bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progesterone Metabolites Inhibit the Human Ether‐a‐go‐go‐Related Gene and Predict QT Interval Length
Authors: Shugg Tyler , Egly Christian , Stamatkin Chris W. , Patil Avinash S. , Tisdale James E. , Overholser Brian R. 
Published: December 2019

AbstractA decrease in the human ether‐a‐go‐go‐related gene (hERG/KCNH2)‐related channel has been linked to intrauterine fetal death. The formation of cytochrome P450 (CYP) 3A‐mediated progesterone metabolites, 6‐beta‐hydroxy‐progesterone (6β‐OHP) and 16α‐hydroxy‐progesterone (16α‐OHP), is variable among adults and differs from fetal metabolism. The primary objective of this study was to assess the potential for progesterone metabolites to inhibithERG‐related current and predict QTc intervals. Whole‐cell voltage‐clamp electrophysiology was performed on human embryonic kidney 293 cells stably expressing hERG exposed to progesterone or metabolites. Both 6β‐OHP and 16α‐OHP positively shifted the voltage dependence of activation relative to vehicle from ‐4.0 ± 0.8 to ‐0.3 ± 0.8 mV,P< .01; and 1.0 ± 0.6 mV,P< .01, respectively. In addition, 6β‐OHP decreased maximal outward tail currents from 49.4 ± 4.9 to 32.5 ± 4.1 pA/pF,P< 0.01, and reduced the expression of fully glycosylated hERG by 42%. Healthy female subjects were administered progesterone 400 mg orally for 7 days, ibutilide 0.003 mg/kg was infused, and serial electrocardiograms and blood samples collected. Relationships between rate‐corrected QT intervals (QTcI) with circulating hormones and metabolites were assessed. The 6β‐OHP and 16α‐OHP metabolites were independent predictors of QTcI intervals prior to and following ibutilide administration. In conclusion, the progesterone metabolites formed via CYP3A cause inhibitory effects on hERG channels and predict QTcI intervals in healthy women pretreated with progesterone. Further study into maternal and fetal exposure to these metabolites and potential to prolong cardiac repolarization is warranted.
Observation of a gerade symmetry state of Cu2 using two‐color resonant four‐wave mixing
Authors: Zhang Qiang , Bornhauser Peter , Knopp Gregor , Radi Peter 
Published: December 2019

AbstractThe first observation of an excited 0
state of dicopper is reported. “g” inversion symmetry states are not observable by direct one‐photon absorption from the X
ground state. Measurements are performed by applying nonlinear two‐color resonant four‐wave mixing (TC‐RFWM) spectroscopy. Cold Cu2 molecules in a molecular beam environment are generated by applying a pulsed laser vaporization source and subsequent near supersonic expansion of the vaporized metal plume entrained in a helium pulse. Spectra in the wavenumber region of the [37.5(v)]0
‐ B0
electronic transition are recorded by using the UNFOLDED double‐resonance scheme. Specific rotational levels of the intermediate state B0
, v′=1 are accessed from the X
ground state. Dipole selection rules from the labeled levels define unambiguously the rotational quantum number and symmetry of the final state (ΔJ=±0,1 and g ↔ u). The UNFOLDED scheme is verified by additional measurements via the origin level, v′=0, of the intermediate B0
state. Spectroscopic constants of the [37.5(v)]0
state have been determined for both 63Cu2 and 63Cu65Cu isotopologues by analysis of the rotationally resolved spectra. The potential of TC‐RFWM to study the unexplored “g” symmetry manifold of Cu2 is discussed.
Successful Treatment of Cosmetic Eyebrow Tattoos in Fitzpatrick III‐IV With Picosecond (1,064, 532‐nm) Neodymium‐Doped Yttrium Aluminum Garnet Laser With a Perfluorodecalin‐Infused Patch: A Pilot Study
Authors: Moustafa Farah , Suggs Amanda , Hamill Selina S. , Friedman Paul M. 
Published: December 2019

