bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral administration of repurposed drug targeting Cyp46A1 increases survival times of prion infected mice
Authors: Ali Tahir , Hannaoui Samia , Nemani Satish , Tahir Waqas , Zemlyankina Irina , Cherry Pearl , Shim Su Yeon , Sim Valerie , Schaetzl Hermann M. , Gilch Sabine 
Published: April 2021

AbstractPrion diseases are fatal, infectious, and incurable neurodegenerative disorders caused by misfolding of the cellular prion protein (PrPC) into the infectious isoform (PrPSc). In humans, there are sporadic, genetic and infectious etiologies, with sporadic Creutzfeldt-Jakob disease (sCJD) being the most common form. Currently, no treatment is available for prion diseases. Cellular cholesterol is known to impact prion conversion, which in turn results in an accumulation of cholesterol in prion-infected neurons. The major elimination of brain cholesterol is achieved by the brain specific enzyme, cholesterol 24-hydroxylase (CYP46A1). Cyp46A1 converts cholesterol into 24(S)-hydroxycholesterol, a membrane-permeable molecule that exits the brain. We have demonstrated for the first time that Cyp46A1 levels are reduced in the brains of prion-infected mice at advanced disease stage, in prion-infected neuronal cells and in post-mortem brains of sCJD patients. We have employed the Cyp46A1 activator efavirenz (EFV) for treatment of prion-infected neuronal cells and mice. EFV is an FDA approved anti-HIV medication effectively crossing the blood brain barrier and has been used for decades to chronically treat HIV patients. EFV significantly mitigated PrPSc propagation in prion-infected cells while preserving physiological PrPC and lipid raft integrity. Notably, oral administration of EFV treatment chronically at very low dosage starting weeks to months after intracerebral prion inoculation of mice significantly prolonged the lifespan of animals. In summary, our results suggest that Cyp46A1 as a novel therapeutic target and that its activation through repurposing the anti-retroviral medication EFV might be valuable treatment approach for prion diseases.
The expression of B7-H3 isoforms in newly diagnosed glioblastoma and recurrence and their functional role
Authors: Digregorio Marina , Coppieters Natacha , Lombard Arnaud , Lumapat Paul Noel , Scholtes Felix , Rogister Bernard 
Published: April 2021

AbstractShort survival of glioblastoma (GBM) patients is due to systematic tumor recurrence. Our laboratory identified a GBM cell subpopulation able to leave the tumor mass (TM) and invade the subventricular zone (SVZ-GBM cells). SVZ-GBM cells escape treatment and appear to contribute to GBM recurrence. This study aims to identify proteins specifically expressed by SVZ-GBM cells and to define their role(s) in GBM aggressiveness and recurrence. The proteome was compared between GBM cells located in the initial TM and SVZ-GBM cells using mass spectrometry. Among differentially expressed proteins, we confirmed B7-H3 by western blot (WB) and quantitative RT-PCR. B7-H3 expression was compared by immunohistochemistry and WB (including expression of its isoforms) between human GBM (N = 14) and non-cancerous brain tissue (N = 8), as well as newly diagnosed GBM and patient-matched recurrences (N = 11). Finally, the expression of B7-H3 was modulated with short hairpin RNA and/or over-expression vectors to determine its functional role in GBM using in vitro assays and a xenograft mouse model of GBM. B7-H3 was a marker for SVZ-GBM cells. It was also increased in human GBM pericytes, myeloid cells and neoplastic cells. B7-H3 inhibition in GBM cells reduced their tumorigenicity. Out of the two B7-H3 isoforms, only 2IgB7-H3 was detected in non-cancerous brain tissue, whereas 4IgB7-H3 was specific for GBM. 2IgB7-H3 expression was higher in GBM recurrences and increased resistance to temozolomide-mediated apoptosis. To conclude, 4IgB7-H3 is an interesting candidate for GBM targeted therapies, while 2IgB7-H3 could be involved in recurrence through resistance to chemotherapy.
Optimization of air traffic management efficiency based on deep learning enriched by the long short-term memory (LSTM) and extreme learning machine (ELM)
Authors: Yousefzadeh Aghdam Mahdi , Kamel Tabbakh Seyed Reza , Mahdavi Chabok Seyed Javad , Kheyrabadi Maryam 
Published: April 2021

