bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered static and dynamic functional network connectivity in post-traumatic headache
Authors: Li Fengfang , Lu Liyan , Shang Song’an , Chen Huiyou , Wang Peng , Muthaiah Vijaya Prakash , Yin Xindao , Chen Yu-Chen 
Published: November 2021

Abstract
Background
Post-traumatic headache (PTH) is a very common symptom following mild traumatic brain injury (mTBI), yet much remains unknown about the underlying pathophysiological mechanisms of PTH. Neuroimaging studies suggest that aberrant functional network connectivity (FNC) may be an important factor in pain disorders. The present study aimed to investigate the functional characteristics of static FNC (sFNC) and dynamic FNC (dFNC) in mTBI patients with PTH.

Methods
With Institutional Review Board (IRB) approval, we prospectively recruited 50 mTBI patients with PTH, who were diagnosed with ICHD-3 beta diagnostic criteria and 39 mTBI without PTH who were well matched for age, gender and education. Resting-state functional magnetic resonance imaging (fMRI) scanning (3.0 T, Philips Medical Systems, Netherlands), Montreal Cognitive Assessment (MoCA) and headache symptom measurement (headache frequency and headache intensity) were performed. The resting-state fMRI sequence took 8 min and 10 s. Independent component analysis and sliding window method were applied to examine the FNC on the basis of nine resting-state networks, namely, default mode network (DMN), sensorimotor network (SMN), executive control network (ECN), auditory network (AuN), attention network (AN), salience network (SN), visual network (VN), and cerebellum network (CN). The differences in sFNC and dFNC were determined and correlated with clinical variables using Pearson rank correlation.

Results
For sFNC, compared with mTBI patients without PTH, mTB with PTH group showed four altered interactions, including decreased interactions in SN-SMN and VN-DMN pairs, increased sFNC in SN-ECN and SMN-DMN pairs. For dFNC, significant group differences were found in State 2, including increased connectivity alteration in the DMN with CN, DMN with SMN, and AuN with CN. Significant reduced connectivity changes in the DMN with VN was found in State 4. Furthermore, the number of transitions (r=0.394, p=0.005) between states was positively associated with headache frequency. Additionally, dwell time (r=-0.320, p=0.025) in State 1 was negatively correlated with MoCA score.

Conclusions
MTBI patients with PTH are characterized with altered sFNC and dFNC, which could provide new perspective to understand the neuropathological mechanism underlying the PTH to determine more appropriate management, and may be a useful imaging biomarker for identifying and predicting mTBI with PTH.
cosinoRmixedeffects: an R package for mixed-effects cosinor models
Authors: Hou Ruixue , Tomalin Lewis E. , Suárez-Fariñas Mayte 
Published: November 2021

Abstract
Background
Wearable devices enable monitoring and measurement of physiological parameters over a 24-h period, and some of which exhibit circadian rhythm characteristics. However, the currently available R package cosinor could only analyze daily cross-sectional data and compare the parameters between groups with two levels. To evaluate longitudinal changes in the circadian patterns, we need to extend the model to a mixed-effect model framework, allowing for random effects and interaction between COSINOR parameters and time-varying covariates.

Results
We developed the cosinoRmixedeffects R package for modelling longitudinal periodic data using mixed-effects cosinor models. The model allows for covariates and interactions with the non-linear parameters MESOR, amplitude, and acrophase. To facilitate ease of use, the package utilizes the syntax and functions of the widely used emmeans package to obtain estimated marginal means and contrasts. Estimation and hypothesis testing involving the non-linear circadian parameters are carried out using bootstrapping. We illustrate the package functionality by modelling daily measurements of heart rate variability (HRV) collected among health care workers over several months. Differences in circadian patterns of HRV between genders, BMI, and during infection with SARS-CoV2 are evaluated to illustrate how to perform hypothesis testing.

Conclusion
cosinoRmixedeffects package provides the model fitting, estimation and hypothesis testing for the mixed-effects COSINOR model, for the linear and non-linear circadian parameters MESOR, amplitude and acrophase. The model accommodates factors with any number of categories, as well as complex interactions with circadian parameters and categorical factors.
Whole-transcriptome sequencing reveals a vernalization-related ceRNA regulatory network in chinese cabbage (Brassica campestris L. ssp. pekinensis)
Authors: Shi Fengyan , Xu Hezi , Liu Chuanhong , Tan Chong , Ren Jie , Ye Xueling , Feng Hui , Liu Zhiyong 
Published: November 2021

Abstract
Background
The transition from vegetative growth to reproductive growth involves various pathways. Vernalization is a crucial process for floral organ formation and regulation of flowering time that is widely utilized in plant breeding. In this study, we aimed to identify the global landscape of mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) related to vernalization in Chinese cabbage. These data were then used to construct a competitive endogenous RNA (ceRNA) network that provides valuable information to better understand the vernalization response.

