bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse events in women giving birth in a labor ward: a retrospective record review study
Authors: Skoogh Annika , Hall-Lord Marie Louise , Bååth Carina , Bojö Ann-Kristin Sandin 
Published: October 2021

Abstract
Background
Childbirth could negatively affect the woman’s health through adverse events. To prevent adverse events and increase patient safety it is important to detect and learn from them. The aim of the study was to describe adverse events, including the preventability and severity of harm during planned vaginal births, in women giving birth in the labor ward.

Methods
The study had a descriptive design with a retrospective birth record review to assess the preventability of adverse events using the Swedish version of the Global Trigger Tool. The setting was a labor ward in Sweden with low-risk and risk childbirths. Descriptive statistics, Pearson’s Chi-square test and Student’s t-test were used.

Results
A total of 38 adverse events (12.2%) were identified in 311 reviewed birth records. Of these, 28 (73.7%) were assessed as preventable. Third- or fourth-degree lacerations and distended urinary bladder were most prevalent together with anesthesia-related adverse events. The majority of the adverse events were classified into the harm categories of ‘prolonged hospital care’ (63.2%) and ‘temporary harm’ (31.6%). No permanent harm were identified, but over two-thirds of the adverse events were assessed as preventable.

Conclusions
This first study using Global Trigger Tool in a labor ward in Sweden identified a higher incidence of adverse events than previous studies in obstetric care. No permanent patient harm was found, but over two-thirds of the adverse events were assessed as preventable. The results draw particular attention to 3rd-or 4th-degree lacerations, distended urinary bladder and anesthesia-related adverse events. The feedback on identified adverse events should be used for systematic quality improvement and clinical recommendations how to prevent adverse events must be implemented.
Working in a minefield; Nurses’ strategies for handling medicine administration interruptions in hospitals, -a qualtiative interview study
Authors: Alteren Johanne , Hermstad Marit , Nerdal Lisbeth , Jordan Sue 
Published: October 2021

Abstract
Background
Administering medicines is one of the most high-risk tasks in health care. However, nurses are frequently interrupted during medicine administration, which jeopardises patient safety. Few studies have examined nurses’ experiences and the strategies they adopt to cope with interruptions during medicine rounds. This paper identifies nurses’ strategies for handling and reducing interruptions and ensuring safety during medicine rounds, within the confines of the hospitals’ organisational systems.

Methods
This descriptive and exploratory research study was undertaken with experienced nurses in Norwegian hospitals in 2015 using semi-structured interviews. Interviews were designed to elicit experiences and strategies used for handling interruptions to medicine rounds. Data were analysed using qualitative content analysis based on inductive reasoning to identify meaningful subjects and reach an interpretive level of understanding regarding nurses’ experiences.

Results
All 19 senior nurses who were approached were interviewed. From 644 condensed meaning units, we identified eight interpretative units and three themes: ‘working in environments of interruptions’, ‘personal coping strategies’, and ‘management-related strategies’. Nurses’ working environments were characterised by interruptions and distractions, which often threatened patient safety. To handle this unpredictability and maintain ward organisation, nurses developed their own personal strategies to overcome inherent problems with their working conditions, the absence of effective management, and colleagues’ reluctance to assume responsibility for minimising interruptions.

Conclusions
Administration of medicines in hospitals can be described as ‘working in a minefield’. Our findings indicate that the hospital management, in cooperation with nurses and other healthcare professionals, should take responsibility for improving the routine process of medicine administration by minimising avoidable interruptions. Patient safety can be improved when the hospital management takes steps to protect nurses’ work environments and assumes responsibility for resolving these challenges.
Short single-stranded DNAs with putative non-canonical structures comprise a new class of plasma cell-free DNA
Authors: Hisano Osamu , Ito Takashi , Miura Fumihito 
Published: October 2021

