bluuebunny/crossref_metadata_2025_split huggingface dataset:
IRIS: Infection with RespIratory Syncytial Virus in infants—a prospective observational cohort study
Authors: Wetzke Martin , Funken Dominik , Lange Mathias , Bejo Levente , Haid Sibylle , Monteiro Joao G. Tereno , Schütz Katharina , Happle Christine , Schulz Thomas F. , Seidenberg Jürgen , Pietschmann Thomas , Hansen Gesine 
Published: March 2022

Abstract
Background
Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in infants. Globally, RSV is responsible for approximately 3.2 million hospital admissions and about 60,000 in-hospital deaths per year.

Methods
Infection with RespIratory Syncytial Virus (IRIS) is an observational, multi-centre study enrolling infants with severe RSV infection and healthy controls. Inclusion criteria are age between 0 and 36 months and hospitalisation due to RSV infection at three German sites. Exclusion criteria are premature birth, congenital or acquired bronchopulmonary or cardiac diseases, and immunodeficiency. Healthy control probands are enrolled via recruitment of patients undergoing routine surgical procedures. Blood and respiratory specimens are collected upon admission, and RSV and other pathogens are analysed by multiplex polymerase chain reaction. Different biomaterials, including plasma, nasal lining fluid, blood cells, DNA, and RNA specimens, are sampled in a dedicated biobank. Detailed information on demographic characteristics and medical history is recorded, and comprehensive clinical data, including vital signs, medication, and interventions.

Discussion
The IRIS study aims to discover host and viral factors controlling RSV disease courses in infants. The approach including multi-omics characterisation in clinically well-characterized children with RSV bronchiolitis seeks to improve our understanding of the immune response against this virus. It may disclose novel diagnostic and treatment approaches for respiratory infections in infants.
Trial registration: ClinicalTrials.gov, NCT04925310. Registered 01 October 2021—Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04925310?cond=NCT04925310&draw=2&rank=1
Circ_0000064 promotes high glucose-induced renal tubular epithelial cells injury to facilitate diabetic nephropathy progression through miR-532-3p/ROCK1 axis
Authors: Wang Huanlan , Huang Shenghua , Hu Taotao , Fei Shizhi , Zhang Huanqiao 
Published: March 2022

Abstract
Background
Circular RNA (circRNA) has been shown to mediate diabetic nephropathy (DN) development by regulating renal tubular epithelial cells (RTECs) injury. However, the role and mechanism of circ_0000064 in high glucose (HG)-induced RTECs injury have not been fully elucidated.

Methods
Human RTECs (HK-2) were exposed to HG to induce cell injury. Cell oxidative stress was assessed by detecting the levels of oxidative stress-markers. Moreover, cell proliferation and apoptosis were determined by CCK8 assay, EDU assay and flow cytometry. The protein levels of proliferation markers, apoptosis markers and Rho-associated coiled-coil-containing kinase 1 (ROCK1) were measured using western blot analysis. Furthermore, quantitative real-time PCR was performed to assess the expression of circ_0000064, microRNA (miR)-532-3p and ROCK1. The interaction between miR-532-3p and circ_0000064 or ROCK1 was confirmed by dual-luciferase reporter assay and RNA pull-down assay.

Results
Our results revealed that HG treatment could promote HK-2 cells oxidative stress, apoptosis, fibrosis, and inhibit proliferation. Circ_0000064 expression was increased in the serum of DN patients and HG-induced HK-2 cells, and silenced circ_0000064 could relieve HG-induced HK-2 cells injury. MiR-532-3p could be sponged by circ_0000064, and its overexpression also alleviated HG-induced HK-2 cells injury. Besides, the regulation of circ_0000064 knockdown on HG-induced HK-2 cells injury could be reversed by miR-532-3p inhibitor. Additionally, ROCK1 was a target of miR-532-3p, and its expression was inhibited by circ_0000064 knockdown. The inhibition effect of circ_0000064 knockdown on HG-induced HK-2 cells injury also could be reversed by overexpressing ROCK1.

