bluuebunny/crossref_metadata_2025_split huggingface dataset:
An underestimated pitfall of oral candidiasis in head and neck cancer patients undergoing radiotherapy: an observation study
Authors: Chitapanarux Imjai , Wongsrita Somying , Sripan Patumrat , Kongsupapsiri Panithan , Phakoetsuk Panchalee , Chachvarat Siriarrayapa , Kittidachanan Kittikun 
Published: July 2021

AbstractBackgroundOral candidiasis is a common problem associated with head and neck radiation therapy (RT) consequences being pain, burning sensation, taste change, and systemic infection. There are difficulties in differentiating between oral candidiasis and radiation induced oral mucositis. We conducted a prospective study to explore the incidence of clinical oral candidiasis and evaluate the accuracy of diagnosis among head and neck cancer (HNC) patients receiving RT or concurrent chemoradiotherapy (CCRT).MethodsThis study included 86 HNC patients who had no clinical signs or symptoms of oral candidiasis. Oral mucosa and tongue swabs were carried out and analyzed three times by fungal cultures at the following time points: (1) before RT, (2) at the time of clinically diagnosed candidiasis or during RT at between the 15th–17th fraction (whichever occurred first), and (3) at the end of RT. The accuracy of clinical oral candidiasis was explored and confirmed by fungal colonization techniques. The incidence and risk factors associated with fungal colonization before and throughout the treatment were analyzed.ResultsThe overall incidence of clinical oral candidiasis was 53.5% throughout the course of RT. Confirmation of fungal colonization was found in 39.5%, 65.9%, and 57.7% of cases before RT, during RT, and end of RT, respectively. The accuracy of the diagnosis using only clinical presentation was demonstrated in 60%, 50%, and 52% before RT, during RT, and end of RT, respectively. Logistic regression analysis showed that age, CCRT, and using 2% viscous lidocaine solution were independent risk factors for fungal colonization.ConclusionsThe results of this study demonstrated an underestimation of clinical oral candidiasis before and throughout the course of radiotherapy from using only clinical sign and symptoms. Crucial attention to detail and testing in the oral examination could improve decision making for detection of oral candidiasis in HNC patients receiving RT or CCRT.
Development of consensus-based aims, contents, intended learning outcomes, teaching, and evaluation methods for a history of medicine and pharmacy course for medical and pharmacy students in the Arab world: a Delphi study
Authors: Shawahna Ramzi 
Published: July 2021

Abstract
Background
History courses are “required” elements among the didactic elements of the medical and pharmacy curricula in many schools around the world. The aim of this study was to develop consensus-based aims, contents, intended learning outcomes, teaching, and evaluation methods of a history of medicine and pharmacy course for medical and pharmacy students in the Arab World.

Methods
A systematic search of PubMed, ScienceDirect, SpringerLink, Scopus, and Google Scholar was conducted to identify course aims, contents, intended learning outcomes from the literature. The search was supplemented by semi-structured in-depth interviews with 5 educators/academicians, 3 pharmacists, and 3 physicians. The Delphi technique was used among panelists (10 educators/academicians, 4 physicians, and 4 pharmacists) to develop consensus-based course aims, contents, intended learning outcomes, teaching, and evaluation methods.

Results
The vast majority of the panelists agreed on the 10 items (agreement ≥88.9%) on the importance of teaching history to medical and pharmacy students. Consensus-based aims (n = 4) and intended learning outcomes (n = 13) were developed in the 1st and 2nd iterative Delphi rounds. The panelists suggested that 16 dedicated meeting hours (1 credit hour) would be required to cover the course. Bloom’s verbs were used to target the lower and higher orders of the cognitive domain. The course could be taught through face-to-face lectures, provision of reading materials, video documentaries, case studies, group discussions and debates. Multiple-choice questions, written reflections, portfolios, group projects, and engagement in discussions and debates might be used to evaluate performance of students.

