bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of weight and height of patients with primary immunodeficiency disorders and group of children with recurrent respiratory tract infections
Authors: Pieniawska-Śmiech Karolina , Bar Kamil , Babicki Mateusz , Śmiech Karol , Lewandowicz-Uszyńska Aleksandra 
Published: July 2020

Abstract
Background
Primary immunodeficiences (PIDs) are a group of chronic, serious disorders in which the immune response is insufficient. In consequence, it leads to an increased susceptibility to infections. Up to date, there are about 350 different disorders classified in that group. There are also patients suffering from recurrent respiratory tract infections (RRTI), however that group doesn’t present any abnormalities in terms of conducted immunological tests. Many factors, including medical, can have an impact on physical development of a child. Data such as birth weight and length, also weight, height, BMI during admission to the hospital were collected from 195 patients’ medical histories from their hospitalization at Clinical Immunology and Paediatrics Ward of J. Gromkowski Hospital in Wrocław. Investigated groups included patients with PIDs, RRTI and a control group of healthy children. Our purpose was to evaluate the physical growth of children with PID and children with RRTI by assessment of their height and weight. All of parameters were evaluated using centile charts, suitable best for the Polish population.

Results
The lowest mean birth weight and height was found among the PIDs patients group. Children with PIDs during hospitalization had statistically relevant lower mean weight than the control group and almost 18% of them had their height situated below 3rd percentile. The statistically relevant differences have been found between them and RRTI group in terms of weight, height and nutritional status. The statistically significant difference was detected between the nutritional status of PID and control group.

Conclusions
There is a higher percentage of PID patients with physical growth abnormalities in comparison to healthy children. Our findings indicate a need for further investigation of immune system irregularities and their influence on physical growth of children.
Optical microscopy reveals the dynamic nature of B. pseudomallei morphology during β-lactam antimicrobial susceptibility testing
Authors: McLaughlin Heather P. , Bugrysheva Julia , Sue David 
Published: July 2020

Abstract
Background
In Gram-negative species, β-lactam antibiotics target penicillin binding proteins (PBPs) resulting in morphological alterations of bacterial cells. Observations of antibiotic-induced cell morphology changes can rapidly and accurately differentiate drug susceptible from resistant bacterial strains; however, resistant cells do not always remain unchanged. Burkholderia pseudomallei is a Gram-negative, biothreat pathogen and the causative agent of melioidosis, an often fatal infectious disease for humans.

Results
Here, we identified β-lactam targets in B. pseudomallei by in silico analysis. Ten genes encoding putative PBPs, including PBP-1, PBP-2, PBP-3 and PBP-6, were detected in the genomes of susceptible and resistant strains. Real-time, live-cell imaging of B. pseudomallei strains demonstrated dynamic morphological changes in broth containing clinically relevant β-lactam antibiotics. At sub-inhibitory concentrations of ceftazidime (CAZ), amoxicillin-clavulanic acid (AMC), and imipenem (IPM), filamentation, varying in length and proportion, was an initial response of the multidrug-resistant strain Bp1651 in exponential phase. However, a dominant morphotype reemerged during stationary phase that resembled cells unexposed to antibiotics. Similar morphology dynamics were observed for AMC-resistant strains, MSHR1655 and 724644, when exposed to sub-inhibitory concentrations of AMC. For all B. pseudomallei strains evaluated, increased exposure time and exposure to increased concentrations of AMC at and above minimal inhibitory concentrations (MICs) in broth resulted in cell morphology shifts from filaments to spheroplasts and/or cell lysis. B. pseudomallei morphology changes were more consistent in IPM. Spheroplast formation followed by cell lysis was observed for all strains in broth containing IPM at concentrations greater than or equal to MICs, however, the time to cell lysis was variable. B. pseudomallei cell lengths were strain-, drug- and drug concentration-dependent.

