bluuebunny/crossref_metadata_2025 huggingface dataset:
Historical floras reflect broad shifts in flowering phenology in response to a warming climate
Authors: Auffret Alistair G.
Published: July 2021

Organisms across the globe are experiencing shifts in phenological events as a result of ongoing climate change. Recently, a variety of novel methods have been applied in order to fill gaps in the phenological data set, in which records often have a patchy temporal, spatial, and/or taxonomic resolution. Here, I tested whether changes in flowering phenology could be detected through the months of flowering stated in 11 guides to the Swedish flora published over a period of 220 yr (1798–2018), focussing on 241 plant species (approximately 8% of the Swedish flora), and accounting for the large increase in herbarium records that have occurred over the same period. Despite the coarse, monthly scale of flowering times reported, historical floras and wildflower guides may hold potential to fill temporal and taxonomic gaps in the plant phenological data set. However, factors other than climate may also influence any apparent phenological shifts over time. Here, flowering was found to start earlier (0.49 d/decade), end later (0.71 d/decade), and carry on longer (1.19 d/decade), with flowering length also associated with increases in the regional temperature anomaly during the 20th century (0.11 months/°C). First flowering occurring earlier in 71% of species (14% showing a significant negative trend), 68% of species ceased flowering later (20%), and 80% flowered for longer (29%). Detected phenological shifts also appeared to be related to species’ flowering seasonality. Later‐flowering species were found to flower later and for longer, while increasing temperatures appeared to drive stronger responses both in flowering onset in early‐flowering species and in flowering cessation in later‐flowering species. Although potential issues exist regarding the largely unknown ways by which authors have determined flowering times and the coarseness of the data, historical floras may be a useful resource in phenological and climate change research, with the potential to both identify and compare the broad climatic responses of a region’s entire flora over long time periods, as well as filling gaps in an otherwise patchy data set.
Conditioned pain modulation and pain sensitivity in functional somatic disorders: The DanFunD study
Authors: Petersen Marie Weinreich , Skovbjerg Sine , Jensen Jens Søndergaard , Wisbech Carstensen Tina Birgitte , Dantoft Thomas Meinertz , Fink Per , Benros Michael Eriksen , Mortensen Erik Lykke , Jørgensen Torben , Gormsen Lise Kirstine
Published: July 2021

Background

Disrupted pain regulation has been proposed as a component in functional somatic disorders (FSD). The objective of this study was to examine a general population sample, encompassing three delimitations of FSD while assessing pain sensitivity and conditioning pain modulation (CPM).

Methods

Pressure pain thresholds (PPTs) at the tibialis and trapezius muscles were recorded at baseline. During cold pressor stimulation of the hand, the tibialis PPTs were re‐assessed and the difference from baseline measures defined the CPM effect. Participants (n = 2,198, 53% females) were randomly selected from the adult Danish population. FSD was established by self‐reported symptom questionnaires.

Results

With a few exceptions, only weak associations were seen between PPTs and CPM in cases with FSD (p > .1). A high PPT was associated with lower odds of having multi‐organ bodily distress syndrome (ORPPT trapezius: 0.66, 95% CI: 0.49–0.88, p = .005), with the symptom profile characterized by all symptoms (ORPPT trapezius: 0.72, 95% CI: 0.58–0.90, p = .003 and ORPPT tibialis: 0.75, 95% CI: 0.62–0.91, p = .004), and with multiple chemical sensitivity (ORPPT trapezius: 0.81, 95% CI: 0.67–0.97, p = .022). High CPM was associated with high odds of having irritable bowel (ORCPM relative: 1.22, 95% CI: 1.04–1.43, p = .013 and ORCPM absolute = 2.66, 95% CI: 1.07–6.45, p = .033).

Conclusion

However, only PPT measured over the trapezius muscle were still significant after correction for multiple testing for the symptom profile characterized by all symptoms. Findings from this study do not support altered pain regulation in questionnaire‐based FSD which is in contrast with the existing presumption. Further epidemiological studies in this field are needed.

Significance

Disrupted pain regulation as measured by abnormal pain thresholds has been hypothesized as a central mechanism in Functional Somatic Disorders (FSD). The hypothesis has been raised in clinical setting where patients presented subjective and objective features of hypersensitivity. The present population‐based study does not support this notion. This points to the importance of further studies into the underlying pathophysiology mechanisms of FSD.
A synopsis of Nimmo’s Croton (Euphorbiaceae: Crotoneae) including an overlooked new species from India
Authors: Dhabak Maniruddin R. , Chaudhari Rushabh B. , Bramhadande Sneha P. , Nandikar Mayur D.
Published: July 2021

Graham’s posthumous publication (Cat. Pl. Bombay, 1839) was completed by Joseph Nimmo, in addition to contributing several new species in it. Croton gibsonianus Nimmo and C. lawianus Nimmo (Euphorbiaceae) were part of this addition, and both were described based on Gibson’s collection from adjoining localities in the Western India. As the diagnosis of the latter species was scant, it was subsequently interpreted in different genera viz. Dimorphocalyx, Trigonostemon and Tritaxis. Due to misinterpretation of the protologue and Gibson’s Croton collection housed at K, the name C. lawianus was wrongly applied to C. gibsonianus by subsequent authors. This inadvertent application of name is corrected here and referred to the hitherto undescribed new species C. chakrabartyi. Our recent collection of C. gibsonianus has turned out to be a rediscovery after 170 years. The nomenclature, description, photographs, and distribution of C. gibsonianus are provided to avoid further taxonomic ambiguity.
Migrating dunes and restinga vegetation in Piauí, northeastern Brazil: The dominance of wild cashew trees (Anacardium occidentale)
Authors: Souza Ruanna Thaimires Brandão , Mayo Simon Joseph , de Andrade Ivanilza Moreira
Published: July 2021

