bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabidiol in patients with Lennox‐Gastaut syndrome: Interim analysis of an open‐label extension study
Authors: Thiele Elizabeth , Marsh Eric , Mazurkiewicz‐Beldzinska Maria , Halford Jonathan J. , Gunning Boudewijn , Devinsky Orrin , Checketts Daniel , Roberts Claire 
Published: February 2019

SummaryObjectivePatients with Lennox‐Gastaut syndrome (LGS) who completed 1 of 2 randomized, double‐blind, placebo‐controlled trials of add‐on cannabidiol (CBD) (GWPCARE3, NCT02224560 or GWPCARE4, NCT02224690) were invited to enroll in an open‐label extension (OLE) study evaluating the long‐term safety and efficacy of CBD (GWPCARE5, NCT02224573). Herein we present an interim analysis of the safety, efficacy, and patient‐reported outcomes from this trial.MethodsPatients received a pharmaceutical formulation of highly purified CBD oral solution (Epidiolex; 100 mg/mL), titrated from 2.5 to 20 mg/kg/d over a 2‐week titration period, in addition to their existing medications. Doses could be reduced if not tolerated or increased up to 30 mg/kg/d if thought to be of benefit.ResultsThis interim analysis was based on a November 2016 data cut. Of 368 patients who completed treatment in GWPCARE3 and GWPCARE4, 366 (99.5%) enrolled in the OLE study (GWPCARE5). Median treatment duration was 38 weeks at a mean modal dose of 23 mg/kg/d. Most patients (92.1%) experienced adverse events (AEs), primarily of mild (32.5%) or moderate (43.4%) severity. The most common AEs were diarrhea (26.8%), somnolence (23.5%), and convulsion (21.3%). Thirty‐five patients (9.6%) discontinued treatment due to AEs. Liver transaminase elevations were reported in 37 patients (10.1%), of whom 29 were receiving concomitant valproic acid; 34 cases resolved spontaneously or with dose modification of CBD or concomitant medication. Median reduction from baseline in drop seizure frequency (quantified monthly over 12‐week periods) ranged from 48% to 60% through week 48. Median reduction in monthly total seizure frequency ranged from 48% to 57% across all 12‐week periods through week 48. Eighty‐eight percent of patients/caregivers reported an improvement in the patient's overall condition per the Subject/Caregiver Global Impression of Change scale.SignificanceIn this study, long‐term add‐on CBD treatment had an acceptable safety profile in patients with LGS and led to sustained reductions in seizures.
A potential contribution of decreased galectin‐7 expression in stratified epithelia to the development of cutaneous and oesophageal manifestations in systemic sclerosis
Authors: Saigusa Ryosuke , Yamashita Takashi , Miura Shunsuke , Hirabayashi Megumi , Nakamura Kouki , Miyagawa Takuya , Fukui Yuki , Yoshizaki Ayumi , Sato Shinichi , Asano Yoshihide 
Published: February 2019

AbstractBackgroundsStratified epithelia have caught much attention as potential contributors to the development of dermal and oesophageal fibrosis in systemic sclerosis (SSc). Galectin‐7 is a marker of all types of stratified epithelia, which is involved in the maintenance of epidermal homeostasis. So far, the role of galectin‐7 has not been studied in SSc.ObjectivesTo investigate the potential contribution of galectin‐7 to the development of clinical manifestations in SSc.MethodsGalectin‐7 expression was examined in skin samples and cultured keratinocytes by immunostaining and/or quantitative reverse transcription PCR. Serum galectin‐7 levels were determined by enzyme‐linked immunosorbent assay in 63 SSc and 20 healthy subjects.ResultsGalectin‐7 expression was markedly decreased in the epidermis of SSc lesional skin compared with that of healthy control skin. Serum galectin‐7 levels were significantly lower in SSc patients than in healthy controls and inversely correlated with skin score. In addition, SSc patients with diffuse pigmentation and those with oesophageal dysfunction had significantly decreased serum galectin‐7 levels as compared to those without each symptom. Importantly, endothelin‐1 stimulation suppressed galectin‐7 expression in normal human keratinocytes, and bosentan, a dual endothelin receptor antagonist, reversed circulating galectin‐7 levels and epidermal galectin‐7 expression in SSc patients.ConclusionsGalectin‐7 downregulation in stratified epithelia, which is mediated at least partially by autocrine endothelin stimulation, may contribute to the development of cutaneous manifestations and oesophageal dysfunction in SSc patients.
The home hemodialysis patient experience: A qualitative assessment of modality use and discontinuation
Authors: Seshasai Rebecca Kurnik , Wong Tiffany , Glickman Joel D. , Shea Judy A. , Dember Laura M. 
Published: February 2019

