bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis
Authors: Gutzmer Ralf , Robert Caroline , Loquai Carmen , Schadendorf Dirk , Squittieri Nicholas , Arntz Ramon , Martelli Serena , Dummer Reinhard
Published: November 2021

Background

The BOLT study for sonidegib, a Hedgehog pathway inhibitor (HHI) approved for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy, used modified Response Evaluation Criteria in Solid Tumors (mRECIST) for laBCC tumor evaluation. The ERIVANCE study for vismodegib, another HHI, used a composite RECIST endpoint of ≥30% reduction in externally visible tumor or radiographic dimension, or complete ulceration resolution. This preplanned sensitivity BOLT analysis evaluated efficacy outcomes using ERIVANCE-like criteria in patients with laBCC who received sonidegib 200 mg once daily.

Methods

This phase 2, double-blind study randomized patients 1:2 to sonidegib 200:800 mg daily, respectively. Key endpoints included objective response rate (ORR), duration of response (DOR), complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). laBCC tumors were assessed by both mRECIST and ERIVANCE-like criteria. Per mRECIST, an overall response of CR was based on negative histology; photographic assessment of CR, PR (scar/fibrosis only), SD (scar/fibrosis only), or not available (NA); and a magnetic resonance imaging response of CR or NA. An overall response of CR was primarily based on negative histology using ERIVANCE-like criteria.

Results

Per mRECIST criteria, ORR (95% confidence interval [CI]) by central and investigator review for patients with laBCC (n = 66) was 56.1% (43.3–68.3%) and 71.2% (58.7–81.7%), respectively. CR per central review was achieved in 3 (4.5%) patients and PR, SD, and PD occurred in 34 (51.5%), 23 (34.8%), and 1 (1.5%) patient, respectively. Median (95% CI) DOR was 26.1 months (not estimable [NE]).

Using ERIVANCE-like criteria, efficacy outcomes per central and investigator review were higher, with an ORR (95% CI) of 60.6% (47.8–72.4%) and 74.2% (62.0–84.2%), respectively. CR per central review was reached in 14 (21.2%) patients and PR, SD, and PD occurred in 26 (39.4%), 20 (30.3%), and 1 (1.5%) patient, respectively. DOR was unchanged with a median (95% CI) of 26.1 months (NE).

Conclusions

Overall, applying ERIVANCE-like criteria to patients with laBCC receiving sonidegib 200 mg daily yielded higher response rates vs mRECIST criteria.

Trial registration

BOLT registration: ClinicalTrials.gov (NCT01327053) on March 30, 2011.
Glaucoma and its predictors among adult patients attending ophthalmic outpatient department: a hospital-based study, North West Ethiopia
Authors: Wubet Gashaw Mehiret , Assefa Abiyu Ayalew
Published: November 2021

Background

Nearly 1.9% of global blindness is caused by glaucoma and this is sadly high in Africa which is around 15% and In Ethiopia, glaucoma is responsible for 5.2% of blindness. It is also the fifth cause of blindness in Ethiopia. Scarce information is available regarding glaucoma in Ethiopia; hence we determined the proportion of glaucoma and its associated factors in North West Ethiopia which will be utilized for future related researches and different stakeholders.

Methods

Institution based cross-sectional study was conducted from September 1/2020 to February 30/21 among 258 adults aged 40 and above years old. The participants were selected using the systematic random sampling technique. The data was collected using an interview-administered questionnaire. Binary and Multi-variable logistic regressions were fitted to identify independent predictors of glaucoma. P-value less than 0.05 were used as a cutoff point for declaring statistical significance.

Results

The prevalence of glaucoma was 66(26%) with a 95% CI of 17.7, 35.4%). Individuals with Positive family history of glaucoma (AOR: 3.72, 95% CI: 1.03–3.53), age (AOR: 3.21, 95% CI: 1.92–5.99) and elevated intraocular pressure (AOR: 3.09, 95% CI: 1.45–6.59) were statistically significant contributing factors for the development of glaucoma.

Conclusion

The study found a relatively high proportion of glaucoma in the study area, which is primarily a disease of the elderly. Age, elevated intraocular pressure, and positive family history of glaucoma was contributing factors for the emergence of glaucoma. Therefore, establishing public awareness programs about the identified risk factors for the prevention and early detection of cases is essential.
The outcome of young vs. old gastric cancer patients following gastrectomy: a propensity score matching analysis
Authors: Cheng Yu-Xi , Tao Wei , Liu Xiao-Yu , Yuan Chao , Zhang Bin , Zhang Wei , Peng Dong
Published: November 2021

Purpose

The purpose of the current study was to compare the postoperative complications, overall survival and disease-free survival in young and old gastric cancer patients after gastrectomy using propensity score matching (PSM).

