bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II randomized trial of sodium oligomannate in Alzheimer’s dementia
Authors: Wang Tao , Kuang Weihong , Chen Wei , Xu Wenwei , Zhang Liming , Li Yingjie , Li Hailin , Peng Ying , Chen Yangmei , Wang Baojun , Xiao Jinsong , Li Honghua , Yan Chuanzhu , Du Yifeng , Tang Mouni , He Zhiyi , Chen Haibo , Li Wei , Lin Hong , Shi Shugui , Bi Jianzhong , Zhou Huadong , Cheng Yan , Gao Xiaoping , Guan Yihui , Huang Qiu , Chen Kewei , Xin Xianliang , Ding Jian , Geng Meiyu , Xiao Shifu 
Published: September 2020

Abstract
Background
Sodium oligomannate (GV-971), a marine-derived oligosaccharide, is a novel agent that may improve cognition in AD patients.

Methods
The 24-week multicenter, randomized, double-blind, placebo parallel controlled clinical trial was conducted in AD in China between 24 October 2011 and 10 July 2013. The study included a 4-week screening/washout period, followed by a 24-week treatment period. Patients were randomized in a 1:1:1 ratio to receive GV-971 900 mg, 600 mg, or placebo capsule in treatment period, respectively. The primary outcome was cognitive improvement as assessed by changes in Alzheimer’s Disease Assessment Scale-cognitive subscale 12-item (ADAS-cog12) scores from baseline to week 24. The secondary efficacy outcomes included CIBIC-Plus, ADCS-ADL, and NPI at 24 weeks after treatment compared with baseline. A subgroup study was assessment of the change in cerebral glucose metabolism by fluorodeoxyglucose positron emission tomography measurements.

Results
Comparing with the placebo group (n = 83, change − 1.45), the ADAS-cog12 score change in the GV-971 600-mg group (n = 76) was − 1.39 (p = 0.89) and the GV-971 900-mg group (n = 83) was − 2.58 (p = 0.30). The treatment responders according to CIBIC-Plus assessment were significantly higher in the GV-971 900-mg group than the placebo group (92.77% vs. 79.52%, p < 0.05). The GV-971 900-mg subgroup showed a lower decline of cerebral metabolic rate for glucose than the placebo subgroup at the left precuneus, right posterior cingulate, bilateral hippocampus, and bilateral inferior orbital frontal at uncorrected p = 0.05. The respective rates of treatment-related AEs were 5.9%, 14.3%, and 3.5%.

Conclusions
GV-971 was safe and well tolerated. GV-971 900 mg was chosen for phase III clinical study.

Trial registration
ClinicalTrials.gov, NCT01453569. Registered on October 18, 2011.
Ethics of research on stem cells and regenerative medicine: ethical guidelines in the Islamic Republic of Iran
Authors: Afshar Leila , Aghayan Hamid-Reza , Sadighi Jila , Arjmand Babak , Hashemi Seyed-Mahmoud , Basiri Mohsen , Samani Reza Omani , Ashtiani Mohammad Kazemi , Azin Seyed-Ali , Hajizadeh-Saffar Ensiyeh , Gooshki Ehsan Shamsi , Hamidieh Amir-Ali , Rezania Moallem Mohammad-Reza , Azin Seyed-Mohammad , Shariatinasab Sadegh , Soleymani-Goloujeh Mehdi , Baharvand Hossein 
Published: September 2020

Abstract
Background
Regenerative medicine plays a major role in biomedicine, and given the ever-expanding boundaries of this knowledge, numerous ethical considerations have been raised.

Main text
Rapid advancement of regenerative medicine science and technology in Iran, emerged the Iranian National Committee for Ethics in Biomedical Research to develop a comprehensive national ethical guideline. Therefore, the present ethical guideline which comprises eleven chapters was developed in 2019 and approved in early 2020. The titles of these chapters were selected based on the ethical considerations of various aspects of the field of regenerative medicine: (1) ethical principles of research on stem cells and regenerative medicine; (2) ethical considerations for research on stem cells (embryonic stem cells, epiblast stem cells, tissue-specific stem cells, stem cells derived from transdifferentiation, induced pluripotent stem cells [iPSCs], germline pluripotent stem cells, germline stem cells, and somatic cell nuclear transfer [SCNT] stem cells); (3) ethical considerations for research on somatic cells in regenerative medicine (adult somatic cells, fetal tissue somatic cells, and somatic cells derived from pregnancy products [other than fetus]); (4) ethical considerations for research on gametes in regenerative medicine; (5) ethical considerations for research related to genetic manipulation (human and animal) in regenerative medicine; (6) ethical considerations for research on tissue engineering in regenerative medicine; (7) ethical considerations for pre-clinical studies in regenerative medicine; (8) ethical considerations for clinical trials in regenerative medicine; (9) ethical considerations for stem cells and regenerative medicine bio-banks; (10) ethical considerations for privacy and confidentiality; and (11) ethical considerations for obtaining informed consent.