AbstractNowadays this concept has been widely assessed due to its complexity and sensitivity for the beneficiaries, including passengers, airlines, regulatory agencies, and other organizations. To date, various methods (e.g., statistical and fuzzy techniques) and data mining algorithms (e.g., neural network) have been used to solve the issues of air traffic management (ATM) and delay the minimization problems. However, each of these techniques has some disadvantages, such as overlooking the data, computational complexities, and uncertainty. In this paper, to increase the air traffic management accuracy and legitimacy we used the bidirectional long short-term memory (Bi-LSTMs) and extreme learning machines (ELM) to design the structure of a deep learning network method. The Kaggle data set and different performance parameters and statistical criteria have been used in MATLAB to validate the proposed method. Using the proposed method has improved the criteria factors of this study. The proposed method has had a % increase in air traffic management in comparison to other papers. Therefore, it can be said that the proposed method has a much higher air traffic management capacity in comparison to the previous methods.
An application of multi-criteria decision-making approach to sustainable drug shortages management: evidence from a developing country
Authors: Moosivand Asiye , Rangchian Maryam , Zarei Leila , Peiravian Farzad , Mehralian Gholamhossein , Sharifnia Hesameddin 
Published: April 2021

Abstract
Background
Drug shortage is a significant public health problem, especially for drugs related to life threatening conditions. Almost all countries affected by variety of supply problems and spent a considerable amount of time and resources responding to shortage. The aim of present study is to determine and prioritize strategies to achieve best solutions for these considerable healthcare system challenges and to evaluate this strategies base on practical criteria.

Methods
To achieve the study objectives, the research was conducted in two phases. Determining of the strategies to control drug shortage, and comprehensive assessments of priority of possible strategies. For each phase, a self-design questionnaire was developed. The five main managerial strategies dimensions including: regulatory, financial, supply chain, information system and policy-making were set out. Forty-five alternatives were elicited from literature, and were evaluated and trimmed to 37 strategies based on experts’ opinion. The Multiple criteria decision-making (MCDM) methods were applied in second phase. Five important criteria including cost, time, labor, compliance with law and culture were weighed by Analytic Hierarchy Process (AHP) technique. Then, 37 alternatives have been rated base on the five criteria on the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) technique.

Results
“Creating integrated Supply chain information system to manage medicines inventory in the country”, “Creating and using the databases to predict the shortage of medicines”, “Using track and trace system” are alternatives 20th, 24th and 25th, which related to supply chain (SC) and information system (IS) dimensions have higher priority in the experts’ point of view. The results show IS dimension has 100 percentage of priority; following that policy and supply chain have higher priority, respectively.

Conclusion
Health systems rely on consistent supplying of pharmaceuticals to support patient care. The results show that information system, policy-making and supply chain are in the top-ranking priorities. Warning system needs to be improved to the advance system via better collaboration with stakeholders, publish precise and explicit national guidelines for drug shortage management, enforce the guidelines, and improve Iran FDA’s pharmaceutical market control capability.
Lung autotransplantation for bronchial necrosis after radiotherapy: a case report
Authors: Nobori Yuya , Sato Masaaki , Morota Mizuki , Shinohara Yoshikazu , Yoshida Daisuke , Karasaki Takahiro , Kitano Kentaro , Nakajima Jun 
Published: April 2021

Abstract
Background
Bronchial necrosis is a rare but fatal complication after radiation therapy. Because of the anatomical complexity and rarity of this condition, determining the most appropriate management for individual patients is extremely challenging. Lung autotransplantation is a surgical technique that has been applied to hilar neoplastic lesions to preserve pulmonary function and avoid pneumonectomy. We herein report a case of bronchial necrosis secondary to radiotherapy that was treated with lung autotransplantation.

