bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel approaches in cancer treatment: preclinical and clinical development of small non-coding RNA therapeutics
Authors: Cuciniello Rossana , Filosa Stefania , Crispi Stefania 
Published: December 2021

AbstractShort or small interfering RNAs (siRNAs) and microRNA (miRNAs) are molecules similar in size and function able to inhibit gene expression based on their complementarity with mRNA sequences, inducing the degradation of the transcript or the inhibition of their translation.siRNAs bind specifically to a single gene location by sequence complementarity and regulate gene expression by specifically targeting transcription units via posttranscriptional gene silencing. miRNAs can regulate the expression of different gene targets through their imperfect base pairing.This process - known as RNA interference (RNAi) - modulates transcription in order to maintain a correct physiological environment, playing a role in almost the totality of the cellular pathways.siRNAs have been evolutionary evolved for the protection of genome integrity in response to exogenous and invasive nucleic acids such as transgenes or transposons. Artificial siRNAs are widely used in molecular biology for transient silencing of genes of interest. This strategy allows to inhibit the expression of any target protein of known sequence and is currently used for the treatment of different human diseases including cancer.Modifications and rearrangements in gene regions encoding for miRNAs have been found in cancer cells, and specific miRNA expression profiles characterize the developmental lineage and the differentiation state of the tumor. miRNAs with different expression patterns in tumors have been reported as oncogenes (oncomirs) or tumor-suppressors (anti-oncomirs). RNA modulation has become important in cancer research not only for development of early and easy diagnosis tools but also as a promising novel therapeutic approach.Despite the emerging discoveries supporting the role of miRNAs in carcinogenesis and their and siRNAs possible use in therapy, a series of concerns regarding their development, delivery and side effects have arisen.In this review we report the biology of miRNAs and siRNAs in relation to cancer summarizing the recent methods described to use them as novel therapeutic drugs and methods to specifically deliver them to cancer cells and overcome the limitations in the use of these molecules.
Complications associated with pre-hospital open thoracostomies: a rapid review
Authors: Mohrsen Stian , McMahon Niall , Corfield Alasdair , McKee Sinéad 
Published: December 2021

Abstract
Background
Open thoracostomies have become the standard of care in pre-hospital critical care in patients with chest injuries receiving positive pressure ventilation. The procedure has embedded itself as a rapid method to decompress air or fluid in the chest cavity since its original description in 1995, with a complication rate equal to or better than the out-of-hospital insertion of indwelling pleural catheters. A literature review was performed to explore potential negative implications of open thoracostomies and discuss its role in mechanically ventilated patients without clinical features of pneumothorax.

Main findings
A rapid review of key healthcare databases showed a significant rate of complications associated with pre-hospital open thoracostomies. Of 352 thoracostomies included in the final analysis, 10.6% (n = 38) led to complications of which most were related to operator error or infection (n = 26). Pneumothoraces were missed in 2.2% (n = 8) of all cases.

Conclusion
There is an appreciable complication rate associated with pre-hospital open thoracostomy. Based on a risk/benefit decision for individual patients, it may be appropriate to withhold intervention in the absence of clinical features, but consideration must be given to the environment where the patient will be monitored during care and transfer. Chest ultrasound can be an effective assessment adjunct to rule in pneumothorax, and may have a role in mitigating the rate of missed cases.
Examining non-technical skills for ad hoc resuscitation teams: a scoping review and taxonomy of team-related concepts
Authors: Evans J. Colin , Evans M. Blair , Slack Meagan , Peddle Michael , Lingard Lorelei 
Published: December 2021

Abstract
Background
Non-technical skills (NTS) concepts from high-risk industries such as aviation have been enthusiastically applied to medical teams for decades. Yet it remains unclear whether—and how—these concepts impact resuscitation team performance. In the context of ad hoc teams in prehospital, emergency department, and trauma domains, even less is known about their relevance and impact.

Methods
This scoping review, guided by PRISMA-ScR and Arksey & O’Malley’s framework, included a systematic search across five databases, followed by article selection and extracting and synthesizing data. Articles were eligible for inclusion if they pertained to NTS for resuscitation teams performing in prehospital, emergency department, or trauma settings. Articles were subjected to descriptive analysis, coherence analysis, and citation network analysis.

Results
Sixty-one articles were included. Descriptive analysis identified fourteen unique non-technical skills. Coherence analysis revealed inconsistencies in both definition and measurement of various NTS constructs, while citation network analysis suggests parallel, disconnected scholarly conversations that foster discordance in their operationalization across domains. To reconcile these inconsistencies, we offer a taxonomy of non-technical skills for ad hoc resuscitation teams.

