bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of plasma and radical control for the low temperature synthesis and properties of a-SiNx:H films using RF-near microwave PECVD
Authors: Sahu Bibhuti Bhusan , Toyoda Hirotaka , Han Jeon Geon
Published: February 2018

By mixing and alternating power conditions of radio frequency and microwave plasma sources, a detailed study of a-SiNx:H films in the SiH4/N2 plasma enhanced chemical vapour deposition processes is undertaken. Data reveal a remarkable coherence between the deposition conditions, material's quality, bond densities, optical property, and stoichiometry of the films. The film composition can simply vary from Si-rich to N-rich by incorporating suitable plasma and atomic radical parameters. Highly transparent and wide bandgap films with N to Si and N to H atomic ratios up to ∼2.3 and 3.1, respectively, are prepared by controlling the plasma parameters and radicals. The presented results pave the way for dual frequency PECVD utilization in a-SiNx:H films for their use in controlled-bandgap nanodevices and light emitting applications.
Thermo-optic coefficient and nonlinear refractive index of silicon oxynitride waveguides
Authors: Trenti A. , Borghi M. , Biasi S. , Ghulinyan M. , Ramiro-Manzano F. , Pucker G. , Pavesi L.
Published: February 2018

Integrated waveguiding devices based on silicon oxynitride (SiON) are appealing for their relatively high refractive index contrast and broadband transparency. The lack of two photon absorption at telecom wavelengths and the possibility to fabricate low loss waveguides make SiON an ideal platform for on-chip nonlinear optics and for the realization of reconfigurable integrated quantum lightwave circuits. Despite this, very few studies on its linear and nonlinear optical properties have been reported so far. In this work, we measured the thermo-optic coefficient dn/dT and the nonlinear refractive index n2 of relatively high (n ∼ 1.83 at a wavelength of 1.55 μm) refractive index SiON by using racetrack resonators. These parameters have been determined to be dndT=(1.84±0.17)× 10−5 K−1 and n2 = (7 ± 1) × 10−16 cm2W−1.
Spatial patterns of tree yield explained by endogenous forces through a correspondence between the Ising model and ecology
Authors: Noble Andrew E. , Rosenstock Todd S. , Brown Patrick H. , Machta Jonathan , Hastings Alan
Published: February 2018

Significance

Explaining correlations across space of cyclic dynamics in ecology is a fundamental challenge. We apply ideas from statistical physics, originally used to explain the behavior of magnets, to a dataset on yield from pistachio trees, obtaining a robust description and potential explanation for the generation of spatial correlations in cyclic dynamics. These results suggest looking for mechanistic underpinnings at the level of interactions between neighboring trees that lead to spatial correlations in dynamics and a surprising correspondence between the descriptions of physical phenomena, magnetization, and ecological dynamics. This work demonstrates with data, and not just models, that correlations in cyclic dynamics can be generated from local interactions and dynamics even in a very noisy ecological system.
Locus coeruleus integrity in old age is selectively related to memories linked with salient negative events
Authors: Hämmerer Dorothea , Callaghan Martina F. , Hopkins Alexandra , Kosciessa Julian , Betts Matthew , Cardenas-Blanco Arturo , Kanowski Martin , Weiskopf Nikolaus , Dayan Peter , Dolan Raymond J. , Düzel Emrah
Published: February 2018

Significance

Locus coeruleus (LC) integrity in cognitively normal older adults is a potentially important preclinical marker in dementia. Our study establishes a link between variability in LC integrity and cognitive decline related to noradrenergic modulation in old age. We find that in older adults, reduced LC integrity explains lower memory performance. This effect was more pronounced for memory related to negative events, and accompanied by increased pupil diameter size in response to negative events. The study provides a strong motivation for future research investigating the role of LC integrity in healthy, as well as in pathological, aging.
Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity
Authors: Davenport A. J. , Cross R. S. , Watson K. A. , Liao Y. , Shi W. , Prince H. M. , Beavis P. A. , Trapani J. A. , Kershaw M. H. , Ritchie D. S. , Darcy P. K. , Neeson P. J. , Jenkins M. R.
Published: February 2018

Significance

Davenport et al. discovered that the chimeric antigen receptor (CAR) immune synapse structure is different from the T cell receptor (TCR) synapse. The CAR immune synapse formed a disorganized pattern of Lck and more rapidly recruited lytic granules compared with the TCR. The differing immune synapse correlated with faster killing of tumor target cells and detachment from dying tumor cells by CAR-T cells. These findings provide a mechanism whereby CAR-T cells can effectively reduce large tumor burden in patients. This study will form a basis upon which to compare future receptor design to modulate signaling and programming of cytotoxic CAR-T cells to improve treatment of solid cancers.
Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive–compulsive disorder
Authors: Reggente Nicco , Moody Teena D. , Morfini Francesca , Sheen Courtney , Rissman Jesse , O’Neill Joseph , Feusner Jamie D.
Published: February 2018