Background and ObjectivesNanosecond Q‐switched lasers have been used for the removal of traditional and cosmetic tattoos. Picosecond lasers utilize pulse durations of 10−12 and provide more efficient clearance of tattoos. Safe and effective removal of tattoos is especially important in cosmetically sensitive areas such as the face. We report four patients with skin types (III–IV) who have had successful removal of eyebrow tattoos with the picosecond (1,064‐, 532‐nm) laser using a perfluorodecalin‐infused patch (PFD).Study Design/Materials and MethodsPatients with eyebrow tattoos underwent treatment with dual‐wavelength picosecond Nd:YAG laser at 1,064‐nm with a 3 mm spot size and fluence of 4–4.6 J/cm2. The 532‐nm wavelength was also used during treatment #1 (patient 2 only) with a 4 mm spot size and fluence of 0.5 J/cm2. Patient 1 had a total of three treatments (6–8 weeks apart). The remaining patients, each had only one treatment. Patients were photographed prior to treatment and subsequently at each follow‐up.ResultsImmediately following each laser treatment, only mild and transient localized erythema and edema was observed. Some epidermal crusting was noted for 3–5 days following each treatment. Eyebrow hair growth was not affected and no adverse events were reported. There was 75% clearance in patient 1 after three treatments over a period of 2.5 months, 75% clearance in patient 2 after one treatment, 90% clearance in patient 3 after one treatment, and 100% clearance in patient 4 after one treatment.ConclusionsThe 532‐ and 1,064‐nm wavelength of the picosecond Nd:YAG laser was safely used to clear brown and black ink eyebrow tattoos in four patients, three of whom were skin type IV, and one of whom underwent eyebrow tattoo via microblading, a novel and popular technique for cosmetic tattoos. The use of picosecond laser provides several treatment advantages to Q‐switched laser when treating eyebrow tattoos. In our experience, it required less number of treatments and lower fluences. This, along with use of the perfluorodecalin‐infused patch resulted in excellent outcomes for our patients with no significant side effects. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
When does every definable nonempty set have a definable element?
Authors: Dorais François G. , Hamkins Joel David 
Published: December 2019

AbstractThe assertion that every definable set has a definable element is equivalent over to the principle , and indeed, we prove, so is the assertion merely that every Π2‐definable set has an ordinal‐definable element. Meanwhile, every model of has a forcing extension satisfying in which every Σ2‐definable set has an ordinal‐definable element. Similar results hold for and and other natural instances of .
Novel FSHR variants causing female resistant ovary syndrome
Authors: Khor Shuzin , Lyu Qifeng , Kuang Yanping , Lu Xuefeng 
Published: December 2019

AbstractBackgroundPathogenic variants of follicle‐stimulating hormone receptor (FSHR) are known to cause amenorrhea and infertility in women. However, only a limited number of pathogenic FSHR variants have been reported, and few reports described detailed characteristics of patients with pathogenic FSHR variants.MethodsThe affected siblings and both parents were subjected to whole‐genome exon sequencing. Transient transfection of HEK 293T cells was performed with constructed vectors. The cellular localization of the FSHR protein was evaluated using confocal microscopy, and cyclic adenosine monophosphate (cAMP) production was detected with a cAMP ELISA kit.ResultsA Chinese family with two siblings carrying compound heterozygous pathogenic variants of FSHR: c.182T>A (p.Ile61Asn) and c.2062C>A (p.Pro688Thr). Both siblings had amenorrhea, infertility, and resistance to gonadotropin (Gn) stimulation but showed high anti‐Müllerian hormone levels and early antral follicles. Molecular dynamics simulations of the FSHR variants revealed significant changes in structural characteristics and electrostatic potential. In vitro analysis indicated that the p.Ile61Asn variant lacked cell surface localization and completely abolished the cAMP second messenger response. The p.Pro688Thr variant retained cell surface localization but caused decreased FSH‐induced cAMP production.ConclusionWe found two novel pathogenic FSHR variants causing resistant ovarian syndrome. This study expands the genotypic spectrum of pathogenic FSHR variants and our knowledge of phenotype–genotype correlations.
Existence results for a class of nonlinear singular transport equations in bounded spatial domains
Authors: Latrach Khalid , Oummi Hssaine , Zeghal Ahmed 
Published: December 2019

