bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED ARTICLE: Knockdown of circRNA_0007534 suppresses the tumorigenesis of cervical cancer via miR-206/GREM1 axis
Authors: Sun Qiang , Qi Xiangying , Zhang Wenyan , Li Xiaoyu 
Published: January 2021

AbstractBackgroundIncreasing evidence manifested that circular RNAs (circRNAs) acted as crucial regulators in human cancers by targeting the miRNA/mRNA axis, including cervical cancer (CC). Circ_0007534 was reported to promote CC cell proliferation and invasion by the miR-498/BMI-1 axis. The aim of this study was to explore a novel miRNA/mRNA network underlying circ_0007534 in CC regulation.MethodsThe quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to examine the levels of circ_0007534, miR-206 and Gremlin1 (GREM1). Cell viability was determined using MTT assay. BrdU and colony formation assays were performed for analyzing cell proliferation. Cell apoptosis was assessed by flow cytometry. The protein levels of GREM1 and apoptotic markers (Bcl-2, Bax, C-Caspase3) were measured via western blot. Cell invasion was detected by transwell assay. The target relationship was analyzed by dual-luciferase reporter assay. The impact of circ_0007534 on CC growth in vivo was ascertained by xenograft assay.ResultsCirc_0007534 expression was aberrantly increased in CC tissues and cells. Functionally, knockdown of circ_0007534 reduced CC cell growth and invasion but motivated apoptosis. In the mechanism, circ_0007534 targeted miR-206 and its regulatory function was associated with sponging miR-206. Moreover, circ_0007534 was found to regulate GREM1 level by targeting miR-206. The inhibitory effect of si-circ_0007534 on the malignant progression of CC was reversed after GREM1 was overexpressed. Furthermore, circ_0007534 inhibition also reduced tumor growth of CC in vivo partially by regulating miR-206/GREM1 axis.ConclusionThese results suggested that knockdown of circ_0007534 promoted the level of miR-206 to induce the expression downregulation of GREM1, consequently inhibiting the progression of CC.
Measuring implanted patient response to tone pips
Authors: Cornejo Juan M. , Quintana Agar K. , Beltran Nohra E. , Granados Pilar 
Published: January 2021

Abstract
Background
An electrical potential not previously reported—electrical cochlear response (ECR)—observed only in implanted patients is described. Its amplitude and growth slope are a measurement of the stimulation achieved by a tone pip on the auditory nerve. The stimulation and recording system constructed for this purpose, the features of this potential obtained in a group of 43 children, and its possible clinical use are described. The ECR is obtained by averaging the EEG epochs acquired each time the cochlear implant (CI) processes a tone pip of known frequency and intensity when the patient is sleeping and using the CI in everyday mode. The ECR is sensitive to tone pip intensity level, microphone sensitivity, sound processor gain, dynamic range of electrical current, and responsiveness to electrical current of the auditory nerve portion involved with the electrode under test. It allows individual evaluation of intracochlear electrodes by choosing, one at the time, the central frequency of the electrode as the test tone pip frequency, so the ECR measurement due to a variable intensity tone pip allows to establish the suitability of the dynamic range of the electrode current.

Results
There is a difference in ECR measurements when patients are grouped based on their auditory behavior. The ECR slope and amplitude for the Sensitive group is 0.2 μV/dBHL and 10 μV at 50 dBHL compared with 0.04 μV/dBHL and 3 μV at 50dBHL for the Inconsistent group. The clinical cases show that adjusting the dynamic range of current based on the ECR improved the patient’s auditory behavior.