Conclusions
Both resistant and susceptible B. pseudomallei strains exhibited filamentation during early exposure to AMC and CAZ at concentrations used to interpret susceptibility (based on CLSI guidelines). While developing a rapid β-lactam antimicrobial susceptibility test based on cell-shape alone requires more extensive analyses, optical microscopy detected B. pseudomallei growth attributes that lend insight into antibiotic response and antibacterial mechanisms of action.
Occurrence, virulence genes, and antimicrobial profiles of Escherichia coli O157 isolated from ruminants slaughtered in Al Ain, United Arab Emirates
Authors: Al-Ajmi Dawood , Rahman Shafeeq , Banu Sharmila 
Published: July 2020

Abstract
Background
Shiga toxin-producing Escherichia coli (STEC) is a major source of food-borne illness around the world. E. coli O157 has been widely reported as the most common STEC serogroup and has emerged as an important enteric pathogen. Cattle, in particular have been identified as a major E. coli O157:H7 reservoir of human infections; however, the prevalence of this organism in camels, sheep, and goats is less understood. The aim of this study was to evaluate the occurrence and concentration of E. coli serotype O157 in the feces of healthy camels (n = 140), cattle (n = 137), sheep (n = 141) and goats (n = 150) slaughtered in United Arab Emirates (UAE) for meat consumption between September 2017 and August 2018. We used immunomagnetic separation coupled with a culture-plating method to detect E. coli O157. Non-sorbitol fermenting colonies were assessed via latex-agglutination testing, and positive cultures were analyzed by performing polymerase chain reactions to detect genes encoding attaching and effacing protein (eaeA), hemolysin A (hlyA, also known as ehxA) and Shiga toxin (stx1 and stx2), and E. coli O157:H7 specific genes (rfb O157, uidA, and fliC). All E. coli O157 isolates were analyzed for their susceptibility to 20 selected antimicrobials.

Results
E. coli O157 was observed in camels, goats, and cattle fecal samples at abundances of 4.3, 2, and 1.46%, respectively, but it was undetectable in sheep feces. The most prevalent E. coli O157 gene in all STEC isolates was stx2;, whereas, stx1 was not detected in any of the samples. The fecal samples from camels, goats, and cattle harbored E. coli O157 isolates that were 100% susceptible to cefotaxime, chloramphenicol, ciprofloxacin, norfloxacin, and polymyxin B.

Conclusion
To our knowledge, this is the first report on the occurrence of E. coli O157 in slaughter animals in the UAE. Our results clearly demonstrate the presence of E. coli O157 in slaughtered animals, which could possibly contaminate meat products intended for human consumption.
Transcriptome analysis reveals ethylene-mediated defense responses to Fusarium oxysporum f. sp. cucumerinum infection in Cucumis sativus L.
Authors: Dong Jingping , Wang Yuean , Xian Qianqian , Chen Xuehao , Xu Jun 
Published: July 2020

Abstract
Background
Fusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (Foc), is a severe disease affecting cucumber (Cucumis sativus L.) production worldwide, but mechanisms underlying Fusarium wilt resistance in cucumber remain unknown. To better understand of the defense mechanisms elicited in response to Foc inoculation, RNA sequencing-based transcriptomic profiling of responses of the Fusarium wilt-resistant cucumber line ‘Rijiecheng’ at 0, 24, 48, 96, and 192 h after Foc inoculation was performed.

Results
We identified 4116 genes that were differentially expressed between 0 h and other time points after inoculation. All ethylene-related and pathogenesis-related genes from the differentially expressed genes were filtered out. Real-time PCR analysis showed that ethylene-related genes were induced in response to Foc infection. Importantly, after Foc infection and exogenous application of ethephon, a donor of ethylene, the ethylene-related genes were highly expressed. In response to exogenous ethephon treatment in conjunction with Foc inoculation, the infection resistance of cucumber seedlings was enhanced and endogenous ethylene biosynthesis increased dramatically.

