bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a fluorine-18 radiolabelled fluorescent chalcone: evaluated for detecting glycogen
Authors: Allott Louis , Brickute Diana , Chen Cen , Braga Marta , Barnes Chris , Wang Ning , Aboagye Eric O. 
Published: June 2020

Abstract
Background
Glycogen is a multibranched polysaccharide of glucose produced by cells to store energy and plays a key role in cancer. A previously reported fluorescent probe (CDg4) was shown to selectively bind glycogen in mouse embryonic stem cells, however the molecule was not evaluated in cancer cells. We report the synthesis and biological evaluation of a dual-modality imaging probe based on CDg4, for positron emission tomography (PET) and fluorescence microscopy.

Results
A fluorine-18 radiolabelled derivative of CDg4, ([18F]5) for in vivo quantification of total glycogen levels in cancer cells was developed and synthesised in 170 min with a non-decay corrected radiochemical yield (RCY n.d.c) of 5.1 ± 0.9% (n = 4) in > 98% radiochemical purity. Compound 5 and [18F]5 were evaluated in vitro for their potential to bind glycogen, but only 5 showed accumulation by fluorescence microscopy. The accumulation of 5 was determined to be specific as fluorescent signal diminished upon the digestion of carbohydrate polymers with α-amylase. PET imaging in non-tumour bearing mice highlighted rapid hepato-biliary-intestinal elimination of [18F]5 and almost complete metabolic degradation after 60 min in the liver, plasma and urine, confirmed by radioactive metabolite analysis.

Conclusions
Fluorescent compound 5 selectively accumulated in glycogen containing cancer cells, identified by fluorescence microscopy; however, rapid in vivo metabolic degradation precludes further investigation of [18F]5 as a PET radiopharmaceutical.
Randomized comparative study of child and caregiver responses to three software functions added to the Japanese version of the electronic Pediatric Quality of Life Inventory (ePedsQL) questionnaire
Authors: Sato Iori , Sakka Mariko , Soejima Takafumi , Kita Sachiko , Kamibeppu Kiyoko 
Published: June 2020

Abstract
Background
Patient-reported outcomes (PROs) refer to any report of the status of a patient’s health condition, health behavior, or experience with healthcare directly from the patient, without interpretation of the patient’s response by a clinician or any other external party. While many PROs, such as the Pediatric Quality of Life Inventory (PedsQL), were originally administered in paper-and-pencil format, these are now available as electronic versions (ePROs). Although ePROs might well have used the same structure as their paper versions, we developed an alternate ePedsQL incorporating three software functions: 1) a non-forcing non-response alert, 2) a conditional question branch of the School Functioning Scale that only displays for (pre) school children, and 3) a vertical item-by-item display for small-screen devices. This report evaluated the effect of these functions on item non-response rate, survey completion time, and user experience.

Methods
All surveys were conducted via the online/computer mode. We compared the dynamic format containing the three functions with the basic format in a randomized comparative study in 2803 children and 6289 caregivers in Japan.

Results
We found that the non-response alert lowered the item non-response rate (0.338% to 0.046%, t = − 4.411, p < 0.001 by generalized linear mixed model analysis). The conditional question branch had mixed effects on survey completion time depending on the respondents’ age. Surprisingly, respondents rated the vertical question display for handheld devices less legible than the matrix format. Further, multigroup structural equation modelling revealed that the same configuration for both formats showed an acceptable fit (CFI 0.933, RMSEA 0.060, SRMR 0.038) but the errors of observed variables were larger for the dynamic format than the basic format.

Conclusions
We confirmed the robustness of the ePedsQL in different formats. The non-response rate of ePedsQL was very low even in the absence of an alert. The branch and item-by-item display were effective but unnecessary for all populations. Our findings further understanding of how humans respond to special software functions and different digital survey formats and provide new insight on how the three tested functions might be most successfully implemented.
Ultrasound-guided injection of platelet-rich plasma (PRP) in rotator cuff tendinopathy: effect on patients’ symptoms and supraspinatus tendon thickness
Authors: Niazi Gamal Eldine , Hassan Mohammed Sobhi , Elfawy Dalia M. 
Published: June 2020

Abstract
Background
Rotator cuff tendinopathy is considered a major cause of shoulder pain and disability that is increasing substantially with age affecting more than half of the general population by the age of 60 years. This study aims to assess the effect of ultrasound-guided injection of platelet-rich plasma on patient symptoms and supraspinatus tendon thickness in cases of rotator cuff tendinopathy.