Conclusions
ECR can be recorded regardless of the artifact due to the electromyographic activity of the patient and the functioning of the CI. Its amplitude and growth slope versus the intensity of the stimulus differs between electrodes. The relationship between minimum ECR detection intensity level and auditory threshold suggests the possibility of estimating patient auditory thresholds this way. ECR does not depend on the subject’s age, cooperation, or health status. It can be obtained at any time after implant surgery and the test procedure is the same regardless of device manufacturer.
A qualitative study of barriers to employment experienced by people living with HIV in Toronto and Ottawa
Authors: Perri Melissa , Craig-Neil Amy , Gaspar Mark , Hunter Charlotte , Kendall Claire , Alexander Ower , Pinto Andrew D. 
Published: January 2021

Abstract
Background
Effective treatment has extended the life expectancy and reduced disability in people living with HIV (PLWH). However, previous research has found 45–65% of working-age PLWH were unemployed compared to 5–10% in the general public of North America and Europe. We examined the barriers to gaining employment among PLWH.

Methods
Thirty-five in-depth interviews were conducted in person or over the phone with PLWH living in Toronto or Ottawa. This included PLWH who were unemployed but actively seeking employment, as well as PLWH who had successfully gained employment through an agency that specifically supported PLWH funded by the AIDS Committee of Toronto. Interviews were conducted between February 2019 and March 2020. All interviews were audio-recorded, transcribed and analyzed using thematic analysis.

Results
The majority of participants were between the ages of 40–55 and identified as male. Participants shared many common barriers when describing their attempts to attain or maintain employment. Although varying in employment status at the time of the study, consistent barriers included experiencing HIV stigma in workplaces, challenges overcoming mental health illnesses, and difficulties in navigating social assistance and unemployment insurance programs when pursuing a return to work.

Conclusions
PLWH face significant barriers when attempting to engage with employment opportunities. Health providers and organizations can do more to support campaigns to end HIV stigma, to support individuals in pursuing employment, and to advocate for policy change that supports reentry into the workforce for PLHA.
Tracking the effects of COVID-19 in rural China over time
Authors: Wang Huan , Zhang Markus , Li Robin , Zhong Oliver , Johnstone Hannah , Zhou Huan , Xue Hao , Sylvia Sean , Boswell Matthew , Loyalka Prashant , Rozelle Scott 
Published: January 2021

Abstract
Background
China issued strict nationwide guidelines to combat the COVID-19 outbreak in January 2020 and gradually loosened the restrictions on movement in early March. Little is known about how these disease control measures affected the 600 million people who live in rural China. The goal of this paper is to document the quarantine measures implemented in rural China outside the epicenter of Hubei Province and to assess the socioeconomic effect of the measures on rural communities over time.

Methods
We conducted three rounds of interviews with informants from 726 villages in seven provinces, accounting for over 25% of China’s overall rural population. The survey collected data on rural quarantine implementation; COVID-19 infections and deaths in the survey villages; and effects of the quarantine on employment, income, education, health care, and government policies to address any negative impacts. The empirical findings of the work established that strict quarantine measures were implemented in rural villages throughout China in February.

Results
There was little spread of COVID-19 in rural communities: an infection rate of 0.001% and zero deaths reported in our sample. However, there were negative social and economic outcomes, including high rates of unemployment, falling household income, rising prices, and disrupted student learning. Health care was generally accessible, but many delayed their non-COVID-19 health care due to the quarantine measures. Only 20% of villagers received any form of local government aid, and only 11% of villages received financial subsidies. There were no reports of national government aid programs that targeted rural villagers in the sample areas.

Conclusions
By examining the economic and social effects of the COVID-19 restrictions in rural communities, this study will help to guide other middle- and low-income countries in their containment and restorative processes. Without consideration for economically vulnerable populations, economic hardships and poverty will likely continue to have a negative impact on the most susceptible communities.
Iran health insurance system in transition: equity concerns and steps to achieve universal health coverage
Authors: Doshmangir Leila , Bazyar Mohammad , Rashidian Arash , Gordeev Vladimir Sergeevich 
Published: January 2021

Abstract
Background
Equity, efficiency, sustainability, acceptability to clients and providers, and quality are the cornerstones of universal health coverage (UHC). No country has a single way to achieve efficient UHC. In this study, we documented the Iranian health insurance reforms, focusing on how and why certain policies were introduced and implemented, and which challenges remain to keep a sustainable UHC.

