bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of oral health education intervention among 12–15-year-old school children in Dharan, Nepal: a randomized controlled trial
Authors: Subedi Krishna , Shrestha Ashish , Bhagat Tarakant , Baral Dharanidhar
Published: October 2021

Background

School-aged adolescents are in particular need of preventive program to ensure positive long-term oral health and hygiene. The objective of this study was to assess the effectiveness of an oral health education (OHE) intervention on oral hygiene knowledge, attitude and practices (KAP), plaque control and gingival health among 12–15 years old school children in Dharan sub-metropolitan city, Nepal.

Methods

A randomized controlled trial was conducted with parallel study groups, comprising 12–15-year-old school children, 120 in each group. OHE was given to the experimental group at baseline, third and sixth months and to the control group after completion of the study. Interview of the participants were done using a 23-item questionnaire for assessment of oral hygiene KAP. For each question, correct answer was scored as 1 and wrong answer was scored zero. An overall composite score was then created, by adding the individual scores. Oral examination was done using mouth mirror and WHO probe to record Turesky–Gilmore–Glickman modification of the Quigley-Hein plaque index, Gingival index and Dentition status and treatment needs. Analysis was done using chi-square test for categorical data and independent t test, Mann–Whitney U test, repeated measures ANOVA and post hoc Tukey’s test for quantitative data. The level of significance was set atP < 0.05.

Results

There was 54.58% improvement in overall oral hygiene KAP in experimental group (P = 0.001) whereas no improvement was seen in control group at the end of the study. The mean plaque score was improved by 57.67% (P = 0.001) in experimental group in comparison to 4.56% in control group. Gingival index was improved by 49.90% (P = 0.001) in experimental group in comparison to 0.7% in control group. Caries experience was increased in both groups but no significant difference was seen.

Conclusions

The study concluded that oral health education was effective in improving oral hygiene KAP, plaque control and gingival health.

Trial registrationThe trial was retrospectively registered with Clinical Trial Registry India (CTRI) with identifier no. CTRI/2018/05/013985, registered on 05/21/2018. (http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=23651&EncHid=&modid=&compid=%27,%2723651det%27). Institutional Review Committee, B. P. Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal provided the ethical approval (Ref. No.: 292/074/075-IRC).
The benefit of combining curcumin, bromelain and harpagophytum to reduce inflammation in osteoarthritic synovial cells
Authors: Brochard Sybille , Pontin Julien , Bernay Benoit , Boumediene Karim , Conrozier Thierry , Baugé Catherine
Published: October 2021

Background

Osteoarthritis (OA) is the most common form of arthritis, affecting millions of people worldwide and characterised by joint pain and inflammation. It is a complex disease involving inflammatory factors and affecting the whole joint, including the synovial membrane. Since drug combination is widely used to treat chronic inflammatory diseases, a similar strategy of designing plant-derived natural products to reduce inflammation in OA joints may be of interest. In this study, we characterised the response of OA synovial cells to lipopolysaccharide (LPS) and investigated the biological action of the combination of curcumin, bromelain and harpagophytum in this original in vitro model of osteoarthritis.

Methods

Firstly, human synovial cells from OA patients were stimulated with LPS and proteomic analysis was performed. Bioinformatics analyses were performed using Cytoscape App and SkeletalVis databases. Additionally, cells were treated with curcumin, bromelain and harpagophytum alone or with the three vegetal compounds together. The gene expression involved in inflammation, pain or catabolism was determined by RT-PCR. The release of the encoded proteins by these genes and of prostaglandin E2 (PGE2) were also assayed by ELISA.

Results

Proteomic analysis demonstrated that LPS induces the expression of numerous proteins involved in the OA process in human OA synovial cells. In particular, it stimulates inflammation through the production of pro-inflammatory cytokines (Interleukin-6, IL-6), catabolism through an increase of metalloproteases (MMP-1, MMP-3, MMP-13), and the production of pain-mediating neurotrophins (Nerve Growth Factor, NGF). These increases were observed in terms of mRNA levels and protein release. LPS also increases the amount of PGE2, another inflammation and pain mediator. At the doses tested, vegetal extracts had little effect: only curcumin slightly counteracted the effects of LPS on NGF and MMP-13 mRNA, and PGE2, IL-6 and MMP-13 release. In contrast, the combination of curcumin with bromelain and harpagophytum reversed lots of effects of LPS in human OA synovial cells. It significantly reduced the gene expression and/or the release of proteins involved in catabolism (MMP-3 and -13), inflammation (IL-6) and pain (PGE2 and NGF).

