bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation and demonstration of a pericarp disc system for studying blossom-end rot of tomatoes
Authors: Reitz Nicholas F. , Mitcham Elizabeth J. 
Published: March 2021

Abstract
Background
Blossom-end rot in tomatoes is often used as a model system to study fruit calcium deficiency. The study of blossom-end rot development in tomatoes has been greatly impeded by the difficulty of directly studying and applying treatments to the affected cells. This manuscript presents a novel method for studying blossom-end rot development after harvest in immature whole fruit and in pericarp discs.

Results
Pericarp discs removed from the bottom pericarp of immature healthy fruit developed blossom-end rot like symptoms, corresponding to a decrease in L* value and an increase in a* value. Symptoms also developed in columella tissue, but not in stem-end pericarp tissue, similar to patterns observed during blossom-end rot development on the plant. Ascorbate oxidase and peroxidase activity, which are elevated in blossom-end rot affected fruit compared to healthy fruit, were both correlated with colorimetric measures of tissue darkening in discs. Respiration rate was higher in discs that later developed blossom-end rot symptoms, with increased respiration in asymptomatic discs on day 1 of storage being associated with symptom development on day 2. Calcium chloride and ascorbic acid treatments inhibited symptom development, demonstrating the potential of this method to provide causal evidence.

Conclusions
Results indicate that symptom development in this system is consistent with blossom-end rot development with regards to location, color change, and the activity of key enzymes. This system has the potential to be used to elucidate the cause of fruit calcium deficiency and improve knowledge of the biological basis for calcium’s diverse effects on fruit.
Growth in ataxia telangiectasia
Authors: Natale Valerie A. I. , Cole Tim J. , Rothblum-Oviatt Cynthia , Wright Jennifer , Crawford Thomas O. , Lefton-Greif Maureen A. , McGrath-Morrow Sharon A. , Schlechter Haley , Lederman Howard M. 
Published: March 2021

AbstractBackgroundAtaxia telangiectasia (A-T) is a DNA repair disorder that affects multiple body systems. Neurological problems and immunodeficiency are two important features of this disease. At this time, two main severity groups are defined in A-T: classic (the more severe form) and mild. Poor growth is a common problem in classic A-T. An objective of this study was to develop growth references for classic A-T. Another objective was to compare growth patterns in classic A-T and mild A-T with each other and with the general population, using the CDC growth references. A final objective was to examine the effects of chronic infection on height.ResultsWe found that classic A-T patients were smaller overall, and suffered from height and weight faltering that continued throughout childhood and adolescence. When compared to the CDC growth references, the median heights and weights for both male and female patients eventually fell to or below the 3rd centile on the CDC charts. Height faltering was more pronounced in females. Birthweight was lower in the classic A-T group compared to mild A-T and the general population, whereas birth length was not. Finally, we investigated height and BMI faltering in relation to number of infections and found no association.ConclusionsClassic A-T appears to affect growth in utero. Although children appear to grow well in very early life, faltering begins early, and is unrelenting.
Reducing posttraumatic stress in parents of patients with a rare inherited metabolic disorder using eye movement desensitization and reprocessing therapy: a case study
Authors: Conijn Thirsa , Haverman Lotte , Wijburg Frits A. , De Roos Carlijn 
Published: March 2021

