bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of model complexity and size on metabolic flux distribution and control: case study in Escherichia coli
Authors: Hameri Tuure , Fengos Georgios , Hatzimanikatis Vassily 
Published: March 2021

Abstract
Background
Significant efforts have been made in building large-scale kinetic models of cellular metabolism in the past two decades. However, most kinetic models published to date, remain focused around central carbon pathways or are built around ad hoc reduced models without clear justification on their derivation and usage. Systematic algorithms exist for reducing genome-scale metabolic reconstructions to build thermodynamically feasible and consistently reduced stoichiometric models. However, it is important to study how network complexity affects conclusions derived from large-scale kinetic models built around consistently reduced models before we can apply them to study biological systems.

Results
We reduced the iJO1366 Escherichia Coli genome-scale metabolic reconstruction systematically to build three stoichiometric models of different size. Since the reduced models are expansions around the core subsystems for which the reduction was performed, the models are nested. We present a method for scaling up the flux profile and the concentration vector reference steady-states from the smallest model to the larger ones, whilst preserving maximum equivalency. Populations of kinetic models, preserving similarity in kinetic parameters, were built around the reference steady-states and their metabolic sensitivity coefficients (MSCs) were computed. The MSCs were sensitive to the model complexity. We proposed a metric for measuring the sensitivity of MSCs to these structural changes.

Conclusions
We proposed for the first time a workflow for scaling up the size of kinetic models while preserving equivalency between the kinetic models. Using this workflow, we demonstrate that model complexity in terms of networks size has significant impact on sensitivity characteristics of kinetic models. Therefore, it is essential to account for the effects of network complexity when constructing kinetic models. The presented metric for measuring MSC sensitivity to structural changes can guide modelers and experimentalists in improving model quality and guide synthetic biology and metabolic engineering. Our proposed workflow enables the testing of the suitability of a kinetic model for answering certain study-specific questions. We argue that the model-based metabolic design targets that are common across models of different size are of higher confidence, while those that are different could be the objective of investigations for model improvement.
Comparing low-pass sequencing and genotyping for trait mapping in pharmacogenetics
Authors: Wasik Kaja , Berisa Tomaz , Pickrell Joseph K. , Li Jeremiah H. , Fraser Dana J. , King Karen , Cox Charles 
Published: March 2021

AbstractBackgroundLow pass sequencing has been proposed as a cost-effective alternative to genotyping arrays to identify genetic variants that influence multifactorial traits in humans. For common diseases this typically has required both large sample sizes and comprehensive variant discovery. Genotyping arrays are also routinely used to perform pharmacogenetic (PGx) experiments where sample sizes are likely to be significantly smaller, but clinically relevant effect sizes likely to be larger.ResultsTo assess how low pass sequencing would compare to array based genotyping for PGx we compared a low-pass assay (in which 1x coverage or less of a target genome is sequenced) along with software for genotype imputation to standard approaches. We sequenced 79 individuals to 1x genome coverage and genotyped the same samples on the Affymetrix Axiom Biobank Precision Medicine Research Array (PMRA). We then down-sampled the sequencing data to 0.8x, 0.6x, and 0.4x coverage, and performed imputation. Both the genotype data and the sequencing data were further used to impute human leukocyte antigen (HLA) genotypes for all samples. We compared the sequencing data and the genotyping array data in terms of four metrics: overall concordance, concordance at single nucleotide polymorphisms in pharmacogenetics-related genes, concordance in imputed HLA genotypes, and imputation r2. Overall concordance between the two assays ranged from 98.2% (for 0.4x coverage sequencing) to 99.2% (for 1x coverage sequencing), with qualitatively similar numbers for the subsets of variants most important in pharmacogenetics. At common single nucleotide polymorphisms (SNPs), the mean imputation r2from the genotyping array was 0.90, which was comparable to the imputation r2from 0.4x coverage sequencing, while the mean imputation r2from 1x sequencing data was 0.96.ConclusionsThese results indicate that low-pass sequencing to a depth above 0.4x coverage attains higher power for association studies when compared to the PMRA and should be considered as a competitive alternative to genotyping arrays for trait mapping in pharmacogenetics.
The myxozoan minicollagen gene repertoire was not simplified by the parasitic lifestyle: computational identification of a novel myxozoan minicollagen gene
Authors: Kyslík Jiří , Kosakyan Anush , Nenarokov Serafim , Holzer Astrid S. , Fiala Ivan 
Published: March 2021

