bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico vaccine design and epitope mapping of New Delhi metallo-beta-lactamase (NDM): an immunoinformatics approach
Authors: Fathollahi Matin , Fathollahi Anwar , Motamedi Hamid , Moradi Jale , Alvandi Amirhooshang , Abiri Ramin 
Published: September 2021

Abstract
Background
Antibiotic resistance is a global health crisis. The adage that “prevention is better than cure” is especially true regarding antibiotic resistance because the resistance appears and spreads much faster than the production of new antibiotics. Vaccination is an important strategy to fight infectious agents; however, this strategy has not attracted sufficient attention in antibiotic resistance prevention. New Delhi metallo-beta-lactamase (NDM) confers resistance to many beta-lactamases, including important carbapenems like imipenem. Our goal in this study is to use an immunoinformatics approach to develop a vaccine that can elicit strong and specific immune responses against NDMs that prevent the development of antibiotic-resistant bacteria.

Results
In this study, 2194 NDM sequences were aligned to obtain a conserved sequence. One continuous B cell epitope and three T cell CD4+ epitopes were selected from NDMs conserved sequence. Epitope conservancy for B cell and HLA-DR, HLA-DQ, and HLA-DP epitopes was 100.00%, 99.82%, 99.41%, and 99.86%, respectively, and population coverage of MHC II epitopes for the world was 99.91%. Permutation of the four epitope fragments resulted in 24 different peptides, of which 6 peptides were selected after toxicity, allergenicity, and antigenicity assessment. After primary vaccine design, only one vaccine sequence with the highest similarity with discontinuous B cell epitope in NDMs was selected. The final vaccine can bind to various Toll-like receptors (TLRs). The prediction implied that the vaccine would be stable with a good half-life. An immune simulation performed by the C-IMMSIM server predicted that two doses of vaccine injection can induce a strong immune response to NDMs. Finally, the GC-Content of the vaccine was designed very similar to E. coli K12.

Conclusions
In this study, immunoinformatics strategies were used to design a vaccine against different NDM variants that could produce an effective immune response against this antibiotic-resistant factor.
Genetic changes involving the coral gastrovascular system support the transition between colonies and bailed-out polyps: evidence from a Pocillopora acuta transcriptome
Authors: Chuang Po-Shun , Mitarai Satoshi 
Published: September 2021

Abstract
Background
A coral colony is composed of physiologically integrated polyps. In stony corals, coloniality adopts a wide diversity of forms and involves complex ontogenetic dynamics. However, molecular mechanisms underlying coloniality have been little studied. To understand the genetic basis of coloniality and its contribution to coral ecology, we induced polyp bail-out in a colonial coral, Pocillopora acuta, and compared transcription profiles of bailed-out polyps and polyps in normal colonies, and their responses to heat shock and hyposalinity.

Results
Consistent with morphological formation of a gastrovascular system and its neural transmission and molecular transport functions, we found genetic activation of neurogenesis and development of tube-like structures in normal colonies that is absent in bailed-out polyps. Moreover, relative to bailed-out polyps, colonies showed significant overexpression of genes for angiotensin-converting enzymes and endothelin-converting enzymes. In response to hyperthermal and hyposaline treatments, a high proportion of genetic regulation proved specific to either bailed-out polyps or colonies. Elevated temperatures even activated NF-κB signaling in colonies. On the other hand, colonies showed no discernible advantage over bailed-out polyps in regard to hyposalinity.

Conclusions
The present study provides a first look at the genetic basis of coloniality and documents different responses to environmental stimuli in P. acuta colonies versus those in bailed-out polyps. Overexpression of angiotensin-converting enzymes and endothelin-converting enzymes in colonies suggests possible involvement of these genes in development of the gastrovascular system in P. acuta. Functional characterization of these coral genes and further investigation of other forms of the transition to coloniality in stony corals should be fruitful areas for future research.
The effect of an eye mask on midazolam requirement for sedation during spinal anesthesia: a randomized controlled trial
Authors: Yoo Seon Woo , Ki Min-Jong , Kim Dal , Oh Yu Jin , Lee Jeongwoo 
Published: September 2021

Abstract
Background
Midazolam is frequently used for sedation during spinal anesthesia. However, external environmental factors, such as bright surgical lights, may hamper patient relaxation, which may lead to an increase in the dose of midazolam required and the likelihood of adverse drug effects. We investigated whether using an eye mask to block the external environment could reduce midazolam requirements during spinal anesthesia.

