of communication. In both settings, PEWS sparked interdisciplinary communication and inspired action. CONCLUSION PEWS enhance interdisciplinary communication in high- and limited-resource study settings by empowering bedside providers. Traditional hierarchies contributed to negative communication and, in well-resourced settings, technology and automation resulted in lack of communication. Understanding contextual elements is integral to optimizing PEWS and improving pediatric oncology outcomes in hospitals of all resource levels.
Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3–Internal Tandem Duplication Mutation (SORMAIN)
Authors: Burchert Andreas , Bug Gesine , Fritz Lea V. , Finke Jürgen , Stelljes Matthias , Röllig Christoph , Wollmer Ellen , Wäsch Ralph , Bornhäuser Martin , Berg Tobias , Lang Fabian , Ehninger Gerhard , Serve Hubert , Zeiser Robert , Wagner Eva-Maria , Kröger Nicolaus , Wolschke Christine , Schleuning Michael , Götze Katharina S. , Schmid Christoph , Crysandt Martina , Eßeling Eva , Wolf Dominik , Wang Ying , Böhm Alexandra , Thiede Christian , Haferlach Torsten , Michel Christian , Bethge Wolfgang , Wündisch Thomas , Brandts Christian , Harnisch Susanne , Wittenberg Michael , Hoeffkes Heinz-Gert , Rospleszcz Susanne , Burchardt Alexander , Neubauer Andreas , Brugger Markus , Strauch Konstantin , Schade-Brittinger Carmen , Metzelder Stephan K. 
Published: July 2020

PURPOSE Despite undergoing allogeneic hematopoietic stem cell transplantation (HCT), patients with acute myeloid leukemia (AML) with internal tandem duplication mutation in the FMS-like tyrosine kinase 3 gene ( FLT3-ITD) have a poor prognosis, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT. PATIENTS AND METHODS In a randomized, placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with FLT3-ITD–positive AML in complete hematologic remission after HCT were randomly assigned to receive for 24 months either the multitargeted and FLT3-kinase inhibitor sorafenib (n = 43) or placebo (n = 40 placebo). Relapse-free survival (RFS) was the primary endpoint of this trial. Relapse was defined as relapse or death, whatever occurred first. RESULTS With a median follow-up of 41.8 months, the hazard ratio (HR) for relapse or death in the sorafenib group versus placebo group was 0.39 (95% CI, 0.18 to 0.85; log-rank P = .013). The 24-month RFS probability was 53.3% (95% CI, 0.36 to 0.68) with placebo versus 85.0% (95% CI, 0.70 to 0.93) with sorafenib (HR, 0.256; 95% CI, 0.10 to 0.65; log-rank P = .002). Exploratory data show that patients with undetectable minimal residual disease (MRD) before HCT and those with detectable MRD after HCT derive the strongest benefit from sorafenib. CONCLUSION Sorafenib maintenance therapy reduces the risk of relapse and death after HCT for FLT3-ITD–positive AML.