bluuebunny/crossref_metadata_2025_split huggingface dataset:
A urine-based Exosomal gene expression test stratifies risk of high-grade prostate Cancer in men with prior negative prostate biopsy undergoing repeat biopsy
Authors: McKiernan James , Noerholm Mikkel , Tadigotla Vasisht , Kumar Sonia , Torkler Phillipp , Sant Grannum , Alter Jason , Donovan Michael J. , Skog Johan 
Published: September 2020

Abstract
Background
Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate (IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established.

Methods
As part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2–10 ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results.

Results
229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35 and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.

Conclusions
The EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2–10 ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.
Influence of adjunctive azithromycin on microbiological and clinical outcomes in periodontitis patients: 6-month results of randomized controlled clinical trial
Authors: Čuk Katarina , Povšič Katja , Milavec Suzana , Seme Katja , Gašperšič Rok 
Published: September 2020

AbstractBackgroundOur aim was to determine if azithromycin therapy, as an adjunct to scaling and root planing (SRP), decreases the number of pathobiontic subgingival plaque species and sites demonstrating pocket depth (PD) ≥ 5 mm and bleeding on probing (BOP) 6 months post-treatment.MethodsIn a double-blind randomized parallel-arm placebo-controlled trial, 40 patients received nonsurgical periodontal treatment in two sessions within 7 days. Patients then received systemic antibiotic therapy (n = 20, azithromycin 500 mg/day for 3 days) or placebo (n = 20). Pooled microbiologic samples were taken before and 6 months after therapy and analysed by established culture methods. The primary outcome variable was the number of sites with PD ≥ 5 mm and BOP at the 6-month re-evaluation. Using multivariate multilevel logistic regression, the effects of gender, age, antibiotic therapy, presence ofP. gingivalisorA. actinomycetemcomitans, smoking, tooth being a molar and interdental location were evaluated.ResultsThe number of sites with PD ≥ 5 mm and BOP after 6 months was similar in the test (Me = 4, IQR = 0–11) and control (Me = 5, IQR = 1–22) group. Adjunctive azithromycin treatment, compared to SRP alone, resulted in more frequent eradication ofA. actinomycetemcomitans(p = 0.013) andC. rectus(p = 0.029), decreased proportion (p = 0.006) and total counts (p = 0.003) ofP. gingivalis, and decreased proportion ofC. rectus(p = 0.012). Both groups showed substantial but equivalent improvements in periodontal parameters, with no intergroups differences at initially shallow or deep sites. The logistic regression showed a lower odds ratio for healing of diseased sites on molars (OR = 0.51;p <  0,001).ConclusionDespite significant changes in numbers ofA. actinomycetemcomitans,P. gingivalisandC. rectus, patients with periodontitis do not benefit from adjunctive systemic azithromycin in terms of number of persisting sites with PD ≥ 5 mm and BOP.Trial registrationEUDRA-CT: 2015–004306-42;https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-004306-42/SI, registered 17. 12. 2015.
The influence of a serious game’s narrative on students’ attitudes and learning experiences regarding delirium: an interview study
Authors: Buijs-Spanjers Kiki R. , Harmsen Anne , Hegge Harianne H. , Spook Jorinde E. , de Rooij Sophia E. , Jaarsma Debbie A. D. C. 
Published: September 2020

Abstract
Background
Delirium is a neuropsychiatric syndrome that affects patients’ attention and awareness as a result of a physical condition. In recent years, persistent gaps in delirium education have led to suboptimal delirium care. Still, little is known about what are the most important aspects of effective delirium education. Serious games are both entertainment and an interactive, safe learning environment where players can experiment and create new knowledge. They have the potential to contribute to improved delirium education. We used a video-based serious games’ narrative to explore aspects essential to enhance students’ attitudes and learning experiences regarding delirium.

Methods
We created a semi-structured interview guide and interviewed seven nursing and nine medical students about their attitudes and learning experiences, after they had played the game. A qualitative descriptive design and inductive content analysis with constant comparison were used.

Results
The patient’s and nurse’s perspective, interactivity to experiment, realistic views on care options, and feedback on care actions were important for enhancing students’ attitudes and learning experiences regarding delirium. Students felt these aspects encouraged them to get actively involved in and experiment with the study material, which in turn led to enhanced reflection on delirium care and education. Our findings highlight the importance of a more patient-oriented focus to delirium education to drive attitudinal change. Students’ learning experiences were further enhanced through their affective responses provoked by the perspectives, interactivity, realism, and feedback.