Methods
This retrospective policy analysis used three sources of data: a comprehensive and chronological scoping review of literature, interviews with Iran health insurance policy actors and stakeholders, and a review of published and unpublished official documents and local media. All data were analysed using thematic content analysis.

Results
Health insurance reforms, especially health transformation plan (HTP) in 2014, helped to progress towards UHC and health equity by expanding population coverage, a benefits package, and enhancing financial protection. However, several challenges can jeopardize sustaining this progress. There is a lack of suitable mechanisms to collect contributions from those without a regular income. The compulsory health insurance coverage law is not implemented in full. A substantial gap between private and public medical tariffs leads to high out-of-pocket health expenditure. Moreover, controlling the total health care expenditures is not the main priority to make keeping UHC more sustainable.

Conclusion
To achieve UHC in Iran, the Ministry of Health and Medical Education and health insurance schemes should devise and follow the policies to control health care expenditures. Working mechanisms should be implemented to extend free health insurance coverage for those in need. More studies are needed to evaluate the impact of health insurance reforms in terms of health equity, sustainability, coverage, and access.
Mitigation of biases in estimating hazard ratios under non-sensitive and non-specific observation of outcomes–applications to influenza vaccine effectiveness
Authors: Baum Ulrike , Kulathinal Sangita , Auranen Kari 
Published: January 2021

Abstract
Background
Non-sensitive and non-specific observation of outcomes in time-to-event data affects event counts as well as the risk sets, thus, biasing the estimation of hazard ratios. We investigate how imperfect observation of incident events affects the estimation of vaccine effectiveness based on hazard ratios.

Methods
Imperfect time-to-event data contain two classes of events: a portion of the true events of interest; and false-positive events mistakenly recorded as events of interest. We develop an estimation method utilising a weighted partial likelihood and probabilistic deletion of false-positive events and assuming the sensitivity and the false-positive rate are known. The performance of the method is evaluated using simulated and Finnish register data.

Results
The novel method enables unbiased semiparametric estimation of hazard ratios from imperfect time-to-event data. False-positive rates that are small can be approximated to be zero without inducing bias. The method is robust to misspecification of the sensitivity as long as the ratio of the sensitivity in the vaccinated and the unvaccinated is specified correctly and the cumulative risk of the true event is small.

Conclusions
The weighted partial likelihood can be used to adjust for outcome measurement errors in the estimation of hazard ratios and effectiveness but requires specifying the sensitivity and the false-positive rate. In absence of exact information about these parameters, the method works as a tool for assessing the potential magnitude of bias given a range of likely parameter values.
Real-time liver tracking algorithm based on LSTM and SVR networks for use in surface-guided radiation therapy
Authors: Wang Guangyu , Li Zhibin , Li Guangjun , Dai Guyu , Xiao Qing , Bai Long , He Yisong , Liu Yaxin , Bai Sen 
Published: January 2021

Abstract
Background
Surface-guided radiation therapy can be used to continuously monitor a patient’s surface motions during radiotherapy by a non-irradiating, noninvasive optical surface imaging technique. In this study, machine learning methods were applied to predict external respiratory motion signals and predict internal liver motion in this therapeutic context.

Methods
Seven groups of interrelated external/internal respiratory liver motion samples lasting from 5 to 6 min collected simultaneously were used as a dataset, Dv. Long short-term memory (LSTM) and support vector regression (SVR) networks were then used to establish external respiratory signal prediction models (LSTMpred/SVRpred) and external/internal respiratory motion correlation models (LSTMcorr/SVRcorr). These external prediction and external/internal correlation models were then combined into an integrated model. Finally, the LSTMcorr model was used to perform five groups of model updating experiments to confirm the necessity of continuously updating the external/internal correlation model. The root-mean-square error (RMSE), mean absolute error (MAE), and maximum absolute error (MAX_AE) were used to evaluate the performance of each model.

