bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of genetic variants in IL‐1B and its interaction with the predisposition of osteoporosis in the northwestern Chinese Han population
Authors: He Zhiyi , Sun Yao , Wu Jiamin , Xiong Zichao , Zhang Shanshan , Liu Jianfeng , Liu Yuanwei , Li Haiyue , Jin Tianbo , Yang Yonghui , Yang Shuya
Published: May 2020

Background

Interleukin (IL)‐1β stimulates the proliferation and differentiation of osteoclast precursors into mature osteoclasts. IL‐1B polymorphisms may influence the gene and protein expression of IL‐1β. The present study aimed to investigate the association of IL‐1B variants (rs2853550, rs1143643, rs3136558, rs1143630, rs1143627, rs16944 and rs1143623) and their interaction with osteoporosis risk among the northwestern Chinese Han population.

Methods

AN Agena MassARRAY system (Agena, San Diego, CA, USA) was employed for genotyping in 594 osteoporosis patients and 599 healthy controls. The possible association between IL‐1B polymorphisms and risks of osteoporosis development was identified with odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Haplotype analysis and multifactor dimension reduction analysis were used to explore the potential association between combined single nucleotide polymorphisms (SNPs) and osteoporosis risk.

Results

The AA genotype of rs2853550 was a protective factor for osteoporosis occurrence (OR = 0.11, p = 0.038), whereas rs16944 (OR = 1.19, p = 0.037) and rs1143623 (OR = 1.21, p = 0.025) conferred an increased risk of osteoporosis. Moreover, rs1143627, rs16944 and rs1143623 were associated with an elevated susceptibility to osteoporosis, especially in females and individuals aged > 60 years or with a body mass index > 24 kg/m2. Haplotype Grs1143630Ars1143627Grs16944 was a risk factor of osteoporosis occurrence (OR = 1.20, p = 0.032). The best model of SNP–SNP analysis was a four‐locus combination of rs1143643, rs3136558, rs1143630 and rs1143623 (testing accuracy = 0.5623).

Conclusions

IL‐1B polymorphisms and haplotype Grs1143630Ars1143627Grs16944 might contribute to susceptibility to osteoporosis. The SNP–SNP interaction of polymorphisms in IL‐1B revealed the accumulated effect on osteoporosis risk.
Opportunities and challenges for antisense oligonucleotide therapies
Authors: Kuijper Elsa C. , Bergsma Atze J. , Pijnappel W.W.M. Pim , Aartsma‐Rus Annemieke
Published: May 2020

Antisense oligonucleotide (AON) therapies involve short strands of modified nucleotides that target RNA in a sequence‐specific manner, inducing targeted protein knockdown or restoration. Currently, 10 AON therapies have been approved in the United States and Europe. Nucleotides are chemically modified to protect AONs from degradation, enhance bioavailability and increase RNA affinity. Whereas single stranded AONs can efficiently be delivered systemically, delivery of double stranded AONs requires capsulation in lipid nanoparticles or binding to a conjugate as the uptake enhancing backbone is hidden in this conformation. With improved chemistry, delivery vehicles and conjugates, doses can be lowered, thereby reducing the risk and occurrence of side effects. AONs can be used to knockdown or restore levels of protein. Knockdown can be achieved by single stranded or double stranded AONs binding the RNA transcript and activating RNaseH‐mediated and RISC‐mediated degradation respectively. Transcript binding by AONs can also prevent translation, hence reducing protein levels. For protein restoration, single stranded AONs are used to modulate pre‐mRNA splicing and either include or skip an exon to restore protein production. Intervening at a genetic level, AONs provide therapeutic options for inherited metabolic diseases as well. This review provides an overview of the different AON approaches, with a focus on AONs developed for inborn errors of metabolism.
SMOFlipid vs Intralipid 20%: Effect of Mixed‐Oil vs Soybean‐Oil Emulsion on Parenteral Nutrition–Associated Cholestasis in the Neonatal Population
Authors: Jackson Rachel Leigh , White Phillip Zachary , Zalla Jennifer
Published: May 2020

Background

Parenteral nutrition (PN) is critical for the growth and development of premature neonates who are unable to reach nutrition goals enterally. Using soybean‐oil emulsions in PN is a risk factor for cholestasis, leading to alternative dosing strategies including a reduction in total lipid prescribed. Recently, SMOFlipid has been utilized with the goal of avoiding cholestasis while maintaining energy intake. The aim of our study was to compare the incidence of PN‐associated cholestasis (PNAC) in patients admitted to the neonatal intensive care unit (NICU) who received either Intralipid 20% or SMOFlipid.

Methods

This single‐center, retrospective study evaluated all NICU patients who received PN for ≥14 days. Patients who received SMOFlipid were compared with those who received Intralipid. The primary end point was incidence of PNAC. Secondary end points included (1) prevalence of elevated liver function tests; (2) effect on select laboratory parameters; (3) development of PNAC by age; and (4) incidence of retinopathy of prematurity.

Results

A total of 136 neonates were included. Nine of 55 patients (16.4%) in the Intralipid group and 2 of 81 patients (2.5%) in the SMOFlipid group developed cholestasis, defined as direct bilirubin > 2 mg/dL or direct bilirubin > 20% of total bilirubin, when total bilirubin is >5 mg/dL, on or before 30 days post initiation of PN (P = .007).

