bluuebunny/crossref_metadata_2025_split huggingface dataset:
Residual positioning errors and uncertainties for pediatric craniospinal irradiation and the impact of image guidance
Authors: Gram Daniel , Haraldsson André , Brodin N. Patrik , Nysom Karsten , Björk-Eriksson Thomas , Munck af Rosenschöld Per 
Published: June 2020

Abstract
Background
Optimal alignment is of utmost importance when treating pediatric patients with craniospinal irradiation (CSI), especially with regards to field junctions and multiple isocenters and techniques applying high dose gradients. Here, we investigated the setup errors and uncertainties for pediatric CSI using different setup verification protocols.

Methods
A total of 38 pediatric patients treated with CSI were identified for whom treatment records and setup images were available. The setup images were registered retrospectively to the reference image using an automated tool and matching on bony anatomy, subsequently, the impact of different correction protocols was simulated.

Results
For an action-level (AL)-protocol and a non-action level (NAL)-protocol, the translational residual setup error can be as large as 24 mm for an individual patient during a single fraction, and the rotational error as large as 6.1°. With daily IGRT, the maximum setup errors were reduced to 1 mm translational and 5.4° rotational versus 1 mm translational and 2.4° rotational for 3- and 6- degrees of freedom (DoF) couch shifts, respectively. With a daily 6-DoF IGRT protocol for a wide field junction irradiation technique, the residual positioning uncertainty was below 1 mm and 1° for translational and rotational directions, respectively. The largest rotational uncertainty was found for the patients’ roll even though this was the least common type of rotational error, while the largest translational uncertainty was found in the patients’ anterior-posterior-axis.

Conclusions
These results allow for informed margin calculation and robust optimization of treatments. Daily IGRT is the superior choice for setup of pediatric patients treated with CSI, although centers that do not have this option could use the results presented here to improve their margins and uncertainty estimates for a more accurate treatment alignment.
Normoxic re-oxygenation ameliorates end-organ injury after cardiopulmonary bypass
Authors: Peng Yun-Wen , Major Terry , Mohammed Azmath , Deatrick Kristopher B. , Charpie John R. 
Published: June 2020

Abstract
Background
In a rabbit model of cardiopulmonary bypass (CPB) and cardioplegic arrest, we previously showed that hyperoxic myocardial reperfusion was associated with increased left ventricular (LV) systolic dysfunction and myocardial injury compared with normoxic reperfusion. The aim of this study was to evaluate in our experimental model the impact of post-CPB reperfusion conditions on other organs potentially vulnerable to ischemic injury such as the brain and kidney.

Methods
After 60 min of CPB, aortic cross-clamp, and cold cardioplegic arrest, rabbits were reperfused under hyperoxic or normoxic conditions for 120 min. Left ventricular systolic contractility (LV + dP/dt) and diastolic relaxation (LV –dP/dt) were continuously recorded, and end-organ injury was assessed by measuring circulating biomarkers specific for kidney (cystatin C and creatinine) and brain injury [S100B and neuron specific enolase (NSE)]. At completion of the protocol, kidney and brain tissues were harvested for measuring oxidant stress (OS), inflammation and apoptosis.

Results
Following aortic cross-clamp removal, rabbits exposed to normoxic reperfusion demonstrated preserved LV systolic and diastolic function compared with hyperoxic reperfusion (LV + dP/dt: 70 ± 14% of pre-CPB vs. 36 ± 21%, p = 0.018; LV -dP/dt: 72 ± 36% of pre-CPB vs. 33 ± 20%, p = 0.023). Similarly, CPB increased plasma creatinine, S100B and NSE that were significantly attenuated by normoxic reperfusion compared with hyperoxic reperfusion (creatinine: 4.0 ± 0.5 vs. 7.1 ± 0.8 mg/dL, p = 0.004; S100B: 4.0 ± 0.8 vs. 6.7 ± 1.0 ng/mL, p = 0.047; NSE: 57.7 ± 6.8 vs. 101.3 ± 16.1 pg/mL, p = 0.040). Furthermore, both kidney and brain tissues showed increased mRNA expression and activation of pathways for OS, inflammation, and apoptosis, that were reduced under normoxic compared with hyperoxic conditions.