Methods
Participants aged 18–‒80 years, scheduled for elective surgery under spinal anesthesia, were randomly divided into a masked group (wearing eye masks during surgery, n = 20) and a control group (no mask, n = 18). The sedation level was assessed using a modified Observer Assessment of Alertness and Sedation (MOAA/S) scale. Midazolam (1 mg) was incrementally administered every 5 min until moderate sedation (MOAA/S score of 3) was achieved. The bispectral index (BIS) was monitored, and the onset and maintenance times of a BIS < 80 were recorded.

Results
The two groups had similar demographic characteristics. The midazolam requirements were significantly lower in the masked group than in the control group (2.8 mg vs. 3.7 mg, P = 0.024). However, the onset and maintenance times for a BIS < 80 were similar. In addition, there were no significant differences in the incidence of side effects or patient satisfaction between the two groups.

Conclusions
Blocking the external environment with an eye mask during spinal anesthesia can reduce the requirement for sedatives, such as midazolam.

Trial registration
The trial was retrospectively registered with the Clinical Research Information Service (No. KCT0005528, 15/10/2020) entitled “Can we reduce an amount of sleeping pills just by blocking light?”.
Development of a simulation-based curriculum for Pediatric prehospital skills: a mixed-methods needs assessment
Authors: Padrez Kevin A. , Brown John , Zanoff Andy , Chen Carol C. , Glomb Nicolaus 
Published: September 2021

Abstract
Background
The assessment and treatment of pediatric patients in the out-of-hospital environment often presents unique difficulties and stress for EMS practitioners.

Objective
Use a mixed-methods approach to assess the current experience of EMS practitioners caring for critically ill and injured children, and the potential role of a simulation-based curriculum to improve pediatric prehospital skills.

Methods
Data were obtained from three sources in a single, urban EMS system: a retrospective review of local pediatric EMS encounters over one year; survey data of EMS practitioners’ comfort with pediatric skills using a 7-point Likert scale; and qualitative data from focus groups with EMS practitioners assessing their experiences with pediatric patients and their preferred training modalities.

Results
2.1% of pediatric prehospital encounters were considered “critical,” the highest acuity level. A total of 136 of approximately 858 prehospital providers responded to the quantitative survey; 34.4% of all respondents either somewhat disagree (16.4%), disagree (10.2%), or strongly disagree (7.8%) with the statement: “I feel comfortable taking care of a critically ill pediatric patient.” Forty-seven providers participated in focus groups that resulted in twelve major themes under three domains. Specific themes included challenges in medication dosing, communication, and airway management. Participants expressed a desire for more repetition and reinforcement of these skills, and they were receptive to the use of high-fidelity simulation as a training modality.

Conclusions
Critically ill pediatric prehospital encounters are rare. Over one third of EMS practitioners expressed a low comfort level in managing critically ill children. High-fidelity simulation may be an effective means to improve the comfort and skills of prehospital providers.
A comparative study of forest methods for time-to-event data: variable selection and predictive performance
Authors: Liu Yingxin , Zhou Shiyu , Wei Hongxia , An Shengli 
Published: September 2021

AbstractBackgroundAs a hot method in machine learning field, the forests approach is an attractive alternative approach to Cox model. Random survival forests (RSF) methodology is the most popular survival forests method, whereas its drawbacks exist such as a selection bias towards covariates with many possible split points. Conditional inference forests (CIF) methodology is known to reduce the selection bias via a two-step split procedure implementing hypothesis tests as it separates the variable selection and splitting, but its computation costs too much time. Random forests with maximally selected rank statistics (MSR-RF) methodology proposed recently seems to be a great improvement on RSF and CIF.MethodsIn this paper we used simulation study and real data application to compare prediction performances and variable selection performances among three survival forests methods, including RSF, CIF and MSR-RF. To evaluate the performance of variable selection, we combined all simulations to calculate the frequency of ranking top of the variable importance measures of the correct variables, where higher frequency means better selection ability. We used Integrated Brier Score (IBS) and c-index to measure the prediction accuracy of all three methods. The smallerIBSvalue, the greater the prediction.ResultsSimulations show that three forests methods differ slightly in prediction performance. MSR-RF and RSF might perform better than CIF when there are only continuous or binary variables in the datasets.For variable selection performance,When there are multiple categorical variables in the datasets, the selection frequency of RSF seems to be lowest in most cases. MSR-RF and CIF have higher selection rates, and CIF perform well especially with the interaction term.The fact that correlation degree of the variables has little effect on the selection frequency indicates that three forest methods can handle data with correlation.When there are only continuous variables in the datasets, MSR-RF perform better. When there are only binary variables in the datasets, RSF and MSR-RF have more advantages than CIF.When the variable dimension increases, MSR-RF and RSF seem to be more robustthan CIFConclusionsAll three methods show advantages in prediction performances and variable selection performances under different situations. The recent proposed methodology MSR-RF possess practical value and is well worth popularizing. It is important to identify the appropriate method in real use according to the research aim and the nature of covariates.
Measuring advance care planning behavior in Dutch adults: translation, cultural adaptation and validation of the Advance Care Planning Engagement Survey
Authors: van der Smissen Doris , van der Heide Agnes , Sudore Rebecca L. , Rietjens Judith A. C. , Korfage Ida J. 
Published: September 2021

Abstract
Background
Advance care planning (ACP) enables people to define, discuss, and record preferences for treatment and care. Measures of ACP behavior are lacking in the Netherlands. We aimed to translate, culturally adapt and validate the 34-item ACP Engagement Survey into Dutch.

