bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation and function of extra‐SCN circadian oscillators in the brain
Authors: Begemann Kimberly , Neumann Anne‐Marie , Oster Henrik
Published: January 2020

Most organisms evolved endogenous, so called circadian clocks as internal timekeeping mechanisms allowing them to adapt to recurring changes in environmental demands brought about by 24‐hour rhythms such as the light‐dark cycle, temperature variations or changes in humidity. The mammalian circadian clock system is based on cellular oscillators found in all tissues of the body that are organized in a hierarchical fashion. A master pacemaker located in the suprachiasmatic nucleus (SCN) synchronizes peripheral tissue clocks and extra‐SCN oscillators in the brain with each other and with external time. Different time cues (so called Zeitgebers) such as light, food intake, activity and hormonal signals reset the clock system through the SCN or by direct action at the tissue clock level. While most studies on non‐SCN clocks so far have focused on peripheral tissues, several extra‐SCN central oscillators were characterized in terms of circadian rhythm regulation and output. Some of them are directly innervated by the SCN pacemaker, while others receive indirect input from the SCN via other neural circuits or extra‐brain structures. The specific physiological function of these non‐SCN brain oscillators as well as their role in the regulation of the circadian clock network remains understudied. In this review we summarize our current knowledge about the regulation and function of extra‐SCN circadian oscillators in different brain regions and devise experimental approaches enabling us to unravel the organization of the circadian clock network in the central nervous system.
The quiet politics and gentle literary activism behind the battle for Utah’s Bears Ears National Monument
Authors: Smith Laura
Published: January 2020

In the closing weeks of his administration, President Obama used his authority under the 1906 Antiquities Act to designate the 1.35‐million‐acre Bears Ears National Monument in southern Utah, a redrock landscape sacred to many Native American tribes. With the designation, Bears Ears became the second national monument in Utah—after Grand Staircase‐Escalante National Monument, designated in 1996—where literature and the literary imagination had formed part of the arsenal of campaigners petitioning for the designation. This discussion looks to the works of writers across the American West who have spoken out in defence of Bears Ears (both pre‐ and post‐designation), to consider the place of literature in environmental activism. In particular, this discussion examines how literary activism emerges as a creative yet gently subversive performance, allowing commentators to speak back to an ethics of (ecological) care and responsibility, and to respond to injustices at Bears Ears. Across these two national monuments, and three accompanying and pivotal anthologies, this discussion unpacks and interrogates an ongoing gentle political rhetoric and dialogue surrounding the Bears Ears National Monument. But this quiet resilience has been disrupted, upended by the Trump administration’s review of more than two dozen national monument designations, which specifically targets Bears Ears, but also includes Grand Staircase‐Escalante.
Experience with ponatinib in paediatric patients with leukaemia
Authors: Rossoff Jenna , Huynh Van , Rau Rachel E. , Macy Margaret E. , Sulis Maria L. , Schultz Kirk R. , Burke Michael J. , Athale Uma , O'Brien Maureen M. , Gregory John J. , van der Sluis Inge M. , Keller Frank G. , Zwaan Christian M. , Suttorp Meinolf , Hijiya Nobuko
Published: January 2020

Ponatinib has proven to be effective in adults with Philadelphia chromosome‐positive leukaemias, but data in paediatrics are scarce. Among paediatric patients with chronic myeloid leukaemia (n = 9) or acute lymphoblastic leukaemia (n = 12) treated with varying doses of ponatinib in 13 centres, 71% showed a decrease in disease burden after a median of three months. Ponatinib was well tolerated, with grade 3 toxicities occurring in 29% of patients. Toxicities were similar to those reported in adults, with the exception of arterial thrombotic events, which were not observed. Ponatinib has a favourable safety profile in this paediatric cohort, but dose‐finding studies are needed.
Modifiable lifestyle behaviours impact the health‐related quality of life of bladder cancer survivors
Authors: Chung Jiil , Kulkarni Girish S. , Bender Jackie , Breau Rodney H. , Guttman David , Maganti Manjula , Matthew Andrew , Morash Robin , Papadakos Janet , Jones Jennifer M.
Published: January 2020

Objective

To examine health behaviours in bladder cancer survivors including physical activity (PA), body mass index, diet quality, smoking and alcohol consumption, and to explore their relationship with health‐related quality of life (HRQoL).

Subjects/Patients and Methods

Cross‐sectional questionnaire packages were distributed to bladder cancer survivors (muscle‐invasive bladder cancer [MIBC] and non‐muscle‐invasive bladder cancer [NMIBC]) aged >18 years, and proficient in English. Lifestyle behaviours were measured using established measures/questions, and reported using descriptive statistics. HRQoL was assessed using the validated Bladder Utility Symptom Scale, and its association with lifestyle behaviours was evaluated using analysis of covariance (ancova) and multivariate regression analyses.

Results

A total of 586 participants completed the questionnaire (52% response rate). The mean (SD) age was 67.3 (10.2) years, and 68% were male. PA guidelines were met by 20% (n = 117) and 22.7% (n = 133) met dietary guidelines. In all, 60.9% (n = 357) were overweight/obese, and the vast majority met alcohol recommendations (n = 521, 92.5%) and were current non‐smokers (n = 535, 91.0%). Health behaviours did not differ between MIBC and NMIBC, and cancer treatment stages. Sufficient PA, healthy diet, and non‐smoking were significantly associated with HRQoL, and the number of health behaviours participants engaged in was positively associated with HRQoL (P < 0.001).

