bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives and ethical considerations for return of genetics and genomics research results: a qualitative study of genomics researchers in Uganda
Authors: Ochieng Joseph , Kwagala Betty , Barugahare John , Mwaka Erisa , Ekusai-Sebatta Deborah , Ali Joseph , Sewankambo Nelson K. 
Published: November 2021

Abstract
Background
The return of genetics and genomics research results has been a subject of ongoing global debate. Such feedback is ethically desirable to update participants on research findings particularly those deemed clinically significant. Although there is limited literature, debate continues in African on what constitutes appropriate practice regarding the return of results for genetics and genomics research. This study explored perspectives and ethical considerations of Ugandan genomics researchers regarding the return of genetics and genomics research results.

Methods
This was a qualitative study that employed in-depth interviews. Thirty participants were purposively selected based on their expertise as genomics researchers in Uganda. Data were analysed through content analysis along the main themes of the study using a comprehensive thematic matrix, to identify common patterns arising from the narratives. NVivo software 12 was used to support data analysis.

Results
The return of genetics and genomics research results was generally acceptable to researchers, and some indicated that they had previously returned individual or aggregate results to participants and communities. The main reasons cited for sharing research results with participants included their clinical utility, actionability and overall benefit to society. Ethical considerations for appropriate return of results included a need for effective community engagement, genetic counselling prior to disclosure of the results, adequate informed consent, and proper assessment of the implications of, or consequences of returning of results. However, the approaches to return of results were perceived as unstandardized due to the lack of appropriate regulatory frameworks.

Conclusions
The return of genetic and genomic research results is generally acceptable to researchers despite the lack of appropriate regulatory frameworks. Ethical considerations for return of genetics and genomics research results are highly divergent, hence the need for national ethical guidelines to appropriately regulate the practice.
Computer-assisted quantification of tumor-associated collagen signatures to improve the prognosis prediction of breast cancer
Authors: Xi Gangqin , Qiu Lida , Xu Shuoyu , Guo Wenhui , Fu Fangmeng , Kang Deyong , Zheng Liqin , He Jiajia , Zhang Qingyuan , Li Lianhuang , Wang Chuan , Chen Jianxin 
Published: November 2021

AbstractBackgroundCollagen fibers play an important role in tumor initiation, progression, and invasion. Our previous research has already shown that large-scale tumor-associated collagen signatures (TACS) are powerful prognostic biomarkers independent of clinicopathological factors in invasive breast cancer. However, they are observed on a macroscale and are more suitable for identifying high-risk patients. It is necessary to investigate the effect of the corresponding microscopic features of TACS so as to more accurately and comprehensively predict the prognosis of breast cancer patients.MethodsIn this retrospective and multicenter study, we included 942 invasive breast cancer patients in both a training cohort (n= 355) and an internal validation cohort (n= 334) from one clinical center and in an external validation cohort (n= 253) from a different clinical center. TACS corresponding microscopic features (TCMFs) were firstly extracted from multiphoton images for each patient, and then least absolute shrinkage and selection operator (LASSO) regression was applied to select the most robust features to build a TCMF-score. Finally, the Cox proportional hazard regression analysis was used to evaluate the association of TCMF-score with disease-free survival (DFS).ResultsTCMF-score is significantly associated with DFS in univariate Cox proportional hazard regression analysis. After adjusting for clinical variables by multivariate Cox regression analysis, the TCMF-score remains an independent prognostic indicator. Remarkably, the TCMF model performs better than the clinical (CLI) model in the three cohorts and is particularly outstanding in the ER-positive and lower-risk subgroups. By contrast, the TACS model is more suitable for the ER-negative and higher-risk subgroups. When the TACS and TCMF are combined, they could complement each other and perform well in all patients. As expected, the full model (CLI+TCMF+TACS) achieves the best performance (AUC0.905, [0.873–0.938]; 0.896, [0.860–0.931]; 0.882, [0.840–0.925] in the three cohorts).ConclusionThese results demonstrate that the TCMF-score is an independent prognostic factor for breast cancer, and the increased prognostic performance (TCMF+TACS-score) may help us develop more appropriate treatment protocols.
MCP mediated active targeting calcium phosphate hybrid nanoparticles for the treatment of orthotopic drug-resistant colon cancer
Authors: Bai Shaobo , Sun Yang , Cheng Ying , Ye Weiliang , Jiang Chenchao , Liu Miao , Ji Qifeng , Zhang Bangle , Mei Qibing , Liu Daozhou , Zhou Siyuan 
Published: November 2021