Conclusion
Consensus-based course of history of medicine and pharmacy course was developed for medical and pharmacy students in the Arab World. Well-designed course aims, contents, intended learning outcomes, teaching, and evaluation methods are more likely to meet the accreditation requirements and might improve performance of medical and pharmacy students. Future studies are still needed to investigate if such consensus-based courses can improve performance of the students.
Consent to research participation: understanding and motivation among German pupils
Authors: Reetz Jana , Richter Gesine , Borzikowsky Christoph , Glinicke Christine , Darabaneanu Stephanie , Buyx Alena 
Published: July 2021

AbstractBackgroundThe EU’s 2006 Paediatric Regulation aims to support authorisation of medicine for children, thus effectively increasing paediatric research. It is ethically imperative to simultaneously establish procedures that protect children’s rights.MethodThis study endeavours (a) to evaluate whether a template consent form designed by the Standing Working Group of the German-Research-Ethics-Committees (AKEK) adequately informs adolescents about research participation, and (b) to investigate associated phenomena like therapeutic misconception and motives for research participation. In March 2016 a questionnaire study was conducted among 279 pupils (mean age 13.1 years) of a secondary school in northern Germany.ResultsA majority of participants showed a general good understanding of foundational research ethics concepts as understood from the AKEK consent form. Nevertheless, our data also suggests possible susceptibility to therapeutic misconception. Own health concerns and pro-social considerations were found to be significant motivational factors for participating in research, while anticipation of pain lessens likelihood of participation. Advice from trusted others is an important decisional influence, too. Furthermore, data security was found to be a relevant aspect of adolescents’ decision-making process.ConclusionBearing in mind adolescents’ generally good understanding, we infer the lack of knowledge about medical research in general to be one source of therapeutic misconception. To further improve the quality of consent we propose a multi-staged approach whereby general research education is completed before an individual becomes a patient or potential participant. To the best of our knowledge this is the first German questionnaire-study addressing issues of informed consent in a large under-age sample.
Using Theoretical Domains Framework (TDF) to understand implementation of a pragmatic clinical trial in Public Dental Service in Norway
Authors: Hovden E. A.S. , Skudutyte-Rysstad Rasa 
Published: July 2021

AbstractBackgroundMost dental research in Norway has traditionally been conducted by universities, and the involvement of clinicians in research projects has not been a common practice.The aim of the present study was to identify behavioral factors that influence effective implementation of a pragmatic clinical trial in the Public Dental Service (PDS) in Norway and to understand which of these factors result in higher patient recruitment.MethodsDentists, dental hygienists, and dental assistants at nine Public Dental Service clinics in three counties in Norway involved in an ongoing pragmatic clinical trial were asked to complete an electronically distributed questionnaire based on the Theoretical Domains Framework (TDF).ResultsThirty-seven out of 69 dentists and dental hygienists (54 %) and seventeen out of 57 dental assistants (30 %) answered the questionnaire. “Knowledge” was the domain with the highest mean response, suggesting strong confidence in personal knowledge and practical skills among the clinicians. Together with “beliefs about consequences,” “organizational resources,” and “environmental context,” “knowledge” was the one of five domains identified as important behavioral determinants in patient recruitment to clinical trials by dental professionals.ConclusionsThe findings suggest that TDF was useful to understand factors affecting implementation of clinical trials in PDS and that several factors such as clinical relevance of trial to be implemented, organizational resources, and communication with the research team require more attention when planning and implementing clinical trials in PDS.
Factors associated with response and remission from depression at 6-months of treatment in a retrospective cohort treated within an integrated care program
Authors: Jeffrey Jessica , Klomhaus Alex , Aralis Hilary , Barrera Wendy , Rosenberg Shanna , Grossman Mark , Lester Patricia 
Published: July 2021

Abstract
Background
Depression causes significant morbidity, which impacts mental health, overall general health outcomes, everyday functioning and quality of life. This study aims to contribute to knowledge in the field through enhanced understanding of factors that influence depression response and remission, with consideration for design of treatment services to optimize depression outcomes within integrated care programs.