Conclusion

We have shown that the stimulation of human OA synovial cells with LPS can induce protein changes similar to inflamed OA synovial tissues. In addition, using this model, we demonstrated that the combination of three vegetal compounds, namely curcumin, bromelain and harpagophytum, have anti-inflammatory and anti-catabolic effects in synovial cells and may thus reduce OA progression and related pain.
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

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

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

Background

Cell-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.

Results

We 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.

Conclusions

We 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

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

Objective

To 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.

Methods

Internal 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.

Results

Joint 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.

Conclusion

Joint 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

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

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

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

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

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

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.
Low-grade intracranial meningioma with bilateral pulmonary metastases incidentally detected postpartum: a case report and review of the literature
Authors: Mardani Parviz , Safarian Arash , Ashari Anita , Pourjafar Sarina , Anbardar Mohammad Hossein , Azarpira Negar , Vafabin Masoud , Yousefi Shahaboddin
Published: October 2021

Introduction

Meningiomas are the most commonly encountered intracranial tumors, usually showing indolent behavior. Extra-axial spreading and distant metastases are seldom detected in these tumors, and lung metastasis from a low-grade meningioma is a rare event.

Case presentation

This case report aimed to present the clinical, imaging, and pathological features of a 37-year-old Caucasian pregnant woman with bilateral lung metastases incidentally detected during preoperative workup ahead of surgery for a primary intracranial meningioma. The possible metastatic routes and risk factors of dissemination to the pulmonary circulation were discussed as well.

Conclusion

Metastasis must be considered in patients with intracranial meningiomas accompanied by venous sinus invasion and extension through the calvarium. Thorough paraclinical investigations are suggested in such cases.
Supported online cognitive behavioural therapy for bulimia nervosa: a study protocol of a randomised controlled trial
Authors: Barakat Sarah , Touyz Stephen , Maloney Danielle , Russell Janice , Hay Phillipa , Cunich Michelle , Lymer Sharyn , Kim Marcellinus , Madden Sloane , Miskovic-Wheatley Jane , Maguire Sarah
Published: October 2021

Background

Despite the availability of effective treatments for bulimia nervosa (BN), a number of barriers to accessibility exist. Examples include access to trained clinicians, the expense of treatment, geographical limitations, and personal limitations such as stigma regarding help seeking. Self-help interventions, delivered via a digital platform, have the potential to overcome treatment gaps by providing patients with standardised, evidence-based treatments that are easily accessible, cost-effective, and require minimal clinician support. Equally, it is important to examine the shortcomings of digital interventions when compared to traditional to face-to-face delivery (e.g., high dropout rates) in order to maximise the therapeutic effectiveness of online, self-help interventions.

Methods

A three-arm, multisite randomised controlled trial will be conducted in Australia examining the effectiveness and cost-effectiveness of a newly developed online self-help intervention, Binge Eating eTherapy (BEeT), in a sample of patients with full or sub-threshold BN. The BEeT program consists of 10, multimedia sessions delivering the core components of cognitive behaviour therapy. Eligible participants will be randomised to one of three groups: independent completion of BEeT as a purely self-help program, completion of BEeT alongside clinician support (in the form of weekly telemedicine sessions), or waitlist control. Assessments will take place at baseline, weekly, post-intervention, and three-month follow up. The primary outcome is frequency of objective binge episodes. Secondary outcomes include frequency of other core eating disorder behavioural symptoms and beliefs, psychological distress, and quality of life. Statistical analyses will examine treatment effectiveness, feasibility, acceptability and cost effectiveness.

Discussion

There is limited capacity within the mental health workforce in Australia to meet the demand of people seeking treatment for eating disorders. This imbalance has only worsened following outbreak of the COVID-19 pandemic. Further research is required into innovative digital modes of treatment delivery with the capacity to service mental health needs in an accessible and affordable manner. Self-help programs may also appeal to individuals who are more reluctant to engage in traditional face-to-face treatment formats. This study will provide rigorous evidence on how to diversify treatment options for individuals with BN, ensuring more people with the illness can access evidence-based treatment.

