bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful treatment of disseminated adenovirus infection with cidofovir and intravenous immunoglobulin in an infant following heart transplant
Authors: Serrano Ryan M. , Darragh Robert K. , Parent John J. 
Published: April 2018

AbstractFor most patients, adenoviruses cause few acute health concerns and are often self-limiting. Patients who are immunocompromised or immunosuppressed, however, are at risk for disseminated adenovirus and suffer high morbidity and mortality, without well-defined treatment options. We report the case of a 9-month-old boy who was successfully treated for disseminated adenovirus infection with intravenous immunoglobulin and cidofovir 3 months post heart transplant, tailored to serum adenoviral load and clinical response. We emphasise the importance of early identification, monitoring, and a potentially novel treatment in the paediatric cardiac transplant population with disseminated adenovirus infection.
Aurangzeb as seen from Gujarat: Shi‘i and Millenarian Challenges to Mughal Sovereignty
Authors: SHEIKH SAMIRA 
Published: April 2018

AbstractThis article argues for a re-evaluation of the ‘Islamist’ policies of the Mughal ruler Aurangzeb ‘Alamgir (r. 1658–1707), many of which were arguably harsher towards Shi‘i and millenarian groups than towards Hindus. By charting Aurangzeb's trials of millenarian leaders throughout his long reign, it suggests that the emperor's desire to introduce a more standardised legal system was at odds with the ‘millennial’ nature of his own kingship. The article further suggests we should look more closely at the influence of regional politics on Mughal policy-making. The fact that Sunni Gujarati clerics acquired a remarkable intimacy with Aurangzeb, both as prince and emperor, demonstrates how Gujarat's sectarian disputes and political economy could play out in the imperial court. Finally, the article calls for a realistic reappraisal of the long shadows cast by Aurangzeb's Islamist legalism.
Transfer of AlGaN/GaN RF-devices onto diamond substrates via van der Waals bonding
Authors: Gerrer Thomas , Cimalla Volker , Waltereit Patrick , Müller Stefan , Benkhelifa Fouad , Maier Thomas , Czap Heiko , Ambacher Oliver , Quay Rüdiger 
Published: April 2018

AbstractWe present a novel bonding process for gallium nitride-based electronic devices on diamond heat spreaders. In the proposed technology, GaN devices are transferred from silicon (Si) onto single (SCD) and polycrystalline diamond (PCD) substrates by van der Waals bonding. Load-pull measurements on Si and SCD heat spreaders at 3 GHz and 50 V drain bias show comparable power-added-efficiency and output power (Pout) levels. A thermal analysis of the hybrids was performed by comparison of 2 × 1mm2AlGaN/GaN Schottky diodes on Si, PCD, and SCD, which exhibit a homogeneous field in the channel in contrast to gated transistors. Significantly different currents are observed due to the temperature dependent mobility in the 2DEG channel. These measurements are supported by a 3D thermal finite element analysis, which suggests a large impact of our transfer technique on the thermal resistance of these devices. In summary, we show a promising new GaN-on-diamond technology for future high-power, microwave GaN device applications.
Large‐Scale Comparison of Polar Cap Ionospheric Velocities Measured by RISR‐C, RISR‐N, and SuperDARN
Authors: Gillies R. G. , Perry G. W. , Koustov A. V. , Varney R. H. , Reimer A. S. , Spanswick E. , St.‐Maurice J.‐P. , Donovan E. 
Published: April 2018