AbstractBackgroundCell-free DNA (cfDNA), which is extracellular DNA present in the circulating plasma and other body fluids, is currently investigated as a minimally invasive, highly informative biomarker. While nucleosome-sized cfDNA fragments have been investigated intensively, shorter DNA fragments in the plasma have not been studied due to several technical limitations.ResultsWe aimed to investigate the existence of shorter cfDNA fragments in the blood. Using an improved cfDNA purification protocol and a 3′-end-labeling method, we found DNA fragments of approximately 50 nucleotides in length in the human plasma, present at a molar concentration comparable to that of nucleosome-sized fragments. Unfortunately, these short fragments cannot be recovered by widely used cfDNA isolation methods. In addition, they are composed of single-stranded DNA (ssDNA), thus escaping detection in previous studies. Therefore, we established a library-preparation protocol based on our unique ssDNA ligation technique and applied it to the isolated cfDNA. Deep sequencing of these libraries revealed that the short fragments are derived from hundreds of thousands of genomic sites in open chromatin regions and enriched with transcription factor-binding sites. Remarkably, antisense strands of putative G-quadruplex motifs occupy as much as one-third of the peaks by these short fragments.ConclusionsWe propose a new class of plasma cfDNA composed of short single-stranded fragments that potentially form non-canonical DNA structures.
Genetic and process engineering strategies for enhanced recombinant N-glycoprotein production in bacteria
Authors: Pratama Fenryco , Linton Dennis , Dixon Neil 
Published: October 2021

Abstract
Background
The production of N-linked glycoproteins in genetically amenable bacterial hosts offers great potential for reduced cost, faster/simpler bioprocesses, greater customisation, and utility for distributed manufacturing of glycoconjugate vaccines and glycoprotein therapeutics. Efforts to optimize production hosts have included heterologous expression of glycosylation enzymes, metabolic engineering, use of alternative secretion pathways, and attenuation of gene expression. However, a major bottleneck to enhance glycosylation efficiency, which limits the utility of the other improvements, is the impact of target protein sequon accessibility during glycosylation.

Results
Here, we explore a series of genetic and process engineering strategies to increase recombinant N-linked glycosylation, mediated by the Campylobacter-derived PglB oligosaccharyltransferase in Escherichia coli. Strategies include increasing membrane residency time of the target protein by modifying the cleavage site of its secretion signal, and modulating protein folding in the periplasm by use of oxygen limitation or strains with compromised oxidoreductase or disulphide-bond isomerase activity. These approaches achieve up to twofold improvement in glycosylation efficiency. Furthermore, we also demonstrate that supplementation with the chemical oxidant cystine enhances the titre of glycoprotein in an oxidoreductase knockout strain by improving total protein production and cell fitness, while at the same time maintaining higher levels of glycosylation efficiency.

Conclusions
In this study, we demonstrate that improved protein glycosylation in the heterologous host could be achieved by mimicking the coordination between protein translocation, folding and glycosylation observed in native host such as Campylobacter jejuni and mammalian cells. Furthermore, it provides insight into strain engineering and bioprocess strategies, to improve glycoprotein yield and titre, and to avoid physiological burden of unfolded protein stress upon cell growth. The process and genetic strategies identified herein will inform further optimisation and scale-up of heterologous recombinant N-glycoprotein production.
In vivo analysis of hip joint loading on Nordic walking novices
Authors: Palmowski Yannick , Popovic Srdan , Schuster Simone G. , Hardt Sebastian , Damm Philipp 
Published: October 2021