Significance

The ability to predict an individual’s potential response to treatment would permit clinicians to more prudently allocate resources that support cognitive behavioral therapy for obsessive–compulsive disorder (OCD), an often stressful and time-consuming treatment. The current study lays important groundwork for an exciting advance toward personalized medicine in psychiatry that up to this point has eluded the field. This study marks a success in using multivariate pattern recognition to identify neurobiological predictors of treatment response. In addition, it advances knowledge of the neurophysiology of OCD and of mechanistic processes involved in the therapeutic response, which could be used to refine existing treatments or to develop novel treatments based on identified potential brain targets.
Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A
Authors: Hashimoto Kyoko , Ochi Hiroki , Sunamura Satoko , Kosaka Nobuyoshi , Mabuchi Yo , Fukuda Toru , Yao Kenta , Kanda Hiroaki , Ae Keisuke , Okawa Atsushi , Akazawa Chihiro , Ochiya Takahiro , Futakuchi Mitsuru , Takeda Shu , Sato Shingo
Published: February 2018

Significance

Prostate cancer is one of most common cancers in men worldwide, and osteoblastic bone metastasis is frequently observed in prostate cancer patients. However, the mechanisms responsible for the predominantly osteoblastic phenotype have not been fully elucidated. Cancer-secreted microRNAs (miRNAs) were recently shown to be significant in the modification of the tumor microenvironment. Here, hsa-miR-940, which was highly secreted by prostate cancer cells, promoted osteogenic differentiation of human mesenchymal stem cells in vitro, and induced extensive osteoblastic lesions in the bone metastatic microenvironment in vivo. Our study provides a demonstration that osteoblastic bone metastasis can be induced by miRNAs secreted by cancer cells in the bone microenvironment.
Bryostatin-1 alleviates experimental multiple sclerosis
Authors: Kornberg Michael D. , Smith Matthew D. , Shirazi Hasti Atashi , Calabresi Peter A. , Snyder Solomon H. , Kim Paul M.
Published: February 2018

Significance

Multiple sclerosis (MS) is an inflammatory disease that targets the central nervous system and leads to severe neurologic disability. Bryostatin-1 is a naturally occurring, brain-penetrant compound that has undergone human testing in cancer and Alzheimer’s disease, but also has immunomodulatory properties that might provide benefit in MS. Here, we show that bryostatin-1 potently prevents disease and reverses neurologic deficits in the major mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Its benefit even in late-stage EAE further suggests potential in progressive forms of MS, in which much disability accrues but treatments are currently lacking. The established clinical safety profile of bryostatin-1 in humans could expedite its development as a therapeutic agent in MS.
Lupus-like autoimmune disease caused by a lack of Xkr8, a caspase-dependent phospholipid scramblase
Authors: Kawano Mahiru , Nagata Shigekazu
Published: February 2018

Significance

Every day in our bodies, billions of neutrophils become senescent and are cleared by macrophages. This number exceeds the number of cells that undergo apoptosis. Xkr8 is a member of the Xkr membrane-protein family and has caspase-dependent phospholipid scramblase activity. Here, we show that not only apoptotic thymocytes and splenocytes, but also senescent neutrophils require Xkr8 for swift clearance in vivo.
Xkr8
-deficient female mice on the MRL background carried high levels of autoantibodies, accumulated effector CD4 T cells, and developed glomerulonephritis. These results indicate that in addition to unengulfed apoptotic cells, uncleared senescent neutrophils contribute to the development of autoimmune diseases.
ATP synthase from
Trypanosoma brucei
has an elaborated canonical F
1
-domain and conventional catalytic sites
Authors: Montgomery Martin G. , Gahura Ondřej , Leslie Andrew G. W. , Zíková Alena , Walker John E.
Published: February 2018

The structures and functions of the components of ATP synthases, especially those subunits involved directly in the catalytic formation of ATP, are widely conserved in metazoans, fungi, eubacteria, and plant chloroplasts. On the basis of a map at 32.5-Å resolution determined in situ in the mitochondria of
Trypanosoma brucei
by electron cryotomography, it has been proposed that the ATP synthase in this species has a noncanonical structure and different catalytic sites in which the catalytically essential arginine finger is provided not by the α-subunit adjacent to the catalytic nucleotide-binding site as in all species investigated to date, but rather by a protein, p18, found only in the euglenozoa. A crystal structure at 3.2-Å resolution of the catalytic domain of the same enzyme demonstrates that this proposal is incorrect. In many respects, the structure is similar to the structures of F
1
-ATPases determined previously. The α
3
β
3
-spherical portion of the catalytic domain in which the three catalytic sites are found, plus the central stalk, are highly conserved, and the arginine finger is provided conventionally by the α-subunits adjacent to each of the three catalytic sites found in the β-subunits. Thus, the enzyme has a conventional catalytic mechanism. The structure differs from previous described structures by the presence of a p18 subunit, identified only in the euglenozoa, associated with the external surface of each of the three α-subunits, thereby elaborating the F
1
-domain. Subunit p18 is a pentatricopeptide repeat (PPR) protein with three PPRs and appears to have no function in the catalytic mechanism of the enzyme.
Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis
Authors: Meng Huyan , Liu Zhen , Li Xingyan , Wang Huibing , Jin Taijie , Wu Guowei , Shan Bing , Christofferson Dana E. , Qi Chunting , Yu Qiang , Li Ying , Yuan Junying
Published: February 2018