Differences resulting from the passage of migrating dunes in coastal restinga vegetation in Ilha Grande, Piauí, Brazil were quantified, especially differential survival of tree species (wild Anacardium occidentale, cajuí; Byrsonima crassifolia, muricí) and successional floristic reestablishment. A phytosociological study totalling 108 quadrats (1.08 ha) and satellite images of the area from the past 16 years were used to examine the vegetation of the upwind tracks of two mobile dunes. Quadrats were arranged in four transects along the central and marginal residual ridges of each dune. Most species recorded were herbaceous. Satellite images suggest that plants along the central dune track are buried for approximately 14 years. Some evidence for progressive re‐establishment of woody species was found in the central dune track areas, but not in the marginal areas. No successional patterns were observed in the herbs and subshrubs. Most trees occur along the marginal (longitudinal) residual ridges. Anacardium occidentale and Byrsonima crassifolia predominated among tree species. Anacardium occidentale predominated in abundance, cover, frequency and basal area and survives partial burial when located at the dune track margins. The passage of migratory dunes is important for long term maintenance of the economically important cajuí and muricí populations of Ilha Grande.
Black clayey soil (Vertisol) in the Lerma valley, Michoacán, North‐Central Mexico: A hint of the environmental and cultural changes during the Late Classic period?
Authors: Solleiro‐Rebolledo Elizabeth , Darras Véronique , Sedov Sergey , Vargas‐Rodríguez Daniela , García‐Zeferino Thania , Leonard Daniel
Published: July 2021

Catastrophic events (climatic, tectonic, volcanic, etc.) frequently cause geomorphological instability, which interrupts normal pedogenesis and switches the processes of surface erosion and/or sedimentation. These processes have an effect on the distribution of ancient settlements and can be the cause of the abandonment of cities. In the Lerma Valley, particularly in the Tres Mezquites area, surveys and extensive excavations have been conducted to estimate the nature and density of pre‐Hispanic settlements on the alluvial plain and in the piedmonts. Most of the archaeological structures are covered by dark clayey soils (Vertisols). This includes the PA3_El Pitayo site, where an accumulation of black earth has been detected on the floors and walls of a collapsed building. We have studied in detail the Vertisols and the black earth around the site to establish to what extent this dark earth is an in situ product of the soil‐forming factors, or if its accumulation is due to erosion/sedimentation processes, which could affect the occupation of the site, or the result of anthropic activity for leveling. The Vertisols and the dark earth are characterized by different means (physical, chemical, micromorphology, clay mineralogy, and radiocarbon dating). The results show that both the Vertisols and the black earth are very clayey, with angular blocky structures and slickensides (properties that are typical of vertic soils), and smectite as the main clay mineral. Besides smectite, under the microscope, a high amount of fresh volcanic glass is identified, suggesting that volcanism could be responsible for the abandonment of the study site. However, there are no known volcanic events related to the age of abandonment. As a consequence, we consider that landslides triggered by seismic activity/climatic events impacted the settlement.
Tele‐antimicrobial stewardship programs: A review of the literature and the role of the pharmacist
Authors: Andrzejewski Christina , McCreary Erin K. , Khadem Tina , Abdel‐Massih Rima C. , Bariola J. Ryan
Published: July 2021

Antimicrobial overuse and multidrug‐resistant pathogens are growing problems throughout the United States, yet most counties in the United States lack access to infectious diseases (ID) expertise. Developing an effective antimicrobial stewardship program (ASP) is challenging for many health care institutions, especially rural, community, and critical access hospitals with limited access to specialty care. Pharmacists are instrumental for the success of ASPs and pharmacy expertise is a requirement to meet federal ASP standards. Antimicrobial stewardship guidelines suggest telehealth consultation as an acceptable alternative to in‐person availability of an ID physician‐pharmacist team and encourage facilities to consider creative solutions for optimizing antimicrobial use. As a result, an understanding of successful telemedicine and tele‐ASP (TASP) models as a sustainable option is crucial. Data on existing TASP models, the role of clinical pharmacy services in TASPs, and future directions are herein described. Existing data on TASP are organized into three main categories of fully remote, integrated, or collaborative TASP models. TASPs may be led by remote ID physicians and/or ID‐trained clinical pharmacists within an affiliated health system or from an unaffiliated private practice, health system, or private telehealth entity. The on‐site stewardship pharmacist champion has a vital role in the success of many of the TASP models described by building trusting relationships with prescribers and key stakeholders, facilitating uptake of interventions and acceptance of the TASP, and ensuring timely therapy changes for patients. Future targets for TASP research should include TASP efforts in critical access hospitals and nonacute settings, the specific role of technology and clinical decision support software tools in TASP to improve and enhance pharmacist impact, and further descriptions of TASP models that improve patient‐centered outcomes.
A novel substrate based on electrospun polyurethane nanofibers and electrosprayed polyvinyl alcohol microparticles for recombinant human erythropoietin delivery
Authors: Ghanbari Elmira , Solouk Atefeh , Mehdinavaz Aghdam Rouhollah , Haghbin Nazarpak Masoumeh , Ahmadi Tafti Seyed Hossein
Published: July 2021