Results
In this study, seeds sampled from the Chinese cabbage doubled haploid (DH) line ‘FT’ with or without vernalization treatment were used for whole-transcriptome sequencing. A total of 2702 differentially expressed (DE) mRNAs, 151 DE lncRNAs, 16 DE circRNAs, and 233 DE miRNAs were identified in the vernalization-treated seeds. Various transcription factors, such as WRKY, MYB, NAC, bHLH, MADS-box, zinc finger protein CONSTANS-like gene, and B3 domain protein, and regulatory proteins that play important roles in the vernalization pathway were identified. Additionally, we constructed a vernalization-related ceRNA–miRNA–target gene network and obtained 199 pairs of ceRNA relationships, including 108 DEmiRNA‒DEmRNA, 67 DEmiRNA‒DElncRNA, and 12 DEmiRNA‒DEcircRNA interactions, in Chinese cabbage. Furthermore, several important vernalization-related genes and their interacting lncRNAs, circRNAs, and miRNAs, which are involved in the regulation of flowering time, floral organ formation, bolting, and flowering, were identified.

Conclusions
Our results reveal the potential mRNA and non-coding RNAs involved in vernalization, providing a foundation for further studies on the molecular mechanisms underlying vernalization in Chinese cabbage.
Whole genome sequencing facilitates intragenic variant interpretation following modifier screening in C. elegans
Authors: Jean Francesca , Stasiuk Susan , Maroilley Tatiana , Diao Catherine , Galbraith Andrew , Tarailo-Graovac Maja 
Published: November 2021

Abstract
Background
Intragenic modifiers (in-phase, second-site variants) are known to have dramatic effects on clinical outcomes, affecting disease attributes such as severity or age of onset. However, despite their clinical importance, the focus of many genetic screens in model systems is on the discovery of extragenic variants, with many labs still relying upon more traditional methods to identify modifiers. However, traditional methods such as PCR and Sanger sequencing can be time-intensive and do not permit a thorough understanding of the intragenic modifier effects in the context of non-isogenic genomic backgrounds.

Results
Here, we apply high throughput approaches to identify and understand intragenic modifiers using Caenorhabditis elegans. Specifically, we applied whole genome sequencing (WGS) to a mutagen-induced forward genetic screen to identify intragenic suppressors of a temperature-sensitive zyg-1(it25) allele in C. elegans. ZYG-1 is a polo kinase that is important for centriole function and cell divisions, and mutations that truncate its human orthologue, PLK4, have been associated with microcephaly. Combining WGS and CRISPR/Cas9, we rapidly identify intragenic modifiers, show that these variants are distributed non-randomly throughout zyg-1 and that genomic context plays an important role on phenotypic outcomes.

Conclusions
Ultimately, our work shows that WGS facilitates high-throughput identification of intragenic modifiers in clinically relevant genes by reducing hands-on research time and overall costs and by allowing thorough understanding of the intragenic phenotypic effects in the context of different genetic backgrounds.
Developmental regulation of lupulin gland-associated genes in aromatic and bitter hops (Humulus lupulus L.)
Authors: Patzak Josef , Henychová Alena , Matoušek Jaroslav 
Published: November 2021

Abstract
Background
Hop (Humulus lupulus L.) bitter acids are valuable metabolites for the brewing industry. They are biosynthesized and accumulate in glandular trichomes of the female inflorescence (hop cone). The content of alpha bitter acids, such as humulones, in hop cones can differentiate aromatic from bitter hop cultivars. These contents are subject to genetic and environmental control but significantly correlate with the number and size of glandular trichomes (lupulin glands).