AbstractThe combined fields of view of the two Resolute Bay Incoherent Scatter Radars (RISR‐Canada and RISR‐North) significantly overlap the field of view of the Super Dual Auroral Radar Network (SuperDARN) radar located in Rankin Inlet. These radars measure ionospheric flow velocities in the polar cap region. Velocity data from the first multiple‐day combined operations of the two RISR radars and Rankin Inlet have been compared. Direct comparisons between line‐of‐sight measurements by both types of radars have been performed. These comparisons included data from 40 days of radar operations and used velocity data from 35 SuperDARN range gates (spanning 1,575 km). Overall, 5.2 × 105 comparison sets were analyzed. In particular during the daytime, signatures of groundscatter in the SuperDARN data often existed at most of the ranges considered in this comparison. This groundscatter could be partially removed from the comparison by only considering SuperDARN data points that had ionospheric velocity measurements in surrounding range cells. It was found that after removing groundscatter contamination at medium SuperDARN ranges (range gates 18–45), velocities measured by the two radar systems agreed when the high‐frequency results were adjusted to account for the refractive index effect. In regions dominated by groundscatter and E region scatter, lower SuperDARN velocities were measured and the overall comparison with the F region RISR velocities was poor.
Modeling NH4NO3 Over the San Joaquin Valley During the 2013 DISCOVER‐AQ Campaign
Authors: Kelly James T. , Parworth Caroline L. , Zhang Qi , Miller David J. , Sun Kang , Zondlo Mark A. , Baker Kirk R. , Wisthaler Armin , Nowak John B. , Pusede Sally E. , Cohen Ronald C. , Weinheimer Andrew J. , Beyersdorf Andreas J. , Tonnesen Gail S. , Bash Jesse O. , Valin Luke C. , Crawford James H. , Fried Alan , Walega James G. 
Published: April 2018

AbstractThe San Joaquin Valley (SJV) of California experiences high concentrations of particulate matter NH4NO3 during episodes of meteorological stagnation in winter. A rich data set of observations related to NH4NO3 formation was acquired during multiple periods of elevated NH4NO3 during the Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER‐AQ) field campaign in SJV in January and February 2013. Here NH4NO3 is simulated during the SJV DISCOVER‐AQ study period with the Community Multiscale Air Quality (CMAQ) model, diagnostic model evaluation is performed using the DISCOVER‐AQ data set, and integrated reaction rate analysis is used to quantify HNO3 production rates. Simulated NO3− generally agrees well with routine monitoring of 24‐hr average NO3−, but comparisons with hourly average NO3− measurements in Fresno revealed differences at higher time resolution. Predictions of gas‐particle partitioning of total nitrate (HNO3 + NO3−) and NHx (NH3 + NH4+) generally agree well with measurements in Fresno, although partitioning of total nitrate to HNO3 is sometimes overestimated at low relative humidity in afternoon. Gas‐particle partitioning results indicate that NH4NO3 formation is limited by HNO3 availability in both the model and ambient. NH3 mixing ratios are underestimated, particularly in areas with large agricultural activity, and additional work on the spatial allocation of NH3 emissions is warranted. During a period of elevated NH4NO3, the model predicted that the OH + NO2 pathway contributed 46% to total HNO3 production in SJV and the N2O5 heterogeneous hydrolysis pathway contributed 54%. The relative importance of the OH + NO2 pathway for HNO3 production is predicted to increase as NOx emissions decrease.
Maternal obesity during lactation may protect offspring from high fat diet-induced metabolic dysfunction
Authors: Monks Jenifer , Orlicky David J. , Stefanski Adrianne L. , Libby Andrew E. , Bales Elise S. , Rudolph Michael C. , Johnson Ginger C. , Sherk Vanessa D. , Jackman Matthew R. , Williamson Kayla , Carlson Nichole E. , MacLean Paul S. , McManaman James L. 
Published: April 2018

Abstract
Background/Objectives
The current obesity epidemic has spurred exploration of the developmental origin of adult heath and disease. A mother’s dietary choices and health can affect both the early wellbeing and lifelong disease-risk of the offspring.

Subjects/Methods
To determine if changes in the mother’s diet and adiposity have long-term effects on the baby’s metabolism, independently from a prenatal insult, we utilized a mouse model of diet-induced-obesity and cross-fostering. All pups were born to lean dams fed a low fat diet but were fostered onto lean or obese dams fed a high fat diet. This study design allowed us to discern the effects of a poor diet from those of mother’s adiposity and metabolism. The weaned offspring were placed on a high fat diet to test their metabolic function.

Results
In this feeding challenge, all male (but not female) offspring developed metabolic dysfunction. We saw increased weight gain in the pups nursed on an obesity-resistant dam fed a high fat diet, and increased pathogenesis including liver steatosis and adipose tissue inflammation, when compared to pups nursed on either obesity-prone dams on a high fat diet or lean dams on a low fat diet.