Methods
Using routine behavioral health screening and electronic health record data, we identified a retrospective cohort consisting of 615 adult patients receiving depression treatment within an integrated care program. Cohort member Patient Health Questionnaire (PHQ-9) data was analyzed for the 6 months following initiation of treatment. Multinomial regression models were estimated to identify factors associated with depression treatment response (PHQ-9 < 10) and remission (PHQ-9 < 5).

Results
At 6 months, 47% of patients demonstrated treatment response and 16% demonstrated remission. Baseline trauma symptoms and suicidal ideation were significantly associated with decreased odds of achieving remission (Odds Ratio (95% CI) [OR] = 0.45 (0.23, 0.88) and OR = 0.49 (0.29, 0.82), respectively). In fully adjusted models, baseline suicidal ideation remained significant (OR = 0.53 (0.31, 0.89)) and some evidence of an association persisted for baseline trauma symptoms (OR = 0.51 (0.25, 1.01)).

Conclusions
After controlling for baseline depression symptoms, the presence of suicidal ideation is associated with reduced likelihood of remission. Increased understanding of factors associated with depression treatment outcomes may be employed to help guide the delivery and design of clinical services. Alongside routine screening for co-morbid anxiety, suicidal ideation and traumatic stress should be assessed and considered when designing depression treatment services.
Radiopharmaceutical and Eu3+ doped gadolinium oxide nanoparticles mediated triple-excited fluorescence imaging and image-guided surgery
Authors: Shi Xiaojing , Cao Caiguang , Zhang Zeyu , Tian Jie , Hu Zhenhua 
Published: July 2021

AbstractCerenkov luminescence imaging (CLI) is a novel optical imaging technique that has been applied in clinic using various radionuclides and radiopharmaceuticals. However, clinical application of CLI has been limited by weak optical signal and restricted tissue penetration depth. Various fluorescent probes have been combined with radiopharmaceuticals for improved imaging performances. However, as most of these probes only interact with Cerenkov luminescence (CL), the low photon fluence of CL greatly restricted it’s interaction with fluorescent probes for in vivo imaging. Therefore, it is important to develop probes that can effectively convert energy beyond CL such as β and γ to the low energy optical signals. In this study, a Eu3+doped gadolinium oxide (Gd2O3:Eu) was synthesized and combined with radiopharmaceuticals to achieve a red-shifted optical spectrum with less tissue scattering and enhanced optical signal intensity in this study. The interaction between Gd2O3:Eu and radiopharmaceutical were investigated using18F-fluorodeoxyglucose (18F-FDG). The ex vivo optical signal intensity of the mixture of Gd2O3:Eu and18F-FDG reached 369 times as high as that of CLI using18F-FDG alone. To achieve improved biocompatibility, the Gd2O3:Eu nanoparticles were then modified with polyvinyl alcohol (PVA), and the resulted nanoprobe PVA modified Gd2O3:Eu (Gd2O3:Eu@PVA) was applied in intraoperative tumor imaging. Compared with18F-FDG alone, intraoperative administration of Gd2O3:Eu@PVA and18F-FDG combination achieved a much higher tumor-to-normal tissue ratio (TNR, 10.24 ± 2.24vs.1.87 ± 0.73,P = 0.0030). The use of Gd2O3:Eu@PVA and18F-FDG also assisted intraoperative detection of tumors that were omitted by preoperative positron emission tomography (PET) imaging. Further experiment of image-guided surgery demonstrated feasibility of image-guided tumor resection using Gd2O3:Eu@PVA and18F-FDG. In summary, Gd2O3:Eu can achieve significantly optimized imaging property when combined with18F-FDG in intraoperative tumor imaging and image-guided tumor resection surgery. It is expected that the development of the Gd2O3:Eu nanoparticle will promote investigation and application of novel nanoparticles that can interact with radiopharmaceuticals for improved imaging properties. This work highlighted the impact of the nanoprobe that can be excited by radiopharmaceuticals emitting CL, β, and γ radiation for precisely imaging of tumor and intraoperatively guide tumor resection.
Growth rate-dependent flexural rigidity of microtubules influences pattern formation in collective motion
Authors: Zhou Hang , Isozaki Naoto , Fujimoto Kazuya , Yokokawa Ryuji 
Published: July 2021

