bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of burnout level among clinical dental students during the COVID-19 pandemic
Authors: Korkmaz Cumhur , Dikicier Sibel , Atay Arzu 
Published: October 2023

Abstract
Background
The Coronavirus Disease (COVID-19) outbreak has caused especially health workers to face mental and physical problems all over the world. The aim of this study is to evaluate burnout, stress perception and perceived social support levels of clinical (the fourth and fifth year) dental students during the COVID-19 pandemic.

Methods
The Sociodemographic Information Form (SIF), Maslach Burnout Inventory (MBI), Sense of Coherence-13 (SoC-13), Perceived Stress Scale-10 (PSS-10), and Multidimensional Scale of Perceived Social Support (MSPSS) were used for data. Questionnaires were answered directly or online by the participants.

Results
A total of 211 participants, 67.8% were female, 32.2% were male. Of these, 96.2% were aged 20–24 years, 84.4% were nuclear family, 11.8% were extended family, and 3.8% were blended family, and 91.5% were willingly for dentistry choice. Based on the results; the total burnout score indicated moderate burnout (41.99 ± 9.94), the SoC-13 scale indicated a strong sense of coherence (55.24 ± 7.21), the PSS-10 score (22.44 ± 3.44) indicated moderate perceived stress and the MSPSS score (65.92 ± 13.22) indicated high perceived social support. A positive correlation was found between perceived stress and burnout. Based on the personal accomplishment subscale; females, those living in extended family, and those who unwillingly choose dentistry among the clinical dental students had higher intense burnout (p < 0.05).

Conclusions
The findings demonstrated that clinical dental students were affected by the emotional stress caused by the COVID-19 pandemic conditions. In the education of dentistry faculties, it would be appropriate to carry out comprehensive studies on adaptation to the changing living conditions with the COVID-19 pandemic and taking the necessary measures for the psychological distress caused by the difficulties experienced.
Intelligent identification system of gastric stromal tumors based on blood biopsy indicators
Authors: Han Shangjun , Song Meijuan , Wang Jiarui , Huang Yalong , Li Zuxi , Yang Aijia , Sui Changsheng , Zhang Zeping , Qiao Jiling , Yang Jing 
Published: October 2023

Abstract
Background
The most prevalent mesenchymal-derived gastrointestinal cancers are gastric stromal tumors (GSTs), which have the highest incidence (60–70%) of all gastrointestinal stromal tumors (GISTs). However, simple and effective diagnostic and screening methods for GST remain a great challenge at home and abroad. This study aimed to build a GST early warning system based on a combination of machine learning algorithms and routine blood, biochemical and tumour marker indicators.

Methods
In total, 697 complete samples were collected from four hospitals in Gansu Province, including 42 blood indicators from 318 pretreatment GST patients, 180 samples of gastric polyps and 199 healthy individuals. In this study, three algorithms, gradient boosting machine (GBM), random forest (RF), and logistic regression (LR), were chosen to build GST prediction models for comparison. The performance and stability of the models were evaluated using two different validation techniques: 5-fold cross-validation and external validation. The DeLong test assesses significant differences in AUC values by comparing different ROC curves, the variance and covariance of the AUC value.

Results
The AUC values of both the GBM and RF models were higher than those of the LR model, and this difference was statistically significant (P < 0.05). The GBM model was considered to be the optimal model, as a larger area was enclosed by the ROC curve, and the axes indicated robust model classification performance according to the accepted model discriminant. Finally, the integration of 8 top-ranked blood indices was proven to be able to distinguish GST from gastric polyps and healthy people with sensitivity, specificity and area under the curve of 0.941, 0.807 and 0.951 for the cross-validation set, respectively.

Conclusion
The GBM demonstrated powerful classification performance and was able to rapidly distinguish GST patients from gastric polyps and healthy individuals. This identification system not only provides an innovative strategy for the diagnosis of GST but also enables the exploration of hidden associations between blood parameters and GST for subsequent studies on the prevention and disease surveillance management of GST. The GST discrimination system is available online for free testing of doctors and high-risk groups at https://jzlyc.gsyy.cn/bear/mobile/index.html.
Perceptions and stress of conscience in relation to burnout among nursing staff in older people care settings: a cross sectional study
Authors: Nazari Shima , Norberg Astrid , Strandberg Gunilla , Åhlin Johan , Ericson-Lidman Eva , Mazaheri Monir 
Published: October 2023

Abstract
Background
Considering cultural influences, it is important to study the perceptions and stress of conscience in different contexts. This study aimed to investigate the association between perceptions of conscience, stress of conscience, and burnout among nursing staff working in older people care settings in Tehran.

