bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic effect of autologous bone grafting with adjuvant bone morphogenetic protein on long bone nonunion: a systematic review and meta-analysis
Authors: Xie Chengxin , Wang Chenglong , Huang Yu , Li Qinglong , Tian Xin , Huang Wenwen , Yin Dong 
Published: June 2022

Abstract
Background
The recombinant human bone morphogenetic protein (rhBMP) is a common graft substitute for treating cases of long bone nonunion. However, the feasibility of combining an autologous bone graft (ABG) with rhBMPs remains uncertain. Thus, this systematic review and meta-analysis aimed to evaluate the synergistic effect of ABG and rhBMPs on the healing of long bone nonunion.

Methods
A systematic literature search was performed on PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. Statistical analyses were performed using Stata 12.0.

Results
Of the 202 citations, five studies involving a total of 394 cases met the eligibility criteria; thus, they were included in this study. The pooled data revealed no significant differences among the groups in terms of postoperative healing rate (risk ratio [RR] = 1.01, 95% confidence interval [CI] = 0.96–1.06, P = 0.744), healing time (standardised mean difference =  − 0.20, 95% CI = − 0.95–0.56, P = 0.610), and pain (RR = 1.44, 95% CI = 0.25–8.29, P = 0.681). The combination of ABG and rhBMPs resulted in good limb function (RR = 1.31, 95% CI = 1.04–1.66, P = 0.023).

Conclusions
The combination of ABG and rhBMPs did not result in the healing of long bone nonunion and pain reduction. Nevertheless, it conferred good limb function. Thus, the findings in this study are insufficient to support the use of rhBMPs as an adjuvant to ABG.
Conservative therapy versus arthroscopic surgery of femoroacetabular impingement syndrome (FAI): a systematic review and meta-analysis
Authors: Zhu Yanlin , Su Peng , Xu Tianhao , Zhang Lei , Fu Weili 
Published: June 2022

Abstract
Purpose
FAI (femoroacetabular impingement syndrome) is a common cause of hip pain, resulting in a decreased life quality. This study aims to compare the postoperative clinical outcome between arthroscopic surgery (AT) and conservative treatment (CT).

Method
The six studies were selected from PubMed, Embase and OVID database. The data were extracted and analyzed by RevMan5.3. Mean differences and 95% confidence intervals were calculated. RevMan5.3 was used to assess the risk of bias.

Result
Six observational studies were assessed. The methodological quality of the trials indicated five of six studies had a low risk of bias and one article had a high risk of bias. The differences were statistically significant between AT and CT for HOS (follow-up for 6 months), iHOT-33 (follow-up for 6 months) improvement, iHOT-33 (follow-up for 12 months) improvement, iHOT-33 (follow-up for 12 months), EQ-5D-5L index score (follow-up for 12 months) and AT showed higher benefits than CT. Meanwhile no statistically significant were found in iHOT-33 (follow-up for 6 months), EQ-5D-5L index score (follow-up for 6 months), EQ5D-VAS (follow-up for 6 months) and EQ5D-VAS (follow-up for 12 months).

Conclusion
AT and CT both can have clinical effects when facing FAI. In our meta-analysis, hip arthroscopy is statistically superior to conservative treatment in both long-term and short-term effects.
A case-driven hypothesis for multi-stage crack growth mechanism in fourth-generation ceramic head fracture
Authors: Lucchini Stefano , Baleani Massimiliano , Giardina Federico , Martelli Andrea , Castagnini Francesco , Bordini Barbara , Traina Francesco 
Published: June 2022

Abstract
Background
Ceramic bearings are used in total hip arthroplasty due to their excellent wear behaviour and biocompatibility. The major concern related to their use is material brittleness, which significantly impacts on the risk of fracture of ceramic components. Fracture toughness improvement has contributed to the decrease in fracture rate, at least of the prosthetic head. However, the root cause behind these rare events is not fully understood. This study evaluated head fracture occurrence in a sizeable cohort of patients with fourth-generation ceramic-on-ceramic implants and described the circumstances reported by patients in the rare cases of head fracture.