After myocardial infarction caused by a heart attack, endothelial cells need to be preserved in order to regenerate new capillaries. Moreover, sufficient mechanical support is necessary for the infarcted myocardium to pump the blood. Herein, we designed a novel substrate containing polyurethane (PU) nanofibrous layers and recombinant human erythropoietin (rhEPO)‐loaded microparticles for both controlled releases of rhEPO and mechanical support of myocardium. In this system, the single‐layer (SL) and double‐layer (DL) PU nanofibers were electrospun, and then microparticles with different rhEPO:polyvinyl alcohol (PVA) ratios were electrosprayed on the layers. The in vitro release behavior of rhEPO from SL substrates was not satisfactory, and then the study focused on DL patches in which the release profile was in accordance with Korsmeyer–Peppas model. The release exponent of 0.89 for the DL PU/120PVA:1rhEPO represented zero‐order release. The results inferred that these substrates possessed highly tailored mechanical properties; Young's modulus and ultimate tensile strength of the substrates were 74–172 kPa and 7.4–9.9 MPa, respectively. The rhEPO release from the substrates was leading to the proper adhesion of endothelial cells and more than 95% cell viability. The results indicated that the patch of elastic nanofibers and microparticles offered a potential substrate for simultaneous rhEPO delivery to endothelial cells and also mechanically supporting the infarcted myocardium.
Retinoic acid‐conjugated chitosan/manganese porphyrin ionic‐complex nanoparticles for improved T1 contrast MR imaging of hepatic fibrosis
Authors: Tran Hoa Phuong , Jiang Yixin , Nguyen Phuong Hong , Kim Jung Joo , Yang Su‐Geun
Published: July 2021

Noninvasive and precise diagnosis of hepatic fibrosis is very important for the preventive therapeutic regimen of hepatic cirrhosis and cancer. In this study, we fabricated T1 contrast Mn‐porphyrin (MnTPPS4)/retinoic acid‐chitosan ionic‐complex nanoparticles (MRC NPs). The functional properties of MRC NPs were evaluated via transmission electron microscopy (TEM) imaging, release study, cytotoxicity assay, hepatocyte‐specific uptake assay, and magnetic resonance (MR) imaging study. TEM images confirmed the typical structure of an ionic‐complex NPs with around 100–200 nm of diameter. MnTPPS4 is released from MRC NPs for up to 24 hr in controlled pattern which implies that more reliable and convenient hepatic MR imaging is possible using of MRC NPs in clinical practice. Hepatocytes uptake assay proved retinoic acid‐specific targeting of MRC NPs. The same results were observed in animal pharmacokinetic studies. In vitro MR phantom study, MRC NPs showed an increased T1 relaxivity (r1 = 6.772 mM−1 s−1) in comparison with 3.242 mM−1 s−1 of MnTPPS4. The result was confirmed again in vivo MR imaging studies. Taken together, MRC NPs displayed a potential for noninvasive diagnostic T1 MR imaging of hepatic fibrosis with improved target specificity and prolonged MR imaging time window.
One‐step simple green method to prepare carbon‐doped graphitic carbon nitride nanosheets for boosting visible‐light photocatalytic degradation of tetracycline
Authors: Shi Yuxing , Li Lingling , Xu Zheng , Sun Haoran , Guo Feng , Shi Weilong
Published: July 2021

BACKGROUND

Graphitic carbon nitride (g‐C3N4) is a rising star amongst semiconductor photocatalysts. However, rapid recombination of electron–hole pairs and poor visible‐light absorption seriously limit its practical applications in photocatalysis.

RESULTS

A carbon (C)‐doped g‐C3N4 (C‐CN) photocatalyst was prepared by a simple one‐step thermal polymerization for the degradation of high‐concentration tetracycline (TC) under visible light irradiation. In particular, the C‐CN‐5 sample had the best TC (30 mg L–1) degradation effect, reaching 77% within 60 min.

CONCLUSION

The photocatalytic performance of C‐CN was enhanced for two main reasons: (i) the doping of C enhances the visible light absorption capacity of g‐C3N4 and (ii) introduction of C promotes higher charge separation efficiency of g‐C3N4. In addition, the reduced toxicity of degraded products of TC over as‐prepared C‐CN photocatalyst was confirmed by a bean sprout cultivation experiment. This work provides a useful design idea for the synthesis of C‐doped g‐C3N4 through a simple and green route. © 2021 Society of Chemical Industry (SCI).
Pharmacist intervention lowers HgbA1c in diabetic patients regardless of HIV status
Authors: Nelson Noelle E. , Hluhanich Rebecca M. , Wilson Machelle , Fine Jeffrey
Published: July 2021

Background

Despite the higher prevalence of type 2 diabetes mellitus (T2DM) co‐morbidity in patients with human immunodeficiency virus (HIV), little research has been done into the ability to meet glycemic targets in HIV‐positive patients versus HIV‐negative patients. More studies are needed to address whether the management of T2DM in patients with co‐morbid HIV is more complex in terms of reaching guideline‐directed glycemic target endpoints compared to the management of T2DM in patients without HIV. The purpose of this study was to evaluate the difference in glycemic control between HIV‐positive and HIV‐negative patients when managed by a clinical pharmacist in a federally qualified health center (FQHC).

Aim

The aim of this research was to compare glycaemic control in HIV‐positive patients on antiretroviral therapy to HIV‐negative patients following pharmacist interventions.