The study has been registered with the Australia New Zealand Clinical Trials Registry (ANZCTR Registration Number: ACTRN12619000123145p). Registered 22 January 2019, https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12619000123145.
Minimal residual disease in multiple myeloma: current status
Authors: Ding Hong , Xu Juan , Lin Zhimei , Huang Jingcao , Wang Fangfang , Yang Yan , Cui Yushan , Luo Hongmei , Gao Yuhan , Zhai Xinyu , Pang Weicui , Zhang Li , Zheng Yuhuan
Published: October 2021

Multiple myeloma (MM) is a treatable plasma cell cancer with no cure. Clinical evidence shows that the status of minimal residual disease (MRD) after treatment is an independent prognostic factor of MM. MRD indicates the depth of post-therapeutic remission. In this review article, we outlined the major clinical trials that have determined the prognostic value of MRD in MM. We also reviewed different methods that were used for MM MRD assessment. Most important, we reviewed our current understanding of MM MRD biology. MRD studies strongly indicate that MRD is not a uniform declination of whole MM tumor population. Rather, MM MRD exhibits unique signatures of cytogenetic aberration and gene expression profiles, unlike those of MM cells before therapy. Diagnostic high-risk MM and low-risk MM exhibited a diversity of MRD features. Clonal evaluation may occur at the MRD stage in MM. The dynamics from the diagnostic MM to MRD correlate with the disease prognosis. Lastly, on the aspect of omics, we performed data-based analysis to address the biological features underlying the course of diagnostic-to-MRD MM. To summarize, the MRD stage of disease represents a critical step in MM pathogenesis and progression. Demonstration of MM MRD biology should help us to deal with the curative difficulties.
Contextual polarity and influence mining in online social networks
Authors: Alzahrani Hassan , Acharya Subrata , Duverger Philippe , Nguyen Nam P.
Published: October 2021

Crowdsourcing is an emerging tool for collaboration and innovation platforms. Recently, crowdsourcing platforms have become a vital tool for firms to generate new ideas, especially large firms such as Dell, Microsoft, and Starbucks, Crowdsourcing provides firms with multiple advantages, notably, rapid solutions, cost savings, and a variety of novel ideas that represent the diversity inherent within a crowd. The literature on crowdsourcing is limited to empirical evidence of the advantage of crowdsourcing for businesses as an innovation strategy. In this study, Starbucks’ crowdsourcing platform, Ideas Starbucks, is examined, with three objectives: first, to determine crowdsourcing participants’ perception of the company by crowdsourcing participants when generating ideas on the platform. The second objective is to map users into a community structure to identify those more likely to produce ideas; the most promising users are grouped into the communities more likely to generate the best ideas. The third is to study the relationship between the users’ ideas’ sentiment scores and the frequency of discussions among crowdsourcing users. The results indicate that sentiment and emotion scores can be used to visualize the social interaction narrative over time. They also suggest that the fast greedy algorithm is the one best suited for community structure with a modularity on agreeable ideas of 0.53 and 8 significant communities using sentiment scores as edge weights. For disagreeable ideas, the modularity is 0.47 with 8 significant communities without edge weights. There is also a statistically significant quadratic relationship between the sentiments scores and the number of conversations between users.
Shared decision making for the initiation and continuation of dialysis: a proposal from the Japanese Society for Dialysis Therapy
Authors: Okada Kazuyoshi , Tsuchiya Ken , Sakai Ken , Kuragano Takahiro , Uchida Akiko , Tsuruya Kazuhiko , Tomo Tadashi , Hamada Chieko , Fukagawa Masafumi , Kawaguchi Yoshindo , Watanabe Yuzo , Aita Kaoruko , Ogawa Yoshitatsu , Uchino Junji , Okada Hirokazu , Koda Yutaka , Komatsu Yasuhiro , Sato Hisamitsu , Hattori Motoshi , Baba Toru , Matsumura Mamiko , Miura Hisayuki , Minakuchi Jun , Nakamoto Hidetomo ,   Committee for Updating the Proposal for Shared Decision Making on Initiation and Continuation of Dialysis, General Affairs Committee of the Japanese Society for Dialysis Therapy, Okada Kazuyoshi , Tsuchiya Ken , Sakai Ken , Kuragano Takahiro , Uchida Akiko , Tsuruya Kazuhiko , Tomo Tadashi , Hamada Chieko , Fukagawa Masafumi , Kawaguchi Yoshindo , Watanabe Yuzo , Aita Kaoruko , Ogawa Yoshitatsu , Uchino Junji , Okada Hirokazu , Koda Yutaka , Komatsu Yasuhiro , Sato Hisamitsu , Hattori Motoshi , Baba Toru , Matsumura Mamiko , Miura Hisayuki , Minakuchi Jun , Nakamoto Hidetomo
Published: October 2021

