bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer
Authors: Liao Qi , Chen Linbo , Zhang Ning , Xi Yang , Hu Shiyun , Ng Derry Minyao , Ahmed Fatma Yislam Hadi , Zhao Guofang , Fan Xiaoxiang , Xie Yangyang , Dai Xiaoyu , Jin Yanping , Ge Jiaxin , Dong Changzheng , Zhang Xinjun , Guo Junming 
Published: September 2020

AbstractBackgroundKLF5is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers.KLF5functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated byKLF5in CRC are currently unknown.MethodsIn this study, we first designed a computational pipeline to determine the PCG and lncRNA targets ofKLF5in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors ofKLF5were then searched for through bioinformatics analysis. We also constructed a regulatory network forKLF5and annotated its functions. Finally, one of theKLF5lncRNA targets,SNHG12, was selected to further explore its expression pattern and functions in CRC.ResultsWe were able to identify 19 lncRNA targets ofKLF5and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factorsARandHSF1as the regulatory co-factors ofKLF5through bioinformatics analysis. Then, through the analysis of the regulatory network, we found thatKLF5may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, theSNHG12up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates thatSNHG12may play a critical part in CRC tumorigenesis and progression. Additionally, expression ofSNHG12was found to be down-regulated in CRC cell lines whenKLF5expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels ofSNHG12andKLF5, further alluding to their regulatory relationship.ConclusionsIn conclusion, the network analysis ofKLF5targets indicates thatSNHG12may be a significant lncRNA in CRC.
Population estimation and harm reduction among people who inject drugs in Addis Ababa, Ethiopia
Authors: Deyessa Negussie , Senbete Bekele , Abdo Aman , Mundia Bernard M. 
Published: September 2020

Abstract
Background
Injecting drug use is known to contribute significantly to the spread of the HIV epidemic in many parts of the developing world. Due to the hidden nature and stigma of the problem, it is difficult to study using routine surveys. Therefore, this study aims to estimate the number of people who inject drugs in Addis Ababa, Ethiopia, and to describe the epidemiological and social situation related to HIV among people who inject drugs.

Methods
The study used rapid assessment methods, followed by combined methods of estimating populations, using nomination and multiplier methods. The combined methods used two datasets: the first includes the proportion of people who use services within a year as a multiplier, and the second, a count of the list of people with a problem who used the specific service within a year as a benchmark. The rapid assessment incorporated different qualitative tools to elicit information related to injectable drugs, using existing data sources, in-depth interviews, and focus group discussions.

Results
The study estimated a total of 4068; with 95% CI (3196, 5207) people who inject drugs (PWIDs) in Addis Ababa. The study found people who inject drugs were young in age, male, with a lower educational status, unmarried, and living in small clerical business. People who inject drugs and participated in the study were more likely to use additional substances like alcohol, khat, and cannabis. The most common form of injectable drug used was heroin, and most of the people who inject drugs reported sharing syringes and needles. A high proportion of study subjects also disclosed having positive test results for HIV, hepatitis B, and C.

Conclusion
The population size of people who inject drugs in Addis Ababa is high. Lack of service in harm reduction in the city has made PWIDs vulnerable and at higher risk for HIV/AIDs and hepatitis B and C. Therefore, responsible bodies must start implementing the essential harm reduction strategies given by the World Health Organization.
Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1
Authors: Yin Ping , Bai Yu , Wang Zhuo , Sun Yu , Gao Jian , Na Lei , Zhang Zhongbo , Wang Wei , Zhao Chenghai 
Published: September 2020