Conclusion
This article discusses the process of developing the present ethical guidelines and its practical points. We hope that it can play an important worldwide role in advancing ethics of research on stem cells and regenerative medicine.
Functional enhancement strategies for immunomodulation of mesenchymal stem cells and their therapeutic application
Authors: Lee Byung-Chul , Kang Kyung-Sun 
Published: September 2020

AbstractMesenchymal stem cells (MSCs) have recently been considered a promising alternative treatment for diverse immune disorders due to their unique biomedical potentials including the immunomodulatory property and ability to promote tissue regeneration. However, despite many years of pre-clinical studies in the research field, results from clinical trials using these cells have been diverse and conflicting. This discrepancy is caused by several factors such as poor engraftment, low survival rate, and donor-dependent variation of the cells. Enhancement of consistency and efficacy of MSCs remains a challenge to overcome the current obstacles to MSC-based therapy and subsequently achieve an improved therapeutic outcome. In this review, we investigated function enhancement strategies by categorizing as preconditioning, genetic manipulation, usage of supportive materials, and co-administration with currently used drugs. Preconditioning prior to MSC application makes up a large proportion of improvement strategies and preconditioning reagents include bioactive substances (cytokines, growth factors, and innate immune receptor agonists), hypoxia, and modification in culture method. With the piled results from previous studies using each method, disease- or patient-specific therapy has become more important than ever. On the other hand, genetic manipulation targeting therapeutic-associated factors or co-administration of biocompatible materials has also arisen as other therapeutic strategies. Thus, we summarized several specialized tactics by analyzing up-to-date results in the field and proposed some promising enhancement methods to improve the clinical outcomes for MSC therapy.
Pulsed focused ultrasound enhances the therapeutic effect of mesenchymal stromal cell-derived extracellular vesicles in acute kidney injury
Authors: Ullah Mujib , Liu Daniel D. , Rai Sravanthi , Razavi Mehdi , Concepcion Waldo , Thakor Avnesh S. 
Published: September 2020

AbstractBackgroundAcute kidney injury (AKI) is characterized by rapid failure of renal function and has no curative therapies. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) are known to carry therapeutic factors, which have shown promise in regenerative medicine applications, including AKI. However, there remains an unmet need to optimize their therapeutic effect. One potential avenue of optimization lies in pulsed focused ultrasound (pFUS), where tissues-of-interest are treated with sound waves. pFUS has been shown to enhance MSC therapy via increased cell homing, but its effects on cell-free EV therapy remain largely unexplored.MethodsWe combine pFUS pretreatment of the kidney with MSC-derived EV therapy in a mouse model of cisplatin-induced AKI.ResultsEVs significantly improved kidney function, reduced injury markers, mediated increased proliferation, and reduced inflammation and apoptosis. While pFUS did not enhance EV homing to the kidney, the combined treatment resulted in a superior therapeutic effect compared to either treatment alone. We identified several molecular mechanisms underlying this synergistic therapeutic effect, including upregulation of proliferative signaling (MAPK/ERK, PI3K/Akt) and regenerative pathways (eNOS, SIRT3), as well as suppression of inflammation.ConclusionTaken together, pFUS may be a strategy for enhancing the therapeutic efficacy of MSC-derived EV treatment for the treatment of AKI.
Exosomes from oral tissue stem cells: biological effects and applications
Authors: Shi Quan , Huo Na , Wang Xing , Yang Shuo , Wang Juncheng , Zhang Tong 
Published: September 2020

