bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hsa_circ_0004296 inhibits metastasis of prostate cancer by interacting with EIF4A3 to prevent nuclear export of ETS1 mRNA
Authors: Mao Shiyu , Zhang Wentao , Yang Fuhan , Guo Yadong , Wang Hong , Wu Yuan , Wang Ruiliang , Maskey Niraj , Zheng Zongtai , Li Cheng , Ma Wenchao , Zhang Junfeng , Yan Yang , Yao Xudong 
Published: October 2021

Abstract
Background
Circular RNAs (circRNAs) have been shown to play vital biological functions in various tumors, including prostate cancer (PCa). However, the roles of circRNAs in the metastasis of PCa remain unclear. In the present study, differentially expressed circRNAs associated with PCa metastasis were screened using high-throughput RNA sequencing, from which hsa_circ_0004296 was identified.

Methods
Quantitative real-time PCR (qRT-PCR) was used to detect the expression of circ_0004296 in PCa tissues and adjacent normal tissues as well as in blood and urine. Gain and loss of function experiments were performed to investigate the function of circ_0004296 in PCa. Bioinformatics analyses, RNA pull-down assay, and mass spectrometry were conducted to identify RNA-binding proteins. RNA immunoprecipitation and RNA and protein nuclear-cytoplasmic fractionation were performed to investigate the underlying mechanism. A xenograft mouse model was used to analyze the effect of circ_0004296 on PCa growth and metastasis in vivo.

Results
The expression of circ_0004296 was decreased in PCa tissues, blood, and urine, which was negatively associated with metastasis. Furthermore, gain and loss of function experiments in vitro and in vivo showed that circ_0004296 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of PCa cells. Mechanistically, circ_0004296 regulated host gene ETS1 expression at the post-transcriptional level. EIF4A3 was identified and confirmed as the downstream binding protein of circ_0004296. EIF4A3 expression was significantly upregulated in PCa tissues and associated with PCa metastasis. Silencing EIF4A3 suppressed PCa cell proliferation, migration, invasion, and EMT.

Conclusions
Circ_0004296 overexpression efficiently inhibited ETS1 mRNA nuclear export by promoting EIF4A3 retention in the nucleus, leading to the downregulation of ETS1 expression and suppression of PCa metastasis; thus, circ_0004296 might be a potential biomarker and therapeutic target for patients with PCa.
Prevention of recurrent respiratory infections
Authors: Chiappini Elena , Santamaria Francesca , Marseglia Gian Luigi , Marchisio Paola , Galli Luisa , Cutrera Renato , de Martino Maurizio , Antonini Sara , Becherucci Paolo , Biasci Paolo , Bortone Barbara , Bottero Sergio , Caldarelli Valeria , Cardinale Fabio , Gattinara Guido Castelli , Ciarcià Martina , Ciofi Daniele , D’Elios Sofia , Di Mauro Giuseppe , Doria Mattia , Indinnimeo Luciana , Lo Vecchio Andrea , Macrì Francesco , Mattina Roberto , Miniello Vito Leonardo , del Giudice Michele Miraglia , Morbin Guido , Motisi Marco Antonio , Novelli Andrea , Palamara Anna Teresa , Panatta Maria Laura , Pasinato Angela , Peroni Diego , Perruccio Katia , Piacentini Giorgio , Pifferi Massimo , Pignataro Lorenzo , Sitzia Emanuela , Tersigni Chiara , Torretta Sara , Trambusti Irene , Trippella Giulia , Valentini Diletta , Valentini Sandro , Varricchio Attilio , Verga Maria Carmen , Vicini Claudio , Zecca Marco , Villani Alberto 
Published: October 2021

AbstractRecurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.
The impact of artificial intelligence on learner–instructor interaction in online learning
Authors: Seo Kyoungwon , Tang Joice , Roll Ido , Fels Sidney , Yoon Dongwook 
Published: October 2021