AbstractMesenchymal-like stemness is characterized by epithelial-mesenchymal transition (EMT). Breast cancer (BC) cell mesenchymal-like stemness is responsible for distal lung metastasis. Interrogation of databases showed that Fzd7 was closely associated with a panel of mesenchymal-related genes and a panel of stemness-related genes. Fzd7 knockdown in mesenchymal-like MDA-MB-231 and Hs578T cells reduced expression of Vimentin, Slug and Zeb1, induced an epithelial-like morphology, inhibited cell motility, impaired mammosphere formation and decreased Lgr5+ subpopulation. In contrast, Fzd7 overexpression in MCF7 cells resulted in opposite changes. Fzd7 knockdown delayed xenograft tumor formation, suppressed tumor growth, and impaired lung metastasis. Mechanistically, Fzd7 combined with Wnt5a/b and modulated expression of phosphorylated Stat3 (p-STAT3), Smad3 and Yes-associated protein 1 (Yap1). Moreover, Fzd7-Wnt5b modulated expression of collagen, type VI, alpha 1 (Col6a1). Both Wnt5b knockdown and Col6a1 knockdown disrupted BC cell mesenchymal phenotype and stemness. Taken together, Fzd7 contributes to BC cell EMT and stemness, inducing tumorigenesis and metastasis, mainly through a non-canonical Wnt5b pathway. Col6a1 is implicated in Fzd7-Wnt5b signaling, and mediates Fzd7-Wnt5b -induced mesenchymal-like stemness.
Non-classical 1p36 deletion in a patient with Duane retraction syndrome: case report and literature review
Authors: Yokoyama Emiy , Villarroel Camilo E. , Diaz Sinhué , Del Castillo Victoria , Pérez-Vera Patricia , Salas Consuelo , Gómez Samuel , Barreda Reneé , Molina Bertha , Frias Sara 
Published: September 2020

Abstract
Background
Monosomy of 1p36 is considered the most common terminal microdeletion syndrome. It is characterized by intellectual disability, growth retardation, seizures, congenital anomalies, and distinctive facial features that are absent when the deletion is proximal, beyond the 1p36.32 region. In patients with proximal deletions, little is known about the associated phenotype, since only a few cases have been reported in the literature. Ocular manifestations in patients with classical 1p36 monosomy are frequent and include strabismus, myopia, hypermetropia, and nystagmus. However, as of today only one patient with 1p36 deletion and Duane retraction syndrome (DRS) has been reported.

Case presentation
We describe a patient with intellectual disability, facial dysmorphism, and bilateral Duane retraction syndrome (DRS) type 1. Array CGH showed a 7.2 Mb de novo deletion from 1p36.31 to 1p36.21.

Discussion
Our patient displayed DRS, which is not part of the classical phenotype and is not a common clinical feature in 1p36 deletion syndrome; we hypothesized that this could be associated with the overlapping deletion between the distal and proximal 1p36 regions. DRS is one of the Congenital Cranial Dysinnervation Disorders, and a genetic basis for the syndrome has been extensively reported. The HES3 gene is located at 1p36.31 and could be associated with oculomotor alterations, including DRS, since this gene is involved in the development of the 3rd cranial nerve and the 6th cranial nerve’s nucleus. We propose that oculomotor anomalies, including DRS, could be related to proximal 1p36 deletion, warranting a detailed ophthalmologic evaluation of these patients.
Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: statistical analysis plan for the Getting it Right: Addressing Shoulder Pain (GRASP) 2 × 2 factorial multicentre randomised controlled trial
Authors: Marian Ioana R. , Hopewell Sally , Keene David J. , Cureton Lucy , Lamb Sarah E. , Dutton Susan J. 
Published: September 2020

Abstract
Background
The Getting it Right: Addressing Shoulder Pain (GRASP) trial assesses the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. This article describes the statistical analysis plan for the GRASP randomised controlled trial.

Methods/design
GRASP is a multicentre randomised controlled trial using a 2 × 2 factorial design. Adults aged ≥ 18 years with a new episode of shoulder pain related to a rotator cuff disorder, not currently receiving physiotherapy or being considered for surgery, are randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (up to 6 physiotherapy sessions), (2) best practice advice (one physiotherapy session), (3) subacromial corticosteroid injection then progressive exercise and (4) subacromial corticosteroid injection then best practice advice. The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score over 12 months. Secondary outcomes are as follows: pain and function SPADI subdomains, health-related quality of life (EuroQol EQ-5D-5L), sleep disturbance, return to activity, global impression of change, health resource use, out-of-pocket expenses and work disability. Here, we describe in detail the following: sample size calculation, descriptive statistics of the primary and secondary outcomes, statistical models used for the analysis of the main outcomes, handling of missing data, planned sensitivity and subgroup analyses. This pre-specified statistical analysis plan was written and submitted without prior knowledge of the trial results.

Discussion
Publication of the statistical analysis plan for the GRASP trial aims to reduce the risk of outcome reporting bias and increase transparency of the data analysis. Any deviations or changes to the current SAP will be described and justified in the final study report and any results publications.