Conclusion

Bladder cancer survivors are not meeting guidelines for important lifestyle behaviours that may improve their overall HRQoL. Future research should investigate the impact of behavioural and educational interventions for health behaviours on HRQoL in this population.
Exploring patients’ experience and perception of being diagnosed with bladder cancer: a mixed‐methods approach
Authors: Tan Wei Shen , Teo Chin Hai , Chan Delcos , Ang Kar Mun , Heinrich Malgorzata , Feber Andrew , Sarpong Rachael , Williams Norman , Brew‐Graves Chris , Ng Chirk Jenn , Kelly John ,   DETECT II trial collaborators
Published: January 2020

Objective

To determine patient experience and perception following a diagnosis of non‐muscle‐invasive bladder cancer (NMIBC).

Patient and methods

Patients were part of a prospective multicentre observational study recruiting patients with NMIBC for a urine biomarker study (DETECT II; ClinicalTrials.gov: NCT02781428). A mixed‐methods approach comprising: (i) the Brief Illness Perception Questionnaire (Brief‐IPQ) and (ii) semi‐structured interviews to explore patients’ experience of having haematuria, and initial and subsequent experience with a NMIBC diagnosis. Both assessments were completed at 6 months after NMIBC diagnosis.

Results

A total of 213 patients completed the Brief‐IPQ. Patients felt that they had minimal symptoms (median [interquartile range, IQR] score 2 [0–5]) and were not particularly affected emotionally (median [IQR] score 3 [1–6]) with a minimal effect to their daily life (median [IQR] score 2 [0–5]). However, they remained concerned about their cancer diagnosis (median [IQR] score 5 [3–8]) and felt that they had no personal control over the cancer (median [IQR] score 2 [2–5]) and believed that their illness would affect them for some time (median [IQR] score 6 [3–10]). A significant association with a lower personal control of the disease (P < 0.05) and a poorer understanding of the management of NMIBC (P < 0.05) was seen in patients aged >70 years. Many patients were uncertain about the cause of bladder cancer. Qualitative analysis found that at initial presentation of haematuria, most patients were not aware of the risk of bladder cancer. Patients were most anxious and psychologically affected between the interval of cystoscopy diagnosis and transurethral resection of bladder tumour (TURBT). Following TURBT, most patients were positive about their cancer prognosis.

Conclusion

Patients with NMIBC have a poor perception of disease control and believe that their disease will continue over a prolonged period of time. This is particularly more pertinent in the elderly. Patients are most psychologically affected during the interval between cancer diagnosis following cystoscopy and TURBT. Health awareness about bladder cancer remained poor with a significant number of patients unaware of the causes of bladder cancer. Psychological support and prompt TURBT following bladder cancer diagnosis would help improve the mental health of patients with NMIBC.
Cathelicidin‐related antimicrobial peptide protects against ischaemia reperfusion‐induced acute kidney injury in mice
Authors: Pan Li‐Long , Liang Wenjie , Ren Zhengnan , Li Chunqing , Chen Yong , Niu Wenying , Fang Xin , Liu Yanyan , Zhang Ming , Diana Julien , Agerberth Birgitta , Sun Jia
Published: January 2020

Background and Purpose

Despite recent advances in understanding its pathophysiology, treatment of acute kidney injury (AKI) remains a major unmet medical need, and novel therapeutic strategies are needed. Cathelicidin‐related antimicrobial peptide (CRAMP) with immunomodulatory properties has an emerging role in various disease contexts. Here, we aimed to investigate the role of CRAMP and its underlying mechanisms in AKI.

Experimental Approach

The human homologue LL‐37 and CRAMP were measured in blood samples of AKI patients and in experimental AKI mice respectively. Experimental AKI was induced in wild‐type and CRAMP‐deficient (Cnlp−/−) mice by ischaemia/reperfusion (I/R). Therapeutic evaluation of CRAMP was performed with exogenous CRAMP (5 mg·kg−1, i.p.) treatment.

Key Results

Cathelicidin expression was inversely related to clinical signs in patients and down‐regulated in renal I/R‐induced injury in mice. Cnlp−/− mice exhibited exacerbated I/R‐induced renal dysfunction, aggravated inflammatory responses and apoptosis. Moreover, over‐activation of the NLRP3 inflammasome in Cnlp−/− mice was associated with I/R‐induced renal injury. Exogenous CRAMP treatment markedly attenuated I/R‐induced renal dysfunction, inflammatory response and apoptosis, correlated with modulation of immune cell infiltration and phenotype. Consistent with Cnlp−/− mouse data, CRAMP administration suppressed renal I/R‐induced NLRP3 inflammasome activation, and its renal protective effects were mimicked by a specific NLRP3 inhibitor CY‐09. The reno‐protective and NLRP3 inhibitory effects of CRAMP required the EGF receptor.