Methods
The clinical survivorship of 29,495 hip prostheses, with fourth-generation ceramic bearings, was determined using data from a joint replacement registry. The average follow-up period was 5.2 years (range 0.1–15.6). Retrieval analysis was performed in one case for which the ceramic components were available.

Results
Clinical outcomes confirmed the extremely low fracture rate of fourth-generation ceramic heads: only two out of 29,495 heads fractured. The two fractures, both involving 36 mm heads, occurred without a concurrent or previous remarkable trauma. Considering the feature of the fractured head, a multi-stage crack growth mechanism has been hypothesized to occur following damage at the head–neck taper interface.

Conclusions
Surgeons must continue to pay attention to the assembly of the femoral head: achieving a proper head seating on a clean taper is a prerequisite to decrease the risk of occurrence of any damage process within head–neck junction, which may cause high stress concentration at the contact surface, promoting crack nucleation and propagation even in toughened ceramics.
Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape
Authors: Wu Qinghua , You Li , Nepovimova Eugenie , Heger Zbynek , Wu Wenda , Kuca Kamil , Adam Vojtech 
Published: June 2022

AbstractHypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia and hypoxia-inducible factors (HIFs) 1 and 2 alpha (HIF1A and HIF2A) are involved in tumor immune escape. Under hypoxia, activation of HIF1A induces a series of signaling events, including through programmed death receptor-1/programmed death ligand-1. Moreover, hypoxia triggers shedding of complex class I chain-associated molecules through nitric oxide signaling impairment to disrupt immune surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances tumor immune escape via increased tumor cell-platelet binding. HIF2A upregulates stem cell factor expression to recruit tumor-infiltrating mast cells and increase levels of cytokines interleukin-10 and transforming growth factor-β, resulting in an immunosuppressive tumor microenvironment. Additionally, HIF1A upregulates expression of tumor-associated long noncoding RNAs and suppresses immune cell function, enabling tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested.
Circ_0004087 interaction with SND1 promotes docetaxel resistance in prostate cancer by boosting the mitosis error correction mechanism
Authors: Chen Liang , Song Yarong , Hou Teng , Li Xuexiang , Cheng Lulin , Li Yunxue , Xing Yifei 
Published: June 2022

Abstract
Background
Acquisition of the chemoresistance to docetaxel (DTX), a microtubule-targeting agent, has been a huge obstacle in treatment for metastatic castration-resistant prostate cancer (mCRPC). Recently, strategies targeting the mitosis error correction mechanism including chromosomal passenger complex (CPC) were reported to reverse the resistance to microtubule-targeting anticancer agents. Meanwhile, accumulating evidence indicated the important roles of circRNAs in DTX resistance of prostate cancer (PCa). However, whether circRNAs could regulate DTX chemosensitivity by affecting the mitosis error correction mechanism remains unclear.

Methods
Expression patterns of circ_0004087 and BUB1 were determined through mining the public circRNA datasets and performing western blot and qRT-PCR assays. Agarose gel electrophoresis, Sanger sequencing, and RNase R treatment were conducted to examine the circular characteristics of circ_0004087. CircRNA pull-down, mass spectrometry analysis, Co-IP, and dual-luciferase reporter assays were performed to uncover the interaction among circ_0004087, SND1, and MYB. The effects of circ_0004087 and BUB1 on docetaxel-based chemotherapy were explored by flow cytometry and in vivo drug studies upon xenografted tumor model.

Results
In the present study, we revealed the profound interaction between a novel circRNA, circ_0004087, and the mitosis error correction mechanism. Mechanistically, circ_0004087 binding with transcriptional coactivator SND1 could stimulate the transactivation of MYB and enhance the expression of downstream target BUB1. In turn, elevated BUB1 expression further recruited CPC to centromeres and guaranteed the error-free mitosis of PCa cells. Biologically, the overexpression of circ_0004087 conferred while the knockdown impaired DTX resistance in PCa cells.