Conclusion

Use of SMOFlipid as the lipid emulsion component of PN may be beneficial in prevention of PNAC in NICU patients that are receiving PN for ≥2 weeks.
Does the exotic equal pollution? Landscape methods for solving the dilemma of using native versus non‐native plant species in drylands
Authors: Kotzen Benz , Branquinho Cristina , Prasse Ruediger
Published: May 2020

There is a need to resolve methods to determine the merits of native versus non‐native plant use in drylands and indeed in more temperate areas around the world. This is because whilst plant introductions may have positive objectives, they can have significant negative landscape and environmental impacts. A key discussion on this issue focuses on whether the use of non‐native plant species can be considered to be pollution and pollutive based on the concept that pollution can be regarded as ‘matter out of place’. The consequences of putting the wrong plant species in the wrong place can be extremely detrimental to the landscape character, quality and value of the land, let alone the effects on ecosystem structure and functioning as well as on biodiversity. These effects can also affect human communities who may rely on the landscape, for example, for tourism. It is thus necessary that the discussion on how decisions are made in determining plant choice evolves so that the right decisions are made when planting is necessary, for the land, for nature and for the people. This discussion has been initiated through COST Action ES1104, which focused on the restoration of degraded dry and arid lands. This article discusses a number of landscape methods based on sustainability principles to determine when and where native and non‐native plants could and should be used.
Monitoring Matang's Mangroves in Peninsular Malaysia through Earth observations: A globally relevant approach
Authors: Lucas Richard , Otero Viviana , Van De Kerchove Ruben , Lagomasino David , Satyanarayana Behara , Fatoyinbo Temilola , Dahdouh‐Guebas Farid
Published: May 2020

Expansion of rotational timber harvesting of mangroves is set to increase, particularly given greater recognition of the economic, societal and environmental benefits. Generic and standardized procedures for monitoring mangroves are, therefore, needed to ensure their long‐term sustainable utilisation. Focusing on the Matang Mangrove Forest Reserve (MMFR), Perak State, Peninsular Malaysia, thematic and continuous environmental descriptors with defined codes or units, including lifeform, forest age (years), canopy cover (%), above‐ground biomass (Mg ha−1) and relative amounts of woody debris (%), were retrieved from time‐series data from spaceborne optical and single/dual polarimetric and interferometric RADAR. These were then combined for multiple points in time to generate land cover and evidence‐based change maps according to the Food and Agriculture Organisation (FAO) Land Cover Classification System (LCCS) and using the framework of the Earth Observation Data for Ecosystem Monitoring (EODESM). Change maps were based on a pre‐defined taxonomy, with focus on clear cutting and regrowth. Uncertainties surrounding the land cover and change maps were based on those determined for the environmental descriptors used for their generation and through comparison with independent retrieval from other EO data sources. For the MMFR and also for other mangroves worldwide where harvesting is occurring or being considered, a new approach and opportunity for supporting management of mangroves is presented, which has application for future planning of mangrove resources.
Flexible and Highly Sensitive Pressure Sensors with Surface Discrete Microdomes Made from Self‐Assembled Polymer Microspheres Array
Authors: Zhang Yuan , Han Fei , Hu Yougen , Xiong Yaoxu , Gu Han , Zhang Guoqi , Zhu Pengli , Sun Rong , Wong Ching‐Ping
Published: May 2020

Flexible pressure sensors with high performances are of great interest for smart wearable devices, health monitoring and artificial electronic skins. However, assembling pressure sensors with low cost, simple structure and high sensitivity are still difficult to achieve. Herein, a fast, novel and facile approach is presented to fabricate piezoresistive flexible pressure sensors with surface uniform dome‐like microstructures which are easily replicated from discrete polystyrene (PS) microspheres array by plasma etching the monolayer array of self‐assembly close‐packed PS microspheres. The flexible pressure sensor with dome‐like array (4.2 µm of diameter, 2.1 µm of height and 1.4 µm of spacing) exhibits a high sensitivity of ‐6.61 kPa−1 in the pressure range below 110 Pa, an ultralow detection limit of 1 Pa, a fast response time of 100 ms, and high stability over 3750 cycles of pressure loading/unloading. The sensor is also successfully demonstrated in monitoring human action and beating a drum. Moreover, a 5 × 5 array of the flexible pressure sensor is fabricated to detect spatial pressure distribution. This work provides a simple and effective protocol to build surface microstructures and improve whole performance of flexible pressure sensors, and shows great prospect in the applications of wearable electronics and human‐machine interaction.
High Molecular‐Weight Cyclic Polyesters from Solvent‐Free Ring‐Opening Polymerization of Lactones with a Pyridyl‐Urea/MTBD
Authors: Feng Rui , Jie Suyun , Braunstein Pierre , Li Bo‐Geng
Published: May 2020