Methods

This retrospective observational cohort study conducted at a FQHC included adults with type II diabetes mellitus who attended at least two clinical pharmacy appointments between 1 January 2018 and 31 July 2019. Exclusion criteria included missing pre‐ or post‐haemoglobin A1c (HgbA1c) values, type 1 diabetes, pregnancy, breastfeeding, deceased, or untreated HIV. The primary endpoint was change in HgbA1c from baseline to month 3. Secondary endpoints were change in HgbA1c at 6, 9, and 12 months, and time to goal. Additional endpoints included changes in number of anti‐diabetic agents, blood pressure, body mass index, hypoglycaemic events, percent of patients on a sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitor or glucagon‐like peptide (GLP‐1) agonist. This study was exempt from the University of California, Davis Institutional Review Board as a continuous quality improvement study. Seventy‐eight patients were included, 17 of whom were HIV‐positive.

Results

At 3 months, HgbA1c was reduced by −1.7% and –1.2% (P = 0.31) for HIV‐positive and ‐negative patients, respectively. In the pooled cohort, HgbA1c was reduced from baseline at all time points, and 24% of patients achieved HgbA1c below 7.0%. The number of antidiabetic medications remained unchanged or was decreased in 60% of patients.

Conclusion

The study demonstrated clinically important HgbA1c reductions without increasing the medication burden in most patients. There was no significant difference in glycaemic management between HIV‐positive and HIV‐negative patients.
A novel ternary approach to quantitatively assess the reactivity of nitroaniline regioisomers by investigation of rapid iodination kinetics using hydrodynamic voltammetry, reduction propensities from polarography, and binding affinities from molecular docking simulations
Authors: Borkar Vitthal T.
Published: July 2021

A novel ternary approach to assess the reactivity of nitroaniline regioisomers on a quantitative scaffold has been manifested on the basis of three complementary tenets: kinetics, polarography, and molecular docking. Data from investigation of rapid iodination kinetics of nitroaniline regioisomers by hydrodynamic voltammetry in aqueous medium, reduction propensities of these regioisomers from polarography, and their binding affinities with hypoxanthine‐guanine phophoribosyltransferase (HPRT1) from molecular docking simulations lead to inferences regarding their reactivity that agree in entirety. The experimentally determined magnitudes of the specific reaction rates, energies of activation, collision frequencies, entropies of activation from kinetic studies, and reduction propensities of nitroaniline regioisomers from polarograms when complemented with in silico binding energies of these regioisomer ligands with the receptor enzyme, assess their relative reactivities in unison on a quantitative scaffold. This novel ternary approach unambiguously assesses the reactivity of the regioisomers of nitroaniline as 4‐nitroaniline > 2‐nitroaniline > 3‐nitroaniline.
Kinetic study of the carbonation of epoxidized fatty acid methyl ester catalyzed over heterogeneous catalyst HBimCl‐NbCl5/HCMC
Authors: Cai Xiaoshuang , Tolvanen Pasi , Virtanen Pasi , Eränen Kari , Rahkila Jani , Leveneur Sébastien , Salmi Tapio
Published: July 2021

The carbonation of epoxidized vegetable oils is a crucial step in the preparation of nonisocyanate polyurethane. Several research groups have screened homogeneous catalysts such as tetra‐n‐butylammonium bromide for this reaction, but the research devoted to the use of heterogeneous catalysts and on the application of kinetic modeling is rare. Hence, to develop this process on an industrial scale, an appropriate heterogeneous catalyst should be found and a kinetic model developed. A catalyst consisting of an ionic liquid supported on carboxymethyl cellulose has been proved to be a suitable heterogeneous catalyst for this carbonation reaction. A catalyst based on 1‐hydroxypropyl‐3‐n‐butylimidazolium chloride and niobium(V) chloride supported on protonated carboxymethyl cellulose (HBimCl‐NbCl5/HCMC) was synthesized and tested for the carbonation of epoxidized fatty acid methyl ester. Effects of the catalyst particle size, agitation speed, catalyst loading, and reaction temperature on the reaction kinetics were investigated. The carbonation reaction proceeded efficiently at a temperature of 443.15 K, agitation speed of 500 rpm, and using native catalyst particles with a median diameter of 652 μm. A kinetic model was developed to simulate the conversion of the epoxide group with time.
Lp‐estimates of the Stokes resolvent with nonhomogeneous Dirichlet boundary conditions in 3D exterior domains
Authors: Deuring Paul
Published: July 2021

The article deals with the homogeneous Stokes resolvent system in a 3D exterior domain, under inhomogeneous Dirichet boundary conditions. Solutions to this boundary value problem are estimated in Lp‐norms, with the bounds in these estimates depending on the absolute value of the resolvent parameter λ in an explicit way. Two types of boundary data are considered, that is, Lp‐ and W2 − 1/p, p‐data. It is shown in particular that the Lp‐norm of the velocity outside a vicinity of the boundary, after subtraction of the gradient of a certain harmonic function, is bounded by a constant times |λ|−1 ‖b‖p. This estimate carries over to the Oseen resolvent system, leading to a result which has applications in the theory of spatial asymptotics of solutions to the 3D time‐dependent Navier‐Stokes system with Oseen term.
Deep learning‐based forward and cross‐scatter correction in dual‐source CT
Authors: Erath Julien , Vöth Tim , Maier Joscha , Fournié Eric , Petersilka Martin , Stierstorfer Karl , Kachelrieß Marc
Published: July 2021

Purpose

Dual‐source computed tomography (DSCT) uses two source‐detector pairs offset by about 90°. In addition to the well‐known forward scatter, a special issue in DSCT is cross‐scattered radiation from X‐ray tube A detected in the detector of system B and vice versa. This effect can lead to artifacts and reduction of the contrast‐to‐noise ratio of the images. The purpose of this work is to present and evaluate different deep learning‐based methods for scatter correction in DSCT.

