bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benchmarking of computational error-correction methods for next-generation sequencing data
Authors: Mitchell Keith , Brito Jaqueline J. , Mandric Igor , Wu Qiaozhen , Knyazev Sergey , Chang Sei , Martin Lana S. , Karlsberg Aaron , Gerasimov Ekaterina , Littman Russell , Hill Brian L. , Wu Nicholas C. , Yang Harry Taegyun , Hsieh Kevin , Chen Linus , Littman Eli , Shabani Taylor , Enik German , Yao Douglas , Sun Ren , Schroeder Jan , Eskin Eleazar , Zelikovsky Alex , Skums Pavel , Pop Mihai , Mangul Serghei 
Published: March 2020

AbstractBackgroundRecent advancements in next-generation sequencing have rapidly improved our ability to study genomic material at an unprecedented scale. Despite substantial improvements in sequencing technologies, errors present in the data still risk confounding downstream analysis and limiting the applicability of sequencing technologies in clinical tools. Computational error correction promises to eliminate sequencing errors, but the relative accuracy of error correction algorithms remains unknown.ResultsIn this paper, we evaluate the ability of error correction algorithms to fix errors across different types of datasets that contain various levels of heterogeneity. We highlight the advantages and limitations of computational error correction techniques across different domains of biology, including immunogenomics and virology. To demonstrate the efficacy of our technique, we apply the UMI-based high-fidelity sequencing protocol to eliminate sequencing errors from both simulated data and the raw reads. We then perform a realistic evaluation of error-correction methods.ConclusionsIn terms of accuracy, we find that method performance varies substantially across different types of datasets with no single method performing best on all types of examined data. Finally, we also identify the techniques that offer a good balance between precision and sensitivity.
Efficacy of Tuina in patients with chronic low back pain: study protocol for a randomized controlled trial
Authors: Zhang Shuaipan , Kong Lingjun , Zhu Qingguang , Wu Zhiwei , Li Jianhua , Fang Min , Sun Wuquan , Cheng Yanbin , Xu Shanda , Guo Guangxin , Zhou Xin , Lv Zhizhen 
Published: March 2020

Abstract
Background
Low back pain is a common reason for medical care and carries a heavy social burden. The efficacy of Tuina or health care education for low back pain has been evaluated in previous systematic reviews. However, there is no evidence to support the superiority of one form of treatment over another. The aim of this study is to compare the efficacy of Tuina with health care education in the management of low back pain.

Methods/design
This study is a randomized controlled trial with parallel-group design including two groups: a Tuina group and a health care education group. A total of 160 eligible participants will be randomly assigned to the groups in a 1:1 ratio. The interventions of both groups will last for 20 min and be carried out twice each week for a period of 12 weeks. The primary outcome is the Oswestry Disability Index. The secondary outcomes include a visual analogue scale and the 36-item Short Form Health Survey. They will be assessed at baseline, at the end of the intervention every month, and during 6 months and 9 months of follow-up by repeated measures analysis of variance. The significance level is 5%. The safety of Tuina and health care education will be evaluated after each treatment session. This study will focus on the value of Tuina and health care education for low back pain and will highlight any differences in the efficacy of the treatments.

Discussion
This study will evaluate the efficacy and safety of Tuina intervention for low back pain, which could provide reliable evidence for clinical decision making for patients with low back pain.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1900022656. Registered on 23 April 2019.
Drosophila enabled promotes synapse morphogenesis and regulates active zone form and function
Authors: McNeill Elizabeth M. , Thompson Cheryl , Berke Brett , Chou Vivian T. , Rusch Jannette , Duckworth April , DeProto Jamin , Taylor Alicia , Gates Julie , Gertler Frank , Keshishian Haig , Van Vactor David 
Published: March 2020

Abstract
Background
Recent studies of synapse form and function highlight the importance of the actin cytoskeleton in regulating multiple aspects of morphogenesis, neurotransmission, and neural plasticity. The conserved actin-associated protein Enabled (Ena) is known to regulate development of the Drosophila larval neuromuscular junction through a postsynaptic mechanism. However, the functions and regulation of Ena within the presynaptic terminal has not been determined.

Methods
Here, we use a conditional genetic approach to address a presynaptic role for Ena on presynaptic morphology and ultrastructure, and also examine the pathway in which Ena functions through epistasis experiments.

