bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects
Authors: Nam H W , Karpyak V M , Hinton D J , Geske J R , Ho A M C , Prieto M L , Biernacka J M , Frye M A , Weinshilboum R M , Choi D-S 
Published: August 2015

AbstractAcamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD.
275–285 GHz balanced frequency quadrupler chain in 45 nm SOI CMOS
Authors: Abbasi M. , Ricketts D.S. 
Published: August 2015

A 280 GHz broadband balanced frequency quadrupler chain is presented. The quadrupler can be used to generate as high as 200 μW over a −3 dB bandwidth of 275–285 GHz, which enables emerging applications in sub‐millimetre‐wave communications and remote sensing. The circuit is designed and fabricated in a 45 nm silicon on insulator (SOI) CMOS technology and occupies an area of 0.21 mm2 including the pads. The chip consumes 85 mA dc current from a 1.1 V supply.
A broadly neutralizing human monoclonal antibody is effective against H7N9
Authors: Tharakaraman Kannan , Subramanian Vidya , Viswanathan Karthik , Sloan Susan , Yen Hui-Ling , Barnard Dale L. , Leung Y. H. Connie , Szretter Kristy J. , Koch Tyree J. , Delaney James C. , Babcock Gregory J. , Wogan Gerald N. , Sasisekharan Ram , Shriver Zachary 
Published: August 2015

Significance
Emerging influenza subtypes, such as the recently identified H7N9 strains, are of considerable public health concern. Although vaccines are an important countermeasure, influenza vaccines tend to be subtype- and strain-specific, such that they may not be widely available in the event of the human adaptation and spread of an unanticipated strain or subtype. Additionally, influenza strains have demonstrated the ability to develop resistance to existing antivirals, including oseltamivir. As such, there is a need for novel interventions that can treat and/or prevent serious influenza infection. We demonstrate that VIS410, a human mAb, neutralizes a wide range of influenza A viruses and effectively manages H7N9 infection.
LINE-1 expression and retrotransposition in Barrett’s esophagus and esophageal carcinoma
Authors: Doucet-O'Hare Tara T. , Rodić Nemanja , Sharma Reema , Darbari Isha , Abril Gabriela , Choi Jungbin A. , Young Ahn Ji , Cheng Yulan , Anders Robert A. , Burns Kathleen H. , Meltzer Stephen J. , Kazazian Haig H. 
Published: August 2015

Significance
By studying premalignant conditions, we can gain a better understanding of the sources of genomic instability and improve cancer prevention and treatment. Because retrotransposition has been observed in many gastrointestinal epithelial cancer types, we focused on L1 mobilization as a source of instability in cancer. Here, we demonstrate that L1 retrotransposition is active in esophageal adenocarcinoma and its precursor, Barrett’s esophagus (BE). We detected clonal populations with precursor cells marked by L1 retrotransposition events either in the normal esophagus or BE. These clones expanded in the BE or esophageal adenocarcinoma (EAC), indicating that somatic L1 insertions are not only potential mutagens in the development of EAC, but also useful markers of tumor clones as well.
Teaching critical thinking
Authors: Holmes N. G. , Wieman Carl E. , Bonn D. A. 
Published: August 2015

Significance
Understanding and thinking critically about scientific evidence is a crucial skill in the modern world. We present a simple learning framework that employs cycles of decisions about making and acting on quantitative comparisons between datasets or data and models. With opportunities to improve the data or models, this structure is appropriate for use in any data-driven science-learning setting. This structure led to significant and sustained improvement in students’ critical thinking behaviors, compared with a control group, with effects far beyond that of statistical significance.
MutL traps MutS at a DNA mismatch
Authors: Qiu Ruoyi , Sakato Miho , Sacho Elizabeth J. , Wilkins Hunter , Zhang Xingdong , Modrich Paul , Hingorani Manju M. , Erie Dorothy A. , Weninger Keith R. 
Published: August 2015

Significance
DNA mismatch repair is the process by which errors generated during DNA replication are corrected. Mutations in the proteins that initiate mismatch repair, MutS and MutL, are associated with greater than 80% of hereditary nonpolyposis colorectal cancer (HNPCC) and many sporadic cancers. The assembly of MutS and MutL at a mismatch is an essential step for initiating repair; however, the nature of these interactions is poorly understood. Here, we have discovered that MutL fundamentally changes the properties of mismatch-bound MutS by preventing it from sliding away from the mismatch, which it normally does when isolated. This finding suggests a mechanism for localizing the activity of repair proteins near the mismatch.
Human hippocampus represents space and time during retrieval of real-world memories
Authors: Nielson Dylan M. , Smith Troy A. , Sreekumar Vishnu , Dennis Simon , Sederberg Per B. 
Published: August 2015

