bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum parity Hall effect in Bernal-stacked trilayer graphene
Authors: Stepanov Petr , Barlas Yafis , Che Shi , Myhro Kevin , Voigt Greyson , Pi Ziqi , Watanabe Kenji , Taniguchi Takashi , Smirnov Dmitry , Zhang Fan , Lake Roger K. , MacDonald Allan H. , Lau Chun Ning
Published: May 2019

Significance

The quantum Hall effect, which is characterized by an insulating bulk and chiral edge states, has recently been generalized from transport of charges to transport of other degrees of freedom, leading to quantum spin Hall and quantum valley Hall effects. Here, we report a class of quantum Hall effect, the quantum parity Hall (QPH) effect, in which boundary channels are distinguished by even or odd parity under the system’s mirror reflection symmetry. The QPH is realized in charge neutral Bernal- or ABA-stacked trilayer graphene, which displays a striking phase diagram with four different phases, arising from an interplay between topologically protected crystalline symmetry and Coulomb interactions. Our results motivate a search for classes of topological states in van der Waals materials.
The sensori-semantic clustering of ideophonic meaning in Pastaza Quichua
Authors: Nuckolls Janis B.
Published: May 2019

I formulate an approach to ideophone semantics which, though based on a corpus from Pastaza Quichua, a South American indigenous language, has potential for analyzing the semantics of ideophone systems more generally. Research on ideophones’ formal properties has preoccupied an increasing number of scholars, while systematic semantic analyses are lagging. Ideophones’ semantics pose challenges because of their intonation and gesture, sound symbolism, and sensory complexity. These qualities require an approach going beyond the traditional mono-sensory classifications, which have dominated ideophones’ semantic descriptions. Using a sensory cluster diagram featuring an implicational logic based on 10 super- and subcategories of sensory experience, this paper analyzes a sample of ideophones drawn from an online corpus featuring 500 archived ideophones.
Ideophones as a measure of multilingualism
Authors: Tucker Childs G.
Published: May 2019

The purpose of the pilot research described here was twofold. The first was to develop a measure for multilingualism, how to characterize what has come to be known in the literature as a linguistic repertoire in a rapid and economical manner. A linguistic repertoire is not a language but the resources and practices of a multilingual in a multilingual community. How this repertoire can be descriptively characterized is problematic. A first pass, as illustrated here, used knowledge of ideophones as the measure of language mastery just because ideophones are so language-specific and deeply embedded in the socio-cultural patterns of the language. The study was limited to one of the three vital languages in the research area but will eventually be extended to the others. The second purpose was to explore the interaction of multilingualism with the mastery of ideophones.
Factors constraining agriculture and livestock technology adoption in Southern Africa.
Authors: Hargreaves M. M. J. , Riveros F. J. L.
Published: May 2019

Southern Africa is comprised of 15 members linked by economical and development reasons. The area has a high potential for agriculture but there are factors (climatic, economic, extension, social and soil) constraining production. Climate change is occurring fast, which has led to the current water crisis in the region. Sugarcane and maize are the major crops produced in the region, and South Africa is the major producer with 43.5% (sugarcane) and 44.8% (maize) of the production in 2016. South Africa, Mauritius and Tanzania are the major producers of raw sugar. Data show that they processed 12% (South Africa), 11% (Mauritius) and 10% (Tanzania) of their sugarcane, respectively, which could reflect a lack of technology or a high level of informal processing. South Africa and Tanzania are the biggest producers of cattle, goats and sheep. South Africa slaughters 11.8% of their cattle, 20.3% of goat and 29.7% of sheep; Tanzania slaughters 27.2% of their cattle, 15.1% of goat and 24.9% of sheep, which leads to a large informal market. Factors affecting technology adoption are mainly geographic (water crisis, climate, soil and land use), social (the poor community's wishes and considerations within a top-down delivery of technology, to gender issues in chieftaincies and to language barriers), financial (unequal access and distribution) and extension (communication between the donors, the community and extension institutions such as the government, NGOs and foundations).
The endoscopic evaluation of the oesophageal phase of swallowing (E-FEES)
Authors: Farneti Daniele , Genovese Elisabetta
Published: May 2019

During a fiberoptic endoscopic evaluation of swallowing (FEES) the study of the oesophagus, complete with tests with bolus (oesophageal FEES, E-FEES) is a procedure rarely used in a phoniatric setting, with patients complaining of swallowing and voice alterations. This extension of FEES toward the oesophagus by a transnasal approach is a procedure used for decades in the instrumental evaluation of patients with ENT complaints. E-FEES is used on out-patients without premedication or local anaesthesia. The patient is sitting upright and a 70 cm flexible endoscope, 3.5 cm diameter, is used. During the procedure the patients undergo tests with bolus. 20 patients (13M/7F, range 19–78 years, mean age 50, 51 years), taken from 437 consecutive outpatients seen in our Department from August to December 2011, underwent E-FEES (retrospective analysis). Patients were selected based on a reflux finding index (RFI) > 13, Reflux finding score (RFS) > 7 and FEES alterations (penetration/aspiration, spillage, residues). E-FEES findings were: 10 esophagitis, 1 gastroesophageal junction incontinence, 2 hiatal hernia, 4 motility alterations, 2 diverticula, 1 carcinoma. oesophageal alterations are not rare in patients with deglutition and voice disorders. E-FEES is a safe, reliable and cost-effective technique, worthy of being implemented in a phoniatric setting. The main steps and characteristic of the procedure are proposed.
Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer
Authors: Tiwari Payal , Blank Ariane , Cui Chang , Schoenfelt Kelly Q. , Zhou Guolin , Xu Yanfei , Khramtsova Galina , Olopade Funmi , Shah Ajay M. , Khan Seema A. , Rosner Marsha Rich , Becker Lev
Published: May 2019

Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice. MMe macrophages release IL-6 in an NADPH oxidase 2 (NOX2)–dependent manner, which signals through glycoprotein 130 (GP130) on TNBC cells to promote stem-like properties including tumor formation. Deleting Nox2 in myeloid cells or depleting GP130 in TNBC cells attenuates obesity-augmented TNBC stemness. Moreover, weight loss reverses the effects of obesity on MMe macrophage inflammation and TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue as a mechanism for promoting TNBC stemness and tumorigenesis during obesity.
Benchmarking irrigation water use in producer fields in the US central Great Plains
Authors: Gibson Katherine E B , Gibson Justin P , Grassini Patricio
Published: May 2019

Efficient use of freshwater resources is necessary to balance food production and long-term sustainability of irrigated agricultural systems. Here we developed a framework to benchmark irrigation water use relative to crop yield for individual fields based on site-specific weather and soil. Subsequently, we used the framework to diagnose on-farm irrigation management, in relation to crop production, in maize and soybean producer fields in Nebraska (USA). We found actual irrigation to be similar to estimated irrigation water requirement in about half of the fields (i.e. small water surplus). Remarkably, these fields attained yields similar to fields where actual irrigation exceeded water requirements (i.e. large water surplus). Underlying causes for water surplus included producer risk aversion in soils with low water storage capacity, use of coarse methods for scheduling irrigation, and tillage. Scenario assessment indicated that total irrigation volume could potentially be reduced up to 25%–40%, without hurting crop yields, by reducing current irrigation surplus in years with above- or near-average seasonal precipitation. About a third of the producer fields already achieved high yields with little water surplus, supporting the contention that achieving high productivity with less irrigation by better matching irrigation amounts in relation with crop water requirements are compatible goals. The proposed framework can be applied to other crops and regions provided there are well-validated models, local soil and weather datasets, and reliable field-level irrigation, yield, and management records.
Caring for a frail older person: the association between informal caregiver burden and being unsatisfied with support from family and friends
Authors: Lopez Hartmann Maja , De Almeida Mello Johanna , Anthierens Sibyl , Declercq Anja , Van Durme Thérèse , Cès Sophie , Verhoeven Véronique , Wens Johan , Macq Jean , Remmen Roy
Published: May 2019

Background/objective

although informal caregivers (ICG) find caring for a relative mainly satisfying, it can be difficult at times and it can lead to a state of subjective burden characterised by -among others- fatigue and stress. The objective of this study is to analyse the relationship between perceived social support and subjective burden in providing informal care to frail older people.

Methods

a descriptive cross-sectional study was conducted using data from a large nationwide longitudinal effectiveness study. Pearson correlations were calculated between the variables for support and burden. Logistic regression models were applied to determine the association between being unsatisfied with support and burden, taking into account multiple confounding variables.

Results

of the 13,229 frail older people included in this study, 85.9% (N = 11,363) had at least one informal caregiver. Almost 60% of the primary informal caregivers manifested subjective burden, measured with the 12-item Zarit-Burden-Interview (ZBI-12). The percentage of informal caregivers that were unsatisfied with support from family and friends was on average 11.5%. Logistic regression analysis showed that being unsatisfied with support is associated with burden (OR1.85; 95%CI1.53–2.23). These results were consistent for the three groups of impairment level of the frail older persons analysed.

Conclusions

the association between perceived social support and subjective caregiver burden was explored in the context of caring for frail older people. ICGs who were unsatisfied with support were more likely to experience burden. Our findings underline the importance of perceived social support in relation to caregiver burden reduction. Therefore efforts to improve perceived social support are worth evaluating.
Expression Pattern of Aquaporin 1 and Aquaporin 3 in Melanocytic and Nonmelanocytic Skin Tumors
Authors: Osorio Giovana , Zulueta-Dorado Teresa , González-Rodríguez Patricia , Bernabéu-Wittel José , Conejo-Mir Julian , Ramírez-Lorca Reposo , Echevarría Miriam
Published: May 2019

Objectives

Study of aquaporin 1 (AQP1) and aquaporin 3 (AQP3) expression to understand its potential role in the pathophysiology of skin cancer.

Methods

Analysis of AQP1 and AQP3 expression by immunohistochemistry of 72 skin biopsy specimens from melanocytic skin tumors, nonmelanocytic tumors, or healthy samples.