Conclusion and Implications

Our results suggest that CRAMP acts as a novel immunomodulatory mediator of AKI and modulation of CRAMP may represent a potential therapeutic strategy.
Basement‐controlled deformation of sedimentary sequences, Anadarko Shelf, Oklahoma
Authors: Kolawole Folarin , Simpson Turko Molly , Carpenter Brett M.
Published: January 2020

Structures rooted in the crystalline basement frequently control the deformation of the host bedrock and the overlying sedimentary sequences. Here, we elucidate the structure of the c. 2‐km deep Precambrian granitic basement in the Anadarko Shelf, Oklahoma, and how the propagation of basement faults deformed the sedimentary cover. Although the basin is foreland in origin, the gently dipping shelf sequences experienced transpressional deformation in the Late Palaeozoic. We analyse a 3‐D seismic reflection data set and basement penetrating well data in an area of 824 km2. We observe: (a) pervasive deformation of the basement by basement‐bounded interconnected mafic sills, and a system of subvertical discontinuity planes (interpreted as faults) of which some penetrate the overlying sedimentary cover; (b) three large (>10 km‐long) through‐going faults, with relatively small (<100 m) vertical separation (Vsep) of the deformed stratigraphic surfaces; (c) upward propagation of the large faults characterized by faulted‐blocks near the basement, and faulted‐monoclines in the deeper sedimentary units that transition into open monoclinal flexures up‐section; (d) cumulative along‐fault deformation of the stratigraphy exhibits systematic trends that varies with offset accrual; (e) two styles of Vsep—Depth distribution which include a unidirectional decrease of Vsep from the basement through the cover rocks (Style‐1) and a bidirectional decrease of Vsep from a deep sedimentary unit towards the basement and shallower sequences (Style‐2). We find that the basement‐driven propagation (Style‐1) shows greater efficiency of driving the fault deformation to shallower depths compared to the intrasedimentary‐driven fault nucleation and propagation (Style‐2). Our study demonstrates an evolution of cumulative Vsep trends with offset accrual on the faults, and the partial inheritance of the heterogeneous intra‐basement deformation by the sedimentary cover. This contribution provides important insight into the upward propagation of basement‐driven faulting associated with structural inheritance in contractional sedimentary basins.
Neonatal jaundice and developmental impairment among infants in Kilifi, Kenya
Authors: Magai Dorcas N. , Mwaniki Michael , Abubakar Amina , Mohammed Shebe , Gordon Anne L. , Kalu Raphael , Mwangi Paul , Koot Hans M. , Newton Charles R.
Published: January 2020

Background

Neonatal jaundice (NNJ) is common in sub‐Saharan Africa (SSA), and it is associated with sepsis. Despite the high incidence, little has been documented about developmental impairments associated with NNJ in SSA. In particular, it is not clear if sepsis is associated with greater impairment following NNJ.

Methods

We followed up 169 participants aged 12 months (57 cases and 112 controls) within the Kilifi Health Demographic Surveillance System. The diagnosis of NNJ was based on clinical laboratory measurement of total serum bilirubin on admission, whereas the developmental outcomes were assessed using the Developmental Milestones Checklist and Kilifi Development Inventory.

Results

There were significant differences between the cases and controls in all developmental domains. Cases scored lower in language functioning (mean [M] = 6.5, standard deviation [SD] = 4.3 vs. M = 8.9, SD = 4.6; p < .001); psychomotor functioning (Mdn = 23, interquartile range [IQR] = 17–34 vs. Mdn = 31.0, IQR = 22.0–44.0; Mann–Whitney U = 4,122, p = .002); and socio‐emotional functioning ([Mdn = 30.0, IQR = 27.0–33.0 vs. Mdn = 34.0, IQR = 30.0–37.0], Mann–Whitney U = 4,289, p < .001). There was no evidence of association between sepsis and psychomotor (rpb = −.2, p = .214), language (rpb = −.1, p = .510), and socio‐emotional functioning (rpb = .0, p = .916). Significant and medium to large portions of the variance (34–64%) in the developmental outcomes among children who survived NNJ were associated with home birth, low maternal education, and feeding problems during the first days of life.

Conclusions

NNJ is associated with developmental impairments in the early childhood years; however, NNJ associated with sepsis does not lead to more severe impairment. Prenatal and postnatal care services are needed to reduce the negative impact of NNJ for children from low resourced settings.
Patterns of Risk and Protective Factors Among Alaska Children: Association With Maternal and Child Well‐Being
Authors: Austin Anna E. , Gottfredson Nisha C. , Halpern Carolyn T. , Zolotor Adam J. , Marshall Stephen W. , Parrish Jared W. , Shanahan Meghan E.
Published: January 2020

This study used population‐representative data to examine associations of risk and protective factor patterns among Alaska Native/American Indian (AN/AI; N = 592) and non‐Native (N = 1,018) children with maternal and child outcomes at age 3 years. Among AN/AI children, a high risk/moderate protection class was associated with child developmental risk and mothers being less likely to feel comfortable asking for help or knowing where to go for parenting information compared to a low socioeconomic status/high protection class. Among non‐Native children, a moderate risk/high protection class was associated with child developmental risk and mothers being less likely to feel comfortable asking for help compared to a low risk/high protection class. Results provide insight on the intersection of risk and protective factors among Alaska families.
Identifying conservation priorities in a defaunated tropical biodiversity hotspot
Authors: Tilker Andrew , Abrams Jesse F. , Nguyen An , Hörig Lisa , Axtner Jan , Louvrier Julie , Rawson Benjamin M. , Nguyen Hoa Anh Quang , Guegan Francois , Nguyen Thanh Van , Le Minh , Sollmann Rahel , Wilting Andreas
Published: January 2020

Aim

Unsustainable hunting is leading to widespread defaunation across the tropics. To mitigate against this threat with limited conservation resources, stakeholders must make decisions on where to focus anti‐poaching activities. Identifying priority areas in a robust way allows decision‐makers to target areas of conservation importance, therefore maximizing the impact of conservation interventions.

