bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Trials [and Tribulations]: The Immediate Effects of COVID-19 on IBD Clinical Research Activity in the UK
Authors: Noor Nurulamin M , Hart Ailsa L , Irving Peter M , Ghosh Subrata , Parkes Miles , Raine Tim 
Published: June 2020

Abstract
There have been immediate and profound impacts of SARS-CoV-2 and COVID-19 on health care services worldwide, with major consequences for non COVID-19 related health care. Alongside efforts to reconfigure services and enable continued delivery of safe clinical care for patients with IBD, consideration must also be given to management of IBD research activity. In many centres there has been an effective shutdown of IBD clinical trial activity as research sites have switched focus to either COVID-19 related research or clinical care only. As a result, the early termination of trial programmes, and loss of potentially effective therapeutic options for IBD, has become a real and worrying prospect. Moreover, in many countries research activity has become embedded into clinical care—with clinical trials often providing access to new therapies or strategies—which would otherwise not have been available in standard clinical pathways. This pandemic has significant implications for the design, conduct, analysis, and reporting of clinical trials in IBD. In this Viewpoint, we share our experiences from a clinical and academic perspective in the UK, highlighting the early challenges encountered, and consider implications for patients and staff at research sites, sponsors, research ethics committees, funders, and regulators. We also offer potential solutions both for now and for when we enter a recovery phase from the pandemic.
Adherence to prescribed medications in patients with heart failure: insights from liquid chromatography–tandem mass spectrometry-based urine analysis
Authors: Simpson Joanne , Jackson Colette E , Haig Caroline , Jhund Pardeep S , Tomaszewski Maciej , Gardner Roy S , Tsorlalis Yannis , Petrie Mark C , McMurray John J V , Squire Iain B , Gupta Pankaj 
Published: June 2020

Abstract

Aims
None of the existing studies on adherence have directly measured levels of all medications (or their metabolites) in patients with heart failure (HF).

Methods and results
We used liquid chromatography–tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4–6 weeks after hospitalization with HF. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent, i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only seven out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed HF drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients.

Conclusion
Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in one of five patients evaluated 4–6 weeks after hospitalization with HF.
Mid-term results of modified L-shaped incision technique for supracardiac total anomalous pulmonary venous connection
Authors: Feng Zicong , Yang Yang , He Fengpu , Pang Kunjing , Ma Kai , Zhang Sen , Qi Lei , Wang Guanxi , Mao Fengqun , Yuan Jianhui , Li Shoujun 
Published: June 2020

Abstract

OBJECTIVES

Surgical outcomes of supracardiac total anomalous pulmonary venous connection (TAPVC) repair by the posterior technique (PT) remain unsatisfactory. This study aimed to compare the outcomes of the modified L-shaped incision technique with the PT for supracardiac TAPVC repair.

METHODS
From January 2009 to December 2019, 121 consecutive patients with supracardiac TAPVC undergoing surgical repair in our institution were included (L-group, n = 53; PT group, n = 68). A propensity score-matched analysis was performed. Patients with single-ventricle physiology or atrial isomerism were excluded. All clinical data were retrospectively analysed.

RESULTS
In the unmatched cohort, the median follow-up duration was 33 months (interquartile range 26–65 months). There were 5 operative mortalities (4.1%) and 12 late mortalities (9.9%). Postoperative pulmonary venous obstruction (PVO) was documented in 21 patients. After matching (52 pairs), the overall survival rate in the L-group was 88.2% at both 3 and 5 years. For the propensity score-matched patients with preoperative PVO (n = 20), statistically significant differences (P = 0.002) were found by Kaplan–Meier curves with freedom from death and postoperative PVO at 1 and 3 years of 100% and 85.7% [standard deviation (SD): 13.2%] in the L-group and 90% (SD: 9.5%) and 22.9% (SD: 14.1%) in the PT group, respectively. Multivariable analysis revealed that the use of the PT was an independent risk factor for death and postoperative PVO (hazard ratio 4.12, 95% confidence interval 1.12–15.16; P = 0.03).