AbstractObjectiveTo evaluate the influence of Nordic walking (NW) on hip joint loads in order to determine whether it can be safely performed during postoperative physiotherapy in patients after orthopeadic surgery of the hip.MethodsInternal hip joint loads were directly measured in vivo in 6 patients using instrumented hip prostheses during NW and ordinary walking (OW). All patients received training in two different NW techniques (double-poling and the diagonal technique) by a certified NW instructor. Measurements were conducted on a treadmill at a speed of 4 km/h on level ground, at 10% inclination and at 10% slope as well as on a level lawn at a self chosen comfortable speed. Resultant contact force (Fres), bending moment (Mbend) and torsional torque (Mtors) were compared between NW and OW as well as between both NW techniques.ResultsJoint loads showed a double peak pattern during all setups. Neither NW technique significantly influenced hip joint loads at the time of the first load peak during contralateral toe-off (CTO), which was also the absolute load peak, in comparison to OW. Compared to OW, double-poling significantly reducedFresandMbendat the time of the second load peak during the contralateral heel strike (CHS) on level ground both on the treadmill (− 6% and − 7%, respectively) and on the lawn (− 7% and − 9%). At 10% inclination, the diagonal technique increasedFresandMbendat CHS (by + 6% and + 7%), but did not increase the absolute load peak at CTO.ConclusionJoint loads during NW are comparable to those of OW. Therefore, NW can be considered a low-impact activity and seems to be safe for patients that are allowed full weight bearing, e.g. during postoperative rehabilitation after THA.
VEGF-A/VEGFR-1 signalling and chemotherapy-induced neuropathic pain: therapeutic potential of a novel anti-VEGFR-1 monoclonal antibody
Authors: Micheli Laura , Parisio Carmen , Lucarini Elena , Vona Alessia , Toti Alessandra , Pacini Alessandra , Mello Tommaso , Boccella Serena , Ricciardi Flavia , Maione Sabatino , Graziani Grazia , Lacal Pedro Miguel , Failli Paola , Ghelardini Carla , Di Cesare Mannelli Lorenzo 
Published: October 2021

Abstract
Background
Neuropathic pain is a clinically relevant adverse effect of several anticancer drugs that markedly impairs patients’ quality of life and frequently leads to dose reduction or therapy discontinuation. The poor knowledge about the mechanisms involved in neuropathy development and pain chronicization, and the lack of effective therapies, make treatment of chemotherapy-induced neuropathic pain an unmet medical need. In this context, the vascular endothelial growth factor A (VEGF-A) has emerged as a candidate neuropathy hallmark and its decrease has been related to pain relief. In the present study, we have investigated the role of VEGF-A and its receptors, VEGFR-1 and VEGFR-2, in pain signalling and in chemotherapy-induced neuropathy establishment as well as the therapeutic potential of receptor blockade in the management of pain.

Methods
Behavioural and electrophysiological analyses were performed in an in vivo murine model, by using selective receptor agonists, blocking monoclonal antibodies or siRNA-mediated silencing of VEGF-A and VEGFRs. Expression of VEGF-A and VEGFR-1 in astrocytes and neurons was detected by immunofluorescence staining and confocal microscopy analysis.

Results
In mice, the intrathecal infusion of VEGF-A (VEGF165 isoforms) induced a dose-dependent noxious hypersensitivity and this effect was mediated by VEGFR-1. Consistently, electrophysiological studies indicated that VEGF-A strongly stimulated the spinal nociceptive neurons activity through VEGFR-1. In the dorsal horn of the spinal cord of animals affected by oxaliplatin-induced neuropathy, VEGF-A expression was increased in astrocytes while VEGFR-1 was mainly detected in neurons, suggesting a VEGF-A/VEGFR-1-mediated astrocyte-neuron cross-talk in neuropathic pain pathophysiology. Accordingly, the selective knockdown of astrocytic VEGF-A by intraspinal injection of shRNAmir blocked the development of oxaliplatin-induced neuropathic hyperalgesia and allodynia. Interestingly, both intrathecal and systemic administration of the novel anti-VEGFR-1 monoclonal antibody D16F7, endowed with anti-angiogenic and antitumor properties, reverted oxaliplatin-induced neuropathic pain. Besides, D16F7 effectively relieved hypersensitivity induced by other neurotoxic chemotherapeutic agents, such as paclitaxel and vincristine.

