bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting Neuropilin 1
Authors: Vescarelli Enrica , Gerini Giulia , Megiorni Francesca , Anastasiadou Eleni , Pontecorvi Paola , Solito Luciana , De Vitis Claudia , Camero Simona , Marchetti Claudia , Mancini Rita , Benedetti Panici Pierluigi , Dominici Carlo , Romano Ferdinando , Angeloni Antonio , Marchese Cinzia , Ceccarelli Simona 
Published: October 2020

Abstract
Background
Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood. The aim of this study is to identify target genes within the tumor cells that might cause resistance to Olaparib. We focused on Neuropilin 1 (NRP1), a transmembrane receptor expressed in OC and correlated with poor survival, which has been also proposed as a key molecule in OC multidrug resistance.

Methods
Using three OC cell lines (UWB, UWB-BRCA and SKOV3) as model systems, we evaluated the biological and molecular effects of Olaparib on OC cell growth, cell cycle, DNA damage and apoptosis/autophagy induction, through MTT and colony forming assays, flow cytometry, immunofluorescence and Western blot analyses. We evaluated NRP1 expression in OC specimens and cell lines by Western blot and qRT-PCR, and used RNA interference to selectively inhibit NRP1. To identify miR-200c as a regulator of NRP1, we used miRNA target prediction algorithms and Pearsons’ correlation analysis in biopsies from OC patients. Then, we used a stable transfection approach to overexpress miR-200c in Olaparib-resistant cells.

Results
We observed that NRP1 is expressed at high levels in resistant cells (SKOV3) and is upmodulated in partially sensitive cells (UWB-BRCA) upon prolonged Olaparib treatment, leading to poor drug response. Our results show that the selective inhibition of NRP1 is able to overcome Olaparib resistance in SKOV3 cells. Moreover, we demonstrated that miR-200c can target NRP1 in OC cells, causing its downmodulation, and that miR-200c overexpression is a valid approach to restore Olaparib sensitivity in OC resistant cells.

Conclusions
These data demonstrate that miR-200c significantly enhanced the anti-cancer efficacy of Olaparib in drug-resistant OC cells. Thus, the combination of Olaparib with miRNA-based therapy may represent a promising treatment for drug resistant OC, and our data may help in designing novel precision medicine trials for optimizing the clinical use of PARPi.
Metabolic engineering of Yarrowia lipolytica for thermoresistance and enhanced erythritol productivity
Authors: Wang Nan , Chi Ping , Zou Yawen , Xu Yirong , Xu Shuo , Bilal Muhammad , Fickers Patrick , Cheng Hairong 
Published: October 2020

Abstract
Background
Functional sugar alcohols have been widely used in the food, medicine, and pharmaceutical industries for their unique properties. Among these, erythritol is a zero calories sweetener produced by the yeast Yarrowia lipolytica. However, in wild-type strains, erythritol is produced with low productivity and yield and only under high osmotic pressure together with other undesired polyols, such as mannitol or d-arabitol. The yeast is also able to catabolize erythritol in non-stressing conditions.

Results
Herein, Y. lipolytica has been metabolically engineered to increase erythritol production titer, yield, and productivity from glucose. This consisted of the disruption of anabolic pathways for mannitol and d-arabitol together with the erythritol catabolic pathway. Genes ZWF1 and GND encoding, respectively, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were also constitutively expressed in regenerating the NADPH2 consumed during erythritol synthesis. Finally, the gene RSP5 gene from Saccharomyces cerevisiae encoding ubiquitin ligase was overexpressed to improve cell thermoresistance. The resulting strain HCY118 is impaired in mannitol or d-arabitol production and erythritol consumption. It can grow well up to 35 °C and retain an efficient erythritol production capacity at 33 °C. The yield, production, and productivity reached 0.63 g/g, 190 g/L, and 1.97 g/L·h in 2-L flasks, and increased to 0.65 g/g, 196 g/L, and 2.51 g/L·h in 30-m3 fermentor, respectively, which has economical practical importance.