Conclusion
Collectively, ethylene signaling pathways play a positive role in regulating the defense response of cucumber to Foc infection. The results provide insight into the cucumber Fusarium wilt defense mechanisms and provide valuable information for breeding new cucumber cultivars with enhanced Fusarium wilt tolerance.
Transcriptomic analysis of flower opening response to relatively low temperatures in Osmanthus fragrans
Authors: Fu Jianxin , Zhang Chao , Liu Yucheng , Pang Tianhong , Dong Bin , Gao Xiaoyue , Zhu Yimin , Zhao Hongbo 
Published: July 2020

Abstract
Background
Sweet osmanthus (Osmanthus fragrans Lour.) is one of the top ten traditional ornamental flowers in China. The flowering time of once-flowering cultivars in O. fragrans is greatly affected by the relatively low temperature, but there are few reports on its molecular mechanism to date. A hypothesis had been raised that genes related with flower opening might be up-regulated in response to relatively low temperature in O. fragrans. Thus, our work was aimed to explore the underlying molecular mechanism of flower opening regulated by relatively low temperature in O. fragrans.

Results
The cell size of adaxial and abaxial petal epidermal cells and ultrastructural morphology of petal cells at different developmental stages were observed. The cell size of adaxial and abaxial petal epidermal cells increased gradually with the process of flower opening. Then the transcriptomic sequencing was employed to analyze the differentially expressed genes (DEGs) under different number of days’ treatments with relatively low temperatures (19 °C) or 23 °C. Analysis of DEGs in Gene Ontology analysis showed that “metabolic process”, “cellular process”, “binding”, “catalytic activity”, “cell”, “cell part”, “membrane”, “membrane part”, “single-organism process”, and “organelle” were highly enriched. In KEGG analysis, “metabolic pathways”, “biosynthesis of secondary metabolites”, “plant-pathogen interaction”, “starch and sucrose metabolism”, and “plant hormone signal transduction” were the top five pathways containing the greatest number of DEGs. The DEGs involved in cell wall metabolism, phytohormone signal transduction pathways, and eight kinds of transcription factors were analyzed in depth.

Conclusions
Several unigenes involved in cell wall metabolism, phytohormone signal transduction pathway, and transcription factors with highly variable expression levels between different temperature treatments may be involved in petal cell expansion during flower opening process in response to the relatively low temperature. These results could improve our understanding of the molecular mechanism of relatively-low-temperature-regulated flower opening of O. fragrans, provide practical information for the prediction and regulation of flowering time in O. fragrans, and ultimately pave the way for genetic modification in O. fragrans.
Modeling adaptive response profiles in a vaccine clinical trial
Authors: Hasdemir Dicle , van den Berg Robert A. , van Kampen Antoine , Smilde Age K. 
Published: July 2020

Abstract
Background
Vaccine clinical studies typically provide time-resolved data on adaptive response read-outs in response to the administration of that particular vaccine to a cohort of individuals. However, modeling such data is challenged by the properties of these time-resolved profiles such as non-linearity, scarcity of measurement points, scheduling of the vaccine at multiple time points. Linear Mixed Models (LMM) are often used for the analysis of longitudinal data but their use in these time-resolved immunological data is not common yet. Apart from the modeling challenges mentioned earlier, selection of the optimal model by using information-criterion-based measures is far from being straight-forward. The aim of this study is to provide guidelines for the application and selection of LMMs that deal with the challenging characteristics of the typical data sets in the field of vaccine clinical studies.

Methods
We used antibody measurements in response to Hepatitis-B vaccine with five different adjuvant formulations for demonstration purposes. We built piecewise-linear, piecewise-quadratic and cubic models with transformations of the axes with pre-selected or optimized knot locations where time is a numerical variable. We also investigated models where time is categorical and random effects are shared intercepts between different measurement points. We compared all models by using Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), Deviance Information Criterion (DIC), variations of conditional AIC and by visual inspection of the model fit in the light of prior biological information.

Results
There are various ways of dealing with the challenges of the data which have their own advantages and disadvantages. We explain these in detail here. Traditional information-criteria-based measures work well for the coarse selection of the model structure and complexity, however are not efficient at fine tuning of the complexity level of the random effects.

Conclusions
We show that common statistical measures for optimal model complexity are not sufficient. Rather, explicitly accounting for model purpose and biological interpretation is needed to arrive at relevant models.