Methods
This was a descriptive, cross-sectional study. A total of 161 participants completed the Perceptions of Conscience Questionnaire, Stress of Conscience Questionnaire, and Oldenburg Burnout Inventory, 2019. All nursing staff working at the 20 contacted nursing homes agreed to participate in the study. The descriptive and inferential analysis was conducted through SPSS, using T-tests and one-way between-groups analysis of variance, Chi-square and t-tests, Cohen's d (d), Eta-squared (η2), and Phi coefficient (φ), Partial least squares regression (PLSR), jackknife approximate t-tests of the regression coefficients, and jackknife 95% confidence intervals of the regression coefficients.

Results
The nursing staff perceived their conscience mainly as an authority, asset, and warning signal. Impact of workload on family life was the most common source of stress for the nursing staff. Dealing with incompatible demands, the impact of workload on family life, witnessing insulated patients, inability to meet one’s standards in providing care, and perception of conscience as a burden were strongly associated with the burnout.

Conclusions
Perceiving conscience as a warning signal or authority may serve as a buffer against burnout among nursing staff. This study highlights the need for further exploration of perceptions of conscience in different cultural and social backgrounds.
Rituximab for the treatment of relapsing-remitting multiple sclerosis in Thailand: an economic evaluation and budget impact analysis
Authors: Aungsumart Saharat , Turongkaravee Saowalak , Youngkong Sitaporn , Apiwattanakul Metha , Thakkinstian Ammarin , Chaikledkaew Usa 
Published: October 2023

Abstract
Background
Multiple sclerosis is an inflammatory demyelination process in the central nervous system (CNS) causing neurological disability and poor quality of life. Currently, Thai Food and Drug Administration (FDA)-approved disease-modifying therapy is costly, and most patients with multiple sclerosis are ineligible for treatment in Thailand as previous studies have challenged its cost-effectiveness. Off-label use of rituximab is inexpensive and highly effective in treating multiple sclerosis, but evidence of its cost-effectiveness in Thailand is yet to be collected.

Methods
This study aimed to evaluate the cost-utility and budget impact of rituximab for multiple sclerosis treatment compared with best supportive care, the standard practice in Thailand to treat the disease. A Markov model with a one-month cycle length and lifetime horizon was applied to compare the costs and outcomes of rituximab and best supportive care based on a societal perspective. Accordingly, incremental cost-effectiveness ratios were estimated. Probabilistic and one-way sensitivity analyses were conducted to investigate parameter uncertainty. In addition, the Markov model was used to assess the 5-year budget impact from the government perspective.

Results
A rituximab biosimilar demonstrated higher effectiveness and lower associated costs, compared to best supportive care, with the highest probability of being cost-effective (96%). The probability of relapse was the most sensitive parameter according to the one-way sensitivity analysis. The calculated budget impact of treating patients with multiple sclerosis in Thailand was 26,360,000 Thai baht (THB) or 844,255 United States dollars (USD) in the first fiscal year, and approximately 20,810,000–23,080,000 THB (666,608–739,388 USD) in the next four fiscal years.

Conclusion
In Thailand, a rituximab biosimilar would reduce the overall costs of multiple sclerosis treatment and should, therefore, be included in the National List of Essential Medicines.
Nr4a1 marks a distinctive ILC2 activation subset in the mouse inflammatory lung
Authors: Xu Shasha , Zhang Yu , Liu Xingjie , Liu Huisheng , Zou Xinya , Zhang Linlin , Wang Jing , Zhang Zhiwei , Xu Xiang , Li Mingxia , Li Kairui , Shi Shuyue , Zhang Ying , Miao Zhichao , Zha Jie , Yu Yong 
Published: October 2023

Abstract
Background
Group 2 innate lymphoid cells (ILC2s) are critical sources of type 2 cytokines and represent one of the major tissue-resident lymphoid cells in the mouse lung. However, the molecular mechanisms underlying ILC2 activation under challenges are not fully understood.