Case presentation
A 46-year-old man developed broad necrosis and infection of the right bronchus secondary to previous stereotactic body-radiation therapy. This treatment was supplied close to a right hilar metastatic pulmonary tumor derived from a mediastinal malignant germ cell tumor that had been surgically resected with the left phrenic nerve. The bronchial necrosis accompanied by infection with Aspergillus fumigatus was progressive despite antibiotics and repetitive bronchoscopic debridement. Because of the patient’s critical condition and limited pulmonary function, right lung autotransplantation with preservation of the right basal segment was selected. An omental flap was placed around the bronchial anastomosis to prevent later complications. The postoperative course involved multiple complications including contralateral pneumonia and delayed wound healing at the bronchial anastomosis with resultant stenosis, the latter of which was overcome by placement of a silicone stent. The patient was discharged 5 months postoperatively. Three months after discharge, however, the patient developed hemoptysis and died of bronchopulmonary arterial fistula formation.

Conclusions
We experienced an extremely challenging case of bronchial necrosis secondary to radiotherapy. The condition was managed with lung autotransplantation and omental wrapping; however, the treatment success was temporary and the patient eventually died of bronchopulmonary arterial fistula formation. This technique seems to be a feasible option for locally advanced refractory bronchial necrosis, although later complications can still be fatal.
Modified Talk Test: a Randomized Cross-over Trial Investigating the Comparative Utility of Two “Talk Tests” for Determining Aerobic Training Zones in Overweight and Obese Patients
Authors: Orizola-Cáceres Ignacio , Cerda-Kohler Hugo , Burgos-Jara Carlos , Meneses-Valdes Roberto , Gutierrez-Pino Rafael , Sepúlveda Carlos 
Published: April 2021

Abstract
Background
To validate the traditional talk test (TTT) and an alternative talk test (ATT; using a visual analog scale) in overweight/obese (OW-OB) patients and to establish its accuracy in determining the aerobic training zones.

Methods
We recruited 19 subjects aged 34.9 ± 6.7 years, diagnosed with overweight/obesity (BMI 31.8 ± 5.7). Every subject underwent incremental cycloergometric tests for maximal oxygen consumption, and TTT in a randomized order. At the end of each stage during the TTT, each subject read out loud a 40 words text and then had to identify the comfort to talk in two modalities: TTT which consisted in answering “Yes,” “I don’t know,” or “No” to the question Was talking comfortable?, or ATT through a 1 to 10 numeric perception scale (visual analog scale (VAS)). The magnitude of differences was interpreted in comparison to the smallest worthwhile change and was used to determine agreement.

Results
There was an agreement between the power output at the VAS 2–3 of ATT and the power output at the ventilatory threshold 1 (VT1) (very likely equivalent; mean difference − 1.3 W, 90% confidence limit (CL) (− 8.2; 5.6), percent chances for higher/similar/lower values of 0.7/99.1/0.2%). Also, there was an agreement between the power output at the VAS 6–7 of ATT and the power output at the ventilatory threshold 2 (VT2) (very likely equivalent; mean difference 11.1 W, 90% CL (2.8; 19.2), percent chances for higher/similar/lower values of 0.0/97.6/2.4%).

Conclusions
ATT is a tool to determine exercise intensity and to establish aerobic training zones for exercise prescription in OW-OB patients.
Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab
Authors: Hamid Mohamed A. , Abdelfattah Nizar S. , Salamzadeh Jamshid , Abdelaziz Sahar T. A. , Sabry Ahmed M. , Mourad Khaled M. , Shehab Azza A. , Kuppermann Baruch D. 
Published: April 2021

Abstract
Background
Despite the good outcomes achieved with intravitreal angiogenic therapy, a subset of neovascular age-related macular degeneration (AMD) patients experience resistance to therapy after repeated injections. Switching drugs could offer benefit to this group of patients.

Purpose
To determine visual and anatomical outcomes in a cohort of neovascular AMD patients resistant to repeated injections of bevacizumab/ranibizumab after switching to aflibercept therapy.

Methods
This was a retrospective chart review of patients who had a diagnosis of neovascular AMD and persistent intraretinal (IRF) and/or subretinal fluid (SRF) on optical coherence tomography (OCT) for at least 3 months despite monthly bevacizumab and/or ranibizumab injections prior to transition to aflibercept. We reviewed patients’ records and OCT images obtained at baseline, 1, 3, 6 and 12 months after transition to aflibercept. Data collected included demographics, best-corrected visual acuity (BCVA), number of injections received and the occurrence of any adverse events. Studied OCT parameters included central macular thickness (CMT) values and the presence or absence of SRF, IRF and/or pigment epithelial detachment (PED) at each visit.