AbstractIntroduction: Home hemodialysis (HHD) is an under‐utilized renal replacement modality in the United States in part because of high rates of discontinuation and transfer to in‐center hemodialysis. Understanding, from the perspective of patients, facilitators, and barriers to sustained use of HHD is important for increasing successful use of this modality.Methods: We conducted 25 semistructured interviews with 15 current and 10 former adult patients treated with home hemodialysis (23 short daily HHD and 2 nocturnal HHD). Interview transcripts were audiotaped, transcribed verbatim, and thematically analyzed.Findings: Five themes related to continuation or discontinuation of HHD emerged: (1) degree of independence (increased flexibility, burden of therapy), (2) availability of support (emotional and physical support and caregiver burden), (3) technical aspects (familiarity with machine), (4) home environment (ability to organize supplies, space in home), and (5) attitude and expectations (positive or negative outlook about performing HHD). For each theme, positive aspects facilitated continuation of HHD and negative aspects contributed to discontinuation of HHD.Discussion: HHD can be burdensome to patients and family members, and some discontinuations may be preventable. Helping patients with scheduling and organization, improving communication about expectations and trouble‐shooting, supporting patients as well as family members, adapting the dialysis prescription to the patient's lifestyle when possible, and providing respite when needed may make HHD more sustainable for patients.
Is there a relationship between plantar foot sensation and static balance, physical performance, fear of falling, and quality of life in hemodialysis patients?
Authors: Erdoğanoğlu Yıldız , Yalçin Berna , Külah Eyyüp , Kaya Defne 
Published: February 2019

AbstractIntroduction: This study was conducted to investigate the relationship between plantar foot sensation and static balance, physical performance, fear of falling, and quality of life in hemodialysis patients.Materials and Methods: The study involved 24 hemodialysis patients and 20 healthy volunteers. Light touch‐pressure sensation (Semmes Weinstein Monofilament test kit), two‐point discrimination sensation (esthesiometer) and vibration sensation (128 Hz diapason) were used to evaluate plantar foot sensation. Static balance was assessed by the one‐leg standing balance test, physical performance by the Timed Up and Go test, fear of falling with the Fall Efficacy Scale, and quality of life with the Ferrans and Powers Quality of Life Index Dialysis Version.Findings: There was a significant difference in plantar foot sensation, static balance, and physical performance of the patients compared to the healthy controls (P < 0.05). There was a strong correlation between static balance and physical performance with foot sensation in the hemodialysis patients (P < 0.05). There was also a strong correlation between static balance, physical performance, and fear of falling in hemodialysis patients (P < 0.05). The correlation between static balance, physical performance, and quality of life in the hemodialysis patients was strong (P < 0.05).Discussion: The most important result of this study is that light touch‐pressure sensation, vibration sensation, two‐point discrimination sensation, static balance, and physical performance, all of which involve the activity of cutaneous sensory receptors on the sole of the foot, are reduced in individuals who undergo hemodialysis. The findings of this study suggest potential rehabilitation strategies that could be applied to this patient group.
Synthesis of nanostructured ThO2 pellets
Authors: De Bona Emanuele , Walter Olaf , Störmer Heike , Wiss Thierry , Baldinozzi Gianguido , Cologna Marco , Popa Karin 
Published: February 2019

AbstractWe present here for the first time the production of 3‐ to 5‐nm–sized thoria nanopowders by decomposition of Th‐hydroxide under hot compressed water and their consolidation by high‐pressure spark plasma sintering into dense nanostructured ThO2 with grain size of 50 nm.
Proliferation dynamics of WSSV in crayfish, Procambarus clarkii, and the host responses at different temperatures
Authors: Jiang Nan , Pan Xiaoyi , Gu Zemao , Liu Wenzhi , Si Kaige , Zhou Yong , Zhou Yongze , Zhai Liwen , Fan Yuding , Zeng Lingbing 
Published: February 2019