Results

AQP1 showed strong labeling in 100% of benign common melanocytic nevi. Small blood vessels, stroma, and melanophages surrounding different types of melanomas tumors also were positive. Tumoral melanocytes in atypical nevi and melanomas were negative for AQP1. AQP3 showed strong labeling in 100% of melanocytic nevi, 100% of atypical melanocytic nevi, and 100% of melanomas. In all basal cell carcinomas and squamous cell carcinomas, staining for AQP3 was positive.

Conclusions

To our knowledge, this work represents the first demonstration of AQP1/AQP3 expression in human melanocytic skin tumors. More studies are needed to understand the underlying molecular mechanisms of expression of both AQPs in melanocytic tumors and their potential as molecular therapeutic targets.
Inter-assessor Agreement for TREXMO and Its Models Outside the Translation Framework
Authors: Savic Nenad , Lee Eun Gyung , Gasic Bojan , Vernez David
Published: May 2019

Within the framework of Registration, Evaluation, Authorization, and restriction of CHemicals (REACH), occupational exposure models are often used to predict the levels of exposure at a workplace. Poor inter-assessor agreement with their use poses a concern that may lead to different and dangerous risk conclusions. TREXMO (v1, 2016), a web tool providing parameter translations between six exposure models under REACH, is expected to improve the inter-assessor agreement. In this study, 18 assessors performed exposure assessment for six exposure situations within and outside the framework of this translation tool. In more than half of the evaluated cases, the results showed better agreement between assessors selecting the exposure parameters within the framework of TREXMO than when manually coding. The most affected were the parameters related to activity (such as “handling types” of Stoffenmanager) and exposure control (such as local controls). Furthermore, the agreement between the estimates calculated by different assessors was also improved when performing the translations between the models. For Stoffenmanager, for example, the relative standard deviation of 70–121%, obtained for vapors without applying the translation system, was 29–94% with the translations from ART. These findings showed a potential of TREXMO to impact the inter-assessor agreement. Because the study was limited to 18 assessors and only six exposure situations were assessed, further investigations are suggested.
Translating Fear Circuitry: Amygdala Projections to Subgenual and Perigenual Anterior Cingulate in the Macaque
Authors: Sharma K K , Kelly E A , Pfeifer C W , Fudge J L
Published: May 2019

Rodent fear-learning models posit that amygdala–infralimbic connections facilitate extinction while amygdala–prelimbic prefrontal connections mediate fear expression. Analogous amygdala–prefrontal circuitry between rodents and primates is not established. Using paired small volumes of neural tracers injected into the perigenual anterior cingulate cortex (pgACC; areas 24b and 32; a potential homologue to rodent prelimbic cortex) and subgenual anterior cingulate cortex (sgACC, areas 25 and 14c; a potential homologue to rodent infralimbic cortex) in a single hemisphere, we mapped amygdala projections to the pgACC and sgACC within single subjects. All injections resulted in dense retrograde labeling specifically within the intermediate division of the basal nucleus (Bi) and the magnocellular division of the accessory basal nucleus (ABmc). Areal analysis revealed a bias for connectivity with the sgACC, with the ABmc showing a greater bias than the Bi. Double fluorescence analysis revealed that sgACC and pgACC projections were intermingled within the Bi and ABmc, where a proportion were double labeled. We conclude that amygdala inputs to the ACC largely originate from the Bi and ABmc, preferentially connect to the sgACC, and that a subset collaterally project to both sgACC and pgACC. These findings advance our understanding of fear extinction and fear expression circuitry across species.
How to Construe a Myth: Neutrality Within the United Nations System Under Special Consideration of the Austrian Case
Authors: Hilpold Peter
Published: May 2019

In the 19th century neutrality was a highly appreciated concept. In the 20th century it widely lost relevance and in principle it should be incompatible with UN membership. However, also under the UN system, some States have opted for neutrality and it can be argued that there is still space for this status within the universal peace order. In fact, this peace order is far from perfect. There are several lacunae in the prohibition of the use of force and this concept is open to different interpretations. New threats, such as international terrorism, are emerging that could threaten the absolute prohibition of the use of force. It is contended here that neutrals could play an important role when it comes to finding an interpretation of this prohibition that best could reconcile the goals of peace and security with the overall—still imperfect—structure of the UN system. These questions are analysed with primary reference to Austrian neutrality which on the one hand seems obsolete but on the other is forcefully looking for a new meaning.
Genetically modulated educational attainment and coronary disease risk
Authors: Zeng Lingyao , Ntalla Ioanna , Kessler Thorsten , Kastrati Adnan , Erdmann Jeanette ,   The UK Biobank CardioMetabolic Consortium CHD Working Group, Danesh John , Watkins Hugh , Samani Nilesh J , Deloukas Panos , Schunkert Heribert
Published: May 2019

Aims

Genetic disposition and lifestyle factors are understood as independent components underlying the risk of multiple diseases. In this study, we aim to investigate the interplay between genetics, educational attainment—an important denominator of lifestyle—and coronary artery disease (CAD) risk.