Methods

We present different neural network‐based methods for forward and cross‐scatter correction in DSCT. These deep scatter estimation (DSE) methods mainly differ in the input and output information that is provided for training and inference and in whether they operate on two‐dimensional (2D) or on three‐dimensional (3D) data. The networks are trained and validated with scatter distributions obtained by our in‐house Monte Carlo simulation. The simulated geometry is adapted to a realistic clinical setup.

Results

All DSE approaches reduce scatter‐induced artifacts and lead to superior results than the measurement‐based scatter correction. Forward scatter, under the presence of cross‐scatter, is best estimated either by our network that uses the current projection and a couple of neighboring views (fDSE 2D few views) or by our 3D network that processes all projections simultaneously (fDSE 3D). Cross‐scatter, under the presence of forward scatter, is best estimated using xSSE XDSE 2D, with xSSE referring to a quick single scatter estimate of cross scatter, or by xDSE 3D that uses all projections simultaneously. By using our proposed networks, the total scatter error in dual could be reduced from about 18 HU to approximately 3 HU.

Conclusions

Deep learning‐based scatter correction can reduce scatter artifacts in DSCT. To achieve more accurate cross‐scatter estimations, the use of a cross‐scatter approximation improves the results. Also, the ability to leverage across different projection angles improves the precision of the algorithm.
Unsupervised learning of reference bony shapes for orthognathic surgical planning with a surface deformation network
Authors: Xiao Deqiang , Deng Hannah , Lian Chunfeng , Kuang Tianshu , Liu Qin , Ma Lei , Lang Yankun , Chen Xu , Kim Daeseung , Gateno Jaime , Shen Steve Guofang , Shen Dinggang , Yap Pew‐Thian , Xia James J.
Published: July 2021

Purpose

The purpose of this study was to reduce the experience dependence during the orthognathic surgical planning that involves virtually simulating the corrective procedure for jaw deformities.

Methods

We introduce a geometric deep learning framework for generating reference facial bone shape models for objective guidance in surgical planning. First, we propose a surface deformation network to warp a patient's deformed bone to a set of normal bones for generating a dictionary of patient‐specific normal bony shapes. Subsequently, sparse representation learning is employed to estimate a reference shape model based on the dictionary.

Results

We evaluated our method on a clinical dataset containing 24 patients, and compared it with a state‐of‐the‐art method that relies on landmark‐based sparse representation. Our method yields significantly higher accuracy than the competing method for estimating normal jaws and maintains the midfaces of patients’ facial bones as well as the conventional way.

Conclusions

Experimental results indicate that our method generates accurate shape models that meet clinical standards.
SuperDTI: Ultrafast DTI and fiber tractography with deep learning
Authors: Li Hongyu , Liang Zifei , Zhang Chaoyi , Liu Ruiying , Li Jing , Zhang Weihong , Liang Dong , Shen Bowen , Zhang Xiaoliang , Ge Yulin , Zhang Jiangyang , Ying Leslie
Published: July 2021

Purpose

To develop a deep learning–based reconstruction framework for ultrafast and robust diffusion tensor imaging and fiber tractography.

Methods

SuperDTI was developed to learn the nonlinear relationship between DWIs and the corresponding diffusion tensor parameter maps. It bypasses the tensor fitting procedure, which is highly susceptible to noises and motions in DWIs. The network was trained and tested using data sets from the Human Connectome Project and patients with ischemic stroke. Results from SuperDTI were compared against widely used methods for tensor parameter estimation and fiber tracking.

Results

Using training and testing data acquired using the same protocol and scanner, SuperDTI was shown to generate fractional anisotropy and mean diffusivity maps, as well as fiber tractography, from as few as six raw DWIs, with a quantification error of less than 5% in all white‐matter and gray‐matter regions of interest. It was robust to noises and motions in the testing data. Furthermore, the network trained using healthy volunteer data showed no apparent reduction in lesion detectability when directly applied to stroke patient data.

Conclusions

Our results demonstrate the feasibility of superfast DTI and fiber tractography using deep learning with as few as six DWIs directly, bypassing tensor fitting. Such a significant reduction in scan time may allow the inclusion of DTI into the clinical routine for many potential applications.
TROIKA‐1: A double‐blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU‐Herceptin® and US‐Herceptin® in healthy male subjects
Authors: Demarchi Martin , Coliat Pierre , Mclendon Kristi , Chung Shii Hii Jocelyn , Feyaerts Peggy , Ang Felicia , Jaison Litha , Deforce Filip , Derde Marie Paule , Kim Michael Jinwoo , Park Lisa Soyeon , Detappe Alexandre , Pivot Xavier
Published: July 2021