Conclusion
This scoping review presents a vigorous investigation into the literature pertaining to how NTS influence optimal resuscitation performance for ad hoc prehospital, emergency department, and trauma teams. Our proposed taxonomy offers a coherent foundation and shared vocabulary for future research and education efforts. Finally, we identify important limitations regarding the traditional measurement of NTS, which constrain our understanding of how and why these concepts support optimal performance in team resuscitation.

Graphical abstract
Changes in carbon dioxide production and oxygen uptake evaluated using indirect calorimetry in mechanically ventilated patients with sepsis
Authors: Hirayama Ichiro , Asada Toshifumi , Yamamoto Miyuki , Hayase Naoki , Hiruma Takahiro , Doi Kent 
Published: December 2021

Abstract
Background
Several clinical guidelines recommend monitoring blood lactate levels and central venous oxygen saturation for hemodynamic management of patients with sepsis. We hypothesized that carbon dioxide production (VCO2) and oxygen extraction (VO2) evaluated using indirect calorimetry (IC) might provide additional information to understand the dynamic metabolic changes in sepsis.

Methods
Adult patients with sepsis who required mechanical ventilation in the intensive care unit (ICU) of our hospital between September 2019 and March 2020 were prospectively enrolled. Sepsis was diagnosed according to Sepsis-3. Continuous measurement of VCO2 and VO2 using IC for 2 h was conducted within 24 h after tracheal intubation, and the changes in VCO2 and VO2 over 2 h were calculated as the slopes by linear regression analysis. Furthermore, temporal lactate changes were evaluated. The primary outcome was 28-day survival.

Results
Thirty-four patients with sepsis were enrolled, 26 of whom survived 76%. Significant differences in the slope of VCO2 (− 1.412 vs. − 0.446) (p = 0.012) and VO2 (− 2.098 vs. − 0.851) (p = 0.023) changes were observed between non-survivors and survivors. Of note, all eight non-survivors and 17 of the 26 survivors showed negative slopes of VCO2 and VO2 changes. For these patients, 17 survivors had a median lactate of − 2.4% changes per hour (%/h), whereas non-survivors had a median lactate of 2.6%/hr (p = 0.023).

Conclusions
The non-survivors in this study showed temporal decreases in both VCO2 and VO2 along with lactate elevation. Monitoring the temporal changes in VCO2 and VO2 along with blood lactate levels may be useful in predicting the prognosis of sepsis.
Study on the mechanism of LOXL1-AS1/miR-3614-5p/YY1 signal axis in the malignant phenotype regulation of hepatocellular carcinoma
Authors: Feng ZhenYu , Ye ZhenYu , Xie JiaMing , Chen Wei , Li Wei , Xing ChunGen 
Published: December 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality worldwide. Accumulating researches have indicated that long non‑coding RNAs (lncRNAs) are involved in varies human cancers, including HCC. Nevertheless, the specific molecular mechanism of lncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in HCC is still unclear.

Methods
LOXL1-AS1 expression was tested via qRT-PCR in HCC cells. Functional and mechanism assays were respectively done to evaluate the biological functions of HCC cells and the potential interaction of LOXL1-AS1 and other factors.

Results
We discovered that LOXL1-AS1 was high expressed in HCC cells. Inhibition of LOXL1-AS1 repressed cell proliferation, migration and invasion, but enhanced cell apoptosis in HCC. Further, miR-3614-5p was proven to be sponged by LOXL1-AS1. Additionally, Yin Yang 1 (YY1) was proven as the target gene of miR-3614-5p, and YY1 depletion could repress HCC cell malignant behaviors. YY1 could also transcriptionally activate LOXL1-AS1 expression. In rescue assays, we confirmed that overexpression of YY1 or miR-3614-5p inhibition could reverse the suppressive effects of LOXL1-AS1 silence on the malignant behaviors of HCC cells.

Conclusion
In short, LOXL1-AS1/miR-3614-5p/YY1 forms a positive loop in modulating HCC cell malignant behaviors.
Impact of perinatal environmental health education intervention on exposure to endocrine disruptors during pregnancy—PREVED study: study protocol for a randomized controlled trial
Authors: Ouazzani Houria El. , Rouillon Steeve , Venisse Nicolas , Sifer-Rivière Lynda , Dupuis Antoine , Cambien Guillaume , Ayraud-Thevenot Sarah , Gourgues Anne-Sophie , Pierre-Eugène Pascale , Pierre Fabrice , Rabouan Sylvie ,   DisProSE Group, Migeot Virginie , Albouy-Llaty Marion 
Published: December 2021

Abstract
Background
The suspected or actual effects on health of endocrine-disrupting chemicals (EDC) and their ubiquitous presence in everyday life justify the implementation of health promotion interventions. These interventions should ideally be applied during critical windows like pregnancy. Perinatal environmental health education interventions may help to reduce EDC exposure during pregnancy.

