bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of perineural invasion in locally advanced bucco alveolar complex carcinomas treated with surgery and postoperative radiation ± concurrent chemotherapy
Authors: Anand Anil Kumar , Agarwal Pankaj , Gulia Abhishek , Goel Vineeta , Jain Jyotika , Chaturvedi Harit , Hazarika Biswajyoti , Mukherjee Urmi , Arora Deepak , Bansal Anil Kumar
Published: April 2017

Background

The purpose of this study was to evaluate prognostic factors, locoregional control, and survival in locally advanced bucco‐alveolar complex cancers.

Methods

A retrospective review of 83 patients treated between January 2009 and December 2012 with bucco‐alveolar complex cancers was conducted. All patients had surgery and adjuvant radiotherapy with intensity‐modulated radiotherapy (IMRT) with/without concurrent chemotherapy. Survival analysis was performed using Kaplan‐Meier and multivariable Cox regression model.

Results

On univariate and multivariate analysis, perineural invasion (PNI) was found to be an independent adverse risk factor. Patients with PNI‐positive disease had significantly worse 2‐year disease‐free survival (DFS), locoregional failure free survival, and overall survival (OS) as compared to patients with PNI‐negative disease (P < 0. 001, 0.001 and < 0. 001) respectively.

Conclusion

Compared with patients with PNI‐negative disease, patients with PNI‐positive disease had much worse outcome despite aggressive adjuvant treatment. It warrants escalation of therapy and modification in radiation portals to cover neural pathways in patients with PNI‐positive disease.
Cross‐sectional study of the feasibility of urinating in a standing position among women in the third trimester of pregnancy
Authors: Yang Pei‐Yu , Chen Chi‐Cheng , Chang Cherry Yin‐Yi , Chou Eric Chieh‐Lung , Meng Nai‐Hsin
Published: April 2017

Using a homemade auxiliary device, urinating in a standing position was a feasible alternative to a seated position for women during pregnancy.
Dismantling the Developmental Education Pipeline: Potent Pedagogies and Promising Practices That Address the College Readiness Gap
Authors: Henry Laurie A. , Stahl Norman A.
Published: April 2017

This commentary explores pedagogical, societal, and political aspects of the college/career readiness reform movement as it impacts students in secondary classrooms. The authors begin with a snapshot of the students often left in the shadows of educational reform efforts, leaving them academically underprepared and destined for college developmental education. Then, the authors share their perspective related to the potential of the Common Core State Standards to raise student achievement and close achievement gaps. Finally, they highlight college preparation programs that seek to address this gap, along with promising practices supporting the aspirations of these students to pursue educational opportunities beyond secondary school.
Trabecular resorption patterns of cement–bone interlock regions in total knee replacements
Authors: Goodheart Jacklyn R. , Miller Mark A. , Oest Megan E. , Mann Kenneth A.
Published: April 2017

With in vivo service, there is loss of mechanical interlock between trabeculae and PMMA cement in total knee replacements. The mechanisms responsible for the loss of interlock are not known, but loss of interlock results in weaker cement–bone interfaces. The goal of this study was to determine the pattern of resorption of interdigitated bone using a series of 20 postmortem retrieved knee replacements with a wide range of time in service (3–22 years). MicroCT scans were obtained of a segment of the cement–bone interface below the tibial tray for each implant. Image processing methods were used to determine interface morphology and to identify supporting, interdigitated, resorbed, and isolated bone as a function of axial position. Overall, the amount of remaining interdigitated bone decreased with time in service (p = 0.0114). The distance from the cement border (at the extent of cement penetration into the bone bed) to 50% of the interdigitated volume decreased with time in service (p = 0.039). Isolated bone, when present, was located deep in the cement layer. Overall, resorption appears to start at the cement border and progresses into the cement layer. Initiation of trabecular resorption near the cement border may be a consequence of proximity to osteoclastic cells in the adjacent marrow space. Clinical Significance: Aseptic loosening of joint replacements remains an important clinical problem. This work explores the process and pattern of trabecular bone resorption responsible for loss of interface fixation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2773–2780, 2017.
Nitrogen mineralization from digestate in comparison to sewage sludge, compost and urea in a laboratory incubated soil experiment
Authors: Tambone Fulvia , Adani Fabrizio
Published: April 2017

This paper evaluated, in a laboratory incubated soil, the properties of digestate as a nitrogen fertilizer in comparison with sewage sludge, compost and urea, this last as a typical mineral fertilizer. The incubation period lasted for 90 d and during this time, pH, CO2andevolution were measured. The maximum concentration of nitrate was reached in the incubated microcosm fertilized by urea (133 mg kg−1after 62 d), and that of digestate was very similar (113 mg kg−1). Soil treated with compost showed a slower nitrate evolution. A significantly negative correlation was detected between cumulative nitrogen nitrified at the end of the trial, and the values of the C:N ratio of the biomasses used (compost, sludge and digestate) (mg kg−1vs. C:N,r = –0.94,n= 3,p< 0.05), and between the alkyl‐C content at the end of the experiment (mg kg−1vs. alkyl‐C,r= –0.95,n= 3,p< 0.05). As expected, pH decreases and soil respiration (CO2evolution) were also well correlated with the content of nitrate. Considering that about 90% of the nitrogen content in the digestate is short acting, the results obtained indicate that the nitrogen rate of mineralization in digestate is very similar to that of urea, confirming that digestate could replace traditional mineral fertilizers.
Investigating the Importance of the Pocket‐estimation Method in Pocket‐based Approaches: An Illustration Using Pocket‐ligand Classification
Authors: Caumes Géraldine , Borrel Alexandre , Abi Hussein Hiba , Camproux Anne‐Claude , Regad Leslie
Published: April 2017