Results
The models established using the LSTM neural network performed better than those established using the SVR network in the tasks of predicting external respiratory signals for latency-compensation (RMSE < 0.5 mm at a latency of 450 ms) and predicting internal liver motion using external signals (RMSE < 0.6 mm). The prediction errors of the integrated model (RMSE ≤ 1.0 mm) were slightly higher than those of the external prediction and external/internal correlation models. The RMSE/MAE of the fifth model update was approximately ten times smaller than that of the first model update.

Conclusions
The LSTM networks outperform SVR networks at predicting external respiratory signals and internal liver motion because of LSTM’s strong ability to deal with time-dependencies. The LSTM-based integrated model performs well at predicting liver motion from external respiratory signals with system latencies of up to 450 ms. It is necessary to update the external/internal correlation model continuously.
Best practice guidelines in managing the craniofacial aspects of skeletal dysplasia
Authors:   on behalf of the Skeletal Dysplasia Management Consortium, Savarirayan Ravi , Tunkel David E. , Sterni Laura M. , Bober Michael B. , Cho Tae-Joon , Goldberg Michael J. , Hoover-Fong Julie , Irving Melita , Kamps Shawn E. , Mackenzie William G. , Raggio Cathleen , Spencer Samantha A. , Bompadre Viviana , White Klane K. 
Published: January 2021

AbstractBackgroundRecognition and appropriate management of the craniofacial manifestations of patients with skeletal dysplasia are challenging, due to the rarity of these conditions, and dearth of literature to support evidence-based clinical decision making.MethodsUsing the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, best practice guidelines in the management of craniofacial aspects of these patients.ResultsAfter a comprehensive literature review, 23 initial statements were generated and critically discussed, with subsequent development of a list of 22 best practice guidelines after a second round voting.ConclusionsThe guidelines are presented and discussed to provide context and assistance for clinicians in their decision making in this important and challenging component of care for patients with skeletal dysplasia, in order standardize care and improve outcomes.
Management of unexplained: poly-consultation and hyperfrequency on Primary Health Chilean Attention. A qualitative and exploratory study
Authors: Fuster Sánchez Nicolás , Rivera López Diego , Sir Retamales Hugo , Gómez Pérez Constanza , Rodríguez Torres Magdalena 
Published: January 2021

Abstract
Background
In Europe, Latin-America, and Asia, poly-consultation has become a complex problem for managing different healthcare systems. However, in the current literature, little attention has been paid to exploring territorial and critical analysis perspectives to manage unexplained symptoms. The purpose of this study is to analyze the socio-structural elements that underlie the users’ phenomenon of poly-consultation or hyperfrequency in the Chilean primary healthcare system (PHCS).

Methods
This paper represents qualitative data collected as part of an exploratory study that used mixed methods across three metropolitan areas of Santiago, Valparaíso, and Concepción, Chile. The study involved a sample of 24 subjects from administrative and management positions in PHC who were recruited from Family Health Care Centers, considering urban municipalities from the low, medium, and high stratum. The study collected data using one set of semi-standardized interviews during a year—data analysis using qualitative content analysis.

Results
This article shows that poly-consultant patients provide a critical clinic category to management that cannot be cover by current biomedical models. Data showed the strain of a somatoform category, especially in the clinic and epistemological exercise. Precisely, the relevance of Chile’s case, a mixed health system, and their effects: the naturalization of collective problems managed as individual problems.

Conclusions
The study results can inform healthcare professionals and managers of developing practical and territorially based. We conclude that hyperfrequency and poly-consultation in Chile reveal relevant stratification in the territory. Those particularities open an opportunity to study quantitative methods, including current analysis categories, to develop new research.
Hyperthyroidism in gestational trophoblastic disease – a literature review
Authors: Pereira Jarett Vanz-Brian , Lim Taylor 
Published: January 2021

Abstract
Objective
Gestational trophoblastic disease (GTD) is a group of pregnancy-related disorders that arise from abnormal proliferation of placental trophoblast. Some patients with GTD develop hyperthyroidism, a rare but potentially life-threatening complication requiring early detection and management. Existing literature on hyperthyroidism in GTD is scant. This review aims to analyse the epidemiology, pathophysiology and management of this phenomenon.