CONCLUSIONS
The modified L-shaped incision technique provided an acceptable outcome for supracardiac TAPVC repair. Compared with PT, the modified L-shaped incision technique was significantly associated with decreased death and postoperative PVO in patients with obstructed supracardiac TAPVC.
Without coal in the age of steam and dams in the age of electricity: an explanation for the failure of Portugal to industrialize before the Second World War
Authors: Henriques Sofia Teives , Sharp Paul 
Published: June 2020

AbstractWe provide a natural resource explanation for the divergence of the Portuguese economy relative to other European countries before the Second World War. First, we demonstrate that a lack of domestic resources meant that Portugal experienced limited and unbalanced growth during the age of steam. Imports of coal were prohibitively expensive for inland areas. Coastal areas industrialized through steam but were constrained by limited demand from the interior. Second, we show that after the First World War, when other coal-poor countries turned to hydro-power, Portugal relied on coal-based thermal-power, creating a vicious circle of high-energy prices and labor-intensive industrialization.
Does the Impact of Intensive Lifestyle Intervention on Cardiovascular Disease Risk Vary According to Frailty as Measured via Deficit Accumulation?
Authors: Simpson Felicia R , Pajewski Nicholas M , Beavers Kristen M , Kritchevsky Stephen , McCaffery Jeanne , Nicklas Barbara J , Wing Rena R , Bertoni Alain , Ingram Frank , Ojeranti Daniel , Espeland Mark A 
Published: June 2020

Abstract

Background
Individuals are often counseled to use behavioral weight loss strategies to reduce risk for cardiovascular disease (CVD). We examined whether any benefits for CVD risk from weight loss intervention extend uniformly to individuals across a range of underlying health states.

Methods
The time until first occurrence of a composite of fatal and nonfatal myocardial infarction and stroke, hospitalized angina, or CVD death was analyzed from 8 to 11 years of follow-up of 4,859 adults who were overweight or obese, aged 45–76 years with Type 2 diabetes. Individuals had been randomly assigned to either an intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Participants were grouped by intervention assignment and a frailty index (FI) based on deficit accumulation, ordered from fewer (first tertile) to more (third tertile) deficits.

Results
Baseline FI scores were unrelated to intervention-induced weight losses and increased physical activity. The relative effectiveness of ILI on CVD incidence was inversely related to baseline FI in a graded fashion (p = .01), with relative benefit (hazard ratio = 0.73 [95% CI 0.55,0.98]) for individuals in the first FI tertile to no benefit (hazard ratio = 1.15 [0.94,1.42]) among those in the third FI tertile. This graded relationship was not seen for individuals ordered by age tertile (p = .52), and was stronger among participants aged 45–59 years (three-way interaction p = .04).

Conclusions
In overweight/obese adults with diabetes, multidomain lifestyle interventions may be most effective in reducing CVD if administered before individuals have accrued many age-related health deficits. However, these exploratory analyses require confirmation by other studies.

Clinical Trial Registration
NCT00017953
Lithospheric stress, strain and displacement changes from GRACE-FO time-variable gravity: case study for Sar-e-Pol Zahab Earthquake 2018
Authors: Eshagh Mehdi , Fatolazadeh Farzam , Tenzer Robert 
Published: June 2020

SUMMARY
Temporal variations in the Earth's gravity field can be used for monitoring of lithospheric deformations. The network of continuously operating gravity stations is required for this purpose but a global coverage by such network is currently extremely sparse. Temporal variations in long-wavelength part of the Earth's gravity field have been, however, observed by two satellite missions, namely the Gravity Recovery And Climate Experiment (GRACE) and the GRACE Follow-On (GRACE-FO). These satellite gravity observations can be used to study long-wavelength deformations of the lithosphere. Consequently, considering the lithosphere as a spherical elastic shell and solving the partial differential equation of elasticity for it, the stress, strain and displacement inside the lithosphere can be estimated. The lower boundary of this shell is assumed to be stressed by mantle convection, which has a direct relation to the Earth's gravity field according to Runcorn's theory. Changes in gravity field lead to changes in the sublithospheric stress and the stress propagated throughout the lithosphere. In this study, we develop mathematical models in spherical coordinates for describing the stress propagation from the sublithosphere through the lithosphere. We then organize a system of observation equations for finding a special solution to the boundary-value problem of elasticity in the way that provides a stable solution. In contrast, models presented in previously published studies are ill-posed. Furthermore, we use constants of the solution determined from the boundary stresses to determine the strain and displacements leading to these stresses, while in previous studies only the stress has been considered according to rheological properties of the lithosphere. We demonstrate a practical applicability of this theoretical model to estimate the stress–strain redistribution caused by the Sar-e-Pol Zahab 2018 earthquake in Iran by using the GRACE-FO monthly solutions.
Systematic investigation of the skin inChst14−/−mice: A model for skin fragility in musculocontractural Ehlers–Danlos syndrome caused byCHST14variants (mcEDS-CHST14)
Authors: Hirose Takuya , Mizumoto Shuji , Hashimoto Ayana , Takahashi Yuki , Yoshizawa Takahiro , Nitahara-Kasahara Yuko , Takahashi Naoki , Nakayama Jun , Takehana Kazushige , Okada Takashi , Nomura Yoshihiro , Yamada Shuhei , Kosho Tomoki , Watanabe Takafumi 
Published: June 2020