Methods

Adult patients (aged ≥ 18 years) who underwent gastrectomy for gastric cancer in a single clinical center from January 2013 to December 2017 were enrolled continuously for retrospective analysis. To minimize the selection bias between the young and old groups, the PSM was conducted in this study.

Results

A total of 558 patients were included in this study, with 51 patients in the young group (aged ≤ 45 years) and 507 patients in the old group (aged > 45 years). After 1:1 matching according to PSM, 51 patients in the young group were matched to 51 patients in the old group. After PSM, there was no difference in the baseline information. In terms of short-term outcomes, no difference was found in operation time (P = 0.190), intraoperative blood loss (P = 0.336), retrieved lymph nodes (P = 0.948), blood transfusion (P = 0.339), postoperative hospital stay (P = 0.194), or postoperative complications (P = 0.477) between the two groups. For overall survival, no statistically significant difference was found in all stages (P = 0.383), stage I (P = 0.431), stage II (P = 0.875) or stage III (P = 0.446) gastric cancer. Furthermore, regarding disease-free survival, no differences were found between the two groups in all stages (P = 0.378), stage I (P = 0.431), stage II (P = 0.879) or stage III (P = 0.510) gastric cancer.

Conclusion

Age might not be an independent prognostic factor for short-term outcomes, OS, or DFS in gastric cancer patients who underwent gastrectomy. The pTNM stage of GC might be an independent prognostic factor for OS and DFS.
Survival of endodontically treated permanent teeth among children: a retrospective cohort study
Authors: Bufersen Saitah , Jones Judith , Shanmugham Jayapriyaa , Hsu Tun-Yi , Rich Sharron , Ziyab Ali H. , Chogle Sami
Published: November 2021

Background

Outcome studies of nonsurgical root canal treatment (NSRCT) in permanent teeth of children are scarce. This study investigated survival and assessed the variables associated with failure of endodontically treated teeth (ETT) in 6- to 18-year-olds.

Methods

Records of subjects who received NSRCT at age 6–18 years at Boston University between 2007 and 2015 were assessed for the occurrence of untoward events. Kaplan–Meier survival curves were used to investigate the survival of ETT in the total sample. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated.

Results

The analysis included 341 patients (424 ETT). Kaplan–Meier survival curves differed according to age at treatment (log-rank P = 0.026), with survival being the lowest among the youngest age group. The estimated 5-year survival probability was 80% for 15- to 18-year-olds, 64.8% for 12- to 14-year-olds and 46.4% for 6- to 11-year-olds. Compared to age at treatment of 15–18 years, age at treatment of 6–11 years (aHR: 2.19, 95% CI 1.02–4.67) and 12–14 years (aHR: 2.02, 95% CI 1.15–3.55) was associated with an increased risk of ETT failure. In the total study sample, the estimated cumulative survival probability was 93.3% at 12 months, 88.0% at 24 months, 76.2% at 36 months, 71.0% at 48 months, and 69.1% at 60 months.

Conclusions

In children, ETT are more likely to survive when NSRCTs are performed at an older age.
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

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

Background

Collagen 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.

Methods

In 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).

Results

TCMF-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).

Conclusion

These 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

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

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

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

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

Background

The 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.

Methods

We 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.

Results

Overall, 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.

Conclusions

Our 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

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

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

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
Genome-wide identification and characterization of circular RNA m6A modification in pancreatic cancer
Authors: Ye Ying , Feng Weiyi , Zhang Jialiang , Zhu Kaiyu , Huang Xudong , Pan Ling , Su Jiachun , Zheng Yanfen , Li Rui , Deng Shuang , Bai Ruihong , Zhuang Lisha , Wei Lusheng , Deng Junge , Li Mei , Chen Rufu , Lin Dongxin , Zuo Zhixiang , Zheng Jian
Published: November 2021

Background

N6-methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells and play critical roles in cancer. While most related studies focus on m6A modifications in linear RNA, transcriptome-wide profiling and exploration of m6A modification in circular RNAs in cancer is still lacking.

Methods

For the detection of m6A modification in circRNAs, we developed a new bioinformatics tools called Circm6A and applied it to the m6A-seq data of 77 tissue samples from 58 individuals with pancreatic ductal adenocarcinoma (PDAC).