Results
This was a single-arm interventional study conducted on 30 patients with age ranging between 27 and 54 years old. Following US-guided injection of PRP, patients were evaluated clinically using the Shoulder Pain and Disability Index (SPADI) scoring system and radiologically using ultrasonographic supraspinatus tendon thickness measurements at 4, 8, 12, and 24 weeks. Our study showed remarkably noticeable changes when comparing the pre-injection and post-injection SPADI scoring system. There is highly statistically significant pain and disability score and percentage improvement, yet on the other hand, the radiological improvement shows no statistically significant difference found between baseline tendon thickness and its follow-up at 4, 8, and 12 weeks while only there was a statistically significant decrease in tendon thickness found at 24 weeks with P value = 0.043.

Conclusions
The ultrasound-guided PRP injection for supraspinatus tendinopathy cases is a safe, cheap, and easily prepared outpatient procedure which showed competitive, promising, and well-proved results when compared to other modality outcomes such as conventional surgeries, arthroscopic procedures, and physiotherapy.
In silico modeling of tetraoxane-8-aminoquinoline hybrids active against Plasmodium falciparum
Authors: Mahmud Aliyu Wappah , Shallangwa Gideon Adamu , Uzairu Adamu 
Published: June 2020

AbstractBackgroundQuantitative structure-activity relationships (QSAR) is a technique that is used to produce a model that connects biological activities of compounds to their chemical structures, and molecular docking is a technique that reveals the binding mode and interactions between a drug and its target enzyme. These techniques have been successfully applied in the design and development of many drug candidates and herein were employed to build a model that could help in the development of more potent antimalaria drugs.ResultsDescriptors of the compounds were calculated using the PaDEL-Descriptor software, and Genetic Function Algorithm (GFA) was used to select descriptors and build the model. A robust and reliable model was generated and validated to have internal and external squared correlation coefficient (R2) of 0.9622 and 0.8191, respectively, adjusted squared correlation coefficient (Radj) of 0.9471, and leave-one-out (LOO) cross-validation coefficient (Q2cv) of 0.9223. The model revealed that the antiplasmodial activities of 1,2,4,5-tetraoxane-8-aminoquinoline hybrids depend on MATS3m, GATS8p, GATS8i, and RDF50s descriptors. MATS3m, GATS8i, and RDF50s influenced the antiplasmodial activities of the compounds positively while GATS8p negatively with the greatest influence. The docking result shows strong interactions between 1,2,4,5-tetraoxane-8-aminoquinoline hybrids andPlasmodium falciparumlactate dehydrogenase (pfLDH) with binding affinities ranging from − 6.3 to − 10.9 kcal/mol which were better than that of chloroquine (− 6.1 kcal/mol), suggesting that these compounds could be better inhibitors ofpfLDH than chloroquine.ConclusionThe results of this study could serve as a model for designing new potent 1,2,4,5-tetraoxane-8-aminoquinolines with better antiplasmodial activities for the development of highly active antimalaria drugs.
Exploring different approaches to improve the success of drug discovery and development projects: a review
Authors: Kiriiri Geoffrey Kabue , Njogu Peter Mbugua , Mwangi Alex Njoroge 
Published: June 2020

Abstract
Background
There has been a significant increase in the cost and timeline of delivering new drugs for clinical use over the last three decades. Despite the increased investments in research infrastructure by pharmaceutical companies and technological advances in the scientific tools available, efforts to increase the number of molecules coming through the drug development pipeline have largely been unfruitful.

Main body
A non-systematic review of the current literature was undertaken to enumerate the various strategies employed to improve the success rates in the pharmaceutical research and development. The review covers the exploitation of genomics and proteomics, complementarity of target-based and phenotypic efficacy screening platforms, drug repurposing and repositioning, collaborative research, focusing on underserved therapeutic fields, outsourcing strategy, and pharmaceutical modeling and artificial intelligence. Examples of successful drug discoveries achieved through application of these strategies are highlighted and discussed herein.