Significance
The rodent hippocampus contains neurons that code for space on the scale of meters, a discovery that was recently awarded a Nobel Prize. However, it remains unclear whether humans harness similar representations for memory at the scale of their lives. Our results reveal that the human hippocampus represents the spatial and temporal location of memories for real-life events at scales of up to 30 km and a month of time. They further suggest that real-world representations of space and time are more intimately entwined in the hippocampus than previously thought, validating the relevance of decades of rodent studies for human memory and providing a potential mechanism for how we weave the episodic memories of our lives.
Regulated proteolysis of a cross-link–specific peptidoglycan hydrolase contributes to bacterial morphogenesis
Authors: Singh Santosh Kumar , Parveen Sadiya , SaiSree L , Reddy Manjula 
Published: August 2015

Significance
Peptidoglycan (PG) is a unique and essential cross-linked, bag-like macromolecule that completely encases the cytoplasmic membrane and confers shape and rigidity to a bacterial cell. Therefore, bacterial cell growth is tightly coupled to PG expansion, requiring the coordinate activity of hydrolases that cleave the cross-links and synthases that catalyze the cross-link formation. This study highlights the importance of cross-link cleavage and its regulation in PG biogenesis by demonstrating the modulation of a cross-link–specific PG hydrolytic enzyme, MepS, by a previously unidentified degradation system consisting of an outer membrane lipoprotein, NlpI and a periplasmic protease, Prc. These studies facilitate better understanding of bacterial cell wall synthesis, which is a target of several antimicrobial therapeutic agents.
Orchestration of three transporters and distinct vascular structures in node for intervascular transfer of silicon in rice
Authors: Yamaji Naoki , Sakurai Gen , Mitani-Ueno Namiki , Ma Jian Feng 
Published: August 2015

Significance
Requirement of mineral elements differs with different organs and tissues; therefore, plants have developed systems for preferentially delivering mineral elements to tissues with high requirement. However, the molecular mechanisms for these systems are poorly understood. We took silicon (Si) as an example and revealed an efficient distribution system occurring in the node of rice, which is a hub for distribution. We found that hyperaccumulation of Si in the husk (more than 10%) is achieved by cooperation of three different Si transporters localized at the different cell layers in the node. Furthermore, mathematical modeling showed that an apoplastic barrier and development of enlarged vascular bundles are also required. Our work revealed a set of players for efficient distribution control in node.
Transforming growth factor-β signaling is constantly shaping memory T-cell population
Authors: Ma Chaoyu , Zhang Nu 
Published: August 2015

Significance
A persistent memory T-cell population is the basis for successful T-cell–based vaccine against pathogens. Numerous extracellular and intracellular molecules have been demonstrated to play critical roles in the differentiation of memory T cells; however, the mechanisms that control the long-term maintenance of memory T cells remain incompletely understood. Here we show that continuous transforming growth factor-β signaling is required to maintain the identity of memory T cells.
Antagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase
Authors: Farha Maya A. , Czarny Tomasz L. , Myers Cullen L. , Worrall Liam J. , French Shawn , Conrady Deborah G. , Wang Yang , Oldfield Eric , Strynadka Natalie C. J. , Brown Eric D. 
Published: August 2015

Significance
Small molecule probes have proved indispensable in dissecting bacterial systems. Their combinations have further expanded their utility as tools by enabling the study of interacting pathways. As such, screens for synergy between compounds have been widely used to reveal functional connections among cellular components. The utility of antagonism, however, has largely been overlooked. This study highlights the value of antagonistic interactions in elucidating genetic networks and mechanisms of drug action. Herein, we report on the discovery of clomiphene, an inhibitor of bacterial cell wall synthesis, uncovered through a systematic screen for antagonism. The discovery of clomiphene shed light on the pathways of cell wall biogenesis and, importantly, represents a new promising lead for the fight against infection.
Talin determines the nanoscale architecture of focal adhesions
Authors: Liu Jaron , Wang Yilin , Goh Wah Ing , Goh Honzhen , Baird Michelle A. , Ruehland Svenja , Teo Shijia , Bate Neil , Critchley David R. , Davidson Michael W. , Kanchanawong Pakorn 
Published: August 2015

Significance
Focal adhesions (FAs) mediate cell–extracellular matrix interactions and consist of integrin receptors linked to the actin cytoskeleton via multiprotein complexes organized into nanoscale strata. In this work, we sought to determine the molecular basis of FA nanostructure. Combining superresolution microscopy and protein engineering, we demonstrate the structural role of talin in regulating the nanoscale architecture of FAs. Talin specifies the dimension of the FA core, akin to a molecular ruler, in a remarkably modular manner. Our results define the molecular geometry of the integrin–talin–actin module that comprises the key mechanical linkage within FAs and elucidate how such interactions serve to integrate multiple cellular forces at adhesion sites.
Semi-analytic model predictions of mass segregation from groups to clusters
Authors: Contini E. , Kang X. 
Published: August 2015