(Thio)urea/base systems have been widely used in the ring‐opening polymerization (ROP) of lactones based on their superior performance in activity and selectivity. Herein, a pyridyl‐urea (6C‐PU)/7‐methyl‐1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene catalytic system is used to prepare the polyesters with cyclic topology via the ROP of lactones in the absence of initiator under solvent‐free conditions. The catalytic system shows high activity in the ROP of δ‐valerolactone (δ‐VL) and cyclic polyvalerolactones (PVLs) with high molecular weights and narrow molecular weight distribution are obtained despite the existence of some linear products generated during the precipitation process. The structure of the resulting polymers is determined by proton and carbon nuclear magnetic resonance spectra, matrix assisted laser desorption/ionization time of flight mass spectrometry, and intrinsic viscosity studies. A possible mechanism is proposed on the basis of NMR analysis and characteristics of polymerization. Thermal and mechanical properties of cyclic PVLs are investigated through differential scanning calorimetry, thermogravimetric analysis, and tensile test.
The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China
Authors: Huang Xiao‐Jun , Wang Shi‐Ge , Guo Xia‐Nan , Tian Wo‐Tu , Zhan Fei‐Xia , Zhu Ze‐Yu , Yin Xiao‐Meng , Liu Qing , Yin Kai‐Li , Liu Xiao‐Rong , Zhang Yu , Liu Zhen‐Guo , Liu Xiao‐Li , Zheng Lan , Wang Tian , Wu Li , Rong Tian‐Yi , Wang Yan , Zhang Mei , Bi Guang‐Hui , Tang Wei‐Guo , Zhang Chao , Zhong Ping , Wang Chun‐Yu , Tang Jian‐Guang , Lu Wei , Zhang Ru‐Xu , Zhao Guo‐Hua , Li Xun‐Hua , Li Hua , Chen Tao , Li Hai‐Yan , Luo Xiao‐Guang , Song Yan‐Yan , Tang Hui‐Dong , Luan Xing‐Hua , Zhou Hai‐Yan , Tang Bei‐Sha , Chen Sheng‐Di , Cao Li
Published: May 2020

Background

Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline‐rich transmembrane protein 2 have been identified as the major pathogenic factor.

Objectives

We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy.

Methods

The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline‐rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype‐phenotype correlation analyses were conducted in patients with and without proline‐rich transmembrane protein 2 mutations. High‐knee exercises were applied in partial patients as a new diagnostic test to induce attacks.

Results

Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline‐rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high‐knee‐exercise test efficiently induced attacks and could assist in diagnosis.

Conclusions

We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society
Targeting telomerase for its advent in cancer therapeutics
Authors: Bajaj Shalini , Kumar Maushmi S , Peters GJ , Mayur YC
Published: May 2020

Telomerase has emerged as an important primary target in anticancer therapy. It is a distinctive reverse transcriptase enzyme, which extends the length of telomere at the 3′ chromosomal end, and uses telomerase reverse transcriptase (TERT) and telomerase RNA template‐containing domains. Telomerase has a vital role and is a contributing factor in human health, mainly affecting cell aging and cell proliferation. Due to its unique feature, it ensures unrestricted cell proliferation in malignancy and plays a major role in cancer disease. The development of telomerase inhibitors with increased specificity and better pharmacokinetics is being considered to design and develop newer potent anticancer agents. Use of natural and synthetic compounds for the inhibition of telomerase activity can lead to an opening of new vistas in cancer treatment. This review details about the telomerase biochemistry, use of natural and synthetic compounds; vaccines and oncolytic virus in therapy that suppress the telomerase activity. We have discussed structure‐activity relationships of various natural and synthetic telomerase inhibitors to help medicinal chemists and chemical biology researchers with a ready reference and updated status of their clinical trials. Suppression of human TERT (hTERT) activity through inhibition of hTERT promoter is an important approach for telomerase inhibition.
Skp2 in the ubiquitin‐proteasome system: A comprehensive review
Authors: Asmamaw Moges Dessale , Liu Ying , Zheng Yi‐Chao , Shi Xiao‐Jing , Liu Hong‐Min
Published: May 2020

The ubiquitin‐proteasome system (UPS) is a complex process that regulates protein stability and activity by the sequential actions of E1, E2 and E3 enzymes to influence diverse aspects of eukaryotic cells. However, due to the diversity of proteins in cells, substrate selection is a highly critical part of the process. As a key player in UPS, E3 ubiquitin ligases recruit substrates for ubiquitination specifically. Among them, RING E3 ubiquitin ligases which are the most abundant E3 ubiquitin ligases contribute to diverse cellular processes. The multisubunit cullin‐RING ligases (CRLs) are the largest family of RING E3 ubiquitin ligases with tremendous plasticity in substrate specificity and regulate a vast array of cellular functions. The F‐box protein Skp2 is a component of CRL1 (the prototype of CRLs) which is expressed in many tissues and participates in multiple cellular functions such as cell proliferation, metabolism, and tumorigenesis by contributing to the ubiquitination and subsequent degradation of several specific tumor suppressors. Most importantly, Skp2 plays a pivotal role in a plethora of cancer‐associated signaling pathways. It enhances cell growth, accelerates cell cycle progression, promotes migration and invasion, and inhibits cell apoptosis among others. Hence, targeting Skp2 may represent a novel and attractive strategy for the treatment of different human cancers overexpressing this oncogene. In this review article, we summarized the known roles of Skp2 both in health and disease states in relation to the UPS.
COVID‐19 in patients with myasthenia gravis
Authors: Anand Pria , Slama Michaël C. C. , Kaku Michelle , Ong Charlene , Cervantes‐Arslanian Anna M. , Zhou Lan , David William S. , Guidon Amanda C.
Published: May 2020

Introduction

Coronavirus disease 2019 (COVID‐19) has rapidly become a global pandemic, but little is known about its potential impact on patients with myasthenia gravis (MG).

Methods

We studied the clinical course of COVID‐19 in five hospitalized patients with autoimmune MG (four with acetylcholine receptor antibodies, one with muscle‐specific tyrosine kinase antibodies) between April 1, 2020‐April 30‐2020.