Results
We evaluated the expression levels of 37 genes involved in bitter acid biosynthesis and morphological and developmental differentiation of glandular trichomes to identify key regulatory factors involved in bitter acid content differences. For bitter acid biosynthesis genes, upregulation of humulone synthase genes, which are important for the biosynthesis of alpha bitter acids in lupulin glands, could explain the higher accumulation of alpha bitter acids in bitter hops. Several transcription factors, including HlETC1, HlMYB61 and HlMYB5 from the MYB family, as well as HlGLABRA2, HlCYCB2–4, HlZFP8 and HlYABBY1, were also more highly expressed in the bitter hop cultivars; therefore, these factors may be important for the higher density of lupulin glands also seen in the bitter hop cultivars.

Conclusions
Gene expression analyses enabled us to investigate the differences between aromatic and bitter hops. This study confirmed that the bitter acid content in glandular trichomes (lupulin glands) is dependent on the last step of alpha bitter acid biosynthesis and glandular trichome density.
Adding a low-concentration sciatic nerve block to total knee arthroplasty in patients susceptible to the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs): a randomized controlled trial
Authors: Sirivanasandha Busara , Sutthivaiyakit Kulwadee , Kerdchan Thippatai , Poolsuppasit Suppachai , Tangwiwat Suwimon , Halilamien Pathom 
Published: November 2021

Abstract
Background
This study compared the effects of adductor canal blocks with those of a low concentration of popliteal-sciatic nerve block (SNB) and dexamethasone as an adjunctive technique for total knee arthroplasties (TKA) in patients susceptible to the adverse effects of NSAIDs.

Methods
A prospective, double-blinded, randomized controlled trial was performed in 50 patients susceptible to the adverse effects of NSAIDs undergoing unilateral TKAs. All patients received spinal anesthesia, adductor canal blocks, and periarticular infiltration. The 25 patients in the intervention group received SNB (0.125% bupivacaine [20 ml] and dexamethasone [5 mg]).

Results
The SNB group significantly had lower median resting pain scores at 6, 12, and 18 h: the control group, 1 (0–4.5), 3 (0–5), and 3 (2–5); the intervention group, 0 (0–0), 0 (0–3), and 1 (0–3); p-values, 0.012, 0.021, and 0.010, respectively. Movement-evoked pain scores at 6, 12, and 18 h were also lower: control group, 3 (0–5.5), 5 (2.5–6.5), and 7 (4–9); intervention group, 0 (0–1.5), 2 (0–4), and 3 (2–5); p-values, 0.019, 0.005, and 0.001, respectively. There were no differences in motor function. Moreover, the mean morphine consumption 24 h was also reduced in the SNB group: control group, 3.80 ± 2.48 mg; intervention group, 1.96 ± 2 mg; p-value, 0.005.

Conclusion
For patients susceptible to the adverse effects of NSAIDs, a low concentration of SNB and dexamethasone is an effective adjunctive technique for early postoperative pain control (especially on movement) following TKAs, without an increase in motor weakness.

Trial registration
ClinicalTrials.gov, NCT03486548, Registered 3 April 2018.
High-protein intake and early exercise in adult intensive care patients: a prospective, randomized controlled trial to evaluate the impact on functional outcomes
Authors: de Azevedo José Raimundo Araujo , Lima Hugo César Martins , Frota Pedro Henrique Dias Brasiliense , Nogueira Ivna Raquel Olimpio Moreira , de Souza Suellen Christine , Fernandes Erika Arana Arraes , Cruz Adlyene Muniz 
Published: November 2021

Abstract
Background
We evaluated the efficacy of high protein intake and early exercise versus standard nutrition care and routine physiotherapy on the outcome of critically ill patients.

Methods
We randomized mechanically ventilated patients expected to stay in the intensive care unit (ICU) for 4 days. We used indirect calorimetry to determine energy expenditure and guide caloric provision to the patients randomized to the high protein and early exercise (HPE) group and the control group. Protein intakes were 1.48 g/kg/day and 1.19 g/kg/day medians respectively; while the former was submitted to two daily sessions of cycle ergometry exercise, the latter received routine physiotherapy. We evaluated the primary outcome physical component summary (PCS) score at 3 and 6 months) and the secondary outcomes (handgrip strength at ICU discharge and ICU and hospital mortality).

Results
We analyzed 181 patients in the HPE (87) and control (94) group. There was no significant difference between groups in relation to calories received. However, the amount of protein received by the HPE group was significantly higher than that received by the control group (p < 0.0001). The PCS score was significantly higher in the HPE group at 3 months (p = 0.01) and 6 months (p = 0.01). The mortality was expressively higher in the control group. We found an independent association between age and 3-month PCS and that between age and group and 6-month PCS.