Conclusions
Genomics and proteomics have uncovered a wide array of potential drug targets and are facilitative of enhanced scrupulous target identification and validation thus reducing efficacy-related drug attrition. When used complementarily, phenotypic and target-based screening platforms would likely allow serendipitous drug discovery while increasing rationality in drug design. Drug repurposing and repositioning reduces financial risks in drug development accompanied by cost and time savings, while prolonging patent exclusivity hence increased returns on investment to the innovator company. Equally important, collaborative research is facilitative of cross-fertilization and refinement of ideas, while sharing resources and expertise, hence reducing overhead costs in the early stages of drug discovery. Underserved therapeutic fields are niche drug discovery areas that may be used to experiment and launch novel drug targets, while exploiting incentivized benefits afforded by drug regulatory authorities. Outsourcing allows the pharma industries to focus on their core competencies while deriving greater efficiency of specialist contract research organizations. The existing and emerging pharmaceutical modeling and artificial intelligence softwares and tools allow for in silico computation enabling more efficient computer-aided drug design. Careful selection and application of these strategies, singly or in combination, may potentially harness pharmaceutical research and innovation.
Health-Related Quality of Life in Patients With Hodgkin Lymphoma: A Longitudinal Analysis of the German Hodgkin Study Group
Authors: Kreissl Stefanie , Müller Horst , Goergen Helen , Meissner Julia , Topp Max , Sökler Martin , Markova Jana , Bernhard Jürg , Greil Richard , von Tresckow Bastian , Behringer Karolin , Rüffer Jens-Ulrich , Flechtner Hans-Henning , Möstl Michaela , Fuchs Michael , Engert Andreas , Diehl Volker , Borchmann Peter 
Published: June 2020

PURPOSE Many important details of health-related quality of life (HRQoL) after diagnosis and treatment of Hodgkin lymphoma (HL) are still unknown because large longitudinal studies of HRQoL are rare. Therefore, we analyzed a systematically assessed, comprehensive range of HRQoL domains in patients with HL of all stages from diagnosis up to 5 years of survivorship. PATIENTS AND METHODS We included patients with HL age 18-60 years at diagnosis from the German Hodgkin Study Group trials HD13, HD14, and HD15. We analyzed HRQoL using all functional and symptom scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 including deviations from reference values. We estimated the effect of different disease, patient, and treatment characteristics using multiple regression and repeated measures analysis and computed correlations of HRQoL scores. RESULTS We analyzed 4,215 patients with any HRQoL assessment within 5 years after treatment. Higher tumor burden at diagnosis was associated with impaired baseline scores in many HRQoL domains. During survivorship, cognitive, emotional, role, and social functioning and fatigue, dyspnea, sleep, and financial problems were severely and persistently affected. From year 2 on, mean deviations from reference values ranged between 12 and 29 points, with 10 points being a commonly used margin of clinical relevance. In all 3 trials, HRQoL domains 2 and 5 years after therapy were significantly influenced by baseline scores and age but not by randomized treatments. Fatigue was most closely correlated with other symptoms and scales. CONCLUSION Our results show a high and persistent amount of different HRQoL deficits in survivors of HL that are largely independent of the applied chemotherapies. Our analysis underscores the high, unmet medical need of these rather young survivors of HL regarding the psychosocial adverse effects of the cancer experience.
Assessing the Impact of the COVID-19 Outbreak on the Attitudes and Practice of Italian Oncologists Toward Breast Cancer Care and Related Research Activities
Authors: Poggio Francesca , Tagliamento Marco , Di Maio Massimo , Martelli Valentino , De Maria Andrea , Barisione Emanuela , Grosso Marco , Boccardo Francesco , Pronzato Paolo , Del Mastro Lucia , Lambertini Matteo 
Published: June 2020