Significance

While the critical role of RIPK1 kinase activity in mediating necroptosis and RIPK1-dependent apoptosis has been established, we still know little about how the nonkinase domains of RIPK1 regulate its kinase activity. Establishing the role of RIPK1-death domain (DD) in mediating RIPK1 activation and formation of complex II provides an important insight into the molecular mechanism by which RIPK1 is activated during the transition from complex I to complex II. These results suggest that RIPK1-DD self-association may provide an amplification mechanism to promote the activation of RIPK1 kinase activity for mediating signal transduction to lead to cell death. Our results also suggest that the activation of RIPK1 may be regulated by its concentration as increased expression of RIPK1 under pathological conditions may promote its dimerization and activation.
Afro-Hispanic contact varieties at the syntax/pragmatics interface
Authors: Sessarego Sandro , Gutiérrez-Rexach Javier
Published: February 2018

The Null Subject Parameter (NSP) has been the focus of much debate in the syntactic and pragmatic literature. Within the realm of Spanish and Portuguese, the analysis of two dialects that do not follow its predictions (Dominican Spanish (DS) and Brazilian Portuguese (BP)) has led to the postulation of new hypotheses to account for their unexpected syntactic patterns. The present study pays attention to yet another dialect of Spanish that does not conform to the NSP, Chinchano Spanish (CS), an Afro-Hispanic variety spoken in Chincha, Peru. In so doing, this paper provides an analysis of null and overt subjects that partially deviates from previous accounts of similar pro-drop phenomena. Additionally, this study proposes a model of contact-induced language transmission that explains why CS – as well as many other Afro-Hispanic languages of the Americas (AHLAs) – presents patterns that do not align this dialect with either null-subject languages (NSLs) like Italian or non-null-subject languages (NNSLs) like English.
Hasta perder la última gota de mi sangre
Authors: King Jeremy
Published: February 2018

In spite of the recent burgeoning of the field of Spanish socio-pragmatics, the category of commissive speech acts has been all but ignored in scholarship, particularly in contact varieties of the language. Colonial Louisiana presents an ideal context for this type of work. The analysis herein involves a corpus of 100 business letters between Spanish government and military officials in 18th century Louisiana. All commissive speech acts were identified and coded according to a modified version of the taxonomy presented in Bilbow (2002). Results of the study reveal that the level of power of the speaker (= letter writer) proved to be the most significant factor in the formulation of commissives. The level of relative power of a speaker appeared to guide not only the general type of commissives employed (e.g., promises vs. offers) but also the specific morphological expression of the speech act (e.g., future vs. present tense).
L2 Spanish in the U.S. and the question of motivation
Authors: Schroth Terri , Smith Bryant
Published: February 2018

University students’ motivation to study Spanish includes a number of practical or instrumental factors (e.g., ease in finding gainful employment and desire to travel) and intrinsic or integrative factors (e.g., personal growth and using Spanish to communicate with family and friends). To better understand students’ current motivation to study Spanish, we examined data collected from university students of lower-division Spanish language courses from two different geographical regions in the United States. The participants completed questionnaires that sought to determine their motivation for studying Spanish. Concurrent with our hypothesis, results of this pilot study indicate that the students of Spanish who participated in this study express more practical (instrumental) motivations to learn the language. A desire to connect with one’s heritage or to speak Spanish with family members proved to be a less important motivator than we had anticipated, as did the geographic region of the students.
Espero estén todos
Authors: Rodríguez-Riccelli Adrián
Published: February 2018

This study adopts a quantitative methodology to investigate variation between null and overt expressions of Spanish complementizer que. I focus on two varieties of Spanish from Mexico City and Los Angeles, California. This research uses a corpus linguistics–inspired methodology, relying on Twitter as a database to extract tokens and Rrbul (Johnson 2008) to perform the multivariate analysis. I extracted and analyzed 1,505 tokens and coded for 9 linguistic and 2 extra-linguistic factors. I showed the internal factors ‘verb modality’ and ‘embedded subject status’ to significantly affect the alternation, favoring the null option. Contrary to what was expected, the external factor ‘city’ did not have any significant effect on the distribution. I discuss the results in light of formal and sociolinguistic studies on the nature of subordinated constructions in Spanish (Brovetto 2002; Etxepare 1996; Subirats-Rüggeberg 1987), English (Tagliamonte & Smith 2005) and Spanish in contact with English (Silva-Corvalán 1993, 1994, 1998).
A usage-based account for the historical reflexes of
ain’t in AAE
Authors: Smith K. Aaron
Published: February 2018

This paper is a comparative and historical study of the grammatical status of
auxiliary ain‘t in African-American English (AAE). Drawing
on the representation of AAE speakers in works of fiction from the 19th
century and present-day, the paper confirms that the broad range of uses of
auxiliary ain‘t are nearly all available in historical AAE.
The study also presents data that certain of the uses (specifically those
not documented or only infrequently documented for non-AAE varieties) have
increased in fictive representations of AAE. The analysis shows that the
increase is led by a specific verb type (and even a specific verb) and thus
suggests an exemplar-based increase and extension of ain‘t.
Moreover, the paper also shows a formal morphosyntactic convergence of
several uses of auxiliary ain‘t and motivates that
convergence through exemplar merging, suggesting an association of that
merged morphosyntactic form with sociolinguistic identity.
look
up about
Authors: Nordquist Dawn
Published: February 2018