Results
We find that Ena is required to promote the morphogenesis of presynaptic boutons and branches, in contrast to its inhibitory role in muscle. Moreover, while postsynaptic Ena is regulated by microRNA-mediated mechanisms, presynaptic Ena relays the output of the highly conserved receptor protein tyrosine phosphatase Dlar and associated proteins including the heparan sulfate proteoglycan Syndecan, and the non-receptor Abelson tyrosine kinase to regulate addition of presynaptic varicosities. Interestingly, Ena also influences active zones, where it restricts active zone size, regulates the recruitment of synaptic vesicles, and controls the amplitude and frequency of spontaneous glutamate release.

Conclusion
We thus show that Ena, under control of the Dlar pathway, is required for presynaptic terminal morphogenesis and bouton addition and that Ena has active zone and neurotransmission phenotypes. Notably, in contrast to Dlar, Ena appears to integrate multiple pathways that regulate synapse form and function.
The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway against experimental osteoarthritis
Authors: Nasi Sonia , Ehirchiou Driss , Chatzianastasiou Athanasia , Nagahara Noriyuki , Papapetropoulos Andreas , Bertrand Jessica , Cirino Giuseppe , So Alexander , Busso Nathalie 
Published: March 2020

AbstractBackgroundOsteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H2S) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the H2S-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development.Methods3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST−/−meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST−/−cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated.Results3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST−/−mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro,genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes.Conclusion3-MST-generated H2S protects against joint calcification and experimental OA. Enhancing H2S production in chondrocytes may represent a potential disease modifier to treat OA.
Selection of human induced pluripotent stem cells lines optimization of cardiomyocytes differentiation in an integrated suspension microcarrier bioreactor
Authors: Laco Filip , Lam Alan Tin-Lun , Woo Tsung-Liang , Tong Gerine , Ho Valerie , Soong Poh-Loong , Grishina Elina , Lin Kun-Han , Reuveny Shaul , Oh Steve Kah-Weng 
Published: March 2020

Abstract
Background
The production of large quantities of cardiomyocyte is essential for the needs of cellular therapies. This study describes the selection of a human-induced pluripotent cell (hiPSC) line suitable for production of cardiomyocytes in a fully integrated bioprocess of stem cell expansion and differentiation in microcarrier stirred tank reactor.

Methods
Five hiPSC lines were evaluated first for their cardiac differentiation efficiency in monolayer cultures followed by their expansion and differentiation compatibility in microcarrier (MC) cultures under continuous stirring conditions.

Results
Three cell lines were highly cardiogenic but only one (FR202) of them was successfully expanded on continuous stirring MC cultures. FR202 was thus selected for cardiac differentiation in a 22-day integrated bioprocess under continuous stirring in a stirred tank bioreactor. In summary, we integrated a MC-based hiPSC expansion (phase 1), CHIR99021-induced cardiomyocyte differentiation step (phase 2), purification using the lactate-based treatment (phase 3) and cell recovery step (phase 4) into one process in one bioreactor, under restricted oxygen control (< 30% DO) and continuous stirring with periodic batch-type media exchanges. High density of undifferentiated hiPSC (2 ± 0.4 × 106 cells/mL) was achieved in the expansion phase. By controlling the stirring speed and DO levels in the bioreactor cultures, 7.36 ± 1.2 × 106 cells/mL cardiomyocytes with > 80% Troponin T were generated in the CHIR99021-induced differentiation phase. By adding lactate in glucose-free purification media, the purity of cardiomyocytes was enhanced (> 90% Troponin T), with minor cell loss as indicated by the increase in sub-G1 phase and the decrease of aggregate sizes. Lastly, we found that the recovery period is important for generating purer and functional cardiomyocytes (> 96% Troponin T). Three independent runs in a 300-ml working volume confirmed the robustness of this process.