Conclusions
Normoxic reperfusion ameliorates cardiac, renal and neural injury compared with hyperoxic reperfusion in an in vivo animal model of CPB and cardioplegic arrest. This protective effect of normoxic reperfusion may be due to a reduction in signaling pathways for OS, inflammation, and apoptosis.
Infective endocarditis at a tertiary-care hospital in China
Authors: Ma Lulu , Ge Ying , Ma Haobo , Zhu Bo , Miao Qi 
Published: June 2020

Abstract
Background
The aim of this study was to describe the clinical features and outcome of infective endocarditis at a general hospital in China and to identify the risk factors associated with in-hospital mortality.

Methods
A retrospective study was conducted and all patients diagnosed with definite or possible infective endocarditis between January 2013 and June 2018 according to the modified Duke criteria were included.

Results
A total of 381 patients were included. The mean age was 46 years old and 66.9% patients were male patients. Community acquired IE was the most common type of infective endocarditis and Viridans Group Streptococci (37.5%) was still the most common causative pathogen. The microbial etiology of infective endocarditis varied with location of acquisition. 97 (25.5%) patients had culture-negative infective endocarditis. Vegetations were detected in 85% patients and mitral valve was the most common involved valve. Operations were performed in 72.7% patients and in-hospital mortality rate was 8.4%. The risk factors of in-hospital mortality were age old than 70 years old, heart failure, stroke and medical therapy.

Conclusions
Older age, heart failure, stroke and medical therapy were risk factors of in-hospital mortality. Infective endocarditis, were mainly caused by Viridans Group Streptococci, characterized by younger patients and lower mortality rate in China.
HIF-1α-dependent miR-424 induction confers cisplatin resistance on bladder cancer cells through down-regulation of pro-apoptotic UNC5B and SIRT4
Authors: Yu Meng , Ozaki Toshinori , Sun Dan , Xing Haotian , Wei Baojun , An Jun , Yang Jieping , Gao Ying , Liu Shuangjie , Kong Chuize , Zhu Yuyan 
Published: June 2020

Abstract
Background
Chemo-resistance of bladder cancer has been considered to be one of the serious issues to be solved. In this study, we revealed pivotal role of miR-424 in the regulation of CDDP sensitivity of bladder cancer cells.

Methods
The cytotoxicity of cisplatin and effect of miR-424 were assessed by flow cytometry and TUNEL. Transcriptional regulation of miR-424 by HIF-1α was assessed by Chromatin immunoprecipitation (ChIP). Effect of miR-424 on expression of UNC5B, SIRT4 (Sirtuin4) and apoptotic markers was measured by QRT-PCR and/or Western blot. The regulation of miR-424 for UNC5B and SIRT4 were tested by luciferase reporter assay. The 5637-inoculated nude mice xenograft model was used for the in vivo study. The clinical significance of miR-424 was demonstrated mainly through data mining and statistical analysis of TCGA.

Results
In this study, we have found for the first time that cisplatin (CDDP) induces the expression of miR-424 in a HIF-1α-dependent manner under normoxia, and miR-424 plays a vital role in the regulation of CDDP resistance of bladder cancer cells in vitro. Mechanistically, we have found that UNC5B and SIRT4 are the direct downstream target genes of miR-424. CDDP-mediated suppression of xenograft bladder tumor growth was prohibited by the addition of miR-424, whereas ectopic expression of UNC5B or SIRT4 partially restored miR-424-dependent decrease in CDDP sensitivity of bladder cancer 5637 and T24 cells. Moreover, knockdown of UNC5B or SIRT4 prohibited CDDP-mediated proteolytic cleavage of PARP and also decreased CDDP sensitivity of these cells. Consistently, the higher expression levels of miR-424 were closely associated with the poor clinical outcome of the bladder cancer patients. There existed a clear inverse relationship between the expression levels of miR-424 and pro-apoptotic UNC5B or SIRT4 in bladder cancer tissues.

Conclusions
Collectively, our current results strongly suggest that miR-424 tightly participates in the acquisition/maintenance of CDDP-resistant phenotype of bladder cancer cells through down-regulation of its targets UNC5B and SIRT4, and thus combination chemotherapy of CDDP plus HIF-1α/miR-424 inhibition might have a significant impact on hypoxic as well as normoxic bladder cancer cells.
An unusual diagnosis for an usual test
Authors: Trombetta Andrea , Migliarino Vanessa , Faletra Flavio , Barbi Egidio , Tornese Gianluca 
Published: June 2020

Abstract
Background
Hereditary multiple osteochondromas (HMO) is a genetic condition characterized by the presence of multiple osteochondromas, usually at the lateral side of the most active growth plate of a long bone. These lesions may persist, be asymptomatic during childhood, and may increase in number and size until growth plates close. Therefore, diagnosis of HMO in children and young people can be challenging; while short stature can be more evident at the onset of puberty, asymptomatic ostheocondromas can progress into different degrees of orthopedic deformity. Moreover, multiple complications may arise due to the presence of osteochondromas, including tendon and compression muscle pain, neurovascular disorders, obstetric problems, scoliosis and malignant transformation into secondary peripheral chondrosarcoma in adulthood.