This chapter investigates the emergence of a new English
phrasal-prepositional verb, look up about, which is found
predominantly in online discourse and is largely synonymous with “to
google”. It is argued that the verb emerged as the result of a reanalysis of
a source syntagm that eroded an internal constituency boundary and resulted
in a new lexical item. In order to understand how reanalysis took place in
the lexicalization of look up about, usage-based processes
such as chunking and holistic and heuristic-based processing are examined,
and Bybee’s (2002) Linear Fusion Hypothesis is also invoked to explain how
this multi-word expression has entered the lexicon of many users.
Retention of Student Pharmacists’ Knowledge and Skills regarding Overdose Management with Naloxone
Authors: Jacobson Anita N. , Bratberg Jeffrey P. , Monk Miranda , Ferrentino John
Published: February 2018

Background

Overdose education and naloxone training was recently implemented into the required curriculum of the College of Pharmacy at the University of Rhode Island. The objective of this study was to compare the retention of knowledge between student pharmacists who received a didactic lecture only versus student pharmacists who received the same lecture plus a skills-based objective structured clinical examination (OSCE) with a standardized patient actor.

Methods

Students in their first-professional year (P1) of the Doctor of Pharmacy program (n = 129) and students in their second-professional (P2) year (n = 123) attended a required lecture on opioid overdose, including detailed naloxone training. P2 students were additionally required to participate in an OSCE assessment following the didactic lecture component. An anonymous, voluntary survey was offered to all students approximately 6 months later. A Chi-Square or Fisher's Exact Test was performed on the survey responses to assess any difference in the responses between the two groups.

Results

A total of 99 P1 students (76.7%) and 116 P2 students (94.3%) completed the survey. P1 students were found to be more knowledgeable regarding the duration of naloxone action and identification of risk factors for opioid overdose. P2 students were found to be more knowledgeable regarding non-medical ways patients may obtain opioids and the correct order of emergency response during a suspected opioid overdose…

Conclusions

P2 students did not demonstrate superior retention of information regarding naloxone and opioid use disorder on survey questions compared with P1 students. There was a trend towards P2 students feeling more confident in their ability to counsel patients for overdose prevention and reporting disagreement with the statement that “overdose prevention for people who use drugs is a waste of time and money” compared with the P1 students, but these did not reach statistical significance. Since the opioid crisis continues unabated, naloxone training using OSCE and didactic methods remain an on-going required part of the pharmacy curriculum.
Overcoming Medication Stigma in Peer Recovery: A New Paradigm
Authors: Krawczyk Noa , Negron Tianna , Nieto Maia , Agus Deborah , Fingerhood Michael I.
Published: February 2018

Background: Treatment for opioid use disorder involving opioid-based pharmacotherapies is considered most effective when accompanied by psychosocial interventions. Peer-led support groups are widely available and have been described by many as fundamental to the recovery process. However, some individuals using medications face stigma in these settings, which can be contradictory and counterproductive to their recovery. Methods: This paper describes the development of the “Ability, Inspiration and Motivation” or “AIM” group, an alternative peer support group that aims to remove medication stigma from peer recovery. Qualitative interviews with staff, peers, and clients of a community-based buprenorphine treatment program were used to establish the core components of the curriculum to support client needs. Results: Staff, peers, and clients of the buprenorphine program indicated a need and desire to establish a peer recovery group that recognizes persons on medication as being in recovery and destigmatizes use of medication to treat opioid addiction. A respectful environment, holistic perspective on health, spirituality, sharing, and celebration were all established as necessary pillars of the AIM group curriculum. Conclusions: The community-based effort to establish and develop the AIM group demonstrates that combining the strengths of a peer support with evidence-based medication treatment is both possible and desirable. Shifting the culture of peer recovery groups to support the use of medications may have implications for improving treatment retention and should be considered as a potential strategy to reduce the burden of the opioid epidemic.
Imaging of native transcription factors and histone phosphorylation at high resolution in live cells
Authors: Conic Sascha , Desplancq Dominique , Ferrand Alexia , Fischer Veronique , Heyer Vincent , Reina San Martin Bernardo , Pontabry Julien , Oulad-Abdelghani Mustapha , Babu N. Kishore , Wright Graham D. , Molina Nacho , Weiss Etienne , Tora László
Published: February 2018

Fluorescent labeling of endogenous proteins for live-cell imaging without exogenous expression of tagged proteins or genetic manipulations has not been routinely possible. We describe a simple versatile antibody-based imaging approach (VANIMA) for the precise localization and tracking of endogenous nuclear factors. Our protocol can be implemented in every laboratory allowing the efficient and nonharmful delivery of organic dye-conjugated antibodies, or antibody fragments, into different metazoan cell types. Live-cell imaging permits following the labeled probes bound to their endogenous targets. By using conventional and super-resolution imaging we show dynamic changes in the distribution of several nuclear transcription factors (i.e., RNA polymerase II or TAF10), and specific phosphorylated histones (γH2AX), upon distinct biological stimuli at the nanometer scale. Hence, considering the large panel of available antibodies and the simplicity of their implementation, VANIMA can be used to uncover novel biological information based on the dynamic behavior of transcription factors or posttranslational modifications in the nucleus of single live cells.
Sustained Id2 regulation of E proteins is required for terminal differentiation of effector CD8+ T cells
Authors: Omilusik Kyla D. , Nadjsombati Marija S. , Shaw Laura A. , Yu Bingfei , Milner J. Justin , Goldrath Ananda W.
Published: February 2018