Trial Registration
Clinical trial registration number for this study: NCT00805389, date of registration: December 9, 2008 (pro-active registration).
Non-inferiority comparative clinical trial between early oral REFEEDING and usual oral REFEEDING in predicted mild acute biliary pancreatitis
Authors: Lozada-Hernández Edgard Efrén , Barrón-González Omar , Vázquez-Romero Santa , Cano-Rosas Martin , Apolinar-Jimenez Evelia 
Published: July 2020

Abstract
Background
The aim of the study was to compare the onset of oral feeding in the first 24 h after hospital admission with usual oral refeeding and determine whether the timing of the onset of oral feeding influences the recurrence of pain or alters the blood levels of pancreatic enzymes in patients with predicted mild acute biliary pancreatitis.

Methods
This non-inferiority randomized controlled trial was carried out between September 2018 and June 2019 after receiving authorization from the ethics committee for health research. Patients with a diagnosis of predicted mild acute biliary pancreatitis were divided into Group A (early oral refeeding, EOR) and Group B (usual oral refeeding, UOR). Outcome measures included pancreatic lipase levels, the systemic inflammatory response (concentrations of leukocytes), feasibility (evaluated by abdominal pain recurrence), the presence and recurrence of gastrointestinal symptoms and the length of hospital stay.

Results
Two patients in the EOR group experienced pain relapse (3.2%), and four patients in the UOR group experienced pain relapse (6.77%) after oral refeeding (p = 0.379). The presence of nausea or vomiting after the onset of oral refeeding was not different between the two groups (p = 0.293). The onset of oral refeeding was approximately 48 h later in the UOR group. The length of hospital stay was 5 days in the EOR group and 8 days in the UOR group (p = 0.042), and this difference was also manifested in higher hospital costs in the UOR group (p = 0.0235).

Conclusion
Compared with usual oral refeeding, early oral refeeding is safe in predicted mild acute biliary pancreatitis patients, does not cause adverse gastrointestinal events, and reduces the length of hospital stay and costs.

Trial registration
Early oral refeeding in mild acute pancreatitis (EORVsUOR). NCT04168801, retrospectively registered (November 19, 2019).
Predictive factors for positive disco-vertebral biopsy culture in pyogenic vertebral osteomyelitis, and impact of fluoroscopic versus scanographic guidance
Authors: Diffre Caroline , Jousset Camille , Roux Anne-Laure , Duran Clara , Noussair Latifa , Rottman Martin , Carlier Robert-Yves , Dinh Aurélien 
Published: July 2020

Abstract
Background
The aims of this study were to identify the predictive factors for microbiological diagnosis through disco-vertebral biopsy (DVB) in patients with pyogenic vertebral osteomyelitis (PVO) and negative blood cultures, and compare the performance of DVB under fluoroscopic versus scanographic guidance.

Methods
We performed a cohort study comparing positive and negative DVB among patients with PVO. All cases of PVO undergoing a DVB for microbiological diagnosis in our center were retrospectively reviewed. Infections due to Mycobacterium tuberculosis, infections on foreign device, and non-septic diseases were excluded. Anamnestic, clinical, biological, microbiological, as well as radiological data were collected from medical charts thanks to a standardized data set.

Results
A total of 111 patients were screened; 88 patients were included. Microbiological cultures were positive in 53/88 (60.2%) patients. A thickening of the paravertebral tissue ≥10 mm on magnetic resonance imaging (MRI) in axial MR scans was a predictive factor of DVB microbiological positivity (52.4% vs. 13.3%; p = 0.006; OR = 5.4). Overall, 51 DVB were performed under fluoroscopic guidance and 37 under scanographic guidance. Considering lumbar DVB, 25/36 (69.4%) of cases yielded positive results under fluoroscopic guidance versus 5/15 (33.3%) under scanographic guidance (p = 0.02; OR = 4.4). No adverse event linked to DVB was notified.