Location

Annamite mountains, Vietnam and Laos.

Methods

We conducted systematic landscape‐scale surveys across five study sites (four protected areas, one unprotected area) using camera‐trapping and leech‐derived environmental DNA. We analysed detections within a Bayesian multispecies occupancy framework to evaluate species responses to environmental and anthropogenic influences. Species responses were then used to predict occurrence to unsampled regions. We used predicted species richness maps and occurrence of endemic species to identify areas of conservation importance for targeted conservation interventions.

Results

Analyses showed that habitat‐based covariates were uninformative. Our final model therefore incorporated three anthropogenic covariates as well as elevation, which reflects both ecological and anthropogenic factors. Conservation‐priority species tended to found in areas that are more remote now or have been less accessible in the past, and at higher elevations. Predicted species richness was low and broadly similar across the sites, but slightly higher in the more remote site. Occupancy of the three endemic species showed a similar trend.

Main conclusion

Identifying spatial patterns of biodiversity in heavily defaunated landscapes may require novel methodological and analytical approaches. Our results indicate that to build robust prediction maps it is beneficial to sample over large spatial scales, use multiple detection methods to increase detections for rare species, include anthropogenic covariates that capture different aspects of hunting pressure and analyse data within a Bayesian multispecies framework. Our models further suggest that more remote areas should be prioritized for anti‐poaching efforts to prevent the loss of rare and endemic species.
Effects of Argentine ants (Hymenoptera: Formicidae) on myrmecophilous lycaenid butterfly, Narathura bazalus (Lepidoptera: Lycaenidae), in western Japan
Authors: Ikenaga Nobuhiro , Touyama Yoshifumi , Kameyama Takeshi , Ito Fuminori
Published: January 2020

Effects of the invasive Argentine ant, Linepithema humile (Mayr), on a myrmecophilous butterfly, Narathura bazalus (Hewiston), were investigated in the field in western Japan. Larvae of N. bazalus were attended by workers of Argentine ants in invaded parks and of ten native and one cosmopolitan ant species in uninvaded parks. The abundance of eggs and larvae were not significantly different between invaded and uninvaded parks. Pupal weight and parasitized ratio by tachinid flies were also not different between the two types of parks. These results indicate that the role of Argentine ants for the butterfly might be almost equivalent to the native ants.
Remembrance–Toward Righteousness and Reparations
Authors: Carruthers Iva E.
Published: January 2020

This article explores “remembrance” as the first part of a planned three‐part paper titled “Remembrance, Righteousness and Reparations,” intended as a conceptual framework and spirit guide of accompaniment for the World Council of Churches’ pilgrimage of healing, justice, and peace. This first part focuses on remembrance to counter the dis‐membering, trauma, and woundedness inflicted by systems of acts of White supremacy, racism, patriarchy, and male privilege. Parts two and three of this paper offer righteousness and reparations as additional conceptual frameworks and spirit guides: righteousness to recentre and deepen our understanding of justice in a world fraught with human suffering, violence, and evil; and reparations to covenant and bind a process of truth‐telling, reckoning, and reconciliation in the face of the consequences and legacies of the transatlantic slave trade system upon people of African descent.
New regulatory mechanism‐based inhibitors of aspartate transcarbamoylase for potential anticancer drug development
Authors: Lei Zhen , Wang Biying , Lu Zhifang , Wang Nan , Tan Hongwei , Zheng Jimin , Jia Zongchao
Published: January 2020

Aspartate transcarbamoylase (ATCase) is a key enzyme which regulates and catalyzes the second step of de novo pyrimidine synthesis in all organisms. Escherichia coli ATCase is a prototypic enzyme regulated by both product feedback and substrate cooperativity, whereas human ATCase is a potential anticancer target. Through structural and biochemical analyses, we revealed that R167/130's loop region in ATCase serves as a gatekeeper for the active site, playing a new and unappreciated regulatory role in the catalytic cycle of ATCase. Based on virtual compound screening simultaneously targeting the new regulatory region and active site of human ATCase, two compounds were identified to exhibit strong inhibition of ATCase activity, proliferation of multiple cancer cell lines, and growth of xenograft tumors. Our work has not only revealed a previously unknown regulatory region of ATCase that helps uncover the catalytic and regulatory mechanism of ATCase, but also successfully guided the identification of new ATCase inhibitors for anticancer drug development using a dual‐targeting strategy.

Database

Structure data are available in Protein Data Bank under the accession numbers: 6KJ7 (G166P ecATCase), 6KJ8 (G166P ecATCase‐holo), 6KJ9 (G128/130A ecATCase), and 6KJA (G128/130A ecATCase‐holo).
The effects of season, sex, age and weather on population‐level variation in the timing of activity in Eurasian Blue TitsCyanistes caeruleus
Authors: Schlicht Lotte , Kempenaers Bart
Published: January 2020