CD8+ T cells responding to infection differentiate into a heterogeneous population composed of progeny that are short-lived and participate in the immediate, acute response and those that provide long-lasting host protection. Although it is appreciated that distinct functional and phenotypic CD8+ T cell subsets persist, it is unclear whether there is plasticity among subsets and what mechanisms maintain subset-specific differences. Here, we show that continued Id2 regulation of E-protein activity is required to maintain the KLRG1hi CD8+ T cell population after lymphocytic choriomeningitis virus infection. Induced deletion of Id2 phenotypically and transcriptionally transformed the KLRG1hi “terminal” effector/effector-memory CD8+ T cell population into a KLRG1lo memory-like population, promoting a gene-expression program that resembled that of central memory T cells. Our results question the idea that KLRG1hi CD8+ T cells are necessarily terminally programmed and suggest that sustained regulation is required to maintain distinct CD8+ T cell states.
Results of the supplementary comparison SIM.M.FF-S12 for volume of liquids at 20 L
Authors: Maldonado M , Castillo E , Rodríguez L D
Published: February 2018

A supplementary comparison was performed in order to compare national measurement systems to determine volume of liquids, particularly at fixed volume of 20 L. The participants were CENAM (Mexico), LACOMET (Costa Rica) and RECOPE (Costa Rica). The measurements were carried out from October 2016 to June 2017. The chosen value of volume (20 L) is representative of the Calibration and Measurement Capabilities (CMCs) declared by the three participants. The transfer standard (TS) was a stainless steel pipette for volume at 20 L. Prior to the beginning of the comparison, the TS was tested by CENAM. The results of the test phase showed excellent values for both repeatability and reproducibility. During the SIM.M.FF-S12, the results of the laboratories showed good agreement with the reference values. The best estimation of the measurands, as reported by the participants, showed a ± 0.0022 % as the largest difference among the laboratories.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
RaMWAS: fast methylome-wide association study pipeline for enrichment platforms
Authors: Shabalin Andrey A , Hattab Mohammad W , Clark Shaunna L , Chan Robin F , Kumar Gaurav , Aberg Karolina A , van den Oord Edwin J C G
Published: February 2018

Motivation

Enrichment-based technologies can provide measurements of DNA methylation at tens of millions of CpGs for thousands of samples. Existing tools for methylome-wide association studies cannot analyze datasets of this size and lack important features like principal component analysis, combined analysis with SNP data and outcome predictions that are based on all informative methylation sites.

Results

We present a Bioconductor R package called RaMWAS with a full set of tools for large-scale methylome-wide association studies. It is free, cross-platform, open source, memory efficient and fast.

Availability and implementation

Release version and vignettes with small case study at bioconductor.org/packages/ramwas Development version at github.com/andreyshabalin/ramwas.

Supplementary information

Supplementary data are available at Bioinformatics online.
ChemDistiller: an engine for metabolite annotation in mass spectrometry
Authors: Laponogov Ivan , Sadawi Noureddin , Galea Dieter , Mirnezami Reza , Veselkov Kirill A
Published: February 2018

Motivation

High-resolution mass spectrometry permits simultaneous detection of thousands of different metabolites in biological samples; however, their automated annotation still presents a challenge due to the limited number of tailored computational solutions freely available to the scientific community.

Results

Here, we introduce ChemDistiller, a customizable engine that combines automated large-scale annotation of metabolites using tandem MS data with a compiled database containing tens of millions of compounds with pre-calculated ‘fingerprints’ and fragmentation patterns. Our tests using publicly and commercially available tandem MS spectra for reference compounds show retrievals rates comparable to or exceeding the ones obtainable by the current state-of-the-art solutions in the field while offering higher throughput, scalability and processing speed.

Availability and implementation

Source code freely available for download at https://bitbucket.org/iAnalytica/chemdistillerpython.

Supplementary information

Supplementary data are available at Bioinformatics online.
Development of Proximal Junctional Kyphosis After Minimally Invasive Lateral Anterior Column Realignment for Adult Spinal Deformity
Authors: Gandhi Shashank V , Januszewski Jacob , Bach Konrad , Graham Randall , Vivas Andrew C , Paluzzi Jason , Kanter Adam , Okonkwo David , Tempel Zachary J , Agarwal Nitin , Uribe Juan S
Published: February 2018

BACKGROUND

Development of proximal junctional kyphosis (PJK) after correction of adult spinal deformity (ASD) undermines sagittal alignment. Minimally invasive anterior column realignment (ACR) is a powerful tool for correction of ASD; however, long-term PJK rates are unknown.

OBJECTIVE

To characterize PJK after utilization of ACR in ASD correction.