Case presentation
We report the case of a girl admitted to our Institute for growth delay. While laboratory tests, including growth hormone stimulation test, were normal, left hand X-ray revealed multiple osteochondromas, suggestive for HMO. The genetic test for EXT1 and EXT2 genes confirmed the radiological diagnosis, with a mutation inherited from the mother who displayed the same radiological abnormalities along with recurrent limb pain episodes.

Conclusions
HMO is a genetic condition whose diagnosis can be challenging, especially in females. Every pediatricians should consider a skeletal dysplasia in case of unexplained growth delay and a skeletal survey might be fundamental in reaching a diagnosis.
Revision of Macroponema Mawson, 1978 (Nematoda: Strongylida) from macropodid marsupials with the description of two new species
Authors: Sukee Tanapan , Jabbar Abdul , Beveridge Ian 
Published: June 2020

Abstract
Background
Species of Macroponema Mawson, 1978 are strongyloid nematodes which occur in the stomachs of macropodid marsupials in Australia. In this study, the genus Macroponema is revised, redescriptions of the two known species are provided, and two new species are added to the genus.

Methods
A molecular characterisation of the internal transcribed spacers of the nuclear ribosomal DNA of representative specimens of Macroponema from all known host species was undertaken to confirm the status of M. cf. comani. This resulted in the identification of a further new species within the genus. Consequently, a review of all available material in museum collections was undertaken.

Results
The two known species M. beveridgei Mawson, 1978 from Osphranter antilopinus (Gould) and O. robustus (Gould), and M. comani Mawson, 1978 from Macropus giganteus Shaw are re-described and their geographical distributions expanded. Two new species added to the genus are M. arundeli n. sp. from Ma. giganteus found in Queensland and the north east of New South Wales, and M. obendorfi n. sp. from O. antilopinus and O. robustus in the Northern Territory, the Kimberley Division of Western Australia and eastern Queensland. The latter species was formerly identified as M. cf. comani based on molecular studies. The specific identification of both of the new species is supported by ribosomal DNA sequence data.

Conclusions
Based on the morphological and molecular characterisation of nematodes, this study has revealed the existence of four species within the genus Macroponema. The current phylogenetic data suggest that Macroponema spp. plausibly evolved by host switching; however, further studies are required to test this hypothesis.
Transinfection of buffalo flies (Haematobia irritans exigua) with Wolbachia and effect on host biology
Authors: Madhav Mukund , Brown Geoff , Morgan Jess A. T. , Asgari Sassan , McGraw Elizabeth A. , James Peter 
Published: June 2020

Abstract
Background
Buffalo flies (Haematobia irritans exigua) (BF) and closely related horn flies (Haematobia irritans irritans) (HF) are invasive haematophagous parasites with significant economic and welfare impacts on cattle production. Wolbachia are intracellular bacteria found widely in insects and currently of much interest for use in novel strategies for the area wide control of insect pests and insect-vectored diseases. In this paper, we report the transinfection of BF towards the development of area-wide controls.

Methods
Three stages of BF; embryos, pupae and adult female flies, were injected with different Wolbachia strains (wAlbB, wMel and wMelPop). The success of transinfection and infection dynamics was compared by real-time PCR and FISH and fitness effects were assessed in transinfected flies.

Results
BF eggs were not easily injected because of their tough outer chorion and embryos were frequently damaged with less than 1% hatch rate of microinjected eggs. No Wolbachia infection was recorded in flies successfully reared from injected eggs. Adult and pupal injection resulted in higher survival rates and somatic and germinal tissue infections, with transmission to the succeeding generations on some occasions. Investigations of infection dynamics in flies from injected pupae confirmed that Wolbachia were actively multiplying in somatic tissues. Ovarian infections were confirmed with wMel and wMelPop in a number of instances, though not with wAlbB. Measurement of fitness traits indicated reduced longevity, decreased and delayed adult emergence, and reduced fecundity in Wolbachia-infected flies compared to mock-injected flies. Effects varied with the Wolbachia strain injected with most marked changes seen in the wMelPop-injected flies and least severe effects seen with wAlbB.