Conclusion
The strategy developed herein yielded an engineered Y. lipolytica strain with enhanced thermoresistance and NADPH supply, resulting in a higher ability to produce erythritol, but not mannitol or d-arabitol from glucose. This is of interest for process development since it will reduce the cost of bioreactor cooling and erythritol purification.
Face individual identity recognition: a potential endophenotype in autism
Authors: Minio-Paluello Ilaria , Porciello Giuseppina , Pascual-Leone Alvaro , Baron-Cohen Simon 
Published: October 2020

AbstractBackgroundFace individual identity recognition skill is heritable and independent of intellectual ability. Difficulties in face individual identity recognition are present in autistic individuals and their family members and are possibly linked to oxytocin polymorphisms in families with an autistic child. While it is reported that developmental prosopagnosia (i.e., impaired face identity recognition) occurs in 2–3% of the general population, no prosopagnosia prevalence estimate is available for autism. Furthermore, an autism within-group approach has not been reported towards characterizing impaired face memory and to investigate its possible links to social and communication difficulties.MethodsThe present study estimated the prevalence of prosopagnosia in 80 autistic adults with no intellectual disability, investigated its cognitive characteristics and links to autism symptoms’ severity, personality traits, and mental state understanding from the eye region by using standardized tests and questionnaires.ResultsMore than one third of autistic participants showed prosopagnosia. Their face memory skill was not associated with their symptom’s severity, empathy, alexithymia, or general intelligence. Face identity recognition was instead linked to mental state recognition from the eye region only in autistic individuals who had prosopagnosia, and this relationship did not depend on participants’ basic face perception skills. Importantly, we found that autistic participants were not aware of their face memory skills.LimitationsWe did not test an epidemiological sample, and additional work is necessary to establish whether these results generalize to the entire autism spectrum.ConclusionsImpaired face individual identity recognition meets the criteria to be a potential endophenotype in autism. In the future, testing for face memory could be used to stratify autistic individuals into genetically meaningful subgroups and be translatable to autism animal models.
Intraventricular synchronism assessment by gated-SPECT myocardial perfusion imaging in cardiac resynchronization therapy. Does cardiomyopathy type influence results?
Authors: Peix Amalia , Padrón Kenia , Cabrera Lázaro O. , Castañeda Osmín , Milán Danet , Castro Jesús , Falcón Roylan , Martínez Frank , Rodríguez Lydia , Sánchez Jesús , Mena Erick , Carrillo Regla , Fernández Yoel , Escarano Ricardo , Páez Diana , Dondi Maurizio 
Published: October 2020

Abstract
Purpose
To analyze the evolution post-cardiac resynchronization therapy (CRT) in left ventricular non-compaction (LVNC) cardiomyopathy (CM) patients compared to other types of CM, according to clinical and functional variables, by using gated-SPECT myocardial perfusion imaging (MPI).

Methods
Ninety-three patients (60 ± 11 years, 28% women) referred for pre-CRT assessment were studied and divided into three groups: 1 (non-ischemic CM with LVNC, 11 patients), 2 (ischemic CM, 28 patients), and 3 (non-ischemic CM, 53 patients). All were studied by a 99mTc-MIBI gated-SPECT MPI at rest pre-CRT implantation and 6 ± 1 months after, including intraventricular dyssynchrony assessment by phase analysis. Quality of life was measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ).

Results
No differences in sex, atherosclerotic risk factors other than smoking habit, and MLHFQ results were found among groups. LVNC CM patients were younger, with greater QRS width and lower left ventricular ejection fraction (LVEF) at baseline, but the differences were not significant. No significant differences were found at baseline regarding ventricular function, although end-systolic volume was slightly higher in LVNC CM patients. Mean SRS was significantly higher (p < 0.0001) in ischemic patients (14.9) versus non-ischemic ones (8.7 in group 1 and 9 in group 2). At baseline, LVNC CM patients were significantly more dyssynchronous: Their phase standard deviation (PSD) was higher (89.5° ± 14.2°) versus groups 2 (65.2° ± 23.3°) and 3 (69.7° ± 21.7°), p = 0.007. Although the quality of life significantly improved in all groups, non-ischemic patients (with or without LVNC) showed a higher LVEF increase and volumes reduction at 6 months post-CRT. Dyssynchrony reduced post-CRT in all groups. Nevertheless, those more dyssynchronous at baseline (LVNC CM) exhibited the most significant intraventricular synchronism improvement: PSD was reduced from 89.5° ± 14.2° at baseline to 63.7° ± 20.5° post-CRT (p = 0.028). Six months post-CRT, 89% of patients were responders: 11 (100%) of those with LVNC CM, 25 (86%) of those with ischemic CM, and 47 (89%) of patients with non-ischemic CM. No patient with LVNC CM had adverse events during the follow-up.

Conclusion
CRT contributes to a marked improvement in non-ischemic CM patients with non-compaction myocardium. Phase analysis in gated-SPECT MPI is a valuable tool to assess the response to CRT.
A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status
Authors: Wang Changpeng , Zhang Siwei , Zou Yuefei , Ma Hongzhao , Jiang Donglang , Sheng Lei , Sang Shaoming , Jin Lirong , Guan Yihui , Gui Yuan , Xu Zhihong , Zhong Chunjiu 
Published: October 2020

Abstract
Background
Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed.