AbstractBackgroundLineage-specific gene expansions represent one of the driving forces in the evolutionary dynamics of unique phylum traits. Myxozoa, a cnidarian subphylum of obligate parasites, are evolutionarily altered and highly reduced organisms with a simple body plan including cnidarian-specific organelles and polar capsules (a type of nematocyst). Minicollagens, a group of structural proteins, are prominent constituents of nematocysts linking Myxozoa and Cnidaria. Despite recent advances in the identification of minicollagens in Myxozoa, the evolutionary history and diversity of minicollagens in Myxozoa and Cnidaria remain elusive.ResultsWe generated new transcriptomes of two myxozoan species using a novel pipeline for filtering of closely related contaminant species in RNA-seq data. Mining of our transcriptomes and published omics data confirmed the existence of myxozoan Ncol-4, reported only once previously, and revealed a novel noncanonical minicollagen, Ncol-5, which is exclusive to Myxozoa. Phylogenetic analyses support a close relationship between myxozoan Ncol-1–3 with minicollagens ofPolypodium hydriforme, but suggest independent evolution in the case of the myxozoan minicollagens Ncol-4 and Ncol-5. Additional genome- and transcriptome-wide searches of cnidarian minicollagens expanded the dataset to better clarify the evolutionary trajectories of minicollagen.ConclusionsThe development of a new approach for the handling of next-generation data contaminated by closely related species represents a useful tool for future applications beyond the field of myxozoan research. This data processing pipeline allowed us to expand the dataset and study the evolution and diversity of minicollagen genes in Myxozoa and Cnidaria. We identified a novel type of minicollagen in Myxozoa (Ncol-5). We suggest that the large number of minicollagen paralogs in some cnidarians is a result of several recent large gene multiplication events. We revealed close juxtaposition of minicollagens Ncol-1 and Ncol-4 in myxozoan genomes, suggesting their common evolutionary history. The unique gene structure of myxozoan Ncol-5 suggests a specific function in the myxozoan polar capsule or tubule. Despite the fact that myxozoans possess only one type of nematocyst, their gene repertoire is similar to those of other cnidarians.
Linking exogenous foliar application of glycine betaine and stomatal characteristics with salinity stress tolerance in cotton (Gossypium hirsutum L.) seedlings
Authors: Hamani Abdoul Kader Mounkaila , Li Shuang , Chen Jinsai , Amin Abubakar Sunusi , Wang Guangshuai , Xiaojun Shen , Zain Muhammad , Gao Yang 
Published: March 2021

Abstract
Background
Glycine betaine (GB) plays a crucial role in plants responding to abiotic stresses. Studying the physiological response of cotton seedlings to exogenous GB under salt stress provides a reference for the application of GB to improve the resistance of cotton seedlings under salt stress. The purpose of this research is to examine the impacts of foliar-applied GB on leaf stomatal structure and characteristics, gas exchange and chlorophyll fluorescence characteristics and plant growth indicators of Gossypium hirsutum L. under NaCl stress conditions.

Results
Under the salinity of 150 mM, the four concentrations of GB are 0, 2.5, 5, and 7.5 mM, and the control (CK) was GB-untreated non-saline. Salt stress negatively affected leaf stomata as well as gas exchange and chlorophyll fluorescence and decreased plant growth parameters of cotton seedlings. The treatment with 5 mM GB significantly increased the evolution of photosynthetic rate (Pn), transpiration rate (Tr), intracellular CO2 concentration (Ci) and stomatal conductance (gs) compared to the GB-untreated saline treatment. The Exogenous foliar-applied GB has sustainably decreased the carboxylation efficiency (Pn/Ci) and water use efficiency (WUE). The concentration of 5 mM GB leads to a significant improvement of leaf stomatal characteristics. The leaf gas exchange attributes correlated positively with stomatal density (SD), stomatal length (SL) and stomatal with (SW).

Conclusion
The overall results suggested that exogenous foliar supplementation with GB can effectively alleviate the damage of salt stress to cotton seedlings. The effect of applying 5 mM GB could be an optional choice for protecting cotton seedlings from NaCl stress through promoting the stomatal functions, photosynthetic activities and growth characteristics.
Moderately prolonged dry intervals between precipitation events promote production in Leymus chinensis in a semi-arid grassland of Northeast China
Authors: Zhang Jinwei , Shen Xiangjin , Mu Bifan , Shi Yujie , Yang Yuheng , Wu Xuefeng , Mu Chunsheng , Wang Junfeng 
Published: March 2021

Abstract
Background
Climate change is predicted to lead to changes in the amount and distribution of precipitation during the growing seasonal. This “repackaging” of rainfall could be particularly important for grassland productivity. Here, we designed a two-factor full factorial experiment (three levels of precipitation amount and six levels of dry intervals) to investigate the effect of precipitation patterns on biomass production in Leymus chinensis (Trin.) Tzvel. (a dominant species in the Eastern Eurasian Steppe).