Conclusions
Adult and pupal injection were the most suitable methods for transinfecting BF and all three strains of Wolbachia successfully replicated in somatic tissues. The Wolbachia-induced fitness effects seen in transinfected BF suggest potential for use of the wMel or wMelPop strains in Wolbachia-based biocontrol programmes for BF.
Dynamic proteomic analysis of Aedes aegypti Aag-2 cells infected with Mayaro virus
Authors: Vasconcellos Anna Fernanda , Mandacaru Samuel Coelho , de Oliveira Athos Silva , Fontes Wagner , Melo Reynaldo Magalhães , de Sousa Marcelo Valle , Resende Renato Oliveira , Charneau Sébastien 
Published: June 2020

Abstract
Background
Mayaro virus (MAYV) is responsible for a mosquito-borne tropical disease with clinical symptoms similar to dengue or chikungunya virus fevers. In addition to the recent territorial expansion of MAYV, this virus may be responsible for an increasing number of outbreaks. Currently, no vaccine is available. Aedes aegypti is promiscuous in its viral transmission and thus an interesting model to understand MAYV-vector interactions. While the life-cycle of MAYV is known, the mechanisms by which this arbovirus affects mosquito host cells are not clearly understood.

Methods
After defining the best conditions for cell culture harvesting using the highest virus titer, Ae. aegypti Aag-2 cells were infected with a Brazilian MAYV isolate at a MOI of 1 in order to perform a comparative proteomic analysis of MAYV-infected Aag-2 cells by using a label-free semi-quantitative bottom-up proteomic analysis. Time-course analyses were performed at 12 and 48 h post-infection (hpi). After spectrum alignment between the triplicates of each time point and changes of the relative abundance level calculation, the identified proteins were annotated and using Gene Ontology database and protein pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes.

Results
After three reproducible biological replicates, the total proteome analysis allowed for the identification of 5330 peptides and the mapping of 459, 376 and 251 protein groups, at time 0, 12 hpi and 48 hpi, respectively. A total of 161 mosquito proteins were found to be differentially abundant during the time-course, mostly related to host cell processes, including redox metabolism, translation, energy metabolism, and host cell defense. MAYV infection also increased host protein expression implicated in viral replication.

Conclusions
To our knowledge, this first proteomic time-course analysis of MAYV-infected mosquito cells sheds light on the molecular basis of the viral infection process and host cell response during the first 48 hpi. Our data highlight several mosquito proteins modulated by the virus, revealing that MAYV manipulates mosquito cell metabolism for its propagation.
MicroRNA-7: expression and function in brain physiological and pathological processes
Authors: Zhao Juanjuan , Zhou Ya , Guo Mengmeng , Yue Dongxu , Chen Chao , Liang Guiyou , Xu Lin 
Published: June 2020

AbstractMicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level and play critical roles in regulating physiological function, and are becoming worldwide research hot spot in brain development and diseases. However, the exact value of miRNAs in brain physiological and pathological processes remain to be fully elucidated, which is vital for the application of miRNAs as diagnostic, prognostic, and therapeutic biomarkers for brain diseases. MicroRNA-7 (miR-7), as a highly expressed miRNA molecule in the mammalian brain, is well documented to play a critical role in development of various diseases. Importantly, accumulating evidence has shown that miR-7 is involved in a range of developmental and pathological processes of brain. Expressively, miR-7, encoded by three genes located different chromosomes, is dominantly expressed in neurons with sensory or neurosecretory. Moreover, the expression of miR-7 is regulated at three levels including gene transcription, process of primary and precursor sequence and formation of mature sequence. Physiologically, miR-7 principally governs the physiological development of Pituitary gland, Optic nervous system and Cerebral cortex. Pathologically, miR-7 can regulate multiple genes thereby manipulating the process of various brain diseases including neurodegenerative diseases, neuroinflammation, and mental disorders and so on. These emerging studies have shown that miR-7, a representative member of miRNA family, might be a novel intrinsic regulatory molecule involved in the physiological and pathological process of brain. Therefore, in-depth studies on the role of miR-7 in brain physiology and pathology undoubtedly not only provide a light on the roles of miRNAs in brain development and diseases, but also are much helpful for ultimate development of therapeutic strategies against brain diseases. In this review, we provide an overview of current scientific knowledge regarding the expression and function of miR-7 in development and disease of brain and raise many issues involved in the relationship between miR-7 and brain physiological and pathological processes.
Disordered eating among Arab and Jewish youth in Israel: the role of eating dinner with the family
Authors: Elran-Barak Roni , Bromberg Michal , Shimony Tal , Dichtiar Rita , Mery Nisim , Nitsan Lesley , Keinan-Boker Lital 
Published: June 2020