Abstract
Background
Colon cancer is a most common malignant cancer in digestive system, and it is prone to develop resistance to the commonly used chemotherapy drugs, leading to local recurrence and metastasis. Paris saponin VII (PSVII) could not only inhibit the proliferation of colon cancer cells but also effectively induce apoptosis of drug-resistant colon cancer cells and reduce the metastasis of drug-resistant colon cancer cells as well. However, PSVII was insoluble in water and fat. It displayed no selective distribution in body and could cause severe hemolysis. Herein, colon cancer targeting calcium phosphate nanoparticles were developed to carry PSVII to treat drug-resistant colon cancer.

Results
PSVII carboxymethyl-β-cyclodextrin inclusion compound was successfully encapsulated in colon cancer targeting calcium phosphate nanoparticles (PSVII@MCP-CaP) by using modified citrus pectin as stabilizer agent and colon cancer cell targeting moiety. PSVII@MCP-CaP significantly reduced the hemolysis of PSVII. Moreover, by specific accumulating in orthotopic drug-resistant colon cancer tissue, PSVII@MCP-CaP markedly inhibited the growth of orthotopic drug-resistant colon cancer in nude mice. PSVII@MCP-CaP promoted the apoptosis of drug-resistant colon cancer cells through mitochondria-mediated apoptosis pathway. Moreover, PSVII@MCP-CaP significantly inhibited the invasion and migration of drug-resistant colon cancer cells by increasing E-cadherin protein expression and reducing N-cadherin and MMP-9 protein expression.

Conclusion
PSVII@MCP-CaP has great potential in the treatment of drug-resistant colon cancer. This study also explores a new method to prepare active targeting calcium phosphate nanoparticles loaded with a fat and water insoluble compound in water.

Graphical Abstract
Macrophage membrane camouflaged reactive oxygen species responsive nanomedicine for efficiently inhibiting the vascular intimal hyperplasia
Authors: Liu Boyan , Yan Wenhua , Luo Li , Wu Shuai , Wang Yi , Zhong Yuan , Tang Dan , Maruf Ali , Yan Meng , Zhang Kun , Qin Xian , Qu Kai , Wu Wei , Wang Guixue 
Published: November 2021

Abstract
Background
Intimal hyperplasia caused by vascular injury is an important pathological process of many vascular diseases, especially occlusive vascular disease. In recent years, Nano-drug delivery system has attracted a wide attention as a novel treatment strategy, but there are still some challenges such as high clearance rate and insufficient targeting.

Results
In this study, we report a biomimetic ROS-responsive MM@PCM/RAP nanoparticle coated with macrophage membrane. The macrophage membrane with the innate “homing” capacity can superiorly regulate the recruitment of MM@PCM/RAP to inflammatory lesion to enhance target efficacy, and can also disguise MM@PCM/RAP nanoparticle as the autologous cell to avoid clearance by the immune system. In addition, MM@PCM/RAP can effectively improve the solubility of rapamycin and respond to the high concentration level of ROS accumulated in pathological lesion for controlling local cargo release, thereby increasing drug availability and reducing toxic side effects.

Conclusions
Our findings validate that the rational design, biomimetic nanoparticles MM@PCM/RAP, can effectively inhibit the pathological process of intimal injury with excellent biocompatibility.

Graphical Abstract
The impact of Taiwan’s implementation of a nationwide harm reduction program in 2006 on the use of various illicit drugs: trend analysis of first-time offenders from 2001 to 2017
Authors: Chen Wei J. , Chen Chi-Ya , Wu Shang-Chi , Wu Kevin Chien-Chang , Jou Susyan , Tung Yu-Chi , Lu Tzu-Pin 
Published: November 2021

Abstract
Background
After implementing a nationwide harm reduction program in 2006, a dramatic decline in the incidence of human immunodeficiency virus (HIV) infection among people with injection drug use (IDU) was observed in Taiwan. The harm reduction program might have sent out the message discouraging the choice of IDU among illicit drug users in early stage. Based on the yearly first-time offense rates from 2001 to 2017, this study aimed to examine (1) whether the nationwide implementation of the harm reduction program in 2006 led to changes in first-time offenders’ use of heroin; (2) whether the intervention had a similar effect on the use of other illicit drugs; and (3) whether the effect of the intervention was limited to the first-time offenders of young age groups.