AbstractArtificial intelligence (AI) systems offer effective support for online learning and teaching, including personalizing learning for students, automating instructors’ routine tasks, and powering adaptive assessments. However, while the opportunities for AI are promising, the impact of AI systems on the culture of, norms in, and expectations about interactions between students and instructors are still elusive. In online learning, learner–instructor interaction (inter alia, communication, support, and presence) has a profound impact on students’ satisfaction and learning outcomes. Thus, identifying how students and instructors perceive the impact of AI systems on their interaction is important to identify any gaps, challenges, or barriers preventing AI systems from achieving their intended potential and risking the safety of these interactions. To address this need for forward-looking decisions, we used Speed Dating with storyboards to analyze the authentic voices of 12 students and 11 instructors on diverse use cases of possible AI systems in online learning. Findings show that participants envision adopting AI systems in online learning can enable personalized learner–instructor interaction at scale but at the risk of violating social boundaries. Although AI systems have been positively recognized for improving the quantity and quality of communication, for providing just-in-time, personalized support for large-scale settings, and for improving the feeling of connection, there were concerns about responsibility, agency, and surveillance issues. These findings have implications for the design of AI systems to ensure explainability, human-in-the-loop, and careful data collection and presentation. Overall, contributions of this study include the design of AI system storyboards which are technically feasible and positively support learner–instructor interaction, capturing students’ and instructors’ concerns of AI systems through Speed Dating, and suggesting practical implications for maximizing the positive impact of AI systems while minimizing the negative ones.
Understanding parental self-medication with antibiotics among parents of different nationalities: a cross-sectional study
Authors: Zhou Zhongliang , Zhao Dantong , Zhang Huarui , Shen Chi , Cao Dan , Liu Guanping , Zhu Liang , Fang Yu 
Published: October 2021

AbstractBackgroundThere is an increasing trend on the practices of parental self-medication with antibiotics (PSMA) around world, accelerating the antibiotic abuse. This study aims to examine the nationality differences in the practices of PSMA and knowledge, attitudes and practices (KAP) toward antibiotic use, and understand the practices of PSMA among parents of various nationalities in China.MethodsA cross-sectional study based on a structured questionnaire survey was conducted in Xi’an, Shaanxi Province, China, from September 2018 to October 2018. A total of 299 respondents participated in. The practices of PSMA (a dichotomous variable) and KAP toward antibiotic use (a continuous variable) served as dependent variables. Participant’s nationality was regarded as the independent variable. Binary logistic regression and ordinary least square regression were employed to examine the association between parent’s nationality and the practices of PSMA, and KAP toward antibiotic use, respectively.Results121 (40.88%) Chinese, 100 (33.76%) other Asians and 75 (25.34%) Occidentals were included in final analysis, with a sample size of 296. Chinese were more likely to practice PSMA (OR = 7.070; 95% CI 1.315, 38.01), with worse knowledge (Coef. = − 0.549; 95% CI − 1.021, − 0.078), attitudes (Coef. = − 3.069; 95% CI − 4.182, − 1.956) and practices (Coef. = − 1.976; 95% CI − 3.162, − 0.790) toward antibiotic use, compared to their Occidental counterparts. The main reasons for the practices of PSMA were enough previous medication experience (80.49%) and same ailments with no need to see a doctor (39.02%), with common symptoms such as fever (60.98%) and cough (58.54%). Purchasing antibiotics at pharmacies (92.08%) and using leftover antibiotics (26.83%) were usual approaches.ConclusionsThe study highlights the gaps in the practices of PSMA and KAP toward antibiotic use among parents of different nationalities. The access to obtain antibiotics from pharmacies reflects the pharmacists’ unaware of laws on prescription of antibiotics, fierce competition in the pharmacy market, and the government’s lax supervision in China. It suggests the need to improve pharmacists’ training, enforce current legislations on pharmacy market regarding the sale of antibiotics, and provide practical and effective educational interventions for residents about antibiotic use.
Voices Carry
Authors: Morgan Cheryl A. 
Published: October 2021