Conclusion
In summary, circ_0000064 knockdown might alleviate HG-induced HK-2 cells injury via regulating the miR-532-3p/ROCK1 axis, which provided a new perspective for DN treatment.
Electronic medical record implementation in a large healthcare system from a leadership perspective
Authors: Arabi Yaseen M , Al Ghamdi Abdullah Ali , Al-Moamary Mohamed , Al Mutrafy Abdullah , AlHazme Raed H. , Al Knawy Bandar Abdulmohsen 
Published: March 2022

Abstract
Background
Information on the use of change management models to guide electronic medical records (EMR) implementation is limited. This case study describes the leadership aspects of a large-scale EMR implementation using Kotter’s change management model.

Methods
This case study presents the experience in implementing a new EMR system from the leadership perspective at King Abdulaziz Medical City, a large tertiary care hospital in Riyadh, Kingdom of Saudi Arabia. We described the process of implementation and outlined the challenges and opportunities, throughout the journey from the pre-implementation to the post-implementation phases.

Results
We described the corresponding actions to the eight domains of Kotter’s change management model: creating a sense of urgency, building the guiding team, developing a change vision and strategy, understanding and buy-in, removing obstacles, creating short-term wins, building on the change and anchoring the changes in corporate culture.

Conclusions
The case study highlights that EMR implementation is not a pure information technology project but rather is a technical-based complex social adaptive project that requires a specific set of leadership competencies that are central to its success. It demonstrates that change management models might be useful for large-scale EMR implementation.
A framework for participatory work environment interventions in home care – success factors and some challenges
Authors: Persson Johanna , Johansson Gerd , Arvidsson Inger , Östlund Britt , Holgersson Charlotte , Persson Roger , Rydenfält Christofer 
Published: March 2022

Abstract
Background
Home care is beset with work environment issues and high staff turnover, while research concerned with interventions to improve the work environment is sparse. Few of the existing interventions apply a participative approach, despite this being associated with more positive outcomes and sustainable change. This paper presents a framework, rooted in action research and action learning, for participatory work environment interventions in home care, and demonstrates how this framework has been implemented in four Swedish home care organizations.

Methods
The framework has three phases (pre-intervention, intervention planning and intervention implementation) and consists of cycles of action and reflection in three constellations: a group of researchers, a reference group with labour market organization representatives and home care managers, and intervention work groups in the home care organizations. The work was documented and analysed with focus on the realization of the framework and challenges that were met on the way. The interventions were evaluated using a pre-/post-test questionnaire design.

Results
Parts of the framework were successfully implemented. The pre-intervention phase and the intervention planning phase, with intervention work groups, worked well. All four groups identified one intervention relevant to their own context. However, only two of the proposed interventions were fully implemented and evaluated. The high staff and management turnover, and the high rate of organizational changes made it impossible to evaluate the interventions statistically. Yet, data from open-ended questions in the post questionnaire showed that the two implemented interventions were perceived as successful.

Conclusions
The participatory framework, presented in this paper, seems promising for work environment interventions in home care. The framework was designed to reduce the risk of known disturbances affecting the process in unstable organizations. Despite this, it proved challenging to execute the framework, and especially the interventions, due to changes happening at high speed. In the two cases where organizational changes were not dominating, the interventions were implemented successfully. While the prerequisites for participation and successful implementation could be improved somewhat, the main issue, the instability of the organizational context, is hard for researchers or the individual home care units to tackle alone.
Effect of xylazine, detomidine, medetomidine and dexmedetomidine during laparoscopic SCNT embryo transfer on pregnancy rate and some physiological variables in goats
Authors: Aghamiri Seyed Morteza , Samimi Amir Saeed , Hajian Mehdi , Samimi Amir Masoud , Oroumieh Amin 
Published: March 2022