In this paper, we prove the existence of solutions to a nonlinear singular transport equation (ie, transport equation with unbounded collision frequency and unbounded collision operator) with vacuum boundary conditions in bounded spatial domain on Lp‐spaces with 1 ≤ p<+∞. This problem was already considered in6,8,9 under the hypothesis that the collision frequency σ(·) and the collision operator are bounded. In this work, we show that these hypotheses are not necessary; it suffices to assume that σ(·) is locally bounded, and the collision operator is bounded between
(a weighted space) and
(cf Section 2). Although the analysis for p∈(1,+∞) is standard in the sense that it uses the Schauder fixed point theorem, the compactness of the involved operator is not easy to derive. However, the analysis in the case p=1 uses the concept of Dunford‐Pettis operators and a new version of the Darbo fixed point theorem for a measure of weak noncompactness introduced in the paper.
Technical Note: An IBEX adaption toward image biomarker standardization
Authors: Bettinelli Andrea , Branchini Marco , De Monte Francesca , Scaggion Alessandro , Paiusco Marta 
Published: December 2019

PurposeInterest in the field of radiomics is rapidly growing because of its potential to characterize tumor phenotype and provide predictive and prognostic information. Nevertheless, the reproducibility and robustness of radiomics studies are hampered by the lack of standardization in feature definition and calculation. In the context of the image biomarker standardization initiative (IBSI), we investigated the grade of compliance of the image biomarker explorer (IBEX), a free open‐source radiomic software, and we developed and validated standardized‐IBEX (S‐IBEX), an adaptation of IBEX to IBSI.MethodsImage biomarker explorer source code was checked against IBSI standard. Both the feature implementation and the overall image preprocessing chain were evaluated. Sections were re‐implemented wherever differences emerged: in particular, contour‐to‐binary‐mask conversion, image sub‐portion extraction, re‐segmentation, gray‐level discretization and interpolation were aligned to IBSI. All reported IBSI features were implemented in S‐IBEX. On a patient phantom, S‐IBEX was validated by benchmarking five different preprocessing configurations proposed by IBSI.ResultsMost IBEX feature definitions are IBSI compliant; however, IBEX preprocessing introduces non‐negligible nonconformities, resulting in feature values not aligned with the corresponding IBSI benchmarks. On the contrary, S‐IBEX features are in agreement with the standard regardless of preprocessing configurations: the percentage of features equal to their benchmark values ranges from 98.1% to 99.5%, with overall maximum percentage error below 1%. Moreover, the impact of noncompliant preprocessing steps has been assessed: in these cases, the percentage of features equal to the standard drops below 35%.ConclusionsThe use of standardized software for radiomic feature extraction is essential to ensure the reproducibility of results across different institutions, easing at the same time their external validation. This work presents and validates S‐IBEX, a free IBSI‐compliant software, developed upon IBEX, for feature extraction that is both easy to use and quantitatively accurate.
Relationship between spiritual health and hope by dietary adherence in haemodialysis patients in 2018
Authors: Musavi Ghahfarokhi Motahareh , Mohammadian Sara , Mohammadi Nezhad Bahar , Kiarsi Maryam 
Published: December 2019

AbstractAimThe present study aimed to determine the relationship between spiritual well‐being and hope through adherence to diet in haemodialysis patients referred to the dialysis centre.DesignThis research was a cross‐sectional study of a descriptive‐analytical type conducted on 120 patients undergoing haemodialysis in a haemodialysis centre of a hospital affiliated to Dezful University of Medical Sciences using the census method.MethodThe data were collected using a questionnaire and through the laboratory information included in the patient's records. The data collection tools were a demographic information questionnaire, the Ellison and Paloutzian spiritual well‐being scale (SWBS), the Hope‐Herth questionnaire and the objective laboratory criteria (phosphorus, potassium). This included the weight difference between the two dialysis sessions from the record to examine the adherence to the diet.ResultsThe results indicate there to be a significant relationship between hope and spiritual well‐being with the objective criteria of the adherence to the diet in dialysis patients (p = .001).
Associations of nurse education level and nurse staffing with patient experiences of hospital care: A cross sectional study in China
Authors: Liu Xu , Zheng Jing , Liu Ke , Baggs Judith G. , Liu Jiali , Wu Yan , You Liming 
Published: December 2019