Small molecules interact with their protein target on surface cavities known as binding pockets. Pocket‐based approaches are very useful in all of the phases of drug design. Their first step is estimating the binding pocket based on protein structure. The available pocket‐estimation methods produce different pockets for the same target. The aim of this work is to investigate the effects of different pocket‐estimation methods on the results of pocket‐based approaches. We focused on the effect of three pocket‐estimation methods on a pocket‐ligand (PL) classification. This pocket‐based approach is useful for understanding the correspondence between the pocket and ligand spaces and to develop pharmacological profiling models. We found pocket‐estimation methods yield different binding pockets in terms of boundaries and properties. These differences are responsible for the variation in the PL classification results that can have an impact on the detected correspondence between pocket and ligand profiles. Thus, we highlighted the importance of the pocket‐estimation method choice in pocket‐based approaches.
Pericardial fat volume and incident atrial fibrillation in the Multi‐Ethnic Study of Atherosclerosis and Jackson Heart Study
Authors: Heckbert Susan R. , Wiggins Kerri L. , Blackshear Chad , Yang Yi , Ding Jingzhong , Liu Jiankang , McKnight Barbara , Alonso Alvaro , Austin Thomas R. , Benjamin Emelia J. , Curtis Lesley H. , Sotoodehnia Nona , Correa Adolfo
Published: April 2017

Objective

To determine whether greater pericardial fat volume would be associated with increased risk of incident atrial fibrillation (AF).

Methods

In the Multi‐Ethnic Study of Atherosclerosis and Jackson Heart Study, pericardial fat volume was quantified by computed tomography. Incident AF was identified from discharge diagnosis codes, study electrocardiograms, and Medicare claims.

Results

Among 7,991 participants, 40% were African American, 32% white, 18% Hispanic, and 10% Chinese American; mean age was 62 years; 55% were women. During an average of 10.0 years of follow‐up in the Multi‐Ethnic Study of Atherosclerosis and 4.5 years in the Jackson Heart Study, 756 incident AF cases were identified. After adjustment for age, sex, study, race/ethnicity, height, glucose status, systolic blood pressure, treated hypertension, and BMI, greater pericardial fat volume was associated with higher AF risk in Hispanics (hazard ratio 1.24 per SD, 95% confidence interval 1.05‐1.46) but not overall (hazard ratio 1.06, 95% confidence interval 0.97‐1.15). In mediation analysis, pericardial fat volume partially mediated the association of BMI with incident AF in Hispanics.

Conclusions

After adjustment for BMI, greater pericardial fat volume was associated with incident AF in Hispanics but not overall. Additional research is needed on the mechanisms by which pericardial fat volume is related to increased AF risk and possible differences by race/ethnicity.
A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis
Authors: Shah Rikin K. , Munson Mary , Wierenga Klaas J. , Pokala Hanumantha R. , Newburger Peter E. , Crawford David
Published: April 2017

VPS45‐associated severe congenital neutropenia (SCN) is a rare disorder characterized by life‐threating infections, neutropenia, neutrophil and platelet dysfunction, poor response to filgrastim, and myelofibrosis with extramedullary hematopoiesis. We present a patient with SCN due to a homozygous c.1403C>T (p.P468L) mutation in VPS45, critical regulator of SNARE‐dependent membrane fusion. Structural modeling indicates that P468, like the T224 and E238 residues affected by previously reported mutations, cluster in a VPS45 “hinge” region, indicating its critical role in membrane fusion and VPS45‐associated SCN. Bone marrow transplantation, complicated by early graft failure rescued with stem cell boost, led to resolution of the hematopoietic phenotype.
Prenatal abnormal features of fetal mainstem bronchi: back to the basics
Authors: Dabadie Alexia , Kheiri Mélinda , Pico Harmony , Gorincour Guillaume , Quarello Edwin
Published: April 2017

What's Already Known About This Topic?

Situs is ideally assessed by the assessment of the atrial appendages. But, prenatally, this remains very difficult. Fetal situs is usually considered indirectly by the assessment of the abdominal aorta and the inferior vena cava.

What Does This Study Add?