Abstract
Background
The present study was conducted to determine if using α2-adrenergic agonists results in decreased stress levels (lower cortisol levels) in goats used for laparoscopic embryo [somatic cell nuclear transfer (SCNT)] transfer; and there is an effect on pregnancy rate when stress levels are lessened. Sixty healthy does aged 24 ± 4 months and weighing 30 ± 3 kg were used in experimental, prospective, randomized and blinded study. In this study, embryos were obtained by the Somatic Cell Nuclear Transfer (SCNT) method. Animals were randomly assigned to five groups: control (normal saline); xylazine (100 μg kg− 1); detomidine (50 μg kg− 1); medetomidine (20 μg kg− 1); and dexmedetomidine (5 μg kg− 1). Embryo transfer (through laparoscopic technique) began at 15 min and continued till 45 min post-treatment. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), and ruminal motility were performed before (baseline) and after drug administration. Pregnancy detection was performed 38 days after embryo transfer.

Results
Compared to control, HR, RR and ruminal motility were significantly lower in α2-adrenergic agonists groups at 5–90, 15–60, and 5–120 min, respectively. Serum cortisol values significantly increased from baseline in the control group 45 min after drug administration (p = 0.001). At time points 45 and 60 min, serum cortisol concentration was significantly lower in α2-adrenergic agonists groups compared with the control. The pregnancy rate in control group (n = 4/12, 33.3%) was significantly lower than xylazine (n = 9/12, 75%; p = 0.041), detomidine (n = 10/12, 83.3%; p = 0.013), medetomidine (n = 9/12, 75%; p = 0.041) and dexmedetomidine (n = 10/12, 83.3%; p = 0.013); but no significant differences were observed among different α2-adrenergic agonists groups.

Conclusion
Alph2-adrenergic agonists were effective on increasing the pregnancy rate of recipient goats receiving cloned embryos. No significant differences were detected among different α2-adrenergic agonists.
Xylanase production by Thermobacillus xylanilyticus is impaired by population diversification but can be mitigated based on the management of cheating behavior
Authors: Bouchat Romain , Vélard Frédéric , Audonnet Sandra , Rioult Damien , Delvigne Frank , Rémond Caroline , Rakotoarivonina Harivony 
Published: March 2022

Abstract
Background
The microbial production of hemicellulasic cocktails is still a challenge for the biorefineries sector and agro-waste valorization. In this work, the production of hemicellulolytic enzymes by Thermobacillus xylanilyticus has been considered. This microorganism is of interest since it is able to produce an original set of thermostable hemicellulolytic enzymes, notably a xylanase GH11, Tx-xyn11. However, cell-to-cell heterogeneity impairs the production capability of the whole microbial population.

Results
Sequential cultivations of the strain on xylan as a carbon source has been considered in order to highlight and better understand this cell-to-cell heterogeneity. Successive cultivations pointed out a fast decrease of xylanase activity (loss of ~ 75%) and Tx-xyn11 gene expression after 23.5 generations. During serial cultivations on xylan, flow cytometry analyses pointed out that two subpopulations, differing at their light-scattering properties, were present. An increase of the recurrence of the subpopulation exhibiting low forward scatter (FSC) signal was correlated with a progressive loss of xylanase activity over several generations. Cell sorting and direct observation of the sorted subpopulations revealed that the low-FSC subpopulation was not sporulating, whereas the high-FSC subpopulation contained cells at the onset of the sporulation stage. The subpopulation differences (growth and xylanase activity) were assessed during independent growth. The low-FSC subpopulation exhibited a lag phase of 10 h of cultivation (and xylanase activities from 0.15 ± 0.21 to 3.89 ± 0.14 IU/mL along the cultivation) and the high-FSC subpopulation exhibited a lag phase of 5 h (and xylanase activities from 0.52 ± 0.00 to 4.43 ± 0.61 over subcultivations). Serial cultivations on glucose, followed by a switch to xylan led to a ~ 1.5-fold to ~ 15-fold improvement of xylanase activity, suggesting that alternating cultivation conditions could lead to an efficient population management strategy for the production of xylanase.