Results

Two patients required intubation for hypoxemic respiratory failure, whereas one required significant supplemental oxygen. One patient with previously stable MG had myasthenic exacerbation. One patient treated with tocilizumab for COVID‐19 was successfully extubated. Two patients were treated for MG with intravenous immunoglobulin without thromboembolic complications.

Discussion

Our findings suggest that the clinical course and outcomes in patients with MG and COVID‐19 are highly variable. Further large studies are needed to define best practices and determinants of outcomes in this unique population.
How I approach hereditary hemolytic anemia and splenectomy
Authors: Rothman Jennifer A. , Stevens Jenny L. , Gray Fabienne L. , Kalfa Theodosia A.
Published: May 2020

Hereditary hemolytic anemias (HHA) are a heterogeneous group of anemias associated with decreased red cell survival. While there can be clinical benefit of splenectomy in many cases, splenectomy is not appropriate for all types of HHA. Additionally, there are significant risks during and following splenectomy including surgical risks, postsplenectomy sepsis, and thrombotic complications. This review discusses the diagnostic approach to HHA as well as the role of splenectomy in the management. Surgical approaches and outcomes for total and partial splenectomy are discussed.
Unoccupied aerial system enabled functional modeling of maize height reveals dynamic expression of loci
Authors: Anderson Steven L. , Murray Seth C. , Chen Yuanyuan , Malambo Lonesome , Chang Anjin , Popescu Sorin , Cope Dale , Jung Jinha
Published: May 2020

Unoccupied aerial systems (UAS) were used to phenotype growth trajectories of inbred maize populations under field conditions. Three recombinant inbred line populations were surveyed on a weekly basis collecting RGB images across two irrigation regimens (irrigated and non‐irrigated/rain fed). Plant height, estimated by the 95th percentile (P95) height from UAS generated 3D point clouds, exceeded 70% correlation (r) to manual ground truth measurements and 51% of experimental variance was explained by genetics. The Weibull sigmoidal function accurately modeled plant growth (R2: >99%; RMSE: <4 cm) from P95 genetic means. The mean asymptote was strongly correlated (r2 = 0.66–0.77) with terminal plant height. Maximum absolute growth rates (mm/day) were weakly correlated with height and flowering time. The average inflection point ranged from 57 to 60 days after sowing (DAS) and was correlated with flowering time (r2 = 0.45–0.68). Functional growth parameters (asymptote, inflection point, growth rate) alone identified 34 genetic loci, each explaining 3–15% of total genetic variation. Plant height was estimated at one‐day intervals to 85 DAS, identifying 58 unique temporal quantitative trait loci (QTL) locations. Genomic hotspots on chromosomes 1 and 3 indicated chromosomal regions associated with functional growth trajectories influencing flowering time, growth rate, and terminal growth. Temporal QTL demonstrated unique dynamic expression patterns not previously observable, and no QTL were significantly expressed throughout the entire growing season. UAS technologies improved phenotypic selection accuracy and permitted monitoring traits on a temporal scale previously infeasible using manual measurements, furthering understanding of crop development and biological trajectories.
Inconsistencies between measures of cognitive dysfunction in childhood acute lymphoblastic leukemia survivors: Description and understanding
Authors: Leclerc Andrée‐Anne , Lippé Sarah , Bertout Laurence , Chapados Pascale , Boulet‐Craig Aubrée , Drouin Simon , Krajinovic Maja , Laverdière Caroline , Michon Bruno , Robaey Philippe , Rondeau Émélie , Sinnett Daniel , Sultan Serge
Published: May 2020

Objectives

The frequency of cognitive difficulties in childhood cancer survivors varies according to the measurement strategy. The goal of this research is to (a) describe agreements and differences between measures of working memory and attention (b) identify contributors of these differences, such as emotional distress, affects, and fatigue.

Methods

We used data available for 138 adults successfully treated for childhood acute lymphoblastic leukemia (ALL) (PETALE cohort). Working memory and attention were assessed using subtests from the WAIS‐IV and self‐reported questionnaires (BRIEF‐SR and CAARS‐S:L). Potential contributors included emotional distress, anxiety, depression (BSI‐18), affects (PANAS), and fatigue (PedsQL‐MFS). We explored measurement agreements and differences using diagnostic indices and multivariate regression models.

Results

The frequencies of working memory and attention deficits were higher when using cognitive tests (15%‐21%) than with self‐reports (10%‐11%). Self‐reported questionnaires showed high specificity (median 0.87) and low sensitivity (median 0.10), suggesting they did not reliably identify positive cases on cognitive tests. We identified negative affectivity as a possible contributor to inconsistencies between self‐report and test results.

Conclusions

When measuring working memory and attention in childhood ALL survivors, cognitive test results and self‐reports should not be considered equivalent. At best, self‐report may be used for screening (high specificity), but not to assess prevalence in large samples. Self‐reported difficulties are also probably influenced by the negative mood in this population.
Classification of hyperspectral endocrine tissue images using support vector machines
Authors: Maktabi Marianne , Köhler Hannes , Ivanova Magarita , Neumuth Thomas , Rayes Nada , Seidemann Lena , Sucher Robert , Jansen‐Winkeln Boris , Gockel Ines , Barberio Manuel , Chalopin Claire
Published: May 2020

Background

Thyroidectomy is one of the most commonly performed surgical procedures. The region of the neck has a very complex structural organization. It would be beneficial to introduce a tool that can assist the surgeon in tissue discrimination during the procedure. One such solution is the noninvasive and contactless technique, called hyperspectral imaging (HSI).