Methods and results

Based on the effect sizes of 74 genetic variants associated with educational attainment, we calculated a ‘genetic education score’ in 13 080 cases and 14 471 controls and observed an inverse correlation between the score and risk of CAD [P = 1.52 × 10−8; odds ratio (OR) 0.79, 95% confidence interval (CI) 0.73–0.85 for the higher compared with the lowest score quintile]. We replicated in 146 514 individuals from UK Biobank (P = 1.85 × 10−6) and also found strong associations between the ‘genetic education score’ with ‘modifiable’ risk factors including smoking (P = 5.36 × 10−23), body mass index (BMI) (P = 1.66 × 10−30), and hypertension (P = 3.86 × 10−8). Interestingly, these associations were only modestly attenuated by adjustment for years spent in school. In contrast, a model adjusting for BMI and smoking abolished the association signal between the ‘genetic education score’ and CAD risk suggesting an intermediary role of these two risk factors. Mendelian randomization analyses performed with summary statistics from large genome-wide meta-analyses and sensitivity analysis using 1271 variants affecting educational attainment (OR 0.68 for the higher compared with the lowest score quintile; 95% CI 0.63–0.74; P = 3.99 × 10−21) further strengthened these findings.

Conclusion

Genetic variants known to affect educational attainment may have implications for a health-conscious lifestyle later in life and subsequently affect the risk of CAD.
Outcomes of cryoballoon or radiofrequency ablation in symptomatic paroxysmal or persistent atrial fibrillation
Authors: Hoffmann Ellen , Straube Florian , Wegscheider Karl , Kuniss Malte , Andresen Dietrich , Wu Li-Qun , Tebbenjohanns Jürgen , Noelker Georg , Tilz Roland Richard , Chun Julian Kyoung Ryul , Franke Andreas , Stellbrink Christoph , Garcia-Alberola Arcadi , Dorwarth Uwe , Metzner Andreas , Ouarrak Taoufik , Brachmann Johannes , Kuck Karl-Heinz , Senges Jochen ,   FREEZE Cohort Study Investigators, Souza J J , Stanley A , Spitzer S G , Willems S , Dierk T , Borchard R , Seidl K H , Zahn R , Groschup G , Obel I W P , Gerds-Li J H , Gopal R R , Schrickel J , Lewalter T , Stanley A , Moshage W , Eckardt L , Jung W , Kremer P , Lubinski A , Schumacher B , Lickfett L , Muenzel T , Steinwender C , Efremidis M , Deneke T , Nguyen D Q , Hochadel M , Schneider s
Published: May 2019

Aims

To evaluate the effectiveness and safety of cryoballoon ablation (CBA) compared with radiofrequency ablation (RFA) for symptomatic paroxysmal or drug-refractory persistent atrial fibrillation (AF).

Methods and results

Prospective cluster cohort study in experienced CBA and RFA centres. Primary endpoint was ‘atrial arrhythmia recurrence’, secondary endpoints were as follows: procedural results, safety, and clinical course. A total of 4189 patients were included: CBA 2329 (55.6%) and RFA 1860 (44.4%). Cryoballoon ablation population was younger, with fewer comorbidities. Procedure time was longer in the RFA group (P = 0.01). Radiation exposure was 2487 (CBA) and 1792 cGycm2 (RFA) (P < 0.001). Follow-up duration was 441 (CBA) and 511 days (RFA) (P < 0.0001). Primary endpoint occurred in 30.7% (CBA) and 39.4% patients (RFA) [adjusted hazard ratio (adjHR) 0.85, 95% confidence interval (CI) 0.70–1.04; P = 0.12). In paroxysmal AF, CBA resulted in a lower risk of recurrence (adjHR 0.80, 95% CI 0.64–0.99; P = 0.047). In persistent AF, the primary outcome was not different between groups. Major adverse cardiovascular and cerebrovascular event rates were 1.0% (CBA) and 2.8% (RFA) (adjHR 0.53, 95% CI 0.26–1.10; P = 0.088). Re-ablations (adjHR 0.46, 95% CI 0.34–0.61; P < 0.0001) and adverse events during follow-up (adjHR 0.64, 95% CI 0.48–0.88; P = 0.005) were less common after CBA. Higher rehospitalization rates with RFA were caused by re-ablations.

Conclusions

The primary endpoint did not differ between CBA and RFA. Cryoballoon ablation was completed rapidly; the radiation exposure was greater. Rehospitalization due to re-ablations and adverse events during follow-up were observed significantly less frequently after CBA than after RFA. Subgroup analysis suggested a lower risk of recurrence after CBA in paroxysmal AF.

Trial Registration

ClinicalTrials.gov (NCT01360008), https://clinicaltrials.gov/ct2/show/NCT01360008.
‘Candidatus Oscillochloris fontis’: a novel mesophilic phototrophic Chloroflexota bacterium belonging to the ubiquitous Oscillochloris genus
Authors: Gaisin Vasil A , Burganskaya Ekaterina I , Grouzdev Denis S , Osipova Natalya S , Ashikhmin Aleksandr A , Sinetova Maria A , Krutkina Maria S , Bryantseva Irina A , Sukhacheva Marina V , Kochetkova Tatiana V , Koziaeva Veronika V , Kalashnikov Aleksandr M , Gorlenko Vladimir M
Published: May 2019