Prestige Biopharma Ltd (Singapore) has developed HD201, a proposed biosimilar to reference product trastuzumab. As a part of the stepwise approach to ensure comparability between the biosimilar candidate and the reference medicinal product, a phase I study in healthy subjects was conducted to demonstrate the pharmacokinetic (PK) equivalence (NCT03776240). The primary objective of the study was to demonstrate (PK) equivalence of HD201, EU‐Herceptin®, and US‐Herceptin® given at 6 mg/kg as a 90‐min i.v. infusion to healthy male subjects. A pairwise comparisons based on the primary endpoint AUC0–inf and secondary PK endpoints, AUC0–last and Cmax were undertaken. PK equivalence was to be concluded if the 90% confidence interval (CI) for the ratio of geometric means for each criterion were within the equivalence margin of 80% to 125%. Secondary objectives included assessment of other PK parameters, safety, tolerability, and immunogenicity in the three arms. A total of 105 healthy male subjects (35/treatment) were randomized in this study. The 90% CI for the ratios of AUC0–inf, Cmax and AUC0–last, were within 80%–125% for the comparisons of HD201 to EU‐Herceptin® or US‐Herceptin® and EU‐Herceptin® to US‐Herceptin®. The frequency of subjects with TEAEs of special interest was slightly lower in the HD201 group (20.0%) compared to the other treatment groups (EU‐Herceptin®: 34.3%; US‐Herceptin®: 31.4%). Only 1 subject (EU‐Herceptin® group) developed anti‐drug antibodies prior to dosing. Overall, HD201 demonstrates PK similarity to both EU‐Herceptin® and US‐Herceptin®. The three study drugs also demonstrated similar safety profiles.
Sample size calculation for recurrent event data with additive rates models
Authors: Zhu Liang , Li Yimei , Tang Yongqiang , Shen Liji , Onar‐Thomas Arzu , Sun Jianguo
Published: July 2021

This paper discusses the design of clinical trials where the primary endpoint is a recurrent event with the focus on the sample size calculation. For the problem, a few methods have been proposed but most of them assume a multiplicative treatment effect on the rate or mean number of recurrent events. In practice, sometimes the additive treatment effect may be preferred or more appealing because of its intuitive clinical meaning and straightforward interpretation compared to a multiplicative relationship. In this paper, new methods are presented and investigated for the sample size calculation based on the additive rates model for superiority, non‐inferiority, and equivalence trials. They allow for flexible baseline rate function, staggered entry, random dropout, and overdispersion in event numbers, and simulation studies show that the proposed methods perform well in a variety of settings. We also illustrate how to use the proposed methods to design a clinical trial based on real data.
Interfacial Protection Engineering of Sodium Nanoparticles toward Dendrite‐Free and Long‐Life Sodium Metal Battery
Authors: You Shunzhang , Ye Minghui , Xiong Jiaming , Hu Zuyang , Zhang Yufei , Yang Yang , Li Cheng Chao
Published: July 2021

The instability of interfacial solid‐electrolyte interphase (SEI) layer of metallic sodium (Na) anode during cycles results in the rapid capacity decay of sodium metal batteries (SMBs). Herein, the concept of interfacial protection engineering of Na nanoparticles (Na‐NPs) is proposed first to achieve stable, dendrite‐free, and long‐life SMB. Employing an ion‐exchange strategy, conformal Sn‐Na alloy‐SEI on the interface of Na‐NPs is constructed, forming Sn@Na‐NPs. The stable alloy‐based SEI layer possesses the following three advantages: 1) significantly enhancing the transport dynamics of Na+ ions and electrons; 2) enabling the well‐distributed deposition of Na+ ions to avoid the growth of dendrites; and 3) protecting the Sn@Na‐NPs anode from the attack of electrolyte, thereby reducing the parasitic reaction and boosting the Coulombic efficiency of SMBs. Because of these virtues, the symmetric Sn@Na‐NPs cell shows an ultralow voltage hysteresis of 0.54 V at 10 mA cm−2 after 600 h. Paired with the Na3V2(PO4)2O2F (NaVPF) cathode, the NaVPF‐Sn@Na‐NPs full cell exhibits an initial discharge capacity of 89.2 mAh g−1 at 1 C and a high capacity retention of 81.6% after 600 cycles.
Second Floor of Flatland: Epitaxial Growth of Graphene on Hexagonal Boron Nitride
Authors: Mehler Alexander , Néel Nicolas , Voloshina Elena , Dedkov Yuriy , Kröger Jörg
Published: July 2021

In the studies presented here, the subsequent growth of graphene on hexagonal boron nitride (h‐BN) is achieved by the thermal decomposition of molecular precursors and the catalytic assistance of metal substrates. The epitaxial growth of h‐BN on Pt(111) is followed by the deposition of a temporary Pt film that acts as a catalyst for the fabrication of the graphene sheet. After intercalation of the intermediate Pt film underneath the boron‐nitride mesh, graphene resides on top of h‐BN. Scanning tunneling microscopy and density functional calculations reveal that the moiré pattern of the van‐der‐Waals‐coupled double layer is due to the interface of h‐BN and Pt(111). While on Pt(111) the graphene honeycomb unit cells uniformly appear as depressions using a clean metal tip for imaging, on h‐BN they are arranged in a honeycomb lattice where six protruding unit cells enframe a topographically dark cell. This superstructure is most clearly observed at small probe–surface distances. Spatially resolved inelastic electron tunneling spectroscopy enables the detection of a previously predicted acoustic hybrid phonon of the stacked materials. Its’ spectroscopic signature is visible in surface regions where the single graphene sheet on Pt(111) transitions into the top layer of the stacking.
Deep‐learning power and perspectives for genomic selection
Authors: Montesinos‐López Osval Antonio , Montesinos‐López Abelardo , Hernandez‐Suarez Carlos Moises , Barrón‐López José Alberto , Crossa José
Published: July 2021