AbstractThe replication profile of white spot syndrome virus (WSSV) in crayfish, Procambarus clarkii, at different water temperature was investigated in this study. The WSSV detections were negative at 15 ± 1°C, and the natural infection ratio increased at 19 ± 1°C (24.2% ± 2.25%), reached 100% at 25 ± 1°C and decreased at 30 ± 1°C (93.2% ± 3.37%). The WSSV genome copies number was much higher at 25 ± 1°C (≥5 × 106.45 ± 0.35/mg) than at 15 ± 1°C (≤5 × 101.13 ± 0.12/mg), 19 ± 1°C (≤5 × 102.74 ± 0.48/mg) and 32 ± 1°C (≤5 × 103.18 ± 0.27/mg). Meanwhile, the significant transcription signals of immediate early gene ie1 and late gene vp28 and a large number of virus particles were detected in epitheliums of stomach, gut and gill, hepatopancreas, heart and muscle cells at 25 ± 1°C by using in situ hybridization (ISH) and transmission electron microscopy. The experimental infection of P. clarkii with WSSV infection showed reduced mortality and lower virus copies number at 19 ± 1°C (23.51% ± 0.84%, ≤5 × 103.41 ± 0.11/mg) and 32 ± 1°C (38.42% ± 1.21%, ≤5 × 103.72 ± 0.13/mg) compared to 25 ± 1°C (100%, ≥5 × 104.99 ± 0.24/mg). The water temperature regulated the transcription of immune‐related genes (crustin2, prophenoloxidase (proPO) and heat shock protein70 (Hsp70)), with some differences between WSSV treatments and control treatments. These results demonstrate that water temperature has effect on WSSV proliferation, which may due to transcriptional response of immune‐related genes to temperature.
Quorum sensing is required for full virulence of Vibrio campbellii towards tiger grouper (Epinephelus fuscoguttatus) larvae
Authors: Noor Noorashikin Md. , Defoirdt Tom , Alipiah Norfarrah , Karim Murni , Daud Hassan , Natrah Ikhsan 
Published: February 2019

ABSTRACTThe link between quorum sensing in Vibrio campbellii and its virulence towards tiger grouper (Epinephelus fuscoguttatus) was investigated using V. campbellii wild type and quorum‐sensing mutants with inactive quorum sensing or constitutively maximal quorum‐sensing activity, and signal molecule synthase mutants. The results showed that wild‐type V. campbellii is pathogenic to grouper larvae, causing more than 50% mortality after 4 days of challenge. Furthermore, the mortality of larvae challenged with the mutant with maximally active quorum sensing was significantly higher than that of larvae challenged with the wild type, whereas a higher survival was observed in the larvae challenged to the mutant with a completely inactive quorum‐sensing system. Grouper larvae challenged with either the signal molecule synthase triple mutant, the harveyi autoinducer‐1 (HAI‐1) synthase mutant and the autoinducer‐2 (AI‐2) synthase mutant showed higher survival than larvae challenged with the wild type. In contrast, larvae challenged with the cholerae autoinducer‐1 (CAI‐1) synthase mutant showed high mortality. This indicates that HAI‐1 and AI‐2, but not CAI‐1, are required for full virulence of V. campbellii towards grouper larvae. Our data suggest that quorum‐sensing inhibition could be an effective strategy to control V. campbellii infections in tiger grouper.
Microstructure and compositional changes across biotite‐rich reaction selvedges around mafic schollen in a semipelitic diatexite migmatite
Authors: Lin Lina , Sawyer Edward W. 
Published: February 2019