Conclusions
Our study uncovered the crucial role of circ_0004087/SND1/MYB/BUB1 axis in modulating the error mitosis correction mechanism and DTX chemoresistance, suggesting that circ_0004087 may serve as a valuable prognostic biomarker and a potential therapeutic target in DTX-resistant PCa patients.
Evolutionary perspectives, heterogeneity and ovarian cancer: a complicated tale from past to present
Authors: Achimas-Cadariu Patriciu , Kubelac Paul , Irimie Alexandru , Berindan-Neagoe Ioana , Rühli Frank 
Published: June 2022

AbstractOvarian cancer is composed of a complex system of cells best described by features such as clonal evolution, spatial and temporal genetic heterogeneity, and development of drug resistance, thus making it the most lethal gynecologic cancer. Seminal work on cancer as an evolutionary process has a long history; however, recent cost-effective large-scale molecular profiling has started to provide novel insights coupled with the development of mathematical algorithms. In the current review, we have systematically searched for articles that focused on the clonal evolution of ovarian cancer to offer the whole landscape of research that has been done and highlight future research avenues given its characteristic features and connections to evolutionary biology.
Characteristics of the cancer stem cell niche and therapeutic strategies
Authors: Ju Feng , Atyah Manar M. , Horstmann Nellie , Gul Sheraz , Vago Razi , Bruns Christiane J. , Zhao Yue , Dong Qiong-Zhu , Ren Ning 
Published: June 2022

AbstractDistinct regions harboring cancer stem cells (CSCs) have been identified within the microenvironment of various tumors, and as in the case of their healthy counterparts, these anatomical regions are termed “niche.” Thus far, a large volume of studies have shown that CSC niches take part in the maintenance, regulation of renewal, differentiation and plasticity of CSCs. In this review, we summarize and discuss the latest findings regarding CSC niche morphology, physical terrain, main signaling pathways and interactions within them. The cellular and molecular components of CSCs also involve genetic and epigenetic modulations that mediate and support their maintenance, ultimately leading to cancer progression. It suggests that the crosstalk between CSCs and their niche plays an important role regarding therapy resistance and recurrence. In addition, we updated diverse therapeutic strategies in different cancers in basic research and clinical trials in this review. Understanding the complex heterogeneity of CSC niches is a necessary pre-requisite for designing superior therapeutic strategies to target CSC-specific factors and/or components of the CSC niche.
Human amniotic mesenchymal stem cells-derived IGFBP-3, DKK-3, and DKK-1 attenuate liver fibrosis through inhibiting hepatic stellate cell activation by blocking Wnt/β-catenin signaling pathway in mice
Authors: Liu Quan-Wen , Ying Yan-Min , Zhou Jia-Xin , Zhang Wen-Jie , Liu Zhao-xiao , Jia Bing-Bing , Gu Hao-Cheng , Zhao Chu-Yu , Guan Xiao-Hui , Deng Ke-Yu , Xin Hong-Bo 
Published: June 2022

Abstract
Background
Liver fibrosis is an outcome of restoring process in chronic liver injury. Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating liver fibrosis. This study aimed to explore the effect and mechanism of hAMSCs on liver fibrosis.

Methods
hAMSCs were transplanted into carbon tetrachloride (CCl4)-induced liver fibrosis mice via tail vein, and the effects of hAMSCs on hepatic fibrosis were assessed. The effects of hAMSCs and hAMSCs conditional medium (CM) on the activation of hepatic stellate cells (HSCs) were investigated in vivo and in vitro. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may inhibit the activation of HSCs. Finally, the underlying mechanisms were explored by assessing IGF-1R/PI3K/AKT and GSK3β/β-catenin signaling pathways in the activated HSCs (LX-2) with hAMSCs and hAMSCs transfected with corresponding siRNAs.

Results
Our results showed that hAMSCs possessed the characterizations of mesenchymal stem cells. hAMSCs significantly reduced liver fibrosis and improved liver function in mice by inhibiting HSCs activation in vivo. Both hAMSCs and hAMSC-CM remarkably inhibited the collagen deposition and activation of LX-2 cells in vitro. Antibody array assay showed that insulin-like growth factor binding protein-3 (IGFBP-3), Dickkopf-3 (DKK-3), and Dickkopf-1 (DKK-1) were highly expressed in the co-culture group and hAMSC-CM group compared with LX-2 group. Western blot assay demonstrated that IGFBP-3, DKK-3, and DKK-1 derived from hAMSCs inhibit LX-2 cell activation through blocking canonical Wnt signaling pathway.