Background

In Japan, forgoing life-sustaining treatment to respect the will of patients at the terminal stage is not stipulated by law. According to the Guidelines for the Decision-Making Process in Terminal-Stage Healthcare published by the Ministry of Health, Labor and Welfare in 2007, the Japanese Society for Dialysis Therapy (JSDT) developed a proposal that was limited to patients at the terminal stage and did not explicitly cover patients with dementia. This proposal for the shared decision-making process regarding the initiation and continuation of maintenance hemodialysis was published in 2014.

Methods and results

In response to changes in social conditions, the JSDT revised the proposal in 2020 to provide guidance for the process by which the healthcare team can provide the best healthcare management and care with respect to the patient's will through advance care planning and shared decision making. For all patients with end-stage kidney disease, including those at the nonterminal stage and those with dementia, the decision-making process includes conservative kidney management.

Conclusions

The proposal is based on consensus rather than evidence-based clinical practice guidelines. The healthcare team is therefore not guaranteed to be legally exempt if the patient dies after the policies in the proposal are implemented and must respond appropriately at the discretion of each institution.
Business confidence as a strong tracker of future growth: is it driven by economic policy uncertainty and oil price shocks in the OECD countries?
Authors: Adekoya Oluwasegun B. , Oliyide Johnson A.
Published: October 2021

Business confidence matters for future growth as it relies on opinion surveys of developments in production activities, orders and stocks of finished products. Is it then affected by economic policy uncertainty and oil price asymmetries in the OECD countries? With limited evidence in the literature, we adopt the Augmented Mean Group (AMG) estimator following the evidence of cross-sectional dependence, non-stationarity and cointegration in the panel series. The full sample results show that business confidence is negatively affected by economic policy uncertainty and oil price. Moreover, the role of asymmetries  cannot be neglected as both positive and negative oil price changes show different impacts on business confidence.  The sub-sample results further reveal that the impacts of economic policy uncertainty and oil price on business confidence are higher in the Eurozone countries than in their non-Eurozone counterparts. We believe this is due to the central economic coordination and higher net-oil dependence and import status of the Eurozone countries.
Patterns of Prostate-Specific Antigen Testing and Prostate Biopsies During the COVID-19 Pandemic
Authors: Kaufman Harvey W. , Chen Zhen , Niles Justin K. , Radcliff Jeff , Fesko Yuri
Published: October 2021

PURPOSE

This study examined changes in prostate disease screening (prostatic-specific antigen [PSA] testing), prostate biopsy testing, and prostate cancer diagnoses during the COVID-19 pandemic through December 2020.

MATERIALS AND METHODS

This analysis included test results from men ≥ 40 years, without prior International Classification of Diseases-10 record of prostate cancer since January 2016, who received PSA or prostate biopsy testing at Quest Diagnostics during January 2018-December 2020. Monthly trends were evaluated for three periods: prepandemic (January 2018-February 2020), early-pandemic (March-May 2020), and late-pandemic (June-December 2020).

RESULTS

Meeting inclusion criteria were 16,365,833 PSA and 48,819 prostate biopsy results. The average monthly number of PSA tests declined from 465,187 prepandemic to 295,786 early-pandemic (36.4% decrease; P = .01) before rebounding to 483,374 (3.9% increase; P = .23) late-pandemic. The monthly average number of PSA results ≥ 50 ng/mL (23,356; 0.14% of all PSA results) dipped from 659 prepandemic to 506 early-pandemic (23.2% decrease; P = .02) and rebounded to 674 late-pandemic (2.3% increase; P = .65). The average monthly number of prostate biopsy results decreased from 1,453 prepandemic to 903 early-pandemic (37.9% decrease; P = .01) before rebounding to 1,190 late-pandemic (18.1% decrease; P = .01). The average monthly number for Gleason score ≥ 8 (6,241; 12.8% of all prostate biopsies) declined from 182 prepandemic to 130 early-pandemic (28.6% decrease; P = .02) and decreased to 161 late-pandemic (11.5% decrease; P = .02).