AbstractAs natural nanoparticles, exosomes are a type of extracellular vesicles that are enclosed by a lipid bilayer and contain various cargos, including miRNA, mRNA, DNA and proteins. Exosomes have rapidly gained attention as a highly promising cell-free therapy. Because the cargo of exosomes changes with the changes in parent cells and status, exosomes from different types of cells may exhibit different biological effects. Considering the particularity of oral tissue stem cells, their exosomes were isolated and used to examine their related biological functions and the possibility of replacing stem cells. A variety of exosomes of oral tissue stem cells were studied, and the results revealed many special biological characteristics of these exosomes and their parent cells, especially immunomodulation, osteogenesis, odontogenesis, neuroprotection, nerve regeneration, wound healing, skin regeneration and vascularization. The oral tissue stem cell exosomes may be loaded with drugs or genes and act as tools for tumor treatment. The relevant results showed that exosomes from oral tissue stem cells were potent therapeutic tools. The present review focuses on the biological function and application of oral tissue stem cell-derived exosomes.
Neuropsychological assessment in the Israeli healthcare system: a practitioners’ survey
Authors: Kavé Gitit , Bloch Ayala , Shabi Adi , Maril Sari 
Published: September 2020

Abstract
Background
The current study examines self-reported professional practices and attitudes of Israeli neuropsychologists, in an attempt to understand how they contribute to funding of neuropsychological assessment (NPA) through the Israeli healthcare system.

Methods
Two hundred seventy-nine neuropsychologists (176 board-certified experts and 103 interns) participated in an online survey that targeted characteristics of NPA practice in Israel, attitudes toward NPA, and familiarity with healthcare referral procedures.

Results
Overall, 68% of respondents conducted NPA, with a smaller proportion of experts (56%) doing so than interns (88%). The most common purpose of NPA was to provide treatment recommendations, and respondents listed indications for NPA that matched indications for neuropsychological rehabilitation. Almost two thirds of respondents reported that none of the NPAs that they performed received healthcare funding. While all practitioners believed that the healthcare system should fund NPA, the majority demonstrated lack of familiarity with referral procedures.

Conclusions
To increase referral rates and create effective neuropsychological services within the Israeli healthcare system, neuropsychologists should work more closely with physicians in integrated care teams. In addition, they should engage in greater advocacy activities that will emphasize the need for publicly funded NPA.
Respiratory virus-associated infections in HIV-infected adults admitted to the intensive care unit for acute respiratory failure: a 6-year bicenter retrospective study (HIV-VIR study)
Authors: Elabbadi Alexandre , Pichon Jérémie , Visseaux Benoit , Schnuriger Aurélie , Bouadma Lila , Philippot Quentin , Patrier Juliette , Labbé Vincent , Ruckly Stéphane , Fartoukh Muriel , Timsit Jean-François , Voiriot Guillaume 
Published: September 2020

Abstract
Introduction
Acute respiratory failure is the main reason for admission to the intensive care unit (ICU) in HIV-infected adults. There is little data about the epidemiology of respiratory viruses in this population.

Methods
HIV-infected adults admitted to two intensive care units over a 6-year period for an acute respiratory failure and explored for respiratory viruses with multiplex polymerase chain reaction (mPCR) were retrospectively selected. Objectives were to describe the prevalence of respiratory viruses, coinfections with non-viral pathogens, and hospital outcome.

Results
A total of 123 episodes were included. An HIV infection was newly diagnosed in 9% of cases and 72% of the population were on antiretroviral therapy. Real-time mPCR tests identified at least one respiratory virus in the respiratory tract of 33 (27%) patients, but with a non-viral copathogen in two-thirds of cases. Rhinovirus was predominant, documented in 15 patients, followed by Influenza and Respiratory Syncytial Viruses (both n = 6). The prevalence of respiratory virus-associated infection did not vary along with the level of the CD4 T-cell deficiency, except for Rhinovirus which was more prevalent in patients with a CD4 lymphocyte count below 200 cells/µL (n = 13 (20%) vs. n = 2 (4%), p < 0.01). In multivariate analysis, respiratory virus-associated infection was not associated with a worse prognosis.