Results
Our results showed that increased amounts of rainfall with prolonged dry intervals promoted biomass production in L. chinensis by increasing soil moisture, except for the longest dry interval (21 days). However, prolonged dry intervals with increased amount of precipitation per event decreased the available soil nitrogen content, especially the soil NO3−-N content. For small with more frequent rainfall events pattern, L. chinensis biomass decreased due to smaller plant size (plant height) and fewer ramets. Under large quantities of rain falling during a few events, the reduction in biomass was not only affected by decreasing plant individual size and lower ramet number but also by withering of aboveground parts, which resulted from both lower soil water content and lower NO3−-N content.

Conclusion
Our study suggests that prolonged dry intervals between rainfall combined with large precipitation events will dramatically change grassland productivity in the future. For certain combinations of prolonged dry intervals and increased amounts of intervening rainfall, semi-arid grassland productivity may improve. However, this rainfall pattern may accelerate the loss of available soil nitrogen. Under extremely prolonged dry intervals, the periods between precipitation events exceeded the soil moisture recharge interval, the available soil moisture became fully depleted, and plant growth ceased. This implies that changes in the seasonal distribution of rainfall due to climate change could have a major impact on grassland productivity.
Whipple's disease: the great masquerader—a high level of suspicion is the key to diagnosis
Authors: Melas Nikolaos , Amin Rasjan , Gyllemark Paula , Younes Amil Haji , Almer Sven 
Published: March 2021

Abstract
Background
Whipple's disease is a chronic infectious disease that primarily affects the small intestine, but several organs can simultaneously be involved. The disease is caused by a gram-positive bacterium called Tropheryma whipplei. The disease is difficult to suspect because it is rare with unspecific and long-term symptoms; it can be lethal if not properly treated.

Case presentation
We here present three patients who presented with a plethora of symptoms, mainly long-standing seronegative arthritis and gastrointestinal symptoms in the form of diarrhea with blood, weight loss, fever, and lymphadenopathy. They were after extensive investigations diagnosed with Whipple's disease, in two of them as long as 8 years after the first occurrence of joint manifestations. The diagnosis was made by PCR targeting the T. whipplei 16S rRNA gene from small bowel specimen in all three patients, and, besides from histopathologic findings from the duodenum and distal ileum in one and mesenteric lymph nodes in another patient.

Conclusions
This report aims to raise awareness of a very rare disease that presents with a combination of symptoms mimicking other and significantly more common diseases.
Expression of Cyr61 is associated with clinical course in patients with Crohn’s disease
Authors: Lee Su-Mi , Lee Kyung-Hwa , Park Seon-Young , Kim Dong Hyun , Chung Jin Ook , Ju Jae Kyun , Lee Jae-Hyuk , Kim Hyun Soo 
Published: March 2021

Abstract
Backgrounds
Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD).

Methods
Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients.

Results
The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P < 0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P = 0.01). Cyr61 mRNA levels in inflamed mucosa were twofold higher than those in non-inflamed lesion (P > 0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P < 0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend = 0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95% CI 0.20–0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P = 0.03).

Conclusions
Cyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.
Interventions for improving self-direction in people with dementia: a systematic review
Authors: Döpp Carola M. E. , Drenth Hermijntje , Verkade Paul-Jeroen , Francke Anneke F. , van der Heide Iris 
Published: March 2021

Abstract
Background
Dementia is a progressive disease that affects people’s everyday functioning, including the ability to express values, needs and wishes, which can be considered key elements of self-direction.
For the purpose of this review, self-direction refers to the organization and/or coordination of your own life, including professional and other care, with the objective of having what you perceive to be a good life. The aim of this systematic review was to assess and describe interventions that aim to improve self-direction of people with dementia.

Methods
A systematic search was conducted in PubMed, Embase, CINAHL, PsycInfo and the Cochrane Library. Empirical studies up to April 2020 were included that used qualitative and/or quantitative methods and reported on interventions for people with dementia aimed at improving self-direction. Stepwise study selection and the assessment of methodological quality were conducted independently by two authors. Data on study and intervention characteristics, outcomes related to self-direction and well-being of people with dementia and factors influencing the feasibility were extracted systematically and described narratively.

Results
Ten studies were identified describing a total of nine interventions. Interventions varied in terms of goals, content, target population and duration. Overall, interventions consisted of multiple components focusing on identifying “Who am I?” (beliefs, strengths, values, goals), identifying “What is important to me?” (meaningful activities and goal setting) and/or communicating about preferences with professionals and/or caregivers. The review provides indications that people with dementia may benefit from the interventions included. Overall, positive effects were found in studies on outcomes related to self-direction and wellbeing. However, outcomes measured using quantitative methods showed inconsistent effects between the studies.