Methods
Yearly first-time illicit-drug offense rates from 2001 to 2017 in Taiwan were derived from two national databases for drug arrests that were verified using urine tests: the Criminal Record Processing System on Schedule I/II Drugs and the Administrative Penalty System for Schedule III/IV Substances. A hierarchy of mutually exclusive categories of drug uses was defined by the drug with the highest schedule level among those tested positive in an arrest. Segmented regression analyses of interrupted time series were used to test for the impact of the 2006 intervention.

Results
There was a decrease of 22.37 per 100,000 in the rate for heroin but no detectable level changes in that for methamphetamine or ecstasy after the 2006 intervention in Taiwan. There were baseline decreasing trends in the first-time offense rate from 2001 to 2017 for heroin and ecstasy and an increasing trend for methamphetamine, with the slopes not altered by the 2006 intervention. The postintervention decrease in the first-time offense rate for heroin was detectable among offenders less than 40 years old.

Conclusions
Our results indicate a diffusion effect of the 2006 intervention on decreasing heroin use among young offenders and have policy implications for better prevention and treatment for different age groups.
A bi-institutional multi-disciplinary failure mode and effects analysis (FMEA) for a Co-60 based total body irradiation technique
Authors: Ahmed Shahbaz , Bossenberger Todd , Nalichowski Adrian , Bredfeldt Jeremy S. , Bartlett Sarah , Bertone Kristen , Dominello Michael , Dziemianowicz Mark , Komajda Melanie , Makrigiorgos G. Mike , Marcus Karen J. , Ng Andrea , Thomas Marvin , Burmeister Jay 
Published: November 2021

Abstract
Background
We aim to assess the risks associated with total body irradiation (TBI) delivered using a commercial dedicated Co-60 irradiator, and to evaluate inter-institutional and inter-professional variations in the estimation of these risks.

Methods
A failure mode and effects analysis (FMEA) was generated using guidance from the AAPM TG-100 report for quantitative estimation of prospective risk metrics. Thirteen radiation oncology professionals from two institutions rated possible failure modes (FMs) for occurrence (O), severity (S), and detectability (D) indices to generate a risk priority number (RPN). The FMs were ranked by descending RPN value. Absolute gross differences (AGD) in resulting RPN values and Jaccard Index (JI; for the top 20 FMs) were calculated. The results were compared between professions and institutions.

Results
A total of 87 potential FMs (57, 15, 10, 3, and 2 for treatment, quality assurance, planning, simulation, and logistics respectively) were identified and ranked, with individual RPN ranging between 1–420 and mean RPN values ranging between 6 and 74. The two institutions shared 6 of their respective top 20 FMs. For various institutional and professional comparison pairs, the number of common FMs in the top 20 FMs ranged from 6 to 13, with JI values of 18–48%. For the top 20 FMs, the trend in inter-professional variability was institution-specific. The mean AGD values ranged between 12.5 and 74.5 for various comparison pairs. AGD values differed the most for medical physicists (MPs) in comparison to other specialties i.e. radiation oncologists (ROs) and radiation therapists (RTs) [MPs-vs-ROs: 36.3 (standard deviation SD = 34.1); MPs-vs-RTs: 41.2 (SD = 37.9); ROs-vs-RTs: 12.5 (SD = 10.8)]. Trends in inter-professional AGD values were similar for both institutions.