Conclusions
Students considered the characters’ perspectives, interactivity, realism, and feedback important aspects of the game to enhance their attitudes towards delirious patients and enrich their learning experiences. A patient-oriented narrative provides a clinically relevant experience in which reflection plays an important role. The serious game also serves as medium to actively experiment with care solutions to create better understanding of how healthcare professionals can influence a delirious patient’s experience.
The obstacles to organ donation following brain death in Iran: a qualitative study
Authors: Abbasi Parvin , Yoosefi Lebni Javad , Nouri Paricher , Ziapour Arash , Jalali Amir 
Published: September 2020

Abstract
Background
Organ donation following brain death has become an important way of supplying organs for transplantation in many countries. This practice is less common in Iran for different reasons. Therefore, this study aims to explore the obstacles to organ donation following brain death in Iran.

Methods
This qualitative research was conducted following the conventional content analysis method. The study population consisted of individuals with a history of brain death among their blood relatives who refused to donate the organs. Snowball sampling was employed to select the participants. In-depth semi-structured interviews were conducted for data gathering. Theoretical saturation was achieved through 20 interviews. Data analysis was done following the steps proposed by Graneheim and Lundman. Lincoln and Guba’s criteria were used to ensure data rigor and transferability of the study.

Results
Data analyses revealed 185 codes, 23 categories, and seven themes including, poor knowledge about brain death and organ transplantation from a dead body, cultural beliefs, religious beliefs, deficiencies of requesting process, fear and concerns, inability to make a decision, and social learning.

Conclusion
There were several factors in families’ reluctance to donate organs of a brain-dead patient. Through improving knowledge and changing cultural beliefs in society, it is possible to take large steps towards promoting organ donation from brain-dead patients.
The challenges of ethical behaviors for drug supply in pharmacies in Iran by a principle-based approach
Authors: Iranmanesh Mahla , Yazdi-Feyzabadi Vahid , Mehrolhassani Mohammad Hossein 
Published: September 2020

AbstractBackgroundPharmacists as the trustee of pharmacy services must adhere to ethical principles and evaluate their professionalism. Pharmacists may sometimes show different unethical behaviors in their interactions, so it is essential to understand these behaviors. The present study aimed to determine the challenges of ethical behaviors based on a principles-based approach in the area of drug supply in pharmacies.MethodsThis qualitative content analysis was conducted in Kerman in 2018. A number of key players in the field of medication supply were selected using snowball sampling to interview. An effort was made to select samples with maximum variation. Exclusion criteria include having less than 3 years of work experience in pharmacy and supervision, not willing to participate in the interview, and not participating in the interview for 3 times. The participants in this study consisted of pharmacy technicians (n = 5), patients (n = 6), pharmacists (n = 8), inspectors of insurance companies (n = 4), and inspectors of food and drug administration (n = 3). Data were analyzed using directed content analysis by Maxqda software version 10 (VERBI Software, Berlin, Germany). The principles of “Beauchamp and Childress Ethics” theory including autonomy, beneficence, non-maleficence, and justice were selected as the main principles.ResultsAfter data analysis, 8 main categories and 26 subcategories were obtained. The main categories include patient privacy, patient independence, communication principles, patient-centered services, drug supplier, patient harm avoidance, supervision, and distributive, procedural, and interactional justice. The subcategories include increasing patient awareness, culturizing prescription, and rational drug use, confidentiality and privacy, and pharmacist-patient relationship/communication, which were the main ethical challenges in the area of drug supply at pharmacies.ConclusionsAccording to a principle-based approach, the greatest challenges were related to two principles of autonomy and beneficence. The policymakers in the healthcare system should emphasize patient independence, patient privacy, and patient-centered services. The results of this study can be used as a tool to introduce ethical challenges to policymakers and develop educational contents, the chart of professional ethics in pharmacies, and accreditation measures of pharmacies.
A participatory surveillance of marsh deer (Blastocerus dichotomus) morbidity and mortality in Argentina: first results
Authors: Orozco M. Marcela , Argibay Hernán D. , Minatel Leonardo , Guillemi Eliana C. , Berra Yanina , Schapira Andrea , Di Nucci Dante , Marcos Andrea , Lois Fernanda , Falzone Martín , Farber Marisa D. 
Published: September 2020