Methods

To interpret the HSI data, we implemented a supervised classification method to automatically discriminate the parathyroid, the thyroid, and the recurrent laryngeal nerve from surrounding tissue(muscle, skin) and materials (instruments, gauze). A leave‐one‐patient‐out cross‐validation was performed.

Results

The best performance was obtained using support vector machine (SVM) with a classification and visualization in less than 1.4 seconds. A mean patient accuracy of 68% ± 23% was obtained for all tissues and material types.

Conclusions

The proposed method showed promising results and have to be confirmed on a larger cohort of patient data.
Intensive agricultural management‐induced subsurface accumulation of labile phosphorus in Midwestern agricultural soils dominated by tile lines
Authors: Xu Suwei , Gentry Lowell , Chen Kai‐Yue , Arai Yuji
Published: May 2020

In addition to surface runoff, subsurface P loss through tile lines in agricultural lands has received attention over the last decade. It is not clearly understood how this strong ligand, phosphate, is distributed in subsoils (≤180 cm), contributing to subsurface P loss. We hypothesized that subsurface accumulation of labile P as a result of long‐term intensive agricultural management contributes to subsurface P loss. The depth sequence distribution of P and its speciation and reactivity were investigated in tile‐line‐dominated Midwestern agricultural fields via chemical extraction and digestion, batch desorption experiments, and X‐ray absorption near‐edge structure spectroscopy. The results suggest that labile P in subsoils exceeds the eutrophication‐inducing level (>0.01 mg L–1). Because of intensive agricultural management, total P was ∼400 mg kg–1 in surface soils and ∼200‐300 mg kg–1 in subsoils. The depth sequence distribution of P indicated the translocation of P to subsoils. Although phosphate and phytic acid adsorbed by Al or Fe (oxyhydro)oxides and calcite were found in surface soils, phosphate adsorbed to calcite, hydroxyapatite, or both were the dominant P species in subsoils. Phosphate was highest in surface soils and decreased sharply with increasing depth. Slightly alkaline soil in subsoils suppressed the release of P but the process was continuous after 30 d. Subsurface P loss was influenced by the dissolution and desorption process of inorganic P phases and preferentially transported P from surface soils. Subsurface P loss should be considered in strategies to reduce agricultural P loss in the Gulf of Mexico.
Serpentine parent materials lead to the formation of atypical hydric soils
Authors: Vaughan Karen L. , DeMoss Jason , Cullum‐Muyres Taylor , Diaz Ariel
Published: May 2020

Hydrologically isolated wetlands offer critical ecosystem services including water filtration and storage, carbon sequestration, and wildlife habitat, among many others. Geomorphic features formed via landslides, termed slump blocks, along the central coast of California can create the ideal, lower angle conditions for wetland hydrology to persist, followed by hydrophytic vegetation and hydric soils. Areas susceptible to the formation of slump block wetlands are those along steep slopes underlain by metamorphosed ultramafic (serpentine) colluvial and residual parent materials due to their propensity to slip along fracture planes. The soils that form in these settings do not exhibit traditional redoximorphic features near the surface that are necessary to identify wetland soils via field observation of morphological features. The objective of this study is to examine the morphology of hydromorphic soils forming in serpentine colluvium and residuum and determine wetland status by employing a combination of biogeochemical, hydrological, and vegetative assessments. These serpentinite‐derived soils forming on slump block geomorphic surfaces meet the technical standard of hydric soils using Indicator of Reduction in Soil tubes as a proxy, despite the lack of traditional observable redoximorphic features. In addition, both wetland hydrology and hydrophytic vegetation communities were documented, therefore meeting the three requirements of wetlands. Ultimately, the importance lies in properly identifying and delineating ecosystems in need of conservation and as such, we propose an alternate field indicator for use in serpentine soils forming in landslide‐susceptible terrain.
Efficiently removing cetyl trimethyl ammonium bromide from wastewater by graphene oxide
Authors: Chang Luping , Cao Yijun , Peng Weijun , Li Chao , Fan Guixia , Song Xiangyu , Shi Xiaoxin
Published: May 2020

Cetyl trimethyl ammonium bromide (CTAB) containing wastewater from dressing plant may pose a detrimental threaten to mineral beneficiation and environment. The adsorption of CTAB in aqueous solutions by graphene oxide (GO) has been studied in this work. X‐ray diffraction, X‐ray photoelectron spectroscopy, Fourier‐transform infrared spectrometer, and atomic force spectroscopy were used to characterize GO. The results indicated that the adsorption followed the Freundlich model could be well described by pseudo‐second order kinetic model. The adsorption capacity was much bigger than activated carbon and many natural clay minerals. The adsorption process was endothermic, and the adsorption mechanism of CTAB onto GO was proven to be controlled by surface complexation, hydrogen bonding, and electrostatic attraction.
One‐Step Preparation of Highly Durable Superhydrophobic Carbon Nanothorn Arrays
Authors: Li Xiaodong , Wang Ning , He Jianjiang , Yang Ze , Zhao Fuhua , Wang Kun , Huang Changshui
Published: May 2020