Conclusion
Every patient with PVO and negative blood cultures should undergo a DVB. A thickening of the paravertebral tissue ≥10 mm on MRI is associated with a higher rate of positive DVB culture. A lumbar DVB under fluoroscopic guidance is more sensitive than under scanographic guidance to identify the micro-organism involved.
The WOMAN trial: clinical and contextual factors surrounding the deaths of 483 women following post-partum haemorrhage in developing countries
Authors: Picetti Roberto , Miller Lori , Shakur-Still Haleema , Pepple Tracey , Beaumont Danielle , Balogun Eni , Asonganyi Etienne , Chaudhri Rizwana , El-Sheikh Mohamed , Vwalika Bellington , Arulkumaran Sabaratnam , Roberts Ian ,   on behalf of the WOMAN trial collaborators
Published: July 2020

Abstract
Background
Post-partum haemorrhage (PPH) is a leading cause of maternal death worldwide. The WOMAN trial assessed the effects of tranexamic acid (TXA) on death and surgical morbidity in women with PPH. The trial recorded 483 maternal deaths. We report the circumstances of the women who died.

Methods
The WOMAN trial recruited 20,060 women with a clinical diagnosis of PPH after a vaginal birth or caesarean section. We randomly allocated women to receive TXA or placebo. When a woman died, we asked participating clinicians to report the cause of death and to provide a short narrative of the events surrounding the death. We collated and edited for clarity the narrative data.

Results
Case fatality rates were 3.0% in Africa and 1.7% in Asia. Nearly three quarters of deaths were within 3 h of delivery and 91% of these deaths were from bleeding. Women who delivered outside a participating hospital (12%) were three times more likely to die (OR = 3.12, 95%CI 2.55–3.81) than those who delivered in hospital. Blood was often unavailable due to shortages or because relatives could not afford to buy it. Clinicians highlighted late presentation, maternal anaemia and poor infrastructure as key contributory factors.

Conclusions
Although TXA use reduces bleeding deaths by almost one third, mortality rates similar to those in high income countries will not be achieved without tackling late presentation, maternal anaemia, availability of blood for transfusion and poor infrastructure.
Transcriptomic insight into salinomycin mechanisms in breast cancer cell lines: synergistic effects with dasatinib and induction of estrogen receptor β
Authors: Bellat Vanessa , Verchère Alice , Ashe Sally A. , Law Benedict 
Published: July 2020

Abstract
Background
Tumors are heterogeneous in nature, composed of different cell populations with various mutations and/or phenotypes. Using a single drug to encounter cancer progression is generally ineffective. To improve the treatment outcome, multiple drugs of distinctive mechanisms but complementary anticancer activities (combination therapy) are often used to enhance antitumor efficacy and minimize the risk of acquiring drug resistance. We report here the synergistic effects of salinomycin (a polyether antibiotic) and dasatinib (a Src kinase inhibitor).

Methods
Functionally, both drugs induce cell cycle arrest, intracellular reactive oxygen species (iROS) production, and apoptosis. We rationalized that an overlapping of the drug activities should offer an enhanced anticancer effect, either through vertical inhibition of the Src-STAT3 axis or horizontal suppression of multiple pathways. We determined the toxicity induced by the drug combination and studied the kinetics of iROS production by fluorescence imaging and flow cytometry. Using genomic and proteomic techniques, including RNA-sequencing (RNA-seq), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western Blot, we subsequently identified the responsible pathways that contributed to the synergistic effects of the drug combination.

Results
Compared to either drug alone, the drug combination showed enhanced potency against MDA-MB-468, MDA-MB-231, and MCF-7 human breast cancer (BC) cell lines and tumor spheroids. The drug combination induces both iROS generation and apoptosis in a time-dependent manner, following a 2-step kinetic profile. RNA-seq data revealed that the drug combination exhibited synergism through horizontal suppression of multiple pathways, possibly through a promotion of cell cycle arrest at the G1/S phase via the estrogen-mediated S-phase entry pathway, and partially via the BRCA1 and DNA damage response pathway.

Conclusion
Transcriptomic analyses revealed for the first time, that the estrogen-mediated S-phase entry pathway partially contributed to the synergistic effect of the drug combination. More importantly, our studies led to the discoveries of new potential therapeutic targets, such as E2F2, as well as a novel drug-induced targeting of estrogen receptor β (ESR2) approach for triple-negative breast cancer treatment, currently lacking of targeted therapies.