Abstract
Background
Microtubules (MTs) are highly dynamic tubular cytoskeleton filaments that are essential for cellular morphology and intracellular transport. In vivo, the flexural rigidity of MTs can be dynamically regulated depending on their intracellular function. In the in vitro reconstructed MT-motor system, flexural rigidity affects MT gliding behaviors and trajectories. Despite the importance of flexural rigidity for both biological functions and in vitro applications, there is no clear interpretation of the regulation of MT flexural rigidity, and the results of many studies are contradictory. These discrepancies impede our understanding of the regulation of MT flexural rigidity, thereby challenging its precise manipulation.

Results
Here, plausible explanations for these discrepancies are provided and a new method to evaluate the MT rigidity is developed. Moreover, a new relationship of the dynamic and mechanic of MTs is revealed that MT flexural rigidity decreases through three phases with the growth rate increases, which offers a method of designing MT flexural rigidity by regulating its growth rate. To test the validity of this method, the gliding performances of MTs with different flexural rigidities polymerized at different growth rates are examined. The growth rate-dependent flexural rigidity of MTs is experimentally found to influence the pattern formation in collective motion using gliding motility assay, which is further validated using machine learning.

Conclusion
Our study establishes a robust quantitative method for measurement and design of MT flexural rigidity to study its influences on MT gliding assays, collective motion, and other biological activities in vitro. The new relationship about the growth rate and rigidity of MTs updates current concepts on the dynamics and mechanics of MTs and provides comparable data for investigating the regulation mechanism of MT rigidity in vivo in the future.

Graphic Abstract
Tumor susceptibility gene 101 is required for the maintenance of uterine epithelial cells during embryo implantation
Authors: Byun Hyunji , Kwon Sojung , Wagner Kay-Uwe , Shin Hyejin , Lim Hyunjung Jade 
Published: July 2021

Abstract
Background
The tumor susceptibility gene 101 (Tsg101), a component of the endosomal sorting complex required for transport (ESCRT) complex I, is involved in multiple biological processes involving endomembranous structures and the plasma membrane. The role of Tsg101 in the uterine epithelium was investigated in Tsg101 floxed mice crossed with Lactoferrin-iCre mice (Tsg101d/d).

Methods
Tsg101d/d mice were bred with stud male mice and the status of pregnancy was examined on days 4 and 6. Histological analyses were performed to examine the uterine architecture. Immunofluorescence staining of several markers was examined by confocal microscopy. Uterine epithelial cells (UECs) were isolated from Tsg101f/f and Tsg101d/d mice, and the expression of necroptosis effectors was examined by RT-PCR, western blotting, and immunofluorescence staining. UECs were also subjected to RNA expression profiling.

Results
Tsg101d/d female mice were subfertile with implantation failure, showing unattached blastocysts on day 6 of pregnancy. Histological and marker analyses revealed that some Tsg101d/d day 4 pregnant uteri showed a disintegrated uterine epithelial structure. Tsg101d/d UECs began to degenerate within 18 h of culture. In UECs, expression of necroptosis effectors, such as RIPK1, RIPK3, and MLKL were first confirmed. UECs responded to a stimulus to activate necroptosis and showed increased cell death.

