bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do programme coordinators contribute to the professional development of residents? an exploratory study
Authors: Aono Mayumi , Obara Haruo , Kawakami Chihiro , Imafuku Rintaro , Saiki Takuya , Barone Michael A. , Suzuki Yasuyuki 
Published: May 2022

Abstract
Background
With the development of training programmes for health professions, the role of programme coordinators has become increasingly important. However, their role in providing educational support for the professional development of resident trainees has not been investigated well. This study aimed to qualitatively analyse the involvement of programme coordinators in educational support for residents.

Methods
Semi-structured reflective writing on ‘support for residents’ was collected from programme coordinators in teaching hospitals in Japan in 2017–18 using a web-based questionnaire. Descriptions were qualitatively analysed thematically, using the professional identity formation (PIF) framework.

Results
A total of 39 cases of “support for residents” by 31 coordinators were analysed. We found that residents most commonly faced prior personal problems, including mental health issues and insufficient social skills/unprofessional behaviour. A thematic analysis revealed that coordinators played a variety of educational roles: 1) requesting supervisors to reconsider their teaching; 2) protecting residents from the negative influence of clinical experiences; 3) facilitating residents’ self-assessment and confidence; 4) creating a safer learning environment; 5) providing support for prior personal problems through 5–1) fostering a better atmosphere for the mental health of residents, and 5–2) intervening for residents with insufficient social skills/unprofessional behaviour; 6) providing support for isolated residents; and 7) preventing problems with peers.

Conclusions
This study identified seven educational roles of programme coordinators for residents from a standpoint of PIF of residents. Based on these findings, four valuable attributes for coordinators were established: non-hierarchical relationships with residents, parenting attitudes, sensitivity to residents’ changes, and the perspective of the citizen and a member of the public. These attributes would underpin coordinators’ educational roles and facilitate the professional development of residents. This study provides a basis for defining and revising the role profiles of programme coordinators, and for improving staff development.
Automatic recognition of micronucleus by combining attention mechanism and AlexNet
Authors: Wei Weiyi , Tao Hong , Chen Wenxia , Wu Xiaoqin 
Published: May 2022

Abstract
Background
Micronucleus (MN) is an abnormal fragment in a human cell caused by disorders in the mechanism regulating chromosome segregation. It can be used as a biomarker for genotoxicity, tumor risk, and tumor malignancy. The in vitro micronucleus assay is a commonly used method to detect micronucleus. However, it is time-consuming and the visual scoring can be inconsistent.

Methods
To alleviate this issue, we proposed a computer-aided diagnosis method combining convolutional neural networks and visual attention for micronucleus recognition. The backbone of our model is AlexNet without any dense layers and it is pretrained on the ImageNet dataset. Two attention modules are applied to extract cell image features and generate attention maps highlighting the region of interest to improve the interpretability of the network. Given the problems in the data set, we leverage data augmentation and focal loss to alleviate the impact.

Results
Experiments show that the proposed network yields better performance with fewer parameters. The AP value, F1 value and AUC value reach 0.932, 0.811 and 0.995, respectively.

Conclusion
In conclusion, the proposed network can effectively recognize micronucleus, and it can play an auxiliary role in clinical diagnosis by doctors.
Comparison of cardiovascular outcomes between SGLT2 inhibitors in diabetes mellitus
Authors: Suzuki Yuta , Kaneko Hidehiro , Okada Akira , Itoh Hidetaka , Matsuoka Satoshi , Fujiu Katsuhito , Michihata Nobuaki , Jo Taisuke , Takeda Norifumi , Morita Hiroyuki , Kamiya Kentaro , Matsunaga Atsuhiko , Ako Junya , Node Koichi , Yasunaga Hideo , Komuro Issei 
Published: May 2022

Abstract
Background
There have been scarce data comparing cardiovascular outcomes between individual sodium-glucose cotransporter-2 (SGLT2) inhibitors. We aimed to compare the subsequent cardiovascular risk between individual SGLT2 inhibitors.

Methods
We analyzed 25,315 patients with diabetes mellitus (DM) newly taking SGLT2 inhibitors (empagliflozin: 5302, dapagliflozin: 4681, canagliflozin: 4411, other SGLT2 inhibitors: 10,921). We compared the risks of developing heart failure (HF), myocardial infarction (MI), angina pectoris (AP), stroke, and atrial fibrillation (AF) between individual SGLT2 inhibitors.