Conclusions
Our results demonstrated that IGFBP-3, Dkk3, and DKK-1 secreted by hAMSCs attenuated liver fibrosis in mice through inhibiting HSCs activation via depression of Wnt/β-catenin signaling pathway, suggesting that hAMSCs or hAMSC-CM provides an alternative therapeutic approach for the treatment of liver fibrosis.
Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model
Authors: Chen Ying-Cheng , Lan Ying-Wei , Huang Shiaw-Min , Yen Chih-Ching , Chen Wei , Wu Wan-Ju , Staniczek Theresa , Chong Kowit-Yu , Chen Chuan-Mu 
Published: June 2022

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in various cancers and they are a strong candidate for treating PDAC.

Methods
To evaluate the effects of hAFMSCs on human pancreatic carcinoma cells (PANC1, AsPC1 and BxPC3 cell lines) and the possible mechanism involved, an in vitro cell coculture system was used. A PANC1 orthotopic xenograft mouse model was established and hAFMSCs were injected intravenously at 4 weeks post-xenograft.

Results
An in vitro coculture assay showed that hAFMSCs inhibited PANC1 cell proliferation by inducing S phase cell cycle arrest and increased cell apoptosis in a time-dependent manner. In PANC1 cells, hAFMSCs caused the downregulation of Cyclin A and Cyclin B1 as well as the upregulation of p21 (CDKN1A) at 24 h post coculture. The upregulation of pro-apoptotic factors Caspase-3/-8 and Bax at 24 h post coculture reduced the migration and invasion ability of PANC1 cells through inhibiting the epithelial-mesenchymal transition (EMT) process. In a PANC1 orthotopic xenograft mouse model, a single injection of hAFMSCs showed significant tumor growth inhibition with evidence of the modulation of cell cycle and pro-apoptotic regulatory genes and various genes involved in matrix metallopeptidase 7 (MMP7) signaling-triggered EMT process. Histopathological staining showed lower Ki67 levels in tumors from hAFMSCs-treated mice.

Conclusions
Our data demonstrated that hAFMSCs strongly inhibit PDAC cell proliferation, tumor growth and invasion, possibly by altering cell cycle arrest and MMP7 signaling-triggered EMT.
Integrating spatial transcriptomics with single-cell transcriptomics reveals a spatiotemporal gene landscape of the human developing kidney
Authors: Wu Hongwei , Liu Fanna , Shangguan Yu , Yang Yane , Shi Wei , Hu Wenlong , Zeng Zhipeng , Hu Nan , Zhang Xinzhou , Hocher Berthold , Tang Donge , Yin Lianghong , Dai Yong 
Published: June 2022

Abstract
Background
Research on spatiotemporal gene landscape can provide insights into the spatial characteristics of human kidney development and facilitate kidney organoid cultivation. Here, we profiled the spatiotemporal gene programs of the human embryonic kidneys at 9 and 18 post-conception weeks (PCW) by integrating the application of microarray-based spatial transcriptomics and single-cell transcriptomics.

Results
We mapped transcriptomic signatures of scRNA-seq cell types upon the 9 and 18 PCW kidney sections based on cell-type deconvolution and multimodal intersection analyses, depicting a spatial landscape of developing cell subpopulations. We established the gene characteristics in the medullary regions and revealed a strong mitochondrial oxidative phosphorylation and glycolysis activity in the deeper medullary region. We also built a regulatory network centered on GDNF-ETV4 for nephrogenic niche development based on the weighted gene co-expression network analysis and highlighted the key roles of Wnt, FGF, and JAG1-Notch2 signaling in maintaining renal branching morphogenesis.