CONCLUSION

The findings suggest that a substantial number of prostate screening opportunities and cancer diagnoses have been missed. Efforts are needed to bring such patients back for screening and diagnostic testing and to restore appropriate care for non–COVID-19–related medical conditions.
Developmental mechanisms of sex differences: from cells to organisms
Authors: Mank Judith E. , Rideout Elizabeth J.
Published: October 2021

Male-female differences in many developmental mechanisms lead to the formation of two morphologically and physiologically distinct sexes. Although this is expected for traits with prominent differences between the sexes, such as the gonads, sex-specific processes also contribute to traits without obvious male-female differences, such as the intestine. Here, we review sex differences in developmental mechanisms that operate at several levels of biological complexity – molecular, cellular, organ and organismal – and discuss how these differences influence organ formation, function and whole-body physiology. Together, the examples we highlight show that one simple way to gain a more accurate and comprehensive understanding of animal development is to include both sexes.
Bivalves rapidly repair shells damaged by fatigue and bolster strength
Authors: Crane R. L. , Diaz Reyes J. L. , Denny M. W.
Published: October 2021

Hard external armors have to defend against a lifetime of threats yet are traditionally understood by their ability to withstand a single attack. Survival of bivalve mollusks thus can depend on the ability to repair shell damage between encounters. We studied the capacity for repair in the intertidal mussel Mytilus californianus by compressing live mussels for 15 cycles at ∼79% of their predicted strength (critically fracturing 46% of shells), then allowing the survivors 0, 1, 2 or 4 weeks to repair. Immediately after fatigue loading, mussel shells were 20% weaker than control shells that had not experienced repetitive loading. However, mussels restored full shell strength within 1 week, and after 4 weeks shells that had experienced greater fatiguing forces were stronger than those repetitively loaded at lower forces. Microscopy supported the hypothesis that crack propagation is a mechanism of fatigue-caused weakening. However, the mechanism of repair was only partially explained, as epifluorescence microscopy of calcein staining for shell deposition showed that only half of the mussels that experienced repetitive loading had initiated direct repair via shell growth around fractures. Our findings document repair weeks to months faster than demonstrated in other mollusks. This rapid repair may be important for the mussels’ success contending with predatory and environmental threats in the harsh environment of wave-swept rocky coasts, allowing them to address non-critical but weakening damage and to initiate plastic changes to shell strength. We highlight the significant insight gained by studying biological armors not as static structures but, instead, as dynamic systems that accumulate, repair and respond to damage.
Flight altitude dynamics of migrating European nightjars across regions and seasons
Authors: Norevik Gabriel , Åkesson Susanne , Andersson Arne , Bäckman Johan , Hedenström Anders
Published: October 2021

Avian migrants may fly at a range of altitudes, but usually concentrate near strata where a combination of flight conditions is favourable. The aerial environment can have a large impact on the performance of the migrant and is usually highly dynamic, making it beneficial for a bird to regularly check the flight conditions at alternative altitudes. We recorded the migrations between northern Europe and sub-Saharan Africa of European nightjars Caprimulgus europaeus to explore their altitudinal space use during spring and autumn flights and to test whether their climbs and descents were performed according to predictions from flight mechanical theory. Spring migration across all regions was associated with more exploratory vertical flights involving major climbs, a higher degree of vertical displacement within flights, and less time spent in level flight, although flight altitude per se was only higher during the Sahara crossing. The nightjars commonly operated at ascent rates below the theoretical maximum, and periods of descent were commonly undertaken by active flight, and rarely by gliding flight, which has been assumed to be a cheaper locomotion mode during descents. The surprisingly frequent shifts in flight altitude further suggest that nightjars can perform vertical displacements at a relatively low cost, which is expected if the birds can allocate potential energy gained during climbs to thrust forward movement during descents. The results should inspire future studies on the potential costs associated with frequent altitude changes and their trade-offs against anticipated flight condition improvements for aerial migrants.