AbstractThis article examines the urban fiction of Jeanne Marni’s 1898 Fiacres, a collection of twenty-five stories that first appeared in the daily newspaper Le Temps. The stories are presented in the form of dialogues transcribed by an invisible spectator from within the horse drawn carriages for hire, the fiacres, the fin de siècle taxi cabs. Training her eye on and lending her ear to Belle Époque Paris, Marni registers the conversations of Parisians as they move about the city. In these feminocentric, and by turns humorous or ironic texts, Marni hones an “urban comic” that merges two nineteenth-century figures: the “invisible” flâneuse and the “inaudible” rieuse, or funny woman. Focusing on the intersection of the representation of urban experience and the humorous in Fiacres, this article situates Marni’s sound bites within a genealogy of women writers and the city that looks back to Delphine Gay de Girardin’s witty chronicles of July Monarchy Paris, the “Courrier de Paris” (1836–1848), and ahead to Annie Ernaux’s ironic journal of urban selfhood in transit, Journal du dehors (1993).
Development of a novel real-time polymerase chain reaction assay for the sensitive detection of Schistosoma japonicum in human stool
Authors: Halili Sara , Grant Jessica R. , Pilotte Nils , Gordon Catherine A. , Williams Steven A. 
Published: October 2021

Background
Elimination and control of Schistosoma japonicum, the most virulent of the schistosomiasis-causing blood flukes, requires the development of sensitive and specific diagnostic tools capable of providing an accurate measurement of the infection prevalence in endemic areas. Typically, detection of S. japonicum has occurred using the Kato-Katz technique, but this methodology, which requires skilled microscopists, has been shown to radically underestimate levels of infection. With the ever-improving capabilities of next-generation sequencing and bioinformatic analysis tools, identification of satellite sequences and other highly repetitive genomic elements for use as real-time PCR diagnostic targets is becoming increasingly common. Assays developed using these targets have the ability to improve the sensitivity and specificity of results for epidemiological studies that can in turn be used to inform mass drug administration and programmatic decision making.

Methodology/Principal findings
Utilizing Tandem Repeat Analyzer (TAREAN) and RepeatExplorer2, a cluster-based analysis of the S. japonicum genome was performed and a tandemly arranged genomic repeat, which we named SjTR1 (Schistosoma japonicum Tandem Repeat 1), was selected as the target for a real-time PCR diagnostic assay. Based on these analyses, a primer/probe set was designed and the assay was optimized. The resulting real-time PCR test was shown to reliably detect as little as 200 ag of S. japonicum genomic DNA and as little as 1 egg per gram of human stool. Based on these results, the index assay reported in this manuscript is more sensitive than previously published real-time PCR assays for the detection of S. japonicum.

Conclusions/Significance
The extremely sensitive and specific diagnostic assay described in this manuscript will facilitate the accurate detection of S. japonicum, particularly in regions with low levels of endemicity. This assay will be useful in providing data to inform programmatic decision makers, aiding disease control and elimination efforts.
Estimation of health impact from digitalizing last-mile Logistics Management Information Systems (LMIS) in Ethiopia, Tanzania, and Mozambique: A Lives Saved Tool (LiST) model analysis
Authors: Fritz Jenna , Herrick Tara , Gilbert Sarah Skye 
Published: October 2021

Background
Digital health has become a widely recognized approach to addressing a range of health needs, including advancing universal health coverage and achieving the Sustainable Development Goals. At present there is limited evidence on the impact of digital interventions on health outcomes. A growing body of peer-reviewed evidence on digitalizing last-mile electronic logistics management information systems (LMIS) presents an opportunity to estimate health impact.

Methods
The impact of LMIS on reductions in stockouts was estimated from primary data and peer-reviewed literature, with three scenarios of impact: 5% stockout reduction (conservative), 10% stockout reduction (base), and 15% stockout reduction (optimistic). Stockout reduction data was inverted to stock availability and improved coverage for vaccines and essential medicines using a 1:1 conversion factor. The Lives Saved Tool (LiST) model was used to estimate health impact from lives saved in newborns and children in Mozambique, Tanzania, and Ethiopia between 2022 and 2026 across the three scenarios.

