bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burnout, employee engagement, and changing organizational contexts in VA primary care during the early COVID-19 pandemic
Authors: Apaydin Eric A. , Rose Danielle E. , McClean Michael R. , Mohr David C. , Yano Elizabeth M. , Shekelle Paul G. , Nelson Karin M. , Guo Rong , Yoo Caroline K. , Stockdale Susan E. 
Published: November 2023

Abstract
Background
The COVID-19 pandemic involved a rapid change to the working conditions of all healthcare workers (HCW), including those in primary care. Organizational responses to the pandemic, including a shift to virtual care, changes in staffing, and reassignments to testing-related work, may have shifted more burden to these HCWs, increasing their burnout and turnover intent, despite their engagement to their organization. Our objectives were (1) to examine changes in burnout and intent to leave rates in VA primary care from 2017–2020 (before and during the pandemic), and (2) to analyze how individual protective factors and organizational context affected burnout and turnover intent among VA primary care HCWs during the early months of the pandemic.

Methods
We analyzed individual- and healthcare system-level data from 19,894 primary care HCWs in 139 healthcare systems in 2020. We modeled potential relationships between individual-level burnout and turnover intent as outcomes, and individual-level employee engagement, perceptions of workload, leadership, and workgroups. At healthcare system-level, we assessed prior-year levels of burnout and turnover intent, COVID-19 burden (number of tests and deaths), and the extent of virtual care use as potential determinants. We conducted multivariable analyses using logistic regression with standard errors clustered by healthcare system controlled for individual-level demographics and healthcare system complexity.

Results
In 2020, 37% of primary care HCWs reported burnout, and 31% reported turnover intent. Highly engaged employees were less burned out (OR = 0.57; 95% CI 0.52–0.63) and had lower turnover intent (OR = 0.62; 95% CI 0.57–0.68). Pre-pandemic healthcare system-level burnout was a major predictor of individual-level pandemic burnout (p = 0.014). Perceptions of reasonable workload, trustworthy leadership, and strong workgroups were also related to lower burnout and turnover intent (p < 0.05 for all). COVID-19 burden, virtual care use, and prior year turnover were not associated with either outcome.

Conclusions
Employee engagement was associated with a lower likelihood of primary care HCW burnout and turnover intent during the pandemic, suggesting it may have a protective effect during stressful times. COVID-19 burden and virtual care use were not related to either outcome. Future research should focus on understanding the relationship between engagement and burnout and improving well-being in primary care.
Different mechanisms of X-ray irradiation-induced male and female sterility in Aedes aegypti
Authors: Zhang Heng , Trueman Emma , Hou Xinjun , Chew De Xian , Deng Lu , Liew Jonathan , Chia Tania , Xi Zhiyong , Tan Cheong Huat , Cai Yu 
Published: November 2023

Abstract
Background
Aedes aegypti (Ae. aegypti) is the major vector that transmits many diseases including dengue, Zika, and filariasis in tropical and subtropical regions. Due to the growing resistance to chemical-based insecticides, biological control methods have become an emerging direction to control mosquito populations. The sterile insect technique (SIT) deploys high doses of ionizing radiation to sterilize male mosquitoes before the release. The Wolbachia-based population suppression method of the incompatible insect technique (IIT) involves the release of Wolbachia-infected males to sterilize uninfected field females. Due to the lack of perfect sex separation tools, a low percentage of female contamination is detected in the male population. To prevent the unintentional release of these Wolbachia-infected females which might result in population replacement, a low dose of X-ray irradiation is deployed to sterilize any female escapees. However, it remains unclear whether these irradiation-induced male and female sterilizations share common mechanisms.

Results
In this work, we set out to define the minimum dose of X-ray radiation required for complete female sterilization in Ae. aegypti (NEA-EHI strain). Further results showed that this minimum dose of X-ray irradiation for female sterilization significantly reduced male fertility. Similar results have been reported previously in several operational trials. By addressing the underlying causes of the sterility, our results showed that male sterility is likely due to chromosomal damage in the germ cells induced by irradiation. In contrast, female sterility appears to differ and is likely initiated by the elimination of the somatic supporting cells, which results in the blockage of the ovariole maturation. Building upon these findings, we identified the minimum dose of X-ray irradiation on the Wolbachia-infected NEA-EHI (wAlbB-SG) strain, which is currently being used in the IIT-SIT field trial. Compared to the uninfected parental strain, a lower irradiation dose could fully sterilize wAlbB-SG females. This suggests that Wolbachia-carrying mosquitoes are more sensitive to irradiation, consistent with a previous report showing that a lower irradiation dose fully sterilized Wolbachia-infected Ae. aegypti females (Brazil and Mexican strains) compared to those uninfected controls.