Conclusions
Taken altogether, the data from this study point out that a cheating behavior is responsible for the progressive reduction in xylanase activity during serial cultivations of T. xylanilyticus. Alternating cultivation conditions between glucose and xylan could be used as an efficient strategy for promoting population stability and higher enzymatic productivity from this bacterium.
BuFeiXiaoJiYin ameliorates the NLRP3 inflammation response and gut microbiota in mice with lung cancer companied with Qi-yin deficiency
Authors: Jiang Rui-yuan , Wang Ting , Lan Qiao-yu , Qin Yan-chun , Man Ting-ting , Sun Hua , Li Zhu-long , Zhong Xiao-ting , Mo Chun-mei , Rong Zhen 
Published: March 2022

Abstract
Introduction
NLRP3 inflammasome responses and gut microbiota have been shown an important role in lung cancer, however, the relationship between gut microbiota and NLRP3 inflammasome responses in lung cancer with Qi-yin deficiency remains elusive.

Methods
To investigate the effect of the traditional Chinese medicine BuFeiXiaoJiYin (BFXJY) on NLRP3 inflammasome responses and dysbiosis in lung cancer with Qi-yin deficiency, the female BALB/cA-nu mice were treated with LPS and ATP to induce inflammation, and were intragastrically treated with warm Chinese medicine and smoked with shavings to induce Qi-yin deficiency, as well as were injected with 1 × 107/ml A549 cells to simulate lung cancer. Then the three different doses of BuFeiXiaoJiYin (BFXJY) and positive control (CRID3) were used for intervention in mice for 27 consecutive days. Then, we estimated the protection effect of BFXJY on lung cancer mice with Qi-yin deficiency, through deterring tumor growth, NLRP3 inflammasome, PKC signaling, and homeostasis of gut microbiota.

Results
In this study, we found that BFXJY could inhibit the tumor growth in lung cancer with Qi-yin deficiency by reducing the production of IL-1β and IL-18 and inhibiting NLRP3 inflammasome activation, which might be associated with the inhibition of PKC signaling. Furthermore, BFXJY could promote microbial diversity and balance the microbial composition changes induced by inflammation and Qi-yin deficiency in lung cancer.

Conclusion
BuFeiXiaoJiYin ameliorates the NLRP3 inflammation response and gut microbiota in mice with lung cancer companied with Qi-yin deficiency. Our study provides a theoretical basis for the clinical development of therapeutic drugs targeting to treat lung cancer.
Prevalence of thoracoabdominal imaging findings in tuberous sclerosis complex
Authors: Ritter David M. , Fessler Bailey K. , Ebrahimi-Fakhari Daniel , Wei Jun , Franz David N. , Krueger Darcy A. , Trout Andrew T. , Towbin Alexander J. 
Published: March 2022

Abstract
Background
Tuberous sclerosis complex (TSC) results in neurodevelopmental phenotypes, benign tumors, and cysts throughout the body. Recent studies show numerous rare findings in TSC. Guidelines suggest routine abdominal and chest imaging to monitor these thoracoabdominal findings, but imaging is not uniformly done across centers. Thus, the prevalence of many findings is unknown. To answer this, we categorized the clinical reads of 1398 thoracoabdominal scans from 649 patients of all ages in the Cincinnati Children’s Hospital TSC Repository Database.

Results
Typical TSC findings were present in many patients: kidney cysts (72%), kidney fat-containing angiomyolipomas (51%), kidney lipid-poor angiomyolipomas (27%), liver angiomyolipomas (19%), and lung nodules thought to represent multifocal micronodular pneumocyte hyperplasia (MMPH) (18%). While many features were more common in TSC2 patients, TSC1 patients had a higher prevalence of MMPH than TSC2 patients (24% versus 13%, p = 0.05). Many rare findings (e.g., lymphatic malformations and liver masses) are more common in TSC than in the general population. Additionally, most thoracoabdominal imaging findings increased with age except kidney cysts which decreased, with the 0–10 years age group having the highest percentage (69% 0–10 years, 49% 10–21 years, 48% 21 + years, p < 0.001). Finally, in our population, no patients had renal cell carcinoma found on abdominal imaging.