Conclusions
Viruses are frequently identified in the respiratory tract of HIV-infected patients with acute respiratory failure that requires ICU admission, but with a non-viral copathogen in two-thirds of cases. Rhinovirus is the predominant viral specie; its prevalence is highest in patients with a CD4 lymphocyte count below 200 cells/µL.
Computation efficiency optimization in UAV-enabled mobile edge computing system with multi-carrier non-orthogonal multiple access
Authors: Xu Fangcheng , Yu Xiangbin , Cai Jiali , Wang Guangying 
Published: September 2020

AbstractIn this paper, we study the issue of fair resource optimization for an unmanned aerial vehicle (UAV)-enabled mobile edge computing (MEC) system with multi-carrier non-orthogonal multiple access (MC-NOMA). A computation efficiency (CE) optimization problem based on the max-min fairness principle under the partial offloading mode is formulated by optimizing the subchannel assignment, the local CPU frequency, and the transmission power jointly. The formulated problem belongs to the non-convex mixed integer nonlinear programming (MINLP), that is NP-hard to find the global optimal solution. Therefore, we design a polynomial-time algorithm based on the big-M reformulation, the penalized sequential convex programming, and the general Dinkelbach’s method, which can choose an arbitrary point as the initial point and eventually converge to a feasible suboptimal solution. The proposed algorithm framework can be also applied to computation offloading only mode. Additionally, we derive the closed-form optimal solution under the local computing only mode. Simulation results validate the convergence performance of the proposed algorithm. Moreover, the proposed partial offloading mode with the CE maximization scheme outperforms that with the computation bits (CB) maximization scheme with respect to CE, and it can achieve higher CE than the benchmark computing modes. Furthermore, the proposed MC-NOMA scheme can attain better CE performance than the conventional OFDMA scheme.
Loneliness in pregnant and postpartum people and parents of children aged 5 years or younger: a scoping review protocol
Authors: Kent-Marvick Jacqueline , Simonsen Sara , Pentecost Ryoko , McFarland Mary M. 
Published: September 2020

Abstract
Background
The experience of loneliness during pregnancy and in new parenthood has not been targeted and developed as a program of research, despite evidence indicating that the incidence of loneliness is highest in those aged 16 to 24 and that loneliness rises during transitional periods. The scarcity of parenthood-loneliness inquiries leaves a gap in our understanding of new parenthood and its effects on the health and well-being of parents and their children. Here, a scoping review protocol will be presented to address this gap. The objective of this study will be to summarize the current knowledge of loneliness experienced during pregnancy and by parents during the postpartum period through the first 5 years of the child’s life.

Methods
A scoping review protocol was designed following Arksey and O’Malley’s framework. We will include all types of literature in English, including all study designs, reviews, opinion articles, dissertations, reports, books, and grey literature. To be considered for inclusion, sources should focus on loneliness in pregnant persons, postpartum people, and parents of children 5 years or younger. We will search the following electronic databases (from inception onwards): MEDLINE, EMBASE, CINAHL Complete, Cochrane Library, PsycINFO, Dissertations & Theses Global, Sociological Abstracts, Scopus, and Web of Science. Grey literature will be identified searching the British governmental website gov.uk, the Jo Cox Commission on Loneliness, the Campaign to End Loneliness, and the British Red Cross’s Action on Loneliness websites. Two reviewers, working independently of each other, will screen the titles and abstracts of the articles returned by the searches, then screen the selected full-text articles, and extract data. A third reviewer will cast the deciding vote in case no consensus is reached. Results will be given in the narrative form, mapped, and illustrated.

Discussion
This scoping review will capture the state of the current literature on loneliness in pregnancy and new parenthood. Results will be published in a peer-reviewed journal. We anticipate that the study will identify gaps and make recommendations for future areas of study and related interventions. The protocol is available on Open Science Framework at DOI 10.17605/OSF.IO/BFVPZ.
What evidence exists related to soil retention of phosphorus from on-site wastewater treatment systems in boreal and temperate climate zones? A systematic map protocol
Authors: Envall Ida , Fagerlund Fritjof , Westholm Lena Johansson , Åberg Charlotte , Bring Arvid , Land Magnus , Gustafsson Jon Petter 
Published: September 2020

Abstract
Background
Soil-based on-site wastewater treatment systems (OWSs) are suspected to contribute to eutrophication of surface waters, due to the discharge of phosphorus (P). However, along the flow path between the facilities and surface waters, different processes contribute to delay the transport of phosphorus through the ground. This may reduce the unwanted impact on receiving water bodies. However, the strength and significance of this so-called soil retention remains unclear.
In Sweden, there are nearly one million OWSs. To protect surface waters, a high P removal rate (up to 90%) is often required by the local municipalities. However, since these requirements may have costly consequences to property owners, it is debated as to whether they are too strict. In this debate, it is often claimed that the retention of P occurring in natural environments may be underestimated by authorities. Accordingly, there is a need for a scrutiny of the available evidence related to soil retention of phosphorus from OWSs. This is the objective of the planned systematic map. Focus will be on boreal and temperate climate zones.