AbstractBackgroundIn an era of unprecedented socio-ecological changes, managing wildlife health demands high-quality data collection and the engagement of local communities.Blastocerus dichotomus, the largest South American deer, is Vulnerable to extinction mainly due to habitat loss. Diseases have been recognised as a potential threat, and winter mortality has been historically described in marsh deer populations from Argentina. Field difficulties have, however, prevented in-depth studies of their health status.ResultsBetween May 2014 and April 2017, we investigated marsh deer morbidity and mortality in the two largest populations in Argentina. We collected data by means of a passive surveillance system that involved a network of researchers, field partners (veterinarians, park rangers, and local community), and decision makers. We sampled marsh deer during as well as outside mortality events. A total of 44 marsh deer with different body condition scores were evaluated. We obtained haematology and biochemistry values from animals with good body condition score. Marsh deer with poor body condition had a high burden of the ticksAmblyomma tristeandRhipicephalus microplus. Vector-borne agents such asTheileria cervi,Trypanosoma theileri, Trypanosoma evansi, Ehrlichia chaffeensis, Anaplasma platys, Anaplasma odocoilei, Anaplasma marginale, andCandidatus Anaplasma boleensewere also found.Haemonchusspp.,Ostertagiaspp., andTrichostrongylusspp. were the most frequent gastrointestinal parasites in deer with poor body condition. A Multiple Correspondence Analysis reinforced a possible association of winter period with lower body score condition, high tick loads, infection withE. chaffeensis, and presence of harmful gastrointestinal parasites.ConclusionsOur approach allowed the establishment of a participatory surveillance network of marsh deer morbidity and mortality in Argentina. We report and analyse the first data obtained opportunistically within the framework of this network, providing information on the infectious and parasitic agents in marsh deer populations. The occurrence ofFasciola hepaticaandLeptospira interrogansserovarpyrogenesis reported for the first time in wild marsh deer from Argentina. Our data will be useful to improve the interpretation of future mortality events. The field implementation of a surveillance network is key to a holistic approach to wildlife diseases.
AKT2 drives cancer progression and is negatively modulated by miR-124 in human lung adenocarcinoma
Authors: Liu Ting , Zhu Jianjie , Du Wenwen , Ning Weiwei , Zhang Yang , Zeng Yuanyuan , Liu Zeyi , Huang Jian-An 
Published: September 2020

Abstract
Background
AKT2 is highly expressed in many human cancers, including non-small cell lung cancer (NSCLC). Accumulating evidence has also revealed that AKT2 can promote NSCLC cell proliferation and metastasis. However, the involved mechanism remains unclear. Herein, our study mainly explored the function of AKT2 during cancer progression and uncovered a new post-transcriptional mechanism of AKT2 expression in lung adenocarcinoma (LUAD).

Methods
Quantitative real-time (qRT-PCR), western blot and immunohistochemistry (IHC) assays were performed to detect the expression of AKT2 and other proteins. Cell counting kit-8 (CCK-8), colony formation and EdU assays were performed to assess cell proliferation. Flow cytometry analysis was used to detect changes in the cell cycle and apoptosis. Transwell assays were used to evaluate cell migration and invasion. Additionally, a luciferase reporter assay and western blotting were employed to assess miR-124 targeting of AKT2. Xenograft mouse model was used to observe the role of miR-124/AKT2 axis on the occurrence and development of LUAD.

Results
We showed that AKT2 was highly expressed in NSCLC tissues and closely related to the poor prognosis of LUAD patients. Moreover, AKT2 affected LUAD cell proliferation, migration and invasion by regulating the cell cycle and promoting the occurrence of epithelial-mesenchymal transition (EMT) and the expression of matrix metalloproteinases (MMPs). In addition, we demonstrated that miR-124 overexpression downregulated AKT2 expression by binding to the 3′-untranslated region (3′- UTR) of AKT2 and thus inhibited the occurrence and development of LUAD in vivo and in vitro.

Conclusions
Our results suggest that miR-124 overexpression can negatively regulate AKT2 and thus inhibit the progression of LUAD. Therefore, the miR-124/AKT2 axis may serve as a potential target for novel therapies for LUAD.
Promoter methylation, transcription, and retrotransposition of LINE-1 in colorectal adenomas and adenocarcinomas
Authors: Shademan Milad , Zare Khadijeh , Zahedi Morteza , Mosannen Mozaffari Hooman , Bagheri Hosseini Hadi , Ghaffarzadegan Kamran , Goshayeshi Ladan , Dehghani Hesam 
Published: September 2020

Abstract
Background
The methylation of the CpG islands of the LINE-1 promoter is a tight control mechanism on the function of mobile elements. However, simultaneous quantification of promoter methylation and transcription of LINE-1 has not been performed in progressive stages of colorectal cancer. In addition, the insertion of mobile elements in the genome of advanced adenoma stage, a precancerous stage before colorectal carcinoma has not been emphasized. In this study, we quantify promoter methylation and transcripts of LINE-1 in three stages of colorectal non-advanced adenoma, advanced adenoma, and adenocarcinoma. In addition, we analyze the insertion of LINE-1, Alu, and SVA elements in the genome of patient tumors with colorectal advanced adenomas.

Methods
LINE-1 hypomethylation status was evaluated by absolute quantitative analysis of methylated alleles (AQAMA) assay. To quantify the level of transcripts for LINE-1, quantitative RT-PCR was performed. To find mobile element insertions, the advanced adenoma tissue samples were subjected to whole genome sequencing and MELT analysis.