Conclusion
This inter-institutional comparison provides prospective risk analysis for a new treatment delivery unit and illustrates the institution-specific nature of FM prioritization, primarily due to operational differences. Despite being subjective in nature, the FMEA is a valuable tool to ensure the identification of the most significant risks, particularly when implementing a novel treatment modality. The creation of a bi-institutional, multidisciplinary FMEA for this unique TBI technique has not only helped identify potential risks but also served as an opportunity to evaluate clinical and safety practices from the perspective of both multiple professional roles and different institutions.
Impact of the COVID-19 Pandemic on road traffic collision injury patterns and severity in Al-Ain City, United Arab Emirates
Authors: Yasin Yasin J. , Alao David O. , Grivna Michal , Abu-Zidan Fikri M. 
Published: November 2021

AbstractBackgroundThe COVID-19 Pandemic lockdowns restricted human and traffic mobility impacting the patterns and severity of road traffic collisions (RTCs).We aimed to study the effects of the COVID-19 Pandemic on incidence, patterns, severity of the injury, and outcomes of hospitalized RTCs trauma patients in Al-Ain City, United Arab Emirates.MethodsWe compared the data of two cohorts of patients which were collected over two periods; the Pandemic period (28 March 2020 to 27 March 2021) and the pre-pandemic period (28 March 2019 to 27 March 2020). All RTCs trauma patients who were hospitalized in the two major trauma centers (Al-Ain and Tawam Hospitals) of Al-Ain City were studied.ResultsOverall, the incidence of hospitalized RTC trauma patients significantly reduced by 33.5% during the Pandemic compared with the pre-pandemic period. The mechanism of injury was significantly different between the two periods (p < 0.0001, Fisher’s Exact test). MVCs were less during the Pandemic (60.5% compared with 72%), while motorcycle injuries were more (23.3% compared with 11.2%). The mortality of hospitalized RTC patients was significantly higher during the Pandemic (4.4% compared with 2.3%,p = 0.045, Fisher’s Exact test). Logistic regression showed that the significant factors that predicted mortality were the low GCS (p < 0.0001), admission to the ICU (p < 0.0001), and the high ISS (p = 0.045). COVID-19 Pandemic had a very strong trend (p = 0.058) for increased mortality.ConclusionsOur study has shown that the numbers of hospitalized RTC trauma patients reduced by 33.5% during the COVID-19 Pandemic compared with the pre-pandemic period in our setting. This was attributed to the reduced motor vehicle, pedestrian and bicycle injuries while motorcycle injuries increased. Mortality was significantly higher during the Pandemic, which was attributed to increased ISS and reduced GCS.
Use of COVID-19 evidence in humanitarian settings: the need for dynamic guidance adapted to changing humanitarian crisis contexts
Authors: Odlum Alex , James Rosemary , Mahieu Audrey , Blanchet Karl , Altare Chiara , Singh Neha , Spiegel Paul 
Published: November 2021

Abstract
Background
For humanitarian organisations to respond effectively to complex crises, they require access to up-to-date evidence-based guidance. The COVID-19 crisis has highlighted the importance of updating global guidance to context-specific and evolving needs in humanitarian settings. Our study aimed to understand the use of evidence-based guidance in humanitarian responses during COVID-19. Primary data collected during the rapidly evolving pandemic sheds new light on evidence-use processes in humanitarian response.

Methods
We collected and analysed COVID-19 guidance documents, and conducted semi-structured interviews remotely with a variety of humanitarian organisations responding and adapting to the COVID-19 pandemic.
We used the COVID-19 Humanitarian platform, a website established by three universities in March 2020, to solicit, collate and document these experiences and knowledge.

Results
We analysed 131 guidance documents and conducted 80 interviews with humanitarian organisations, generating 61 published field experiences. Although COVID-19 guidance was quickly developed and disseminated in the initial phases of the crisis (from January to May 2020), updates or ongoing revision of the guidance has been limited. Interviews conducted between April and September 2020 showed that humanitarian organisations have responded to COVID-19 in innovative and context-specific ways, but have often had to adapt existing guidance to inform their operations in complex humanitarian settings.

Conclusions
Experiences from the field indicate that humanitarian organisations consulted guidance to respond and adapt to COVID-19, but whether referring to available guidance indicates evidence use depends on its accessibility, coherence, contextual relevance and trustworthiness. Feedback loops through online platforms like the COVID-19 Humanitarian platform that relay details of these evidence-use processes to global guidance setters could improve future humanitarian response.
MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A
Authors: Wang Jin , Liu Lingxia 
Published: November 2021

Abstract
Background
Ovarian cancer (OC), a kind of gynecological cancer, is characterized by high mortality rate, with microRNAs (miRNAs) playing essential roles in it. However, the clinical significance of miRNAs and their molecular mechanisms in OC are mostly unknown.