PURPOSE: To investigate the impact of the COVID-19 outbreak on the attitudes and practice of Italian oncologists toward breast cancer care and related research activities. METHODS: A 29-question anonymous online survey was sent by e-mail to members of the Italian Association of Medical Oncology and the Italian Breast Cancer Study Group on April 3, 2020. Only medical oncologists (both those in training and specialists) were invited to complete the questionnaire. RESULTS: Out of 165 responding oncologists, 121 (73.3.%) worked in breast units. In the (neo)adjuvant setting, compared with before the emergency, fewer oncologists adopted weekly paclitaxel (68.5% v 93.9%) and a dose-dense schedule for anthracycline-based chemotherapy (43% v 58.8%) during the COVID-19 outbreak. In the metastatic setting, compared with before the emergency, fewer oncologists adopted first-line weekly paclitaxel for HER2-positive disease (41.8% v 53.9%) or CDK4/6 inhibitors for luminal tumors with less-aggressive characteristics (55.8% v 80.0%) during the COVID-19 outbreak. A significant change was also observed in delaying the timing for monitoring therapy with CDK4/6 inhibitors, assessing treatment response with imaging tests, and flushing central venous devices. Clinical research and scientific activities were reduced in 80.3% and 80.1% of respondents previously implicated in these activities, respectively. CONCLUSION: Medical oncologists face many challenges in providing cancer care during the COVID-19 outbreak. Although most of the changes in their attitudes and practice were reasonable responses to the current health care emergency without expected major negative impact on patient outcomes, some potentially alarming signals of undertreatment were observed.
Histone modification dynamics as revealed by multicolor immunofluorescence-based single-cell analysis
Authors: Hayashi-Takanaka Yoko , Kina Yuto , Nakamura Fumiaki , Becking Leontine E. , Nakao Yoichi , Nagase Takahiro , Nozaki Naohito , Kimura Hiroshi 
Published: June 2020

ABSTRACT
Post-translational modifications on histones can be stable epigenetic marks or transient signals that can occur in response to internal and external stimuli. Levels of histone modifications fluctuate during the cell cycle and vary among different cell types. Here, we describe a simple system to monitor the levels of multiple histone modifications in single cells by multicolor immunofluorescence using directly labeled modification-specific antibodies. We analyzed histone H3 and H4 modifications during the cell cycle. Levels of active marks, such as acetylation and H3K4 methylation, were increased during the S phase, in association with chromatin duplication. By contrast, levels of some repressive modifications gradually increased during G2 and the next G1 phases. We applied this method to validate the target modifications of various histone demethylases in cells using a transient overexpression system. In extracts of marine organisms, we also screened chemical compounds that affect histone modifications and identified psammaplin A, which was previously reported to inhibit histone deacetylases. Thus, the method presented here is a powerful and convenient tool for analyzing the changes in histone modifications.
Radioactive Seed Versus Wire-Guided Localization for Ductal Carcinoma in Situ of the Breast: Comparable Resection Margins
Authors: Agahozo Marie Colombe , Berghuis Sofie A.M. , van den Broek Esther , Koppert Linetta B. , Obdeijn Inge-Marie , van Deurzen Carolien H. M. 
Published: June 2020

Abstract
Background
There are currently two widely used methods for preoperative localization of ductal carcinoma in situ (DCIS) of the breast: wire-guided localization (WGL) and radioactive seed localization (RSL). Several studies compared these localization techniques in small cohorts.

Objective
The aim of this study was to compare the surgical resection margin status between RSL and WGL in a large national cohort of patients with DCIS.

Patients and Methods
We included patients from the Dutch Pathology Registry who underwent breast-conserving surgery for DCIS by either RSL (n = 1851) or WGL (n = 2187) between 2009 and 2019. Several clinicopathological characteristics were compared between these two groups, including resection margin status and number of re-excisions.

Results
Patients undergoing RSL were younger (p = 0.014) and were more often diagnosed with a large DCIS (p = 0.013), high grade DCIS (p < 0.001) and comedonecrosis (p < 0.001) compared with patients undergoing WGL. There was no significant difference in resection margin status between both groups (p = 0.089) and the number of re-excisions (p = 0.429). However, in case of re-excision, patients in the RSL group were more often treated with breast-conserving surgery (p = 0.029).

Conclusion
In this large national cohort study of patients with DCIS, we demonstrated that there was no difference in resection margin status between both procedures, or in the number of re-excisions, but patients in the RSL group were more often treated with breast-conserving therapy in case of a re-excision.
Automatic diagnosis for cysts and tumors of both jaws on panoramic radiographs using a deep convolution neural network
Authors: Kwon Odeuk , Yong Tae-Hoon , Kang Se-Ryong , Kim Jo-Eun , Huh Kyung-Hoe , Heo Min-Suk , Lee Sam-Sun , Choi Soon-Chul , Yi Won-Jin 
Published: June 2020