This study proposes a one‐step method for growing superhydrophobic carbon nanothorn arrays (NTAs) directly on various substrates. The fabricated carbon material (named methyl‐substituted graphdiyne (MGDY)) comprises sp and sp2 carbons in a conjugated‐backbone form, as well as methyl groups introduced into the framework as hydrophobic‐enhanced functional groups. MGDY NTAs exhibit excellent hydrophobicity (contact angle ≥152°), substantial long‐period hydrophobic durability (the contact angle decreased by only 3.2% over 800 days), and acid/alkali tolerance. Owing to the enhanced durability and specific stability of carbon, a superhydrophobic interface can easily be constructed using MGDY NTAs, which can be applied to achieve successful long‐term metal‐corrosion protection and efficient oil–water separation.
Hydrogen Terminated Germanene for a Robust Self‐Powered Flexible Photoelectrochemical Photodetector
Authors: Liu Nana , Qiao Hui , Xu Kang , Xi Yilian , Ren Long , Cheng Ningyan , Cui Dandan , Qi Xiang , Xu Xun , Hao Weichang , Dou Shi Xue , Du Yi
Published: May 2020

As a rising star in the family of graphene analogues, germanene shows great potential for electronic and optical device applications due to its unique structure and electronic properties. It is revealed that the hydrogen terminated germanene not only maintains a high carrier mobility similar to that of germanene, but also exhibits strong light–matter interaction with a direct band gap, exhibiting great potential for photoelectronics. In this work, few‐layer germanane (GeH) nanosheets with controllable thickness are successfully synthesized by a solution‐based exfoliation–centrifugation route. Instead of complicated microfabrication techniques, a robust photoelectrochemical (PEC)‐type photodetector, which can be extended to flexible device, is developed by simply using the GeH nanosheet film as an active electrode. The device exhibits an outstanding photocurrent density of 2.9 µA cm−2 with zero bias potential, excellent responsivity at around 22 µA W−1 under illumination with intensity ranging from 60 to 140 mW cm−2, as well as short response time (with rise and decay times, tr = 0.24 s and td = 0.74 s). This efficient strategy for a constructing GeH‐based PEC‐type photodetector suggests a path to promising high‐performance, self‐powered, flexible photodetectors, and it also paves the way to a practical application of germanene.
Application of Derivatization in Fatty Acids and Fatty Acyls Detection: Mass Spectrometry‐Based Targeted Lipidomics
Authors: Xiang Li , Zhu Lin , Huang Yu , Cai Zongwei
Published: May 2020

Mass spectrometry (MS) has become an indispensable technique in the analysis of fatty acids (FAs) and fatty acyls due to its superior sensitivity and selectivity. Chemical derivatization is often introduced in MS‐based analysis because of the inherent poor ionization efficiency and selectivity of FAs and fatty acyls. This critical review presents an overview of commonly used MS platforms including gas chromatography‐MS, liquid chromatography‐MS, and mass spectrometry imaging combined with representative derivatization reagents for FAs and fatty acyls based on different chain‐lengths, saturation degrees, and conjugation groups. The method applications and limitations as well as critical derivatization conditions in different biological matrices are summarized. Special remarks on the chemical derivatization for MS‐based analysis are provided. Future perspectives associated with the detection of FAs and fatty acyls are discussed. This review provides valuable information and suggestions for the targeted detection of interested FAs and fatty acyls using different MS‐based platforms.
Numerical metrics, curvature expansions and Calabi-Yau manifolds
Authors: Cui Wei , Gray James
Published: May 2020

Abstract

We discuss the extent to which numerical techniques for computing approximations to Ricci-flat metrics can be used to investigate hierarchies of curvature scales on Calabi-Yau manifolds. Control of such hierarchies is integral to the validity of curvature expansions in string effective theories. Nevertheless, for seemingly generic points in moduli space it can be difficult to analytically determine if there might be a highly curved region localized somewhere on the Calabi-Yau manifold. We show that numerical techniques are rather efficient at deciding this issue.
Open-closed hyperbolic string vertices
Authors: Cho Minjae
Published: May 2020

Abstract

We construct a family of hyperbolic string vertices in the oriented open-closed string field theory, generalizing the recent result on hyperbolic closed string vertices by Costello and Zwiebach. The vertices are described by certain bordered hyperbolic surfaces and we explain relevant collar theorems which provide restrictions on the systolic conditions for the hyperbolic vertices. We also give explicit descriptions of the vertices for all zero and one-dimensional moduli spaces.
Deep learning and k-means clustering in heterotic string vacua with line bundles
Authors: Otsuka Hajime , Takemoto Kenta
Published: May 2020

Abstract

We apply deep-learning techniques to the string landscape, in particular, SO(32) heterotic string theory on simply-connected Calabi-Yau threefolds with line bundles. It turns out that three-generation models cluster in particular islands specified by deep autoencoder networks and k-means++ clustering. Especially, we explore mutual relations between model parameters and the cluster with densest three-generation models (called “3-generation island”). We find that the 3-generation island has a strong correlation with the topological data of Calabi-Yau threefolds, in particular, second Chern class of the tangent bundle of the Calabi-Yau threefolds. Our results also predict a large number of Higgs pairs in the 3-generation island.
Handlungsempfehlungen zur Gentherapie der spinalen Muskelatrophie mit Onasemnogene Abeparvovec – AVXS-101
Authors: Ziegler Andreas , Wilichowski Ekkehard , Schara Ulrike , Hahn Andreas , Müller-Felber Wolfgang , Johannsen Jessika , von der Hagen Maja , von Moers Arpad , Stoltenburg Corinna , Saffari Afshin , Walter Maggie C. , Husain Ralf A. , Pechmann Astrid , Köhler Cornelia , Horber Veronka , Schwartz Oliver , Kirschner Janbernd
Published: May 2020

Hintergrund

Die spinale Muskelatrophie (SMA) ist eine schwere, lebenslimitierende neurodegenerative Erkrankung. Seit Juli 2017 steht in Deutschland eine krankheitsmodifizierende und zugelassene Therapie mit Nusinersen zur Verfügung. Eine weitere vielversprechende Behandlungsmöglichkeit durch eine einmalige Applikation bieten konzeptionell Gentherapien. Im Mai 2019 wurde erstmals eine kausale Genersatztherapie zur Behandlung der spinalen Muskelatrophie von der U.S. Food and Drug Administration (FDA) zugelassen, die Zulassung in Europa ist beantragt.