Conclusions
These data strongly support the role of the VEGF-A/VEGFR-1 system in mediating chemotherapy-induced neuropathic pain at the central nervous system level. Thus, treatment with the anti-VEGFR-1 mAb D16F7, besides exerting antitumor activity, might result in the additional advantage of attenuating neuropathic pain when combined with neurotoxic anticancer agents.
KrasG12D induces changes in chromatin territories that differentially impact early nuclear reprogramming in pancreatic cells
Authors: Mathison Angela J. , Kerketta Romica , de Assuncao Thiago Milech , Leverence Elise , Zeighami Atefeh , Urrutia Guillermo , Stodola Timothy J. , di Magliano Marina Pasca , Iovanna Juan L. , Zimmermann Michael T. , Lomberk Gwen , Urrutia Raul 
Published: October 2021

Abstract
Background
Pancreatic ductal adenocarcinoma initiation is most frequently caused by Kras mutations.

Results
Here, we apply biological, biochemical, and network biology methods to validate GEMM-derived cell models using inducible KrasG12D expression. We describe the time-dependent, chromatin remodeling program that impacts function during early oncogenic signaling. We find that the KrasG12D-induced transcriptional response is dominated by downregulated expression concordant with layers of epigenetic events. More open chromatin characterizes the ATAC-seq profile associated with a smaller group of upregulated genes and epigenetic marks. RRBS demonstrates that promoter hypermethylation does not account for the silencing of the extensive gene promoter network. Moreover, ChIP-Seq reveals that heterochromatin reorganization plays little role in this early transcriptional program. Notably, both gene activation and silencing primarily depend on the marking of genes with a combination of H3K27ac, H3K4me3, and H3K36me3. Indeed, integrated modeling of all these datasets shows that KrasG12D regulates its transcriptional program primarily through unique super-enhancers and enhancers, and marking specific gene promoters and bodies. We also report chromatin remodeling across genomic areas that, although not contributing directly to cis-gene transcription, are likely important for KrasG12D functions.

Conclusions
In summary, we report a comprehensive, time-dependent, and coordinated early epigenomic program for KrasG12D in pancreatic cells, which is mechanistically relevant to understanding chromatin remodeling events underlying transcriptional outcomes needed for the function of this oncogene.
Circ_0067680 expedites the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells through miR-4429/CTNNB1/Wnt/β-catenin pathway
Authors: Huang Yuansheng , Wan Su , Yang Min 
Published: October 2021

Abstract
Background
Human bone marrow-derived mesenchymal stem cells (hBMSCs) are the primary source of osteoblasts in vivo. Emerging literatures have unveiled that circular RNAs (circRNAs) are actively drawn in the osteogenic differentiation of mesenchymal stem cells (MSCs). This research mainly illuminated the role of circ_0067680 as well as its regulatory mechanism in osteoblastic differentiation.

Methods
In this study, RT-qPCR was to measure the expression of circ_0067680. Functional assays were implemented to assess the role of circ_0067680 in osteogenic differentiation. Besides, RNA pull down, RIP and luciferase reporter assays were carried out to investigate the regulatory mechanism of circ_0067680.

Results
Circ_0067680, which derived from its host gene divergent protein kinase domain 2A (C3orf58), was up-regulated during osteogenic differentiation of hBMSCs. Besides, circ_0067680 deficiency impeded the osteoblastic differentiation of hBMSCs. Moreover, circ_0067680 served as a ceRNA via sequestering miR-4429 to regulate the expression of catenin beta 1 (CTNNB1), thereby activating the Wnt/β-catenin signaling pathway.

Conclusion
Circ_0067680 accelerated hBMSCs osteogenic differentiation by the miR-4429/CTNNB1/Wnt/β-catenin signaling, which might be used as a potential biomarker for osteoblastic differentiation.

Graphic abstract
YinQiSanHuang Jiedu decoction for the treatment of hepatitis B-related compensated liver cirrhosis: study protocol for a multi-center randomized controlled trial
Authors: Wu Qing-Juan , Lv Wen-Liang , Li Juan-Mei , Zhang Ting-Ting , Zhou Wen-Hui , Zhang Qiang , Wang Jiu-Chong , Wang Qing-Nan , Yao Zi-Ang , Qiang Rui , Chen Si-Tong , Zhao Xin , Liu Shuang , Cao Zheng-Min , Xu Lei , Li Gao-Hui , Chen Jing , Wang Li 
Published: October 2021