Results
We included 53 eyes of 48 patients. Mean change in BCVA from baseline was 0.05 ± 0.13 (P = 0.01) at M1, 0.04 ± 0.16 (P = 0.08) at M3, 0.01 ± 0.22 (P = 0.9) at M6, and 0.02 ± 0.28 (P = 1) at M12, while the mean change in CMT from baseline was 64 ± 75 μm (P < 0.0001) at M1, 42 ± 85 μm (P = 0.002) at M3, 47 ± 69 μm (P < 0.0001) at M6, and 46 ± 99 μm (P = 0.001) at M12. The percentage of eyes with SRF decreased from 77.4% at baseline to 39.6% at M1, then increased to 47.2% at M3, then decreased to 43.4% at M6, and to 41.5% at M12 (All p < 0.001, compared to baseline). Compared to baseline, there was a statistically significant decrease in the percentage of eyes having IRF from 47.2 to 20.8% at M1 (p < 0.001), 30.2% at M3, 24.5% at M6 and 26.4% at M12 (p < 0.01, each). The number of bevacizumab and/or ranibizumab injections (7.36 ± 1.85) was significantly higher than that of aflibercept (6.47 ± 2.45, p = 0.001). A significant direct relationship between CMT reduction and BCVA improvement was demonstrated at M1 (p = 0.01, r = 0.36), M3 (p = 0.03, r = 0.30) and M12 (p = 0.03, r = 0.30). Eyes with IRF had significantly poorer BCVA than eyes without IRF at baseline (p = 0.02) and M3 (p = 0.04).

Conclusion
Switching to intravitreal aflibercept therapy in a cohort of neovascular AMD patients resistant to chronic bevacizumab and/or ranibizumab injections can lead to significant visual improvement in the short term and sustained reduction of central macular thickness over 1 year of followup.
The yield and usefulness of PAIN+ and PubMed databases for accessing research evidence on pain management: a randomized crossover trial
Authors: Arumugam Vanitha , MacDermid Joy C. , Walton Dave , Grewal Ruby 
Published: April 2021

AbstractIntroductionPAIN+and PubMed are two electronic databases with two different mechanisms of evidence retrieval. PubMed is used to “Pull” evidence where clinicians can enter search terms to find answers while PAIN+is a newly developed evidence repository where along with “Pull” service there is a “Push” service that alerts users about new research and the associated quality ratings, based on the individual preferences for content and altering criteria.PurposeThe primary purpose of the study was to compare yield and usefulness of PubMed and PAIN+in retrieving evidence to address clinical research questions on pain management. The secondary purpose of the study was to identify what search terms and methods were used by clinicians to target pain research.Study designTwo-phase double blinded randomized crossover trial.MethodsClinicians (n = 76) who were exposed to PAIN+for at least 1 year took part in this study. Participants were required to search for evidence 2 clinical question scenarios independently. The first clinical question was provided to all participants and thus, was multi-disciplinary. Participants were randomly assigned to search for evidence on their clinical question using either PAIN+or PubMed through the electronic interface. Upon completion of the search with one search engine, they were crossed over to the other search engine. A similar process was done for a second scenario that was discipline-specific. The yield was calculated using number of retrieved articles presented to participants and usefulness was evaluated using a series of Likert scale questions embedded in the testing.ResultsMultidisciplinary scenario:Overall, the participants had an overall one-page yield of 715 articles for PAIN+and 1135 articles for PubMed. The topmost article retrieved by PAIN+was rated as more useful (p = 0.001). While, the topmost article retrieved by PubMed was rated as consistent with current clinical practice (p = 0.02). PubMed (48%) was preferred over PAIN+(39%) to perform multidisciplinary search (p = 0.02).Discipline specific scenario:The participants had an overall one-page yield of 1046 articles for PAIN+and 1398 articles for PubMed. The topmost article retrieved by PAIN+was rated as more useful (p = 0.001) and consistent with current clinical practice (p = 0.02) than the articles retrieved by PubMed. PAIN+(52%) was preferred over PubMed (29%) to perform discipline specific search.ConclusionClinicians from different disciplines find both PAIN+and PubMed useful for retrieving research studies to address clinical questions about pain management. Greater preferences and perceived usefulness of the top 3 retrieved papers was observed for PAIN+, but other dimensions of usefulness did not consistently favor either search engine.Trial registrationRegistered with ClinicalTrials.gov Identifier:NCT01348802, Date: May 5, 2011.
Patient-centered outcomes used in pediatric focused manual therapies research studies: a secondary data analysis of a systematic review
Authors: Carleo Beth , Anderson Kristian , Prevost Carol Parnell , Pohlman Katherine A. 
Published: April 2021