Results

Circm6A performs better than the existing circRNA identification tools, which achieved highest F1 score among these tools in the detection of circRNAs with m6A modifications. By using Circm6A, we identified a total of 8807 m6A-circRNAs from our m6A-seq data. The m6A-circRNAs tend to be hypermethylated in PDAC tumor tissues compared with normal tissues. The hypermethylated m6A-circRNAs were associated with a significant gain of circRNA-mRNA coexpression network, leading to the dysregulation of many important cancer-related pathways. Moreover, we found the cues that hypermethylated m6A-circRNAs may promote the circularization and translation of circRNAs.

Conclusions

These comprehensive findings further bridged the knowledge gaps between m6A modification and circRNAs fields by depicting the m6A-circRNAs genomic landscape of PDAC patients and revealed the emerging roles played by m6A-circRNAs in pancreatic cancer. Circm6A is available at https://github.com/canceromics/circm6a.
How do overweight people dropout of a weight loss diet? A qualitative study
Authors: Bazrafkan Leila , Choobineh Mohammad Amin , Shojaei Mehrnaz , Bozorgi Alireza , Sharifi Mohammad Hossein
Published: November 2021

Background

The growing trend of overweight and obesity in many developed and developing countries in recent years has made obesity one of the most significant health problems in the world. The treatment of overweight and obese people is challenging, as patients have difficulty adhering to a weight-loss diet. Thus, the present study aimed to identify the reasons for the dropout of weight-loss diets.

Methods

This qualitative study using content analysis was conducted in a comprehensive health center in Shiraz, southern Iran, between April and October 2020. The study was performed on 27 participants with a history of obesity and diet dropout selected via purposive and theoretical sampling. The data were gathered through semi-structured interviews and were thematically analyzed.

Results

The participants included 25 females (92.6%) and two males (7.4%) with a mean age of 33.4 ± 8.4 years. Data analysis resulted in the emergence of three themes and 14 sub-themes. The first theme was personal reasons for diet dropout, which included six sub-themes; i.e., misunderstanding of diet, not having enough motivation, stress and hormonal disorder, having the feel of “being harmful to health”, lack of mental and psychological preparation, and personal taste. The second theme was familial and social reasons for diet dropout, including two sub-themes, i.e., social and familial problems. Finally, the third theme was the reasons related to diet characteristics, including six sub-themes: ineffectiveness of diet, expensiveness of diet food and dietary supplements, family problems, unavailability of food, unscientific and unconventional diets feeling bad about the diet, and unpalatable diet food. All the concepts were related to each other and resulted in a pattern revealing the experiences of overweight people and who had dropped out of weight-loss diets.

Conclusion

The reasons for diet dropout were divided into three levels: personal reasons, familial and social reasons, and diet characteristics. Overall, clinicians should pay attention to the complexity of diets to increase the success rate of weight management. Based on the current study findings, a guideline is recommended to guide patients who dropout of weight-loss diets.
A Case–Control Study of Tackle-Based Head Injury Assessment (HIA) Risk Factors in the National Rugby League
Authors: Gardner Andrew J. , Iverson Grant L. , Edwards Suzi , Tucker Ross
Published: November 2021

Background

The tackle is the in-game activity carrying the greatest risk for concussion in rugby. A recent evaluation of tackle characteristics in rugby union precipitated a rule modification to reduce head impact risk during tackles. This study aims to replicate the work conducted in rugby union by examining the association between tackle characteristics and head injury events in professional rugby league.

Methods

There were 446 tackles resulting in a head injury assessment (HIA) and 5,694 tackles that did not result in a head injury from two National Rugby League (NRL) seasons that were reviewed and coded. Tackle height, body position of players, and contact area on an opponent’s body were evaluated, with the propensity of each situation to cause an HIA calculated as HIAs per 1000 events.

Results

The propensity for tacklers to sustain a head injury was 0.99 HIAs per 1000 tackles, 1.74-fold greater than for the ball carrier (0.57 HIAs per 1000 tackles). There was a 3.2-fold higher risk for an HIA when the tackler was upright compared to bent-at-the-waist. The greatest risk of a tackler HIA occurred when head contact was very low (knee, boot) or high (head and elbow). HIAs were most common following head-to-head impacts. The lowest propensity for tackler HIA was found when the tackler’s head was in proximity with the ball carrier’s torso.