Conclusions
Our findings thus reveal the distinct mechanisms of ionizing X-ray irradiation-induced male or female sterility in Ae. aegypti mosquitoes, which may help the design of X-ray irradiation-based vector control methods.
Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study
Authors: Liu Ting , Dong Di , Zhao Xun , Ou Xiao-Min , Yi Jun-Lin , Guan Jian , Zhang Ye , Xiao-Fei Lv , Xie Chuan-Miao , Luo Dong-Hua , Sun Rui , Chen Qiu-Yan , Xing Lv , Guo Shan-Shan , Liu Li-Ting , Lin Da-Feng , Chen Yan-Zhou , Lin Jie-Yi , Luo Mei-Juan , Yan Wen-Bin , He Mei-Lin , Mao Meng-Yuan , Zhu Man-Yi , Chen Wen-Hui , Shen Bo-Wen , Wang Shi-Qian , Li Hai-Lin , Zhong Lian-Zhen , Hu Chao-Su , Wu De-Hua , Mai Hai-Qiang , Tian Jie , Tang Lin-Quan 
Published: November 2023

Abstract
Background
Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC.

Methods
This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes.

Results
The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713–0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2–62.5% vs. 16.3–18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07–6.75, P < 0.001) and all causes of deaths (HR 1.53–2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity.

Conclusions
We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.
A novel approach to risk exposure and epigenetics—the use of multidimensional context to gain insights into the early origins of cardiometabolic and neurocognitive health
Authors: Ng Jane W. Y. , Felix Janine F. , Olson David M. 
Published: November 2023

Abstract
Background
Each mother–child dyad represents a unique combination of genetic and environmental factors. This constellation of variables impacts the expression of countless genes. Numerous studies have uncovered changes in DNA methylation (DNAm), a form of epigenetic regulation, in offspring related to maternal risk factors. How these changes work together to link maternal-child risks to childhood cardiometabolic and neurocognitive traits remains unknown. This question is a key research priority as such traits predispose to future non-communicable diseases (NCDs). We propose viewing risk and the genome through a multidimensional lens to identify common DNAm patterns shared among diverse risk profiles.

Methods
We identified multifactorial Maternal Risk Profiles (MRPs) generated from population-based data (n = 15,454, Avon Longitudinal Study of Parents and Children (ALSPAC)). Using cord blood HumanMethylation450 BeadChip data, we identified genome-wide patterns of DNAm that co-vary with these MRPs. We tested the prospective relation of these DNAm patterns (n = 914) to future outcomes using decision tree analysis. We then tested the reproducibility of these patterns in (1) DNAm data at age 7 and 17 years within the same cohort (n = 973 and 974, respectively) and (2) cord DNAm in an independent cohort, the Generation R Study (n = 686).

Results
We identified twenty MRP-related DNAm patterns at birth in ALSPAC. Four were prospectively related to cardiometabolic and/or neurocognitive childhood outcomes. These patterns were replicated in DNAm data from blood collected at later ages. Three of these patterns were externally validated in cord DNAm data in Generation R. Compared to previous literature, DNAm patterns exhibited novel spatial distribution across the genome that intersects with chromatin functional and tissue-specific signatures.

Conclusions
To our knowledge, we are the first to leverage multifactorial population-wide data to detect patterns of variability in DNAm. This context-based approach decreases biases stemming from overreliance on specific samples or variables. We discovered molecular patterns demonstrating prospective and replicable relations to complex traits. Moreover, results suggest that patterns harbour a genome-wide organisation specific to chromatin regulation and target tissues. These preliminary findings warrant further investigation to better reflect the reality of human context in molecular studies of NCDs.

Graphical Abstract
Response of rumen fermentation and microbiota to dietary supplementation of sodium selenite and bio-nanostructured selenium in lactating Barki sheep
Authors: Rabee Alaa Emara , Khalil Mayada M. H. , Khadiga Galal Abou , Elmahdy Ahmed , Sabra Ebrahim A. , Zommara Mohsen A. , Khattab Ibrahim M. 
Published: November 2023