Results
We found that the LINE-1 promoter methylation in advanced adenoma and adenocarcinoma was significantly lower than that in non-advanced adenomas. Accordingly, the copy number of LINE-1 transcripts in advanced adenoma was significantly higher than that in non-advanced adenomas, and in adenocarcinomas was significantly higher than that in the advanced adenomas. Whole-genome sequencing analysis of colorectal advanced adenomas revealed that at this stage polymorphic insertions of LINE-1, Alu, and SVA comprise approximately 16%, 51%, and 74% of total insertions, respectively.

Conclusions
Our correlative analysis showing a decreased methylation of LINE-1 promoter accompanied by the higher level of LINE-1 transcription, and polymorphic genomic insertions in advanced adenoma, suggests that the early and advanced polyp stages may host very important pathogenic processes concluding to cancer.
Is Anopheles gambiae attraction to floral and human skin-based odours and their combination modulated by previous blood meal experience?
Authors: Kemibala Elison E. , Mafra-Neto Agenor , Saroli Jesse , Silva Rodrigo , Philbert Anitha , Ng’habi Kija , Foster Woodbridge A. , Dekker Teun , Mboera Leonard E. G. 
Published: September 2020

Abstract
Background
Mosquitoes use odours to find energy resources, blood hosts and oviposition sites. While these odour sources are normally spatio-temporally segregated in a mosquito’s life history, here this study explored to what extent a combination of flower- and human-mimicking synthetic volatiles would attract the malaria vector Anopheles gambiae sensu stricto (s.s.)

Methods
In the laboratory and in large (80 m2) outdoor cages in Tanzania, nulliparous and parous A. gambiae s.s. were offered choices between a blend of human skin volatiles (Skin Lure), a blend of floral volatiles (Vectrax), or a combination thereof. The blends consisted of odours that induce distinct, non-overlapping activation patterns in the olfactory circuitry, in sensory neurons expressing olfactory receptors (ORs) and ionotropic receptors (IRs), respectively. Catches were compared between treatments.

Results
In the laboratory nulliparous and parous mosquitoes preferred skin odours and combinations thereof over floral odours. However, in semi-field settings nulliparous were significantly more caught with floral odours, whereas no differences were observed for parous females. Combining floral and human volatiles did not augment attractiveness.

Conclusions
Nulliparous and parous A. gambiae s.s. are attracted to combinations of odours derived from spatio-temporally segregated resources in mosquito life-history (floral and human volatiles). This is favourable as mosquito populations are comprised of individuals whose nutritional and developmental state steer them to diverging odours sources, baits that attract irrespective of mosquito status could enhance overall effectiveness and use in monitoring and control. However, combinations of floral and skin odours did not augment attraction in semi-field settings, in spite of the fact that these blends activate distinct sets of sensory neurons. Instead, mosquito preference appeared to be modulated by blood meal experience from floral to a more generic attraction to odour blends. Results are discussed both from an odour coding, as well as from an application perspective.
A health care professionals training needs assessment for oncology in Uganda
Authors: Byamugisha Josaphat , Munabi Ian G. , Mubuuke Aloysius G. , Mwaka Amos D. , Kagawa Mike , Okullo Isaac , Niyonzima Nixon , Lusiba Pastan , Ainembabazi Peruth , Kankunda Caroline , Muhumuza Dennis D. , Orem Jackson , Atwine Diana , Ibingira Charles 
Published: September 2020

Abstract
Background
Cancer incidence and mortality in sub-Saharan Africa are increasing and do account for significant premature death. The expertise of health care providers is critical to downstaging cancer at diagnosis and improving survival in low- and middle-income countries. We set out to determine the training needs of health care providers for a comprehensive oncology services package in selected hospitals in Uganda, in order to inform capacity development intervention to improve cancer outcomes in the East African region.

Methods
This was a cross-sectional survey using the WHO Hennessey-Hicks questionnaire to identify the training needs of health workers involved in cancer care, across 22 hospitals in Uganda. Data were captured in real time using the Open Data Kit platform from which the data was exported to Stata version 15 for analysis using the Wilcoxon signed-rank test and Somers-Delta.

Results
There were 199 respondent health professionals who were predominately female (146/199, 73.37%), with an average age of 38.97 years. There were 158/199 (79.40%) nurses, 24/199 (12.06%) medical doctors and 17/199 (8.54%) allied health professionals. Overall, the research and audit domain had the highest ranking for all the health workers (Somers-D = 0.60). The respondent’s level of education had a significant effect on the observed ranking (P value = 0.03). Most of the continuing medical education (CME) topics suggested by the participants were in the clinical task-related category.

Conclusion
The “research and audit” domain was identified as the priority area for training interventions to improve oncology services in Uganda. There are opportunities for addressing the identified training needs with an expanded cancer CME programme content, peer support networks and tailored training for the individual health care provider.