AbstractParents of children with severe inborn errors of metabolism frequently face stressful events related to the disease of their child and are consequently at high risk for developing parental posttraumatic stress disorder (PTSD). Assessment and subsequent treatment of PTSD in these parents is however not common in clinical practice. PTSD can be effectively treated by Eye Movement Desensitization and Reprocessing (EMDR), however no studies have been conducted yet regarding the effect of EMDR for parental PTSD. EMDR is generally offered in multiple weekly sessions which may preclude participation of parents as they are generally overburdened by the ongoing and often intensive care for their child. Therefore, we offered time-limited EMDR with a maximum of four sessions over two subsequent days to two parents of mucopolysaccharidosis type III (MPS III) patients to explore its potential effects. Both qualitative and quantitative outcomes were used to evaluate treatment effects. Both parents felt more resilient and competent to face future difficulties related to the disease of their child, and no adverse effects were reported. Quantitative outcomes showed a clinically significant decrease in post traumatic stress symptoms and comorbid psychological distress from pre- to post treatment, and these beneficial effects were maintained at follow-up. In conclusion, time-limited EMDR may be a highly relevant treatment for traumatized parents of children with MPS III, and probably also for parents of children with other rare progressive disorders. Further research is needed to validate the efficacy of EMDR in this specific population.
Impact of a diagnostic therapeutic educational pathway program for asthma management in preschool children
Authors: Guarnaccia Sebastiano , Quecchia Cristina , Festa Andrea , Magoni Michele , Zenoni Giuseppe , D’Agata Emanuele , Brivio Valentina , Zanardini Elena , Scarcella Carmelo , Gretter Valeria , Facchetti Susanna , Gasparotti Cinzia , Pluda Ada , Frassine Malica , Limina Rosa Maria , Spiazzi Raffaele , Badolato Raffaele , Bender Bruce , Donato Francesco 
Published: March 2021

Abstract
Background
Preschool children with clinically-diagnosed asthma have a higher rate of emergency department visits and consume more resources for management than older children. However, no clinical trials have yet been performed measuring the impact of a combined diagnostic, therapeutic and educational pathway regimen for evaluation of wheezing control in children aged less than 6 years.
The purpose of the present study was to assess the impact of a pediatric program developed in Italy, the Diagnostic Therapeutic Educational Pathway (DTEP), for asthma management in children less than 6 years old attending an asthma referral center.

Methods
This is a retrospective population-based cohort study performed in children with asthma aged 0–5 years, attending at “Io e l’Asma center”, Brescia, Italy between September 2007 and December 2014. The incidence rates (IRs) of hospitalization, emergency room visits, use of outpatient services and drug usage for dyspnea, wheezing, or respiratory symptoms were evaluated for time periods prior to and after DTEP intervention.

Results
A total of 741 patients, aged 0–5 years completed the DTEP, including 391 and 350 children aged 0–2 and 3–5 years, respectively. The percentage of children aged 0–2 and 3–5 years showing improved control of wheezing symptoms during the 1st to 3rd visit interval as a result of the DTEP intervention increased from 39.5 to 60.9% and from 25.5 to 75.5%, respectively. During these periods, the IRs showed a significant decrease for all outcomes, from-8.6% to − 80.4%. Although specific IRs for drug prescriptions declined, particularly for LABA plus corticosteroids, antibiotics, and systemic corticosteroids, they increased for SABA, inhaled corticosteroid and leukotriene receptor antagonist usage.

Conclusions
The results suggest that a real-world assessment of the integrated DTEP program for preschool children provides evidence for improved wheezing control and reduction of adverse therapeutic related outcomes.
gapseq: informed prediction of bacterial metabolic pathways and reconstruction of accurate metabolic models
Authors: Zimmermann Johannes , Kaleta Christoph , Waschina Silvio 
Published: March 2021

AbstractGenome-scale metabolic models of microorganisms are powerful frameworks to predict phenotypes from an organism’s genotype. While manual reconstructions are laborious, automated reconstructions often fail to recapitulate known metabolic processes. Here we present (https://github.com/jotech/gapseq), a new tool to predict metabolic pathways and automatically reconstruct microbial metabolic models using a curated reaction database and a novel gap-filling algorithm. On the basis of scientific literature and experimental data for 14,931 bacterial phenotypes, we demonstrate that gapseq outperforms state-of-the-art tools in predicting enzyme activity, carbon source utilisation, fermentation products, and metabolic interactions within microbial communities.
Personal protection with PBO-pyrethroid synergist-treated nets after 2 years of household use against pyrethroid-resistant Anopheles in Tanzania
Authors: Martin Jackline L. , Mosha Franklin W. , Lukole Eliud , Rowland Mark , Todd Jim , Charlwood Jacques D. , Mosha Jacklin F. , Protopopoff Natacha 
Published: March 2021

Abstract
Background
The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of the World Health Organization first-in-class PBO-Py LLIN (Olyset Plus) versus the standard LLIN (Olyset net) against pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) and An. funestus in North-West Tanzania after 20 months of household use.