Conclusion
This study showed that a high-protein intake and resistance exercise improved the physical quality of life and survival of critically ill patients.

Trial registration
Research Ethics Committee of Hospital São Domingos: Approval number 1.487.683, April 09, 2018. The study protocol was registered in ClinicalTrials.gov (NCT03469882, March 19,2018).
Value of addition of coronary artery calcium to risk scores in the prediction of major cardiovascular events in patients with type 2 diabetes
Authors: Zafrir Barak , Saliba Walid , Widder Rachel Shay Li , Khoury Razi , Shemesh Elad , Halon David A. 
Published: November 2021

Abstract
Background
The increased risk for cardiovascular events in diabetics is heterogeneous and contemporary clinical risk score calculators have limited predictive value. We therefore examined the additional value of coronary artery calcium score (CACS) in outcome prediction in type 2 diabetics without clinical coronary artery disease (CAD).

Methods
The study examined a population-based cohort of type 2 diabetics (n = 735) aged 55–74 years, recruited between 2006 and 2008. Patients had at least one additional risk factor and no history or symptoms of CAD. Risk assessment tools included Pooled Cohort Equations (PCE) and Multi-Ethnic Study of Atherosclerosis (MESA) 10-year risk score calculators and CACS. The occurrence of myocardial infarction (MI), stroke or cardiovascular death (MACE) was assessed over 10-years.

Results
Risk score calculators predicted MACE and MI and cardiovascular death individually but not stroke. Increasing levels of CACS predicted MACE and its components independently of clinical risk scores, glycated hemoglobin and other baseline variables: hazard ratio (95% confidence interval) 2.92 (1.06–7.86), 6.53 (2.47–17.29) and 8.3 (3.28–21) for CACS of 1–100, 101–300 and > 300 Agatston units respectively, compared to CACS = 0. Addition of CACS to PCE improved discrimination of MACE [AUC of PCE 0.615 (0.555–0.676) versus PCE + CACS 0.696 (0.642–0.749); p = 0.0024]. Coronary artery calcium was absent in 24% of the study population and was associated with very low event rates even in those with high estimated risk scores.

Conclusions
CACS in asymptomatic type 2 diabetics provides additional prognostic information beyond that obtained from clinical risk scores alone leading to better discrimination between risk categories.
Does the time of the day affect multiple trauma care in hospitals? A retrospective analysis of data from the TraumaRegister DGU®
Authors: Fitschen-Oestern Stefanie , Lippross Sebastian , Lefering Rolf , Klüter Tim , Weuster Matthias , Franke Georg Maximilian , Kirsten Nora , Müller Michael , Schröder Ove , Seekamp Andreas ,   TraumaRegister DGU
Published: November 2021

Abstract
Background
Optimal multiple trauma care should be continuously provided during the day and night. Several studies have demonstrated worse outcomes and higher mortality in patients admitted at night. This study involved the analysis of a population of multiple trauma patients admitted at night and a comparison of various indicators of the quality of care at different admission times.

Methods
Data from 58,939 multiple trauma patients from 2007 to 2017 were analyzed retrospectively. All data were obtained from TraumaRegister DGU®. Patients were grouped by the time of their admission to the trauma center (6.00 am–11.59 am (morning), 12.00 pm–5.59 pm (afternoon), 6.00 pm–11.59 pm (evening), 0.00 am–5.59 am (night)). Incidences, patient demographics, injury patterns, trauma center levels and trauma care times and outcomes were evaluated.

Results
Fewer patients were admitted during the night (6.00 pm–11.59 pm: 18.8% of the patients, 0.00–5.59 am: 4.6% of the patients) than during the day. Patients who arrived between 0.00 am–5.59 am were younger (49.4 ± 22.8 years) and had a higher injury severity score (ISS) (21.4 ± 11.5) and lower Glasgow Coma Scale (GCS) score (11.6 ± 4.4) than those admitted during the day (12.00 pm–05.59 pm; age: 55.3 ± 21.6 years, ISS: 20.6 ± 11.4, GCS: 12.6 ± 4.0). Time in the trauma department and time to an emergency operation were only marginally different. Time to imaging was slightly prolonged during the night (0.00 am–5.59 am: X-ray 16.2 ± 19.8 min; CT scan 24.3 ± 18.1 min versus 12.00 pm- 5.59 pm: X-ray 15.4 ± 19.7 min; CT scan 22.5 ± 17.8 min), but the delay did not affect the outcome. The outcome was also not affected by level of the trauma center. There was no relevant difference in the Revised Injury Severity Classification II (RISC II) score or mortality rate between patients admitted during the day and at night. There were no differences in RISC II scores or mortality rates according to time period. Admission at night was not a predictor of a higher mortality rate.