Methods
Searches will be made for peer-reviewed articles and grey literature using bibliographic databases, search engines, specialist websites and stakeholder contacts. The references will be screened for relevance according to a predefined set of eligibility criteria. At stage one, after testing and clarifying the eligibility criteria, the references will be single-screened based on title and abstract. At stage two, potentially relevant references will be screened in full-text independently by two reviewers. We will compile a detailed database of the relevant studies. Moreover, a narrative report will be produced, describing the research landscape in general terms. This will be carried out with a conceptual model, describing the processes involved in P retention in natural environments, as a foundation. It will be discussed where the respective studies/study types fit into the conceptual model, and also evaluated how each study/study type can be related to the overarching question of eutrophication. Moreover, we will describe identified knowledge gaps that warrant further primary research effort, as well as identified knowledge clusters that could be suitable for systematic reviews.
Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer
Authors: Xue Chen , Zhao Yalei , Li Lanjuan 
Published: September 2020

AbstractAs an important posttranscriptional modification of RNA, 5-methylcytosine (m5C) has attracted increasing interest recently, with accumulating evidence suggesting the involvement of RNA m5C modification in multiple cellular processes as well as tumorigenesis. Cooperatively, advances in m5C detection techniques have enabled transcriptome mapping of RNA methylation at single-nucleotide resolution, thus stimulating m5C-based investigations. In this review, we summarize currently available approaches for detecting m5C distribution in RNA as well as the advantages and disadvantages of these techniques. Moreover, we elucidate the regulatory mechanisms of RNA m5C modification by introducing the molecular structure, catalytic substrates, cellular distributions and biological functions of RNA m5C regulators. The functional consequences of m5C modification on mRNAs, tRNAs, rRNAs and other RNA species, including viral RNAs and vault RNAs, are also discussed. Finally, we review the role of RNA m5C modification in cancer pathogenesis and progression, in hopes of providing new insights into cancer treatment.
Aggregate-selective antibody attenuates seeded aggregation but not spontaneously evolving disease in SOD1 ALS model mice
Authors: Lehmann Manuela , Marklund Matthew , Bolender Anna-Lena , Bidhendi Elaheh E. , Zetterström Per , Andersen Peter M. , Brännström Thomas , Marklund Stefan L. , Gilthorpe Jonathan D. , Nordström Ulrika 
Published: September 2020

AbstractIncreasing evidence suggests that propagation of the motor neuron disease amyotrophic lateral sclerosis (ALS) involves the pathogenic aggregation of disease-associated proteins that spread in a prion-like manner. We have identified two aggregate strains of human superoxide dismutase 1 (hSOD1) that arise in the CNS of transgenic mouse models of SOD1-mediated ALS. Both strains transmit template-directed aggregation and premature fatal paralysis when inoculated into the spinal cord of adult hSOD1 transgenic mice. This spread of pathogenic aggregation could be a potential target for immunotherapeutic intervention. Here we generated mouse monoclonal antibodies (mAbs) directed to exposed epitopes in hSOD1 aggregate strains and identified an aggregate selective mAb that targets the aa 143–153 C-terminal extremity of hSOD1 (αSOD1143–153). Both pre-incubation of seeds with αSOD1143–153 prior to inoculation, and weekly intraperitoneal (i.p.) administration attenuated transmission of pathogenic aggregation and prolonged the survival of seed-inoculated hSOD1G85R Tg mice. In contrast, administration of a mAb targeting aa 65–72 (αSOD165–72), which exhibits high affinity towards monomeric disordered hSOD1, had an adverse effect and aggravated seed induced premature ALS-like disease. Although the mAbs reached similar concentrations in CSF, only αSOD1143–153 was found in association with aggregated hSOD1 in spinal cord homogenates. Our results suggest that an aggregate-selective immunotherapeutic approach may suppress seeded transmission of pathogenic aggregation in ALS. However, long-term administration of αSOD1143–153 was unable to prolong the lifespan of non-inoculated hSOD1G85R Tg mice. Thus, spontaneously initiated hSOD1 aggregation in spinal motor neurons may be poorly accessible to therapeutic antibodies.