Methods
From a household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected. The physical integrity and hole index (HI) of the nets were assessed, and resting mosquitoes were collected from inside nets and from room walls. The indoor abundance was estimated using CDC light traps and species identified using PCR. The bioefficacy of PBO and standard LLINs against wild Anopheles was assessed using 30-minute cylinder bioassays.

Results
Of 2397 Anopheles collected, 8.9% (n = 213) were resting inside standard Olyset nets, while none were found inside Olyset Plus nets (PBO-Py LLINs) of any HI category. Resting density of blood-fed mosquitoes was higher on walls of sleeping rooms with Olyset nets compared to Olyset Plus (0.62 vs 0.10, density ratio [DR]: 0.03, 95% CI 0.01–0.13, p < 0.001). Mosquitoes were found inside Olyset nets of all WHO HI categories, but more were collected inside the more damaged nets (HI ≥ 643) than in less damaged (HI 0–64) nets (DR: 6.4, 95% CI 1.1–36.0, p = 0.037). In bioassay, mortality of An. gambiae s.l. was higher with Olyset Plus than with Olyset nets for new nets (76.8% vs 27.5%) and nets used for 20 months (56.8% vs 12.8%); similar trends were observed with An. funestus.

Conclusion
The PBO-Py LLINs provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid-resistant An. gambiae sensu stricto (s.s.) and An. funestus collected from inside Olyset Plus nets, irrespective of HI category, as compared to Olyset nets.

Graphical Abstract
New mosquito repellency bioassay for evaluation of repellents and pyrethroids using an attractive blood-feeding device
Authors: Morimoto Yasue , Kawada Hitoshi , Kuramoto Kan-ya , Mitsuhashi Takuya , Saitoh Toshinobu , Minakawa Noboru 
Published: March 2021

Abstract
Background
With the increasing threat of the worldwide spread of mosquito-borne infectious diseases, consumer interest in anti-mosquito textiles that protect against mosquito bites is also increasing. Accordingly, repellent- or insecticide-treated textiles are gaining popularity. The standardization of commercial textile products is, therefore, indispensable for an authentic and objective evaluation of these products. Here we report a textile testing method using an artificial blood-feeding system that does not involve human volunteers or live animals, which aligns with the policy of protecting human and animal welfare.

Methods
The attractive blood-feeding device (ABFD) was designed using the Hemotek® membrane feeding system. The repellency of DEET, icaridin and permethrin was assayed using unfed female adults of Aedes albopictus (Skuse) under two different test conditions, namely choice and no-choice tests. The choice test consisted of two feeding units, one chemically treated and untreated, that were installed on the ABFD; mosquitoes attracted to and resting on the feeding units were counted and the overall blood-feeding rates recorded. The no-choice test consisted of two feeding units treated with the same chemical that were installed on the ABFD; mosquitoes attracted to and resting on the feeding units were counted and the blood-feeding rates were recorded. A control test was conducted using two feeding units, both sides of which were untreated.

Results
In the choice test, high repellency (> 95% inhibition of resting on the treated surface) of 1% DEET and 2% icaridin was observed, whereas 2% permethrin was not an effective repellent. Also, high blood-feeding inhibition (> 95%) was observed for 2% DEET and 2% icaridin. In the no-choice test, high repellency was observed for 1% DEET and 2% icaridin, whereas the repellency of 2% permethrin was low. Also, high blood-feeding inhibition was observed for 2% DEET, 4% icaridin and 2% permethrin.

Conclusions
The accuracy and reproducibility of the developed method demonstrate that the ABFD may be widely used for fundamental experiments in the field of mosquito physiology, for the development of new repellent chemicals and in evaluation studies of mosquito repellent products, such as anti-mosquito textiles. The further development of the membrane and feeding unit systems will enable a more practical evaluation of mosquito repellents and blood-feeding inhibitors, such as pyrethroids.