AbstractBiotite‐rich selvedges developed between mafic schollen and semipelitic diatexite in migmatites at Lac Kénogami in the Grenville Province of Quebec. Mineral equilibria modelling indicates that partial melting occurred in the mid‐crust (4.8–5.8 kbar) in the range 820–850°C. The field relations, petrography, mineral chemistry and whole‐rock composition of selvedges along with their adjacent mafic schollen and host migmatites are documented for the first time. The selvedges measured in the field are relatively uniform in width (~1 cm wide) irrespective of the shape or size of their mafic scholle. In thin section, the petrographic boundary between mafic scholle and selvedge is defined by the appearance of biotite and the boundary between selvedge and diatexite by the change in microstructure for biotite, garnet, plagioclase and quartz. Three subtypes of selvedges are identified according to mineral assemblage and microstructure. Subtype I have orthopyroxene but of different microstructure and Mg# to orthopyroxene in the mafic scholle; subtype II contain garnet with many mineral inclusions, especially of ilmenite, in contrast to garnet in the diatexite host which has few inclusions; subtype III lack orthopyroxene or garnet, but has abundant apatite. Profiles showing the change in plagioclase composition from the mafic schollen across the selvedge and into the diatexite show that each subtype of selvedge has a characteristic pattern.Four types of biotite are identified in the selvedges and host diatexite based on their microstructural characteristics. (a) Residual biotite forms small rounded red‐brown grains, mostly as inclusions in peritectic cordierite and garnet in diatexite; (b) selvedge biotite forms tabular subhedral grains with high respect ratio; (c) diatexite biotite forms tabular subhedral grains common in the matrix of the diatexite; and (d) retrograde biotite that partially replaces peritectic cordierite and garnet in the diatexite. The four groups of biotite are also discriminated by their major element (EMPA) and trace elements (LA‐Q‐ICP‐MS) compositions. Residual biotite is high in TiO2 and low in Sc and S, whereas retrograde biotite has high Al2O3, but low Sc and Cr. Selvedge and diatexite biotite are generally very similar, but selvedge biotite has higher Sc and S contents. Whole‐rock compositional profiles across the selvedges constructed from micro‐XRF and LA‐Q‐ICP‐MS analyses show: (a) Al2O3, FeO, MgO and CaO all decrease from mafic scholle across the selvedge and into the diatexite; (b) Na2O is lowest in the mafic scholle, rises through the selvedge and reaches its maximum about 20–30 mm into the diatexite host; (c) K2O is lowest in the mafic scholle and reaches its highest value in the first half of the selvedge, then declines before reaching a higher, but intermediate value, about 20 mm into the diatexite. Of the trace elements, Cs and Rb show distributions very similar to K2O.
A brief history of circannual time
Authors: Lincoln Gerald 
Published: February 2019

Innate circannual timing is an ancestral trait that first evolved in free‐living eukaryotic cells some 2000 million years ago, with marine algae of the genus Allexandrium providing a living unicellular model. This species shows the primitive trait of ‘alternation of generations’, where the organism alternates between fast replicating vegetative cells in the summer and a dormant cystic cell over the winter. The resistant cysts sink into the cold ocean sediments. Remarkably, excystment in spring is governed by an endogenous circannual timing mechanism. Thus, a tiny, short‐lived unicell can utilise a circannual clock as part of the life‐history programme of the species. Innate timing allows for major adjustments in physiology and behaviour in anticipation of the seasons, and provides an internalised sense of seasonal time for the many species where standard environmental cues are weak or ambiguous. This is a highly adaptive strategy irrespective of the size and longevity of an organism. Circannual rhythms are expressed by a diverse range of organisms, from flowering plants to mammals, interwoven into the life‐history programme of each species, being a consequence of forever living in a periodic world. In complex vertebrates, the early division of the zygote potentially carries circannual timer genes into all progeny cells and tissues. This supports the concept of a ‘clock‐shop’ where cell‐autonomous long‐term rhythms are generated in each tissue, orchestrated by a central circannual pacemaker system. This is analogous to the organisation of the circadian timing system. For the circannual time‐scale, specialised thyrotroph cells located in the pars tuberalis of the pituitary gland and adjacent tanycyte cells located in the ependymal wall of the third cerebral ventricle of the brain act as putative central circannual pacemakers. At a molecular level, epigenetically regulated, cyclical remodelling of chromatin, which determines whether specific circannual timer genes are transcriptionally active, or not, is considered to drive the oscillation between the summer and winter phenotypes.
Exploring the structure of narcissism: Toward an integrated solution
Authors: Crowe Michael L. , Lynam Donald R. , Campbell W. Keith , Miller Joshua D. 
Published: February 2019

AbstractObjectiveDespite decades of work on narcissism, there remain many active areas of exploration and debate including a clear and consensual description of its underlying components. Understanding narcissism's factor structure is necessary for the precise measurement and investigation of specific psychological and behavioral processes. The aim of the current study was to explore the structure of narcissism by examining it at varying hierarchical levels.MethodParticipants recruited from Amazon's Mechanical Turk (N = 591) completed 303 narcissism items encompassing 46 narcissism scales and subscales. Criterion variables measuring the five‐factor model, self‐esteem, aggression, and externalizing behavior were also collected.ResultsA series of factor analyses reveal the factor structure of narcissism at a range of specificities. No more than five meaningful factors (i.e., Grandiosity, Neuroticism, Antagonism, Distrustful Self‐reliance, Attention‐seeking) were identified and the most parsimonious model appears to be a three‐factor structure. Narcissism scales that effectively capture each of the identified factors are identified. Factors diverged in their associations with criterion variables.ConclusionsA three‐factor model (i.e., Agentic Extraversion, Narcissistic Neuroticism, Self‐centered Antagonism) seems to be the most parsimonious conceptualization. Larger factor solutions are discussed, but future research will be necessary to determine the value of these increasingly narrow factors.
Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy
Authors: Rahman Shadab A. , Bibbo Carolina , Olcese James , Czeisler Charles A. , Robinson Julian N. , Klerman Elizabeth B. 
Published: February 2019