Conclusions

The result of this study replicated the findings in professional rugby union. This has implications for the injury prevention initiatives implemented to reduce HIA risk because the majority of injuries are sustained by the tackler.
Hospital admissions for stress-related presentations among school-aged adolescents during term time versus holidays in England: weekly time series and retrospective cross-sectional analysis
Authors: Blackburn Ruth , Ajetunmobi Omotomilola , Mc Grath-Lone Louise , Hardelid Pia , Shafran Roz , Gilbert Ruth , Wijlaars Linda
Published: November 2021

Background

Schools are a potential stressor for adolescents and may contribute to emergency hospital admissions.

Aims

We describe rates of stress-related presentations (SRPs) among school-aged adolescents (11–17 years) during school terms and holidays, and explore differences by age and gender.

Method

Using national administrative hospital data, we defined an SRP as an emergency hospital admission with a primary diagnosis related to pain, psychosomatic symptoms (e.g. fatigue) or mental health problems, or with self-harm indicated in any diagnostic position. We estimated incidence rate ratios for weekly SRPs in term time versus holidays from 2014–2015 to 2017–2018, using negative binomial regression models, stratified by age and gender. We estimated the cumulative incidence of any SRP between 11 and 17 years by analysing prior hospital admission histories of adolescents with an SRP in 2017–2018.

Results

Over the 4-year study period, 305 491 SRPs in 171 013 school-aged adolescents accounted for 31% of emergency admissions for this group. SRPs were predominantly for mental health problems or self-harm (38%), or pain (35%). Weekly admission rates for SRPs were higher in term time than holidays for all ages (age-specific incidence rate ratios were 1.15–1.49 for girls and 1.08–1.60 for boys). Rates were highest for girls aged 14 and 15 years. The estimated cumulative incidence of any SRP between 11 and 17 years was 7.9% for girls and 4.1% for boys.

Conclusions

Hospital admissions for SRPs are common among adolescents, affecting around two girls and one boy in every classroom. Higher rates in term time than holidays suggest that school factors may contribute.
Quantification of Compatibility Between Polymeric Excipients and Atenolol Using Principal Component Analysis and Hierarchical Cluster Analysis
Authors: Rojek Barbara , Gazda Maria , Wesolowski Marek
Published: November 2021

An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients can be selected, among others, by compatibility studies since incompatibilities between ingredients of the drug formulations adversely affect their bioavailability, stability, efficacy, and safety. Therefore, new, fast, and reliable methods for detecting incompatibility are constantly being sought. Hence, the purpose of this work was to assess the usefulness of a heating, cooling, and reheating differential scanning calorimetry (DSC) program for detecting potential incompatibilities between atenolol, an active pharmaceutical ingredient (API), and polymeric excipients. Hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) were used as supporting techniques. Additionally, principal component analysis (PCA) and hierarchical cluster analysis (HCA) served as tools to support the interpretation of the data acquired from the DSC curves and FTIR spectra. As the alterations in the shape of the DSC peak of atenolol which are indicative of incompatibility are visible only on the cooling and reheating curves of the mixtures, the DSC heating–cooling–reheating program was found to be very useful for identifying potential incompatibilities in the binary mixtures of atenolol and polymeric excipients. The melting and recrystallization of atenolol alone and in its mixtures were also confirmed by HSM, while FTIR displayed changes in the spectra of mixtures due to incompatibility. These studies revealed that atenolol is incompatible with hydroxyethylcellulose, hypromellose, and methylcellulose. PXRD measurements at room temperature revealed that the crystallinity of atenolol did not change in these mixtures. However, its crystallinity was reduced in the mixtures previously heated up to 155 °C and then cooled to 25 °C.

Graphical abstract
Spontaneous emission mediated by graphene/hexagonal boron nitride/graphene sandwich structure
Authors: Mu Hong-Qian , Zhou Ying , Wang Tong-Biao , Zhang De-Jian , Liu Wen-Xing , Yu Tian-Bao , Liao Qing-Hua
Published: November 2021

Controlling the spontaneous emission of atoms or molecules is an interesting research topic in the field of quantum optics. Here we provide a perspective on modulating the interaction between two quantum emitters through a sandwich structure composed of graphene and hexagonal boron nitride (hBN). The dependence of interaction between quantum emitters on the thickness of hBN and chemical potential of graphene is investigated in detail. When the transition frequency of quantum emitter is located in the hyperbolic band of type I supported by hBN, the radiative state can be easily modulated by adjusting the chemical potential of graphene. So it is easy to switch the interaction of quantum emitters from superradiant state to subradiant state by external electric field. When the transition frequency of quantum emitter is located in hyperbolic band of type II, the system can be always in the superradiant state. We predict the further research perspectives of spontaneous emission and superradiance with the help of metasurfaces based on two-dimensional materials.
The Structure of Scares: Art, Horror, and Immersion in Marisha Pessl'sNight Film
Authors: Macero Melissa C.
Published: November 2021