Results
Median age was 52 years, and 82.5% were men. The median fasting plasma glucose and HbA1c levels were 149 (Q1-Q3:127–182) mg/dL and 7.5 (Q1-Q3:6.9–8.6) %. During a mean follow-up of 814 ± 591 days, 855 HF, 143 MI, 815 AP, 340 stroke, and 139 AF events were recorded. Compared with empagliflozin, the risk of developing HF, MI, AP, stroke, and AF was not significantly different in dapagliflozin, canagliflozin, and other SGLT inhibitors. For developing HF, compared with empagliflozin, hazard ratios of dapagliflozin, canagliflozin, and other SGLT2 inhibitors were 1.02 (95% confidence interval [CI] 0.81–1.27), 1.08 (95% CI 0.87–1.35), and 0.88 (95% CI 0.73–1.07), respectively. Wald tests showed that there was no significant difference in the risk of developing HF, MI, AP, stroke, and AF among individual SGLT2 inhibitors. We confirmed the robustness of these results through a multitude of sensitivity analyses.

Conclusion
The risks for subsequent development of HF, MI, AP, stroke, and AF were comparable between individual SGLT2 inhibitors. This is the first study comparing the wide-range cardiovascular outcomes of patients with DM treated with individual SGLT2 inhibitors using large-scale real-world data.
Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations
Authors: Zou Jiale , Wang Shuang , Chai Ningli , Yue Hua , Ye Peng , Guo Peilin , Li Feng , Wei Bo , Ma Guanghui , Wei Wei , Linghu Enqiang 
Published: May 2022

Abstract
Background
Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal.

Results
Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route.

Conclusions
This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy.

Graphical Abstract
Predictors of health-related quality of life after cardiac surgery: a systematic review
Authors: Sanders Julie , Bowden Tracey , Woolfe-Loftus Nicholas , Sekhon Mandeep , Aitken Leanne M. 
Published: May 2022

Abstract
Background
Health-related quality of life (HRQoL) is important in determining surgical success, particularly from the patients’ perspective.

Aims
To identify predictors for HRQoL outcome after cardiac surgery in order to identify potentially modifiable factors where interventions to improve patient outcomes could be targeted.

Methods
Electronic databases (including MEDLINE, CINAHL, Embase) were searched between January 2001 and December 2020 for studies determining predictors of HRQoL (using a recognised and validated tool) in adult patients undergoing cardiac surgery. Data extraction and quality assessments were undertaken and data was summarised using descriptive statistics and narrative synthesis, as appropriate.

Results
Overall, 3924 papers were screened with 41 papers included in the review. Considerable methodological heterogeneity between studies was observed. Most were single-centre (75.6%) prospective observational studies (73.2%) conducted in patients undergoing coronary artery bypass graft (CABG) (n = 51.2%) using a version of the SF-36 (n = 63.4%). Overall, 103 independent predictors (62 pre-operative, five intra-operative and 36 post-operative) were identified, where 34 (33.0%) were reported in more than one study. Potential pre-operative modifiable predictors include alcohol use, BMI/weight, depression, pre-operative quality of life and smoking while in the post-operative period pain and strategies to reduce post-operative complications and intensive care and hospital length of stay are potential therapeutic targets.

Conclusion
Despite a lack of consistency across studies, several potentially modifiable predictors were identified that could be targeted in interventions to improve patient or treatment outcomes. This may contribute to delivering more person-centred care involving shared decision-making to improve patient HRQoL after cardiac surgery.
Thrombin generation capacity is enhanced by low antithrombin activity and depends on the activity of the related coagulation factors
Authors: Tsuchida Takumi , Hayakawa Mineji , Kawahara Shota , Kumano Osamu 
Published: May 2022

Abstract
Background
Supplementation with antithrombin (AT) concentrates is now common in the treatment of congenital and acquired AT deficiency. However, there is no established consensus on the target and timing of supplementation. We aimed to elucidate the effects of AT deficiency on the balance between coagulation activation and inhibition using a thrombin generation assay as in vitro global assay.