Methods
miR-149-3p expression was predicted through Gene Expression Omnibus (GEO) data in OC and confirmed by q-PCR in various OC cells and tissues from patients with different clinical characteristics. Moreover, its roles in terms of proliferation, migration and invasion were measured by CCK-8, colony formation, wound healing and transwell assays in OC cells including cisplatin-resistant and cisplatin-sensitive cells. And its effect on epithelial-mesenchymal transition was also assessed through detecting related protein expression. Additionally, its potential targets were verified by dual luciferase assay and Ago-RIP assay. Finally, its oncogenic functions were explored in vivo.

Results
In data from GSE79943, GSE131790, and TCGA, miR-149-3p was found to be highly expressed in OC tissues and associated with poor survival. In metastasis and chemoresistant tissues and cisplatin-resistant OC cells, its high expression was confirmed. In terms of tumorigenic effects, miR-149-3p knockdown in cisplatin-resistant OC cells inhibited its cisplatin resistance and other malignant phenotypes, while miR-149-3p overexpression in cisplatin-resistant OC cells led to contrary results. Mechanistically, miR-149-3p targeted 3’UTR of CDKN1A and TIMP2 to function as an oncogenic miRNA.

Conclusion
In brief, miR-149-3p promoted cisplatin resistance and EMT in OC by downregulating CDKN1A and TIMP2, which might provide a potential therapeutic target for OC treatment.
Establishing a core outcome set for mucopolysaccharidoses (MPS) in children: study protocol for a rapid literature review, candidate outcomes survey, and Delphi surveys
Authors: Howie Alison H. , Tingley Kylie , Inbar-Feigenberg Michal , Mitchell John J. , Butcher Nancy J. , Offringa Martin , Smith Maureen , Angel Kim , Gentle Jenifer , Wyatt Alexandra , Campeau Philippe M. , Chan Alicia , Chakraborty Pranesh , El Turk Farah , Mamak Eva , Mhanni Aizeddin , Skidmore Becky , Sparkes Rebecca , Stockler Sylvia , Potter Beth K. ,   in collaboration with the INFORM RARE Network
Published: November 2021

Abstract
Background
Mucopolysaccharidoses (MPS) are a group of inherited metabolic diseases characterized by chronic, progressive multi-system manifestations with varying degrees of severity. Disease-modifying therapies exist to treat some types of MPS; however, they are not curative, underscoring the need to identify and evaluate co-interventions that optimize functioning, participation in preferred activities, and quality of life. A Canadian pediatric MPS registry is under development and may serve as a platform to launch randomized controlled trials to evaluate such interventions. To promote the standardized collection of patient/family-reported and clinical outcomes considered important to patients/families, health care providers (HCPs), and policymakers, the choice of outcomes to include in the registry will be informed by a core outcome set (COS). We aim to establish a patient-oriented COS for pediatric MPS using a multi-stakeholder approach.

Methods
In step 1 of the six-step process to develop the COS, we will identify relevant outcomes through a rapid literature review and candidate outcomes survey. A two-phase screening approach will be implemented to identify eligible publications, followed by extraction of outcomes and other pre-specified data elements. Simultaneously, we will conduct a candidate outcomes survey with children with MPS and their families to identify outcomes most important to them. In step 2, HCPs experienced in treating patients with MPS will be invited to review the list of outcomes generated in step 1 and identify additional clinically relevant outcomes. We will then ask patients/families, HCPs, and policymakers to rate the outcomes in a set of Delphi Surveys (step 3), and to participate in a subsequent consensus meeting to finalize the COS (step 4). Step 5 involves establishing a set of outcome measurement instruments for the COS. Finally, we will disseminate the COS to knowledge users (step 6).

Discussion
The proposed COS will inform the choice of outcomes to include in the MPS registry and, more broadly, promote the standardized collection of patient-oriented outcomes for pediatric MPS research. By involving patients/families from the earliest stage of the research, we will ensure that the COS will be relevant to those who will ultimately benefit from the research.

Trial registration
PROSPERO CRD42021267531, COMET