Objectives: The purpose of this study was to automatically diagnose odontogenic cysts and tumors of both jaws on panoramic radiographs using deep learning. We proposed a novel framework of deep convolution neural network (CNN) with data augmentation for detection and classification of the multiple diseases. Methods: We developed a deep CNN modified from YOLOv3 for detecting and classifying odontogenic cysts and tumors of both jaws. Our data set of 1282 panoramic radiographs comprised 350 dentigerous cysts (DCs), 302 periapical cysts (PCs), 300 odontogenic keratocysts (OKCs), 230 ameloblastomas (ABs), and 100 normal jaws with no disease. In addition, the number of radiographs was augmented 12-fold by flip, rotation, and intensity changes. We evaluated the classification performance of the developed CNN by calculating sensitivity, specificity, accuracy, and area under the curve (AUC) for diseases of both jaws. Results: The overall classification performance for the diseases improved from 78.2% sensitivity, 93.9% specificity,91.3% accuracy, and 0.86 AUC using the CNN with unaugmented data set to 88.9% sensitivity, 97.2% specificity, 95.6% accuracy, and 0.94 AUC using the CNN with augmented data set. CNN using augmented data set had the following sensitivities, specificities, accuracies, and AUCs: 91.4%, 99.2%, 97.8%, and 0.96 for DCs, 82.8%, 99.2%, 96.2%, and 0.92 for PCs, 98.4%,92.3%,94.0%, and 0.97 for OKCs, 71.7%, 100%, 94.3%, and 0.86 for ABs, and 100.0%, 95.1%, 96.0%, and 0.97 for normal jaws, respectively. Conclusion: The CNN method we developed for automatically diagnosing odontogenic cysts and tumors of both jaws on panoramic radiographs using data augmentation showed high sensitivity, specificity, accuracy, and AUC despite the limited number of panoramic images involved.
Elevated Plasmodium sporozoite infection and multiple insecticide resistance in the principal malaria vectors Anopheles funestus and Anopheles gambiae in a forested locality close to the Yaoundé airport, Cameroon
Authors: Nkemngo Francis N. , Mugenzi Leon M. J. , Terence Ebai , Niang Abdoulaye , Wondji Murielle J. , Tchoupo Micareme , Nguete Nguiffo D. , Tchapga Williams , Irving Helen , Ntabi Jacques D. M. , Agonhossou Romuald , Boussougou-Sambe Terence S. , Akoton Romaric B. , Koukouikila-Koussounda Felix , Pinilla Yudi T. , Ntoumi Francine , Djogbenou Luc S. , Ghogomu Stephen M. , Ndo Cyrille , Adegnika Ayola A. , Borrmann Steffen , Wondji Charles S. 
Published: June 2020

Background:Reducing the burden of malaria requires better understanding of vector populations, particularly in forested regions where the incidence remains elevated. Here, we characterized malaria vectors in a locality near the Yaoundé international airport, Cameroon, including species composition, abundance,Plasmodiuminfection rate, insecticide resistance profiles and underlying resistance mechanisms.Methods:Blood-fed adult mosquitoes resting indoors were aspirated from houses in April 2019 at Elende, a village located 2 km from the Yaoundé-Nsimalen airport. Female mosquitoes were forced to lay eggs to generate F1adult progeny. Bioassays were performed to assess resistance profile to insecticides. The threshold of insecticide susceptibility was defined above 98% mortality rate and mortality rates below 90% were indicative of confirmed insecticide resistance. Furthermore, the molecular basis of resistance andPlasmodiuminfection rates were investigated.Results:Anopheles funestuss.s. was most abundant species in Elende (85%) followed byAnopheles gambiaes.s. (15%) with both having a similar sporozoite rate. Both species exhibited high levels of resistance to pyrethroids (<40% mortality).An. gambiaes.s. was also resistant to DDT (9.9% mortality) and bendiocarb (54% mortality) while susceptible to organophosphate.An. funestuss.s. was resistant to dieldrin (1% mortality), DDT (86% mortality) but susceptible to carbamates and organophosphates. The L119F-GSTe2 resistance allele (8%) and G119Sace-1 resistance allele (15%) were detected inAn. funestuss.s. andAn. gambiaes.s., respectively.Furthermore, the high pyrethroid/DDT resistances inAn. gambiaes.s. corresponded with an increase frequency of 1014Fkdrallele (95%). Transcriptional profiling of candidate cytochrome P450 genes reveals the over-expression ofCYP6P5,CYP6P9aandCYP6P9b.Conclusion:The resistance to multiple insecticide classes observed in these vector populations alongside the highPlasmodiumsporozoite rate highlights the challenges that vector control programs encounter in sustaining the regular benefits of contemporary insecticide-based control interventions in forested areas.