Deep learning (DL) is revolutionizing the development of artificial intelligence systems. For example, before 2015, humans were better than artificial machines at classifying images and solving many problems of computer vision (related to object localization and detection using images), but nowadays, artificial machines have surpassed the ability of humans in this specific task. This is just one example of how the application of these models has surpassed human abilities and the performance of other machine‐learning algorithms. For this reason, DL models have been adopted for genomic selection (GS). In this article we provide insight about the power of DL in solving complex prediction tasks and how combining GS and DL models can accelerate the revolution provoked by GS methodology in plant breeding. Furthermore, we will mention some trends of DL methods, emphasizing some areas of opportunity to really exploit the DL methodology in GS; however, we are aware that considerable research is required to be able not only to use the existing DL in conjunction with GS, but to adapt and develop DL methods that take the peculiarities of breeding inputs and GS into consideration.
Inhibition of NAE‐dependent protein hyper‐NEDDylation in cystic cholangiocytes halts cystogenesis in experimental models of polycystic liver disease
Authors: Lee‐Law Pui Y. , Olaizola Paula , Caballero‐Camino Francisco J. , Izquierdo‐Sanchez Laura , Rodrigues Pedro M. , Perugorria Maria J. , Azkargorta Mikel , Elortza Felix , Martinez‐Chantar Maria L. , Aspichueta Patricia , Marzioni Marco , Bujanda Luis , Drenth Joost P. H. , Banales Jesus M.
Published: July 2021

Background

Polycystic liver diseases (PLDs) are genetic inherited disorders characterized by the progressive growth of numerous intrahepatic biliary cysts, which are the main cause of morbidity. Previous studies revealed that cystic cholangiocytes are characterized by endoplasmic reticulum stress and aberrant posttranslational modification (PTM) of proteins, in particular hyper‐SUMOylation, that promote PLD pathobiology. Protein NEDDylation is a newly characterized PTM that modulates a plethora of biological processes and its dysregulation is associated with the development and progression of several human diseases. However, the role of NEDDylation in PLD remains elusive.

Objective

To explore the role of protein NEDDylation in PLD and its potential therapeutic regulatory value.

Methods

Levels and functional effects of NEDDylation, including response to Pevonedistat (first‐in‐class selective inhibitor of the NEDDylation E1 enzyme NAE), were assessed in vitro, in vivo, and/or in patients with PLD. NEDDylated protein levels in normal and cystic human cholangiocytes were assessed by immunoprecipitation, and the proteomic profile was further analyzed by mass spectrometry.

Results and Conclusion

The genes involved in the NEDDylation pathway were found overexpressed (mRNA) in polycystic human and rat liver tissue, as well as in cystic cholangiocytes in culture, compared to controls. Elevated levels of NEDDylated proteins were further confirmed in cystic cholangiocytes in vitro, which diminished under Pevonedistat incubation. Pevonedistat promoted apoptotic cell death and reduced proliferation in cystic cholangiocytes in vitro. Comparative proteomic profiling of NEDD8‐immunoprecipitated proteins between normal and cystic cholangiocytes in culture reported candidate proteins involved in cystogenesis, mostly associated with protein biogenesis and quality control. All these data indicate that cystic cholangiocytes display increased protein NEDDylation, contributing to cell survival and proliferation, ultimately supporting hepatic cystogenesis. Targeting of protein hyper‐NEDDylation in cystic cholangiocytes inhibits cystogenesis in experimental models, representing a novel therapeutic opportunity in PLD.
Contingent screening in stratification of pregnancy care based on risk of pre‐eclampsia at 19–24 weeks' gestation
Authors: Litwinska M. , Litwinska E. , Bouariu A. , Syngelaki A. , Wright A. , Nicolaides K. H.
Published: July 2021

Objective

To explore the possibility of carrying out routine screening for pre‐eclampsia (PE) with delivery at < 28, < 32, < 36 weeks' gestation by maternal factors, uterine artery pulsatility index (UtA‐PI) and mean arterial pressure (MAP) in all pregnancies and reserving measurements of placental growth factor (PlGF) and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) for only a subgroup of the population.

Methods

This was a prospective observational study in two UK maternity hospitals involving women with singleton pregnancy attending for routine assessment at 19–24 weeks' gestation. The improvement in performance of screening for PE, at fixed risk cut‐offs, by the addition of serum PlGF and sFlt‐1 to screening by maternal factors, UtA‐PI and MAP, was estimated. We examined a policy of contingent screening in which biochemical testing was reserved for only a subgroup of the population. The main outcome measures were the additional contribution of PlGF and sFlt‐1 to the performance of screening for PE and the proportion of the population requiring measurement of PlGF and sFlt‐1 for maximum performance of screening.

Results

The study population included 37 886 singleton pregnancies. At each risk cut‐off, the highest detection rates for delivery with PE and the lowest screen‐positive rates were achieved in screening with maternal factors, UtA‐PI, MAP, PlGF and sFlt‐1. The maximum performance by such screening was also achieved by contingent screening in which PlGF and sFlt‐1 were measured in only about 40% of the population.