Conclusion
A streamlined and controllable platform for large quantity manufacturing of pure functional atrial, ventricular and nodal cardiomyocytes on MCs in conventional-type stirred tank bioreactors was established, which can be further scaled up and translated to a good manufacturing practice-compliant production process, to fulfill the quantity requirements of the cellular therapeutic industry.
Adipose stem cells isolated from diabetic mice improve cutaneous wound healing in streptozotocin-induced diabetic mice
Authors: An Ran , Zhang Yong , Qiao Yu , Song Lili , Wang Hongjun , Dong Xiao 
Published: March 2020

Abstract
Background
Adipose-derived mesenchymal stem cells (ASCs) therapy is emerging as a novel therapeutic option for the treatment of a variety of diseases including diabetes and diabetic wound healing. Multiple studies indicate that ASCs could promote wound healing and reverse diabetes. However, whether ASCs from diabetic donors retain their therapeutic functions and the mechanisms of how ASCs contribute to wound healing remain largely unknown. In this study, we explored the cutaneous wound healing ability of ASCs collected from C57BL/6 mice that had been rendered diabetic with streptozotocin (STZ).

Methods
ASCs were harvested from adipose tissues of type 1 diabetic (T1D) or normal C57BL/6 mice. Cell phenotypes were evaluated by flow cytometry analysis, and cell differentiation into adipocytes, chondrocytes, and osteocytes was compared. Secretions of transforming growth factor β (TGF-β1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) by ASCs were assessed by ELISA. Migration and proliferation of fibroblasts co-cultured with T1D ASCs or control ASCs were also compared. The therapeutic effects of T1D and control ASCs in promoting wound closure were measured in vivo in a T1D wound mouse model. Granulation tissues were collected and stained with H&E at 14th day. CD34 and collagen I were detected by immunohistochemistry. Expressions of IL-6, α-SMA, CD31, collagen I, and collagen III were quantified by real-time PCR. GFP-expressing ASCs were used to trace in vivo cell differentiation.

Results
T1D ASCs and control ASCs showed similar expression of cell surface markers (CD29, CD34, CD105) and proliferation pattern. They can both differentiate into different cell types. T1D ASCs secreted similar amounts of VEGF and bFGF, but less TGF-β compared with control ASCs. Like control ASCs, T1D ASCs promoted the proliferation and migration of skin fibroblast cells. When injected in cutaneous wound of T1D mice, T1D ASCs increased wound closure and hair follicle regeneration at a comparable extent as ASCs. Mice receiving T1D ASCs or ASCs exhibited significantly higher expressions of collagen I, collagen III, and CD31 and reduced expression of IL-6 in wound tissues. Immunohistochemistry staining showed increased angiogenesis in mice receiving ASCs as was evident by increased CD34+ cells and collagen I staining. GFP+ ASCs injection showed that ASCs differentiated into fibroblasts and endothelial cells in vivo.

Conclusions
Our results suggest that T1D ASCs could accelerate cutaneous wound healing. Mechanisms may include increasing fibroblast growth and migration, skin angiogenesis, and differentiation into fibroblasts and endothelial cells. This study provides evidence that diabetic ASCs may be used as a therapeutic option in cutaneous wound healing in diabetic recipients.
Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
Authors: García-Bonilla María , Ojeda-Pérez Betsaida , García-Martín María L. , Muñoz-Hernández M. Carmen , Vitorica Javier , Jiménez Sebastián , Cifuentes Manuel , Santos-Ruíz Leonor , Shumilov Kirill , Claros Silvia , Gutiérrez Antonia , Páez-González Patricia , Jiménez Antonio J. 
Published: March 2020

Abstract
Background
In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model.

Methods
BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay.

Results
Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering.

Conclusions
BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.
Targeting prostate cancer stem-like cells by an immunotherapeutic platform based on immunogenic peptide-sensitized dendritic cells-cytokine-induced killer cells
Authors: Wang Zhu , Li Youjia , Wang Yuliang , Wu Dinglan , Lau Alaster Hang Yung , Zhao Pan , Zou Chang , Dai Yong , Chan Franky Leung 
Published: March 2020

Abstract
Background
Autologous cellular immunotherapy or immune enhancement therapy has demonstrated some promising benefits for prostate cancer. T cell-based immunotherapy or sipuleucel-T therapy has yielded certain beneficial responses and a slight improvement on the overall survival of patients with metastatic castration-resistant prostate cancer (mCRPC) as shown in some clinical trials, suggesting that prostate cancer is immunoresponsive.