Conclusions
Although the methodological quality of all the studies included was ‘good’ or at least ‘fair’, the evidence base of interventions aiming to improve self-direction is still limited due to the low number of studies, the low number of participants and the frequent use of and their authors’ own non-standardized measures. Nevertheless, the review points towards positive effects on self-direction and well-being. Identifying individual beliefs, strengths, values, goals and meaningful activities can be essential components of these interventions, as well as communication about the desired care and support.
The outcomes of a person-centered, non-pharmacological intervention in reducing agitation in residents with dementia in Australian rural nursing homes
Authors: Isaac Vivian , Kuot Abraham , Hamiduzzaman Mohammad , Strivens Edward , Greenhill Jennene 
Published: March 2021

Abstract
Background
There is limited best- practice evidence to address behavioral and psychiatric symptoms for those with dementia in Australian rural nursing homes. This study aims to evaluate the outcomes of a person-centered, non-pharmacological dementia care model, ‘Harmony in the Bush’, based on the Progressively Lowered Stress Threshold principles and person-centered music in rural Australia.

Methods
A quasi-experimental (nonrandomized, pre-post) intervention study was conducted in five rural nursing homes in Queensland and South Australia. Seventy-four residents with dementia participated in this intervention study, which yielded a sample power of 80%. Eighty-seven staff completed the Caregiver Stress Inventory at pre-post four-weeks of intervention. Staff training workshops focused on the theory of the Progressively Lowered Stress Threshold principles and delivery of person-centered care plan with integrated music intervention. We used reported changes in agitation of the residents, measured using Cohen- Mansfield Agitation Inventory, and staff’s caregiving stress, using Caregivers Stress Inventory. This study adheres to the CONSORT guidelines.

Results
Mean age of residents with dementia was 82.4 (7.7) years and 69% were females. The mean age of admission was 80.1(8.4) years. Baseline measures indicated that 32.7% had mild- severe pain and 30.5% reported mild-severe sadness. The results showed statistically significant decline in aggressive behaviors, physically non-aggressive behaviors, verbally agitated behavior and hiding and hoarding. There was similar reduction in staff stress in the domains of aggressive behaviors, inappropriate behaviors, resident safety, and resource deficiency.

Conclusions
The Harmony in the Bush model is effective in reducing agitation among dementia residents with significant reduction in staff stress levels in nursing homes in rural Australia.

Trial registration
Australian and New Zealand Clinical Trials Registry (ANZCTR) on 20/2/2018 (Registration No: ACTRN12618000263291p). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374458
Fluid requirement in adult dengue haemorrhagic fever patients during the critical phase of the illness: an observational study
Authors: Madanayake PMW , Jayawardena AEU , Wijekoon S L , Perera N , Wanigasuriya JKP 
Published: March 2021

AbstractBackgroundDengue fever prevalence is rising globally and it causes significant morbidity and mortality. Fluid extravasation during the critical phase of dengue haemorrhagic fever (DHF) leads to shock, multi-organ failure and death if not resuscitated appropriately with fluids. The mainstay of management is judicious fluid replacement using a guideline based, calculated fluid quota of maintenance (M) fluid plus 5% deficit (M +  5% deficit) to prevent organ hypoperfusion.MethodsWe conducted an observational follow-up study in Sri Lanka from January–July 2017 to identify the fluid requirements of DHF patients and to identify whether features of fluid overload are present in patients who exceeded the fluid quota. Patients who developed DHF following admission to the place of study, were recruited and the amount of fluid received during the critical phase was documented.ResultsA total of 115 DHF patients with a mean age of 30.3 (SD 12.2) years were recruited to the study. There were 65 (56.5%) males and the mean fluid requirement was 5279.7 ml (SD 735) over the 48 h. Majority of the study participants (n = 80, 69.6%) received fluid in excess of the recommended maintenance + 5% deficit and this group had higher body mass index (22.75 vs 20.76, p0.03) and a lower white cell count at the onset of the critical phase (3.22 × 103vs 4.78 × 103,p < 0.001). The highest fluid requirement was seen within the first 12 and 24 h of the critical phase in patients requiring fluid M +  5%–7.5% deficit and ≥ M +  7.5% deficit respectively. Patients exceeding M + 5% deficit had narrow pulse pressure and hypotension compared to the rest. DHF grades III and IV were seen exclusively in patients exceeding the fluid quota indicating higher amount of fluid was given for resuscitation. Fluid overload was detected in 14 (12.1%) patients and diuretic therapy was required in 6 (5.2%) patients.ConclusionsThe majority of patients received fluid in excess of the recommended quota and this group represents patients with narrow pulse pressure and hypotension. Although, fluid overload was infrequent in the study population, clinicians should be cautious when administering fluid in excess of M +  7.5% deficit.