This study described a method allowing us to distinguish prenatally the fetal situs in the setting of fetal heterotaxia by considering the features of the mainstem bronchi.
In vitro metabolism of exemestane by hepatic cytochrome P450s: impact of nonsynonymous polymorphisms on formation of the active metabolite 17β‐dihydroexemestane
Authors: Peterson Amity , Xia Zuping , Chen Gang , Lazarus Philip
Published: April 2017

Exemestane (EXE) is an endocrine therapy commonly used by postmenopausal women with hormone‐responsive breast cancer due to its potency in inhibiting aromatase‐catalyzed estrogen synthesis. Preliminary in vitro studies sought to identify phase I EXE metabolites and hepatic cytochrome P450s (CYP450s) that participate in EXE biotransformation. Phase I metabolites were identified by incubating EXE with HEK293‐overexpressed CYP450s. CYP450s 1A2, 2C8, 2C9, 2C19, 2D6, 3A4, and 3A5 produce 17β‐dihydroexemestane (17β‐DHE), an active major metabolite, as well as two inactive metabolites. 17β‐DHE formation in pooled human liver microsomes subjected to isoform‐specific CYP450 inhibition was also monitored using tandem mass spectrometry. 17β‐DHE production in human liver microsomes was unaffected by isoform‐specific inhibition of CYP450s 2A6, 2B6, and 2E1 but decreased 12–39% following inhibition of drug‐metabolizing enzymes from CYP450 subfamilies 1A, 2C, 2D, and 3A. These results suggest that redundancy exists in the EXE metabolic pathway with multiple hepatic CYP450s catalyzing 17β‐DHE formation in vitro. To further expand the knowledge of phase I EXE metabolism, the impact of CYP450 genetic variation on 17β‐DHE formation was assessed via enzyme kinetic parameters. Affinity for EXE substrate and enzyme catalytic velocity were calculated for hepatic wild‐type CYP450s and their common nonsynonymous variants by monitoring the reduction of EXE to 17β‐DHE. Several functional polymorphisms in xenobiotic‐metabolizing CYP450s 1A2, 2C8, 2C9, and 2D6 resulted in deviant enzymatic activity relative to wild‐type enzyme. Thus, it is possible that functional polymorphisms in EXE‐metabolizing CYP450s contribute to inter‐individual variability in patient outcomes by mediating overall exposure to the drug and its active metabolite, 17β‐DHE.
An uncommon cause of miliary pattern of pulmonary nodules—diffuse pulmonary meningotheliomatosis
Authors: Jayaschandran Vivek , Gjorgova‐Gjeorgjievski Sandra , Siddique Haamid
Published: April 2017

Pulmonary meningothelial‐like nodules are benign lesions that are often incidentally detected in surgically resected lung tissue. These nodules are usually asymptomatic and single. Rarely, they present as diffuse micronodules similar to the miliary pattern seen in tuberculosis or metastatic cancer. While diffuse meningothelial‐like micronodules are usually benign, it is important to include this condition in the differential diagnosis of patients presenting with diffuse micronodules. We present the case of a 74‐year‐old asymptomatic female referred to the pulmonary clinic for evaluation of incidentally detected diffuse bilateral pulmonary nodules. A transbronchial biopsy established a diagnosis of diffuse pulmonary meningotheliomatosis, obviating the need for further invasive workup. She remains stable after more than 2 years of follow‐up.
Investigating the Efficacy of a Web‐Based Early Reading and Professional Development Intervention for Young English Learners
Authors: Amendum Steven J. , Bratsch‐Hines Mary , Vernon‐Feagans Lynne
Published: April 2017

The purpose of this study was to evaluate whether the Targeted Reading Intervention (TRI), a professional development and early reading intervention program delivered via webcam technology, could support the early reading progress of English learners (ELs). Participants for the current study were drawn from a larger three‐year randomized controlled trial and included 108ELs from 47 classrooms randomly assigned to treatment and control conditions. Teachers in treatment classrooms used theTRIin one‐on‐one sessions in the regular classroom for approximately 15 minutes per day. Weekly, and later biweekly, webcam coaching sessions between aTRIcoach and each classroom teacher allowed the coach to interact with both the teacher and students in real time and allowed classroom teachers to receive real‐time feedback from the coach. Two‐level hierarchical linear models suggested thatELs struggling with learning to read in intervention classrooms significantly outperformed their peers in control classrooms on word‐level measures of early reading, with effect sizes of .43 and .45, but not on text‐level measures. Results also suggested thatELs struggling with learning to read were gaining at the same rate as their nonstruggling peers but were unable to catch up within the study year.
High‐Performance Piezoelectric Nanogenerators with Imprinted P(VDF‐TrFE)/BaTiO3 Nanocomposite Micropillars for Self‐Powered Flexible Sensors
Authors: Chen Xiaoliang , Li Xiangming , Shao Jinyou , An Ningli , Tian Hongmiao , Wang Chao , Han Tianyi , Wang Li , Lu Bingheng
Published: April 2017