Abstract
Taking advantage of a high-resolution simulation coupled with a state-of-art semi-analytic model of galaxy formation, we probe the mass segregation of galaxies in groups and clusters, focusing on which physical mechanisms are driving it. We find evidence of mass segregation in groups and clusters up to the virial radius, both looking at the galaxy stellar mass and subhalo mass. The physical mechanism responsible for that is consistent with dynamical friction, a drag-force that brings more massive galaxies faster towards the innermost regions of the halo. At odds with observational results, we do not find the inclusion of low-mass galaxies in the samples, down to stellar mass M* = 109 M⊙, to change the overall trend shown by intermediate and massive galaxies. Moreover, stellar stripping as well as the growth of galaxies after their accretion, do not contribute either in shaping mass segregation or mixing the radial mass distribution. Beyond the virial radius we find an ‘antimass segregation’ in groups that progressively weakens in clusters. The continuous accretion of new objects and recent merger events play a different role depending on the halo mass on to which accreting material is falling.
Durability of Response in Children Treated With Pegylated Interferon alfa‐2a ± Ribavirin for Chronic Hepatitis C
Authors: Schwarz Kathleen B. , Molleston Jean P. , Jonas Maureen M. , Wen Jessica , Murray Karen F. , Rosenthal Philip , Gonzalez‐Peralta Regino P. , Lobritto Steven J. , Mogul Douglas , Pavlovic Vedran , Warne Charles , Wat Cynthia , Thompson Bruce 
Published: August 2015

ABSTRACTObjectives:No long‐term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C. This prospective, multicenter, long‐term follow‐up (LTFU) study aimed to assess long‐term durability of sustained virological response (SVR), long‐term safety and tolerability, and the association between IL28B genotype and treatment response, in children previously treated with PegIFN alfa‐2a ± ribavirin (RBV) in the PEDS‐C trial.Methods:A total of 93 patients were assessed for enrollment, and 38 enrolled in the study. Patients attended 2 study visits: 5 (mean 5.6, range 4.1–6.6) and 6 (6.6, 5.1–7.7) years after treatment cessation. Standardized medical history, physical examination, and laboratory testing were performed at these visits. Reminder telephone calls were conducted at 4 and 8 months after the initial visit.Results:The LTFU cohort was the representative of the original PEDS‐C cohort because both baseline and treatment characteristics were comparable. Of the 38 participants, 21 achieved SVR (responders) during the PEDS‐C trial and 17 had not (nonresponders). All 21 responders maintained undetectable hepatitis C virus RNA during the LTFU (4.4–7.0 years after achieving SVR) in contrast to the nonresponders who demonstrated persistent viremia. IL28B CC genotype was associated with SVR (67% vs 30% in non‐CC, P = 0.028).Conclusion:Long‐term durability of SVR is excellent following PegIFN alfa‐2a treatment in children with chronic hepatitis C; SVR is higher in those with IL28B CC versus non‐CC.
Practice Variations in the Management of Inflammatory Bowel Disease Between Pediatric and Adult Gastroenterologists
Authors: Assa Amit , Avni Irit , Ben‐Bassat Ofer , Niv Yaron , Shamir Raanan 
Published: August 2015

ABSTRACTBackground:Different practice guidelines and consensus statements for both pediatric‐ and adult‐onset inflammatory bowel disease exist. Although variations in medical care among gastroenterologists are common, it is unknown whether there are fundamental differences between disciplines. The primary aim of the present study was to investigate differences in common practices across disciplines.Methods:This was a prospective, questionnaire‐based survey of gastroenterologists attending gastroenterology meetings in Israel. The questionnaire covered attitudes to medical resources, diagnostic and follow‐up measures as well as therapeutic approaches.Results:Overall, 120 (60%) of the approached adult gastroenterologists (AGs) and 49 (75%) pediatric gastroenterologists (PGs) completed the questionnaire. The 2 groups differed significantly in various practice areas. Pediatric patients are seen more frequently and for longer appointments. PGs tend to assess thiopurine metabolites (96% vs 47%) more often during treatment. There is a significant variation in practice between groups concerning infectious serology status and vaccinations. Methotrexate in Crohn patients is used more commonly by PGs (55% vs 22%). Long‐term combination therapy of thiopurines and anti‐tumor necrosis factorα agents is used more often by AGs. In patients with ulcerative colitis AGs use oral 5‐aminosalicylic acid once daily (51% vs 21%) and add rectal agents from the first day of treatment (72% vs 35%) more often as compared with PGs.Conclusions:This study demonstrates that common practices in inflammatory bowel disease patients differ significantly between adult and pediatric practitioners. These findings call for investigating the reasons for these differences and promoting strategies to diminish these gaps.
Do Distinct Functional Dyspepsia Subtypes Exist in Children?
Authors: Turco Rossella , Russo Marina , Martinelli Massimo , Castiello Rosa , Coppola Vincenzo , Miele Erasmo , Staiano Annamaria 
Published: August 2015