Methods
A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high-performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, and biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 min after injection as represented by the area under the curve (AUC) and blood thiamine levels was investigated.

Results
The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61 ± 0.53 in the liver within 1 min, 18.67 ± 7.04 in the kidney within half a minute. The SUV dropped to 0.72 ± 0.05 and 0.77 ± 0.35 after 60 min of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 min after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 min was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = − 0.985, p = 0.015).

Conclusion
The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.
The future of telemedicine visits after COVID-19: perceptions of primary care pediatricians
Authors: Grossman Zachi , Chodick Gabriel , Reingold Stephen M. , Chapnick Gil , Ashkenazi Shai 
Published: October 2020

Abstract
Background
Facing the global health crisis of COVID-19, health systems are increasingly supporting the use of telemedicine in ambulatory care settings. It is not clear whether the increased use of telemedicine will persist after the pandemic has resolved. The aims of this study were to assess the use of telemedicine by Israeli pediatricians before and during the first lockdown phase of the pandemic, and to elucidate how they foresee telemedicine as a medium of medical practice in the post-pandemic era.

Methods
A web-based survey was distributed among Israeli pediatricians in May 2020, soon after the end of first lockdown was announced. The survey assessed the frequency of telemedicine use as well as its influence on clinical decision making before and during the first COVID-19 lockdown, using two hypothetical clinical scenarios. The same scenarios were also used to assess how the pediatricians foresaw telemedicine in the post-pandemic period. In addition, administrative data from Maccabi on telemedicine use before, during and after the first lockdown were retrieved and analyzed.

Results
One hundred and sixty-nine pediatricians responded to the survey (response rate = 40%). The percentage of respondents who reported daily use of text messages, pictures and videoconferencing increased from 24, 15 and 1% before COVID-19 to 40, 40 and 12% during the lockdown, respectively (p < 0.05). After the pandemic, projected use of text messages and pictures/videoclips was expected to decrease to 27 and 26% of respondents, respectively (p < 0.05), but pictures/videoclips were expected to increase from 15% of respondents before to 26% of respondents after (p < 0.05). The reported high likelihood of treating suspected pneumonia or prescribing antibiotics for suspected otitis media via telemedicine was expected to decrease from 20% of respondents during the COVID-19 lockdown to 6%% of respondents after (p < 0.05), and from 14% of respondents during the lockdown to 3% of respondents after, respectively. (p < 0.05).
Maccabi administrative data indicated that during the lockdown, there was an increase in phone visits and a decrease in in-person visits compared to the pre-lockdown levels of use. One month after the end of the first lock-down there was a partial return to baseline levels of in-person visits and a sustained increase in phone visits. Phone visits accounted for 0% of pediatrician visits before the first lockdown, 17% of them during the lockdown, and 19% of them 1 month after the lockdown relaxation.

Conclusions
The study indicates that use of telemedicine technologies by primary care pediatricians increased substantially during the first COVID-19 lockdown. The study also found that pediatricians expected that use levels will recede after the pandemic. As the pandemic continues and evolves, it will be important to continue to monitor the level of telemedicine use as well as expectations regarding post-pandemic use levels.
Income assurances are a crucial factor in determining public compliance with self-isolation regulations during the COVID-19 outbreak – cohort study in Israel
Authors: Bodas Moran , Peleg Kobi 
Published: October 2020

AbstractBackgroundThe outbreak of a new Coronavirus disease (COVID-19) poses dramatic challenges to public health authorities worldwide. One measure put in place to contain the spread of the disease is self-quarantine of individuals who may have been exposed to the disease. While officials expect the public to comply with such regulation, studies suggest that a major obstacle to compliance for self-quarantine is concern over loss of income or employment due to the prolonged absence from work.MethodsA cohort study of the adult population of Israel was conducted in two time points during the COVID-19 outbreak, the last week of February and the third week of March 2020, in order to assess public attitudes. In particular, public compliance rates to self-quarantine with and without State-sponsored compensation for lost wages were assessed.ResultsThe results suggest that public attitudes changed as the threat increased, making people more compliant with regulations. In February 2020, compliance rate for self-quarantine dropped from 94% to less than 57% when monetary compensation for lost wages was removed; however, in March 2020 this drop became more moderate (from 96 to 71%). The multivariate logistic regression revealed that older, non-Jewish, worried over COVID-19, and trusting the Ministry of Health were more likely than their counterparts to comply with self-isolation, even when monetary compensation was not assumed.ConclusionsDespite the effects of threat on people’s obedience with regulations, this study demonstrates that providing people with assurances about their livelihood during absence from work remains an important component in compliance with public health regulations.
Sepsis and septic shock in France: incidences, outcomes and costs of care
Authors: Dupuis Claire , Bouadma Lila , Ruckly Stéphane , Perozziello Anne , Van-Gysel Damien , Mageau Arthur , Mourvillier Bruno , de Montmollin Etienne , Bailly Sébastien , Papin Gregory , Sinnah Fabrice , Vinclair Camille , Abid Sonia , Sonneville Romain , Timsit Jean-François 
Published: October 2020