Piezoelectric nanogenerators with large output, high sensitivity, and good flexibility have attracted extensive interest in wearable electronics and personal healthcare. In this paper, the authors propose a high‐performance flexible piezoelectric nanogenerator based on piezoelectrically enhanced nanocomposite micropillar array of polyvinylidene fluoride‐trifluoroethylene (P(VDF‐TrFE))/barium titanate (BaTiO3) for energy harvesting and highly sensitive self‐powered sensing. By a reliable and scalable nanoimprinting process, the piezoelectrically enhanced vertically aligned P(VDF‐TrFE)/BaTiO3 nanocomposite micropillar arrays are fabricated. The piezoelectric device exhibits enhanced voltage of 13.2 V and a current density of 0.33 µA cm−2, which an enhancement by a factor of 7.3 relatives to the pristine P(VDF‐TrFE) bulk film. The mechanisms of high performance are mainly attributed to the enhanced piezoelectricity of the P(VDF‐TrFE)/BaTiO3 nanocomposite materials and the improved mechanical flexibility of the micropillar array. Under mechanical impact, stable electricity is stably generated from the nanogenerator and used to drive various electronic devices to work continuously, implying its significance in the field of consumer electronic devices. Furthermore, it can be applied as self‐powered flexible sensor work in a noncontact mode for detecting air pressure and wearable sensors for detecting some human vital signs including different modes of breath and heartbeat pulse, which shows its potential applications in flexible electronics and medical sciences.
Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL‐III trial
Authors: Nijman T. A. J. , Goedhart M. M. , Naaktgeboren C. N. , de Haan T. R. , Vijlbrief D. C. , Mol B. W. , Benders M. J. N. , Franx A. , Oudijk M. A.
Published: April 2017

Objective

Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely.

Methods

This was a secondary analysis of the APOSTEL‐III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury.

Results

A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29–1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25–1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36–4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42–1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27–1.27).

Conclusion

In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Politics in the Age of Fox, Pitt and Liverpool
Authors: Derry John W.
Published: April 2017

For many people the late eighteenth century was a period of political corruption, with the political world waiting for the triumph of reform. In this lucidly written study, now in a revised edition, John Derry shows that the traditional political system was more remarkable for its resilience than for its defects, and that it succeeded to an astonishing extent in meeting the challenges of war, the threat from the French Revolution, and the problems caused by unprecedented social and economic change. A vigorous narrative is combined with pungent analysis of the assumptions on which the practice of politics was based and the fashion in which politicians responded to the demands made of them.

Due weight is given to the element of continuity. The king continued to play a significant role in politics and no ministry could survive without the confidence of the crown and the support of the country gentlemen, and Pitt and Liverpool owed their success to their ability to appeal to these two powerful political forces. The importance of the French Revolution is not underplayed, but war is seen as a greater factor than ideology in bringing about a polarisation of opinion and the dominance of a conservatism which rested squarely upon traditional values. But trasnformation was also part of the story, and this study is fascinating in the manner in which it demonstrates the subtle blend of the old and the new which gave politics their unique flavour. The personalities of George III, Fox, Pitt and Liverpool are brought to life with deft and succinct characterisation in a style which will entertain as well as inform.
The Association Between Atherosclerosis and Low Back Pain: A Systematic Review
Authors: Shcherbina Anton , Longacre Mckenna
Published: April 2017

Objective

To assess the evidence of association between atherosclerosis and low back pain (LBP).

Type

Focused systematic review.

Literature Survey

PubMed, Web of Science, CINAHL, and EMBASE were searched for original research articles, not limited by language, from January 1, 1990, to October 31, 2016.

Methodology

Titles and then abstracts were identified using predefined search terms and excluded based on lack of relevancy. This was followed by full‐text reviews. Two authors independently assessed methodological quality based on Cochrane Handbook for Systematic Reviews of Interventions.

Synthesis

A total of 26 studies met the inclusion criteria. The quality of the studies was low to moderate. There was significant heterogeneity across articles with respect to methodology. There was insufficient evidence to support an association between ischemia and low back pain.

Conclusions

The cause of LBP remains poorly understood. Better insight into how intervertebral disk changes relate to LBP is needed to guide future research. High‐quality prospective studies are needed to answer the question of whether atherosclerosis is a risk factor for LBP.

Level of Evidence

II
Citizens or Cosmopolitans? Constructing Scientific Identity in the Early American College
Authors: Nelson Adam R.
Published: April 2017

Modern American scientific identity has its roots in the colleges of the late eighteenth and early nineteenth centuries. Using the botanical sciences as an example, this essay examines the conflicts between those who viewed scientists as cosmopolitan (or international) and those who viewed scientists as citizens (or servants) of the national state. Whereas today many American scientists claim a cosmopolitan identity, even as they decry steady declines in state aid, two centuries ago, they did just the opposite: to win public support, they quietly subsumed the ideals of cosmopolitanism within a commitment to national service, even as they deftly cultivated a new professional image rooted in a rhetoric of scientific internationalism. The construction of this new self-image was, I argue, a necessary precondition for the creation of the modern American research university—particularly the public research university—which sought to reconcile the competing ideals of scientific cosmopolitanism and citizenship.
Radiocarbon Chronology of the DSDDP Core at the Deepest Floor of the Dead Sea
Authors: Kitagawa Hiroyuki , Stein Mordechai , Goldstein Steven L , Nakamura Toshio , Lazar Boaz ,   DSDDP Scientific Party
Published: April 2017