Ziele

Dieses Konsensuspapier wurde auf Einladung der Deutschen Gesellschaft für Muskelkranke e. V. (DGM) unter Beteiligung der deutschen neuromuskulären Behandlungszentren, der deutschen Sektion der Gesellschaft für Neuropädiatrie (GNP) und unter Mitwirkung des Medizinisch-Wissenschaftlichen Beirates der DGM erarbeitet. Ziel ist es, die notwendigen Voraussetzungen für eine qualitätsgesicherte Anwendung der neuen Gentherapie zu definieren und die Grundlage für die Umsetzung in der klinischen Praxis zu schaffen.

Diskussion

Die Gentherapie mit Onasemnogene Abeparvovec besitzt das Potenzial, den Krankheitsverlauf der spinalen Muskelatrophie signifikant zu beeinflussen. Langzeitdaten über die Nachhaltigkeit der Wirkung und mögliche unerwünschte Wirkungen liegen derzeit noch nicht vor. Die Anwendung dieser innovativen Therapieform muss in spezialisierten und entsprechend qualifizierten Behandlungszentren unter strengen Sicherheitsauflagen erfolgen. Die vorliegende Arbeit schlägt die hierfür notwendigen Rahmenbedingungen und Empfehlungen für die systematische Vor- und Nachsorge unter Gentherapie vor. Wirksamkeit und Sicherheit der Therapie sollten in einem industrieunabhängigen, krankheitsspezifischen Register systematisch erfasst werden.
Integrity of plasma DNA is inversely correlated with vaccine-induced antitumor immunity in ovarian cancer patients
Authors: Waki Kayoko , Yokomizo Kanako , Kawano Kouichiro , Tsuda Naotake , Komatsu Nobukazu , Yamada Akira
Published: May 2020

Cancer immunotherapy including vaccine therapy is a promising modality for cancer treatment, but few patients show its clinical benefits currently. The identification of biomarkers that can identify patients who will benefit from cancer immunotherapy is thus important. Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity—a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene—as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or recurrent ovarian cancer enrolled in clinical trials for personalized peptide vaccinations. We observed that (1) the cfDNA integrity was decreased after the first cycle of vaccination, and (2) the decreased levels of cfDNA integrity were correlated with vaccine-induced immune responses; i.e., decreased cfDNA integrity was observed in 91.7% and 59.3% of the IgG-positive and negative patients, respectively (p = 0.0445). Similarly, decreased cfDNA integrity was observed in 92.9% and 56.0% of CTL response-positive and negative patients, respectively (p = 0.0283). These results suggest that the circulating cfDNA integrity is a possible biomarker for cancer vaccine therapy.
Risk Factors and Outcome of Portal Vein Thrombosis After Laparoscopic and Open Hepatectomy for Primary Liver Cancer: A Single‐Center Experience
Authors: Mori Akira , Arimoto Akira , Hamaguchi Yuhei , Kajiwara Masatoshi , Nakajima Akio , Kanaya Seiichiro
Published: May 2020

Background

Post‐hepatectomy portal vein thrombosis (PH‐PVT) is a severe complication. The risk factors of PH‐PVT after laparoscopic and open hepatectomy have not been clarified yet. We aimed to retrospectively investigate the risk factors and outcome of PH‐PVT in patients with primary liver cancer.

Methods

We enrolled 622 consecutive patients who underwent hepatectomy in our hospital between January 2006 and August 2016.

Results

Of 21 patients (3.4%) with PH‐PVT, 7 had grade I; 13, grade II; and 1, grade III. The patients with PH‐PVT were significantly older than those without PH‐PVT. Of the 413 patients who underwent open hepatectomy, those who underwent a major right hepatectomy (4.1%) had a slightly higher incidence of PH‐PVT. Of the 209 patients who underwent laparoscopic hepatectomy, those who underwent a left lateral sectionectomy (21.2%) and major right hepatectomy (16.7%) had high incidence rates of PH‐PVT. The treatment was only observation in five patients, medication with an antithrombotic drug in 15 patients, and reoperation in one patient. PH‐PVT diminished in 17 patients. Cavernous transformation and/or stenosis of the portal vein developed in three patients. The patient with grade III PH‐PVT after open right hemihepatectomy underwent reoperation but died of hepatic failure.