AbstractLoss-of-function variants in CHST14 cause a dermatan 4-O-sulfotransferase deficiency named musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), resulting in complete depletion of the dermatan sulfate moiety of decorin glycosaminoglycan (GAG) chains, which is replaced by chondroitin sulfate. Recently, we uncovered structural alteration of GAG chains in the skin of patients with mcEDS-CHST14. Here, we conducted the first systematic investigation of Chst14 gene-deleted homozygote (Chst14−/−) mice. We used skin samples of wild-type (Chst14+/+) and Chst14−/− mice. Mechanical fragility of the skin was measured with a tensile test. Pathology was observed using light microscopy, decorin immunohistochemistry and electron microscopy (EM) including cupromeronic blue (CB) staining. Quantification of chondroitin sulfate and dermatan sulfate was performed using enzymatic digestion followed by anion-exchange HPLC. In Chst14−/− mice, skin tensile strength was significantly decreased compared with that in Chst14+/+ mice. EM showed that collagen fibrils were oriented in various directions to form disorganized collagen fibers in the reticular layer. Through EM-based CB staining, rod-shaped linear GAG chains were found to be attached at one end to collagen fibrils and protruded outside of the fibrils, in contrast to them being round and wrapping the collagen fibrils in Chst14+/+ mice. A very low level of dermatan sulfate disaccharides was detected in the skin of Chst14−/− mice by anion-exchange chromatography. Chst14−/− mice, exhibiting similar abnormalities in the GAG structure of decorin and collagen networks in the skin, could be a reasonable model for skin fragility of patients with mcEDS-CHST14, shedding light on the role of dermatan sulfate in maintaining skin strength.
Nonlinear generalization of the monotone single index model
Authors: Kereta Željko , Klock Timo , Naumova Valeriya 
Published: June 2020

Abstract
Single index model is a powerful yet simple model, widely used in statistics, machine learning and other scientific fields. It models the regression function as $g(\left &lt;{a},{x}\right&gt;)$, where $a$ is an unknown index vector and $x$ are the features. This paper deals with a nonlinear generalization of this framework to allow for a regressor that uses multiple index vectors, adapting to local changes in the responses. To do so, we exploit the conditional distribution over function-driven partitions and use linear regression to locally estimate index vectors. We then regress by applying a k-nearest neighbor-type estimator that uses a localized proxy of the geodesic metric. We present theoretical guarantees for estimation of local index vectors and out-of-sample prediction and demonstrate the performance of our method with experiments on synthetic and real-world data sets, comparing it with state-of-the-art methods.
Surveillance of HIV-1 transmitted integrase strand transfer inhibitor resistance in the UK
Authors: Mbisa Jean L , Ledesma Juan , Kirwan Peter , Bibby David F , Manso Carmen , Skingsley Andrew , Murphy Gary , Brown Alison , Dunn David T , Delpech Valerie , Geretti Anna Maria 
Published: June 2020