This study establishes the chronological framework of the sedimentary sequence deposited Dead Sea, ICDP 5017-1, Radiocarbon chronology during the past 50 ka at the deepest part of the Dead Sea (the ICDP 5017-1 site), which was recovered by the Dead Sea Deep Drilling Project (DSDDP) under the auspices of the International Continental Scientific Drilling Program (ICDP). The age-depth model is constructed using 3814C dates of terrestrial plant remains in a composite 150-m-long profile, generated by anchoring 32 marker layers identified in five cores. The sedimentary records at the ICDP 5017-1 site fills gaps in those obtained from the exposed sections at the high margins of the lake, particularly in times of lake-level retreat, and allows for a high-resolution comparison between the lake’s margins and deepest floor.
Iceberg Surge During Last Deglaciation May Have Had Two Pulses
Authors: Stanley Sarah
Published: April 2017

Seafloor sediment cores provide new clues that could help clarify the influence of ice sheet collapse on a period of ocean cooling marked by slowed deepwater circulation.
Climate Change’s Pulse Is in Central America and the Caribbean
Authors: González J. , Georgescu M. , Lemos M. , Hosannah N. , Niyogi D.
Published: April 2017

Nations that border the Gulf of Mexico and Caribbean Sea are ideally placed for tracking the effects of global climate change and testing innovative ways to adapt to future changes.
Science Offers New Clues About Paintings by Munch and da Vinci
Authors: den Hond Bas
Published: April 2017

An unusual type of cloud might explain the sky in The Scream, and scientific verisimilitude reveals which is the real da Vinci masterpiece, new studies suggest.
Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia
Authors: Togasaki E , Takeda J , Yoshida K , Shiozawa Y , Takeuchi M , Oshima M , Saraya A , Iwama A , Yokote K , Sakaida E , Hirase C , Takeshita A , Imai K , Okumura H , Morishita Y , Usui N , Takahashi N , Fujisawa S , Shiraishi Y , Chiba K , Tanaka H , Kiyoi H , Ohnishi K , Ohtake S , Asou N , Kobayashi Y , Miyazaki Y , Miyano S , Ogawa S , Matsumura I , Nakaseko C , Naoe T ,   for the Japan Adult Leukemia Study Group (JALSG)
Published: April 2017

Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1–17). Age, hemoglobin concentration and white blood cell counts were correlated with the number of mutations. Patients with mutations ⩾6 showed higher rate of achieving major molecular response than those<6 (P=0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were significantly enriched with cell signaling and cell division pathways. Furthermore, DNA copy number analysis showed that 2 of 24 patients had uniparental disomy of chromosome 1p or 3q, which disappeared major molecular response was achieved. These mutations may play significant roles in CML pathogenesis in addition to the strong driver mutation BCR-ABL1.
Optical coherence tomography-based contact indentation for diaphragm mechanics in a mouse model of transforming growth factor alpha induced lung disease
Authors: Wang Kimberley C. W. , Astell Chrissie J. , Wijesinghe Philip , Larcombe Alexander N. , Pinniger Gavin J. , Zosky Graeme R. , Kennedy Brendan F. , Berry Luke J. , Sampson David D. , James Alan L. , Le Cras Timothy D. , Noble Peter B.
Published: April 2017

This study tested the utility of optical coherence tomography (OCT)-based indentation to assess mechanical properties of respiratory tissues in disease. Using OCT-based indentation, the elastic modulus of mouse diaphragm was measured from changes in diaphragm thickness in response to an applied force provided by an indenter. We used a transgenic mouse model of chronic lung disease induced by the overexpression of transforming growth factor-alpha (TGF-α), established by the presence of pleural and peribronchial fibrosis and impaired lung mechanics determined by the forced oscillation technique and plethysmography. Diaphragm elastic modulus assessed by OCT-based indentation was reduced by TGF-α at both left and right lateral locations (p < 0.05). Diaphragm elastic modulus at left and right lateral locations were correlated within mice (r = 0.67, p < 0.01) suggesting that measurements were representative of tissue beyond the indenter field. Co-localised images of diaphragm after TGF-α overexpression revealed a layered fibrotic appearance. Maximum diaphragm force in conventional organ bath studies was also reduced by TGF-α overexpression (p < 0.01). Results show that OCT-based indentation provided clear delineation of diseased diaphragm, and together with organ bath assessment, provides new evidence suggesting that TGF-α overexpression produces impairment in diaphragm function and, therefore, an increase in the work of breathing in chronic lung disease.
Rationally co-targeting divergent pathways in KRAS wild-type colorectal cancers by CANscript technology reveals tumor dependence on Notch and Erbb2
Authors: Brijwani Nilesh , Jain Misti , Dhandapani Muthu , Zahed Farrah , Mukhopadhyay Pragnashree , Biswas Manjusha , Khatri Deepak , Radhakrishna Vinod D. , Majumder Biswanath , Radhakrishnan Padhma , Thiyagarajan Saravanan
Published: April 2017