All birds sleep and many do so in a specific location, the roost. Thus, every day each individual needs to decide when to go to (enter) and leave the roosting place. This determines the timing of activity, a trait shaped by both natural and sexual selection. Despite its importance in a variety of contexts, including foraging, predation, mating success and parental care, variation in the timing of activity has rarely been studied. Here, we describe this variation in a population of Eurasian Blue TitsCyanistes caeruleusroosting in nestboxes using data collected over 7 years. We investigate seasonal changes in the start and end of activity and assess to what extent these parameters are sex‐ and age‐specific and affected by weather. We show that the start of activity is relatively constant in relation to sunrise during winter but undergoes drastic changes during the breeding season. The end of activity is markedly later relative to sunset in mid‐winter and is also strongly influenced by breeding behaviour. Females generally start their activity later and end it earlier than males. The duration of daily activity is shorter during periods of rain and longer when temperatures are relatively high for the time of year.
PANEL DATA HEDONICS: ROSEN'S FIRST STAGE AS A “SUFFICIENT STATISTIC”
Authors: Banzhaf H. Spencer
Published: January 2020

Traditional cross‐sectional estimates of hedonic price functions can recover marginal willingness to pay for characteristics, but face endogeneity problems for estimating nonmarginal welfare measures. This article shows that when panel data on household demands are available, one can construct a second‐order approximation to nonmarginal welfare measures using only the first‐stage marginal prices. With repeated cross sections of product prices, the measure can be set identified or, under a single‐crossing restriction, point identified. Bounds also can be constructed when there are mobility costs. Finally, a variant remains valid when individual preferences shift over time.
Pressure‐induced anomalous behavior of thaumasite crystal
Authors: Moon Juhyuk , Kim Seungchan , Bae Sungchul , Clark Simon Martin
Published: January 2020

This work investigated the structural responses of thaumasite crystal, an important phase to understand the structural integrity of concrete‐based structures, using synchrotron‐based X‐ray diffraction and first‐principles calculations. The 100 peak was immediately diffused upon the contact of pressure‐transmitting medium, but regenerated under subsequent pressurization. Under high pressure, it showed complex nonlinear responses; lattice parameters a and b became stiffer first (between 1.06 and 2.32 GPa) then lattice parameter c became significantly incompressible (beyond 2.32 GPa). The densification of hydrogen bond network in the channels surrounded by calcium silicate columns and the interaction between the network and the medium caused the first nonlinear response and completely weakened the periodicity of lattice parameters a and b (beyond 5.37 GPa). However, this amorphization phenomenon did not leave a permanent damage on the crystal, leading to the reshaping of the weakened crystallinity upon the release of pressure. Simulation results further elucidated the compressive mechanism of thaumasite crystal. It confirmed that deformation due to pressure mainly took place in the channel space, thus strengthening the hydrogen bonds. It also suggested a potential symmetry breaking of hexagonal structure that makes the stiffness characteristics of the crystal highly anisotropic under pressure.
Internal information quality and patent‐related innovation
Authors: Huang Kelly , Lao Brent , McPhee Gregory
Published: January 2020

This study investigates how the quality of information available within a firm affects patent‐related innovative activities. Relying on recent theoretical and empirical research, we use externally observable information attributes to proxy for the quality of internal information. Our empirical results indicate that firms with higher internal information quality generate more patents and patent citations. Cross‐sectional analyses show that this positive effect is greater when firms are susceptible to greater internal information frictions due to firm decentralization, short management team tenure, and long product development cycles. We also document that firms experience an increase in patents and patent citations following an improvement of internal information quality proxied by internal control weakness remediation. Overall, our results suggest that the positive relation between internal information quality and task performance extends to patent‐related innovation, a non‐routine type of task that may rely on information originating from sources other than firms’ formal internal information systems.
Outcome of non‐vitamin K oral anticoagulants in the treatment of left atrial/left atrial appendage thrombus in patients with nonvalvular atrial fibrillation
Authors: Lin Changjian , Quan Jinwei , Bao Yangyang , Hua Wei , Ke Ming , Zhang Ning , Jin Qi , Xie Yun , Wei Yue , Ling Tianyou , Pan Wenqi , Wu Liqun , Xie Yucai
Published: January 2020

Background

Data comparing dabigatran with rivaroxaban regarding the resolution of left atrial/left atrial appendage (LA/LAA) thrombus in patients with nonvalvular atrial fibrillation (AF) are scarce. This study aimed to compare the efficacy and safety of dabigatran vs rivaroxaban regarding the resolution of LA/LAA thrombus in patients with nonvalvular AF.

Methods

This retrospective study enrolled nonvalvular AF patients scheduled to undergo catheter ablation or cardioversion in Shanghai Ruijin Hospital between January 2014 and January 2019. Altogether, 34 patients with LA/LAA thrombus detected by transesophageal echocardiography (TEE) were enrolled. Among them, 12 patients were treated with dabigatran 150 mg bid and the other 22 with rivaroxaban 20 mg qd. Follow‐up TEE was performed within greater than or equal to 3 weeks to less than 6 months of the initial TEE to evaluate the resolution of the LA/LAA thrombus.

Results

Baseline patient characteristics were similar in the two groups. Overall, 18 patients (81.8%) in the rivaroxaban group had complete thrombus resolution after 70.3 ± 22.1 treatment days, and 10 patients (83.3%) in the dabigatran group had complete thrombus resolution after 69.3 ± 47.9 treatment days. There was no significant difference between the groups (P = .6). TEE showed that the average length, width, and area of thrombus significantly decreased in both groups after treatment, although there was no significant difference in the amount of change in these parameters between the two groups after treatment (P = .6). Undissolved thrombus in two patients in the rivaroxaban group did dissolve after switching to dabigatran.