Methods
Following validation guidelines, we tested content validity, internal consistency, reproducibility, construct validity, interpretability and criterion validity among persons with and without chronic disease.

Results
Forward-backward translation indicated the need of only minor adaptations. Two hundred thirty-two persons completed baseline and retest surveys; 121 were aged ≥60 years. Persons with chronic disease (n = 151) considered the survey more valuable than those without (66 vs. 59, p < 0.001, scale of 20–100), indicating good content validity. Internal consistency (Cronbach’s alpha: 0.97) and reproducibility (intraclass correlation: 0.88) were good. Total ACP Engagement was higher among persons with chronic disease than those without (2.9 vs. 2.4, p < 0.01, scale of 1 to 5), indicating good psychometric support for construct validity and interpretability. Positive correlations of the ACP Engagement Survey and the General Self-Efficacy survey indicated good criterion validity (p < 0.05).

Conclusions
This study provided good psychometric support for the validity and reliability of the Dutch 34-item ACP Engagement Survey. This instrument can be used to assess involvement in ACP in adults with and without chronic disease.
A novel pN3 gastric cancer staging system with superior prognostic utility based upon the examination of over 31 lymph nodes: a propensity score-matching analysis
Authors: Hu Qiantao , Pan Siwei , Guo Zijun 
Published: September 2021

Abstract
Background
Individuals with pN3 gastric cancer (GC) account for a large proportion of pN + GC, and exhibit poor survival outcomes. The pN3 stage is defined based upon the number of metastatic lymph nodes (mLNs), but the subclassification of pN3 patients based upon the number of examined LNs (eLNs) is rarely performed.

Methods
In total, 2894 pTxN3M0 GC patients in the Surveillance, Epidemiology, and End Results database that had undergone surgery from 2000 to 2016 were selected for analysis. The X-tile software was used to select the optimal cutoff values. Cox proportional regression analyses were used to evaluated hazard ratios corresponding to the risk of death. Selection bias was minimized via propensity score matching (PSM).

Results
As the number of eLNs rose, the risk of death for patients trended downwards. Survival analyses indicated that patients with ≤ 31 eLNs exhibited significantly poorer survival outcomes as compared to patients with > 31 eLNs (5-year OS: 18.4% vs. 24.7%), and this result remained significant when analyzing 857 pairs of patients following PSM analysis. Significant differences in prognosis were additionally observed when comparing pN3a and pN3b patients with ≤ 31 or > 31 eLNs under pT3/4a stage. For pT4b stage, pN3a patients with > 31 eLNs also exhibited a better prognosis than other patients. The novel TNM staging system designed exhibited excellent utility as a tool for the prognostic evaluation of this GC patient population.

Conclusions
These results suggest that in pN3 GC, a minimum of 32 LNs should be examined. The novel TNM staging system for pN3 patients described herein, which was developed based upon the number of eLNs, may thus be of value in clinical settings.
The PSC scientific community resource: an asset for multi-omics interrogation of primary sclerosing cholangitis
Authors: Ali Ahmad Hassan , Juran Brian D. , Schlicht Erik M. , Bianchi Jackie K. , McCauley Bryan M. , Atkinson Elizabeth J. , Lazaridis Konstantinos N. 
Published: September 2021

Abstract
Background
Primary sclerosing cholangitis (PSC) is a rare, chronic cholestatic liver disease that often progresses to end-stage liver disease and/or the development of hepatobiliary neoplasia. Lack of prognostic tools and treatment options for PSC is driven in part by our poor understanding of its pathogenesis, which is thought to be complex, the interaction of genetic variants, environmental influences and biological response throughout the course of disease. The PSC Scientific Community Resource (PSC-SCR) seeks to overcome previous shortcomings by facilitating novel research in PSC with the ultimate goals of individualizing patient care and improving patient outcomes.