Results
Here, using single-cell transcriptomics, genetic reporters, and gene knockouts, we identify four ILC2 subsets, including two non-activation subsets and two activation subsets, in the mouse acute inflammatory lung. Of note, a distinct activation subset, marked by the transcription factor Nr4a1, paradoxically expresses both tissue-resident memory T cell (Trm), and effector/central memory T cell (Tem/Tcm) signature genes, as well as higher scores of proliferation, activation, and wound healing, all driven by its particular regulons. Furthermore, we demonstrate that the Nr4a1+ILC2s are restrained from activating by the programmed cell death protein-1 (PD-1), which negatively modulates their activation-related regulons. PD-1 deficiency places the non-activation ILC2s in a state that is prone to activation, resulting in Nr4a1+ILC2 differentiation through different activation trajectories. Loss of PD-1 also leads to the expansion of Nr4a1+ILC2s by the increase of their proliferation ability.

Conclusions
The findings show that activated ILC2s are a heterogenous population encompassing distinct subsets that have different propensities, and therefore provide an opportunity to explore PD-1's role in modulating the activity of ILC2s for disease prevention and therapy.
The neck as a keystone structure in avian macroevolution and mosaicism
Authors: Marek Ryan D. , Felice Ryan N. 
Published: October 2023

Abstract
Background
The origin of birds from non-avian theropod dinosaur ancestors required a comprehensive restructuring of the body plan to enable the evolution of powered flight. One of the proposed key mechanisms that allowed birds to acquire flight and modify the associated anatomical structures into diverse forms is mosaic evolution, which describes the parcelization of phenotypic traits into separate modules that evolve with heterogeneous tempo and mode. Avian mosaicism has been investigated with a focus on the cranial and appendicular skeleton, and as such, we do not understand the role of the axial column in avian macroevolution. The long, flexible neck of extant birds lies between the cranial and pectoral modules and represents an opportunity to study the contribution of the axial skeleton to avian mosaicism.

Results
Here, we use 3D geometric morphometrics in tandem with phylogenetic comparative methods to provide, to our knowledge, the first integrative analysis of avian neck evolution in context with the head and wing and to interrogate how the interactions between these anatomical systems have influenced macroevolutionary trends across a broad sample of extant birds. We find that the neck is integrated with both the head and the forelimb. These patterns of integration are variable across clades, and only specific ecological groups exhibit either head-neck or neck-forelimb integration. Finally, we find that ecological groups that display head-neck and neck-forelimb integration tend to display significant shifts in the rate of neck morphological evolution.

Conclusions
Combined, these results suggest that the interaction between trophic ecology and head-neck-forelimb mosaicism influences the evolutionary variance of the avian neck. By linking together the biomechanical functions of these distinct anatomical systems, the cervical vertebral column serves as a keystone structure in avian mosaicism and macroevolution.
Direct regulation of the cardiac ryanodine receptor (RyR2) by O-GlcNAcylation
Authors: Okolo Chidinma A , Khaing Ei-Phyo , Mereacre Valeria , Wallace Rachel S , Munro Michelle L , Erickson Jeffrey R , Jones Peter P. 
Published: October 2023

Abstract
Background
O-GlcNAcylation is the enzymatic addition of a sugar, O-linked β-N-Acetylglucosamine, to the serine and threonine residues of proteins, and is abundant in diabetic conditions. We have previously shown that O-GlcNAcylation can trigger arrhythmias by indirectly increasing pathological Ca2+ leak through the cardiac ryanodine receptor (RyR2) via Ca2+/calmodulin-dependent kinase II (CaMKII). However, RyR2 is well known to be directly regulated by other forms of serine and threonine modification, therefore, this study aimed to determine whether RyR2 is directly modified by O-GlcNAcylation and if this also alters the function of RyR2 and Ca2+ leak.

Methods
O-GlcNAcylation of RyR2 in diabetic human and animal hearts was determined using western blotting. O-GlcNAcylation of RyR2 was pharmacologically controlled and the propensity for Ca2+ leak was determined using single cell imaging. The site of O-GlcNAcylation within RyR2 was determined using site-directed mutagenesis of RyR2.

Results
We found that RyR2 is modified by O-GlcNAcylation in human, animal and HEK293 cell models. Under hyperglycaemic conditions O-GlcNAcylation was associated with an increase in Ca2+ leak through RyR2 which persisted after CaMKII inhibition. Conversion of serine-2808 to alanine prevented an O-GlcNAcylation induced increase in Ca2+ leak.