Conclusions
Our findings obtained by this spatiotemporal gene program are expected to improve the current understanding of kidney development.
The evidence synthesis and meta-analysis in R conference (ESMARConf): levelling the playing field of conference accessibility and equitability
Authors: Haddaway Neal R. , Bannach-Brown Alexandra , Grainger Matthew J. , Hamilton W. Kyle , Hennessy Emily A. , Keenan Ciara , Pritchard Chris C. , Stojanova Jana 
Published: June 2022

AbstractRigorous evidence is vital in all disciplines to ensure efficient, appropriate, and fit-for-purpose decision-making with minimised risk of unintended harm. To date, however, disciplines have been slow to share evidence synthesis frameworks, best practices, and tools amongst one another. Recent progress in collaborative digital and programmatic frameworks, such as the free and Open Source software R, have significantly expanded the opportunities for development of free-to-use, incrementally improvable, community driven tools to support evidence synthesis (e.g. EviAtlas, robvis, PRISMA2020 flow diagrams and metadat). Despite this, evidence synthesis (and meta-analysis) practitioners and methodologists who make use of R remain relatively disconnected from one another. Here, we report on a new virtual conference for evidence synthesis and meta-analysis in the R programming environment (ESMARConf) that aims to connect these communities. By designing an entirely free and online conference from scratch, we have been able to focus efforts on maximising accessibility and equity—making these core missions for our new community of practice. As a community of practice, ESMARConf builds on the success and groundwork of the broader R community and systematic review coordinating bodies (e.g. Cochrane), but fills an important niche. ESMARConf aims to maximise accessibility and equity of participants across regions, contexts, and social backgrounds, forging a level playing field in a digital, connected, and online future of evidence synthesis. We believe that everyone should have the same access to participation and involvement, and we believe ESMARConf provides a vital opportunity to push for equitability across disciplines, regions, and personal situations.
On boundary value problems of Caputo fractional differential equation of variable order via Kuratowski MNC technique
Authors: Benkerrouche Amar , Souid Mohammed Said , Jarad Fahd , Hakem Ali 
Published: June 2022

AbstractIn this manuscript, we examine both the existence and the stability of solutions to the boundary value problem of Caputo fractional differential equations of variable order by converting it into an equivalent standard Caputo boundary value problem of the fractional constant order with the help of the generalized intervals and the piece-wise constant functions. All results in this study are established using Darbo’s fixed point theorem combined with the Kuratowski measure of noncompactness. Further, the Ulam–Hyers stability of the given problem is examined; and finally, we construct an example to illustrate the validity of the observed results.
Tolerance of biofilm of a carbapenem-resistant Klebsiella pneumoniae involved in a duodenoscopy-associated outbreak to the disinfectant used in reprocessing
Authors: Brunke Melanie S. , Konrat Katharina , Schaudinn Christoph , Piening Brar , Pfeifer Yvonne , Becker Laura , Schwebke Ingeborg , Arvand Mardjan 
Published: June 2022

Abstract
Background
One possible transmission route for nosocomial pathogens is contaminated medical devices. Formation of biofilms can exacerbate the problem. We report on a carbapenemase-producing Klebsiella pneumoniae that had caused an outbreak linked to contaminated duodenoscopes. To determine whether increased tolerance to disinfectants may have contributed to the outbreak, we investigated the susceptibility of the outbreak strain to disinfectants commonly used for duodenoscope reprocessing. Disinfection efficacy was tested on planktonic bacteria and on biofilm.

Methods
Disinfectant efficacy testing was performed for planktonic bacteria according to EN standards 13727 and 14561 and for biofilm using the Bead Assay for Biofilms. Disinfection was defined as ≥ 5log10 reduction in recoverable colony forming units (CFU).

Results
The outbreak strain was an OXA-48 carbapenemase-producing K. pneumoniae of sequence type 101. We found a slightly increased tolerance of the outbreak strain in planktonic form to peracetic acid (PAA), but not to other disinfectants tested. Since PAA was the disinfectant used for duodenoscope reprocessing, we investigated the effect of PAA on biofilm of the outbreak strain. Remarkably, disinfection of biofilm of the outbreak strain could not be achieved by the standard PAA concentration used for duodenoscope reprocessing at the time of outbreak. An increased tolerance to PAA was not observed in a K. pneumoniae type strain tested in parallel.

Conclusions
Biofilm of the K. pneumoniae outbreak strain was tolerant to standard disinfection during duodenoscope reprocessing. This study establishes for the first time a direct link between biofilm formation, increased tolerance to disinfectants, reprocessing failure of duodenoscopes and nosocomial transmission of carbapenem-resistant K. pneumoniae.