AbstractDietary selenium (Se) sources affects the structure of the rumen microbial community and rumen fermentation. This study evaluated the effects of sodium selenite (SS) and bio-nanostructured selenium (SeNSM) on rumen fermentation and structure of rumen microbial community of lactating Barki ewes. Twenty one lactating Barki ewes were assigned into three groups based on their body weight and milk yield. The experiment lasted for 50 days, whenever, the control group was fed basal diet; group SS received basal diets plus sodium selenite as inorganic source of Se; and group SeNSM received basal diet plus organic selenium bio-nanostructured. Ruminal pH and volatile Fatty Acids (VFA) was lower (P < 0.05) in SeNSM group compared to control. Principle Coordinate Analysis separated the microbial communities into three clusters based on feeding treatment. The bacterial community was dominated by phylum Bacteroidetes and Firmicutes that were affected (P < 0.05) by Se sources. Specifically Bacteriodetes was higher (P < 0.05) in SS and SeNSM groups; and Firmicutes was higher (P < 0.05) in the control group. Moreover, the predominant bacterial genera were Prevotella, Rikenellaceae RC9 gut group, Unclassified_Bacteroidales, which were higher (P < 0.05) in SeNSM group. The methanogenic community belonged to phylum Euryarchaeota and was significantly decreased (P < 0.05) by Se supplementation. Principal component analysis based on rumen fermentation parameters, and relative abundances of bacteria and methanogens revealed three distinct clusters. These findings suggest that Se supplementation affected the relative abundances of dominant bacterial groups, declined rumen methanogens and SeNSM supplementation showed some positive impacts on some fibrolytic bacteria.
Modular bioengineering of whole-cell catalysis for sialo-oligosaccharide production: coordinated co-expression of CMP-sialic acid synthetase and sialyltransferase
Authors: Schelch Sabine , Eibinger Manuel , Zuson Jasmin , Kuballa Jürgen , Nidetzky Bernd 
Published: November 2023

Abstract
Background
In whole-cell bio-catalysis, the biosystems engineering paradigm shifts from the global reconfiguration of cellular metabolism as in fermentation to a more focused, and more easily modularized, optimization of comparably short cascade reactions. Human milk oligosaccharides (HMO) constitute an important field for the synthetic application of cascade bio-catalysis in resting or non-living cells. Here, we analyzed the central catalytic module for synthesis of HMO-type sialo-oligosaccharides, comprised of CMP-sialic acid synthetase (CSS) and sialyltransferase (SiaT), with the specific aim of coordinated enzyme co-expression in E. coli for reaction flux optimization in whole cell conversions producing 3′-sialyllactose (3SL).

Results
Difference in enzyme specific activity (CSS from Neisseria meningitidis: 36 U/mg; α2,3-SiaT from Pasteurella dagmatis: 5.7 U/mg) was compensated by differential protein co-expression from tailored plasmid constructs, giving balance between the individual activities at a high level of both (α2,3-SiaT: 9.4 × 102 U/g cell dry mass; CSS: 3.4 × 102 U/g cell dry mass). Finally, plasmid selection was guided by kinetic modeling of the coupled CSS-SiaT reactions in combination with comprehensive analytical tracking of the multistep conversion (lactose, N-acetyl neuraminic acid (Neu5Ac), cytidine 5′-triphosphate; each up to 100 mM). The half-life of SiaT in permeabilized cells (≤ 4 h) determined the efficiency of 3SL production at 37 °C. Reaction at 25 °C gave 3SL (40 ± 4 g/L) in ∼ 70% yield within 3 h, reaching a cell dry mass-specific productivity of ∼ 3 g/(g h) and avoiding intermediary CMP-Neu5Ac accumulation.

Conclusions
Collectively, balanced co-expression of CSS and SiaT yields an efficient (high-flux) sialylation module to support flexible development of E. coli whole-cell catalysts for sialo-oligosaccharide production.
Revealing associations between spatial time series trends of COVID-19 incidence and human mobility: an analysis of bidirectionality and spatiotemporal heterogeneity
Authors: Kwon Hoeyun , Koylu Caglar 
Published: November 2023

Abstract
Background
Using human mobility as a proxy for social interaction, previous studies revealed bidirectional associations between COVID-19 incidence and human mobility. For example, while an increase in COVID-19 cases may affect mobility to decrease due to lockdowns or fear, conversely, an increase in mobility can potentially amplify social interactions, thereby contributing to an upsurge in COVID-19 cases. Nevertheless, these bidirectional relationships exhibit variations in their nature, evolve over time, and lack generalizability across different geographical contexts. Consequently, a systematic approach is required to detect functional, spatial, and temporal variations within the intricate relationship between disease incidence and mobility.

Methods
We introduce a spatial time series workflow to investigate the bidirectional associations between human mobility and disease incidence, examining how these associations differ across geographic space and throughout different waves of a pandemic. By utilizing daily COVID-19 cases and mobility flows at the county level during three pandemic waves in the US, we conduct bidirectional Granger causality tests for each county and wave. Furthermore, we employ dynamic time warping to quantify the similarity between the trends of disease incidence and mobility, enabling us to map the spatial distribution of trends that are either similar or dissimilar.