KRAS mutation status can distinguish between metastatic colorectal carcinoma (mCRC) patients who may benefit from therapies that target the epidermal growth factor receptor (EGFR), such as cetuximab. However, patients whose tumors harbor mutant KRAS (codons 12/13, 61 and 146) are often excluded from EGFR-targeted regimens, while other patients with wild type KRAS will sometimes respond favorably to these same drugs. These conflicting observations suggest that a more robust approach to individualize therapy may enable greater frequency of positive clinical outcome for mCRC patients. Here, we utilized alive tumor tissues in ex-vivo platform termed CANscript, which preserves the native tumor heterogeneity, in order to interrogate the antitumor effects of EGFR-targeted drugs in mCRC (n = 40). We demonstrated that, irrespective of KRAS status, cetuximab did not induce an antitumor response in a majority of patient tumors. In the subset of non-responsive tumors, data showed that expression levels of EGFR ligands contributed to a mechanism of resistance. Transcriptomic and phosphoproteomic profiling revealed deregulation of multiple pathways, significantly the Notch and Erbb2. Targeting these nodes concurrently resulted in antitumor efficacy in a majority of cetuximab-resistant tumors. These findings highlight the importance of integrating molecular profile and functional testing tools for optimization of alternate strategies in resistant population.
Accumulation of multiple neurodegenerative disease-related proteins in familial frontotemporal lobar degeneration associated with granulin mutation
Authors: Hosokawa Masato , Kondo Hiromi , Serrano Geidy E. , Beach Thomas G. , Robinson Andrew C. , Mann David M. , Akiyama Haruhiko , Hasegawa Masato , Arai Tetsuaki
Published: April 2017

In 2006, mutations in the granulin gene were identified in patients with familial Frontotemporal Lobar Degeneration. Granulin transcript haploinsufficiency has been proposed as a disease mechanism that leads to the loss of functional progranulin protein. Granulin mutations were initially found in tau-negative patients, though recent findings indicate that these mutations are associated with other neurodegenerative disorders with tau pathology, including Alzheimer’s disease and corticobasal degeneration. Moreover, a reduction in progranulin in tau transgenic mice is associated with increasing tau accumulation. To investigate the influence of a decline in progranulin protein on other forms of neurodegenerative-related protein accumulation, human granulin mutation cases were investigated by histochemical and biochemical analyses. Results showed a neuronal and glial tau accumulation in granulin mutation cases. Tau staining revealed neuronal pretangle forms and glial tau in both astrocytes and oligodendrocytes. Furthermore, phosphorylated α-synuclein-positive structures were also found in oligodendrocytes and the neuropil. Immunoblot analysis of fresh frozen brain tissues revealed that tau was present in the sarkosyl-insoluble fraction, and composed of three- and four-repeat tau isoforms, resembling Alzheimer’s disease. Our data suggest that progranulin reduction might be the cause of multiple proteinopathies due to the accelerating accumulation of abnormal proteins including TDP-43 proteinopathy, tauopathy and α-synucleinopathy.
Bioinformatic and expression analysis of the Brassica napus L. cyclophilins
Authors: Hanhart Patrizia , Thieß Melanie , Amari Khalid , Bajdzienko Krzysztof , Giavalisco Patrick , Heinlein Manfred , Kehr Julia
Published: April 2017

Cyclophilins (CYPs) are a group of ubiquitous proteins characterized by their ability to bind to the immunosuppressive drug cyclosporin A. The CYP family occurs in a wide range of organisms and contains a conserved peptidyl-prolyl cis/trans isomerase domain. In addition to fulfilling a basic role in protein folding, CYPs may also play diverse important roles, e.g. in protein degradation, mRNA processing, development, and stress responses. We performed a genome-wide database survey and identified a total of 94 CYP genes encoding 91 distinct proteins. Sequence alignment analysis of the putative BnCYP cyclophilin-like domains revealed highly conserved motifs. By using RNA-Seq, we could verify the presence of 77 BnCYP genes under control conditions. To identify phloem-specific BnCYP proteins in a complementary approach, we used LC-MS/MS to determine protein abundances in leaf and phloem extracts. We detected 26 BnCYPs in total with 12 being unique to phloem sap. Our analysis provides the basis for future studies concentrating on the functional characterization of individual members of this gene family in a plant of dual importance: as a crop and a model system for polyploidization and long-distance signalling.
Device performance enhancement via a Si-rich silicon oxynitride buffer layer for the organic photodetecting device
Authors: Heo Sung , lee Jooho , Kim Seong Heon , Yun Dong-Jin , Park Jong-Bong , Kim Kihong , Kim NamJeong , Kim Yongsung , Lee Dongwook , Kim Kyu-Sik , Kang Hee Jae
Published: April 2017

An advanced organic photodetector (OPD) with a butter layer of Si-rich silicon oxynitride (SiOxNy) was fabricated. The detector structure is as follows: Indium tin oxide (ITO) coated glass substrate/SiOxNy(10 nm)/naphthalene-based donor:C60(1:1)/ITO. Values of x and y in SiOxNy were carefully controlled and the detector performances such as dark current and thermal stability were investigated. When the values of x and y are 0.16 and 0.66, the detector illustrates low dark current as well as excellent thermal stability. In the OPD, silicon oxynitride layer works as electron barrier under reverse bias, leading to the decrease of dark current and increase of detectivity. Since the band gap of silicon oxynitride unlike conventional buffer layers can also be controlled by adjusting x and y values, it can be adapted into various photodiode applications.
Vegetation Controls on the Spatio-Temporal Heterogeneity of Deep Moisture in the Unsaturated Zone: A Hydrogeophysical Evaluation
Authors: Acharya Bharat S. , Halihan Todd , Zou Chris B. , Will Rodney E.
Published: April 2017