We present the results of a study of mesophilic anoxygenic phototrophic Chloroflexota bacteria from Mechigmen hot spring (the Chukotka Peninsula) and Siberia. According to 16S rRNA phylogenetic analysis, these bacteria belong to Oscillochloris trichoides. However, sequencing the draft genome of the bacterium from the Chukotka and analysis of the average nucleotide identity, as well as in silico DNA-DNA hybridization, reveal that this bacterium belongs to a novel species within the Oscillochloris genus. We, therefore, propose ‘Candidatus Oscillochloris fontis’ as a novel taxon to represent this mesophilic alkaliphilic anaerobic anoxygenic phototrophic bacterium. Spectrophotometry and high-performance liquid chromatography analysis show that the bacterium possesses bacteriochlorophylls c and a, as well as lycopene, β-carotene and γ-carotene. In addition, transmission electron microscopy shows the presence of chlorosomes, polyhydroxyalkanoate- and polyphosphate-like granules. The genome of ‘Ca. Oscillochloris fontis’ and the Siberian strains of Oscillochloris sp. possess the key genes for nitrogenase complex (nifH) and ribulose-1,5-bisphosphate carboxylase/oxygenase (cbbL), as previously described for O. trichoides DG-6. The results presented here, and previously published data, show that Oscillochloris bacteria from different aquatic environments have the potential for CO2 and N2 fixation. Additionally, we describe a new primer system for the detection of RuBisCo form I.
Negative impact of polycystic ovary syndrome on bone health: a systematic review and meta-analysis
Authors: Piovezan Júlia Mottecy , Premaor Melissa Orlandin , Comim Fábio Vasconcellos
Published: May 2019

BACKGROUND

Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of fractures, bone mineral density (BMD) or bone markers led to uncertainty whether PCOS might improve or deteriorate bone health.

OBJECTIVE AND RATIONALE

This study aimed to investigate the impact of PCOS on bone markers, BMD and fracture risk.

SEARCH METHODS

A systematic review and a meta-analysis were carried out. PubMed, EMBASE and Cochrane databases were searched for eligible studies from 1st of January of 1990 to 9th of October of 2018. Eligible studies enrolled women older than 18 years with PCOS, which should be diagnosed according to the Rotterdam Consensus, the Androgen Excess Society, the National Institutes of Health Consensus or the International Classification of Diseases. The studies were grouped according to patient mean BMI: <27 kg/m2 or ≥27 kg/m2. The results were polled as mean difference (MD), standardized MD (SMD) and hazard ratio (HR).

OUTCOMES

Overall, 921 studies were retrieved, and 31 duplicated studies were removed. After screening the titles and abstracts, 80 studies were eligible for full text reading. Of those, 23 studies remained for qualitative synthesis. With the exception of one study, all studies were considered high quality based on the Newcastle–Ottawa scale (NOS; score ≥6). Meta-analysis was performed in 21 studies, with a total of 31 383 women with PCOS and 102 797 controls. Women with PCOS with BMI <27 kg/m2 had lower BMD of the total femur (MD, −0.04; 95% CI, −0.07 to 0.00; I2 = 31%; P = 0.22) and spine (MD, −0.07; 95% CI, −0.13 to −0.01; I2 = 70%; P < 0.01) when compared with the control group, whereas for women with BMI ≥27 kg/m2 no difference was observed (femur: MD, 0.02; 95% CI, −0.02 to 0.05; I2 = 20%, P = 0.29; spine: MD, 0.02; 95% CI, −0.06 to 0.05; I2 = 0%; P = 0.84). Osteocalcin was remarkably reduced in women with PCOS with BMI <27 kg/m2 (SMD, −2.68; 95% CI, −4.70 to −0.67; I2 = 98%; P < 0.01), but in women with BMI ≥27 kg/m2, there were no differences between PCOS and controls. Few studies (n = 3) addressed the incidence of bone fractures in women with PCOS. The HR for total bone fractures did not identify differences between women with PCOS and controls.

WIDER IMPLICATIONS

On the basis of the available evidence, it is possible to assume that PCOS in women with BMI <27 kg/m2 is associated with reduced BMD in the spine and femur, and decreased bone formation, as manifested by lower levels of circulating osteocalcin. These findings suggest that bone parameters in PCOS may be linked, to some extent, to adiposity. These studies included premenopausal women, who have already achieved peak bone mass. Hence, further prospective studies are necessary to clarify the existence of increased risk of fractures in women with PCOS.
Changes in Vedolizumab Utilization Across US Academic Centers and Community Practice Are Associated With Improved Effectiveness and Disease Outcomes
Authors: Koliani-Pace Jenna L , Singh Siddharth , Luo Michelle , Hirten Robert , Aniwan Satimai , Kochhar Gursimran , Chang Shannon , Lukin Dana , Gao Youran , Bohm Matthew , Swaminath Arun , Gupta Nitin , Shmidt Eugenia , Meserve Joseph , Winters Adam , Chablaney Shreya , Faleck David M , Yang Jiao , Huang Zhongwen , Boland Brigid S , Shashi Preeti , Weiss Aaron , Hudesman David , Varma Sashidhar , Fischer Monika , Sultan Keith , Shen Bo , Kane Sunanda , Loftus Edward V , Sands Bruce E , Colombel Jean-Frederic , Sandborn William J , Lasch Karen , Siegel Corey A , Dulai Parambir S
Published: May 2019

Background

Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval.