METHODS

A retrospective multi-institution cohort analysis per STROBE criteria was conducted of all patients who underwent lateral lumbar interbody fusion (LLIF) or ACR for ASD from 2010 to 2015. All patients obtained preoperative and follow-up upright radiographs, assessing spinal alignment and development of PJK. Patients without proper imaging or minimum 1-yr follow-up were excluded.

RESULTS

A total of 73 of 112 patients who underwent either LLIF or ACR for ASD met inclusion criteria. Mean follow-up was 22.8 mo. There was significant improvement of all spinopelvic parameters. Overall, PJK and proximal junctional failure (PJF) rates were 20.5% and 11%, respectively. The incidence of PJK increased with greater corrective surgery (0% LLIF, 30% ACR, 42.9% ACR + posterior column osteotomy (PCO); P < .001). PJF rates increased (0% LLIF, 11% ACR, 40% ACR + PCO; P = .005). Risk factors included location of the upper-instrumented vertebra at T10-L1 vs L2-L4 (P = .007), age (P = .029), severity of ASD, and overcorrection of sagittal imbalance.

CONCLUSION

The incidence of PJK after minimally invasive ACR is slightly lower than reported after open surgery but greater than in LLIF only and increases with PCO utilization. The PJK rate increases when crossing the TL junction, sagittal imbalance severity, and overcorrection. Elderly patients are at an increased risk, suggesting need for age appropriate correction goals.
Cognitive Functional Therapy: An Integrated Behavioral Approach for the Targeted Management of Disabling Low Back Pain
Authors: O’Sullivan Peter B , Caneiro J P , O’Keeffe Mary , Smith Anne , Dankaerts Wim , Fersum Kjartan , O’Sullivan Kieran
Published: February 2018

Biomedical approaches for diagnosing and managing disabling low back pain (LBP) have failed to arrest the exponential increase in health care costs, with a concurrent increase in disability and chronicity. Health messages regarding the vulnerability of the spine and a failure to target the interplay among multiple factors that contribute to pain and disability may partly explain this situation. Although many approaches and subgrouping systems for disabling LBP have been proposed in an attempt to deal with this complexity, they have been criticized for being unidimensional and reductionist and for not improving outcomes. Cognitive functional therapy was developed as a flexible integrated behavioral approach for individualizing the management of disabling LBP. This approach has evolved from an integration of foundational behavioral psychology and neuroscience within physical therapist practice. It is underpinned by a multidimensional clinical reasoning framework in order to identify the modifiable and nonmodifiable factors associated with an individual's disabling LBP. This article illustrates the application of cognitive functional therapy to provide care that can be adapted to an individual with disabling LBP.
Understanding the Etiology of Chronic Pain From a Psychological Perspective
Authors: Linton Steven J , Flink Ida K , Vlaeyen Johan W S
Published: February 2018

The etiology of chronic pain–related disability is not fully understood, particularly from a clinical perspective. Investigations to date have identified risk factors and elucidated some important processes driving the development of persistent pain problems. Yet this knowledge and its application are not always accessible to practicing physical therapists or other clinicians. This article aims to summarize the main psychological processes involved in the development of chronic pain disability and to derive some guidelines for treatment and future research. To this end, the focus is on the paradox of why coping strategies that are helpful in the short term continue to be used even when—ironically—they maintain the problem in the long term. To aid in summarizing current knowledge, 4 tenets that elucidate the etiology of chronic pain are described. These tenets emphasize that chronic pain disability is a developmental process over time, contextual factors set the stage for this development, underlying transdiagnostic psychological factors fuel this development, and the principles of learning steer the development of pain behaviors. With these tenets, an explanation of how a chronic problem develops for one person but not another is provided. Finally, hypotheses that can be empirically tested to guide clinical application as well as basic research are generated. In conclusion, understanding the psychological processes underlying the etiology of chronic pain provides testable ideas and a path forward for improving treatment interventions.
A Mechanism-Based Approach to Physical Therapist Management of Pain
Authors: Chimenti Ruth L , Frey-Law Laura A , Sluka Kathleen A
Published: February 2018

Pain reduction is a primary goal of physical therapy for patients who present with acute or persistent pain conditions. The purpose of this review is to describe a mechanism-based approach to physical therapy pain management. It is increasingly clear that patients need to be evaluated for changes in peripheral tissues and nociceptors, neuropathic pain signs and symptoms, reduced central inhibition and enhanced central excitability, psychosocial factors, and alterations of the movement system. In this Perspective, 5 categories of pain mechanisms (nociceptive, central, neuropathic, psychosocial, and movement system) are defined, and principles on how to evaluate signs and symptoms for each mechanism are provided. In addition, the underlying mechanisms targeted by common physical therapist treatments and how they affect each of the 5 categories are described. Several different mechanisms can simultaneously contribute to a patient's pain; alternatively, 1 or 2 primary mechanisms may cause a patient's pain. Further, within a single pain mechanism, there are likely many possible subgroups. For example, reduced central inhibition does not necessarily correlate with enhanced central excitability. To individualize care, common physical therapist interventions, such as education, exercise, manual therapy, and transcutaneous electrical nerve stimulation, can be used to target specific pain mechanisms. Although the evidence elucidating these pain mechanisms will continue to evolve, the approach outlined here provides a conceptual framework for applying new knowledge as advances are made.
Effects of Clariva Complete Beans Seed Treatment on Heterodera glycines Reproduction and Soybean Yield in Iowa
Authors: Bissonnette Kaitlyn M. , Marett Christopher C. , Mullaney Mark P. , Gebhart Gregory D. , Kyveryga Peter , Mueller Tristan A. , Tylka Gregory L.
Published: February 2018