Information on the spatio-temporal variability of soil moisture in the vadose zone is important to assess groundwater recharge and solute transport in unconsolidated substrate as influenced by biological processes. Time-lapse electrical resistivity imaging (ERI) was used to monitor soil moisture dynamics to a depth of 9 m in a grassland, a grassland encroached by a juniper species (eastern redcedar,Juniperus virginiana), a juniper woodland and an oak forest in the south-central Great Plains, Oklahoma, USA. A site-specific relationship between moisture content and electrical conductivity data was developed for the soil zone, and a perched water zone was monitored at two of the sites. Results showed that (a) change in soil moisture content was linearly correlated to change in electric conductivity in the soil zone; (b) vegetation cover type induced differences in vertical bulk electrical resistivity (ER) profiles and influenced the temporal evolution of soil moisture profiles; and (c) juniper encroachment lowered the water level in the perched groundwater aquifer. Our results suggest land use and vegetation cover type, as opposed to rock properties, controls deep water drainage for the vegetation transition zone. Methods used to measure hydrogeophysical changes, such as ERI, can be used for broader understanding of geological, physical, and biological processes and their links in Earth’s critical zones.
Erratum: High affinity anchoring of the decoration protein pb10 onto the bacteriophage T5 capsid
Authors: Vernhes Emeline , Renouard Madalena , Gilquin Bernard , Cuniasse Philippe , Durand Dominique , England Patrick , Hoos Sylviane , Huet Alexis , Conway James F. , Glukhov Anatoly , Ksenzenko Vladimir , Jacquet Eric , Nhiri Naïma , Zinn-Justin Sophie , Boulanger Pascale
Published: April 2017

Scientific Reports 7: Article number: 41662; published online: 06 February 2017; updated: 28 April 2017 This Article contains typographical errors. In the results section under subheading ‘The C-terminal domain adopts an immunoglobulin fold in solution’, “A search for structurally similar proteins possessing using the Dali server identified many proteins containing an Ig-like fold, including immunoglobulin receptors, fibroblast growth factor receptors and the T-cell surface glycoprotein CD4.
Pluronic based β-cyclodextrin polyrotaxanes for treatment of Niemann-Pick Type C disease
Authors: Collins Christopher J. , Loren Bradley P. , Alam Md Suhail , Mondjinou Yawo , Skulsky Joseph L. , Chaplain Cheyenne R. , Haldar Kasturi , Thompson David H.
Published: April 2017

Niemann-Pick Type C disease (NPC) is a rare metabolic disorder characterized by disruption of normal cholesterol trafficking within the cells of the body. There are no FDA approved treatments available for NPC patients. Recently, the cycloheptaglucoside 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has shown efficacy as a potential NPC therapeutic by extending lifetime in NPC mice, delaying neurodegeneration, and decreasing visceral and neurological cholesterol burden. Although promising, systemic HP-β-CD treatment is limited by a pharmacokinetic profile characterized by rapid loss through renal filtration. To address these shortcomings, we sought to design a family of HP-β-CD pro-drug delivery vehicles, known as polyrotaxanes (PR), capable of increasing the efficacy of a given injected dose by improving both pharmacokinetic profile and bioavailability of the HP-β-CD agent. PR can effectively diminish the cholesterol pool within the liver, spleen, and kidney at molar concentrations 10-to-100-fold lower than monomeric HP-β-CD. In addition to this proof-of-concept, use of PR scaffolds with differing physiochemical properties reveal structure-activity relationships in which PR characteristics, including hydrophobicity, threading efficiency and surface charge, were found to both decisively and subtly effect therapeutic efficacy. PR scaffolds exhibit absorption, pharmacokinetics, and biodistribution patterns that are significantly altered from monomeric HP-β-CD. In all, PR scaffolds hold great promise as potential treatments for visceral disease in NPC patients.
CO2 activation on Cu-based Zr-decorated nanoparticles
Authors: Austin Natalie , Ye Jingyun , Mpourmpakis Giannis
Published: April 2017

This work reveals a strong CO2 activation on CuZr nanoparticles with the catalyst ionization potential determining the CO2 interaction strength.
Synergistic effect of zinc selenide–reduced graphene oxide towards enhanced solar light-responsive photocurrent generation and photocatalytic 4-nitrophenol degradation
Authors: Chakraborty Koushik , Chakrabarty Sankalpita , Pal Tanusri , Ghosh Surajit
Published: April 2017

Herein, we report the in situ synthesis of zinc selenide decorated reduced graphene oxide by solvothermal reaction for application in large-area, thin-film photodetector devices and photocatalytic 4-nitrophenol degradation.
Enhanced removal of cephalosporin based antibiotics (CBA) from water by one-pot electrosynthesized Mg(OH)2: a combined theoretical and experimental study to pilot scale
Authors: Pandiarajan Aarthi , Kamaraj Ramakrishnan , Vasudevan Subramanyan
Published: April 2017