Abstract
Background
Sepsis is one of the leading causes of death worldwide. The associated incidence, mortality and trends do not differ greatly between documented reports. The purpose of this study was to provide an in-depth description of patients with sepsis and septic shock hospitalized in France from 2010 to 2015 and to explore the temporal trends of their clinical characteristics, costs and outcomes.

Methods
Retrospective cohort study of the French hospital administrative database in which organ failure therapies and severity scores are systematically registered. All patients admitted between 2010 and 2015 for sepsis and septic shock as defined by an ICD-10 code for infection, and for organ failure or the use of organ failure supplementation were included. Incidence, outcomes and trends were analyzed. Subgroup analyses based on several coding strategies and adjusted for severity scores were performed.

Results
A total of 737,147 patients with sepsis and 492,902 patients with septic shock were included. From 2010 to 2015, the incidence of sepsis and septic shock increased, respectively, from 206 to 243 and from 135 to 171 cases per 100,000 population. Case fatality remained at 34% for sepsis, but decreased from 46 to 44% for septic shock.
Median hospital stay costs amounted to €11,400 (IQR: 5036; 24,364) for patients with sepsis and €16,439 (IQR: 7339; 29,360) for patients with septic shock.
After adjustment for case-mix and illness severity, the risk of death was stable for sepsis (0.08% [− 0.04; 0.20] per year), but decreased for sepsis patients admitted to the intensive care unit and for cases of septic shock (− 0.33%[ − 0.40; − 0.27] per year).

Conclusions
Sepsis is common, frequently fatal and expensive to treat. Its incidence has increased. Case fatality has decreased in most severely affected patients, owing partly to general improvements in care.
Acceptance of the proposed social health insurance among government-owned company employees in Northwest Ethiopia: implications for starting social health insurance implementation
Authors: Zemene Abuneh , Kebede Adane , Atnafu Asmamaw , Gebremedhin Tsegaye 
Published: October 2020

Abstract
Background
Ethiopia is currently planning to introduce Social Health Insurance (SHI) that will lead to universal health coverage and assist a country to achieve its health system’s objectives and to prevent the catastrophic health expenditure. But there is no evidence until now about the level of acceptance of the proposed SHI among government-owned companies’ employees. Therefore, this study was intended to assess the acceptance of SHI and associated factors among government-owned companies’ employees in northwest Ethiopia.

Methods
An institution-based cross-sectional study was conducted from February 1 to April 30, 2019. A randomly selected 541 government-owned companies’ employees were participated in the study. A pretested self-administered structured questionnaire was used that consisted sociodemographic and economic, health status-related factors, attitude (measured by 12 items), organizational related factors and knowledge about SHI (measured by 11 items). Finally, binary logistic regression analysis was performed and in the multivariable logistic regression analysis, a significant level at a p-value of < 0.05 and Adjusted Odds Ratio (AOR) with 95% confidence interval (CI) were used to identify factors statistically associated with SHI acceptance.

Results
Overall, 32% (95% CI: 27.7–36.2) of the government-owned companies’ employees accepted the proposed Ethiopian SHI scheme. Self-perceived health status (AOR: 8.55, 95% CI: 2.69–27.13), heard about SHI (AOR: 1.69, 95% CI: 1.12–2.54), coverage of medical healthcare cost (AOR: 0.60, 95% CI: 0.39–0.92), work experience (AOR: 0.49, 95% CI: 0.26–0.89) and quality of healthcare service at the facilities (AOR: 0.17, 95% CI: 0.04–0.71) were significantly associated with acceptance of SHI among government-owned companies’ employees.

Conclusions
One-third of the study participants accepted the proposed Ethiopian SHI scheme. Self-perceived health status, quality of healthcare service at health facilities, coverage of the medical cost by their organization, heard about SHI and work experience were the factors that affect acceptance of the proposed SHI among the government-owned company employees. Therefore, policymakers should devise a plan to promote the benefit packages of SHI for the formal sector employees to start the implementation.