Methods
Samples were prepared by admixing commercially acquired AT-deficient plasma with < 1% AT activity with pooled normal plasma. The AT activity in each sample was adjusted to 100, 90, 70, 50, 40, 30, 10, 5, and < 1%. A thrombin generation assay was performed in each sample. AT concentrate-spiked samples were also prepared by adjusting the AT activities in four types of the concentrates: one recombinant and three plasma-derived AT concentrates. The final targeted AT activities in the samples were adjusted to 100, 50, 30, and 5% by spiking each concentrate into the AT-deficient plasma. We also prepared samples with five levels of prothrombin time (PT) % in coagulation factors with the AT activity fixed at 30% by dilution by mixing AT-deficient plasma and normal plasma with Owren’s veronal buffer to adjust the coagulation factor activities in several proportions. The theoretical target PT% values were 100, 66, 50, 40, and 30%. A thrombin generation assay was performed on all samples.

Results
The ability to generate thrombin depended on the AT activity, and the amount of thrombin generation was increased as AT was decreased. Additionally, the amount of thrombin generation was changed significantly when AT activity was ≤ 50%, indicating that AT suppressed thrombin generation. In particular, thrombin generation was remarkable when AT activity was < 30%, and it can be assumed that the prognosis is poor due to organ failure from thrombotic tendency.

Conclusions
The results presented in this basic research were found to be consistent with the clinical findings to date. The mechanism by which 30–50% of AT activity is set as the clinical boundary was elucidated by the thrombin generation assay.
Optogenetic control of NOTCH1 signaling
Authors: Kałafut Joanna , Czapiński Jakub , Przybyszewska-Podstawka Alicja , Czerwonka Arkadiusz , Odrzywolski Adrian , Sahlgren Cecilia , Rivero-Müller Adolfo 
Published: May 2022

AbstractThe Notch signaling pathway is a crucial regulator of cell differentiation as well as tissue organization, whose deregulation is linked to the pathogenesis of different diseases. NOTCH1 plays a key role in breast cancer progression by increasing proliferation, maintenance of cancer stem cells, and impairment of cell death. NOTCH1 is a mechanosensitive receptor, where mechanical force is required to activate the proteolytic cleavage and release of the Notch intracellular domain (NICD). We circumvent this limitation by regulating Notch activity by light. To achieve this, we have engineered an optogenetic NOTCH1 receptor (optoNotch) to control the activation of NOTCH1 intracellular domain (N1ICD) and its downstream transcriptional activities. Using optoNotch we confirm that NOTCH1 activation increases cell proliferation in MCF7 and MDA-MB-468 breast cancer cells in 2D and spheroid 3D cultures, although causing distinct cell-type specific migratory phenotypes. Additionally, optoNotch activation induced chemoresistance on the same cell lines. OptoNotch allows the fine-tuning, ligand-independent, regulation of N1ICD activity and thus a better understanding of the spatiotemporal complexity of Notch signaling.
Associations of neighborhood walkability with moderate to vigorous physical activity: an application of compositional data analysis comparing compositional and non-compositional approaches
Authors: Bird Madeleine , Datta Geetanjali D , Chinerman Deanna , Kakinami Lisa , Mathieu Marie-Eve , Henderson Mélanie , Barnett Tracie A 
Published: May 2022

Abstract
Background
We compared the relation between neighborhood features and moderate to vigorous physical activity (MVPA) using linear regression analysis and the more novel compositional data analysis (CoDA). Compositional data analysis allows us to take the time children allocate to different movement behaviours during a 24-hour time period into account.

Methodology
Data from youth participants (n = 409) in the QUALITY (QUebec Adipose and Lifestyle InvesTigation in Youth) cohort were included. Time spent in MVPA, light physical activity, sedentary behavior, and sleep (“24-hour movement behaviours”) was measured using accelerometers. Neighborhood data were collected using a geographic information system and through direct observation. In CoDA models, we used orthogonal logratio coordinates, which allows for the association of neighbourhood walkability with MVPA to be estimated with respect to the average composition of all other behaviours within a 24-hour time frame. In baseline linear regression models, MVPA was regressed cross-sectionally on neighborhood walkability. All models were stratified by sex, and controlled for BMI z-scores, pubertal development, seasonal variation, parental education, and neighbourhood safety.