Abstract
Background
Patient-reported outcome measurements (PROM) are instruments that seek a patient’s health or functional status. Inclusion of standardized PROMs in research studies and clinical practice provides a more comprehensive understanding of an intervention from the patient’s viewpoint. This secondary analysis identified PROM usage and appropriateness of references for property measurements from clinical trials included in a recent systematic review of pediatric manual therapy.

Methods
All included manuscripts within a recent systematic review had two authors extract PROM and associated property measurement data, including the property measurements supporting citations. Inclusion criteria for the articles were published clinical trials (observational or experimental) of pediatric children receiving manual therapy (any profession) for any condition between 2001-March 2018. For each PROM’s associated property measurement, two authors used the COSMIN study design checklist to appraise the quality of the cited study to evaluate the property measurement.

Results
Of the 50 manuscripts included in the systematic review, 20 manuscripts reported the use of 52 PROMs. Of the 52 PROMs assessed, 31 did not make a statement about the instrument’s property measurement, 7 PROMs had property measurements stated but not referenced, 4 PROMs stated that the property measurement information was unknown, and 10 had property measurement data with reference(s). These 10 PROMs with referenced property measurements were from 7 unique PROMs: constipation assessment scale, satisfaction visual analog scale (VAS), crying time diary, sleep diary, fear avoidance belief questionnaire (FABQ), pain VAS, and autism treatment evaluation checklist. The assessment of the referenced property measurements found that several property measurement’s dimensions had not been assessed and those that had were evaluated were done so with poor or fair standards.

Conclusions
This secondary analysis finds that clinical studies of pediatric manual therapy lack consistent use of PROMs with high quality property measurements. Further research to establish and implement PROMs to be used in future research studies and in clinical settings should become a priority for professions using manual therapy in children.
Predictive factors of epilepsy outcome in a sample of Egyptian pre-elderly and elderly population
Authors: Gerges Steven Emil , El Rakawy Mahmoud Hemeda , El Khayat Naglaa Mohammed , Abdelhamid Yousry Abo Elnaga , Hazzou Ahmed Mohammed , Shokri Hossam Mohammed , Wahid El din Mona Mokthar 
Published: April 2021

Abstract
Background
Elderly people with epilepsy are large, but neglected group. Data on the predictive factors for recurrent seizures in the elderly population are inconclusive or are not known for the majority of patients. This is especially true for the Egyptian population as no specific study was concluded to address this issue before.

Objectives
The aim of this study was to detect the predictive factors of epilepsy outcome in a sample of Egyptian aged population.

Materials and methods
A total of 100 patients aged 50 years or older with epilepsy diagnosed according to International League Against Epilepsy (ILAE) latest definition were included in the study and followed up for 6 months as regards seizure control. All participants were prospectively evaluated for epidemiological, clinical, radiological, electrodiagnostic, and laboratory data.

Results
The outcome was statistically significant affected in relation to absence of medical comorbidities (P = 0.037), seizure etiology (P = 0.007), history of status epilepticus (P <  0.001), MRI brain findings (P = 0.005), EEG changes (P <  0.001), Ca (P = 0.01), and Mg level (P = 0.046).

Conclusion
We conclude that aged Egyptian epileptic population with no medical comorbidities, normal MRI brain, or normal EEG can be predicted to have good outcome of their epilepsy while patients with post stroke epilepsy, abnormal MRI brain, and abnormal EEG, with low serum Ca or Mg level can be predicted to have poor outcome.