Methods
A comprehensive search of MEDLINE, EMBASE and Cochrane Library was performed to obtain articles that explored hyperthyroidism in GTD. A total of 405 articles were screened and 228 articles were considered for full-text review. We selected articles that explored epidemiology, pathophysiology and outcomes/management of hyperthyroidism in GTD.

Results
The pathophysiology of hyperthyroidism in GTD is well-investigated. Placental trophoblastic tissue secretes excessive hCG, which is structurally similar to thyroid stimulating hormone and also has enhanced thyrotropic activity compared to normal hCG. The incidence and prevalence of hyperthyroidism in GTD varies worldwide, with lower rates associated with high uptake of early antenatal screening and early GTD detection. No clear risk factors for hyperthyroidism in GTD were identified. While hyperthyroidism can be definitively managed with surgical evacuation of the uterus, severe complications associated with hyperthyroidism in GTD have been reported, including thyroid storm-induced multi-organ failure, ARDS, and pulmonary hypertension.

Conclusion
Early detection of GTD is critical to prevent development of hyperthyroidism and its associated complications. Hyperthyroidism should be recognised as an important perioperative consideration for women undergoing surgery for GTD, and requires appropriate management. Future studies should explore risk factors for hyperthyroidism in GTD, which may facilitate earlier identification of high-risk women.
STOML2 potentiates metastasis of hepatocellular carcinoma by promoting PINK1-mediated mitophagy and regulates sensitivity to lenvatinib
Authors: Zheng Yahui , Huang Chong , Lu Lu , Yu Kangkang , Zhao Jing , Chen Mingquan , Liu Lu , Sun Qingfeng , Lin Zhifei , Zheng Jianming , Chen Jinhong , Zhang Jubo 
Published: January 2021

Abstract
Background
Dysregulation of both mitochondrial biogenesis and mitophagy is critical to sustain oncogenic signaling pathways. However, the mechanism of mitophagy in promoting hepatocellular carcinoma (HCC) progression remains poorly understood. In this study, we investigated the clinical significance and biological involvement of mitochondrial inner membrane protein STOML2 in HCC.

Methods
STOML2 was identified by gene expression profiles of HCC tissues and was measured in tissue microarray and cell lines. Gain/loss-of-function experiment was applied to study the biological function of STOML2 in HCC. Flow cytometry, Western blotting, laser confocal microscopy, transmission electron microscopy, and co-immunoprecipitation were used to detect and analyze mitophagy. ChIP and luciferase reporter assay were conducted to evaluate the relationship between STOML2 and HIF-1α. The sensitivity to lenvatinib was assessed in HCC both in vitro and in vivo.

Results
Increased expression of STOML2 was found in HCC compared with paired peritumoral tissues. It was more significant in HCC with metastasis and correlated with worse overall survival and higher probability of recurrence after hepatectomy. Upregulation of STOML2 accelerated HCC cells colony formation, migration and invasion. Mechanically, TCGA dataset-based analysis showed enrichment of autophagy-related pathways in STOML2 highly-expressed HCC. Next, STOML2 was demonstrated to interact and stabilize PINK1 under cellular stress, amplify PINK1-Parkin-mediated mitophagy and then promote HCC growth and metastasis. Most interestingly, HIF-1α was upregulated and transcriptionally increased STOML2 expression in HCC cells under the treatment of lenvatinib. Furthermore, higher sensitivity to lenvatinib was found in HCC cells when STOML2 was downregulated. Combination therapy with lenvatinib and mitophagy inhibitor hydroxychloroquine obtained best efficacy.

Conclusions
Our findings suggested that STOML2 could amplify mitophagy through interacting and stabilizing PINK1, which promote HCC metastasis and modulate the response of HCC to lenvatinib. Combinations of pharmacologic inhibitors that concurrently block both angiogenesis and mitophagy may serve as an effective treatment for HCC.