Is immersion merely a subjective response to a work, or can it be an objective formal feature of the work itself? This article examines the unique situation of horror as a genre that demands a substantial level of immersion in order to be successful and will begin to answer this question through a close reading of Marisha Pessl's Night Film (2013). Through the novel's intricate staging of different forms of immersion that is made possible by its extended length, this article argues that Pessl and the horror genre more generally seek to establish a difference between something like literal immersion, which requires the engrossment of a reader or viewer in the world of the story, and immersion as a formal technique, which is for the most part indifferent to the actual engagement of the audience and instead produces a claim immanent to the work itself.
A scalable, clinically severe pig model for Duchenne muscular dystrophy
Authors: Stirm Michael , Fonteyne Lina Marie , Shashikadze Bachuki , Lindner Magdalena , Chirivi Maila , Lange Andreas , Kaufhold Clara , Mayer Christian , Medugorac Ivica , Kessler Barbara , Kurome Mayuko , Zakhartchenko Valeri , Hinrichs Arne , Kemter Elisabeth , Krause Sabine , Wanke Rüdiger , Arnold Georg J. , Wess Gerhard , Nagashima Hiroshi , Hrabĕ de Angelis Martin , Flenkenthaler Florian , Kobelke Levin Arne , Bearzi Claudia , Rizzi Roberto , Bähr Andrea , Reese Sven , Matiasek Kaspar , Walter Maggie C. , Kupatt Christian , Ziegler Sibylle , Bartenstein Peter , Fröhlich Thomas , Klymiuk Nikolai , Blutke Andreas , Wolf Eckhard
Published: November 2021

Large-animal models for Duchenne muscular dystrophy (DMD) are crucial for the evaluation of diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMDΔ52) exhibit molecular, clinical and pathological hallmarks of DMD, but die before sexual maturity and cannot be propagated by breeding. Therefore, we generated female DMD+/− carriers. A single founder animal had 11 litters with 29 DMDY/−, 34 DMD+/− as well as 36 male and 29 female wild-type offspring. Breeding with F1 and F2 DMD+/− carriers resulted in an additional 114 DMDY/− piglets. With intensive neonatal management, the majority survived for 3-4 months, providing statistically relevant cohorts for experimental studies. Pathological investigations and proteome studies of skeletal muscles and myocardium confirmed the resemblance to human disease mechanisms. Importantly, DMDY/− pigs displayed progressive myocardial fibrosis and increased expression of connexin-43, associated with significantly reduced left ventricular ejection fraction, at 3 months. Furthermore, behavioral tests provided evidence for impaired cognitive ability. Our breeding cohort of DMDΔ52 pigs and standardized tissue repositories provide important resources for studying DMD disease mechanisms and for testing novel treatment strategies.
Recent Progress in Prussian Blue/Prussian Blue Analogue-Derived Metallic Compounds
Authors: Shan Yang , Zhang Guangxun , Yin Wei , Pang Huan , Xu Qiang
Published: November 2021

Prussian blue (PB) and its analogues (PBAs) are promising coordination polymers (CPs) with an adjustable composition and open framework. Nonetheless, their intrinsic electrochemical activity and electrical conductivity are poor, which hinder their applications in energy conversion and storage. In catalytic applications, metal compounds derived from PB/PBAs have a lot of advantages, such as outstanding stability, selectivity, and electrical conductivity. Furthermore, they can be used as electrode materials for electrochemical energy storage and conversion, while having preferable electronic conductivity, sufficient catalytic active sites, as well as a larger specific surface area and tunable size to achieve an optimized performance. This review summarizes the current achievements of PB/PBA-derived metallic nanomaterials, as well as the existing limitations, urgent challenges and future development.
Birefringence Control of Photoalignable Liquid Crystalline Polymers Based on anIn SituExchange of Oriented Mesogenic Side Groups
Authors: Sakai Ayaka , Noshizono Toshiki , Kondo Mizuho , Sasaki Tomoyuki , Sakamoto Moritsugu , Ono Hiroshi , Kawatsuki Nobuhiro
Published: November 2021

An in situ exchange of oriented mesogenic side groups containing Schiff base moieties realized birefringence control of photoalignable liquid crystalline polymers between 0.13 and 0.44. Both thermal hydrolysis of the oriented side groups and in situ condensation using phenyl amine derivatives with a high inherent birefringence vary the birefringence and thermal stability of oriented films without distortion of the oriented structure.