Conclusions
These data suggest that the function of RyR2 can be directly regulated by O-GlcNAcylation and requires the presence of serine-2808.
Microbial synthesis of the plant natural product precursor p-coumaric acid with Corynebacterium glutamicum
Authors: Mutz Mario , Kösters Dominic , Wynands Benedikt , Wierckx Nick , Marienhagen Jan 
Published: October 2023

Abstract
Background
Phenylpropanoids such as p-coumaric acid represent important precursors for the synthesis of a broad range of plant secondary metabolites including stilbenoids, flavonoids, and lignans, which are of pharmacological interest due to their health-promoting properties. Although extraction from plant material or chemical synthesis is possible, microbial synthesis of p-coumaric acid from glucose has the advantage of being less expensive and more resource efficient. In this study, Corynebacterium glutamicum was engineered for the production of the plant polyphenol precursor p-coumaric acid from glucose.

Results
Heterologous expression of the tyrosine ammonia-lyase encoding gene from Flavobacterium johnsoniae enabled the conversion of endogenously provided tyrosine to p-coumaric acid. Product consumption was avoided by abolishing essential reactions of the phenylpropanoid degradation pathway. Accumulation of anthranilate as a major byproduct was eliminated by reducing the activity of anthranilate synthase through targeted mutagenesis to avoid tryptophan auxotrophy. Subsequently, the carbon flux into the shikimate pathway was increased, phenylalanine biosynthesis was reduced, and phosphoenolpyruvate availability was improved to boost p-coumaric acid accumulation. A maximum titer of 661 mg/L p-coumaric acid (4 mM) in defined mineral medium was reached. Finally, the production strain was utilized in co-cultivations with a C. glutamicum strain previously engineered for the conversion of p-coumaric acid into the polyphenol resveratrol. These co-cultivations enabled the synthesis of 31.2 mg/L (0.14 mM) resveratrol from glucose without any p-coumaric acid supplementation.

Conclusions
The utilization of a heterologous tyrosine ammonia-lyase in combination with optimization of the shikimate pathway enabled the efficient production of p-coumaric acid with C. glutamicum. Reducing the carbon flux into the phenylalanine and tryptophan branches was the key to success along with the introduction of feedback-resistant enzyme variants.
EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells
Authors: Gonzalez Suarez Narjara , Fernandez-Marrero Yuniel , Hébert Mathieu P. A. , Roy Marie-Eve , Boudreau Luc H. , Annabi Borhane 
Published: October 2023

AbstractBackgroundTriple-negative breast cancer (TNBC) cells’ secretome can induce a pro-inflammatory phenotype in human adipose-derived mesenchymal stem cells (hADMSC). This can be prevented by the green tea polyphenol epigallocatechin-3-gallate (EGCG). The impact of EGCG on the paracrine regulation that the extracellular vesicles (EVs) specifically exert within the TNBC secretome remains unknown.MethodsEVs were obtained from a TNBC-derived serum-starved MDA-MB-231 cell model treated or not with EGCG under normoxic or hypoxic (< 1% O2) culture conditions. RNA-Seq analysis was used to assess the EVs’ genetic content. The modulation of inflammatory and senescence markers in hADMSC was evaluated by RT-qPCR using cDNA arrays and validated by immunoblotting. A protein profiler phospho-kinase array was used to explore signaling pathways.ResultsWhile hypoxic culture conditions did not significantly alter the genetic content of MDA-MB-231-secreted EVs, the addition of EGCG significantly modified EVs genetic material at low oxygen tension. Gene expression of cancer-associated adipocyte pro-inflammatory markersCXCL8,CCL2andIL-1βwas increased in hADMSC treated with EVs. Concomitantly, EVs isolated from MDA-MB-231 treated with EGCG (EGCG-EVs) downregulatedCCL2andIL-1β,while inducing higher expression ofCXCL8andIL-6levels. EVs activated CHK-2, c-Jun, AKT and GSK-3β signaling pathways in hADMSC, whereas EGCG-EVs specifically reduced the latter two as well as the serum starvation-induced senescence markers p21 and β-galactosidase. Finally, the mitochondrial content within the TNBC cells-derived EVs was found reduced upon EGCG treatment.ConclusionThis proof of concept study demonstrates that the chemopreventive properties of diet-derived polyphenols may efficiently target the paracrine regulation that TNBC cells could exert upon their surrounding adipose tissue microenvironment.
Assessing caregivers’ perceptions of treatment-seeking for suspected severe malaria in the Democratic Republic of the Congo
Authors: Okitawutshu Jean , Tshefu Antoinette , Kalenga Jean-Claude , Delvento Giulia , Burri Christian , Hetzel Manuel W. , Lengeler Christian , Signorell Aita 
Published: October 2023

Abstract
Background
Malaria remains a major public health issue in the Democratic Republic of the Congo (DRC), accounting for 44% deaths among outpatient visits in children < 5 years of age, and 22% of facility deaths. Understanding determinants of caregivers’ treatment-seeking patterns and decision-making is crucial in reducing the malaria burden.