Graphical Abstract
Transcriptome-wide study of TNF-inhibitor therapy in rheumatoid arthritis reveals early signature of successful treatment
Authors: Oliver James , Nair Nisha , Orozco Gisela , Smith Samantha , Hyrich Kimme L. , Morgan Ann , Isaacs John , Wilson Anthony G. ,   BRAGGSS, Barton Anne , Plant Darren 
Published: March 2021

Abstract
Background
Despite the success of TNF-inhibitor therapy in rheumatoid arthritis treatment, up to 40% of patients fail to respond adequately. This study aimed to identify transcriptome-based biomarkers of adalimumab response in rheumatoid arthritis (RA) to aid timely switching in non-responder patients and provide a better mechanistic understanding of the pathways involved in response/non-response.

Methods
The Affymetrix Human Transcriptome Array 2.0 (HTA) was used to measure the transcriptome in whole blood at pre-treatment and at 3 months in EULAR good- and non-responders to adalimumab therapy. Differential expression of transcripts was analysed at the transcript level using multiple linear regression. Differentially expressed genes were validated in independent samples using OpenArray™ RT-qPCR.

Results
In total, 813 transcripts were differentially expressed between pre-treatment and 3 months in adalimumab good-responders. No significant differential expression was observed between good- and non-responders at either time-point and no significant changes were observed in non-responders between time-points. OpenArray™ RT-qPCR was performed for 104 differentially expressed transcripts in good-responders, selected based on magnitude of effect or p value or based on prior association with RA or the immune system, validating differential expression for 17 transcripts.

Conclusions
An early transcriptome signature of DAS28 response to adalimumab has been identified and replicated in independent datasets. Whilst treat-to-target approaches encourage early switching in non-responsive patients, registry evidence suggests that this does not always occur. The results herein could guide the development of a blood test to distinguish responders from non-responders at 3 months and support clinical decisions to switch non-responsive patients to an alternative therapy.
Integrating transcriptome-wide association study and mRNA expression profile identified candidate genes related to hand osteoarthritis
Authors: Xu Jiawen , Zeng Yi , Si Haibo , Liu Yuan , Li Mingyang , Zeng Junfeng , Shen Bin 
Published: March 2021

Abstract
Background
Osteoarthritis (OA) is a common skeletal system disease that has been partially attributed to genetic factors. The hand is frequently affected, which seriously affects the patient’s quality of life. However, the pathogenetic mechanism of hand osteoarthritis (hand OA) is still elusive.

Methods
A genome-wide association study (GWAS) summary of hand OA was obtained from the UK Biobank dataset, which contains data from a total of 452,264 White British individuals, including 37,782 OA patients. The transcriptome-wide association study (TWAS) of hand OA was performed using FUnctional Summary-based ImputatiON (FUSION) with the skeletal muscle and blood as gene expression references. The significant genes identified by TWAS were further subjected to gene set enrichment analysis (GSEA) with the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. Furthermore, we compared the genes and gene sets identified by our TWAS with that of a knee OA mRNA expression profile to detect the genes and gene sets shared by TWAS and mRNA expression profiles in OA. The mRNA expression profiles of 18 normal knee cartilages and 20 OA knee cartilages were acquired from the Gene Expression Omnibus database (accession number: GSE114007).

Results
TWAS identified 177 genes with P < 0.05 for the skeletal muscle, including ANKRD44 (P = 0.0001), RIC3 (P = 0.0003), and AC005154.6 (P = 0.0004). TWAS identified 423 genes with P < 0.05 for the blood, including CRIM1 (P = 0.0002), ZNF880 (P = 0.0002), and NCKIPSD (P = 0.0003). After comparing the results of the TWAS to those of the mRNA expression profiling of OA, we identified 5 common genes, including DHRS3 (log2fold = − 1.85, P = 3.31 × 10− 9) and SKP2 (log2fold = 1.36, P = 1.62 × 10− 8). GSEA of TWAS identified 51 gene ontology (GO) terms for hand OA, for example, protein binding (P = 0.0003) and cytosol (P = 0.0020). We also detected 6 common GO terms shared by TWAS and mRNA expression profiling, including protein binding (PTWAS = 2.54 × 10− 4, PmRNA = 3.42 × 10− 8), extracellular exosome (PTWAS = 0.02, PmRNA = 1.18 × 10− 4), and cytoplasm (PTWAS = 0.0183, PmRNA = 0.0048).