Trial registration
International Standard Randomised Controlled Trial Number ISRCTN16539266. Registered on 14 June 2016. EudraCT number 2016-002991-28. Registered on 12 June 2016.
Morphological identification keys for adults of sand flies (Diptera: Psychodidae) in Sri Lanka
Authors: Wijerathna Tharaka , Gunathilaka Nayana 
Published: September 2020

Abstract
Background
Phlebotomine sand flies are a medically important group of insects that is responsible for the transmission of leishmaniasis. Surveillance plays a major role in vector control programmes through exploring species abundance, potential entomological risk and designing appropriate control measures. In field surveillance programmes of such nature, morphological identification of vector species is of paramount importance. However, in Sri Lanka, there is no published taxonomic key available for the identification of leishmaniasis vectors.

Method
Identification keys for both male and females of the sand flies recorded in Sri Lanka were developed using morphological features. Main identification features were compared with the original observation of specimens collected from surveys and the use of published literature. Photographic illustrations of morphological features are included with the intention of making the keys user-friendly for non-taxonomists.

Results
A total of 22 sand fly species (Diptera: Psychodidae) of the genera Phlebotomus and Sergentomyia reported in Sri Lanka from 1910 to 2019 are included in the present work.

Conclusion
This simplified key, along with photographs taken from specimens would be beneficial to the health staff, entomologists and research staff who deal with leishmaniasis control programmes and vector-related studies.
Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica
Authors: Bai Xueqi , Li Maining , Wang Xinyue , Chang Hao , Ni Yangyue , Li Chen , He Kaiyue , Wang Huiquan , Yang Yuxuan , Tian Tian , Hou Min , Ji Minjun , Xu Zhipeng 
Published: September 2020

AbstractBackgroundHepatic granuloma formation and fibrosis as the consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology ofSchistosoma japonicuminfection. It has been proposed that fucoidan, a sulfated polysaccharide existing naturally in brown seaweedFucus vesiculosus, plays a diversified role to perform immunomodulatory activities. However, whether fucoidan functions in the host hepatic pathology is unknown and identifying the potential mechanism that is responsible for hepatic improvement is still necessary.MethodsWe evaluated the hepatic pathology fromS. japonicum-infected mice after treatment with fucoidan. qRT-PCR and immunofluorescence were used to detect the pro- or anti-inflammatory factors and the phosphorylated p65 in the livers. In addition, flow cytometry was also performed to investigate the T cell subsets in theS. japonicum-infected mice after treatment with fucoidan, and functional molecules relatively specific to Treg cells were detectedin vitro. Furthermore, macrophages were treated with fucoidanin vitroand to detect the inflammatory cytokines.ResultsTreatment with fucoidan significantly reduced the hepatic granuloma size and fibrosis response duringS. japonicuminfection. The attenuated phospho-p65 protein levels and the mRNA levels of pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) were observed in the livers from fucoidan-treatedS. japonicum-infected mice; however, the mRNA levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased. In addition, the infiltration of Treg cells was significantly enhanced both in the livers and spleens from fucoidan-treatedS. japonicum-infected mice. Consistent with this, the mRNA levels of IL-10 and TGF-β were dramatically increased in the livers fromS. japonicum-infected mice after fucoidan treatment. Furthermore,in vitrostimulated splenocytes with fucoidan resulted in increasing Treg cells in splenocytes as well as the functional expression of CC chemokine receptor type 4 (CCR4) and CXC chemokine receptor type 5 (CXCR5) in Treg cells. Additionally, fucoidan promoted the mRNA levels of IL-4 and IL-13 in macrophages.ConclusionsThese findings suggest an important role of natural fucoidan in reducing hepatic pathology in the progress ofS. japonicuminfection with a stronger Treg response, which may reveal a new potential therapeutic strategy for hepatic disease caused by parasitic chronic infection.
Short-wave enhances mesenchymal stem cell recruitment in fracture healing by increasing HIF-1 in callus
Authors: Ye Dongmei , Chen Chen , Wang Qiwen , Zhang Qi , Li Sha , Liu Hongwei 
Published: September 2020

Abstract
Background
As a type of high-frequency electrotherapy, a short-wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms remain unclear.

Purpose
To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing.

Materials and methods
For in vivo study, the effect of Short-Wave therapy to fracture healing was examined in a stabilized femur fracture model of 40 SD rats. Radiography was used to analyze the morphology and microarchitecture of the callus. Additionally, fluorescence assays were used to analyze the GFP-labeled MSC homing after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast from newborn rats simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC from rats was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot.