Methods
In the frame of the Community Access to Rectal Artesunate for Malaria (CARAMAL) project, cross-sectional household surveys that randomly sampled villages and households were carried-out in three rural DRC health zones prior to the rollout of pre-referral Rectal Artesunate (RAS) and then 9 and 19 months after RAS rollout (post-RAS). Data were captured electronically through face-to-face interviews with the main caregivers of children < 5 years. Capillary blood samples of the children were tested for malaria and anaemia. The main study outcome was whether caregiver “sought treatment outside home” when the child had fever. Multilevel mixed effects logistic regression models using village as random effect and health zone as a fixed effect was performed to assess treatment-seeking predictors.

Results
2439 household interviews were completed (pre-RAS 888 and post-RAS 1551), including 316 and 653 treatment-seeking interviews. Overall, 3499 children < 5 years were tested for malaria and anaemia (pre-RAS 1,315 and post-RAS 2184). Caregiver’s recognition of severe malaria signs was poor, while knowledge of symptoms of uncomplicated malaria seemed high. Despite this, danger signs significantly increased the odds of seeking treatment (aOR = 2.12, 95%CI 1.03–4.38), the same was found for the “least poor” quintile (aOR = 3.01, 95%CI 1.03–8.82), as well as residents of Kingandu (aOR = 2.78, 95%CI 1.01–7.65). “Doing something at home” against fever negatively affected treatment-seeking in both study phases. RAS acceptance was high, at almost 100%. Malaria prevalence was higher post-RAS (45.2%) compared to pre-RAS (34.4%), p = 0.003, but anaemia, although high (≥ 75%), was similar in both study phases (p = 0.92).

Conclusion
In remote communities with high malaria prevalence in the DRC, malaria remains a major problem. Improving the recognition of danger signs of severe disease and introducing pre-referral RAS may improve treatment-seeking and contribute to reducing malaria-related mortality among children—if quality of care can be guaranteed.
Deep learning for automated left ventricular outflow tract diameter measurements in 2D echocardiography
Authors: Zha Sigurd Zijun , Rogstadkjernet Magnus , Klæboe Lars Gunnar , Skulstad Helge , Singstad Bjørn-Jostein , Gilbert Andrew , Edvardsen Thor , Samset Eigil , Brekke Pål Haugar 
Published: October 2023

Abstract
Background
Measurement of the left ventricular outflow tract diameter (LVOTd) in echocardiography is a common source of error when used to calculate the stroke volume. The aim of this study is to assess whether a deep learning (DL) model, trained on a clinical echocardiographic dataset, can perform automatic LVOTd measurements on par with expert cardiologists.

Methods
Data consisted of 649 consecutive transthoracic echocardiographic examinations of patients with coronary artery disease admitted to a university hospital. 1304 LVOTd measurements in the parasternal long axis (PLAX) and zoomed parasternal long axis views (ZPLAX) were collected, with each patient having 1–6 measurements per examination. Data quality control was performed by an expert cardiologist, and spatial geometry data was preserved for each LVOTd measurement to convert DL predictions into metric units. A convolutional neural network based on the U-Net was used as the DL model.

Results
The mean absolute LVOTd error was 1.04 (95% confidence interval [CI] 0.90–1.19) mm for DL predictions on the test set. The mean relative LVOTd errors across all data subgroups ranged from 3.8 to 5.1% for the test set. Generally, the DL model had superior performance on the ZPLAX view compared to the PLAX view. DL model precision for patients with repeated LVOTd measurements had a mean coefficient of variation of 2.2 (95% CI 1.6–2.7) %, which was comparable to the clinicians for the test set.

Conclusion
DL for automatic LVOTd measurements in PLAX and ZPLAX views is feasible when trained on a limited clinical dataset. While the DL predicted LVOTd measurements were within the expected range of clinical inter-observer variability, the robustness of the DL model requires validation on independent datasets. Future experiments using temporal information and anatomical constraints could improve valvular identification and reduce outliers, which are challenges that must be addressed before clinical utilization.

Graphical Abstract