AbstractIn humans, circulating levels of the hormone melatonin and the initiation of spontaneous labor are both higher at night than during the day. Since activation of uterine melatonin receptors can stimulate human in vitro uterine contractions and these receptors are only expressed on the uterine tissue of women in labor, we hypothesized that circulating melatonin concentrations would affect uterine contractions in vivo. We evaluated the impact of light‐induced modulation of melatonin secretion on uterine contractions in women during late third trimester (~36‐39 weeks) of pregnancy in two inpatient protocols. We found a significant (P < 0.05) positive linear association between circulating melatonin concentrations and the number of uterine contractions under both protocols. On average, uterine contractions increased between 1.4 and 2.1 contractions per 30 minutes for every 10 pg/mL*h increase in melatonin concentration. These findings have both basic science and clinical implications for pregnant women, since endogenous melatonin levels and melatonin receptor activity can be altered by light and/or pharmaceutical agents.
Anthropometrical phenotypes are important when explaining obstructive sleep apnea in female bariatric cohorts
Authors: Gasa Mercè , López‐Padrós Carla , Monasterio Carmen , Salord Neus , Mayos Mercedes , Vilarrasa Núria , Fernandez‐Aranda Fernando , Montserrat Josep M. , Dorca Jordi 
Published: February 2019

AbstractCentral obesity is the main risk factor for obstructive sleep apnea (OSA). Whether there exists a central‐obesity anthropometric that better explains apnea–hypopnea index (AHI) variability in the general population and in sleep cohorts is unknown, and this is even less explored among increasing grades of obesity. The objective of the study is to investigate whether there is an anthropometric that better explains AHI variability in a sample of morbidly obese women awaiting bariatric surgery (BS). A prospective multicentre cross‐sectional study was conducted in consecutive women before BS. Demographic and anthropometric characteristics included age, body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC) and waist‐to‐hip ratio (WHR). OSA was diagnosed by polysomnography. The capacity of anthropometrics to explain AHI variance was investigated using regression linear models. A total of 115 women were evaluated: age, 44 ± 10 years; BMI, 46 ± 5 kg/m2; AHI, 35 ± 26 events/hr. AHI was associated with all anthropometrics except weight, height and HC. The best univariate predictor was WHR, which accounted for 15% of AHI variance. The simplest model (age + BMI) accounted for 9%, which increased to 20% when applying more complex measurements (age + BMI + NC + WC + HC). The explanatory capacity did not change significantly when applying a simpler model (age + WHR + NC, 19%). In this female morbidly obese cohort, anthropometrics explained one‐fifth of AHI variability. WHR is the best univariate parameter and models including waist and neck data provide more information than BMI when explaining AHI variability. Thus, even in young women with extreme obesity, OSA seems to be linked to a specific central‐obesity phenotype rather than to a whole‐obesity pattern.
Social ontology, practical reasonableness, and collective reasons for action
Authors: Ikuenobe Polycarp 
Published: February 2019

AbstractI argue that the ontology of human social institutions and collective intentionality could be anchored in the normative notion of ‘practical reasonableness’ as collective reason for action. This involves the deontic idea of mutuality, accepted rules, and shared attitudes of other‐regardedness. I examine John Searle's three primitive notions of social ontology: collective intentionality, assignment of social functions, and constitutive rules and procedures. I use these notions to provide a plausible basis for understanding how people reason, in order to arrive at practically reasonable decisions and collective agency. Searle argues that social reality, institutions, processes, and facts are grounded in collective intentionality and the acceptance of social rules, procedures, and functions. I argue that collective intentionality and socially accepted rules are anchored in the need for human interdependence that engenders the social rules and norms or attitudes of ‘practical reasonableness’. I analyze the concept of ‘practical reasonableness’ as a representation of human mode of reasoning that involves collective intentionality.