Conclusions
Tsg101 deficiency in the uterine epithelium causes implantation failure, which may be caused by epithelial defects. This study provides evidence that UECs harbor a necroptotic machinery that responds to death-inducing signals. Thus, Tsg101 expression in the uterine epithelium is required for normal pregnancy in mice.
Predictive models for chronic kidney disease after radical or partial nephrectomy in renal cell cancer using early postoperative serum creatinine levels
Authors: Chae Dongwoo , Kim Na Young , Kim Ki Jun , Park Kyemyung , Oh Chaerim , Kim So Yeon 
Published: July 2021

Abstract
Background
Several predictive factors for chronic kidney disease (CKD) following radical nephrectomy (RN) or partial nephrectomy (PN) have been identified. However, early postoperative laboratory values were infrequently considered as potential predictors. Therefore, this study aimed to develop predictive models for CKD 1 year after RN or PN using early postoperative laboratory values, including serum creatinine (SCr) levels, in addition to preoperative and intraoperative factors. Moreover, the optimal SCr sampling time point for the best prediction of CKD was determined.

Methods
Data were retrospectively collected from patients with renal cell cancer who underwent laparoscopic or robotic RN (n = 557) or PN (n = 999). Preoperative, intraoperative, and postoperative factors, including laboratory values, were incorporated during model development. We developed 8 final models using information collected at different time points (preoperative, postoperative day [POD] 0 to 5, and postoperative 1 month). Lastly, we combined all possible subsets of the developed models to generate 120 meta-models. Furthermore, we built a web application to facilitate the implementation of the model.

Results
The magnitude of postoperative elevation of SCr and history of CKD were the most important predictors for CKD at 1 year, followed by RN (compared to PN) and older age. Among the final models, the model using features of POD 4 showed the best performance for correctly predicting the stages of CKD at 1 year compared to other models (accuracy: 79% of POD 4 model versus 75% of POD 0 model, 76% of POD 1 model, 77% of POD 2 model, 78% of POD 3 model, 76% of POD 5 model, and 73% in postoperative 1 month model). Therefore, POD 4 may be the optimal sampling time point for postoperative SCr. A web application is hosted at https://dongy.shinyapps.io/aki_ckd.

Conclusions
Our predictive model, which incorporated postoperative laboratory values, especially SCr levels, in addition to preoperative and intraoperative factors, effectively predicted the occurrence of CKD 1 year after RN or PN and may be helpful for comprehensive management planning.
Exploring secondary SARS-CoV-2 transmission from asymptomatic cases using contact tracing data
Authors: Nakajo Ko , Nishiura Hiroshi 
Published: July 2021

Abstract
Background
Individuals with asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can propagate the virus unknowingly and thus have been a focus of public health attentions since the early stages of the pandemic. Understanding viral transmissibility among asymptomatic individuals is critical for successful control of coronavirus disease 2019 (COVID-19). The present study aimed to understand SARS-CoV-2 transmissibility among young asymptomatic individuals and to assess whether symptomatology was associated with transmission of symptomatic vs. asymptomatic infections.

Methods
We analyzed one of the first-identified clusters of SARS-CoV-2 infections with multiple chains of transmission that occurred among university students in March 2020 in Kyoto prefecture, Japan, using discrete and two-type branching process models. Assuming that the number of secondary cases resulting from either primary symptomatic or asymptomatic cases independently followed negative binomial distributions, we estimated the relative reproduction numbers of an asymptomatic case compared with a symptomatic case. To explore the potential association between symptomatology and transmission of symptomatic vs. asymptomatic incident infections, we also estimated the proportion of secondary symptomatic cases produced by primary symptomatic and asymptomatic cases.

Results
The reproduction number for a symptomatic primary case was estimated at 1.14 (95% confidence interval [CI]: 0.61–2.09). The relative reproduction number for asymptomatic cases was estimated at 0.19 (95% CI: 0.03–0.66), indicating that asymptomatic primary cases did not result in sufficient numbers of secondary infections to maintain chains of transmission. There was no apparent tendency for symptomatic primary cases to preferentially produce symptomatic secondary cases.

Conclusions
Using data from a transmission network during the early epidemic in Japan, we successfully estimated the relative transmissibility of asymptomatic cases of SARS-CoV-2 infection at 0.22. These results suggest that contract tracing focusing on symptomatic index cases may be justified given limited testing capacity.