Conclusion
Exposure to maternal over-nutrition, through the milk, is sufficient to shape offspring health outcomes in a sex- and organ-specific manner, and milk from a mother who is obesity-prone may partially protect the offspring from the insult of a poor diet.
Evaluation of a 12-week lifestyle education intervention with or without partial meal replacement in Thai adults with obesity and metabolic syndrome: a randomised trial
Authors: Chaiyasoot Kusuma , Sarasak Rungnapha , Pheungruang Banchamaphon , Dawilai Suwitcha , Pramyothin Pornpoj , Boonyasiri Adhiratha , Supapueng Orawan , Jassil Friedrich C. , Yamwong Preyanuj , Batterham Rachel L. 
Published: April 2018

Abstract
Background/Objectives
There have been no studies examining the efficacy of meal replacement (MR) on weight loss and metabolic syndrome (MS) improvement in Southeast Asians. Thus, we undertook a 12-week randomised trial to evaluate the effect of a lifestyle education intervention alone (LEI) or with partial MR (LEI + MR) in obese Thai adults with MS.

Subjects/Methods
A total of 110 patients were randomised to receive either LEI or LEI + MR. Both groups received LEI to achieve weight loss. LEI + MR group additionally received two MR daily to replace either breakfast, lunch or dinner. Mean ± SE body mass index of all participants was 34.6 ± 0.6 kg/m2, mean ± SE age was 42.5 ± 1.1 years and 83% of patients were female. Both groups were compared for anthropometric and cardiometabolic indices at 12-week. Body weight was also compared at weeks 38 and 64.

Results
At 12 weeks, both groups exhibited statistically significant percentage weight loss (%WL) compared to initial weight but greater %WL was observed in LEI + MR compared to LEI, 2.9% vs. 1.5%, respectively (p < 0.05). MS criteria such as waist circumference and blood pressure improved significantly in both groups compared to baseline. However, improvement in fasting plasma glucose (FPG) was only significant in LEI + MR, and more participants with impaired FPG at baseline in LEI + MR (42.9%) than LEI (19%) returned to normal FPG at 12 weeks (p < 0.05). HbA1c, fasting insulin and HOMA-IR in LEI + MR were significantly lower than with LEI. At the end of the 12-week intervention period, 16% of participants no longer fulfilled MS criteria. A statistically significant weight loss from baseline persisted until 38 weeks but no longer reached statistically significant difference between groups

Conclusions
LEI and LEI + MR were acceptable and led to improvement in weight and MS. LEI + MR group exhibited additional weight reduction and glycemic benefits at 12 weeks.
Regulation of DNA damage repair and lipid uptake by CX3CR1 in epithelial ovarian carcinoma
Authors: Xie Jia , Gurler Main Hilal , Sacks Joelle D. , Muralidhar Goda G. , Barbolina Maria V. 
Published: April 2018

AbstractFailure of currently used cytotoxic chemotherapy is one of the main reasons behind high mortality from metastatic high grade serous ovarian carcinoma. We found that high expression of a receptor for fractalkine (CX3CR1) significantly correlated with shorter survival of patients with serous ovarian carcinoma treated with cytotoxic DNA damage chemotherapies, and reduction of CX3CR1 expression resulted in sensitization to several DNA damaging modalities, including x-ray radiation and cisplatin. Here, we show that CX3CR1 plays a role in double-strand DNA break response and repair by regulating expression of RAD50 by a MYC-dependent mechanism. We demonstrate that downregulation of CX3CR1 alone and in a combination with irradiation affects peritoneal metastasis in an organ-specific manner; we show that CX3CR1 regulates lipid uptake which could control omental metastasis. This study identifies CX3CR1 as a novel potential target for sensitization of ovarian carcinoma to DNA damage therapies and reduction of peritoneal carcinomatosis.
Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone
Authors: Pickett Julie E. , Thompson John M. , Sadowska Agnieszka , Tkaczyk Christine , Sellman Bret R. , Minola Andrea , Corti Davide , Lanzavecchia Antonio , Miller Lloyd S. , Thorek Daniel LJ 
Published: April 2018

AbstractDiscriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immunoPET imaging in an in vivo mouse model of prosthetic joint infection (PJI). In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry. The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography (PET) with [18F]FDG and [18F]NaF as well as X-ray computed tomography (CT), before being evaluated with the zirconium-89-labeled antibody specific for LTA ([89Zr]SAC55). The anti-LTA mAb exhibited specific binding in vitro to LTA-expressing bacteria. Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater (P < 0.05) uptake at S. aureus-infected prosthesis sites over either the same antibody at sterile prosthesis sites or of control non-specific antibody at infected prosthesis sites. Taken together, the radiolabeled anti-LTA mAb, [89Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI. Future studies are needed to determine whether these findings will translate to human PJI.
Mitochondrial NADP+-dependent isocitrate dehydrogenase deficiency increases cisplatin-induced oxidative damage in the kidney tubule cells
Authors: Kong Min Jung , Han Sang Jun , Kim Jee In , Park Jeen-Woo , Park Kwon Moo 
Published: April 2018

AbstractMitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) plays an important role in the formation of NADPH, which is critical for the maintenance of mitochondrial redox balance. Cis-diamminedichloroplatinum II (cisplatin), an effective anticancer drug, induces oxidative stress-related nephrotoxicity, limiting its use. Therefore, we investigated whether IDH2, which is a critical enzyme in the NADPH-associated mitochondrial antioxidant system, is involved in cisplatin nephrotoxicity. Idh2 gene-deleted (Idh2−/−) mice and wild-type (Idh2
+/+
) littermates were treated with cisplatin, with or without 2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito-T), a mitochondria-specific antioxidant. Cisplatin-induced renal functional and morphological impairments were greater in Idh2−/− mice than in Idh2
+/+
mice. Mito-T mitigated those impairments in both Idh2−/− and Idh2
+/+
mice and this mitigation was greater in Idh2−/− than in Idh2
+/+
mice. Cisplatin impaired IDH2 function in the mitochondria, decreasing mitochondrial NADPH and GSH levels and increasing H2O2 generation; protein, lipid, and DNA oxidation; mitochondrial damage; and apoptosis. These cisplatin-induced changes were much more severe in Idh2−/− mice than in Idh2
+/+
mice. Mito-T treatment attenuated cisplatin-induced alterations in both Idh2−/− and Idh2
+/+
mice and this mitigation was greater in Idh2−/− than in Idh2
+/+
mice. Altogether, these data demonstrate that cisplatin induces the impairment of the mitochondrial IDH2-NADPH-GSH antioxidant system and IDH2 deficiency aggravates cisplatin-induced mitochondrial oxidative damage, inducing more severe nephrotoxicity. This suggests that the mitochondrial IDH2-NADPH-GSH antioxidant system is a target for the prevention of cisplatin-induced kidney cell death.
Modulation of alternative splicing induced by paclitaxel in human lung cancer
Authors: Zhu Ziran , Chen Dan , Zhang Wenjing , Zhao Jinyao , Zhi Lili , Huang Fang , Ji Haoyu , Zhang Jinrui , Liu Han , Zou Lijuan , Wang Yang 
Published: April 2018

AbstractPaclitaxel is utilized as the first-line chemotherapeutic regimen for the majority of advanced non-small-cell lung carcinoma. However, whether paclitaxel could suppress cancer progression through modulating RNA alternative splicing remains largely unknown. Here, we demonstrated the effects of paclitaxel on cell proliferation inhibition, cell cycle arrest, and apoptosis. Mechanistically, paclitaxel leads to transcriptional alteration of networks involved in DNA replication and repair, chromosome segregation, chromatin silencing at rDNA, and mitosis at the transcriptional level. Moreover, paclitaxel regulates a number of cancer-associated RNA alternative splicing events, including genes involved in cellular response to DNA damage stimulus, preassembly of GPI anchor in ER membrane, transcription, and DNA repair. In particular, paclitaxel modulates the splicing of ECT2, a key factor involved in the regulation of cytokinesis. Briefly, paclitaxel favors the production of ECT2-S, the short splicing isoforms of ECT2, thereby inhibiting cancer cell proliferation. Our study provides mechanistic insights of paclitaxel on RNA alternative splicing regulation, thus to offer a potential novel route for paclitaxel to inhibit cancer progression.
Distinct mutational signatures characterize concurrent loss of polymerase proofreading and mismatch repair
Authors: Haradhvala N. J. , Kim J. , Maruvka Y. E. , Polak P. , Rosebrock D. , Livitz D. , Hess J. M. , Leshchiner I. , Kamburov A. , Mouw K. W. , Lawrence M. S. , Getz G. 
Published: April 2018