Conclusions
These results show that regular thoracoabdominal scans in TSC may show several findings that should not be ignored or, conversely, over-reacted to when found in patients with TSC. Female sex, TSC2 mutation, and age are risk factors for many thoracoabdominal findings. The data suggest novel interactions of genetic mutation with pulmonary nodules and age with renal cysts. Finally, in agreement with other works, these findings indicate that several rare thoracoabdominal imaging findings occur at higher rates in the TSC population than in the general population. This work supports obtaining detailed thoracoabdominal imaging in patients with TSC.
The route of SARS-CoV-2 to brain infection: have we been barking up the wrong tree?
Authors: Butowt Rafal , von Bartheld Christopher S. 
Published: March 2022

AbstractThis letter draws attention to recent work supporting the notion that the SARS-CoV-2 virus may use the nervus terminalis rather than the olfactory nerve as a shortcut route from the nasal cavity to infect the brain.
LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond
Authors: Huang Wanxu , Li Hua , Yu Qingsong , Xiao Wei , Wang Dan Ohtan 
Published: March 2022

AbstractDNA methylation is one of the most important epigenetic mechanisms to regulate gene expression, which is highly dynamic during development and specifically maintained in somatic cells. Aberrant DNA methylation patterns are strongly associated with human diseases including cancer. How are the cell-specific DNA methylation patterns established or disturbed is a pivotal question in developmental biology and cancer epigenetics. Currently, compelling evidence has emerged that long non-coding RNA (lncRNA) mediates DNA methylation in both physiological and pathological conditions. In this review, we provide an overview of the current understanding of lncRNA-mediated DNA methylation, with emphasis on the roles of this mechanism in cancer, which to the best of our knowledge, has not been systematically summarized. In addition, we also discuss the potential clinical applications of this mechanism in RNA-targeting drug development.
Effect of application time of 38% silver diamine fluoride solution on arresting early childhood caries in preschool children: a randomised double-blinded controlled trial protocol
Authors: Yan Iliana Gehui , Zheng Faith Miaomiao , Gao Sherry Shiqian , Duangthip Duangporn , Lo Edward Chin Man , Chu Chun Hung 
Published: March 2022

AbstractBackgroundTo study the caries lesion activity response to topical 38% silver diamine fluoride (SDF) therapy with increasing treatment application time.Methods/designThe design is a stratified-randomised, double-blind, active-controlled, parallel-group clinical trial with nine treatment arms. The trial will involve recruiting at least 414 3- to 5-year-old kindergarten children with caries, who will receive approximately 0.004 mL of 38% SDF (the typical amount applied per the manufacturer’s instructions) to treat each caries lesion. The children will be stratified by caries status, randomised by blocks, and allocated to nine groups of SDF application times: 3, 5, 10, 15, 30, 45, 60, 120, and 180 s. The outcome measure is caries lesion activity (active/arrest) at the tooth-surface level at 6 months post-initial treatment. A calibrated dentist will conduct the blinded clinical examinations at baseline and at the 6-month follow-up. In addition, the parents will be surveyed to examine the effects of the moderating variables, such as oral hygiene, on caries lesion activity. The hypothesis is that a monotonically increasing trend can be found between the SDF application time and the proportion of caries lesions that are arrested. The Cochran-Armitage test for trends in proportions, corrected for clustering within children, will be used to determine the relationship between the exposure to SDF (the SDF application time) and the response (proportion of lesions arrested) in children, taking into consideration the effect of the moderating variables as well as the nesting of multiple caries lesions within an individual child. An EC 80 analysis (an 80% maximal concentration) will be used to determine the exposure (the SDF application time) for 80% caries lesion arrest. Bootstrap methods will be used for clustered data and will be resampled by clustering to determine the 95% confidence interval.DiscussionThis study will help with determining the optimal application time for SDF treatment. It will provide an evidence-based protocol for the use of SDF to arrest tooth decay in the primary teeth of young children. The results will inform an evidence-based SDF protocol to arrest caries, which affects 573 million children with tooth decay worldwide.Trial registrationClinicalTrials.govNCT04655430. Registered on 7th December 2020.