Abstract
Background
Disordered eating (DE), defined as unhealthy eating attitudes and behaviors, is considered a major public health problem among adolescents. Nevertheless, rates of DE among Arab and Jewish adolescents in Israel are still unknown. Furthermore, while previous studies have highlighted the role of frequent family meals as a protective factor against DE, studies examining home family dinners relative to other common dinner options (e.g., eating at home alone, eating out of the home, not eating dinner at all) are largely unavailable. We sought to use representative data of middle and high-school children in Israel in order to identify rates of DE among Arabs and Jews, while examining the relations of home family dinners (vs. other dinner options) with DE.

Methods
A nationally representative school-based survey of 4926 middle and high-school children (11–19 years old) was conducted during 2015–2016. Participants indicated where and with whom they had eaten dinner the day before. The 5-item SCOFF questionnaire was used (> 2 affirmative items were considered a likely case of DE). Height and weight were measured by personnel.

Results
DE was more prevalent among girls (29.7%) relative to boys (12.2%), Arabs (25.1%) relative to Jews (19.5%), and older (25.3%) relative to younger (17.6%) adolescents. Arabs were more likely to eat dinner at home with parents/family (chi2 = 10.75, p = .001), or not to eat dinner at all (chi2 = 63.27, p < .001), while Jews were more likely to eat dinner alone (chi2 = 5.37, p = .021) or to eat dinner out of the home (chi2 = 67.65, p < .001). Logistic regressions (stratified by ethnicity and adjusted for gender, age, weight) revealed that family dinners acted as a protective factor against DE, relative to eating out of the home or relative to not eating dinner at all among both ethnic groups, and relative to eating dinner alone among Arabs.

Conclusion
There are differences between Arab and Jewish adolescents in terms of rates of yesterday’s family dinners and DE. Given that eating dinner with the family was linked with lower rates of DE, possible interventions to reduce DE may include educating parents of both Arab and Jewish adolescents regarding the importance of family meals.
Dyslipidemia in adolescents and young adults with type 1 and type 2 diabetes: a retrospective analysis
Authors: Kim Grace , DeSalvo Daniel , Guffey Danielle , Minard Charles G. , Cephus Constance , Moodie Douglas , Lyons Sarah 
Published: June 2020

Abstract
Background
Youth onset type 1 diabetes (T1D) and type 2 diabetes (T2D) is increasing and associated with earlier vascular complications and mortality. Dyslipidemia is an important modifiable cardiovascular (CVD) risk factor that is under-recognized and undertreated in youth with T1D and T2D. Given this, we evaluated the prevalence and associations between lipid concentrations and clinical CVD risk factors in youth with T1D compared to T2D at our large ethnically diverse diabetes center.

Methods
A retrospective chart review was performed, evaluating patients with T1D or T2D seen at least once in clinic from 2015 to 2017, age 10–22 years of age, duration of diabetes at least 6 months on the date of most recent LDL-cholesterol (LDL-C) concentration, and not on statin therapy. We performed independent and multivariable linear regressions of LDL-C and HDL-cholesterol (HDL-C) concentrations.

Results
There were 32.7% with T1D (n = 1701) and 47.7% with T2D (n = 298) with LDL-C above recommend goal (> 100 mg/dL/2.6 mmol/L). Furthermore, there were 9% with T1D and 16.4% with T2D with LDL > 130 mg/dL (> 3.4 mmol/L), who likely met criteria for starting statin therapy. Higher LDL-C and/or lower HDL-C were associated with increased age, diabetes duration, higher HbA1C, female sex, Hispanic ethnicity, obesity, and T2D. After adjusting for these risk factors in a multivariable linear regression model, the association of higher LDL-C and lower HDL-C was higher with T2D than T1D.

Conclusions
This highlights the need for more aggressive dyslipidemia screening and treatment in youth with diabetes, especially T2D. At our institution we have created and instituted quality improvement algorithms to try to address this need.