AbstractStrengthening the nursing workforce is core to health system reform in China. Patient experiences of hospital care have been recognized as important in this endeavor. Studies exploring the relationships between nursing workforce and patient experiences of hospital care, however, are scarce. The aim of this cross‐sectional study was to examine the associations between nurse education level, nurse staffing, and hospitalized patients’ experiences of hospital care. Participants were 1,582 nurses responsible for direct care and 1,305 hospitalized patients from 23 hospitals in Guangdong province, China in 2014. Education level of nurses was measured by the proportion of nurses holding a baccalaureate or higher degree. Nurse staffing was measured by the unit nurse‐patient ratio. The Hospital Consumer Assessment of Health care Providers and Systems Scale was used to measure patient experiences of hospital care. Structural equation modeling demonstrated that a higher proportion of nurses holding a baccalaureate or higher degree was related directly to better patient perceptions of communication with nurses, responsiveness of nurses, pain management, and physical environment, and related indirectly to overall hospital ratings and recommendation of the hospital. A higher nurse‐patient staffing ratio was associated directly with better patient perceptions of communication with nurses, education about new medications given in hospital, and physical environment, and indirectly with overall ratings and recommendation of the hospital. Our findings add new evidence in the Chinese societal context about the relationship between the nursing workforce and patient experiences of hospital care. Upgrading nurse education level and increasing nurse staffing could potentially improve patient experiences of hospital care.
Interpretation of somatic POLE mutations in endometrial carcinoma
Authors: León‐Castillo Alicia , Britton Heidi , McConechy Melissa K , McAlpine Jessica N , Nout Remi , Kommoss Stefan , Brucker Sara Y , Carlson Joseph W , Epstein Elisabeth , Rau Tilman T , Bosse Tjalling , Church David N , Gilks C Blake 
Published: December 2019

AbstractPathogenic somatic missense mutations within the DNA polymerase epsilon (POLE) exonuclease domain define the important subtype of ultramutated tumours (‘POLE‐ultramutated’) within the novel molecular classification of endometrial carcinoma (EC). However, clinical implementation of this classifier requires systematic evaluation of the pathogenicity of POLE mutations. To address this, we examined base changes, tumour mutational burden (TMB), DNA microsatellite instability (MSI) status, POLE variant frequency, and the results from six in silico tools on 82 ECs with whole‐exome sequencing from The Cancer Genome Atlas (TCGA). Of these, 41 had one of five known pathogenic POLE exonuclease domain mutations (EDM) and showed characteristic genomic alterations: C>A substitution > 20%, T>G substitutions > 4%, C>G substitutions < 0.6%, indels < 5%, TMB > 100 mut/Mb. A scoring system to assess these alterations (POLE‐score) was developed; based on their scores, 7/18 (39%) additional tumours with EDM were classified as POLE‐ultramutated ECs, and the six POLE mutations present in these tumours were considered pathogenic. Only 1/23 (4%) tumours with non‐EDM showed these genomic alterations, indicating that a large majority of mutations outside the exonuclease domain are not pathogenic. The infrequent combination of MSI‐H with POLE EDM led us to investigate the clinical significance of this association. Tumours with pathogenic POLE EDM co‐existent with MSI‐H showed genomic alterations characteristic of POLE‐ultramutated ECs. In a pooled analysis of 3361 ECs, 13 ECs with DNA mismatch repair deficiency (MMRd)/MSI‐H and a pathogenic POLE EDM had a 5‐year recurrence‐free survival (RFS) of 92.3%, comparable to previously reported POLE‐ultramutated ECs. Additionally, 14 cases with non‐pathogenic POLE EDM and MMRd/MSI‐H had a 5‐year RFS of 76.2%, similar to MMRd/MSI‐H, POLE wild‐type ECs, suggesting that these should be categorised as MMRd, rather than POLE‐ultramutated ECs for prognostication. This work provides guidance on classification of ECs with POLE mutations, facilitating implementation of POLE testing in routine clinical care. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Pharmaceutically treated comorbidities and associated healthcare costs among triptan users in Switzerland: A pharmacoepidemiological study from a nationwide health insurance database
Authors: Huber Carola A. , Agosti Reto , Näpflin Markus , Blozik Eva 
Published: December 2019