Results
Improving coverage of vaccines with a digital LMIS intervention in the base scenario (conservative, optimistic) could prevent 4,924 (2,578–6,094), 3,998 (1,621–4,915), and 17,648 (12,656–22,776) deaths in Mozambique, Tanzania, and Ethiopia, respectively over the forecast timeframe. In addition, scaling up coverage of non-vaccine medications could prevent 17,044 (8,561–25,392), 21,772 (10,976–32,401), and 34,981 (17,543–52,194) deaths in Mozambique, Tanzania, and Ethiopia, respectively. In the base model scenario, the maximum percent reduction in deaths across all geographies was 1.6% for vaccines and 4.1% for non-vaccine medications.

Interpretation
This study projects that digitalization of last-mile LMIS would reduce child mortality by improving coverage of lifesaving health commodities. This analysis helps to build the evidence base around the benefits of deploying digital solutions to address health challenges. Findings should be interpreted carefully as stockout reduction estimates are derived from a small number of studies.
Costs and cost-effectiveness of Gene Xpert compared to smear microscopy for the diagnosis of pulmonary tuberculosis using real-world data from Arsi zone, Ethiopia
Authors: Kaso Abdene Weya , Hailu Alemayehu 
Published: October 2021

Background
Early diagnosis and treatment are one of the key strategies of tuberculosis control globally, and there are strong efforts in detecting and treating tuberculosis cases in Ethiopia. Smear microscopy examination has been a routine diagnostic test for pulmonary tuberculosis diagnosis in resource-constrained settings for decades. Recently, many countries, including Ethiopia, are scaling up the use of Gene Xpert without the evaluation of the cost and cost-effectiveness implications of this strategy. Therefore, this study evaluated the cost and cost-effectiveness of Gene Xpert (MTB/RIF) and smear microscopy tests to diagnosis tuberculosis patients in Ethiopia.

Methods
We compared the costs and cost-effectiveness of tuberculosis diagnosis using smear microscopy and Gene Xpert among 1332 patients per intervention in the Arsi zone. We applied combinations of top-down and bottom-up costing approaches. The costs were estimated from the health providers’ perspective within one year (2017–2018). We employed “cases detected” as an effectiveness measure, and the incremental cost-effectiveness ratio was calculated by dividing the changes in cost and change in effectiveness. All costs and incremental cost-effectiveness ratio were reported in 2018 US$.

Results
The unit cost per test for Gene Xpert was $12.9 whereas it is $3.1 for AFB smear microscopy testing. The cost per TB case detected was $77.9 for Gene Xpert while it was $55.8 for the smear microscopy method. The cartridge kit cost accounted for 42% of the overall Gene Xpert’s costs and the cost of the reagents and consumables accounted for 41.3% ($1.3) of the unit cost for the smear microscopy method. The ICER for the Gene Xpert strategy was $20.0 per tuberculosis case detected.

Conclusion
Using Gene Xpert as a routine test instead of standard care (smear microscopy) can be potentially cost-effective. In the cost scenario analysis, the price of the cartridge, the number of tests performed per day, and the life span of the capital equipment were the drivers of the unit cost of the Gene Xpert method. Therefore, Gene Xpert can be a part of the routine TB diagnostic testing strategy in Ethiopia.
Enabling access to molecular monitoring for chronic myeloid leukemia patients is cost effective in China
Authors: Maheshwari Vikalp Kumar , Slader Cassandra , Dani Nidhi , Gkitzia Christina , Yuan Quan , Xiong Tengbin , Liu Yu , Viana Ricardo 
Published: October 2021

Objective
To determine the cost effectiveness of molecular monitoring in patients with chronic myeloid leukemia in the chronic phase (CML-CP) compared to no molecular monitoring from a Chinese payer perspective.

Methods
Analyses were conducted using a semi-Markov model with a 50-year time horizon. Population data from multicenter registry-based studies of Chinese patients with CML-CP informed the model. Transition probabilities were based on time-to-event data from the literature. Utility values were obtained from published studies and were assumed to be the same for patients with and without molecular monitoring. Costs were based on values commonly used in the Chinese healthcare system, including drug acquisition, drug administration, follow-up, treatment for disease progression, molecular monitoring, and terminal care costs, and were in the local currency (2020 Chinese Yuan RMB [¥]). Outcomes were total life-years (LYs) and quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio.