In recent years, nematode-protectant seed treatments have become available to supplement resistant soybean cultivars to manage soybean cyst nematode (Heterodera glycines; SCN). Twenty-seven small-plot and 18 strip-trial experiments were conducted comparing the effects of Clariva Complete Beans (CCB) and CruiserMaxx Advanced plus Vibrance (CMV) on SCN reproduction and soybean yield on a moderately resistant (2014) and resistant (2015 to 2016) soybean cultivar. Yield data were collected, and an SCN reproductive factor was calculated by dividing final (at harvest) SCN egg population densities by initial (at planting) population densities from soil samples collected in each small plot or sampled area in the strip trials. Relative to the CMV treatment, CCB significantly decreased SCN reproductive factor in two small-plot experiments (one each in 2014 and 2015) but not in any of the strip trials in any year. Soybean yields were significantly greater with CCB versus CMV in 5 of the 18 strip trials but not in any of the small-plot experiments, even when there were significant decreases in SCN reproduction. For unknown reasons, CCB significantly decreased yields in two small-plot experiments and at one strip-trial location. In summary, the effects of CCB seed treatment on SCN reproduction and soybean yields were variable in the years that these experiments were conducted in Iowa.
Prevalence and Cropping System Impacts on Soybean Vein Necrosis Disease in Delaware Soybeans
Authors: Kleczewski Nathan M.
Published: February 2018

Soybean vein necrosis disease (SVN) is the most widespread virus of soybeans in the United States. This thrip-vetcored virus can cause foliar chlorosis and necrosis, and it can reduce soybean oil content, which may impact producers of high-oleic acid soybeans in the mid-Atlantic. The prevalence of SVN in Delaware is unknown. In addition, we hypothesized that cropping system (i.e., full-season versus double-cropped) beans may differ in SVN, likely owing to duration of exposure to viruliferous thrips. SVN incidence was assessed in 88 soybean fields (48 full season, 40 double crop following small grains) from 2015 to 2017. Each field was assessed at the vegetative growth stage and early reproductive stage. Following statistical analysis using a random mixed repeated measures model, data indicated that SVN incidence increased from 4.5 to 29.8% when comparing vegetative versus reproductive growth stages. SVN incidence was 50% lower in full-season compared with double-cropped soybeans. Our data indicate that double-cropped soybeans or late-planted soybeans may be at higher risk for SVN, and therefore producers of high-oleic acid soybeans should avoid late planting dates.
Red Rust of Neoregelia Bromeliads Caused by a Parasitic Alga Cephaleuros parasiticus in Florida
Authors: Sanahuja G. , Lopez P. , Palmateer A. J. , Chase A. R.
Published: February 2018

A newly emerging disease affecting proprietary hybrids of Neoregelia bromeliads was found in nursery production throughout south Florida. Initial symptoms appeared as small, reddish leaf spots with signs of fungal-like growth on the abaxial leaf surface closely resembling a rust. Closer examination of diseased tissue revealed the growth to be an alga with morphological and molecular characteristics of Cephaleuros parasiticus. This genus of plant parasitic thalloid green algae occurs worldwide in tropical and subtropical regions. Isolates of C. parasiticus collected from Neoregelia hybrid bromeliads were compared with two common Cephaleuros spp. (C. parasiticus and C. virescens) causing leaf spots on guava (Psidium guajava) in south Florida. Further, pathogenicity tests were conducted on healthy Neoregelia hybrids using C. parasiticus isolates collected from diseased leaves of bromeliads and guava. Isolates from both sources produced symptoms consistent with those originally described as “red rust” on Neoregelia hybrids. Florida has 165 plant species belonging to 53 families that have been reported as hosts of Cephaleuros spp., but this is the first report on Neoregelia hybrid bromeliads.
A novel antimicrobial alternative of microbiota metabolic product deoxycholic acid controls chicken necrotic enteritis
Authors: Wang Hong , Latorre Juan D. , Bansal Mohit , Al-Rubaye Bilal , Tellez Guillermo , Hargis Billy , Sun Xiaolun
Published: February 2018