Methods/design
PREVED (Pregnancy, PreVention, Endocrine Disruptors) is an open-label randomized controlled trial assessing the impact of environmental health education intervention on EDC exposure during pregnancy. Inclusion, consent, and randomization take place during the first trimester. The participants are randomly allocated into three groups: (i) control group (information leaflet on EDCs), (ii) intervention group in neutral location (information leaflet and workshops in a meeting room), and (iii) intervention group in contextualized location (information leaflet and workshops in a real apartment). Workshops are organized between the second and third trimesters of pregnancy. Main outcome is the percentage of participants who reported consuming manufactured/industrial food. Secondary outcomes are as follows: (i) psycho-social dimensions, (ii) EDC concentrations in urine, (iii) EDC concentration in colostrum, and (iv) percentage of participants who reported consuming paraben-free personal care products.

Discussion
PREVED is a ground-breaking intervention research project dedicated to perinatal environmental health education that aims to identify pollutant sources in daily life and to offer accessible and realistic alternative solutions, by promoting the sharing of know-how and experience in a positive and non-alarmist approach.

Trial registration
ClinicalTrials.gov: NCT03233984 (current status: ongoing). Retrospectively registered on 31 July 2017 (https://clinicaltrials.gov/ct2/show/NCT03233984) because when the first participant was enrolled in this non-drug intervention, ClinicalTrials.gov was centered in therapeutic trials.
The World Health Organization Trial Registration Data Set is in Additional file 1.
What do parents think of using informational videos to support recruitment for parenting trials? A qualitative study
Authors: Pontoppidan Maiken , Blower Sarah , Solvang Julie Nygaard , Bywater Tracey 
Published: December 2021

AbstractBackgroundLower than expected recruitment and retention rates are common challenges in parenting trials—particularly for community-based trials targeting parents of young children that rely on face-to-face recruitment by frontline workers. Recruitment requires parental informed consent, yet information sheets have been criticized for being lengthy and complex, and particularly challenging for parents with low literacy. Recent innovations include ‘talking head’ information videos. This paper aims to explore parent perceptions of using a ‘talking head’ video to support informed consent, recruitment, and retention procedures in parenting trials.MethodsWe conducted semi-structured interviews with a sample of 24 mothers recruited after their final follow-ups in two different parenting trials in Denmark. Before consenting to participate in the trials, parents were invited to view a video of a member of the study team giving information about the study, and again before the interviews for the current study. The audio data was transcribed and thematic analysis was conducted.ResultsWe identified three overarching themes: (1) general impression of the video, (2) thoughts on participation in research, and (3) recruitment and retention. Participants were generally positive in their appraisal of the two talking head informational videos. We found that participants felt that a mix of paper-based and video-based sources of information would enable them to make an informed choice about whether to participate in a research study. We also found that a professionally produced video featuring a key member of the study team produced a feeling of commitment to the study that could impact retention rates.ConclusionsInformational videos are acceptable to parents; however, co-production or participant/patient involvement in the development of such videos is recommended. Informational videos may not increase recruitment but have the potential for improving retention. Key design recommendations are to ensure a ‘professional’ look to the video, to supplement videos with paper-based information, to keep the length to < 3 min, and for the ‘talking head’ part to feature a key member of the study team.
Study protocol for a randomized clinical trial to evaluate the effect of the use of Xylitol gum in the prevention of caries lesions in children living in Ladakh—the Caries Prevention Xylitol in Children (CaPreXCh) trial
Authors: Cagetti Maria Grazia , Cocco Fabio , Calzavara Ezio , Augello Davide , Zangpoo Phunchok , Campus Guglielmo 
Published: December 2021

Abstract
Background
Xylitol use is reported to be able to reduce dental plaque amount and cariogenic bacteria and, as a consequence, the caries increment. Only few data on the oral health of Ladakh’s population are available. The aim of the present protocol will be to record the caries prevalence of primary and permanent molars of schoolchildren living in Ladakh and to implement a school-based Xylitol programme, named the Caries Prevention Xylitol in Children (CaPreXCh) trial, using chewing gums.

Methods
The protocol is designed as a triple-blind randomized, controlled, parallel-group clinical trial in children aged 5–14 years. The study should have been carried out from August 2021 to August 2024 in Zanskar Valley (Ladakh), but the COVID-19 pandemic does not allow today to make predictions on the exact start. Participants will be randomly allocated into two groups: subjects who will receive a chewing gum with Xylitol (70% w/v) as only sweetener, and those who will receive a sugared chewing gum containing Maltitol (23% w/v). The subjects will be instructed to chew a total of 6 pellets for 5 min divided into 3 intakes a day (2 in the morning, 2 after the midday meal and 2 in the afternoon) for one school year. Clinical examination will comprise an oral examination in which caries index (ICDAS scores), bleeding on probing and plaque pH evaluation after sucrose challenge will be recorded at baseline (t0); the clinical examination will be repeated after 12 months since the beginning of the chewing gum administration period (t1), after another 12-month period (t2) and finally after further 12 months (t3) (24 months from the end of the chewing gum use). The primary outcome will be the caries increment measured both at enamel and dentinal levels on primary and permanent molars. Data analysis will be conducted through Kaplan-Meyer graphs to evaluate caries increment. A comparison of the methods will be carried out with Cox regression with shared frailty. The net caries increment for initial, moderate and severe caries levels, using ICDAS (Δ-initial, Δ-moderate and Δ-severe), will be calculated.