Results
Molecular monitoring was dominant to no molecular monitoring, with increased LYs (1.52) and QALYs (1.90) and costs savings (¥93,840) over a lifetime compared to no monitoring in discounted analyses. The opportunity of patients that receive molecular monitoring to discontinue treatment during treatment-free remission, an opportunity not afforded to those without molecular monitoring, was the principle driver of this result. Results were similar across multiple clinical scenarios. Particularly, molecular monitoring remained dominant even if the proportion of patients achieving deep molecular response (DMR) was reduced by 10%-30%, or the proportion of patients maintaining DMR for 1 year was reduced by 10%-30% or increased by 10%. Cost savings in these scenarios ranged from ¥62,230 to ¥103,964.

Conclusions
Overall, this analysis demonstrates that adherence to guideline recommendations of regular molecular monitoring of patients with CML-CP treated with TKIs provides significant clinical benefit that leads to substantial cost savings compared to no molecular monitoring from the perspective of a Chinese payer. In a time where healthcare systems have limited resources to allocate to optimal patient care, investment in molecular monitoring is an ideal choice for improving patient benefits at a reduced cost.
Persistent hypoaldosteronism post-adrenalectomy for primary aldosteronism – a role for pre-operative spironolactone?
Authors: Angus Lachlan M , Yang Jun , Cheung Ada S 
Published: October 2021

Summary
Primary aldosteronism is one of the most common (affecting up to 10%) yet treatable causes of hypertension in our community, notable due to an associated elevated risk of atrial fibrillation, stroke and myocardial infarction compared to essential hypertension. Guidelines have focussed on improving case detection due to significant underdiagnosis in the community. While our case experienced significant delay in diagnosis, we highlight a state of protracted, persistent post-operative hypoaldosteronism which manifested with severe hyponatraemia and hyperkalaemia, necessitating long-term mineralocorticoid replacement. We discuss whether pre-operative mineralocorticoid receptor antagonists to stimulate aldosterone secretion from the contralateral gland may have prevented this complication.

Learning points

Hypoaldosteronism is an uncommon complication of adrenalectomy for primary aldosteronism, typically manifesting with hyperkalaemia and hyponatraemia. While most cases are transient, it may be persistent, necessitating ongoing mineralocorticoid replacement.

Routine electrolyte monitoring is recommended post-adrenalectomy.

Risk factors for hypoaldosteronism include age >50 years, duration of hypertension >10 years, pre-existing renal impairment and adrenal adenoma size >2 cm.

Mineralocorticoid receptor antagonists may assist in the management of hypokalaemia and hypertension pre-operatively. However, it is unclear whether this reduces the risk of post-operative hypoaldosteronism.
To study the clinical course of rhino orbital mucormycosis in post COVID-19 patients: A case series
Authors: Jhunjhunwala Aditi , Kumar Ram 
Published: October 2021

Rhino orbital cerebral mucormycosis is an opportunistic fungal infection with high morbidity and mortality which has seen the rise during the second wave of covid 19 in our country. Aim of our study was to study the clinical course, diagnosis and management of patient of rhino orbital mucormycosis in post covid phase presenting at our tertiary care centre. 4 cases of rhino-orbital mucormycosis who presented to us in post covid phase was followed and details recorded and analyzed to study its clinical course, diagnosis and management. 4 patients presented to us in post covid phase with signs of orbital cellulitis like periorbital swelling with pain, drooping of eyelids, proptosis, restriction of extraocular movements, decrease and loss of vision and sluggish reacting pupil. MRI/CT of the patients showed intraconal and extraconal involvement suggestive of orbital cellulitis. Diagnostic Nasal Endoscopy (DNE) was done and tissue sent for KOH mounting, culture and histopathology. After KOH mount showed fungal hyphae, patients were started on IV liposomal amphotericin B and retrobulbar amphotericin B. Patients were then taken up for endoscopic debridement and significant improvement in proptosis, ptosis, peribulbar swelling and pain was seen in immediate post op period. significant improvement was seen in patients with IV amphotericin B, retrobulbar amphotericin B and endoscopic debridement. Patients with rhino orbital mucormycosis can be managed with amphotericin and endoscopic debridement when exenteration is not possible.