Conclusion
In this study, we identified 5 candidate genes and 6 GO terms related to hand OA, which may help to uncover the pathogenesis of hand OA. It should be noted that the possible difference in the gene expression profiles between hand OA and knee OA may affect our study results, which should be interpreted with caution.
Beneficial effect of omarigliptin on diabetic patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis
Authors: Hattori Sachiko , Nomoto Kazuomi , Suzuki Tomohiko , Hayashi Seishu 
Published: March 2021

Abstract
Background
Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis.

Method
We examined whether weekly DPP4 inhibitor omarigliptin (OMG) can improve liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Further, we investigated the effects of OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH).

Results
In NAFLD patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c or body mass index. In the NASH patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Slight but clear improvements in intrahepatic fat deposition and fibrosis appeared to be seen on diagnostic ultrasonography.

Conclusion
Weekly administration of the DPP4 inhibitor OMG in ameliorating hepatic insulin resistance may cause beneficial effects in liver with NAFLD/NASH.
Association between fasting insulin and C-reactive protein among adults without diabetes using a two-part model: NHANES 2005–2010
Authors: Missel Amanda L. , Saslow Laura R. , Griauzde Dina H. , Marvicsin Donna , Sen Ananda , Richardson Caroline R. , Liu Xuefeng 
Published: March 2021

Abstract
Introduction
Chronic inflammation is associated with the development, progression and long-term complications of type 2 diabetes. Hyperglycemia is associated with chronic low-grade inflammation, and thus has become the focus of many screening and treatment recommendations. We hypothesize that insulin may also be associated with inflammation and may be an additional factor to consider in screening and treatment.

Methods
This study used National Health and Nutrition Examination Survey data from 2005 to 2010 to analyze the association between fasting insulin and C-reactive protein (CRP). A two-part model was used due to the high number of values reported as 0.1 mg/L. Two models were analyzed, both with and without the addition of waist circumference to other covariates in the model.

Results
The final sample included 4527 adults with a mean age of 43.31 years. In the first model, higher fasting insulin was associated with increased odds of CRP > 0.1 mg/L (OR = 1.02, p < .001) and with higher CRP (β = 0.03, p < .001). In the adjusted model, including waist circumference as a covariate, higher fasting insulin was not associated with CRP > 0.1 mg/L (OR = 1.00, p = .307) but the association between higher fasting insulin and higher continuous CRP remained significant (β = 0.01, p = .012).

Conclusion
This study found that higher fasting insulin is associated with higher CRP. These results suggest that treatment approaches that simultaneously decrease insulin levels as well as glucose levels may provide additive anti-inflammatory effects, and therefore may improve long-term outcomes for adults with type 2 diabetes.
Association of tyrosine hydroxylase expression in brain and tumor with increased tumor growth in sympathectomized mice
Authors: Gomez-Flores R. , Gutierrez-Leal I. , Caballero-Hernández D. , Orozco-Flores A. , Tamez-Guerra P. , Tamez-Guerra R. , Rodríguez-Padilla C. 
Published: March 2021

AbstractObjectiveLymphocytes express tyrosine hydroxylase (TH), the rate-limiting enzyme for the synthesis of dopamine, norepinephrine and epinephrine. This suggests a broader role for cathecholamines in lymphocyte function, as well as the potential secretion of catecholamines by tumors of lymphoid origin. Our aim was to evaluate the expression ofThby murine lymphoma cells in an in vivo mouse model. For this, L5178Y-R lymphoma cells were implanted in nerve-intact and sympathectomized male BALB/c mice. RelativeThgene expression in tumor and brain was determined by quantitative PCR. Body composition, tumor volume, and plasma TH1/TH2/TH17 cytokines were also evaluated as markers of tumor-host condition and anti-tumor immune response in absence of adrenergic innervation.ResultsWe found a significant (p = 0.045) 3.3-fold decrease ofThgene expression in tumor and a non-significant (p = 0.60) 6.9-fold increase in brain after sympathectomy. Sympathectomized mice also showed a significant increase in tumor mass at days 18 (p = 0.032) and 28 (p = 0.022) and increased interscapular fat (p = 0.04). TH1/TH2 and TH17 cytokines levels in plasma from sympathectomized tumor-bearing mice were not different from control mice.ConclusionThe L5178Y-R lymphoma does not expressThduring in vivo progression.