Methods
In this study, we developed an adaptive cytokine-induced killer cell (CIK)-based immunotherapeutic application targeting the prostate cancer stem-like cells (PCSCs). In this therapeutic platform, dendritic cells (DC) were isolated from the peripheral blood mononuclear cells (PBMCs) and preloaded or sensitized with immunogenic peptides derived from two PCSC-associated cell membrane molecules, CD44 and EpCAM, followed by co-culture with the expanded peripheral blood lymphocyte (PBL)-derived CIK cells. The in vitro cytotoxic activity of DC-activated CIK cells against PCSCs was determined by CCK8 and TUNEL assays, and the in vivo anti-tumor effect of DC-activated CIK cells on prostate cancer xenograft tumors was evaluated in subcutaneous and orthotopic xenograft models.

Results
Our results showed that the peptide-sensitized DC-CIK cell preparation manifested significant in vitro cytotoxic activity against the PCSC-enriched prostatospheroids and also in vivo anti-tumor effect against prostate cancer xenografts derived from the PCSC-enriched prostatospheroids.

Conclusions
Together, our established immunogenic peptide-sensitized DC-CIK-based cell preparation platform manifests its potential immunotherapeutic application in targeting the PCSCs and also prostate cancer.
Screening for efficient nitrogen sources for overproduction of the biomass of the functionally probiotic L. plantarum strain RPR42 in a cane molasses-based medium
Authors: Papizadeh Moslem , Rohani Mahdi , Hosseini Seyed Nezamedin , Shojaosadati Seyed Abbas , Nahrevanian Hossein , Talebi Malihe , Pourshafie Mohammad Reza 
Published: March 2020

AbstractNitrogen source has a vital role for the efficient growth of lactobacilli. The effects of cheese whey, corn steep liquor, and wheat germ extract on the growth of L. plantarum strain RPR42 in cane molasses-based media was evaluated using various approaches of design of experiments. Our results showed that such protein-rich agricultural by-products significantly increase the biomass production of the strain RPR42 in cane molasses-based media. The most affecting nitrogenous material was cheese whey followed by CSL and the minor effect was reported for wheat germ extract as revealed in factorial and Box–Behnken design experiments. The replacement of costly beef extract and yeast extract with a defined mixtures of the above nitrogenous agricultural by-products in cane molasses-based medium led to production of up to 12.64 g/L/24 h of dry biomass of strain RPR42. A detectable cell density of strain RPR42 (~ 9.81 × 109 CFU/mL 24 h) which was observed in such an economic medium showed that the large-scale production of the strain RPR42 tend to be feasible at significantly low costs.
Mapping evidence on the prevalence, incidence, risk factors and cost associated with chronic low back pain among adults in Sub-Saharan Africa: a systematic scoping review protocol
Authors: Kahere Morris , Ginindza Themba 
Published: March 2020

Abstract
Background
Globally, low back pain (LBP) is a major public health problem affecting mainly adults of the working class and is the leading cause of disability. The estimated lifetime prevalence of LBP is 50 to 80%. From 1990 to 2015, the years lived with disability caused by LBP have scaled up by 54% with the greatest increase observed in low-middle-income countries (LMICs). LBP poses a significant socio-economic burden to the society regardless of all the technological advancement in diagnosis and intervention approaches in recent years. Despite an increase in the literature of LBP in LMICs, chronic low back pain (CLBP) is poorly investigated yet it is responsible for the largest amount of burden. The purpose of this scoping review is to map the existing evidence on the prevalence, incidence, mortality, risk factors, and cost associated with CLBP among adults in Sub-Saharan Africa (SSA).

Methods
We will conduct a scoping review to explore, describe, and map literature on the prevalence, incidence, mortality, risk factors, and costs associated with CLBP among adults in SSA. The search will be performed using the EBSCOhost platform by searching the following databases within the platform: Academic search complete, health source: nursing/academic edition, CINAHL with full text, Embase, PubMed, MEDLINE, Science Direct databases, Google Scholar, and the World Health Organization library databases. The search will include peer-reviewed, review articles, and gray literature. The first (title and abstract) and the second (full text) screening phases will be performed by two independent reviewers, with the third reviewer employed to adjudicate discrepancies. The reference list of all included articles will also be searched for eligible articles. This scoping review will be reported in accordance to the MOOSE and PRISMA-ScR guidelines. The NVivo 12 data analysis software will be used to generate themes, and a thematic content analysis will be used to give the narrative account of the review.

Discussion
The study anticipates finding relevant literature on the prevalence, incidence, risk factors, mortality, and cost associated with CLBP among adults in SSA. The study outcomes will aid in identifying research gaps, planning, informing policy, commissioning of future research, and funding prioritization.