AbstractPurposeIn course of the new migraine drug development on the global market it is important to quantify the current burden of migraine medication. This study aimed to estimate the comorbidity burden and its relation to healthcare costs in patients using triptans in Switzerland by analyzing a large population‐based database.MethodsThis retrospective cohort study was based on Swiss health insurance claims data (2015/2016). The study sample comprised adult patients with ≥1 triptan prescription in 2015. We evaluated pharmaceutically treated comorbid conditions (CCs) and costs (12 months after index prescription) of patients using triptan. Multivariable linear regression models with log‐transformed outcomes were performed to identify the factors related to healthcare costs.ResultsFrom a total of 749 092, we identified 10,090 patients using triptans (1‐year prevalence of 1.35%), whereas 58.9% had ≥2 CCs. The most frequent CCs were pain‐ and rheumatologic‐related diseases and psychological disorders. Among triptan users, the mean total healthcare costs were highest in older patients with ≥2 CCs (>64 years: migraine with ≥2 CC “12 331 SFr”). Multivariate regression analyses showed that psychological disorders had the strongest impact on healthcare costs (Coefficient: 1.29; 95%‐CI: 1.27‐1.31).ConclusionsThe present study provides an overview of comorbidities and its related costs in migraine patients, which helps to quantify the current burden of migraine. This is relevant as the recently licensed CGRP antagonists are likely to change current treatment schemes for migraine, which strongly depends also on the comorbidities. The present study might therefore be helpful for the future development of treatment guidelines.
Rhythms, flows, and structures of cross‐boundary schooling: state power and educational mobilities between Shenzhen and Hong Kong
Authors: Waters Johanna L. , Leung Maggi W.H. 
Published: December 2019

AbstractThis paper explores the phenomenon of cross‐boundary schooling (CBS), where more than 30,000 children undertake a daily, checkpoint‐crossing commute to school and back again, over the Hong Kong–Shenzhen border. It elaborates on the notion of “state assemblage” to consider how the power of the state (in this case, both the People's Republic of China and Hong Kong authorities) manifests in CBS and, in particular, how the state attempts to exert control over children's and parents' bodies. This view of CBS contrasts with a sense of “agency” that prevails around discussions of educational mobilities, and we explore this tension here. The paper focuses on two related aspects of CBS—materiality and the role of habit and rhythm in directing, guiding, and cajoling children to conform to an extremely rigid and regimented daily routine. We found that the material structures that make up the border are crucial in enabling CBS to “function” and that notions of rhythm and habit are very useful for understanding how the “flow” of educational mobilities is achieved. At the same time, we considered instances where flow was disrupted, rhythms were changed, and individuals somehow resisted the material constraints of the border.
Discussion on statistical analysis of carcinogenicity studies with an early terminated treated group
Authors: Saul Jim , Ashcroft‐Hawley Kelly 
Published: December 2019

SUMMARYHigh rates of mortality on long term carcinogenicity studies can often result in challenges when it comes to the statistical analysis of tumor incidence. The current regulatory advice often results in treated groups being terminated earlier than the control group. However, this advice rarely considers the impact of this action on the statistical analyses. The nature of these analyses means that groups terminated at different times may not be directly comparable due to age differences of the animals. Here we discuss the issues related to this and investigate several approaches of how to incorporate these groups within the statistical analyses. Although no single method appears to resolve these issues consistently, inclusion of the early terminated group is still informative. Depending on the timing of the early termination, either pooling of the groups into a single terminal kill (TK) interval or reassignment of intervals based purely on time of death (ie, no separate TK interval) appear preferable. However, to draw meaningful conclusions the time of onset of a given tumor must also be considered alongside incident rates and any statistical findings.
Ongoing forest disturbance in Guatemala's protected areas
Authors: Bullock Eric L. , Nolte Christoph , Reboredo Segovia Ana L. , Woodcock Curtis E. 
Published: December 2019

AbstractProtected areas in Guatemala provide habitat for diverse tropical ecosystems, contain ancient archeological sites, sequester carbon, and support economic activity through eco‐tourism. However, many of the forests in these protected areas have been converted to other uses or degraded by human activity, and therefore are considered “paper parks”. In this study, we analyzed time series of satellite data to monitor deforestation, degradation, and natural disturbance throughout Guatemala from 2000 to 2017. A recently developed methodology, Continuous Degradation Detection (CODED), was used to detect forest disturbances of varying size and magnitude. Through sample‐based statistical inference, we estimated that 854 137 ha (± 83 133 ha) were deforested and 1 012 947 ha (±139 512 ha) of forest was disturbed but not converted during our study period. Forest disturbance in protected areas ranged from under 1% of a park's area to over 95%. Our estimate of the extent of deforestation is similar to previous studies, however, degradation and natural disturbance affect a larger area. These results suggest that the total amount of forest disturbance can be significantly underestimated if degradation and natural disturbance are not taken into account. As a consequence, we found that the protected areas of Guatemala are more affected by disturbance than previously realized.