Methods

We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses.

Results

A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD.

Conclusion

Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.
Root System Chip-Firing II: Central-Firing
Authors: Galashin Pavel , Hopkins Sam , McConville Thomas , Postnikov Alexander
Published: May 2019

Jim Propp recently proposed a labeled version of chip-firing on a line and conjectured that this process is confluent from some initial configurations. This was proved by Hopkins–McConville–Propp. We reinterpret Propp’s labeled chip-firing moves in terms of root systems; a “central-firing” move consists of replacing a weight $\lambda$ by $\lambda +\alpha$ for any positive root $\alpha$ that is orthogonal to $\lambda$. We show that central-firing is always confluent from any initial weight after modding out by the Weyl group, giving a generalization of unlabeled chip-firing on a line to other types. For simply-laced root systems we describe this unlabeled chip-firing as a number game on the Dynkin diagram. We also offer a conjectural classification of when central-firing is confluent from the origin or a fundamental weight.
Product Formula for the Limits of Normalized Characters of Kirillov–Reshetikhin Modules
Authors: Lee Chul-hee
Published: May 2019

The normalized characters of Kirillov–Reshetikhin modules over a quantum affine algebra have a limit as a formal power series. Mukhin and Young found a conjectural product formula for this limit, which resembles the Weyl denominator formula. We prove this formula except for some cases in type $E_8$ by employing an algebraic relation among these limits, which is a variant of $Q\widetilde{Q}$-relations.
Conjoined twins in Aegla uruguayana Schmitt, 1942 (Decapoda: Anomura: Aeglidae)
Authors: Diawol Valeria P , Negro Carlos L , Musin Gabriela E , Collins Pablo A
Published: May 2019

The first instance of a pair of conjoined embryos in Aegla uruguayanaSchmitt, 1942 is reported. Collected in a stream in Entre Ríos province, Argentina, the embryos were detected among 550 eggs containing embryos with normal morphological development, and constitute the second observed case of twins in AeglaLeach, 1820. The twins were joined together by their dorsum and lived for a few days in the laboratory; however, they did not hatch, dying inside the egg envelope.
Modulation of oxidative damage by lipopolysaccharides and antioxidant responses in the freshwater crab Sinopotamon henanense Bott 1967 (Decapoda: Brachyura: Potamonidae) during cadmium exposure
Authors: Zhou Yanying , Luo Zhengming , Wang Lan
Published: May 2019

Cadmium (Cd) is a toxic pollutant that exerts adverse effects on organisms. We examined oxidative damage and antioxidative parameters in hemocytes of the freshwater crab Sinopotamon henanense Bott 1967 exposed to sublethal levels of Cd for 21 d. We also examined the immunomodulation of lipopolysaccharides (LPS) on oxidation caused by Cd in the crab. Cd induced higher reactive oxygen species (ROS) levels but ROS production in crab hemocytes was down-regulated after LPS injection. The contents of malondialdehyde (MDA) and protein carbonyl derivatives (PCO), DNA-protein crosslinks (DPCs) coefficient in the hemocytes of crabs exposed to Cd increased. LPS injection could decrease these oxidative parameters. The total antioxidant capacity (T-AOC) was significantly inhibited by Cd and LPS enhanced the activity of T-AOC in crab hemocytes. Cd treatment also up-regulated activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Only CAT activity decreased when crabs were exposed to Cd followed by LPS stimulation. Peroxidase (POD) activities showed little change after Cd or LPS treatments. The oxidative damage caused by Cd exposure may be reduced by LPS, suggesting its possible use in aquaculture as an immunostimulant for crustaceans.
Plant vibrations at all scales: a review
Authors: de Langre Emmanuel
Published: May 2019

Plant vibrations is a wide subject that covers topics ranging from the swaying of trees under wind to elastic waves made by an insect on a leaf to communicate with its neighbors. For this reason, the state of the art is somehow fragmented over several communities. This review aims at giving a general overview of the main results and challenges in plant vibrations. Several scales are considered, from the very small and local, in leaves or fruits, to large canopies of many plants.
Rhodanese domain-containing sulfurtransferases: multifaceted proteins involved in sulfur trafficking in plants
Authors: Selles Benjamin , Moseler Anna , Rouhier Nicolas , Couturier Jérémy
Published: May 2019

Sulfur is an essential element for the growth and development of plants, which synthesize cysteine and methionine from the reductive assimilation of sulfate. Besides its incorporation into proteins, cysteine is the building block for the biosynthesis of numerous sulfur-containing molecules and cofactors. The required sulfur atoms are extracted either directly from cysteine by cysteine desulfurases or indirectly after its catabolic transformation to 3-mercaptopyruvate, a substrate for sulfurtransferases (STRs). Both enzymes are transiently persulfidated in their reaction cycle, i.e. the abstracted sulfur atom is bound to a reactive cysteine residue in the form of a persulfide group. Trans-persulfidation reactions occur when sulfur atoms are transferred to nucleophilic acceptors such as glutathione, proteins, or small metabolites. STRs form a ubiquitous, multigenic protein family. They are characterized by the presence of at least one rhodanese homology domain (Rhd), which usually contains the catalytic, persulfidated cysteine. In this review, we focus on Arabidopsis STRs, presenting the sequence characteristics of all family members as well as their biochemical and structural features. The physiological functions of particular STRs in the biosynthesis of molybdenum cofactor, thio-modification of cytosolic tRNAs, arsenate tolerance, cysteine catabolism, and hydrogen sulfide formation are also discussed.
Hyperons and quarks in proto-neutron stars
Authors: Roark J , Du X , Constantinou C , Dexheimer V , Steiner A W , Stone J R
Published: May 2019