Discussion
This trial will be the first trial conducted in India assessing the efficacy of a school-based caries preventive programme through the use of chewing gum containing only Xylitol as a sweetener. The findings could help strengthen the evidence for the efficacy of Xylitol use in community-based caries prevention programmes in children.

Trial registration
Clinical trials.govNCT04420780. Registered on June 9, 2020
Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial
Authors: van Erp Inge A. M. , van Essen Thomas A. , Fluiter Kees , van Zwet Erik , van Vliet Peter , Baas Frank , Haitsma Iain , Verbaan Dagmar , Coert Bert , de Ruiter Godard C. W. , Moojen Wouter A. , van der Jagt Mathieu , Peul Wilco C. 
Published: December 2021

AbstractBackgroundTraumatic brain injury (TBI) is a major cause of death and disability across all ages. After the primary impact, the pathophysiologic process of secondary brain injury consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system could therefore be a therapeutic target in TBI.ObjectiveTo study the safety and efficacy of C1-inhibitor (C1-INH) compared to placebo in patients with TBI. By temporarily blocking the complement system, we hypothesize a decrease in the posttraumatic neuroinflammatory response resulting in a less unfavorable clinical outcome for TBI patients.MethodsCIAO@TBI is a multicenter, randomized, blinded, phase II placebo-controlled trial. Adult TBI patients with GCS < 13 requiring intracranial pressure (ICP) monitoring will be randomized, using block randomization, within 12 h after trauma to one dose 6000 IU C1-INH or placebo. A total of 106 patients will be included, and follow-up will occur up to 12 months. The primary endpoints are (1) Therapy Intensity Level (TIL) Scale, (2) Glasgow Outcome Scale-Extended (GOSE) at 6 months, and (3) complication rate during hospitalization. Outcomes will be determined by a trial nurse blinded for the treatment allocation. Analyses will be conducted in an intention-to-treat analysis.DiscussionWe expect that C1-INH administration will be safe and potentially effective to improve clinical outcomes by reducing neuroinflammation in TBI patients.Trial registrationClinicalTrials.govNCT04489160. Registered on 27 July 2020. EudraCT 2020-000140-58
Effectiveness and safety of Bushen Huoxue granules in treatment of premature ovarian insufficiency: study protocol for a randomized, double-blinded, placebo-controlled, and multicenter clinical trial
Authors: Cao Ying , Peijuan-Wang  , Lu Yan , Chen Yue , Chen Si , Weibo-Zhao  
Published: December 2021

Abstract
Introduction
Premature ovarian insufficiency (POI) seriously affects the quality of life, endocrine function, and fertility of women of childbearing age. Currently, hormone replacement therapy for POI has some limitations, either with low efficacies or high side effects. Bushen Huoxue (BSHX) plays an important role in alleviating clinical symptoms and improving health status of POI patients. This placebo-controlled, randomized, double-blind, and multicenter clinical trial protocol aims to evaluate the effectiveness and safety of BSHX in women with POI.

Methods and design
We plan to recruit 150 women with POI from four participating hospitals in China. Participants will be randomized in a 1:1 to receive oral BSHX or BSHX placebo. All participants will be treated for 3 months and will be followed up for another 3 month. The primary outcome is questionnaire scores based on the changes in the total symptoms, which is the Chinese version of the Menopause-Specific Quality of Life (CMS) (Nie G, Yang H, Liu J, Zhao C, Wang X, Menopause 24(5):546–554, 2017). CMS will be measured before the intervention, at 3 months and 6 months after randomization for all participants. The other measurements include serum sex hormone levels, anti-Müllerian hormone (AMH) levels, ovarian peak systolic velocity (PSV; cm/s), and antral follicle count (AFC). In this study, the regulatory effects of traditional Chinese medicine on hormones were evaluated by the changes of serum sex hormone levels, which include serum estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). These indicators will be measured before intervention and at 3 months after randomization.

Ethics and dissemination
This study was approved by the Research Ethics Committee of Jiangsu Province Hospital on Integration of Chinese and Western Medicine (2019LWKY014). All participants will provide written informed consent prior to randomization. The results of this research will be presented to academic conferences and peer-reviewed journals.

Trial registration
ChiCTR1900028451. Registered on 22 December 2019, https://www.chictr.org.cn/index.aspx.