AbstractFidelity of DNA replication is maintained using polymerase proofreading and the mismatch repair pathway. Tumors with loss of function of either mechanism have elevated mutation rates with characteristic mutational signatures. Here we report that tumors with concurrent loss of both polymerase proofreading and mismatch repair function have mutational patterns that are not a simple sum of the signatures of the individual alterations, but correspond to distinct, previously unexplained signatures: COSMIC database signatures 14 and 20. We then demonstrate that in all five cases in which the chronological order of events could be determined, polymerase epsilon proofreading alterations precede the defect in mismatch repair. Overall, we illustrate that multiple distinct mutational signatures can result from different combinations of a smaller number of mutational processes (of either damage or repair), which can influence the interpretation and discovery of mutational signatures.
The topological requirements for robust perfect adaptation in networks of any size
Authors: Araujo Robyn P. , Liotta Lance A. 
Published: April 2018

AbstractRobustness, and the ability to function and thrive amid changing and unfavorable environments, is a fundamental requirement for living systems. Until now it has been an open question how large and complex biological networks can exhibit robust behaviors, such as perfect adaptation to a variable stimulus, since complexity is generally associated with fragility. Here we report that all networks that exhibit robust perfect adaptation (RPA) to a persistent change in stimulus are decomposable into well-defined modules, of which there exist two distinct classes. These two modular classes represent a topological basis for all RPA-capable networks, and generate the full set of topological realizations of the internal model principle for RPA in complex, self-organizing, evolvable bionetworks. This unexpected result supports the notion that evolutionary processes are empowered by simple and scalable modular design principles that promote robust performance no matter how large or complex the underlying networks become.
A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis
Authors: Powell Emily , Shao Jiansu , Picon Hector M. , Bristow Christopher , Ge Zhongqi , Peoples Michael , Robinson Frederick , Jeter-Jones Sabrina L. , Schlosberg Christopher , Grzeskowiak Caitlin L. , Yang Fei , Wu Yun , Wistuba Ignacio , Moulder Stacy L. , Symmans William F. , Scott Kenneth L. , Edwards John R. , Liang Han , Heffernan Timothy P. , Piwnica-Worms Helen 
Published: April 2018

AbstractTumor cells disseminate early in tumor development making metastasis-prevention strategies difficult. Identifying proteins that promote the outgrowth of disseminated tumor cells may provide opportunities for novel therapeutic strategies. Despite multiple studies demonstrating that the mesenchymal-to-epithelial transition (MET) is critical for metastatic colonization, key regulators that initiate this transition remain unknown. We serially passaged lung metastases from a primary triple negative breast cancer xenograft to the mammary fat pads of recipient mice to enrich for gene expression changes that drive metastasis. An unbiased transcriptomic signature of potential metastatic drivers was generated, and a high throughput gain-of-function screen was performed in vivo to validate candidates. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) was identified as a metastatic driver. CEACAM5 overproduction enriched for an epithelial gene expression pattern and facilitated tumor outgrowth at metastatic sites. Tissues from patients with metastatic breast cancer confirmed elevated levels of CEACAM5 in lung metastases relative to breast tumors, and an inverse correlation between CEACAM5 and the mesenchymal marker vimentin was demonstrated. Thus, CEACAM5 facilitates tumor outgrowth at metastatic sites by promoting MET, warranting its investigation as a therapeutic target and biomarker of aggressiveness in breast cancer.