Results
Based on CoDA, girls who lived in more walkable neighborhoods had 10% higher daily MVPA (95% CI: 2%, 19%), taking into account all other movement behaviours. Based on linear regression, girls who resided in more walkable neighborhoods engaged in 4.2 (95% confidence interval [CI]: 1.2, 6.6) more minutes of MVPA per day on average than girls residing in less walkable neighborhoods.

Conclusions
Unlike with traditional linear models, all movement behaviours were included in a single model using CoDA, allowing for a more complete picture of the strength and direction of the association between neighbourhood Walkability and MVPA. Application of CoDA to investigate determinants of physical activity provides additional insight into potential mechanisms and the ways in which people allocate their time.
No evidence of bovine leukemia virus proviral DNA and antibodies in human specimens from Japan
Authors: Yamanaka Meripet Polat , Saito Susumu , Hara Yukiko , Matsuura Ryosuke , Takeshima Shin-nosuke , Hosomichi Kazuyoshi , Matsumoto Yasunobu , Furuta Rika A. , Takei Masami , Aida Yoko 
Published: May 2022

Abstract
Background
The potential risk and association of bovine leukemia virus (BLV) with human remains controversial as it has been reported to be both positive and negative in human breast cancer and blood samples. Therefore, establishing the presence of BLV in comprehensive human clinical samples in different geographical locations is essential.

Result
In this study, we examined the presence of BLV proviral DNA in human blood and breast cancer tissue specimens from Japan. PCR analysis of BLV provirus in 97 Japanese human blood samples and 23 breast cancer tissues showed negative result for all samples tested using long-fragment PCR and highly-sensitive short-fragment PCR amplification. No IgG and IgM antibodies were detected in any of the 97 human serum samples using BLV gp51 and p24 indirect ELISA test. Western blot analysis also showed negative result for IgG and IgM antibodies in all tested human serum samples.

Conclusion
Our results indicate that Japanese human specimens including 97 human blood, 23 breast cancer tissues, and 97 serum samples were negative for BLV.
Non-linear transformation of enzyme-linked immunosorbent assay (ELISA) measurements allows usage of linear models for data analysis
Authors: Lange Thomas M. , Rotärmel Maria , Müller Dominik , Mahone Gregory S. , Kopisch-Obuch Friedrich , Keunecke Harald , Schmitt Armin O. 
Published: May 2022

AbstractBackgroundIn research questions such as in resistance breeding against theBeet necrotic yellow vein virusit is of interest to compare the virus concentrations of samples from different groups. The enzyme-linked immunosorbent assay (ELISA) counts as the standard tool to measure virus concentrations. Simple methods for data analysis such as analysis of variance (ANOVA), however, are impaired due to non-normality of the resulting optical density (OD) values as well as unequal variances in different groups.MethodsTo understand the relationship between the OD values from an ELISA test and the virus concentration per sample, we used a large serial dilution and modelled its non-linear form using a five parameter logistic regression model. Furthermore, we examined if the quality of the model can be increased if one or several of the model parameters are defined beforehand. Subsequently, we used the inverse of the best model to estimate the virus concentration for every measured OD value.ResultsWe show that the transformed data are essentially normally distributed but provide unequal variances per group. Thus, we propose a generalised least squares model which allows for unequal variances of the groups to analyse the transformed data.ConclusionsANOVA requires normally distributed data as well as equal variances. Both requirements are not met with raw OD values from an ELISA test. A transformation with an inverse logistic function, however, gives the possibility to use linear models for data analysis of virus concentrations. We conclude that this method can be applied in every trial where virus concentrations of samples from different groups are to be compared via OD values from an ELISA test. To encourage researchers to use this method in their studies, we provide an R script for data transformation as well as the data from our trial.
Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN)
Authors: Matejovic Martin , Huet Olivier , Dams Karolien , Elke Gunnar , Vaquerizo Alonso Clara , Csomos Akos , Krzych Łukasz J. , Tetamo Romano , Puthucheary Zudin , Rooyackers Olav , Tjäder Inga , Kuechenhoff Helmut , Hartl Wolfgang H. , Hiesmayr Michael 
Published: May 2022

Abstract
Background
Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes.

Methods
Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10–20 kcal/kg, 0.8–1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV).

Results
A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (− 2.74 [− 3.28; − 2.21] and − 0.12 [− 0.15; − 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements.

Conclusions
Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes.
Trial registrationNCT04143503, registered on October 25, 2019.

Graphical abstract