An electrocoagulant, nano-sized Mg(OH)2, is active for the adsorption of antibiotics from water. It was preparedviaa simple, cheap, and eco-friendly method.
Integrating natural biomass electro-oxidation and hydrogen evolution: using a porous Fe-doped CoP nanosheet array as a bifunctional catalyst
Authors: Hao Shuai , Yang Libin , Liu Danni , Kong Rongmei , Du Gu , Asiri Abdullah M. , Yang Yingchun , Sun Xuping
Published: April 2017

An Fe-doped CoP nanosheet array acts as an efficient catalyst electrode for aloe extract oxidation reaction (AOR) and hydrogen evolution reaction (HER). Its two-electrode alkaline electrolyzer requires 1.51 V for 20 mA cm−2.
The use of carboxylic acids as traceless directing groups for regioselective C–H bond functionalisation
Authors: Font Marc , Quibell Jacob M. , Perry Gregory J. P. , Larrosa Igor
Published: April 2017

This feature article focuses on the use of carboxylic acids as traceless directing groups and the application of this concept to achieve regiochemical control in organic chemistry.
Analyte-triggered autocatalytic amplification combined with gold nanoparticle probes for colorimetric detection of heavy-metal ions
Authors: Yang Juanhua , Zhang Yun , Zhang Lang , Wang Huili , Nie Jinfang , Qin Zhongxiang , Li Jiao , Xiao Wencheng
Published: April 2017

This work reports a new nanosensor based on analyte-triggered autocatalytic amplification and label-free gold nanoparticles for the colorimetric detection of Hg2+, Cu2+and Ag+with detection limits less than 3 nM.
Electron stimulated desorption from condensed pyrimidine and pyridazine
Authors: Ellis-Gibbings L. , Bass A. D. , Cloutier P. , García G. , Sanche L.
Published: April 2017

Experimental electron stimulated desorption results indicate resonances and fragmentation pathways of condensed biomolecules not seen in gas phase.
Solution-processed two-dimensional layered heterostructure thin-film with optimized thermoelectric performance
Authors: Wang Tongzhou , Liu Congcong , Jiang Fengxing , Xu Zhaofen , Wang Xiaodong , Li Xia , Li Changcun , Xu Jingkun , Yang Xiaowei
Published: April 2017

The content of rGO could alter the carrier transport barrier, and the optimizing power factor was achieved at rGO–MS2 junctions.
Correction: Atomic layer deposition of Cu(i) oxide films using Cu(ii) bis(dimethylamino-2-propoxide) and water
Authors: Avila J. R. , Peters A. W. , Li Zhanyong , Ortuño M. A. , Martinson A. B. F. , Cramer C. J. , Hupp J. T. , Farha O. K.
Published: April 2017

Correction for ‘Atomic layer deposition of Cu(i) oxide films using Cu(ii) bis(dimethylamino-2-propoxide) and water’ by J. R. Avila, et al., Dalton Trans., 2017, DOI: 10.1039/c6dt02572b.
Mobile microrobots for bioengineering applications
Authors: Ceylan Hakan , Giltinan Joshua , Kozielski Kristen , Sitti Metin
Published: April 2017

Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells.
Optimized droplet digital CFU assay (ddCFU) provides precise quantification of bacteria over a dynamic range of 6 logs and beyond
Authors: Scheler O. , Pacocha N. , Debski P. R. , Ruszczak A. , Kaminski T. S. , Garstecki P.
Published: April 2017

We optimized the droplet digital bacterial assay by reducing the number of compartments while maintaining precise quantification.
Microfluidic-assisted fabrication of carriers for controlled drug delivery
Authors: Liu Dongfei , Zhang Hongbo , Fontana Flavia , Hirvonen Jouni T. , Santos Hélder A.
Published: April 2017

We reviewed different fluidic principles to produce drug delivery systems, especially the factors affecting drug release.
Copper and silver nanoparticles stabilized by bistriazole-based dendritic amphiphile micelles for 4-nitrophenol reduction
Authors: Patil Naganath G. , Basutkar Nitin B. , Ambade Ashootosh V.
Published: April 2017

Copper and silver nanoparticles stabilized on dendritic amphiphiles catalyzed 4-nitrophenol reduction at the ppm level, with particle size influencing catalytic efficiency.
Pd-Catalyzed thiophene directed regioselective functionalization of arenes: a direct approach to multiply-substituted benzyl amines
Authors: Hu Jundie , Li Guobao , Huang Zhi-Bin , Zhang Jingyu , Shi Da-Qing , Zhao Yingsheng
Published: April 2017

A thiophene directed ortho-C–H functionalization via a palladium catalyst in the synthesis of multiply-substituted benzyl amines has been developed.
Pincer cobalt complex-catalyzed Z-selective hydrosilylation of terminal alkynes
Authors: Du Xiaoyong , Hou Wenjun , Zhang Yanlu , Huang Zheng
Published: April 2017

Co-Catalyzed Z-selective hydrosilylation of terminal alkynes produces (Z)-β-vinylsilanes, which are further converted to (Z)-disubstituted alkenes by Pd-catalyzed cross couplings.