Necrotic enteritis (NE) caused by Clostridium perfringens infection has reemerged as a prevalent poultry disease worldwide due to reduced usage of prophylactic antibiotics. The lack of alternative antimicrobial strategies to control this disease is mainly due to limited insight into NE pathogenesis, microbiome relationships, and host responses. Here we reported that the metabolic byproduct of microbial metabolism of bile acids to deoxycholic acid (DCA), at as low as 50 μM, inhibited 82.8% of C. perfringens growth in Tryptic Soy Broth (P < 0.05). Sequential Eimeria maxima and C. perfringens challenge strongly induced NE, severe intestinal inflammation, and body weight (BW) loss in broiler chickens. These negative effects were diminished by 1.5 g/kg DCA diet. At the cellular level, DCA alleviated NE-associated ileal epithelial death and lamina propria immune cell apoptosis. Interestingly, DCA reduced C. perfringens invasion into villi without significantly altering the bacterial luminal colonization. Molecular analysis showed that DCA reduced inflammatory mediators of Infγ, Litaf (Tnfα), Il1β, and Mmp9 mRNA accumulation in ileal tissue. Mechanically, C. perfringens induced elevated expression of inflammatory cytokines of Infγ, Litaf, and Ptgs2 (COX-2 gene) in chicken splenocytes. Inhibiting the COX signaling by aspirin attenuated INFγ- or TNFa-induced inflammatory response in the splenocytes. Consistently, chickens fed 0.12 g/kg aspirin diet resisted against NE-induced BW loss, ileal inflammation, and villus apoptosis. In conclusion, microbial metabolic product DCA prevents NE-induced BW loss and ileal inflammation through curbing inflammatory response. These novel findings could serve as a stepping-stone for developing next generation antimicrobial alternatives against NE.
CD117/c-kit in Cancer Stem Cell-Mediated Progression and Therapeutic Resistance
Authors: Foster Brittni M. , Zaidi Danish , Young Tyler R. , Mobley Mary E. , Kerr Bethany A.
Published: February 2018

Metastasis is the primary cause of cancer patient morbidity and mortality but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patients' tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven by a cancer stem-like cell or tumor progenitor cell, while recurrence at a secondary site is driven by metastatic cancer stem cells or metastasis-initiating cells. Ongoing efforts are aimed at identifying and characterizing these stem-like cells driving recurrence and metastasis. One potential marker for the cancer stem-like cell subpopulation is CD117/c-kit, a tyrosine kinase receptor associated with cancer progression and normal stem cell maintenance. In our analyses, CD117 was expressed in several tissues and was highly expressed in bone marrow progenitor cells. Also, we uncovered that CD117 gene amplifications and mutations occurred in multiple cancers. Further, activation of CD117 by its ligand stem cell factor (SCF; kit ligand) in the progenitor cell niche stimulates several signaling pathways driving proliferation, survival, and migration. These signaling pathways were commonly altered in patients with CD117 amplifications and mutations. Here, we examine evidence that the SCF/CD117 signaling axis controls cancer progression through the regulation of stemness and resistance to tyrosine kinase inhibitors.

Abbreviations

AML

acute myeloid leukemia

CML

chronic myeloid leukemia

CTC

circulating tumor cell

CSC

cancer stem cell

DTC

disseminated tumor cell

GIST

gastrointestinal stromal tumor

HSC

hematopoietic stem cell

SCF

stem cell factor

TKI

tyrosine kinase inhibitor
Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences1
Authors: Linnér Richard Karlsson , Biroli Pietro , Kong Edward , Meddens S Fleur W , Wedow Robbee , Fontana Mark Alan , Lebreton Maël , Abdellaoui Abdel , Hammerschlag Anke R , Nivard Michel G , Okbay Aysu , Rietveld Cornelius A , Timshel Pascal N , Tino Stephen P , Trzaskowski Maciej , Vlaming Ronald de , Zünd Christian L , Bao Yanchun , Buzdugan Laura , Caplin Ann H , Chen Chia-Yen , Eibich Peter , Fontanillas Pierre , Gonzalez Juan R , Joshi Peter K , Karhunen Ville , Kleinman Aaron , Levin Remy Z , Lill Christina M , Meddens Gerardus A , Muntané Gerard , Sanchez-Roige Sandra , Rooij Frank J van , Taskesen Erdogan , Wu Yang , Zhang Futao ,   23andMe Research Team, eQTLgen Consortium, International Cannabis Consortium, Psychiatric Genomics Consortium, Social Science Genetic Association Consortium,, Auton Adam , Boardman Jason D , Clark David W , Conlin Andrew , Dolan Conor C , Fischbacher Urs , Groenen Patrick JF , Harris Kathleen Mullan , Hasler Gregor , Hofman Albert , Ikram Mohammad A , Jain Sonia , Karlsson Robert , Kessler Ronald C , Kooyman Maarten , MacKillop James , Männikkö Minna , Morcillo-Suarez Carlos , McQueen Matthew B , Schmidt Klaus M , Smart Melissa C , Sutter Matthias , Thurik A Roy , Uitterlinden Andre G , White Jon , Wit Harriet de , Yang Jian , Bertram Lars , Boomsma Dorret , Esko Tõnu , Fehr Ernst , Hinds David A , Johannesson Magnus , Kumari Meena , Laibson David , Magnusson Patrik KE , Meyer Michelle N , Navarro Arcadi , Palmer Abraham A , Pers Tune H , Posthuma Danielle , Schunk Daniel , Stein Murray B , Svento Rauli , Tiemeier Henning , Timmers Paul RHJ , Turley Patrick , Ursano Robert J , Wagner Gert G , Wilson James F , Gratten Jacob , Lee James J , Cesarini David , Benjamin Daniel J , Koellinger Philipp D , Beauchamp Jonathan P
Published: February 2018

Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to strongly genetically correlated (to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near general-risk-tolerance-associated SNPs are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We find no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.