Conclusions

The results suggest that both dabigatran and rivaroxaban are potential options for treating LA/LAA thrombus in patients with nonvalvular AF. Dabigatran could be an alternative option for the resolution of LA/LAA thrombus resistant to rivaroxaban.
Mean dietary salt intake in Nepal: A population survey with 24‐hour urine collections
Authors: Neupane Dinesh , Rijal Anupa , Henry Megan E. , Kallestrup Per , Koirala Bhagawan , Mclachlan Craig S. , Ghimire Kamal , Zhao Di , Sharma Shailendra , Pokharel Yashashwi , Joseph Kristy , Olsen Michael Hecht , Schutte Aletta E. , Appel Lawrence J.
Published: January 2020

High salt (sodium chloride) intake raises blood pressure and increases the risk of developing hypertension, a major risk factor for cardiovascular disease. Little is known about salt intake in Nepal, and no study has estimated salt consumption from 24‐hour urinary sodium excretion. Participants (n = 451) were recruited from the Community‐Based Management of Non‐Communicable Diseases in Nepal (COBIN) cohort in 2018. Salt intake was estimated by analyzing 24‐hour urinary sodium excretion. Multivariate linear regression was used to estimate differences in salt intake. The mean (±SD) age and salt intake were 49.6 (±9.8) years and 13.3 (±4.7) g/person/d, respectively. Higher salt intake was significantly associated with male gender (β for female = −2.4; 95% CI: −3.3, −1.4) and younger age (β10 years = −1.4; 95% CI: −1.4, −0.5) and higher BMI (β = 0.1; 95% CI: 0.0, 0.2). A significant association was also found between increase in systolic blood pressure and higher salt intake (β = 0.3; 95% CI: 0.0, 0.7). While 55% reported that they consumed just the right amount of salt, 98% were consuming more than the WHO recommended salt amount (<5 g/person/d). Daily salt intake in this population was over twice the limit recommended by the WHO, suggesting a substantial need to reduce salt intake in this population. It also supports the need of global initiatives such as WHO's Global Hearts Initiative SHAKE technical package and Resolves to Save Lives for sodium reduction in low‐ and middle‐income countries like Nepal.
Monthly changes in serum levels of S100B protein as a predictor of metastasis development in high‐risk melanoma patients
Authors: Ertekin S.S. , Podlipnik S. , Ribero S. , Molina R. , Rios J. , Carrera C. , Malvehy J. , Puig S.
Published: January 2020

Background

The role of S100B protein in detecting early melanoma relapses is controversial, since most metastasis occur within normal values of S100B.

Objective

The aim of this study was to assess the performance of S100B in detecting early disease progression in high‐risk melanoma patients.

Methods

Retrospective cohort study including patients with an initial diagnosis of stage IIB, IIC and III melanoma between January 2003 and July 2013. All patients were followed up in accordance with an intensive protocol based on imaging studies and serum S100B levels every 3–6 months. We compared two methods to evaluate changes in S100B. The classic method referring to a single determination of S100B above the cut‐off level at the time of metastasis, which was evaluated in all patients. And a new method based on monthly changes of S100, which was used in the setting of patients with S100B levels within the normal range.

Results

Overall, 289 of patients were followed up for 44 months (IQR 17–73) and 45% developed metastases. During the study period, 129 patients relapsed of which 46 (35.7%) present elevated values of S100B at the time of relapse. The classic method had a sensitivity and specificity of S100B protein of 35.7% and 92.5%, respectively. Furthermore, for the patients that relapsed with normal values of S100B, the new method was applied and showed a sensitivity and specificity of 41.1% and 92.4%, respectively, allowing to detect additional relapses that were missing by the classic method.

Conclusion

During follow‐up of high‐risk melanoma patients, rising serum S100B values within the normal range can be an important clue to disease progression.
Shorting in Speculative Markets
Authors: NUTZ MARCEL , SCHEINKMAN JOSÉ A.
Published: January 2020

In models of trading with heterogeneous beliefs following Harrison‐Kreps, short selling is prohibited and agents face constant marginal costs‐of‐carry. The resale option guarantees that prices exceed buy‐and‐hold prices and the difference is identified as a bubble. We propose a model where risk‐neutral agents face asymmetric increasing marginal costs on long and short positions. Here, agents also value an option to delay, and a Hamilton‐Jacobi‐Bellman equation quantifies the influence of costs on prices. An unexpected decrease in shorting costs may deflate a bubble, linking financial innovations that facilitated shorting of mortgage‐backed securities to the collapse of prices.
Prognostic value of systemic inflammatory response syndrome and serum concentrations of acute phase proteins, cholesterol, and total thyroxine in cats with panleukopenia
Authors: Petini Matteo , Drigo Michele , Zoia Andrea
Published: January 2020

Background

Feline parvovirus (FPV) is a common and potentially lethal infectious agent in cats.

Objective

To assess the prognostic value of age, neuter status, serum concentrations of serum amyloid A (SAA), haptoglobin, cholesterol and total thyroxine (tT4), and the presence of systemic inflammatory response syndrome (SIRS) in cats with panleukopenia.

Animals

Client‐owned cats with FPV infection diagnosed by a positive fecal ELISA test, positive PCR on feces or blood or both.

Methods

Retrospective cohort study. The electronic medical database was searched for cats with FPV infection presented between January 2010 and January 2018. Cats were divided into survivors and nonsurvivors according to their survival status 28 days after hospital admission. The prognostic importance of each variable was investigated univariately and by multivariable Cox's proportional‐hazards regression. Finally, receiver operator characteristic (ROC) curve analysis was used to identify the best cutoff value for discriminating survivors from nonsurvivors for the statistically significant prognostic predictors identified by multivariable analysis.