In this work, we study matter in the cores of proto-neutron stars, focusing on the impact of their composition on the stellar structure. We begin by examining the effects of finite temperature (through a fixed entropy per baryon) and lepton fraction on purely nucleonic matter by making use of the DSH (Du, Steiner & Holt) model. We then turn our attention to a relativistic mean-field model containing exotic degrees of freedom, the Chiral Mean Field (CMF) model, again, under the conditions of finite temperature and trapped neutrinos. In the latter, since both hyperons and quarks are found in the cores of large-mass stars, their interplay and the possibility of mixtures of phases is taken into account and analysed. Finally, we discuss how stellar rotation can affect our results.
The plasmoid instability in a confined solar flare
Authors: MacTaggart David , Fletcher Lyndsay
Published: May 2019

Eruptive flares (EFs) are associated with erupting filaments and, in some models, filament eruption drives flare reconnection. Recently, however, observations of a confined flare (CF) have revealed all the hallmarks of an EF (impulsive phase, flare ribbons, etc.) without the filament eruption itself. Therefore, if the filament is not primarily responsible for impulsive flare reconnection, what is? In this Letter, we argue, based on mimimal requirements, that the plasmoid instability is a strong candidate for explaining the impulsive phase in the observed CF. We present magnetohydrodynamic simulation results of the non-linear development of the plasmoid instability, in a model active region magnetic field geometry, to strengthen our claim. We also discuss how the ideas described in this Letter can be generalized to other situations, including EFs.
The Legacy of Sexual Ancestors in Phenotypic Variability, Gene Expression, and Homoeolog Regulation of Asexual Hybrids and Polyploids
Authors: Bartoš Oldřich , Röslein Jan , Kotusz Jan , Paces Jan , Pekárik Ladislav , Petrtýl Miloslav , Halačka Karel , Štefková Kašparová Eva , Mendel Jan , Boroń Alicja , Juchno Dorota , Leska Anna , Jablonska Olga , Benes Vladimir , Šídová Monika , Janko Karel
Published: May 2019

Hybridization and polyploidization are important evolutionary processes whose impacts range from the alteration of gene expression and phenotypic variation to the triggering of asexual reproduction. We investigated fishes of the Cobitis taenia-elongatoides hybrid complex, which allowed us to disentangle the direct effects of both processes, due to the co-occurrence of parental species with their diploid and triploid hybrids. Employing morphological, ecological, and RNAseq approaches, we investigated the molecular determinants of hybrid and polyploid forms.

In contrast with other studies, hybridization and polyploidy induced relatively very little transgressivity. Instead, Cobitis hybrids appeared intermediate with a clear effect of genomic dosing when triploids expressed higher similarity to the parent contributing two genome sets. This dosage effect was symmetric in the germline (oocyte gene expression), interestingly though, we observed an overall bias toward C. taenia in somatic tissues and traits. At the level of individual genes, expression-level dominance vastly prevailed over additivity or transgressivity. Also, trans-regulation of gene expression was less efficient in diploid hybrids than in triploids, where the expression modulation of homoeologs derived from the “haploid” parent was stronger than those derived from the “diploid” parent.

Our findings suggest that the apparent intermediacy of hybrid phenotypes results from the combination of individual genes with dominant expression rather than from simple additivity. The efficiency of cross-talk between trans-regulatory elements further appears dosage dependent. Important effects of polyploidization may thus stem from changes in relative concentrations of trans-regulatory elements and their binding sites between hybridizing genomes. Links between gene regulation and asexuality are discussed.
Inclusion of an extended treatment with recovery improves the results for the human peripheral blood lymphocyte micronucleus assay
Authors: Whitwell James , Smith Robert , Chirom Teresa , Watters Gary , Hargreaves Victoria , Lloyd Mel , Phillips Sarah , Clements Julie
Published: May 2019