Methods
PSC patients who receive their health care at Mayo Clinic or a collaborating site are identified by chart review and invited in person or by mail to participate. Non-Mayo patients are offered enrollment if they provide sufficient access to their medical records to evaluate inclusion/exclusion criteria. Controls without liver disease are identified with assistance of the Mayo Clinic Biobank. Participant consent is obtained at the beginning of the recruitment process by mail-in, electronic or face-to-face protocols. Clinical data is extracted from the medical record by qualified physicians and entered in a custom designed database. Participants fill out a custom-designed, comprehensive questionnaire, which collects scientifically relevant demographic and clinical information. Biospecimens are collected using mail-in kits thar are returned via overnight carrier service and processed by the biospecimen accessioning and processing facility at Mayo Clinic, which coordinates sample transfers and provides required sample preparation services. The resource is currently being utilized to perform omics-scale projects investigating the exposome, metabolome, methylome, immunome and microbiome in PSC. Datasets and residual biospecimens will be shared with researchers proposing scientifically sound PSC-focused research with approval of the appropriate review boards.

Discussion
Patient-based studies leveraging the latest technologies for targeted and wide-scale interrogation of multiple omics layers offer promise to accelerate PSC research through discovery of unappreciated aspects of disease pathogenesis. However, the rarity of PSC severely limits such studies. Here we describe our effort to overcome this limitation, the PSC-SCR, a repository of patient biospecimens coupled with clinical and omics data for use by the broader PSC research community.
Effect of virtual reality exercises on balance and fall in elderly people with fall risk: a randomized controlled trial
Authors: Zahedian-Nasab Noorolla , Jaberi Azita , Shirazi Fatemeh , Kavousipor Somayyeh 
Published: September 2021

Abstract
Background
Deficient balance and fear of falling in elderly people can lead to disturbed daily activities, falling, and finally reduced quality of life. Therefore, evaluation of low-risk methods that might partially improve balance in this group of people is of utmost importance. The present study aimed to investigate the impact of Virtual Reality (VR) exercises based on Xbox Kinect on balance and fear of falling among elderly people.

Methods
This clinical trial was performed on 60 elderly individuals living in nursing homes divided into two groups of control and Xbox. The participants in the intervention group received VR exercises based on Xbox Kinect in form of two 30–45-min sessions held on a weekly basis for 6 weeks. The individuals in the control group, on the other hand, received routine exercises of the nursing homes. The research tools used in this study included a demographic questionnaire, the Berg Balance Scale (BBS), the Timed Up and Go (TUG) test, and the Falling Efficacy Scale (FES).

Results
The findings of the current study demonstrated that the scores of BBS and TUG test as the indices of balance among elderly people improved significantly in the Xbox group after the intervention (p < 0.001 for both BBS and TUG test). Moreover, the score of fear of falling diminished significantly in the intervention group compared to the control group (p < 0.001).

Conclusion
According to the results of the present investigation, 6 weeks of VR balance exercises could enhance balance and fear of falling among elderly people living in nursing homes.

Trial registration
Code:IRCT20190727044347N1, Date: 17-8-2019.
Expectations and behaviour of older adults with neurological disorders regarding general practitioner consultations: an observational study
Authors: Schönenberg Aline , Teschner Ulrike , Prell Tino 
Published: September 2021

Abstract
Background
Patients’ relationship with their GPs is linked to adherence, patient behaviour and satisfaction with healthcare. Several factors pertaining to this relationship have already been identified, however expectations and preferences vary depending on age and diagnosis. Chronically ill elderly patients constitute a group of patients with specific needs that are not yet understood.

Methods
For this observational study, 100 (44 female, mean age 72.72 + − 8.28 years) patients were interviewed. Multiple linear or binary logistic regression as well as analysis of variance was used to understand the link between factors pertaining to GP relationship and patient behaviour, and principal component analysis was performed to understand the underlying structure of patients’ needs.

Results
Patients attribute high importance to their GP’s opinion of them. On average, what the GP thinks about the patients is almost as important as what their partners think. Patients primarily want to be perceived as engaged, friendly and respected individuals, and it is important for patients to be liked by their GP. This importance is linked to active preparation; 65% of the patients prepared actively for GP consultations. Expectations regarding GP consultations can be split into two components: a medical aspect with a subfactor concerning emotional support, and a social component. Prominent factors influencing the relationship are the possibility to talk about emotions and mental well-being, trust, and GP competency. Satisfaction and trust were mainly linked to medical competency. Being able to show emotions or talk about mental well-being enhances perceived GP competence, satisfaction, and active patient preparation. However, a focus on the social component such as frequent talking about private topics reduces both perceived GP competency as well as active patient preparation.

Conclusion
Older patients take GP consultations seriously, and their expectations regarding GP consultations focus on medical competence and care as well as empathetic listening and understanding. Older persons seek a deeper connection to their GPs and are willing to be active and cooperative. As the patient–GP relationship influences health outcomes, treatment of older patients should be adjusted to enable this active participation.