ABSTRACTBackground and Aim:Two different subtypes of functional dyspepsia (FD) are recognized in adults: epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). The aim of the study was to assess the presence of FD subtypes in childhood at diagnosis and to observe changes at follow‐up.Methods:A total of 100 patients with a diagnosis of FD based on pediatric Rome III criteria were consecutively enrolled. FD subtypes were successively classified through adult Rome III classification. Children were revaluated after 6 months of follow‐up (T1).Results:At T0, 17 (17%) of 100 patients were classified as EPS, whereas 47 (47%) of 100 patients fulfilled criteria for PDS. In 36 (36%) of 100 children an overlap between the 2 subtypes was identified. Nausea was significantly higher in PDS and overlap groups when compared with EPS (χ2 = 21.7, P = 0.0001; χ2 = 20.7, P = 0.0001). Headache was significantly increased in PDS and overlap groups compared with patients with EPS (χ2 = 9.8, P = 0.001; χ2 = 13.1, P = 0.0001, respectively). At T1 among children belonging to PDS group at enrolment, 9 of 47 (19.1%) changed to EPS group, and 9 of 47 (19.1%) changed to the overlap group. Five (29.4%) of 17 patients and 2 (11.8%) of 17 children diagnosed as having EPS at T0 switched to PDS and overlap group, respectively. Of the 36 patients with overlap at enrollment, 11 (30.6%) satisfied criteria for PDS, and 7 (19.4%) switched to EPS group.Conclusions:Two distinct FD subtypes are identifiable in pediatric population. A high percentage of overlap and a variation of subtype over time were found, suggesting a common pathophysiologic mechanism.
Solitary Hepatic Nodule Adjacent to the Right Portal Vein
Authors: Alhammad Abdullah , Kamath Binita M. , Chami Rose , Ng Vicky L. , Chavhan Govind B. 
Published: August 2015

ABSTRACTBackground:Hepatic lesions have been described in Alagille syndrome (ALGS) in isolated case reports, and most of these have been reported to be hepatocellular carcinoma.Objectives:The aim of the present study was to determine the frequency, imaging, and histopathologic characteristics of hepatic lesions in children with ALGS.Methods:Available abdominal imaging of children with ALGS was retrospectively reviewed to note the presence of any focal liver lesion, its location, and imaging characteristics. Other findings including signs of portal hypertension, portal lymph nodes, and splenic and renal abnormalities were also noted. Findings were correlated with pathology in available cases and with clinical follow‐up.Results:Of 55 children with clinically and/or genetically confirmed ALGS followed in the liver clinic, 39 (19 boys, 20 girls; mean age 8.9 years) with imaging available on picture archival and communication system were included in the study. Focal hepatic lesions were seen in 12 of the 39 (30%) children, solitary in 11 and multiple in 1. Ten of these children had a large nodule adjacent to the right portal vein. The median diameter of the lesions was 8.1 cm (range 5.6–9.8 cm). Magnetic resonance imaging features and pathology in available cases were suggestive of a regenerative nodule. α‐fetoprotein levels were normal in all except 1 child who had mild elevation.Conclusions:Combining our series and previous case reports, the presence of a large nodule adjacent to the right portal vein appears to be a common finding in ALGS. The typical location, normal α‐fetoprotein levels, and magnetic resonance imaging features with vessels coursing through the lesion can reliably differentiate this benign nodule from hepatocellular carcinoma.
Local population structure and patterns of Western Hemisphere dispersal forCoccidioides spp., the fungal cause of Valley Fever
Authors: Engelthaler David M. , Roe Chandler C. , Hepp Crystal M. , Teixeira Marcus , Driebe Elizabeth M. , Schupp James M. , Gade Lalitha , Waddell Victor , Komatsu Kenneth , Arathoon Eduardo , Logemann Heidi , Thompson George R. , Chiller Tom , Barker Bridget , Keim Paul , Litvintseva Anastastia P. 
Published: August 2015

AbstractCoccidioidomycosis (or Valley Fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species,Coccidioides immitisandC. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding as new endemic clusters have been identified in the state of Washington, well outside of the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we perform multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure inC. posadasiiand demonstrate presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America and Central America. Although a smaller number ofC. immitisstrains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja Mexico. Bayesian analyses indicated thatC. posadasiiis the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin forC. posadasiiand describe a pathway for dispersal and distribution out of this region.