Conclusion

The performance of screening for PE by a combination of maternal factors, UtA‐PI and MAP is improved by measurement of PlGF and sFlt‐1 in about 40% of the population. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Peripartum echocardiographic changes in women with hypertensive disorders of pregnancy
Authors: Giorgione V. , O'Driscoll J. , Coutinho C. M. , Di Fabrizio C. , Sharma R. , Khalil A. , Thilaganathan B.
Published: July 2021

Objective

Hypertensive disorders of pregnancy (HDP) are associated with significant myocardial dysfunction on echocardiography. The impact of hemodynamic changes related to volume redistribution following delivery on myocardial function in women with HDP has not been evaluated systematically. The aim of this study was to compare echocardiographic findings immediately before and after delivery in women with HDP.

Methods

This was a prospective longitudinal study including 30 women with a diagnosis of HDP who underwent two consecutive transthoracic echocardiographic (TTE) examinations, before delivery and in the early postpartum period. Paired comparisons of the findings from the two assessments were performed.

Results

Left‐ventricular (LV) concentric remodeling or hypertrophy was detected in 21 (70%) patients. There was no significant difference in cardiac morphology indices such as LV mass index (78.9 ± 16.3 g/m2 vs 77.9 ± 15.4 g/m2; P = 0.611) or relative wall thickness (0.45 ± 0.1 vs 0.44 ± 0.1; P = 0.453) before vs after delivery. LV diastolic function did not demonstrate any peripartum variation, with similar left‐atrial volume (52.4 ± 15.3 mL vs 51.0 ± 15.6 mL; P = 0.433), lateral E′ (0.12 ± 0.03 m/s vs 0.12 ± 0.03 m/s; P = 0.307) and E/E′ ratio (7.9 ± 2.2 vs 7.9 ± 1.7; P = 0.934) before vs after delivery. Systolic function indices, such as LV ejection fraction (57.5 ± 3.4% vs 56.4 ± 2.1%; P = 0.295) and global longitudinal strain (−15.3 ± 2.6% vs −15.1 ± 3.1%; P = 0.582), also remained unchanged between before vs after delivery.

Conclusions

Maternal hemodynamic changes associated with delivery did not influence significantly peripartum TTE indices in women with HDP. Suboptimal maternal echocardiographic findings in HDP are likely to be the consequence of chronic pregnancy cardiovascular load changes or pre‐existing maternal cardiovascular impairment. Severity and persistence of myocardial dysfunction in the postpartum period may be related to the long‐term maternal cardiovascular disease legacy of HDP. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Highly resistant Mycobacterium abscessus subsp. abscessus infection in a Swiss cat
Authors: Peterhans Sophie , Grest Paula , Friedel Ute , Roosje Petra , Ghielmetti Giovanni
Published: July 2021

A 2‐year‐old European shorthair cat was presented with a nonhealing skin lesion on the right abdominal wall. Repeated surgical excision and antimicrobial treatment with cefovecin, clindamycin, and trimethoprim‐sulfamethoxazole did not lead to clinical improvement. Histopathology of the skin lesion showed pyogranulomatous dermatitis and panniculitis. Definitive diagnosis was made by mycobacterial culture and rpoB sequencing, revealing Mycobacterium abscessus subsp. abscessus. To the authors’ knowledge, this is the first report of Mycobacterium abscessus subsp. abscessus infection in a cat in Switzerland and the second case in Europe. The isolated strain carried a functional erm(41) gene that confers inducible macrolide resistance. Further phenotypic resistances to doxycycline, minocycline, and imipenem were detected, resulting in little chance of successful antimicrobial treatment. Mycobacterium abscessus subsp. abscessus is an emerging pathogen in human medicine and poses a non‐negligible zoonotic risk for the owners of the cat.
Knowledge‐guided machine learning for improving daily soil temperature prediction across the United States
Authors: Abimbola Olufemi P. , Meyer George E. , Mittelstet Aaron R. , Rudnick Daran R. , Franz Trenton E.
Published: July 2021

Data‐driven models used for predicting soil temperature usually have increasing errors with increasing depth. By exploring the integration of knowledge‐based and machine learning approaches, this study used a novel transformation of meteorological variables to increase prediction accuracy of soil temperature with increasing soil depth. Using datasets for two soil textures (silty clay loam and loamy coarse sand) at two locations with different climates, predictive models were developed for five depths (5, 10, 20, 50, and 100 cm) as a function of meteorological features using an adaptive neuro‐fuzzy inference system (ANFIS). For each depth, soil temperature was predicted with nontransformation (NT), autocorrelation (AC), moving average (MA), and a combination of transformations (NT‐ACMA) of meteorological features. Across all depths, the predictive accuracy of NT‐ACMA models was significantly higher than that of NT, AC, and MA models for both soil textures (R2 = .99, RMSE = 1 °C for silty clay loam; R2 = .99, RMSE = 1.2 °C for loamy coarse sand), with increasing prediction accuracy as soil depth increases. Results for different soil textures and climates in 11 locations across the contiguous United States show that, except for 100‐cm depth, there seems to be significant positive linear relationships between the best moving average and the solar inclination. This makes our NT‐ACMA technique transferable to any location in the contiguous United States irrespective of the location, climate, and soil texture. We conclude that integrating lag times and moving averages of meteorological features can lead to better prediction of soil temperature at different soil depths.
An exact solution of a fluid‐structure interaction problem
Authors: Marušić‐Paloka Eduard
Published: July 2021

We construct an exact solution for a stationary fluid flow through a channel with upper wall attached to an elastic spring. The position of the upper wall is determined from the interaction between the fluid and the wall. It is displacement computed from a quartic equation that can be solved by radicals and the solution is proved to be physically reasonable.