AbstractBackgroundHIV treatment guidelines have traditionally recommended that all HIV-positive individuals are tested for evidence of drug resistance prior to starting ART. Testing for resistance to reverse transcriptase inhibitors and PIs is well established in routine care. However, testing for integrase strand transfer inhibitor (InSTI) resistance is less consistent.ObjectivesTo inform treatment guidelines by determining the prevalence of InSTI resistance in a national cohort of recently infected individuals.Patients and methodsRecent (within 4 months) HIV-1 infections were identified using a Recent Infection Testing Algorithm of new HIV-1 diagnoses in the UK. Resistance-associated mutations (RAMs) in integrase, protease and reverse transcriptase were detected by ultradeep sequencing, which allows for the sensitive estimation of the frequency of each resistant variant in a sample.ResultsThe analysis included 655 randomly selected individuals (median age = 33 years, 95% male, 83% MSM, 78% white) sampled in the period 2014 to 2016 and determined to have a recent infection. These comprised 320, 138 and 197 samples from 2014, 2015 and 2016, respectively. None of the samples had major InSTI RAMs occurring at high variant frequency (≥20%). A subset (25/640, 3.9%) had major InSTI RAMs occurring only as low-frequency variants (2%–20%). In contrast, 47/588 (8.0%) had major reverse transcriptase inhibitor and PI RAMs at high frequency.ConclusionsBetween 2014 and 2016, major InSTI RAMs were uncommon in adults with recent HIV-1 infection, only occurring as low-frequency variants of doubtful clinical significance. Continued surveillance of newly diagnosed patients for evidence of transmitted InSTI resistance is recommended to inform clinical practice.
Technical note: fluorescein as an indicator of enteric mucosal barrier function in preruminant lambs
Authors: Duff Audrey F , Bielke Lisa R , Relling Alejandro E 
Published: June 2020

Abstract
Increased intestinal permeability can be observed during the physiologic stress response and has been linked to suppression of animal health and performance. Previously published data have shown the efficacy of fluorescein isothiocyanate dextran (FITC-d; 4.17 mg/kg) as a marker of enteric inflammation and mucosal barrier function in multiple species. Fluorescein is a smaller, less expensive alternative molecule possessing similar properties. The following two experiments compared FITC-d and fluorescein as potential indicators of intestinal permeability in pre- and postweaned lambs administered daily intramuscular injections of dexamethasone (Dex; 0.1 mg/kg) for 1 wk. Experiment 1 consisted of five preweaned lambs that were placed in one of two treatment groups: fluorescein with Dex (F+Dex) or fluorescein only (F). On day 7, blood was collected before and 1 h after oral administration of fluorescein (50 mg/kg). Experiment 2 included 12 weaned lambs and four treatment groups: F+Dex, F, FITC-d with Dex (Fd+Dex), and FITC-d only (Fd). On day 7, blood was collected before and 2 h after oral administration of FITC-d (4.17 mg/kg) or fluorescein (50 mg/kg). Plasma fluorescence was reported as the ratio between T1h/T0 or T2h/T0 for experiment 1 or 2, respectively. Experiment 1 showed a significant increase in T1h/T0 ratio of F+Dex relative to F lambs (P = 0.05) indicative of increased leaky gut; however, no differences (P = 0.22) were obtained in experiment 2. Results of these experiments suggest fluorescein may serve as a suitable marker of enteric permeability in preruminant lambs, but not in those with functional rumens.
A new source of high-protein distillers dried grains with solubles (DDGS) has greater digestibility of amino acids and energy, but less digestibility of phosphorus, than de-oiled DDGS when fed to growing pigs
Authors: Cristobal Minoy , Acosta Jessica P , Lee Su A , Stein Hans H 
Published: June 2020