The in vitro micronucleus (IVMN) test was endorsed for regulatory genotoxicity testing with adoption of the Organisation for Economic Co-operation and Development (OECD) test guideline (TG) 487 in 2010. This included two equally acceptable options for extended treatment in the absence of metabolic activation: a treatment for 1.5–2.0 cell cycles with harvest at the end of treatment (Option A) or treatment for 1.5–2.0 cell cycles followed by recovery for 1.5–2.0 cell cycles prior to harvest (Option B). Although no preferences were discussed, TG 487 cautions that Option B may not be appropriate for stimulated lymphocytes where exponential growth may be declining at 96 h after phytohaemagglutinin (PHA) stimulation. Following revision of TG 487 in 2014 and 2016, emphasis has been placed on using Option A. Given the purpose of the IVMN assay is to determine both clastogenic and aneugenic potential, the authors believe the assay is compromised if an extended treatment with recovery is not included for sensitive detection of certain classes of chemical. In this study, average generation time (via bromodeoxyuridine incorporation) of human peripheral blood lymphocytes (HPBL) was measured up to 144 h after PHA stimulation. In addition, the HPBL micronucleus (MN) assay was performed using Option A and B treatment schedules. Cytotoxicity (replication index) and MN induction were determined following treatment with 14 chemicals. The data demonstrate that lymphocytes actively divide beyond 96 h after PHA stimulation. Furthermore, MN induction was only observed with some aneugenic chemicals and nucleoside analogues in HPBLs following extended treatment with a recovery period. For the majority of chemicals tested the magnitude of MN induction was generally greater and MN induction was observed across a wider concentration range following the Option B treatment schedule. In addition, steep concentration-related toxicity following treatment without recovery is more common, making selection of suitable concentrations (within regulatory toxicity limits) for MN analysis challenging.
The Gene Sculpt Suite: a set of tools for genome editing
Authors: Mann Carla M , Martínez-Gálvez Gabriel , Welker Jordan M , Wierson Wesley A , Ata Hirotaka , Almeida Maira P , Clark Karl J , Essner Jeffrey J , McGrail Maura , Ekker Stephen C , Dobbs Drena
Published: May 2019

The discovery and development of DNA-editing nucleases (Zinc Finger Nucleases, TALENs, CRISPR/Cas systems) has given scientists the ability to precisely engineer or edit genomes as never before. Several different platforms, protocols and vectors for precision genome editing are now available, leading to the development of supporting web-based software. Here we present the Gene Sculpt Suite (GSS), which comprises three tools: (i) GTagHD, which automatically designs and generates oligonucleotides for use with the GeneWeld knock-in protocol; (ii) MEDJED, a machine learning method, which predicts the extent to which a double-stranded DNA break site will utilize the microhomology-mediated repair pathway; and (iii) MENTHU, a tool for identifying genomic locations likely to give rise to a single predominant microhomology-mediated end joining allele (PreMA) repair outcome. All tools in the GSS are freely available for download under the GPL v3.0 license and can be run locally on Windows, Mac and Linux systems capable of running R and/or Docker. The GSS is also freely available online at www.genesculpt.org.
Bundle Theory with Kinds
Authors: Keinänen Markku , Tahko Tuomas E
Published: May 2019

Is it possible to get by with just one ontological category? We evaluate L.A. Paul's attempt to do so: the mereological bundle theory. The upshot is that Paul's attempt to construct a one category ontology may be challenged with some of her own arguments. In the positive part of the paper we outline a two category ontology with property universals and kind universals. We will also examine Paul's arguments against a version of universal bundle theory that takes spatiotemporal co-location instead of compresence or coinstantiation as the feature by which we can identify genuine bundles. We compare this novel theory, bundle theory with kinds, and Paul's mereological bundle theory and apply them to a case study concerning entangled fermions and co-located bosons.
Investment Timing and Incentive Costs*
Authors: Gryglewicz Sebastian , Hartman-Glaser Barney
Published: May 2019

We analyze how the costs of smoothly adjusting capital, such as incentive costs, affect investment timing. In our model, the owner of a firm holds a real option to increase a lumpy form of capital and can also smoothly adjust an incremental form of capital. Increasing the cost of incremental capital can delay or accelerate investment in lumpy capital. Incentive costs due to moral hazard are a natural source of costs for the accumulation of incremental capital. When moral hazard is severe, delaying investment in lumpy capital is costly, and overinvesting relative to the first-best case is optimal.

Received January 24, 2017; editorial decision March 15, 2019 by Editor Itay Goldstein.
Ventromedial and dorsolateral prefrontal interactions underlie will to fight and die for a cause
Authors: Pretus Clara , Hamid Nafees , Sheikh Hammad , Gómez Ángel , Ginges Jeremy , Tobeña Adolf , Davis Richard , Vilarroya Oscar , Atran Scott
Published: May 2019

Willingness to fight and die (WFD) has been developed as a measure to capture willingness to incur costly sacrifices for the sake of a greater cause in the context of entrenched conflict. WFD measures have been repeatedly used in field studies, including studies on the battlefield, although their neurofunctional correlates remain unexplored. Our aim was to identify the neural underpinnings of WFD, focusing on neural activity and interconnectivity of brain areas previously associated with value-based decision-making, such as the ventromedial prefrontal cortex (vmPFC) and the dorsolateral prefrontal cortex (dlPFC). A sample of Pakistani participants supporting the Kashmiri cause was selected and invited to participate in an functional magnetic resonance (fMRI) paradigm where they were asked to convey their WFD for a series of values related to Islam and current politics. As predicted, higher compared to lower WFD was associated with increased ventromedial prefrontal activity and decreased dorsolateral activity, as well as lower connectivity between the vmPFC and the dlPFC. Our findings suggest that WFD more prominently relies on brain areas typically associated with subjective value (vmPFC) rather than integration of material costs (dlPFC) during decision-making, supporting the notion that decisions on costly sacrifices may not be mediated by cost-benefit computation.