Results

Seventy cats were enrolled in the study. Multivariable analysis determined that only serum tT4 concentration at hospital admission was significantly (P= .01) associated with survival. A cutoff value of 0.82 μg/dL was identified by ROC curve analysis for serum tT4 concentration in discriminating survivors from nonsurvivors. Sensitivity at this cutoff was 73.9% and specificity was 82.9% (area under the curve, 0.783; 95% confidence interval, 0.668‐0.873;P < .0001).

Conclusion and Clinical Relevance

Serum tT4 concentration at hospital admission has prognostic value in cats with FPV infection.
Hepatitis C virus therapy in children: No one should be left behind
Authors: Indolfi Giuseppe , Giannini Edoardo G.
Published: January 2020

See Article on Page 319
Association of HSD17B13 rs72613567:TA with non‐alcoholic fatty liver disease in Hispanics/Latinos
Authors: Kallwitz Eric , Tayo Bamidele O. , Kuniholm Mark H. , Daviglus Martha , Zeng Donglin , Isasi Carmen R. , Cotler Scott J.
Published: January 2020

Introduction

Non‐alcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic/Latinos and rates of NAFLD vary among Hispanics from different background groups. Genetic variants and continental ancestry contribute to NAFLD disparities among Hispanics. We evaluated two newly identified NAFLD‐associated single nucleotide polymorphisms of HSD17B13, rs72613567:TA and rs62305723:A in Hispanics/Latinos.

Methods

Clinical data, genotypes of variants of interest and estimates of continental ancestry were extracted from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) database, which includes a cohort of 16 415 US Hispanic/Latinos. Surrogate endpoints for NAFLD were suspected NAFLD based on unexplained aminotransferase elevation, continuous ALT levels and FIB‐4 scores to estimate hepatic fibrosis.

Results

In all, 9342 participants were included for analysis. The rs72613567:TA allele was found in 15.3% and the rs62305723:A allele was identified in 4.5% of HCHS/SOL participants. rs72613567:TA was less frequent in persons with vs without suspected NAFLD (12.4% vs 15.7%, P < .001) and rs72613567:TA was associated with lower FIB‐4 scores (P = .01). For persons with the NAFLD‐associated PNPLA3 rs738409:G allele, the presence of rs72613567:TA was associated with a lower rate of suspected NAFD (odds ratio = 0.76, P < .001). rs72613567:TA was less frequent in Hispanic/Latino background groups with higher rates of suspected NAFLD. The rs62305723:A allele was not associated with suspected NAFLD or FIB‐4 score.

Conclusion

The rs72613567:TA allele is associated with lower rates of suspected NAFLD and lower FIB‐4 scores among Hispanic/Latinos and with lower rates of suspected NAFLD in persons with the PNPLA3 rs738409:G allele. The rs72613567:TA allele contributes to NAFLD disparities among Hispanic/Latino background groups.
A Proposal for the Demarcation of Theory and Knowledge
Authors: Kampen Jarl K.
Published: January 2020

Research communication in interdisciplinary research projects requires a way of demarcation of theory and knowledge that is easy to communicate, is inconsequential for the framework of concepts, results, and procedures within existing scientific disciplines, and abstains from trying to resolve the dispute between (neo)positivists and constructivists. A simple way of demarcation starts from the notion of language‐independent and language‐dependent reality. Currently, what passes for knowledge (“news”) and myth (“fake news”) depends, besides on sheer volume and frequency of the messages, increasingly on the internal consistency of (computer) language‐dependent reality and decreasingly on language‐independent reality. All language is instruction, and knowledge is to know which instructions (that is, theory) are predictive of a result, state, or situation in language‐independent reality. Any theory that doesn’t reduce outcome space, or contains one or more empirically/physically impossible instructions, or produces wrong predictions, or falls short of demonstration is not knowledge.
Intransitivity, Essential Comparativeness, and Objective Value
Authors: Goldman Alan H.
Published: January 2020

Building on Goldman 2008 and 2009, which argue that objective values would be strange in coming in degrees but in no determinate number of degrees, this paper argues that related properties having to do with degrees of value make a further case against objective values. The properties of giving rise to intransitive orderings and being essentially comparative are explained by Larry Temkin in Rethinking the Good. He shows that “better than” is intransitively ordered. Many subjective states are too. But similar arguments for the intransitive orderings of intrinsic objective properties fail. Furthermore, subjective properties and states can change without these changes being explained by changes in their objects. This is similar to the essentially comparative nature of goodness. Given the analogies to subjective states and lack of analogies to objective properties that the present article points out, it argues that we should infer, as Temkin does not, that values are subjective.
Using Linguistic Corpora as a Philosophical Tool
Authors: Caton Jacob N.
Published: January 2020

The central aims of this paper are to show how linguistic corpora have been used and can be used in philosophy and to argue that linguistic corpora and corpus analysis should be added to the philosopher’s toolkit of ways to address philosophical questions. A linguistic corpus is a curated collection of texts representing language use that can be queried to answer research questions. Among many other uses, linguistic corpora can help answer questions about the meaning of words and the structure of discourse. Through a discussion of examples, the paper shows that there are many philosophical questions that can be addressed by using a linguistic corpus. However, linguistic corpora need not (and often cannot) replace traditional philosophical methods. Lastly, it argues that the special properties of linguistic corpora, including their independence and the current ease and cheapness of access, make them an indispensable resource for philosophers.
Leishmania dual‐specificity tyrosine‐regulated kinase 1 (DYRK1) is required for sustaining Leishmania stationary phase phenotype
Authors: Rocha Vinícius Pinto Costa , Dacher Mariko , Young Simon Alan , Kolokousi Foteini , Efstathiou Antonia , Späth Gerald Frank , Soares Milena Botelho Pereira , Smirlis Despina
Published: January 2020