Results
Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Wave therapy upregulated HIF-1 and SDF-1 expression in osteoblast and its cultured medium, as well as the expression of CXCR-4, β-catenin, F-actin, and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC.

Conclusions
These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.
Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats
Authors: Sun Junyi , Ding Xianfei , Liu Shaohua , Duan Xiaoguang , Liang Huoyan , Sun Tongwen 
Published: September 2020

Abstract
Background
We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsis-induced acute lung injury (ALI) and change microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes.

Methods
A total of 60 male adult Sprague-Dawley (SD) rats were separated into three groups: the sham control (SC) group, the sepsis induced by cecal ligation and puncture (CLP) group, and the ADMSC treatment (CLP-ADMSCs) group, in which rats underwent the CLP procedure and then received 1 × 106 ADMSCs. Rats were sacrificed 24 h after the SC or CLP procedures. To study the role of ADMSCs during ALI caused by sepsis and examine the impact of ADMSCs on the gut microbiome composition, rat lungs were histologically evaluated using hematoxylin and eosin (H&E) staining, serum levels of pro-inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA), and fecal samples were collected and analyzed using 16S rDNA sequencing.

Results
The serum levels of inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, were significantly increased in rats after the CLP procedure, but were significantly decreased in rats treated with ADMSCs. Histological evaluation of the rat lungs yielded results consistent with the changes in IL-6 levels among all groups. Treatment with ADMSCs significantly increased the diversity of the gut microbiota in rats with sepsis. The principal coordinates analysis (PCoA) results showed that there was a significant difference between the gut microbiota of the CLP-ADMSCs group and that of the CLP group. In rats with sepsis, the proportion of Escherichia–Shigella (P = 0.01) related to lipopolysaccharide production increased, and the proportion of Akkermansia (P = 0.02) related to the regulation of intestinal mucosal thickness and the maintenance of intestinal barrier function decreased. These changes in the gut microbiota break the energy balance, aggravate inflammatory reactions, reduce intestinal barrier functions, and promote the translocation of intestinal bacteria. Intervention with ADMSCs increased the proportion of beneficial bacteria, reduced the proportion of harmful bacteria, and normalized the gut microbiota.

Conclusions
Therapeutically administered ADMSCs ameliorate CLP-induced ALI and improves gut microbiota, which provides a potential therapeutic mechanism for ADMSCs in the treatment of sepsis.
Double sperm cloning (DSC) is a promising strategy in mammalian genetic engineering and stem cell research
Authors: Zhang Zhi-ping , Zhang Jun-tao , Huang Shu-cheng , He Xiu-yuan , Deng Li-xin 
Published: September 2020

AbstractEmbryonic stem cells (ESCs) derived from somatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) are promising tools for meeting the personalized requirements of regenerative medicine. However, some obstacles need to be overcome before clinical trials can be undertaken. First, donor cells vary, and the reprogramming procedures are diverse, so standardization is a great obstacle regarding SCNT and iPSCs. Second, somatic cells derived from a patient may carry mitochondrial DNA mutations and exhibit telomere instability with aging or disease, and SCNT-ESCs and iPSCs retain the epigenetic memory or epigenetic modification errors. Third, reprogramming efficiency has remained low. Therefore, in addition to improving their success rate, other alternatives for producing ESCs should be explored. Producing androgenetic diploid embryos could be an outstanding strategy; androgenic diploid embryos are produced through double sperm cloning (DSC), in which two capacitated sperms (XY or XX, sorted by flow cytometer) are injected into a denucleated oocyte by intracytoplasmic sperm injection (ICSI) to reconstruct embryo and derive DSC-ESCs. This process could avoid some potential issues, such as mitochondrial interference, telomere shortening, and somatic epigenetic memory, all of which accompany somatic donor cells. Oocytes are naturally activated by sperm, which is unlike the artificial activation that occurs in SCNT. The procedure is simple and practical and can be easily standardized. In addition, DSC-ESCs can overcome ethical concerns and resolve immunological response matching with sperm providers. Certainly, some challenges must be faced regarding imprinted genes, epigenetics, X chromosome inactivation, and dosage compensation. In mice, DSC-ESCs have been produced and have shown excellent differentiation ability. Therefore, the many advantages of DSC make the study of this process worthwhile for regenerative medicine and animal breeding.