AbstractAbstractThree experiments were conducted to test the hypothesis that standardized ileal digestibility (SID) of amino acids (AA), concentration of metabolizable (ME), and standardized total tract digestibility (STTD) of P in a new source of distillers dried grains with solubles (DDGS; ProCap DDGS) are greater than in conventional de-oiled DDGS. In experiment 1, nine barrows (initial BW: 67.2 ± 6.4 kg) with a T-cannula in the distal ileum were allotted to a triplicated 3 × 3 Latin square design with three diets and three periods for a total of nine replicate pigs per diet. Two diets included ProCap DDGS or de-oiled DDGS as the sole source of crude protein (CP) and AA. An N-free diet was used to determine the basal endogenous losses of CP and AA. Ileal digesta were collected on days 5 and 6 of each period after 4 d of adaptation to diets. Results from experiment 1 indicated that ProCap DDGS contained more CP and AA compared with de-oiled DDGS. The SID of all AA in ProCap DDGS was greater (P &lt; 0.001) compared with de-oiled DDGS with the exception that the SID of Pro was not different between the two sources of DDGS. In experiment 2, 24 growing barrows (initial BW: 32.7 ± 3.1 kg) were housed individually in metabolism crates and used in a randomized complete block design and fed a corn-based diet or two diets containing corn and each source of DDGS with eight replicate pigs per diet. Fecal and urine samples were collected for 4 d after 7 d of adaptation. Results from experiment 2 indicated that concentration of ME in ProCap DDGS was greater (P &lt; 0.05) compared with corn or de-oiled DDGS. In experiment 3, 32 growing barrows (initial BW: 20.2 ± 0.9 kg) were placed in metabolism crates and allotted to four diets with eight pigs per diet using a 2 × 2 factorial treatment arrangement. The de-oiled DDGS and ProCap DDGS were both included in a diet without microbial phytase and a diet with microbial phytase (500 units/kg diet). Pigs were adapted to the diets for 5 d and fecal samples were collected for 4 d. Results from experiment 3 indicated that inclusion of phytase in the diet containing ProCap DDGS increased (P &lt; 0.05) the STTD of P, but addition of phytase to the de-oiled DDGS diet did not increase STTD of P (interaction, P &lt; 0.001), but the STTD of P was greater (P &lt; 0.05) in de-oiled DDGS compared with ProCap DDGS. In conclusion, ProCap DDGS has greater SID of AA and contains more ME, but has reduced STTD of P compared with conventional de-oiled DDGS.
Pollinator-dependent evolution of floral trait combinations in an orchid herb
Authors: Wu Yun , Duan Xu-Yu , Xiang Yong , Weng Shao-Bin , Zhong Jin-Yu , Li Jing , Li Qing-Jun 
Published: June 2020

Abstract

Aims
As one of the most important agents driving floral evolution, pollinators shape the diversity of flowers in angiosperms. However, most previous studies have only quantified pollinators driving the evolution of a single floral trait, and experimental estimates of the potential role of pollinators in shaping the evolution of floral trait associations are relatively rare.

Methods
We experimentally identified and estimated the pollinator-mediated directional and correlational selection on single floral traits and trait combinations across 2 years in an orchid species, Spiranthes sinensis.

Important Findings
Pollinators mediated directional selection for an earlier flowering start date and larger corolla size. Pollinators mediated positive correlational selection on the combinations of floral display traits and negative correlational selection on the combinations of flowering phenology and floral display traits. In addition, the strength of selection differed over time. Our results highlight the potential role of pollinators in driving the evolution of floral trait combinations and suggest that it is necessary to consider floral character functional associations when seeking to understand and predict the evolutionary trajectory of flowers in angiosperms.
TB1: from domestication gene to tool for many trades
Authors: Igartua Ernesto , Contreras-Moreira Bruno , Casas Ana M 
Published: June 2020

This article comments on:Dixon LE, Pasquariello M, Boden SA. 2020. TEOSINTE BRANCHED1 regulates height and stem internode length in bread wheat. Journal of Experimental Botany 71, 4742–4750.
EPIC simulations of Neptune’s dark spots using an active cloud microphysical model
Authors: Hadland Nathan , Sankar Ramanakumar , LeBeau Raymond Paul , Palotai Csaba 
Published: June 2020

ABSTRACT
The Great Dark Spot (GDS-89) observed by Voyager 2 was the first of several large-scale vortices observed on Neptune, the most recent of which was observed in 2018 in the Northern hemisphere (NDS-2018). Ongoing observations of these features are constraining cloud formation, drift, shape oscillations, and other dynamic properties. In order to effectively model these characteristics, an explicit calculation of methane cloud microphysics is needed. Using an updated version of the Explicit Planetary Isentropic Coordinate General Circulation Model (EPIC GCM) and its active cloud microphysics module to account for the condensation of methane, we investigate the evolution of large-scale vortices on Neptune. We model the effect of methane deep abundance and cloud formation on vortex stability and dynamics. In our simulations, the vortex shows a sharp contrast in methane vapour density inside compared to outside the vortex. Methane vapour column density is analogous to optical depth and provides a more consistent tracer to track the vortex, so we use that variable over potential vorticity. We match the meridional drift rate of the GDS and gain an initial insight into the evolution of vortices in the Northern hemisphere, such as the NDS-2018.