Conclusion

This study demonstrated that patient age, left lateral sectionectomy were risk factors of PH‐PVT. Laparoscopic left lateral sectionectomy and major right hepatectomy might bring about relatively higher risk of PH‐PVT. Major right hepatectomy tends to lead to severe PH‐PVT. Careful handling of the PV during hepatectomy and early treatment of PH‐PVT are necessary.
Simulation Training in Neuroangiography: Transfer to Reality
Authors: Kreiser Kornelia , Gehling Kim G. , Ströber Lea , Zimmer Claus , Kirschke Jan S.
Published: May 2020

Purpose

Endovascular simulation is an established and validated training method, but there is still no proof of direct patient’s benefit, defined as lower complication rate. In this study, the impact of such a training was investigated for rehearsal of patient-specific cases as well as for a structured simulation curriculum to teach angiographer novices.

Materials and Methods

A total of 40 patients undergoing a diagnostic neuroangiography were randomized in a training and control group. In all training group patients, the angiographer received a patient-anatomy-specific rehearsal on a high-fidelity simulator prior to the real angiography. Radiation exposure, total duration, fluoroscopy time and amount of contrast agent of the real angiography were recorded. Silent cerebral ischemia was counted by magnetic resonance diffusion-weighted imaging (DWI). Additionally, the first 30 diagnostic neuroangiographies of six novices were compared (ntotal = 180). Three novices had undergone a structured simulation curriculum; three had acquired angiographic skills without simulation.

Results

No differences were found in the number of DWI lesions or in other quality measures of the angiographies performed with and without patient-specific rehearsal. A structured simulation curriculum for angiographer novices reduced fluoroscopy time significantly and radiation exposure. The curriculum had no influence on the total duration of the examination, the amount of contrast medium or the number of catheters used.

Conclusion

There was no measurable benefit of patient-anatomy-specific rehearsal for an unselected patient cohort. A structured simulation-based curriculum to teach angiographic skills resulted in a reduction of fluoroscopy time and radiation dose in the first real angiographies of novice angiographers.

Level of Evidence

Level 4, part 1: randomized trial, part 2: historically controlled study.
In vivo assessment of the drug interaction between sorafenib and paracetamol in rats
Authors: Karbownik Agnieszka , Sobańska Katarzyna , Grabowski Tomasz , Stanisławiak-Rudowicz Joanna , Wolc Anna , Grześkowiak Edmund , Szałek Edyta
Published: May 2020

Purpose

Sorafenib is a multi-targeted tyrosine kinase inhibitor (TKI) used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. Neoplastic diseases are the cause of pain, which may occur regardless of the stage of the disease. Paracetamol is a non-opioid analgesic used alone or in combination with opioids for the treatment of cancer pain. Numerous studies have pointed out changes in the pharmacokinetic parameters of TKIs when co-administered with paracetamol. The aim of the study was to assess drug–drug interactions (DDIs) between sorafenib and paracetamol.

Methods

Rats were divided into three groups, each consisting of eight animals. The first group received sorafenib (IIS), the second group received sorafenib + paracetamol (IS+PA), whereas the third group received only paracetamol (IIIPA). A single dose of sorafenib (100 mg/kg b.w.) and paracetamol (100 mg/kg b.w.) was administered orally. The plasma concentrations of sorafenib and its metabolite–N-oxide as well as paracetamol and its glucuronide and sulphate metabolites were measured using validated high-performance liquid chromatography (HPLC) method with ultraviolet detection.

Results

The co-administration of sorafenib and paracetamol increased the maximum concentration (Cmax) of paracetamol by 33% (p = 0.0372). In the IS+ PA group the Cmax of paracetamol glucuronide was reduced by 48% (p =  < 0.0001), whereas the Cmax of paracetamol sulphate was higher by 153% (p = 0.0012) than in the IIIPA group. Paracetamol increased sorafenib and sorafenib N-oxide Cmax by 60% (p = 0.0068) and 83% (p = 0.0023), respectively.

Conclusions

A greater knowledge of DDI between sorafenib and paracetamol may help adjust dose properly and avoid toxicity effects in individual patients.
Spot urine iodine levels below the WHO recommendation are not related to impaired thyroid function in healthy children and adolescents
Authors: Wallborn Tillmann , Vogel Mandy , Kneuer Antje , Thamm Michael , Dittrich Katalin , Kiess Wieland , Kratzsch Jürgen
Published: May 2020

Purpose

Iodine deficiency in childhood and adolescence may lead to later thyroid dysfunction, stunted growth and cognitive impairment. The World Health Organization (WHO) has issued recommended age-dependent urine iodine concentration targets, but a critical threshold beyond which clinical sequelae are to be expected remains undefined. Our study aimed to investigate spot urine iodine concentration in a typical Central European cohort of children and adolescents, and consider the implications of these values in regard to laboratory parameters for evaluating thyroid function.

Methods

Using the Sandell-Kolthoff method, spot urine iodine concentration was measured cross-sectionally from 1802 healthy children and adolescent in the age range of 0.25–18 years within the LIFE-Child epidemiological study based in and around the city of Leipzig (Germany). Additionally, serum thyroid biomarkers of these subjects were measured and correlated to urine iodine levels.

Results

In our cohort, 61.39% of boys and 65.91% of girls had an iodine level of < 100 µg/L (57%, 67%, 65% of the age groups 0–5, 6–12 and 13–18 years), the median iodine excretion was 86 µg/L in boys and 80 µg/L in girls. The iodine levels revealed no significant correlation with the thyroid biomarkers TSH, FT4 and FT3. Moreover, iodine values revealed no correlation with levels of antibodies against thyroid peroxidase or thyroglobulin.

Conclusion

In our cohort of children and adolescents, the relatively high number of iodine levels below the WHO recommendation appears not to be related to clinical or subclinical thyroid diseases in the respective participants.