Although the multiplicative and growth‐arrested states play key roles in Leishmania development, the regulators of these transitions are largely unknown. In an attempt to gain a better understanding of these processes, we characterised one member of a family of protein kinases with dual specificity, LinDYRK1, which acts as a stasis regulator in other organisms. LinDYRK1 overexpressing parasites displayed a decrease in proliferation and in cell cycle re‐entry of arrested cells. Parasites lacking LinDYRK1 displayed distinct fitness phenotypes in logarithmic and stationary growth phases. In logarithmic growth phase, LinDYRK1−/− parasites proliferated better than control lines, supporting a role of this kinase in stasis, while in stationary growth phase, LinDYRK1−/− parasites had important defects as they rounded up, accumulated vacuoles and lipid bodies and displayed subtle but consistent differences in lipid composition. Moreover, they expressed less metacyclic‐enriched transcripts, displayed increased sensitivity to complement lysis and a significant reduction in survival within peritoneal macrophages. The distinct LinDYRK1−/− growth phase phenotypes were mirrored by the distinct LinDYRK1 localisations in logarithmic (mainly in flagellar pocket area and endosomes) and late stationary phase (mitochondrion). Overall, this work provides first evidence for the role of a DYRK family member in sustaining promastigote stationary phase phenotype and infectivity.
The translucens group of Xanthomonas translucens: Complicated and important pathogens causing bacterial leaf streak on cereals
Authors: Sapkota Suraj , Mergoum Mohamed , Liu Zhaohui
Published: January 2020

Xanthomonas translucens is a group of gram‐negative bacteria that can cause important diseases in cereal crops and forage grasses. Different pathovars have been defined according to their host ranges, and molecular and biochemical characteristics. Pathovars have been placed into two major groups: translucens and graminis. The translucens group contains the pathovars causing bacterial leaf streak (BLS) on cereal crops such as wheat, barley, triticale, rye, and oat. In recent years, BLS has re‐emerged as a major problem for many wheat‐ and barley‐producing areas worldwide. The biology of the pathogens and the host–pathogen interactions in cereal BLS diseases were poorly understood. However, recent genome sequence data have provided an insight into the bacterial phylogeny and identification and pathogenicity/virulence. Furthermore, identification of sources of resistance to BLS and mapping of the resistance genes have been initiated.

Taxonomy

Kingdom Bacteria; Phylum Proteobacteria; Class Gammaproteobacteria; Order Xanthomonadales; Family Xanthomonadaceae; Genus Xanthomonas; Species X. translucens; translucens group pathovars: undulosa, translucens, cerealis, hordei, and secalis; graminis group pathovars: arrhenatheri, graminis, poae, phlei; newly established pathovar: pistaciae.

Host range

X. translucens mainly infects plant species in the Poaceae with the translucens group on cereal crop species and the graminis group on forage grass species. However, some strains have been isolated from, and are able to infect, ornamental asparagus and pistachio trees. Most pathovars have a narrow host range, while a few can infect a broad range of hosts.

Genome

The complete genome sequence is available for two X. translucens pv. undulosa strains and one pv. translucens strain. A draft genome sequence is also available for at least one strain from each pathovar. The X. translucens pv. undulosa strain Xt4699 was the first to have its complete genome sequenced, which consists of 4,561,137 bp with total GC content approximately at 68% and 3,528 predicted genes.

Virulence mechanisms

Like most xanthomonads, X. translucens utilizes a type III secretion system (T3SS) to deliver a suite of T3SS effectors (T3Es) inside plant cells. Transcription activator‐like effectors, a special group of T3Es, have been identified in most of the X. translucens genomes, some of which have been implicated in virulence. Genetic factors determining host range virulence have also been identified.
Welfare and Redistributive Effects of Social Assistance in the Global South
Authors: Niño‐Zarazúa Miguel
Published: January 2020

This paper presents an analysis of the recent evolution of social assistance in the developing world, looking at its complex typological configuration, which has interlinked with, and partly reflects the complex demographic and epidemiological transitions and rapid urbanization and economic convergence that many developing countries have exhibited over the past decades. The paper underscores the principles of the poverty focus of social assistance and presents an overview of existence evidence of first‐ and second‐order effects of social assistance, particularly in the domains of poverty, education, health, and labor markets. Moreover, the paper highlights the knowledge gaps with regard to the longer term and gender‐specific welfare effects of social assistance, and the redistributive effects, and the incentives and distortion mechanisms that transfer programs can generate in the labor and insurance markets.
Oral erosions associated with surreptitious marijuana vaping in an adolescent boy
Authors: Ali Nora S. , Billings Marcie L. , Tollefson Megha M. , Davis Dawn M. R. , Hand Jennifer L.
Published: January 2020

A 15‐year‐old boy presented with painful ulcerations affecting the oral mucosa that were eventually attributed to marijuana vaping. In this case report, we highlight cannabis vaping as a potential cause of oral erosions due to injury and chronic inflammation of the oral mucosa.