Results
Our analysis reveals significant bidirectional associations between COVID-19 incidence and mobility, and we develop a typology to explain the variations in these associations across waves and counties. Overall, COVID-19 incidence exerts a greater influence on mobility than vice versa, but the correlation between the two variables exhibits a stronger connection during the initial wave and weakens over time. Additionally, the relationship between COVID-19 incidence and mobility undergoes changes in direction and significance for certain counties across different waves. These shifts can be attributed to alterations in disease control measures and the presence of evolving confounding factors that differ both spatially and temporally.

Conclusions
This study provides insights into the spatial and temporal dynamics of the relationship between COVID-19 incidence and human mobility across different waves. Understanding these variations is crucial for informing the development of more targeted and effective healthcare policies and interventions, particularly at the city or county level where such policies must be implemented. Although we study the association between mobility and COVID-19 incidence, our workflow can be applied to investigate the associations between the time series trends of various infectious diseases and relevant contributing factors, which play a role in disease transmission.
Micro electrical fields induced MSC-sEVs attenuate neuronal cell apoptosis by activating autophagy via lncRNA MALAT1/miR-22-3p/SIRT1/AMPK axis in spinal cord injury
Authors: Li Kewei , Liu Zhong , Wu Peipei , Chen Shenyuan , Wang Min , Liu Wenhui , Zhang Leilei , Guo Song , Liu Yanbin , Liu Pengcheng , Zhang Beiting , Tao Lin , Ding Hua , Qian Hui , Fu Qiang 
Published: November 2023

AbstractSpinal cord injury (SCI) is a traumatic condition of the central nervous system that causes paralysis of the limbs. Micro electric fields (EF) have been implicated in a novel therapeutic approach for nerve injury repair and regeneration, but the effects of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles that are induced by micro electric fields (EF-sEVs) stimulation on SCI remain unknown. The aim of the present study was to investigate whether EF-sEVs have therapeutic effects a rat model of SCI. EF-sEVs and normally conditioned human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (CON-sEVs) were collected and injected intralesionally into SCI model rats to evaluate the therapeutic effects. We detect the expression of candidate long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA-MALAT1) in EF-sEVs and CON-sEVs. The targets and downstream effectors of lncRNA-MALAT1 were investigated using luciferase reporter assays. Using both in vivo and in vitro experiments, we demonstrated that EF-sEVs increased autophagy and decreased apoptosis after SCI, which promoted the recovery of motor function. We further confirmed that the neuroprotective effects of EF-sEVs in vitro and in vivo correlated with the presence of encapsulated lncRNA-MALAT1 in sEVs. lncRNA-MALAT1 targeted miR-22-3p via sponging, reducing miR-22-3p’s suppressive effects on its target, SIRT1, and this translated into AMPK phosphorylation and increased levels of the antiapoptotic protein Bcl-2. Collectively, the present study identified that the lncRNA-MALAT1 in EF-sEVs plays a neuroprotective role via the miRNA-22-3p/SIRT1/AMPK axis and offers a fresh perspective and a potential therapeutic approach using sEVs to improve SCI.
Nurses’ job preferences for working in deprived areas in Tehran: a discrete choice experiment
Authors: Haddadfar Amirmohammad , Emamgholipour Sara , Razani Mohsen , Salehnejad Mohammad Hassan 
Published: November 2023

Abstract
Background
In Iran, the issue of the nursing shortage and unequal distribution exist simultaneously. The shortage of healthcare workers is one of the most important concerns of the health systems. In addition, the disparity in the distribution of healthcare workers between large metropolises and remote or non-capital areas has become a serious concern and a top priority to address. We conducted this study to identify and create a sufficient understanding of the different financial and non-financial preferences of nurses for working in deprived areas.

Methods
This research was carried out in June and April 2022. It was carried out in three major phases. The factors influencing the nurses' job preferences were first discovered using qualitative methods. The second phase was conducting a pilot study and determining the best design for discrete choice experiment scenarios. The last phase involved publishing the questionnaire to gather information. Data were analyzed (discrete choice analysis) using JMP Pro 16 software.

Results
A desirable job for the participants (nurses) in this study would have a higher salary, work in a city, the Rasmi employment contract, a low workload, adequate workplace facilities, an appropriate work schedule, and 1 to 3 years spent on the assigned job to promote to a higher position. Willingness to pay (WTP) and the probability of selecting different attribute levels were also calculated and reported. For example, the highest amount of money that a nurse expected to be paid was for changing the geographical location of the workplace from a city to a deprived area. In this case, a nurse tends to receive 91.87 million IRR more to move from a city to a deprived area to work. This amount of money was by far the most among other WTPs.

Conclusion
The results of this study indicated that nurses are willing to forego net income in exchange for other favorable characteristics of their working environment and conditions. This shows that a variety of actions are accessible to policymakers that can greatly enhance the working conditions for nurses. The WTP and the probability of selecting various attributes may help policymakers plan more effectively.