Abstract
Introduction
Hepatitis B-related compensated liver cirrhosis is related to a higher risk of hepatocellular carcinoma, and antiviral therapy is the preferred method. As the pathological mechanisms of liver fibrosis are complex, drugs developed for a single target are difficult to be effective in clinical practice, so there are no chemical drugs or biological drugs with clear efficacy available for clinical application at present. Traditional Chinese medicine is a kind of medical science that has been gradually formed during thousands of years and continuously enriched by the people of all ethnic groups in China. Traditional Chinese medicine shows curative effects in the treatment of liver diseases, especially in the field of liver fibrosis prevention and treatment. This study aims to test the integrative medicine (Chinese medicine plus antiviral therapy) effective on lowing hepatocellular carcinoma risk among patients with hepatitis-related compensated liver cirrhosis.

Methods and analysis
This is a multi-center randomized controlled trial, and a total of 5 hospitals and 802 patients will be involved in. All the subjects are randomly allocated to the YinQiSanHuang Jiedu decoction (YQSHD) group (n = 401) or the placebo group (n = 401). The YQSHD group receives YQSHD granule with entecavir (ETV), and the placebo group receives YQSHD placebo with ETV. The treatment period will last for 52 weeks, and the follow-up period for 52 ± 2 weeks. The primary outcome measure is the annual incidence of HCC. Outcomes will be assessed at baseline and after treatment. The objective of this trial is “the integrative of YQSHD with ETV reduce the annual incidence of HCC to 1%.”

Ethics and dissemination
The protocol has been approved by the Medical Ethics Committee of Guang’anmen Hospital, China (No.2019-006-KY), and the other centers in the trial will not begin recruiting until the local ethical approval has been obtained. Trial final results will be disseminated via publication.

Trial registration
Chinese Clinical Trial Registry ChiCTR1900021532. Registered on February 26, 2019
Reduction of autofluorescence in whole adult worms of Schistosoma japonicum for immunofluorescence assay
Authors: Wu Qunfeng , Feng Zheng , Hu Wei 
Published: October 2021

Abstract
Immunofluorescence assay is one of methods to understand the spatial biology by visualizing localization of biomolecules in cells and tissues. Autofluorescence, as a common phenomenon in organisms, is a background signal interfering the immunolocalization assay of schistosome biomolecules, and may lead to misinterpretation of the biomolecular function. However, applicable method for reducing the autofluorescence in Schistosoma remains unclear. In order to find a suitable method for reducing autofluorescence of schistosomes, different chemical reagents, such as Sudan black B (SBB), trypan blue (TB), copper sulfate (CuSO4), Tris-glycine (Gly), and ammonia/ethanol (AE), at different concentrations and treatment time were tested, and SBB and CuSO4 were verified for the effect of blocking autofluorescence in immunofluorescence to localize the target with anti-SjCRT antibody. By comparing the autofluorescence characteristics of different conditions, it was found that SBB, TB and CuSO4 had a certain degree of reducing autofluorescence effect, and the best effect in females was using 50 mM CuSO4 for 6 h and in males was 0.5% SBB for 6 h. Furthermore, we have applied the optimized conditions to the immunofluorescence of SjCRT protein, and the results revealed that the immunofluorescence signal of SjCRT was clearly visible without autofluorescence interference. We present an effective method to reduce autofluorescence in male and female worm of Schistosoma japonicum for immunofluorescence assay, which could be helpful to better understand biomolecular functions. Our method provides an idea for immunofluorescence assay in other flukes with autofluoresence.
Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants
Authors: Yi Chunyan , Sun Xiaoyu , Lin Yixiao , Gu Chenjian , Ding Longfei , Lu Xiao , Yang Zhuo , Zhang Yaguang , Ma Liyan , Gu Wangpeng , Qu Aidong , Zhou Xu , Li Xiuling , Xu Jianqing , Ling Zhiyang , Xie Youhua , Lu Hongzhou , Sun Bing 
Published: October 2021

Abstract
Background
The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed.

Methods
Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses.

Results
Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect.

Conclusions
Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.