Conclusion
The patient population and injury severity vary between the day and night with regard to age, injury pattern and trauma mechanism. Despite the differences in these factors, arrival at night did not have a negative effect on the outcome.
Qualitative development and content validation of the “SPART” model; a focused ethnography study of observable diagnostic and therapeutic activities in the emergency medical services care process
Authors: Dercksen Bert , Struys Michel M. R. F. , Cnossen Fokie , Paans Wolter 
Published: November 2021

Abstract
Background
Clinical reasoning is a crucial task within the Emergency Medical Services (EMS) care process. Both contextual and cognitive factors make the task susceptible to errors. Understanding the EMS care process’ structure could help identify and address issues that interfere with clinical reasoning. The EMS care process is complex and only basically described.
In this research, we aimed to define the different phases of the process and develop an overarching model that can help detect and correct potential error sources, improve clinical reasoning and optimize patient care.

Methods
We conducted a focused ethnography study utilizing non-participant video observations of real-life EMS deployments combined with thematic analysis of peer interviews.
After an initial qualitative analysis of 7 video observations, we formulated a tentative conceptual model of the EMS care process. To test and refine this model, we carried out a qualitative, thematic analysis of 28 video-recorded cases. We validated the resulting model by evaluating its recognizability with a peer content analysis utilizing semi-structured interviews.

Results
Based on real-life observations, we were able to define and validate a model covering the distinct phases of an EMS deployment. We have introduced the acronym “SPART” to describe ten different phases: Start, Situation, Prologue, Presentation, Anamnesis, Assessment, Reasoning, Resolution, Treatment, and Transfer.

Conclusions
The “SPART” model describes the EMS care process and helps to understand it. We expect it to facilitate identifying and addressing factors that influence both the care process and the clinical reasoning task embedded in this process.
A simulation study for evaluating the performance of clustering measures in multilevel logistic regression
Authors: Adam Nicholas Siame , Twabi Halima S. , Manda Samuel O.M. 
Published: November 2021

Abstract
Background
Multilevel logistic regression models are widely used in health sciences research to account for clustering in multilevel data when estimating effects on subject binary outcomes of individual-level and cluster-level covariates. Several measures for quantifying between-cluster heterogeneity have been proposed. This study compared the performance of between-cluster variance based heterogeneity measures (the Intra-class Correlation Coefficient (ICC) and the Median Odds Ratio (MOR)), and cluster-level covariate based heterogeneity measures (the 80% Interval Odds Ratio (IOR-80) and the Sorting Out Index (SOI)).

Methods
We used several simulation datasets of a two-level logistic regression model to assess the performance of the four clustering measures for a multilevel logistic regression model. We also empirically compared the four measures of cluster variation with an analysis of childhood anemia to investigate the importance of unexplained heterogeneity between communities and community geographic type (rural vs urban) effect in Malawi.

Results
Our findings showed that the estimates of SOI and ICC were generally unbiased with at least 10 clusters and a cluster size of at least 20. On the other hand, estimates of MOR and IOR-80 were less accurate with 50 or fewer clusters regardless of the cluster size. The performance of the four clustering measures improved with increased clusters and cluster size at all cluster variances. In the analysis of childhood anemia, the estimate of the between-community variance was 0.455, and the effect of community geographic type (rural vs urban) had an odds ratio (OR)=1.21 (95% CI: 0.97, 1.52). The resulting estimates of ICC, MOR, IOR-80 and SOI were 0.122 (indicative of low homogeneity of childhood anemia in the same community); 1.898 (indicative of large unexplained heterogeneity); 0.345-3.978 and 56.7% (implying that the between community heterogeneity was more significant in explaining the variations in childhood anemia than the estimated effect of community geographic type (rural vs urban)), respectively.

Conclusion
At least 300 clusters with sizes of at least 50 would be adequate to estimate the strength of clustering in multilevel logistic regression with negligible bias. We recommend using the SOI to assess unexplained heterogeneity between clusters when the interest also involves the effect of cluster-level covariates, otherwise, the usual intra-cluster correlation coefficient would suffice in multilevel logistic regression analyses.